Volume 15 Supplement 1

Proceedings of the 23rd Paediatric Rheumatology European Society Congress

Open Access

Proceedings of the 23rd Paediatric Rheumatology European Society Congress: part three

Genoa, Italy. 28 September – 01 October 2016
  • Riccardo Papa1,
  • Alessandro Consolaro1,
  • Francesca Minoia1,
  • Roberta Caorsi1,
  • Gianmichele Magnano2,
  • Marco Gattorno1,
  • Angelo Ravelli1,
  • Paolo Picco1,
  • Roberto Pillon3,
  • Denise Pires Marafon4,
  • Lidia Meli4,
  • Claudia Bracaglia4,
  • Andrea Taddio3, 5,
  • Fabrizio De Benedetti4,
  • Enes Turan6,
  • Sara Sebnem Kilic6,
  • Yasuhiko Itoh7,
  • Tomoko Shigemori7,
  • Shingo Yamanishi7,
  • Hidehiko Nagasaki7,
  • Ela Tarakci8,
  • Nilay Arman8,
  • Devrim Tarakci8,
  • Yusuf S. Akgul9,
  • Ozgur Kasapcopur10,
  • Emily Wilson11,
  • Hanna Lythgoe11,
  • Eve Smith11, 12,
  • Jenny Preston11, 13,
  • Michael W. Beresford11, 12, 13,
  • Lynn R. Spiegel14, 15,
  • Jennifer Stinson16, 17,
  • Mark Connelly18,
  • Adam Huber19,
  • Nadia Luca20,
  • Argerie Tsimicalis21,
  • Stephanie Luca22,
  • Naweed Tajuddin16,
  • Roberta Berard23,
  • Julie Barsalou24,
  • Sarah Campillo25,
  • Brian Feldman14,
  • Shirley Tse14,
  • Paul Dancey26,
  • Ciaran Duffy27,
  • Nicole Johnson20,
  • Patrick McGrath28,
  • Natalie Shiff29,
  • Lori Tucker30,
  • Charles Victor31,
  • Lynn R. Spiegel32, 33,
  • Chitra Lalloo34, 35,
  • Lauren Harris35,
  • Joseph Cafazzo36,
  • Lori Tucker37,
  • Kristin Houghton37,
  • Brian Feldman32, 38,
  • Nadia Luca39,
  • Ronald Laxer32, 40,
  • Jennifer Stinson34, 35,
  • Nilay Arman41,
  • Ela Tarakci41,
  • Ozgur Kasapcopur42,
  • Madeleine Rooney43,
  • Roisin Campbell44,
  • Catherine Wright45,
  • Wineke Armbrust46,
  • Otto Lelieveld47,
  • Jolanda Tuinstra48,
  • Nico Wulffraat49,
  • Joyce Bos47,
  • Jeanette Cappon50,
  • Marion van Rossum50,
  • Mariët Hagedoorn51,
  • Anna Vermé52,
  • Ylva Lampela53,
  • Ayse Huri Ozdogan54,
  • S. Ugurlu54,
  • K. Barut55,
  • A. Androvic55,
  • O. Kasapçopu56,
  • Emily Wilson57,
  • Jody Etheridge57,
  • Eve Smith57, 58,
  • Katie Dobson57,
  • Sue Kemp57,
  • Michael W. Beresford57, 58,
  • AnnaCarin Horne59,
  • Karin Palmblad59,
  • Malin Höglund59,
  • Natalia Stepanenko60,
  • Svetlana Salugina60,
  • Evgeny Fedorov60,
  • Irina Nikishina60,
  • Maria Kaleda60,
  • Nilay Arman61,
  • Ela Tarakci61,
  • Kenan Barut62,
  • Amra Adrovic62,
  • Sezgin Sahin62,
  • Ozgur Kasapcopur62,
  • Nilay Arman63,
  • Ela Tarakci63,
  • Ozgur Kasapcopur64,
  • Laurence Toumoulin65,
  • Johnny Frossard65,
  • Stephanie Archimbaut65,
  • Anne Paitier65,
  • Rolande Guastalli65,
  • Severine Guillaume Czitrom66,
  • Sirirat Charuvanij67,
  • Chollada Chaiyadech67,
  • Takako Miyamae68,
  • Hisashi Yamanaka68,
  • Cecile Picard69, 70,
  • Guillaume Thouvenin71,
  • Caroline Kannengiesser72,
  • Jean-Christophe Dubus73,
  • Nadia Jeremiah74,
  • Frédéric Rieux-Laucat74,
  • Bruno Crestani75,
  • Véronique Secq76,
  • Christelle Ménard77,
  • Martine Reynaud-Gaubert78,
  • Françoise Thivolet-Bejui69,
  • Philippe Reix79,
  • Alexandre Belot70, 80,
  • Ezgi Deniz Batu81,
  • Hafize Emine Sonmez81,
  • Abdulsamet Erden82,
  • Ekim Z. Taskiran83,
  • Omer Karadag82,
  • Umut Kalyoncu82,
  • İbrahim Oncel84,
  • Berkan Kaplan85,
  • Zehra Serap Arici81,
  • Cagri Mesut Temucin85,
  • Haluk Topaloglu84,
  • Yelda Bilginer81,
  • Mehmet Alikasifoglu83,
  • Seza Ozen81,
  • Lien Van Eyck86, 87,
  • Ellen De Langhe88,
  • Isabelle Jéru89, 90,
  • Erika Van Nieuwenhove86, 87,
  • Vasiliki Lagou87, 91,
  • Paul J. Baker92, 93,
  • Jocelyn Garcia-Perez86, 87,
  • James Dooley86, 87,
  • Lien De Somer94,
  • Raf Sciot95,
  • Pierre-Yves Jeandel96,
  • Julia Ruuth-Praz89, 90,
  • Bruno Copin90,
  • Myrna Medley-Hashim97,
  • Andre Megarbane98,
  • Sinisa Savic99,
  • An Goris91,
  • Serge Amselem89, 90,
  • Adrian Liston86, 87,
  • Seth Masters92, 93,
  • Carine Wouters86, 94,
  • Nami Okamoto100,
  • Yuko Sugita101,
  • Kousuke Shabana101,
  • Takuji Murata101,
  • Hiroshi Tamai100,
  • Juliana Ferenczová102,
  • Erika Banóova102,
  • Pavol Mrážik102,
  • Veronika Vargova102,
  • Dubravko Bajramovic103,
  • Ksenija Stekic Novacki103,
  • Kristina Potocki103,
  • Marijan Frkovic104,
  • Marija Jelusic104,
  • Irina Nikishina105,
  • Olga Kostareva105,
  • Svetlana Arsenyeva105,
  • Maria Kaleda105,
  • Anna Shapovalenko105,
  • Lennart Jans106,
  • Nele Herregods106,
  • Jacob Jaremko107,
  • Rik Joos106,
  • Joke Dehoorne106,
  • Nele Herregods108,
  • Jacob Jaremko109,
  • Xenofon Baraliakos110,
  • Joke Dehoorne111,
  • Rik Joos111,
  • Lennart Jans108,
  • Sofia Ramiro112,
  • Julio C. Casasola-Vargas113,
  • Désirée van der Heijde112,
  • Robert Landewé114,
  • Ruben Burgos-Vargas113,
  • Ruben Burgos-Vargas115,
  • Shirley M. Tse116,
  • Gerd Horneff117,
  • Kristina Unnebrink118,
  • Jaclyn K. Anderson119,
  • Aysenur Paç Kisaarslan120,
  • Betül Sözeri120,
  • Zübeyde Gündüz120,
  • Gökmen Zararsız121,
  • Hakan Poyrazoğlu120,
  • Ruhan Düşünsel120,
  • Kazutaka Ouchi122,
  • Shinji Akioka122,
  • Hiroshi Kubo122,
  • Norio Nakagawa122,
  • Hajime Hosoi122,
  • Lovro Lamot123, 124,
  • Fran Borovecki124,
  • Sanja Kapitanovic125,
  • Kristina Gotovac124,
  • Mandica Vidovic123,
  • Mirta Lamot123,
  • Edi Paleka Bosak123,
  • Miroslav Harjacek123,
  • Ricardo A. Russo126,
  • María M. Katsicas126,
  • Ruben Burgos Vargas127,
  • Ana L. Ortiz-Peyegahud128,
  • Zhang Pingping129,
  • Mou Yikun129,
  • Qi Jun130,
  • Jiang Yutong130,
  • Gu Jieruo130,
  • Mikhail M. Kostik131,
  • Shilova Ekaterina131,
  • Ilia Avrusin131,
  • Yuriy Korin131,
  • Olga Kopchak132,
  • Eugenia Isupova131,
  • Irina Chikova131,
  • Panova Tatyana133,
  • Margarita Dubko1,
  • Vera Masalova131,
  • Ludmila Snegireva131,
  • Tatyana Kornishina131,
  • Olga Kalashnikova131,
  • Vyacheslav Chasnyk131,
  • Mikhail M. Kostik134,
  • Irina Chikova134,
  • Eugenia Isupova134,
  • Margarita Dubko134,
  • Vera Masalova134,
  • Ludmila Snegireva134,
  • Tatyana Kornishina134,
  • Tatyana Likhacheva134,
  • Olga Kalashnikova134,
  • Vyacheslav Chasnyk134,
  • N. Ruperto135,
  • H. I. Brunner136,
  • P. Quartier137,
  • T. Constantin135,
  • E. Alexeeva135,
  • R. Schneider136,
  • I. Kone-Paut135,
  • K. Schikler136,
  • K. Marzan136,
  • N. Wulffraat135,
  • S. Padeh135,
  • V. Chasnyk135,
  • C. Wouters135,
  • J. B. Kuemmerle-Deschner135,
  • T. Kallinich135,
  • B. Lauwerys138,
  • E. Haddad136,
  • E. Nasonov135,
  • M. Trachana135,
  • O. Vougiouka135,
  • K. Leon139,
  • A. Speziale140,
  • K. Lheritier140,
  • E. Vritzali140,
  • A. Martini135,
  • D. Lovell136,
  • PRINTO/PRCSG,
  • Nienke Ter Haar141, 142,
  • Rianne Scholman141,
  • Wilco de Jager141,
  • Tamar Tak141,
  • Pieter Leliefeld141,
  • Bas Vastert142,
  • Sytze de Roock141, 142,
  • Nienke Ter Haar143, 144,
  • Rianne Scholman143,
  • Wilco de Jager143,
  • Ariane de Ganck145,
  • Nadia Ryter146,
  • Miha Lavric147,
  • Dirk Foell147,
  • Sytze de Roock143, 144,
  • Bas Vastert144,
  • Renee F. Modica148,
  • Kathleen G. Lomax149,
  • Pamela Batzel150,
  • Armelle Cassanas150,
  • Melissa E. Elder148,
  • Rina Denisova151,
  • Ekaterina Alexeeva151,
  • Saniya Valieva151,
  • Tatyana Bzarova151,
  • Kseniya Isayeva151,
  • Tatyana Sleptsova151,
  • Olga Lomakina151,
  • Alexandra Chomahidze151,
  • Margarita Soloshenko151,
  • Meyry Shingarova152,
  • Elena Kachshenko151,
  • Wilco De Jager153,
  • Sebastiaan J. Vastert153,
  • Gerdien Mijnheer153,
  • Berent J. Prakken153,
  • Nico M. Wulffraat153,
  • Hafize E. Sönmez154,
  • Asuman N. Karhan155,
  • Ezgi D. Batu154,
  • Yelda Bilginer154,
  • Zehra S. Arıcı154,
  • Ersin Gümüş155,
  • Hülya Demir155,
  • Aysel Yüce155,
  • Seza Özen154,
  • Jasmina Ahluwalia156,
  • Bhavneet Bharti157,
  • Sweta Rajpal156,
  • Varun Uppal156,
  • Alaknanda Walia156,
  • Surjit S. Samlok157,
  • Narender Kumar156,
  • Clarissa C. Valões158,
  • Beatriz C. Molinari158,
  • Ana Claudia G. Pitta158,
  • Natali W. Gormezano159,
  • Sylvia C. Farhat158,
  • Kátia Kozu158,
  • Adriana M. Sallum158,
  • Simone Appenzeller160,
  • Ana Paula Sakamoto161,
  • Maria T. Terreri161,
  • Rosa M. Pereira159,
  • Claudia S. Magalhães162,
  • Cássia Maria Barbosa163,
  • Francisco Hugo Gomes164,
  • Eloisa Bonfá159,
  • Clovis A. Silva158,
  • Kubra Ozturk165,
  • Zelal Ekinci165,
  • Maie Helal166,
  • Natalia Cabrera167,
  • Alexandre Belot167,
  • Jean Christophe Lega168,
  • Jocelyne Drai169,
  • Rene Ecochard170,
  • O. V. Shpitonkova171,
  • N. S. Podchernyaeva171,
  • Y. O. Kostina171,
  • N. G. Dashkova171,
  • M. K. Osminina171,
  • Gozde Yucel172,
  • Sezgin Sahin172,
  • Amra Adrovic172,
  • Kenan Barut172,
  • Ela Tarakci172,
  • Ahmet Arvas173,
  • Nandini Moorthy174,
  • Ozgur Kasapcopur172,
  • Paraskevi Dimou175,
  • Angela Midgley175,
  • Matthew Peak175, 176,
  • Simon C. Satchell177,
  • Rachael D. Wright175,
  • Michael W. Beresford175, 176,
  • Rachel Corkhill178,
  • Eve M. Smith178,
  • Michael W. Beresford178,
  • Sagar Bhattad179,
  • Amit Rawat179,
  • Surjit Singh179,
  • Anju Gupta179,
  • Deepti Suri179,
  • Martin de Boer180,
  • Taco Kuijpers180,
  • Sagar Bhattad181,
  • Amit Rawat181,
  • Anju Gupta181,
  • Deepti Suri181,
  • Vignesh Pandiarajan181,
  • Surjit Singh181,
  • Sapna Sandal182,
  • Amit Rawat182,
  • Anju Gupta182,
  • Surjit Singh182,
  • Sebastian Giraldo183, 184,
  • Roy Sanguino185,
  • Adriana S. Diaz186, 187,
  • Selcuk Uzuner188,
  • Sezgin Sahin189,
  • Gizem Durcan190,
  • Amra Adrovic189,
  • Kenan Barut189,
  • Ali Guven Kilicoglu191,
  • Ayhan Bilgic192,
  • Kayhan Bahali191,
  • Ozgur Kasapcopur189,
  • Sezgin Sahin193,
  • Amra Adrovic193,
  • Kenan Barut193,
  • Sinem Durmus194,
  • Hafize Uzun194,
  • Ozgur Kasapcopur193,
  • Sezgin Sahin195,
  • Amra Adrovic195,
  • Kenan Barut195,
  • Nur Canpolat196,
  • Salim Caliskan196,
  • Lale Sever196,
  • Ozgur Kasapcopur195,
  • Tomomi Sato197,
  • Fuminori Kimura198,
  • Wafaa Suwairi199,
  • Reem Abdwani200,
  • Abdulaziz Al Rowais201,
  • Jubran Al qanatish199,
  • Abdulrahman Al Asiri201,
  • Kubra Ozturk202,
  • Zelal Ekinci202,
  • Ekaterina Gaidar203,
  • Mikhail Kostik203,
  • Margarita Dubko203,
  • Vera Masalova203,
  • Elena Serogodskaya203,
  • Ludmila Snegireva203,
  • Tatyana Nikitina203,
  • Vyacheslav Chasnyk203,
  • Olga Kalashnikova203,
  • Evgenia Isupova203,
  • Elham Sardar204,
  • Perrine Dusser204,
  • Antoine Rousseau205,
  • Marc Labetoulle205,
  • Emanuel Barreau205,
  • Bahram Bodaghi206,
  • Isabelle Kone-Paut204,
  • Ivan Foeldvari207,
  • Jordi Anton208,
  • Rosa Bou208,
  • Sheila Angeles-Han209,
  • Regitze Bangsgaard210,
  • Gabriele Brumm211,
  • Tamas Constantin212,
  • Clive Edelsten213,
  • Jens Klotsche214,
  • Kirsten Minden214,
  • Elisabetta Miserocchi215,
  • Susan Nielsen210,
  • Gabriele Simonini216,
  • Arnd Heiligenhaus217,
  • Ivan Foeldvari218,
  • Jordi Anton219,
  • Rosa Bou219,
  • Sheila Angeles-Han220,
  • Regitze Bangsgaard221,
  • Gabriele Brumm222,
  • Tamas Constantin223,
  • Clive Edelsten224,
  • Jens Klotsche225,
  • Kirsten Minden225,
  • Elisabetta Miserocchi226,
  • Susan Nielsen221,
  • Gabriele Simonini227,
  • Arnd Heiligenhaus228,
  • Ivan Foeldvari229,
  • Jordi Anton230,
  • Rosa Bou230,
  • Sheila Angeles-Han231,
  • Regitze Bangsgaard232,
  • Gabriele Brumm233,
  • Tamas Constantin234,
  • Clive Edelsten235,
  • Jens Klotsche236,
  • Kirsten Minden236,
  • Elisabetta Miserocchi237,
  • Susan Nielsen234,
  • Gabriele Simonini238,
  • Arnd Heiligenhaus239,
  • Ivan Foeldvari240,
  • Jordi Anton241,
  • Rosa Bou241,
  • Sheila Angeles-Han242,
  • Regitze Bangsgaard243,
  • Gabriele Brumm244,
  • Tamas Constantin245,
  • Clive Edelsten246,
  • Jens Klotsche247,
  • Kirsten Minden247,
  • Elisabetta Miserocchi248,
  • Susan Nielsen243,
  • Gabriele Simonini249,
  • Arnd Heiligenhaus250,
  • Juan Manuel Mosquera Angarita251,
  • Rosa Bou251,
  • Carmen Garcia de Vicuña251,
  • Maria Victoria Hernandez252,
  • Alfredo Adan252,
  • Victor Llorens252,
  • Rosa Alcobendas253,
  • Susana Noval253,
  • Juan Carlos Lopez Robledillo254,
  • Isabel Valls254,
  • Mari Carmen Pinedo255,
  • Alejandro Fonollosa255,
  • Jaime de Inocencio256,
  • Pilar Tejada256,
  • Beatriz Bravo257,
  • Manuel Torribio257,
  • María Jesús García de Yebenes258,
  • Jordi Antón251,
  • Uveitis Working Group of the Spanish Pediatric Rheumatology Society,
  • Lorenza Maria Argolini259,
  • Irene Pontikaki259,
  • Maria Orietta Borghi260,
  • Laura Cesana260,
  • Elisabetta Miserocchi261,
  • Barbara Castiglioni262,
  • Maurizio Gattinara259,
  • Pierluigi Meroni259,
  • Pierre Quartier263,
  • Veronique Despert264,
  • Sylvaine Poignant265,
  • Amandine Baptiste266,
  • Caroline Elie266,
  • Isabelle Kone-Paut267,
  • Alexandre Belot268,
  • Laurent Kodjikian269,
  • Dominique Monnet270,
  • Michel Weber271,
  • Bahram Bodaghi272,
  • Laura Moal273,
  • Antoine Rousseau274,
  • LuuLy Pham273,
  • Emmanuel Barreau274,
  • Cherif Titah275,
  • Pascal Dureau275,
  • Marc Labetoulle274,
  • Bahram Bodaghi276,
  • Severine Guillaume Czitrom277,
  • Vanessa Cecchin278, 279,
  • Maria Elisabetta Zannin278, 279,
  • Daniele Ferrari279,
  • Francesco Comacchio279,
  • Irene Pontikaki279,
  • Claudia Bracaglia279,
  • Rolando Cimaz279,
  • Fernanda Falcini279,
  • Antonella Petaccia279,
  • Stefania Viola279,
  • Luciana Breda279,
  • Francesco La Torre279,
  • Fabio Vittadello279,
  • Giorgia Martini278, 279,
  • Francesco Zulian278, 279,
  • Caroline Galeotti280,
  • Guillaume Sarrabay281,
  • Olivier Fogel282,
  • Isabelle Touitou281,
  • Bahram Bodaghi283,
  • Corinne Miceli-Richard282,
  • Isabelle Koné-Paut280,
  • Hala Etayari284,
  • Hashad Soad284,
  • Ihab El Kadry285,
  • Habibullah Eatamadi286,
  • Kais AlAlgawi287,
  • Mustafa Al Maini288,
  • Khulood Khawaja288,
  • Sophie Van den Berghe289,
  • Ilse de Schryver290,
  • Ann Raes289,
  • Rik Joos289,
  • Joke Dehoorne289,
  • Lídia L. C. Teixeira291,
  • Ana Duarte291,
  • Sandra Sousa291,
  • Filipe Vinagre291,
  • Maria J. Santos291,
  • Nataly S. Shevchenko292,
  • Ludmila F. Bogmat292,
  • Marina V. Demyanenko292,
  • Navdha R. Ramchurn293,
  • Mark Friswell294,
  • Rebecca A. James295,
  • Lucy R. Wedderburn295, 296, 297,
  • Clive Edelsten295,
  • Reshma Pattani295,
  • Clarissa A. Pilkington295, 296,
  • Sandrine Compeyrot-Lacassagne295,
  • Rebecca A. James298,
  • Sandrine Compeyrot-Lacassagne298,
  • Clive Edelsten298,
  • Reshma Pattani298,
  • Clarissa A. Pilkington298, 299,
  • Lucy R. Wedderburn298, 299, 300,
  • Ana V. Villarreal301,
  • Nydia Acevedo302,
  • Enrique Faugier301,
  • Rocio Maldonado301,
  • Dilek Yılmaz303,
  • Hilal Bektaş Uysal304,
  • Evgeny Fedorov305,
  • Svetlana Salugina305,
  • Elena Kamenets306,
  • Ekaterina Zaharova306,
  • Stefka Radenska-Lopovok307,
  • Joao Nascimento308,
  • Helena Sofia309,
  • Carla Zilhão308, 310,
  • Rui Almeida311,
  • Margarida Guedes308, 310,
  • Kubra Ozturk312,
  • Murat Deveci313,
  • Zelal Ekinci312,
  • Svetlana Rodionovskaya314, 315,
  • Vera Vinnikova314,
  • Svetlana Salugina315,
  • Evgeny Fedorov315,
  • Irina Tsymbal314,
  • Edyta Olesińska316,
  • Jacek Postępski317,
  • Agnieszka Mroczkowska-Juchkiewicz318,
  • Agnieszka Pawłowska-Kamieniak318,
  • Beata Chrapko319,
  • Damjana Ključevšek320,
  • Nina Emeršič321,
  • Nataša Toplak322,
  • Tadej Avčin322,
  • Faina Rokhlina323,
  • Galina Glazyrina324,
  • Natalia Kolyadina325,
  • Kwangnam Kim326,
  • Sinae Eom326,
  • Daeyoung Kim327,
  • Jungwoo Rhim328,
  • Francesca Ricci329,
  • Paola Montesano329,
  • Barbara Bonafini329,
  • Veronica Medeghini329,
  • Ilaria Parissenti329,
  • Antonella Meini329,
  • Marco Cattalini329,
  • Paolo Airò330,
  • Nataliya Panko331,
  • Nataliya Shevchenko332,
  • Iryna Lebec332,
  • Yevgeniya Zajceva333,
  • Sara Rostlund334,
  • Marie André335,
  • Takuma Hara336,
  • Takayuki Kishi337,
  • Yumi Tani337,
  • Aki Hanaya337,
  • Takako Miyamae336,
  • Satoru Nagata337,
  • Hisashi Yamanaka336,
  • Velma Selmanovic338,
  • Aida Omercahic-Dizdarevic338,
  • Adisa Cengic338,
  • Almira Cosickic339,
  • Aida Omerčahić Dizdarević340,
  • Gemma Lepri341,
  • Paolo Picco342,
  • Clara Malattia343,
  • Eleonora Bellucci341,
  • Marco Matucci-Cerinic341,
  • Fernanda Falcini341,
  • Margarita Dubko344,
  • Anton Solovyev344,
  • Elena Fedotova344,
  • Rocio Maldonado345,
  • Enrique Faugier345,
  • Ana Victoria Villarreal345,
  • Nydia Acevedo345,
  • Talia Diaz345,
  • Yuridiana Ramirez345,
  • Teresa Giani346,
  • Achille Marino346,
  • Gabriele Simonini346,
  • Rolando Cimaz346,
  • Daniel Hunt347,
  • Muthana Al Obaidi348,
  • Veli Veli347,
  • Charalampia Papadopoulou348,
  • Jochen Kammermeier349,
  • Edyta Olesińska350,
  • Anna Poluha351,
  • Jacek Postępski352,
  • Gangadhara C. Bharmappanavara353,
  • Alison Kelly353,
  • Lindsay Shaw354,
  • Teresa Giani355,
  • Giovanna Ferrara356,
  • Michele Luzzati355,
  • Achille Marino355,
  • Mattia Giovannini355,
  • Gabriele Simonini355,
  • Rolando Cimaz355,
  • Liliana Jurado357,
  • Sebastian Giraldo358, 359,
  • Juliana Chamorro360,
  • Lorena Sarmiento361,
  • Adriana S. Diaz362, 363,
  • Veronica Medeghini364,
  • Francesca Ricci364,
  • Paola Montesano364,
  • Barbara Bonafini364,
  • Ilaria Parissenti364,
  • Antonella Meini364,
  • Ester Conversano364,
  • Marco Cattalini364,
  • Maria Francesca Gicchino365,
  • Giulia Macchini365,
  • Carmela Granato365,
  • Assunta Tirelli365,
  • Alma N. Olivieri365,
  • Marija Perica366,
  • Lana Tambić Bukovac366,
  • Ludmila F. Bogmat367,
  • Nataly S. Shevchenko367,
  • Marina V. Demyanenko367,
  • Reza Sinaei368,
  • Vadood Javadi Parvaneh368,
  • Reza Shiari368,
  • Khosro Rahmani368,
  • Fatemeh F. Mehregan368,
  • Mehrnoush Hassas Yeganeh368,
  • Inmaculada Calvo Penadés369,
  • Berta López Montesinos369,
  • Ma Isabel González Fernández369,
  • Adriana Rodríguez Vidal369,
  • Anand Prahalad Rao370,
  • Ayesha Romana371,
  • Jyothi Raghuram370,
  • Ankur Kumar372,
  • Deepti Suri372,
  • Vishali Gupta373,
  • Amit Rawat372,
  • Surjit Singh372,
  • Elif Comak374,
  • Gülşah Kaya Aksoy374,
  • Aygen Yılmaz375,
  • Atike Atalay375,
  • Mustafa Koyun374,
  • Reha Artan375,
  • Sema Akman374,
  • Maria Francesca Gicchino376,
  • Giulia Macchini376,
  • Carmela Granato376,
  • Alma N. Olivieri376,
  • Maria I. Kaleda377,
  • Irina P. Nikishina377,
  • Sergei K. Soloviev377,
  • Victor A. Malievsky378,
  • Ekaterina V. Nikolaeva377,
  • Teresa Giani379,
  • Achille Marino379,
  • Gabriele Simonini379,
  • Rolando Cimaz379,
  • Agnieszka Gazda380,
  • Beata Kołodziejczyk380,
  • Lidia Rutkowska-Sak380,
  • Angela Mauro381,
  • Teresa Giani382,
  • Gabriele Simonini382,
  • Rolando Cimaz382,
  • Maria Francesca Gicchino383,
  • Pierluigi Marzuillo383,
  • Stefano Guarino383,
  • Alma N. Olivieri383 and
  • Angela La Manna383
Pediatric Rheumatology201715(Suppl 1):43

https://doi.org/10.1186/s12969-017-0143-7

Published: 30 May 2017

Poster Session: Miscellaneous rheumatic diseases

P381 Transient periosteal hyperostosis with dysproteinemia (Goldbloom syndrome): two cases report

Riccardo Papa1, Alessandro Consolaro1, Francesca Minoia1, Roberta Caorsi1, Gianmichele Magnano2, Marco Gattorno1, Angelo Ravelli1, Paolo Picco1

1Pediatria II, Reumatologia, Istituto Giannina Gaslini, Genoa, Italy; 2Radiologia, Istituto Giannina Gaslini, Genoa, Italy
Presenting author: Riccardo Papa

Introduction: Transient periosteal hyperostosis with dysproteinemia, also named Goldbloom syndrome (GS), is a rare pediatric disease characterized by recurrent crisis of bone pain, fever, increased inflammatory markers and dysproteinemia. From 1966 only few cases have been reported in the English literature.

Objectives: To better define the clinical and epidemiological features of GS.

Methods: We report clinical, laboratory and radiological features of our patients in Table 1, comparing with the English literature.

Results: Case 1 was a 9-year-old girl who presented daily crisis of bone pain at the lower limbs, associated with fever spikes, limping and nocturnal awakenings. Physical examination was normal. Laboratory tests showed mild anemia, thrombocytosis, increased inflammatory markers and high antibody levels against streptolysine O and DNase-B (ASO 4280 IU/ml and ADN-B 6310 UI/ml, respectively). Throat swab was positive for group A β-hemolytic streptococcus (GAS). Unusual dysproteinemia, characterized by hypoalbuminemia with increased a1, a2 and g globulinemia, was noted. X-ray evaluation of the lower limbs showed increased bone density at femurs and tibias with signs of periostitis: on STIR sequence MRI these bones presented areas of hyperintense signal. Bone biopsy revealed a thickened periosteum that was strongly adherent to the underlying tissue. Histopathologic study showed signs of chronic inflammation. Steroid treatment was started, leading to a prompt resolution of the clinical picture within few days.

Case 2 was a 6-years-old girl who developed, two weeks after an untreated febrile pharyngitis, daily attacks of severe pain at ankles with fever. Joint examination was normal. Throat swab was positive for GAS. In the following weeks, recurrent crisis of bone pain persisted with a severe weight loss. She was hospitalized and laboratory tests showed mild anemia, thrombocytosis and unusual dysproteinemia with hypoalbuminemia and high a1, a2 and g globulinemia. Inflammatory markers and antibodies against GAS were elevated (ASO 775 IU/ml, AND-B 1660 U/ml). STIR sequence MRI showed hyperintense areas at the femurs, tibias, humerus and ulnas, associated with a thickened pretibial soft tissue. Bone marrow biopsy showed signs of chronic inflammation. A short cycle of steroids was administered with rapid resolution of symptoms, turning off inflammatory markers. Immaging became normal after three months.

Conclusion: Our patients fulfill the GS features with evidence of previous GAS infection. Our patients lived in the same area of Northern Italy and presented the onset of GS a week apart. Our experience suggests that a timely diagnosis and a short cycle of steroid may rapidly change the history of GS.

Disclosure of Interest: None Declared
Table 1 (abstract P381).

Main features of our patients with English literature review

 

Case 1

Case 2

English literature (7 patients)

Demographic data: gender; age at onset (years)

F; 9

F; 6

M:F = 3:4; 8 (0.3-14)

Previous intercurrent episode

pharyngitis

pharyngitis

pharyngitis (4), scarlet fever (1), otitis (1)

Fever and bone pain at the limbs

+

+

all

Increased inflammatory markers

+

+

6 (86%)

Characteristic dysproteinemia (hypoalbuminemia with increased a1, a2 and g globulinemia)

+

+

all

Throat swab culture positive for GAS

+

+

ND

Presence of antibodies against GAS

+

+

1 (14%)

Radiographic periosteal reaction

+

+

all

Complete resolution (months)

1

3

24 (10-66)

ND not done

P382 Diagnosis of acute rheumatic fever with the 2015 revision of Jones criteria

Roberto Pillon1, Denise Pires Marafon2, Lidia Meli2, Claudia Bracaglia2, Andrea Taddio1,3, Fabrizio De Benedetti2

1University of Trieste, Trieste, Italy; 2Division of Rheumatology, Ospedale Pediatrico Bambino Gesù IRCCS, Roma, Italy; 3Institute for Maternal and Child Health - IRCCS “Burlo Garofolo”, Trieste, Italy
Presenting author: Roberto Pillon

Introduction: In 2015 the historic Jones criteria for the diagnosis of Acute Rheumatic Fever (ARF) were revised introducing two different sets of criteria for low-risk and for moderate/high-risk populations (according to ARF incidence). In Italy the exact ARF incidence is unknown but small regional or local reports suggest an incidence of 2-5/100.000 per year, suggesting that our population might be considered at moderate risk for ARF.

Objectives: To evaluate the performance of the revised Jones criteria in a retrospective population and to compare it with the performance of the previous version of Jones criteria.

Methods: We conducted a retrospective study on 288 patients with ARF (108 female; median age 8.5 years, IQR 7.1-10.3) diagnosed from 2001 to 2015 in a Pediatric Rheumatology Division by pediatric rheumatologists, discharged with an ICD 9 code consistent with ARF. We retrospectively applied the two sets (for low-risk and for moderate/high-risk) of the 2015 revised Jones criteria and the 1992 version of the Jones criteria.

Results: Of 288 patients, 253 (87.8%) met the 1992 version of the Jones criteria, 237 (82.3%) met the revised criteria for low-risk populations and 259 (89.9%) for moderate/high-risk populations. None of these differences was significant. Prevalence of major and minor criteria is shown in Table. With the exception of difference in arthritis, the 1992 version and the 2015 revised version did not show major differences. Of the 288 patients with a clinical diagnosis of ARF 29 did not meet any version of the Jones criteria. Patients in this group presented with isolated chorea or silent carditis without other manifestations.

Prevalence of the clinical characteristics and comparison among the 1992 version of Jones criteria and the 2015 revised Jones criteria (low risk and moderate-high risk populations):
 

1992 version

2015 low risk

2015 mod-high risk

1992 version vs 2015 low risk*

1992 version vs 2015 mod-high risk*

Total of patients

253

237

259

0.08

0.51

MAJOR CRITERIA

Arthritis

94 (37.2)

88 (37.1)

209 (75.3)

1.0

<0.0001

Erythema marginatum

3 (1.2)

3 (1.3)

3 (1.2)

1.0

1.0

Chorea

48 (19)

49 (17)

49 (17)

0.73

0.91

Carditis

230 (90.9)

247 (85.8)

247 (85.8)

0.51

0.39

MINOR CRITERIA

ESR/CRP

218/236 (92.4)

208/259 (80.3)

226/259 (87.3)

0.0026

0.13

Fever

140 (55.3)

157 (54.5)

196 (68.1)

0.65

0.0004

Arthralgia

186/249 (74.7)

166/235 (70.6)

8/257 (3.1)

0.36

<0.0001

Prolonged PR

38 (15)

34 (14.3)

35 (13.5)

0.90

0.70

Values are expressed in Number (percentage). *p value (Fisher Exact test)

Conclusion: The revised Jones criteria for low-risk populations are slightly more sensitive than the 1992 version of Jones criteria, while the revised Jones criteria for moderate/high populations are slightly less sensitive than the 1992 version. In this population, the revised criteria did not substantially modify the diagnosis of ARF. Approximately 10% of patients presented with isolated chorea or silent carditis.

Bibliography:

1. Gewitz M, et al. Revision of the Jones Criteria for the Diagnosis of Acute Rheumatic Fever in the Era of Doppler Echocardiography: A Scientific Statement From the American Heart Association. Circulation. 2015.

2. Breda L, et al. Population-Based Study of Incidence and Clinical Characteristics of Rheumatic Fever in Abruzzo, Central Italy, 2000-2009. The Journal of Pediatrics 2012

Disclosure of Interest: None Declared

P383 Restrospective view of primary raynaud’s phenomenon in childhood

Enes Turan, Sara Sebnem Kilic

Pediatric Rheumatology, Uludag University Medical Faculty, Bursa, Turkey
Presenting author: Sara Sebnem Kilic

Introduction: Raynaud’s phenomenon (RP) refers to transient vasospasm of peripheral arteries and arterioles, usually involving peripheral small vessels of the fingers or toes and resulting in a triple-colour change starting with pallor and followed by cyanosis and erythema. Attacks are typically triggered by cold or emotional stress. The diagnosis of RP can be made on the basis of the patient’s clinical symptoms. Primary RP occurs without underlying disease and is considered a benign. Connective tissue diseases are the most common cause of secondary RP. Objectives: Detailed history, physical, and laboratory findings of the patients with primary RP were evaluated restrospectively.

Methods: Data collection was performed via the patient files. The study was approved by the Ethical Committee of the Uludag University Faculty of Medicine.

Results: Out of the 58 patients, 38 were girls whereas 20 were boys. The patients’ boy/girl ratio was 1.9 (38/20) and their ages ranged from 6 to 21 years (median:16 years). The median age at onset of complaints due to RP was 13 (minimum:2, maximum:17), median age at diagnosis:15 (minimum:3, maximum:17). In 37.9% cases (n = 22) There were similar complaints in first-degree relatives in 37.9% of patients. The most common symptom was feeling cold in the extremities ends (100%), followed by pain (87%) and tingling sensation (70.7%). While 38 patients(65.5%) had biphasic colour changes, 20 (34.5%) had triphasic colour changes. Triphasic colour change was statistically significant with high incidence (p = 0.026) in cases with ANA positivity and family history. Low titer positive ANA was present in 14 patients(24.1%). Presence of migraine in 29,3% of the cases was the most common disease associated with RP. Migraine was significantly more frequent in the girls compared to the boys (p = 0.02). Furthermore, cases with migraine had a significant lower hemoglobin levels and significant higher mean platelet volume. Apart from preventive measures, calcium channel blockers (CCB) were the most used drugs (n = 32, 55.2%) and were beneficial in 78.1% (25 out of 32). Nitroglycerin patch was applied to the rest of patients (n = 26, 44.8%), which was useful to relieve the symptoms in 50% of them. Sildenafil was used in one patient who was resistant to both of the drugs and the result was positive.

Conclusion: There is very limited data concerning childhood RP. In previous studies conducted in children there is no data on association between RP and migraine. Anemia in patients with RP was thought to be a predisposition to migraine development. Calcium channel blockers were found to be more effective than nitroglycerin patch treatment. Further studies with a greater number of patients are required in order to confirm our results.

Disclosure of Interest: None Declared

P384 Prevention of Sjögren’s syndrome by immunosuppressants in children with positive anti-ro antibodies and chronic nonspecific complaints

Yasuhiko Itoh, Tomoko Shigemori, Shingo Yamanishi, Hidehiko Nagasaki

Department of Pediatrics, NIPPON MEDICAL SCHOOL, Tokyo, Japan
Presenting author: Yasuhiko Itoh

Introduction: Anti-Ro antibodies are found in children with either Sjögren’s syndrome (SS), systemic lupus erythematosus (SLE) or, occasionally, chronic nonspecific complaints such as fatigue and low-grade fever. We have reported that about 10% of children with chronic nonspecific complaints and with positive antinuclear antibodies were positive for anti-Ro antibodies.

Objectives: Although a few of them showed positive lip biopsy findings equivalent to that of SS (subclinical SS), the majority of such children exhibited no evidence of SS. To clarify the pathogenic role of anti-Ro antibodies in various conditions and the future development of dryness, those children have been followed for more than 10 years, both clinically and immunologically.

Methods: The patients included in this study were as follows: 1) 27 children with chronic nonspecific complaints, with anti-Ro antibodies, and with negative lip biopsies; 2) 10 children with chronic nonspecific complaints, with anti-Ro antibodies, and with positive biopsies; 3) nine children with SLE and with positive anti-Ro antibodies; 4) three children with MCTD and with positive anti-Ro antibodies. They have been followed for more than 10 years. Anti-Ro antibodies were measured by using either the Ouchterlony, ELISA, western immunoblot or, in some cases, RNA-immunoprecipitation methods.

Results: Twenty-three out of 27 patients in group 1 showed no evidence of SS even after more than 10 years. Most of the patients in group 2 who had not been treated by immunosuppressants have gradually developed dryness. On the other hand, patients who had been treated have developed no or little dryness. Patients in the groups 3 and 4 have developed no dryness.

All patients in groups 3 and 4 had been treated by immunosuppressants against their basic diseases and developed no dryness. In the same way, most patients with only nonspecific complaints treated with immunosuppressants did not develop dryness.

Conclusion: These results suggest that there may be a chance to prevent SS with immunosuppressants in children with positive anti-Ro antibodies as long as the treatment is initiated before they develop dryness.

Disclosure of Interest: None Declared

Poster Session: Psycho-social aspects and rehabilitation

P385 Invention of rehabilitative games using the leap motion controller for hand rehabilitation in children with juvenile idiopathic arthritis and investigation of its’ effectiveness

Ela Tarakci1, Nilay Arman1, Devrim Tarakci1, Yusuf S. Akgul2, Ozgur Kasapcopur3

1Faculty of Health Sciences, Division of Physiotherapy and Rehabilitaiton, Istanbul University, Istanbul, Turkey; 2Department of Computer Engineering, Gebze Institute of Technology, Kocaeli, Turkey; 3Department of Pediatric Rheumatology, Medical Faculty of Cerrahpasa, Istanbul University, Istanbul, Turkey
Presenting author: Ela Tarakci

Introduction: Juvenile idiopathic arthritis (JIA) is the most common chronic pediatric rheumatic disease. Depending on the underlying pathologies, the common symptoms of this disorder are the limitations of the upper extremity joint movement angles, muscle imbalance and the functional limitations caused by the contracture due to these patients. By utilizing exciting new sensor technologies, such as Microsoft Kinect, Nintendo Wii and Leap Motion, practical game based rehabilitation applications have been becoming popular in the current.

Objectives: The aim of this study was to investigation of effectiveness of invented rehabilitative games using The Leap Motion Controller (LMC) for hand rehabilitation in patients with JIA.

Methods: 18 patients with JIA (14 girls, 4 boys), age range 8-18 participated in this study. Range of motion (ROM) of hand, grip strength, functional ability, fatique and quality of life were assessed with a goniometer, hand dynamometer, Childhood Health Assessment Questionnaire (CHAQ), Numeric Rating Scale (NRS), and the Pediatric Quality of Life Inventory (PedsQL), respectively. In order to improve hand functions, two games were invented with hand free LMC by our team. One of the games, “Leapball” was invented as picking the ball and throw to the basket. The game is to ensure the activities of repeated hold and release by simulating the hand grip function. The other game, “CatchAPet” is to intend touching the rabbits going out its burrow for simulating wrist flexion and extension. The patients completed a 8 week individually planned leap motion based exercise programme 3 times a week at the department of physical therapy and rehabilitation. Duration of the each treatment session was 30-45 minutes. Parameters of the games (Time, size of ball, speed of rabbits) were adjusted according to patient’s functional ability and progressed during the treatment.

Results: The mean age and duration of disease was 12.22 ± 3.30 (age range 8-18), 7.28 ± 4.22 years, respectively. The means of the pre/post treatment scores of NRS fatigue were 6.11 ± 1.53 / 2.22 ± 1.21, PedsQL-patients 63.71 ± 18.13 / 85.93 ± 12.08, PedsQL-parents 57.63 ± 18.88 / 80.80 ± 13.21, CHAQ-total 1.36 ± 0.67 / 0.30 ± 0.28, CHAQ-pain 31.94 ± 30.49 / 6.94 ± 11.77, and CHAQ-well being scores were 55.28 ± 19.28 / 21.94 ± 15.44, respectively. Table 2 shows ROM of wrist flexion and extension, fingertip to palm distance, hand grip and pinch grips scores for pre and post treatment. Significant statistical differences were found between pre and post-treatment all outcomes. (p < 0.001).

Conclusion: The study demonstrated that participating in a 8-week individually planned leap motion based exercise programme improves the range of motion of hand, grip strength, fatigue, physical function and the quality of life in patients with JIA. We think that improvements of the results may base on realistic animations of hand, virtual environments, patient motivation, consistent visual feedback and feasible and easy progression options of the invented games.

Disclosure of Interest: None Declared
Table 2 (abstract P385).

ROM of wrist flexion and extension, fingertip to palm distance, hand grip and pinch grips scores for pre and post treatment

 

Pre-treatment

Post-treatment

p

Mean ± SD

Mean ± SD

R

L

R

L

R

L

ROM-wrist flexion

58.72 ± 20.55

53.61 ± 23.56

80.28 ± 12.42

78.61 ± 14.32

0.000

0.000

ROM-Wrist extension

36.94 ± 20.51

34.17 ± 17.25

62.78 ± 10.74

62.50 ± 15.74

0.000

0.000

Fingertip to palm distance (cm)

1.05 ± 1.93

1.08 ± 1.78

0.58 ± 1.43

0.38 ± 0.84

0.001

0.009

Hand Grip (kg)

14.15 ± 9.99

9.04 ± 7.49

21.44 ± 11.10

18.08 ± 10.18

0.000

0.000

Lateral Pinch Grip (kg)

6.16 ± 3.08

5.14 ± 3.31

8.16 ± 3.72

6.87 ± 3.44

0.000

0.001

Tip Pinch Grip (kg)

2.14 ± 2.59

1.14 ± 1.19

3.58 ± 2.21

2.69 ± 1.77

0.002

0.001

Palmar Pinch Grip (kg)

3.18 ± 2.44

2.61 ± 2.97

5.83 ± 3.10

5.30 ± 2.82

0.000

0.000

P386 Lupus and you: developing a workshop for young people with lupus and their families

Emily Wilson1, Hanna Lythgoe1, Eve Smith1,2, Jenny Preston1,3, Michael W. Beresford1,2,3

1Department of Paediatric Rheumatology and Psychology, Alder Hey Children’s NHS Foundation Trust, Liverpool, UK; 2Department of Women’s and Children’s Health, Institute of Translational Medicine, Liverpool, UK; 3UK Experimental Arthritis Treatment Centre for Children, University of Liverpool, Liverpool, United Kingdom
Presenting author: Emily Wilson

Introduction: Lupus is a severe, autoimmune disease, potentially affecting any organ in the body. It is very rare in children and young people. As a regional service and the UK’s only ‘Centre of Excellence for Childhood Lupus’, our patients live across a large geographical catchment area. Many of the patients accessing our service report never having had the chance to meet another young person with the condition and how isolating this could feel. The mental health needs of young people with chronic health conditions are well known and potentially debilitating.

Objectives: We aimed to develop a series of day-long multidisciplinary “Lupus and You” workshops to be attended by young people with lupus and their families, within the Lupus Centre at Alder Hey Children’s Hospital. We wanted to continue to be responsive to the ongoing needs of our patients whilst also looking to intervene proactively to support them in developing resilience and coping strategies to minimise the impact of their condition on their lives.

Methods: 7 families participated in the first workshop which focused on two main themes; managing fatigue and research participation.

Fatigue was one of the most commonly reported concerns identified by young people and their parents on a routinely completed pre-clinic screening tool. A recent survey of young people with lupus suggested patients wanted to know more about research participation.

All participants completed a range of standardized measures to capture psychological well-being (including fatigue, emotional well-being, resilience and quality of life) at the time of attendance. Evaluations forms were given out to all attendees in order to review the day and identify areas for consideration within future workshops.

Results: Participants participated in exercises designed to facilitate sharing of difficulties as well as examples of strategies utilized to manage fatigue. The team’s psychologist, physiotherapist and occupational therapist also shared ideas and strategies for families to consider. Information about local and national research in paediatric lupus was shared in an interactive session.

High levels of fatigue were identified amongst lupus patients (mean score on the fatigue severity scale 5.1 (range 4 – 5.8) where people scoring above 3 points are considered to suffer with fatigue). Young people and their families reported increased confidence in managing fatigue when pre- and post-workshop data were compared.

Otherwise there was considerable variation in the extent to which young people were coping with having lupus. The results will be reviewed with the individuals and their parents in order to inform ongoing intervention and support.

Feedback from workshop evaluations indicated that attendees found the activities to be helpful and convenient to attend. Support for siblings, medication, and knowledge of common symptoms were identified as potential topics for future workshops.

Conclusion: The “Lupus and You” workshop allowed young people with lupus and their families to share experiences of managing this chronic illness, to develop supportive relationships whilst also developing resilience and practical strategies for living their lives fully despite their ongoing health needs.

Workshops such as this could be used as a forum to facilitate collection of important data from patients with rare diseases, whilst simultaneously benefitting patients and their families.

The workshops are being considered as part of a stepped-care model of psychological support offered to lupus patients.

Disclosure of Interest: None Declared

P387 Development and usability testing of an ipad and desktop psycho-educational game for children with juvenile idiopathic arthritis and their parents

Lynn R. Spiegel1,2, Jennifer Stinson3,4, Mark Connelly5, Adam Huber6, Nadia Luca7, Argerie Tsimicalis8, Stephanie Luca9, Naweed Tajuddin3, Roberta Berard10, Julie Barsalou11, Sarah Campillo12, Brian Feldman1, Shirley Tse1, Paul Dancey13, Ciaran Duffy14, Nicole Johnson7, Patrick McGrath15, Natalie Shiff16, Lori Tucker17, Charles Victor18

1Rheumatology, Hospital for Sick Children, Toronto, Canada; 2Pediatrics, University of Toronto, Toronto, Canada; 3Child Evaluative Health Sciences, The Hospital for Sick Children, Toronto, Canada; 4Lawrence S. Bloomberg Faculty of Medicine, University of Toronto, Toronto, Canada; 5Psychology, University of Kansas Medical Center, Lawrence, KS, United States; 6Rheumatology, IWK Health Center, Halifax, Canada; 7Rheumatology, Alberta children’s Hospital, Calgary, Canada; 8Ingram School of Nursing, Mcgill University, Montreal, Canada; 9Child Health Evaluative Sciences, Hospital for Sick Children, Toronto, Canada; 10Rheumatology, Children’s Hospital of Western Ontario, London, Canada; 11Rheumatology, CHU Ste-Justine, Montreal, Canada; 12Rheumatology, Montreal Children’s Hospital, Montreal, Canada; 13Pediatrics, Memorial University of Newfoundland, St John’s, Canada; 14Pediatrics, Children’s Hospital of Eastern Ontario, Ottawa, Canada; 15Research, Innovation and Knowledge Translation, IWK Health Center, Halifax, Canada; 16Pediatrics, University of Florida, Gainesville, FL, United States; 17Rheumatology, BC Children’s Hospital, Vancouver, Canada; 18Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada
Presenting author: Lynn R. Spiegel

This abstract is not included here as it has already been published.

P388 Icancope: user-centred design and development of a smartphone app to support self-management for youth with arthritis pain

Lynn R. Spiegel1,2, Chitra Lalloo3,4, Lauren Harris4, Joseph Cafazzo5, Lori Tucker6, Kristin Houghton6, Brian Feldman1,7, Nadia Luca8, Ronald Laxer1,9, Jennifer Stinson3,4

1Pediatrics, University of Toronto, Toronto, Canada; 2Rheumatology, The Hospital for Sick Children, Toronto, Canada; 3Lawrence S. Bloomberg Faculty of Nursing, University of Toronto, Toronto, Canada; 4Child Health Evaluative Sciences, The Hospital for Sick Children, Toronto, Canada; 5Centre for Global eHealth Innovation, University Health Network, Toronto, Canada; 6Pediatrics, University of British Columbia, Vancouver, Canada; 7Rheumatology, Hospital for Sick Children, Toronto, Canada; 8Rheumatology, Alberta Children’s Hospital, Calgary, Canada; 9Rheumatology, The Hospital for Sick Children, Toronto, Canada
Presenting author: Lynn R. Spiegel

This abstract is not included here as it has already been published.

P389 Use of the Xbox Kinect virtual gaming system to improve upper extremity functions and activity performance in patients with with juvenile idiopathic arthritis

Nilay Arman1, Ela Tarakci1, Ozgur Kasapcopur2

1Faculty of Health Sciences, Division of Physiotherapy And Rehabilitation, Istanbul University, Istanbul, Turkey; 2Department of Pediatric Rheumatology, Medical Faculty of Cerrahpasa, Istanbul University, Istanbul, Turkey
Presenting author: Nilay Arman

Introduction: Juvenile idiopathic arthritis (JIA) is most common chronic rheumatic disease in childhood. The upper extremity involvement in JIA causes muscle imbalance, joint destruction, pain, stiffness and limitations on activities of daily living (ADL) in varying degrees. It has been reported that improvements of upper extremity functions were achieved by video-based games (VBG) in various disease groups.

Objectives: The aim of this preliminary study was to investigate effects of client-centered task-oriented activity training (TOAT) with VBG on upper extremity functions and activity performance in children with JIA.

Methods: 23 patients (19 girls, 4 boys) with JIA (7 oligoarticular, 16 polyarticular) have upper extremity involvements, participated in this study. Muscular strength was measured by using a portable digital handheld dynamometer. Also, hand grip and pinch strength evaluations was done by a dynamometer and pinchmeter. ADL was evaluated by Duruoz Hand Index (DHI) and Childhood Health Assessment Questionnaire (CHAQ). Activity performance was performed by Jebsen Hand Function Test (JHFT). Also, activity performance and satisfaction were measured by The Canadian Occupational Performance Measure (COPM). Five most important problems of activity performance were determined with the patient and his/her parents. Fatigue severity was measured by Numeric Rating Scale (NRS). We have created training protocol with Xbox 360 games. We prefered ‘Dance Central2’, one of the Xbox 360 games, for warming (macerana dancing, 10 minutes). Other games, ‘Fruit Ninja’, ‘Table Tennis’, ‘Boxing’, ‘Volleyball’, ‘Darts’ and ‘Bowling’ were selected appropriately for TOAT according gto 5 most important limited ADL of each patient that determined with COPM. The games were set as client-centered for 45-60 minutes by the physiotherapist. All the participants completed 8 weeks (3 times in a week) of client-centered TOAT with Xbox 360 Kinect™ games.

Results: The mean age and duration of disease was 12,26 ± 3,09 (age range 8-18), 6,78 ± 4,16 years, respectively. 20 of patients had bilateral involvement of upper extremity. Wilcoxon test showed significant statistically differences pre and post-treatment, in almost all the values, except some scores of subtasks of JHFT (p < 0.001). All muscles strength of upper extremities were statistically significant increased (p < 0.001). Table 3 shows the scores of functional ability, fatigue, grip and pinch strength and activity performance outcomes pre and post-treatment.

Conclusion: Our Kinect Xbox 360 protocol that inclued client-centered TOAT has showed improvements on upper extremity functions and activity performance in patients with JIA. We think that TOAT with VBG improves the activity performance and physical functions via being stimulative and interactive in order to provide feedback and to increase interest and motivation. Xbox Kinect virtual gaming system is more fun and provides motivation, and may be a preferable method of treatment for patients with JIA but further studies are needed to compare with the potential benefits of VBG and conventional therapy in patients with JIA.

Disclosure of Interest: None Declared
Table 3 (abstract P389).

Scores of outcome measures pre and post-treatment

 

Pre-treatment

Post-treatment

p

 

Pre-treatment

Post-treatment

p

Mean ± SD

Mean ± SD

Mean ± SD

Mean ± SD

R

L

R

L

R/L

CHAQ-total

1.30 ± 0.66

0.30 ± 0.30

0.000

Hand Grip (kg)

15.68 ± 10.50

11.13 ± 9.50

23.19 ± 10.78

20.49 ± 10.40

0.000 / 0.000

DHI

20.35 ± 11.90

0 ± 0

0.000

Lateral Pinch Grip (kg)

6.19 ± 3.11

5.39 ± 3.16

8.37 ± 3.64

7.35 ± 3.30

0.000 / 0.000

COPM-performance

3.56 ± 1.63

8.64 ± 1.06

0.000

Tip Pinch Grip (kg)

2.14 ± 2.35

1.29 ± 1.29

3.72 ± 2.0

3.07 ± 1.81

0.003 / 0.000

COPM-satisfaction

1.50 ± 0.63

9.42 ± 0.77

0.000

Palmar Pinch Grip (kg)

3.35 ± 2.34

2.90 ± 2.94

6.43 ± 3.25

5.99 ± 3.16

0.000 / 0.000

NRS-fatigue

6.30 ± 1.57

2.35 ± 1.46

0.000

 

P390 The truth, the whole truth and nothing but the truth: methotrexate and compliance; the JIA patient perspective

Madeleine Rooney1, Roisin Campbell2, Catherine Wright3

1Center Experimental Medicine, QUEENS UNIVERSITY BELFAST, Belfast, United Kingdom; 2Pharmacy, Belfast Hospital Trust, Belfast, United Kingdom; 3Arthritis Care, Belfast, United Kingdom
Presenting author: Roisin Campbell

Introduction: Methotrexate is the first-choice disease-modifying drug (DMARD) for the treatment of JIA. It is accepted as an effective drug that induces remission in more than 70% of patients. Serious adverse effects are infrequent and usually transient due to rigid monitoring guidelines. However the impact on the quality of a child’s and their family lives has yet to be adequately researched.

Objectives: The aim of this research was to investigate the JIA patient’s perspective and tolerance and compliance of oral or parental Methotrexate in accordance with BSPAR guidelines.

Methods: Children between 10-17 years of age with a diagnosis of JIA (all sub-types included) attending the Paediatric Rheumatology Day Ward were asked to complete an adapted MISS (Methotrexate Intolerance Severity Score) questionnaire during their routine medicines reconciliation and compliance interview, carried out by the paediatric rheumatology pharmacist. A total of 15 questionnaires were completed.

Arthritis Care, host activity weekends for children between 10 – 17 years of age with a diagnosis of JIA, during one such weekend they devoted a group session to discussing and completing the adapted MISS questionnaire. To date a total of 15 questionnaires have been completed in the two different settings and with two interviewees of differing provenance.

Results: Results

Venue

MISS score range

MISS average score

Rheumatology Day Ward

0 – 8

3.6

Activity Weekend

4 - 32

19

The children were asked “choose one word to describe how you feel about taking Methotrexate”.

Children attending Rheumatology Day Ward examples – Fine, Ok, Necessary, Annoying.

Children at the Activity Weekend examples – Evil, Depressed, Stressed, Sore, Terrible, Hate.

Conclusion: The MISS questionnaire is a well -designed validated tool widely used by Paediatric Rheumatology teams to assess Methotrexate tolerance in JIA patients. Anticipatory nausea and behavioural effects of Methotrexate are not clinically evident during physical assessment but may be detected by the MISS questionnaire. However this research poses the question how much value can we place upon the results we receive if they are so profoundly affected by the environment in which they are completed and the person who is requesting the information.

The narrow score range and low average MISS score obtained when completed with the rheumatology pharmacist creates the impression that Methotrexate is a well-tolerated drug which young patients find at worst “annoying”. Is it safe to dismiss this as the Hawthorne effect? (or should we say young patients simply trying to please us?).

Yet the dramatically higher average score and broad score range obtained at the Activity weekend indicate that Methotrexate has a significant detrimental effect on young patients creating a greatly anticipated stressful event every week.

Arthritis Care, activity weekends create an environment where young patients are free to express themselves in their own language and allow their anger and emotions to be expressed away from reproachful and anxious parents.

These findings challenge the validity of this questionnaire if it is so dependent on the environment and the questioner. Our preliminary finding demonstrate the need for further research in this field and highlight the already underestimated degree of morbidity and non-compliance associated with MTX in children with rheumatic diseases.

Disclosure of Interest: None Declared

P391 Fatigue in patients with juvenile idiopathic arthritis: relationship to perceived health, physical health, self-efficacy, and participation

Wineke Armbrust1, Otto Lelieveld2, Jolanda Tuinstra3, Nico Wulffraat4, Joyce Bos2, Jeanette Cappon5, Marion van Rossum5, Mariët Hagedoorn6

1Beatrix Children’s Hospital, Department of Pediatric Rheumatology and immunology, Groningen, Netherlands; 2Center for Rehabilitation, Groningen, Netherlands; 3Department of Health Sciences, University of Groningen, University Medical Center Groningen, Groningen, Netherlands; 4Department of Pediatric Immunology, University Medical Center Utrecht, Wilhelmina Children’s Hospital, Utrecht, Netherlands; 5location: Dr. Jan van Breemenstraat, Reade, Center for Rehabilitation and Rheumatology, Amsterdam, Netherlands; 6Department of Health Sciences, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
Presenting author: Wineke Armbrust

Introduction: Fatigue is present in 60-75% of patients with JIA. Fatigue is multidimensional, meaning that it can be physical or mental in its manifestation and cause. The causes and consequences of fatigue are not well known.

Objectives: To assess the presence and severity of fatigue in patients with JIA, including factors presumed associated with fatigue (e.g., disease activity, disability, pain, physical activity, exercise capacity, and self-efficacy), and whether fatigue is related to participation in physical education classes, school attendance, and sports frequency.

Methods: Eighty patients with JIA (age 8-13) were included. Primary outcome measurements were fatigue (multi dimensional Pediatric-Quality-of-Life-Inventory (PedsQl)-Fatigue-scale) and energy level (uni dimensional VAS scale (0-10; 0 meaning respectively lowest an highest energy)). Predictors of fatigue were disease activity (PGAS (0-10 cm)), disability(CHAQ), physical activity (accelerometer), exercise capacity (Bruce test) and self-efficacy (Childhood Arthritis Self-Efficacy Scale). Consequences of fatigue were school attendance and participation to physical education class and sports using a questionnaire.

Results: Median age was 9.8 years [8.7; 11.0], disease duration was 2.95 years [1.22; 6.19], disease activity was .03 [.00;.90] and 60 patients were on medication. Sixty percent of patients with JIA suffer from daily low-energy levels; 27% suffer from very low-energy levels more than half the week. Fatigue measured with the PEDsQL was higher compared to the norm-population (77.5 compared to 80.5). High fatigue was correlated with low energy levels (P < .01). Patients who reported higher levels of fatigue showed higher disability (P < .01), higher pain (p < .01), lower exercise capacity p = .05), lower physical activity (<.01), and lower self-efficacy scores (P < .01). Disability (p = .01) and low self-efficacy (p = .04) were main predictors of fatigue in a multivariate model. Self-efficacy was a predictor of fatigue but did not act as moderator. Low energy levels were correlated with high disability (p < .01), pain (p = .01), a lower PAL (p < .01), and being on medication (p = .03). Low energy levels were best predicted by disability (p < .01)and low physical activity (p < .01) in a multidimensional model. Fatigue was a predictor for sports frequency (p = .01) but not for school attendance (p = .08).

Conclusion: Fatigue is present in more than half of the patients with JIA. Uni- and multidimensional measurements can be used to determine the level of fatigue. However, related factors were different for both measurements as single correlations as well as in a prediction model, indicating that they are not interchangeable. Interventions aimed at reducing perceived disability, stimulating physical activity, and enhancing self-efficacy might reduce fatigue and thereby enhance participation.

Trial registration identifying number: R@W Trial number ISRCTN92733069

Disclosure of Interest: None Declared
Table 4 (abstract P391).

Patient characteristics and outcome measurements of 80 (52 female) patients

Characteristic

M N

[IQR] / (%)

Fatigue

77.8

[68.1; 86.1]

Daily energy level (cm)

6.00

[4.92; 7.49]

Exercise capacity (seconds)

592

[489; 638]

Physical activity level

1.53

[1.46; 1.60]

Full participation physical education class

53

(66)

Full school attendance

56

(70)

Sports frequency/week

1

[.25; 3.00]

Self-efficacy symptom

3.75

[2.50; 6.72]

Self-efficacy Activity

6.88

[4.38; 9.38]

M Median, IQR Inter Quartile Range, N Number, yr years, cm centimeters

P392 Nurses’ experiences of meeting children afraid of needlestick

Anna Vermé1, Ylva Lampela2

1Pediatric Rheumathology, Karolinska, Sweden; 2Youth clinic, Södersjukhuset, Stockholm, Sweden
Presenting author: Anna Vermé

Introduction: Regardless where nurses work they meet both adults and children who are scared of needle stick. Both the empirical and the literature reveals that the meeting with the children who are afraid of needle stick can be challenging and difficult to manage. According to competence description to pediatric nurses work to ensure that blood tests, examinations and treatments are tailored to the individual child. When meeting with children who are afraid of needle stick and meeting their families, it is important that the nurse takes into account several factors: the child’s age, developmental stage, previous experience and the situation the child is in. The parents’ past experiences and feelings about needle stick can affect how the child reacts to different procedures.

Objectives: To describe nurses’ experiences of meeting children scared of needle stick and meeting their families.

Methods: The study was qualitative and the collected material was analyzed using qualitative content analysis. Five nurses who worked in child care 3-42 years participated in the study.

Results: The results were reported as three categories and eleven subcategories. The categories were: Challenging encounters with children who are afraid of needle stick, Cooperation and Child different reactions. The meeting was affected by various things such as the nurse’s own experience of meeting children who are afraid of needle stick, the circumstances and the nurse’s ability to build trust and confidence. A working relationship with colleagues, children and parents was crucial so the situation would be as good as possible.

Conclusion: Fear of needle stick is a common phenomenon, especially in pediatrics. Sharing experiences and gaining knowledge on this subject make it easier for nurses who feel insecure about meeting children who are afraid of needle stick and their families. We also hope that this work will lead to discussions on this topic in the working groups who in their daily work meet children who are afraid of needle stick.

Disclosure of Interest: None Declared

P393 The first transition clinic from pediatric to adult rheumatology in Turkey

Ayse Huri Ozdogan1, S Ugurlu1, K Barut2, A Androvic2, O Kasapçopu3

1Department of Adult Rheumatology, Cerrahpasa Medical Faculty, İstanbul, Turkey; 2Department of Pediatric Rheumatology, Cerrahpasa Medical Faculty, İstanbul, Turkey; 3Department of Pediatric Rheumatology, Cerrahpasa Medical Faculty, İstanbul, Turkey
Presenting author: Ayse Huri Ozdogan

Introduction: -

Objectives: To assess the outcome of the first transition clinic from pediatric to adult rheumatology in İstanbul, Turkey

Methods: A transition outpatient clinic has been started in 2014 in Cerrahpaşa Medical Faculty with the contribution of 2 adult and 4 pediatric rheumatologists who get together once every 2 to 3 months. Patients who have been followed in the pediatric rheumatology clinic were asked to attend the transition OPC after the age of 18. These patients are seen by all the attending physicians initially in the pediatric clinic. A standardized form is filled for all which includes information on diseases history, last physical and laboratory examinations, and treatment. The next appointment is given for the adult rheumatology clinic where they are seen by one of the adult rheumatologist who have attended the first visit. All patients seen in the transition clinic during this 2 year period were contacted to assess the follow-up and outcome.

Results: Since 2014, 82 patients (52 F, 30 M) were seen in the transition OPC. The mean age was 21 years (18-24). The diagnoses of the patients were FMF in 44, JIA in 28, BD in 3, SLE in 2, vasculitis 2 and others 3. Fifty six patients were regularly attending the adult rheumatology clinic (68%), whereas 3 were being followed in another center, 9 never attended to a visit in the adult clinic and 14 were lost to follow up. The attendance rate was somewhat higher in girls compared to boys (71% vs 60%). Their main complaints were the crowdness of the adult clinics (8 patients) and insufficient attention (7 patients).

Conclusion: These are the preliminary results of the first transition clinic from pediaitric to adult rheumatology from Turkey. Compared to well established clinics from other countries like Canada, the attendance rate and the age at transition are comparable. In order to increase the attendance and the overall satisfaction of the patients the programme needs to be improved.

Disclosure of Interest: None Declared

P394 The use of a screening tool to support children and young people with lupus and their families in prioritising issues for discussion in clinic appointments

Emily Wilson1, Jody Etheridge1, Eve Smith1,2, Katie Dobson1, Sue Kemp1, Michael W. Beresford1,2

1Department of Paediatric Rheumatology and Psychology, Alder Hey Children’s NHS Foundation Trust, Liverpool, UK; 2Department of Women’s and Children’s Health, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom
Presenting author: Emily Wilson

Introduction: Patients attending the UK’s only ‘Centre of Excellence for Childhood Lupus’ at Alder Hey Children’s Hospital, Liverpool, routinely attend clinic appointments every three months. During these appointments there is pressure for clinicians to review complex medical presentations and treatment in a timely manner. As a service we recognise the importance of holistic, multi-disciplinary care and the need to consider the priorities of patients and their families in relation to the illness and its management.

The challenges faced by patients in asking questions and asserting influence over a medial consultation are widely acknowledged and so a ‘screening tool’ was developed to facilitate this process.

Objectives: To develop a screening tool to facilitate conversations with young people with lupus and their families in order to identify areas of concern that they would like to discuss within or outside of a given clinic appointment.

Methods: Immediately prior to each clinic appointment, patients with juvenile-onset systemic lupus erythematosus (‘lupus’) and the parent or guardian accompanying them were asked to complete a bespoke screening questionnaire.

The tool was developed through detailed consultation with patients, parents and multi-disciplinary team members (nursing, occupational therapy, physiotherapy and psychology). Several versions were developed to enable the tool to be utilised by children of different ages as well as their parents. Parents of all children were encouraged to identify issues that concerned them about their child but also areas in which they felt they were struggling themselves regarding their child’s condition.

The completed tools were brought into the consultation for consideration by the attending clinicians and team. Where appropriate, the screening questionnaires influenced the topics of conversation within the appointment, otherwise, plans were made to contact the multi-disciplinary team separately.

The completed questionnaires formed part of the patients’ case notes. Data were also collated and used to inform wider service development within the lupus service.

Results: Completed screening tools were reviewed over a 10-month period. 36 were completed (19 young people, 17 parents).

Amongst the young people, the most frequently reported concerns were: fatigue (81%), appearance (58%), pain (53%) and exercise (53%). Parents were most concerned for their children regarding: fatigue (65%), pain (65%), emotions (59%), sleep (59%) and support from school or college (53%). In terms of areas in which parents were concerned about themselves, most frequently reported were: concerns regarding the future (82%), feeling upset regarding their child’s condition (59%), supporting their child (59%) and having adequate support from others (59%).

Conclusion: The questionnaires have received positive feedback from patients, parents and staff in terms of their ease of completion and their utility in terms of highlighting issues for further discussion either within clinic or otherwise. They have also helped especially to normalise the role of psychological well-being in the management of lupus.

The data have been used to influence service development including:
  • Development of a ‘health passport’ document to facilitate communication between family, hospital and school

  • Development of a workshop for patients with lupus and their families focussing on fatigue management

  • Development of a future workshop for patients and their families focussing on transition, the future and becoming a young adult with lupus.

Disclosure of Interest: None Declared

P395 “On the journey diagnosed with juvenile idiopathic arthritis (JIA)”– a bag with relevant information that generates trust

AnnaCarin Horne, Karin Palmblad, Malin Höglund

Pediatric rheumathology, Karolinska Hospital, Stockholm, Sweden
Presenting author: Malin Höglund

Introduction: When a child is diagnosed with juvenile idiopathic arthritis (JIA) a lot of questions evolve among family members and the social surrounding. The initial information provided by the doctor may be overwhelming and it may be hard to take in all the details. Many seek additional information from literature or from the internet but feel overwhelmed by all the different information available.

Objectives: To provide parents and children with correct information included in an information bag and to evaluate the response on this initiative.

Methods: “On the journey diagnosed with JIA” is a information bag created in collaboration between the pediatric rheumatology unit at Astrid Lindgren Children’s Hospital, the Swedish Rheumatism Association, Young Rheumatic Patients, and AbbVie Sweden. The information bag contains informative brochures, lists of adequate web sites with balanced information, and information from parent and patients associations. In addition, a calendar is provided to encourage self-management of the disease. All information is carefully checked by the clinic and based on medically correct information. The bag is a compliment to the information that the family receives at the clinic; a way for the patient and family to continue the journey at their own pace back home. The pilot project consisted of 20 bags that were handed out at the pediatric rheumatology clinic at Astrid Lindgren Children’s Hospital to children newly diagnosed with JIA. The children were between 2-17 years old. After a month an assistant nurse at the clinic contacted the family by mail or by phone to evaluate how the bag had been used. The families were asked whether the information added value and if they found answers to any questions that arose after the doctor’s visit.

Results: All of the 20 families were positive to the bag and its content. They found that the information helped them to explain about JIA to people around them, in school or preschool, or on activities after schools. The content of the bag had increased understanding and knowledge of what the disease means for the child in everyday life. The material had also helped the parents to get a good basic information so that they then had a better perspective on all the information online and in social media.

Conclusion: The information bag has been an appreciated complement to the information given at the hospital and will now be implemented as a tool provided to children diagnosed with JIA at Astrid Lindgren Children’s Hospital.

Disclosure of Interest: A. Horne: None Declared, K. Palmblad: None Declared, M. Höglund Grant / Research Support from: Travel grant from AbbVie

P396 Psychological peculiarities in patients with cryopyrin-associated periodic syndromes and systemic juvenile idiopathic arthritis

Natalia Stepanenko, Svetlana Salugina, Evgeny Fedorov, Irina Nikishina, Maria Kaleda

Nasonova Research Institute of Rheumatology, Moscow, Russian Federation
Presenting author: Natalia Stepanenko

Introduction: Cryopyrin-associated periodic syndromes (CAPS) and systemic juvenile idiopathic arthritis (sJIA) formally belong to the same group of autoinflammatory diseases (AID) and have a number of clinical similarities, and approaches to therapy. At the same time CAPS (cryopyrin-associated periodic syndromes) refer to AID group, associated with NLRP3 gene mutation with multiorgan damage and involvement of the central nervous system (CNS) that can result in the development of cognitive functions and determine certain psychological peculiarities.

Objectives: to carry out a fundamental psychological testing aimed at identifying peculiarities of the emotional sphere and cognitive deficits in patients with CAPS and systemic juvenile idiopathic arthritis (sJIA).

Methods: A detailed psychological examination was performed under a single diagnostic plan: 12 patients consecutively admitted to the clinic: 6 patients with CAPS (4 - MWS, 2 - CINCA-NOMID), aged from 9 to 17 years, 4 males, 2 females; average disease duration of 9 years and 6 patients with sJIA aged from 7 to 16 years, 4 males, 2 females; average disease duration of 7 years.

Methodology: clinical interview, 8-Luscher color test, Spielberger - Khanin test to identify the level of anxiety, CMAS, methods of pathodiagnostic survey.

Results: CAPS patients showed a reduction of attention functions in a part of concentration and distribution (by 66.7%), insufficient attention efficacy (increase in the time consumed in vigorous activities) in 83.3%, the low-speed entry (50%), reduced level of performance efficiency in 83.3%. Irregularities in the process of memorization, short-term memory (16%) and storage of data (long-term memory, LTM) were observed in a half. The concreteness of ideation which did not meet the age norm and reduced level of factuality were observed (50%).

An increased level of personal anxiety (66.7%), dissatisfaction with their appearance (50%), difficulty in communicating with agemates (50%), reduced level of social adaptation were observed in the emotional sphere (7%). Patients with sJIA showed the reduction of focus functions - in a part of concentration (50%), the distribution of attention (16.7%), insufficient attention efficacy (33.3%), and low speed entry (16.7%). Abnormalities in the short-term memory link were observed in 33.3%, long-term – in 16.7%. The thinking processes did not show reducing level of factuality in 33.3% and specificity of ideation inconsistent with age norm. In the emotional sphere there were revealed an increased level of personal anxiety (50%), difficulty in communicating with agemates (83.3%), dissatisfaction with appearance and reduced level of social adaptation - in a half.

Conclusion: Differences in the psychological status of patients with CAPS and sJIA were revealed. CAPS patients showed the most dramatic abnormalities in the cognitive functioning - in all functions of attention, memory and thinking, which may be indicative of the major organ damage. Disturbances in the emotional sphere are dominated in patients with sJIA (difficulty in communicating with agemates and low social adaptation). Dissatisfaction with their own appearance is equally characteristic of both groups. Clinical and psychological status of patients with CAPS and sJIA requires further study at a greater volume of material to identify sustainable patterns of regularities, assess the impact of targeted therapies and develop psychocorrective programs for cognitive and emotional disorders.

Disclosure of Interest: None Declared

P397 The perceptions of patients with juvenile idiopathic arthritis about “having a rheumatic disease” and “doing exercise” via metaphors

Nilay Arman1, Ela Tarakci1, Kenan Barut2, Amra Adrovic2, Sezgin Sahin2, Ozgur Kasapcopur2

1Faculty of Health Sciences, Division of Physiotherapy and Rehabilitaiton, Medical Faculty of Cerrahpasa, Istanbul University, Istanbul, Turkey; 2Department of Pediatric Rheumatology, Medical Faculty of Cerrahpasa, Istanbul University, Istanbul, Turkey
Presenting author: Nilay Arman

Introduction: A metaphor is considered the strongest device for an individual to comprehend and explain a hypothetical or an abstract, complex fact in a high level. Metaphors shape our perceptions, beliefs, attitudes and thoughts and they may influence the actions we take in the real world. Metaphors are among the most powerful cognitive tools to understand children with chronic disease. Juvenile idiopathic arthritis (JIA) affects social, emotional, and cognitive development of children, because it is a chronic disease in childhood. Understanding the perceptions about their disease helps to accomplish cognitive barriers of the rehabilitation in children. However, in the literature, no study has been found about perceptions about their disease in children with arthritis.

Objectives: The aim of the study was to understand the perceptions of patients with JIA about having a rheumatic disease and doing exercise via metaphors.

Methods: The population of the study included 20 (16 girls and 4 boys) patients with JIA. Each patient with JIA was asked to complete the blanks in the sentences, “Having a rheumatic disease is like a/an.....................because..................” and “Doing exercise is like a/an.....................because..................” The data were analysed using qualitative (content analysis) method.

Results: The mean age of the patients was 11.35 ± 2.20 (age range 8-18). According to the findings of the study, patients with JIA identified 24 metaphors (15 metaphors for “having a rheumatic disease”, 9 metaphors for “doing exercise”) in total. The metaphors for “having a rheumatic disease” developed by patients with JIA were analysed and interpreted at two categories: animals and objects. While the animal metaphors indicated three characteristics as “slow-moving”, “coping difficult” and “frightening” for “having a rheumatic disease”. The object metaphors indicated five characteristics as “Chaotic”,“ Stiffness”, “Formidable”, “Puffy” and “Uncertainty” for it. The metaphors for “doing exercise” indicated three characteristics as “Beneficial for Health”, “Tedious” and “Hard”.

Conclusion: As a result, the metaphors can be used as a strong research tool in understanding, revealing and explaining the cognitive images of patients with JIA about their disease and doing exercise. This study showed that patients with JIA prefered different metaphors for explaining their perceptions of disease and exercise but the reasons were similar. According to their metaphors, “Having a rheumatic disease” is similar to solving a difficult problem, “Doing exercise” is necessary for getting better but it requires the responsibility.

Disclosure of Interest: None Declared

P398 The effects of kinect based dance therapy on lower extremity functions of a patient with oligo articular jia: case report

Nilay Arman1, Ela Tarakci1, Ozgur Kasapcopur2

1Faculty of Health Sciences, Division of Physiotherapy and Rehabilitaiton, Istanbul University, Istanbul, Turkey; 2Department of Pediatric Rheumatology, Medical Faculty of Cerrahpasa, Istanbul University, Istanbul, Turkey
Presenting author: Nilay Arman

Introduction: Juvenile idiopathic arthritis (JIA) is characterized by joint pain, swelling and a limitation of movement caused by inflammation. Subsequent joint damage can lead to disability and activity restriction. In the literature, some evidence reports that patients with JIA are physically less active when compared with healthy children. Active video gaming such as Xbox 360 Kinect is a promising physical activity alternative given that children are encouraged to move whilst engaging in an activity they enjoy.

Objectives: The purpose of this case report is to describe effects of Kinect based dance therapy (KBDT) on lower extremity functions of a patient with oligo articular JIA.

Methods: The patient was 18-year-old girl with oligo articular JIA. She had left hip arthritis. So, she had dissatisfaction about her appearance during the walking because of limitation of hip range of motion and increased anterior pelvic tilt. Also, she complained of pain and fatigue at rest and during the walking. Pain during rest and activity was assessed using a 0-to-10 Numeric Rating Scale (NRS). Fatigue severity was also measured by NRS with higher scores indicating high fatigue, Active and passive Range of motion (ROM) of lower extremity was measured using a standard goniometer. Muscular strength was estimated at maximal isometric force for the muscles of the lower extremities by using a portable digital handheld dynamometer. Static balance was measured by using the Functional Reach Test (FRT) and Lateral Reach Test (LRT). Functional ability was assessed by Childhood Health Assessment Questionnaire (CHAQ). Functional capacity was assessed by 6 minutes walking test (6MWT). The total distance was recorded during walking for 6 minutes. Our KBDT program was composed of “Dance Central 2”. Dance Central 2 is a rhythm game developed exclusively for the Xbox 360 Kinect. During the game, players perform given dance moves similar to a mirror, which are tracked by the Kinect. The more accurately the player performs the move, the more points he/she scores. Higher difficulties increase move complexity. 4-5 different dances that included weight bearing and balance actions for lower extremity were selected for our KBDT program. She completed 8 weeks (3 times in a week) of her specific KBDT program.

Results: Pain scores of NRS-rest and NRS-activity and NRS-fatigue were 5 point before the treatment. After treatment NRS-activity was 1 point, both NRS-rest and NRS-fatigue were 0 point, Active ROM of Hip flexion was 70, hip extension 20, abduction 20, internal rotation 30, and external rotation was 30 degrees before the treatment. After the treatment, Active ROM hip flexion was 90, hip extension 35, abduction 45, internal rotation 45, and external rotation was 40 degrees. FRT scores of pre and post-treatment were 36 and 45 cm respectively. LRT scores of pre and post-treatment were 22 and 30.5 cm respectively. Pre and post-treatment scores of 6MWT were 406 and 522 meters, respectively. CHAQ total, CHAQ-walking, CHAQ- activities scores were 1.12, 2 and 2 before the treatment respectively. All CHAQ scores dropped to 0 after the treatment. Also, all muscle strength scores of both lower extremities were improved after the treatment.

Conclusion: In this study, we found clinically significant improvements of lower extremity functions, functional capacity, pain and fatigue for a patient with oligo articular JIA. This indicates that repeated actions with visual and auditory feedback provided by Kinect-based virtual reality may increase patient focus and motivation and thereby improving the quality of movements. This case report describes a novel approach to rehabilitation of patients with JIA but further investigation into the effectiveness of KBDT for children with JIA is warranted.

Disclosure of Interest: None Declared

P399 AJIados, a francophone patient association for adolescents and young adults with JIA

Laurence Toumoulin1, Johnny Frossard1, Stephanie Archimbaut1, Anne Paitier1, Rolande Guastalli1, Severine Guillaume Czitrom2

1AJIADOS, Le Kremlin Bicetre Cedex, France; 2Service de Medecine des Adolescents, CHU DE BICETRE, Le Kremlin Bicetre Cedex, France
Presenting author: Severine Guillaume Czitrom

Introduction: Adolescent departments in France are usually devoted to the care of mental health disorders. Yet, there is a huge need for chronic organ-diseases care, focused on adolescents specifically. Adolescence is often a difficult period but chronic organ-disease as JIA, may amplify the troubles, thus requiring a particular effort.

Objectives: Improve the daily life of adolescents and young adults with JIA with practical actions.

Methods: We chose to start with the improvement of patient education in adolescents and young adults having juvenile idiopathic arthritis in France. We created the first patient association “AJIados” involved in adolescent/ young adults in France.

Results: AJIados supports different actions : (i) collective meetings between the young people, between their parents/families, between them and caregivers. We organize 4 times a year, collective assemblies on various themes, generally chosen by the patients; all together, we create small documents to help solving practical problems (school, physiotherapy, living with a uveitis…) and distribute them across our country as well as in the Maghreb. We also send to interested people our newsletter every 3 months. Our efforts have had a great success with always more adolescents and families; (ii) we organized nice encounters with key figures in french sport and music, who are vectors of hope and will go on this way; (iii) we created a web-site (www.ajiado.org) to help patients in their daily life: there are 5 modules (a forum, a tool box, news on research as well as surveys, an agenda with referral caregivers that is built and improved by the patients themselves and a growing part devoted to patient education).

Conclusion: Presently, the success is « au rendez-vous » with the adolescents and young adults, justifying to pursue all our efforts.

Disclosure of Interest: None Declared

P400 Health-related quality of life in Thai children with juvenile idiopathic arthritis

Sirirat Charuvanij, Chollada Chaiyadech

Department of Pediatrics, Siriraj Hospital, Mahidol University, Bangkok, Thailand
Presenting author: Sirirat Charuvanij

Introduction: Juvenile idiopathic arthritis (JIA) is a chronic disease resulting in pain and disability. There has been no study focusing on health-related quality of life (HRQOL) among Thai children with JIA.

Objectives: To describe HRQOL and determine factors influencing the HRQOL of Thai JIA patients.

Methods: A cross-sectional descriptive study was conducted in JIA patients and their parents followed up at a pediatric rheumatology clinic, Siriraj Hospital, Bangkok, Thailand. HRQOL was measured by using the Pediatrics Quality of Life (PedsQL) 4.0 generic core scale, Thai version, during January 2015-December 2015. Suboptimal HRQOL is defined as a PedsQL total mean score of < 78.6.1

Results: Sixty-five patients and their parents were included. Thirty-three patients were female (50.8%). Mean age of patients was 9.6 ± 3.9 years and the median of duration of the disease was 1.1 (0.0-9.43) years. Systemic JIA was the most common JIA subtype (40%). The median of Juvenile Arthritis Disease Activity Score-71 (JADAS-71) was 7 (0-27.2). Forty-nine (75.4%) patients were having active disease. The median of total PedsQL score reported by patients was 80.6 (36.9, 100); physical functioning score 78.1 (34.4, 100), emotional functioning score 85 (35, 100), social functioning score 90 (30, 100), school functioning score 80 (25, 100). There were 25 (45.4%) patients classified as having suboptimal HRQOL. The median of total PedsQL scores reported by parents was 71.7 (33.3, 100); physical functioning 75.0 (0, 100), emotional functioning 80 (40, 100), social functioning 85 (25, 100) and school functioning 65 (25, 100). Suboptimal HRQOL was identified in 39 (60%) patients based on parent reports. There was positive correlation between total PedsQL scores reported by children and their parents (rs = 0.662). There were no statistically significant factors associated with suboptimal HRQOL reported by children. Non- oligoarthritis; OR 3.8 (95%CI: 1.0, 14.6), joint pain; OR 4.1 (95%CI: 1.4, 11.5), limping; OR 4.7 (95%CI: 1.2, 18.7), wrist arthritis; OR 8.6 (95%CI: 1.0, 72.1), elevated erythrocyte sedimentation rate: OR 2.8 (95%CI: 1.0, 7.9), elevated C- reactive protein: OR 3.2 (95%CI: 1.1, 9.2), active disease; OR 4.9 (95%CI: 1.2, 16.8), high disease activity (JADAS-71 ≥ 10.5); OR 12.6 (95%CI: 2.6, 60.9) and oral steroid use; OR 3.2 (95%CI: 1.0, 10.3) were associated with suboptimal HRQOL reported by parents. However, only high disease activity influenced on the suboptimal HRQOL by multiple logistic regression analysis; adjusted OR 20.2 (95%CI: 1.4, 291.7).

Conclusion: Almost half of Thai JIA patients had suboptimal HRQOL. The physical functioning score was the lowest aspect. The factor associated with suboptimal HRQOL reported by parents was high disease activity.

Trial registration identifying number: N/A

Disclosure of Interest: None Declared

P401 Attitude surveys of pediatric and non-pediatric rheumatologists regarding transition of care

Takako Miyamae, Hisashi Yamanaka

Institute of Rheumatology, Tokyo Women’s Medical University, Tokyo, Japan
Presenting author: Takako Miyamae

Introduction: The goal of planned adolescent healthcare transition procedures is to optimize the functioning and well-being of all young people, including those with special healthcare needs. In this regard, the transitioning of young people with childhood-onset rheumatic diseases to adult healthcare is increasingly important, as many of these patients might continue to have active disease or considerable sequelae well into their adult lives.

Objectives: Attitude surveys of pediatric and non-pediatric rheumatologists about transition procedures were performed.

Methods: Overall, 28 operation commissioners of the Pediatric Rheumatology Association of Japan and 37 non-pediatric rheumatologists belonging to the Institute of Rheumatology, Tokyo Women’s Medical University participated in the surveys. Experiences of adult patients with childhood-onset rheumatic diseases, ideal medical care for adults, and factors contributing to challenges associated with the transition to adult care were examined.

Results: In total, 19% of pediatric rheumatologists still see their patients as adults, whereas 62% of non-pediatric rheumatologist have experiences with childhood-onset patients. Transition to non-pediatric medical care was supported by 81% and 95% of pediatric and non-pediatric rheumatologists, respectively. A preparatory step of visiting both a pediatrician and a non-pediatrician is recommended by some physicians. Two major factors, incomplete facilitation of personal independence to make the transition to adult care and the sharing of pediatric rheumatology knowledge and skills with non-pediatric rheumatologists, particularly with respect to autoinflammatory disorders, were identified as contributing to challenges associated with successful transition. Overall, 33 of 37 (89%) non-pediatric rheumatologists required education about childhood-onset rheumatic diseases.

Conclusion: Key elements for effective transitions include the development of education programs to help pediatric patients manage their illness independently and to share pediatric rheumatology knowledge within the non-pediatric rheumatology community.

Disclosure of Interest: None Declared

Poster Session: New diseases

P402 Interstitial lung disease with TMEM173 mutations is associated with a strong IFN-stimulated protein induction in situ

Cecile Picard1,2, Guillaume Thouvenin3, Caroline Kannengiesser4, Jean-Christophe Dubus5, Nadia Jeremiah6, Frédéric Rieux-Laucat6, Bruno Crestani7, Véronique Secq8, Christelle Ménard9, Martine Reynaud-Gaubert10, Françoise Thivolet-Bejui1, Philippe Reix11, Alexandre Belot2,12

1Pathology, Hospices civils de Lyon, Hôpital Femme-Mère-Enfant, Lyon, France; 2Inserm U1111, Lyon, France; 3Pediatric Pulmonology, Assistance publique-Hôpitaux de Paris, Paris, France; 4Genetic, Assistance publique-Hôpitaux de Paris, Paris, France; 5Assistance publique-Hôpitaux de Marseille, Marseille, France; 6Institut Imagine, hôpital Necker, Paris, France; 7INSERM, Unité 1152, Université de Paris Diderot, Paris, France; 8Pathology, Assistance publique-Hôpitaux de Marseille, Hôpital de la Timone, Marseille, France; 9Pediatric Pulmonology, Assistance publique-Hôpitaux de Paris, hôpital Armand Trousseau, Paris, France; 10Pulmonology Department, CHU Nord, Assistance publique-Hôpitaux de Marseille, Marseille, France; 11Pediatric Pulmonology, Nephrology and Dermatology, Hospices civils de Lyon, Hôpital Femme-Mère-Enfant, Lyon, France; 12Pediatric Rheumatology, Nephrology and Dermatology, Hospices civils de Lyon, Hôpital Femme-Mère-Enfant, Lyon, France
Presenting author: Cecile Picard

Introduction: Inherited inflammatory syndromes related to the transmembrane protein 173 (TMEM173) gene gain-of-function mutation were described so far by the triad early-onset systemic inflammation, marked cutaneous vasculopathy and pulmonary fibrosis, with variable clinical expression even in familial cases (1,2). Recently, we have reported that TMEM173 mutations can be associated to inaugural lung interstitial disease (ILD) with late-onset systemic symptoms (3).

Objectives: To investigate pathological features of the lung disease of STING-associated ILD.

Methods: Clinical and biological data, chest HRCT and lung biopsies were collected retrospectively in 2 children and one adult with TMEM173 mutation. Paraffine-embedded tissues were stained for IFNa (clone MMHA-2), CXCL10, IFNAR1 and MxA and compared to healthy controls and non genetic ILD (systemic sclerosis).

Results: Initial presentation was related to symptoms suggestive of pulmonary fibrosis for all patients. Few systemic features appeared later on life and skin damage was mild, delaying the evocation of a systemic disease. Classical causes of familial interstitial lung disease were all excluded genetically and all three patients had an already known genetic variant of TMEM173. Cystic lesions on HRCT predominated in upper lobes with relative preservation of lower lobes. Immunohistological analysis showed fibrosis with destruction of alveolar architecture associated with follicular lymphoid infiltrates (neolymphogenesis) containing a majority of B cells CD20+. The overall architecture differs from other common ILD. Intra-alveolar infiltrate was made of macrophages and cholesterol crystal clefts was noticed for the 3 patients. Interestingly, there was no evidence for vasculopathy or microangiopathy. By contrast, a huge induction of IFN-related protein in the lung section of patients was observed as compared with controls. A strong interferon signature was found in all three cases.

Conclusion: The diagnosis of STING-related lung fibrosis should be considered as a differential diagnosis of ILD in children even with no or mild systemic features. The pathological study may represent a useful procedure to support the diagnosis.

Written informed consent were obtained from all the participants of the study.

References

1. Liu Y, Jesus AA, Marrero B, Yang D, Ramsey SE, Montealegre Sanchez GA, et al. Activated STING in a vascular and pulmonary syndrome. N Engl J Med. 2014 Aug 7;371(6):507–18.

2. Crow YJ, Casanova J-L. STING-associated vasculopathy with onset in infancy--a new interferonopathy. N Engl J Med. 2014 Aug 7;371(6):568–71.

3. Picard C, Thouvenin G, Kannengiesser C, Dubus JC, Jeremiah N, Rieux-Laucat et al. Severe pulmonary fibrosis as the first manifestation of interferonopathy (TMEM173 mutation). Chest. 2016 Accepted/In Press

Disclosure of Interest: None Declared

P403 The characteristic features of the patients with deficiency of adenosine deaminase 2 (DADA2)

Ezgi Deniz Batu1, Hafize Emine Sonmez1, Abdulsamet Erden2, Ekim Z. Taskiran3, Omer Karadag2, Umut Kalyoncu2, İbrahim Oncel4, Berkan Kaplan5, Zehra Serap Arici1, Cagri Mesut Temucin5, Haluk Topaloglu4, Yelda Bilginer1, Mehmet Alikasifoglu3, Seza Ozen1

1Department of Pediatrics, Division of Rheumatology, Ankara, Turkey; 2Department of Internal Medicine, Division of Rheumatology, Ankara, Turkey; 3Department of Medical Genetics, Ankara, Turkey; 4Department of Pediatrics, Division of Neurology, Ankara, Turkey; 5Department of Neurology, Hacettepe University Faculty of Medicine, Ankara, Turkey
Presenting author: Ezgi Deniz Batu

Introduction: Deficiency of adenosine deaminase 2 (DADA2) is an autosomal recessive autoinflammatory disease resulting from a loss-of-function mutation in CERC1 gene encoding for ADA2 protein. The patients present with systemic inflammation and vasculopathy.

Objectives: We aimed to present the characteristics of the pediatric DADA2 cases.

Methods: The clinical and laboratory features of thirteen pediatric patients (8 M, 5 F), who were diagnosed with DADA2 at Hacettepe University Pediatric Rheumatology Department between 2014-2016, have been summarized. Mutations in CECR1 were detected by Sanger sequencing.

Results: Eleven patients were homozygous for G47R mutation in CECR1 gene, one was compound heterozygous for G47R and G47V while one patient was heterozygous for G47R. Seven of these patients had been followed up in our clinic with the diagnosis of polyarteritis nodosa (PAN). There was consanguinity in four cases, and two patients were siblings. The median (min-max) age at onset of the symptoms and diagnosis was 5.5 (1.4-19) and 120 (36-211) months, respectively. All patients suffered from recurrent episodes of fever with elevated acute phase reactants. Skin manifestations were as follows: livedo reticularis (n = 13), erythema nodosum (n = 4), and necrotic ulcers (n = 2). Neurological and musculoskeletal involvement was in the form of myalgia (n = 5), arthralgia (n = 10), arthritis (n = 5), stroke (n = 8), strabismus (n = 3), peripheral neuropathy (n = 6), and spinal cord atrophy (n = 1). One patient had been diagnosed with core myopathy through muscle biopsy which was thought as a co-incidental finding. Optic neuritis was detected in one patient. There was Raynaud’s phenomenon in two patients. Four patients had aneurysms in different middle-sized arteries (hepatic artery, renal artery, and superior mesenteric artery). One patient had intestinal perforation and ileostomy at the age of eight. As renal involvement, one patient had focal segmental glomerulosclerosis (collapsing variant), one mesangial proliferative glomerulonephritis (renal subcapsular hematoma after renal biopsy), and one had renal amyloidosis. There was testicular torsion in one patient. Three patients had positive antinuclear antibody while there was low levels of immunoglobulin M in two patients. Two adult patients died soon after diagnosis of DADA2. One patient was asymptomatic on only colchicine for almost 10 years. One responded to mycophenolate mofetil treatment. Rest of the patients responded well to anti- tumor necrosis factor therapy (etanercept).

Conclusion: ADA2 protein is a growth factor for endothelial cells and leukocytes and is important for stabilization of endothelial cells. For this reason, it causes autoinflammatory symptoms as well as vasculitis symptoms similar to PAN. ADA2 deficiency is a recently defined disease and the data about its phenotype increases with the introduction of new cases with different symptoms. This is the first description of spinal cord atrophy, core myopathy, and mesangial proliferative glomerulonephritis in DADA2 patients. Similar to the patients in the literature, most of our patients responded to etanercept therapy. Our cases suggest the diverse phenotype of DADA2.

Disclosure of Interest: None Declared

P404 Pyrin-associated autoinflammation with neutrophilic dermatosis (PAAND): preliminary results of a proof-of-concept trial with anakinra

Lien Van Eyck1,2, Ellen De Langhe3, Isabelle Jéru4,5, Erika Van Nieuwenhove1,2, Vasiliki Lagou2,6, Paul J. Baker7,8, Jocelyn Garcia-Perez1,2, James Dooley1,2, Lien De Somer9, Raf Sciot10, Pierre-Yves Jeandel11, Julia Ruuth-Praz4,5, Bruno Copin5, Myrna Medley-Hashim12, Andre Megarbane13, Sinisa Savic14, An Goris6, Serge Amselem4,5, Adrian Liston1,2, Seth Masters7,8, Carine Wouters1,9

1Department of Immunology and Microbiology, University of Leuven, Leuven, Belgium; 2Translational Immunology Laboratory, VIB, Leuven, Belgium; 3Department of Rheumatology, University Hospitals Leuven, Leuven, Belgium; 4Université Pierre et Marie Curie-Paris, UMR_S933, Paris, France; 5Service de Génétique et d’Embryologie médicales, Assistance Publique Hôpitaux de Paris, Hôpital Trousseau, Paris, France; 6Department of Neurosciences, University of Leuven, Leuven, Belgium; 7Inflammation division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia; 8Department of Medical Biology, University of Melbourne, Parkville, Australia; 9Department of pediatrics, University Hospitals Leuven, Leuven, Belgium; 10Department of pathology, University Hospitals Leuven, Leuven, Belgium; 11Département de Médecine Interne, Hôpital Archet 1, Nice, France; 12Department of Life and Earth Sciences, Lebanese University, Beirut, Lebanon; 13Al-Jawhara Center, Arabian Gulf University, Manama, Bahrain; 14Department of Clinical Immunology and Allergy, St James’s University Hospital, Leeds, United Kingdom
Presenting author: Lien Van Eyck

Introduction: Recently, we identified a S242R mutation in pyrin in 12 patients from a three-generation Belgian family suffering from childhood-onset recurrent episodes of severe neutrophilic dermatosis, arthralgias/myalgias and systemic inflammation. The mutation results in the loss of a 14-3-3 binding motif at phosphorylated S242, resulting in continuous pyrin-inflammasome activation and excessive IL-1β production. Because of the genetic causation by pyrin mutation and the characteristic features of systemic inflammation and dermatosis, we termed this disease pyrin-associated autoinflammation with neutrophilic dermatosis (PAAND). We found additional patients in Lebanon, France and UK, where one patient received treatment with the IL-1 receptor antagonist monoclonal antibody (mAb) anakinra leading to a resolution of symptoms and normalisation of inflammatory markers.

Objectives: To assess the efficacy of the IL-1 receptor antagonist mAb anakinra (Sobi) in controlling the clinical and biochemical consequences of constitutive activation of the pyrin inflammasome in patients with PAAND.

Methods: Three Belgian patients with the S242R pyrin mutation are treated with daily subcutaneous injections of Anakinra 100 mg for 12 weeks. Previous therapy with TNF-antagonists was stopped and concomitant immunosuppressive treatment was limited to low-dose corticosteroids. Clinical cutaneous, articular/muscular manifestations and inflammatory markers are assessed at baseline, and after 2, 4, 8 and 12 weeks. In addition presence of cytokines and activated caspase1 as well as inflammasome activation in vitro are assessed at baseline, 4 and 12 weeks.

Results: At baseline, all three patients manifested neutrophilic dermatosis in the form of severe cystic acne and sterile abscesses, diffuse myalgias and arthralgias, fatigue and night sweats, and abdominal pain associated with diarrhea. Inflammatory markers were increased and mild anemia was present.

At the time of writing, i.e. two weeks after the start of anakinra treatment inflammatory markers were normalized in all three patients. All patients showed manifest improvement of the cutaneous manifestations, reduction of the gastro-intestinal pain with normalization of the stools and a reduction of the musculoskeletal pain. Night sweats had disappeared, but fatigue was still present.

Conclusion: PAAND is a new autosomal dominant autoinflammatory disease caused by a specific S242R mutation in MEFV leading to constitutive activation of the pyrin-inflammasome. The clinical phenotype is dominated by severe neutrophilic dermatosis and systemic inflammation. Treatment with Anakinra resulted in suppression of clinical manifestations and control of inflammatory markers, endorsing the key pathogenic role of IL-1 in PAAND.

Disclosure of Interest: None Declared

P405 A fourteen-year-old girl with immunoglobulin G4-related disease

Nami Okamoto1, Yuko Sugita2, Kousuke Shabana2, Takuji Murata2, Hiroshi Tamai1

1Department of Pediatrics, Graduate School of Medicine, Takatsuki-city, Japan; 2Pediatrics, Osaka Medical and Pharmaceutical University, Takatsuki-city, Japan
Presenting author: Nami Okamoto

Introduction: We will report a girl with immunoglobulin G4-related disease (IgG4-RD), a newly recognized disorder that share particular pathologic (infiltration of IgG4-rich plasma cells or fibrosis), serologic (elevated serum IgG4), and clinical features (multifocal phymatoid or hypertrophic lesions).

Objectives: Child patient with IgG4-RD is very rare and its pathophysiology is thought to be different from adult cases1). We will report our patient whom treated with mycophenolate mofetil (MMF) for the purpose.

Methods: Retrospective analysis based on charts.

This report was approved by Ethics Committee of Osaka Medical and Pharmaceutical University.

Results: She complained exophthalmos when she was twelve years old. MRI was performed at former hospital that revealed tumefaction of lacrimal gland and salivary gland. Serum IgG4 concentration was significantly high (1090mg/dl) and biopsy specimen from salivary gland showed infiltration of IgG4-positive plasma cells (>50%). She was diagnosed as IgG4-RD and oral prednisolone (1mg/kg) was administered. Because of steroid-induced glaucoma, the disease control was difficult to manage and she was introduced to our hospital at age of thirteen. Laboratory data: WBC 10020/μl, PLT 31万/μl, CRP 0.01mg/dl, ESR 23mm/1h, IgG 2960mg/dl, IgA 45mg/dl, IgM 115mg/dl, IgE >5000Iu/ml, IgG4 1370mg/dl, CH50 41 U/ml, C3 90mg/dl, C4 15.6 mg/dl, AST/ALT 13/22U/L, γGTP 19U/L, BUN 15mg/dl, CRN 0.54mg/dl, autoantibodies negative, no abnormality in urine test. Abdominal CT and MRI were performed that showed IgG4-related cholangitis, cholecystitis and nephropathy. Bile duct wall was edematous and wall thickening was exhausted, so we diagnosed her status as CS-resistant. We prescribed MMF (800mg/kg) and she was responded clinically and serologically. Her disease activity has been controlled well since then. IgG4-RD is a male dominant disease and peak age is between forties and seventies in adults. Among pediatric patient of IgG4-RD, girls are double to boys and their age ranged from two to seventeen. Despite the recognition that pediatric IgG4-RD shows different characteristics, little was known about the pathogenesis, adequate therapy and prognosis yet. Though corticosteroid (CS) therapy was effective for most patients, half of them experienced relapse or recurrence with reducing CS2). CS-sparing agents that include azathioprine, rituximab, cyclophosphamide and MMF are required for them. But it is not clear when it should be started and which agent would be adequate as a maintenance therapy.

Conclusion: Our patient with pediatric IgG4-RD who was resistant to CS monotherapy responded to MMF. Further study about children with this rare disorder and confirming the response to maintenance therapy is necessary in worldwide.

References:

1) Karim F, et al. IgG4-related disease: a systematic review of this unrecognized disease in pediatrics. Ped Rheumatol. 2016;14:18.

2) Sekiguchi H, et al. Immunoglobulin G4-related disease: Retrospective analysis of 166 patients. Arthritis Rheumatol. 2016 Mar 18. doi:10.1002/art.39686. [Epub ahead of print]

Disclosure of Interest: None Declared

P406 Autoimmune damage of CNS - a newly recognized clinical manifestation of autoimmune polyendocrine syndrome type 1?

Juliana Ferenczová, Erika Banóova, Pavol Mrážik, Veronika Vargova

Department of Paediatrics and Adolescent Medicine, Šafárik University and children faculty hospital in košice, Košice, Slovakia
Presenting author: Veronika Vargova

Introduction: Autoimmune polyendocrine syndrome (APS) type 1, also known as autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), is a rare autosomal recessive disease. The classic features are chronic mucocutaneous candidiasis, hypoparathyroidism and adrenocortical failure. Several non-classic presentations of the disease have been described over the last few years.

Objectives: Authors present a case of 14-year old girl with prolonged seizures as a new serious non-classic presentation of APS type 1.

Methods: case report

Results: Patient was diagnosed with a mucocutaneous candidiasis and hypoparathyroidism at the age of 3 years. APS 1 was diagnosed at 9 years of age shortly after diabetes mellitus type 1 had been recognized. Mutational analysis of the AIRE gene showed R257X (c.769C > T) mutation. Typical symptoms of Addison disease - weakness, fatigue and hyperpigmentation - developed at 13 years of age. At 14 years she was admitted to hospital for prolonged seizures. Hypoglycemia and hypocalcemia were excluded as a cause of the seizures. EEG showed finding non-specific for epilepsy. Examination of the CSF was performed to exclude infection (herpetic viruses, etc.). MRI angiography did not show vasculitis or other organic changes of cerebral vessels. Specific autoantibodies for autoimmune encephalitis turned out to be positive in CSF (antiGAD65 > 2000 MU/L) as well as in blood (>2000 MU/L). Immunosuppressive treatment (glucocorticoids and i.v. immunoglobulins) in combination with antiepileptics resulted in a clinical course without seizures.

Conclusion: Differential diagnosis of autoimmune damage of CNS is a new challenge for pediatric rheumatologists. Autoimmune GAD65-positive encephalitis should be considered a new component of the clinical spectrum of APS in patient with new onset neuropsychiatric symptoms.

Disclosure of Interest: None Declared

Poster Session: Spondyloarthritis (SpA) and enthesitis related arthritis (ERA)

P407 Color Doppler us as an alternative to MRI for detecting sacroiliitis - a pilot study

Dubravko Bajramovic1, Ksenija Stekic Novacki1, Kristina Potocki1, Marijan Frkovic2, Marija Jelusic2

1Department of radiology, University Hospital Center Zagreb, Zagreb, Croatia; 2Department of pediatrics, University Hospital Center Zagreb, Zagreb, Croatia
Presenting author: Dubravko Bajramovic

Introduction: Considering that the ultrasound is a validated method for assessing inflammation activity in peripheral joints our aim in this pilot study was to determine whether the ultrasound/Color Doppler could be used to diagnose sacroiliitis in juvenile SpA patients.

Objectives: To determine the value of ultrasound/Color Doppler in diagnosing acute sacroiliitis in comparison with the established method which is considered a standard - the MRI. To compare data collected from our jSpA patients with previously published predisposing factors for the development of sacroiliitis.

Methods: We performed ultrasound/Color Doppler and MRI of sacroiliac joints using a standardized protocol on 112 patients observed for jSpA. All patients had low back pain and clinically suspected acute sacroiliitis. Out of 112 patients 43 were male and 69 female with average age of 13.9. Patients age at the beginning of the disease, number and sequence of joint involvement, history of rheumatic diseases in the family and results of HLA serotyping were recorded. All ultrasound and MRI examinations were performed by two MSK radiologists with an experience in imaging methods and protocols for rheumatic diseases.

Results: Active disease or acute sacroiliitis was noted using ultrasound/Color Doppler examination in 31 patients while 81 showed no signs of synovitis. MRI detected 28 patients with active disease. Only eight patients had ultrasound signs of disease activity confirmed on MRI. Based on preliminary results sensitivity of ultrasound/Color Doppler examination in detecting acute sacroiliitis in jSpA patients is 28.6% and specificity is 72.6%. Positive predictive value is 0.26 while negative predictive value is 0.75. Out of 41 patients with sacroiliitis confirmed on the MRI (both active and chronic) 27 of them had positive HLA- B27 serotyping, 9 had hip joint inflammation at the disease onset and only 5 had positive family history of rheumatic diseases.

Conclusion: MRI is a method of choice for detection of acute sacroiliitis but due to the waiting lists it can take a substantial amount of time before the examination can be performed. In order to get the diagnostic information as soon as possible ultrasound examination is often indicated. Ultrasound is an available, cheap and relatively easy method to perform and it doesn’t have the harmful effects of radiation which is especially important in the pediatric population. In sacroiliac joints imaging ultrasound has serious limitations due to the complex joint anatomy and a relatively small imaging “window” that enables us to visualize and analyze only the dorsal aspect of the joint. Evaluator has to make sure to that the Doppler signals acquired are the result of the increased vascularization within the synovia in the intraarticular space and not the result of imaging of the blood vessels in the periarticular soft tissues. Optimizing the image parameters is extremely important as well as imaging experience. As our preliminary results show using ultrasound CD as an alternative to MRI is questionable due to the low sensitivity and specificity of the method resulting from the limitations mentioned. Ultrasound is not the adequate method for demonstrating acute sacroiliitis and patients with high clinical suspicion of sacroiliitis should perform MRI in order to confirm the diagnosis.

Disclosure of Interest: None Declared

P408 Longterm experience of biologics therapy in juvenile spondyloarthritis: focus for the drug survival

Irina Nikishina, Olga Kostareva, Svetlana Arsenyeva, Maria Kaleda, Anna Shapovalenko

V.A.Nasonova research Institute of Rheumatology, MOSCOW, Russian Federation
Presenting author: Irina Nikishina

Introduction: Juvenile spondyloarthritis (JSpA) included several subtypes of juvenile arthritis, the main of there are follows: juvenile onset of ankylosing spondylitis (JAS), enthesitis-related arthritis (ERA), juvenile psoriatic arthritis (JPsA). Biologics, TNF-inhibitor mostly, provided excellent progress in JSpA outcome for the last 15 years. Drug survival is a general marker of the treatment success as it depends of its efficiency and safety.

Objectives: To compare drug survival of biologics depending on the subtype in JSpA patients (pts) in real clinical practice of single center.

Methods: The study involved a prospective cohort of JSpA pts treated by different TNF-inhibitors in our clinic from 2004 to 2016. Analyze included drug survival with Kaplan-Meier, reasons of withdrawals and adverse event (AE) rates.

Results: 177 JSpA pts, treated with one or more biologics were analyzed. At the start of biologics pts average age was 13.19 ± 3.7 years (range 3.58-17.9); mean disease duration was 50,4 month (range 2-163). JSpA subtypes were as follows: JAS, fulfilled to modified New-York criteria - 48(26%), ERA - 106(60%) and JPsA - 23(13%), diagnosed according to ILAR (2001) criteria, 149(83%) were HLA-B27positive. 24(13,4%) had uveitis. In total, 205 treatment series, including 79 for etanercept (185 patient-year PY), 73-adalimumab (160 PY), 53-infliximab (182 PY) were evaluated. There were 62 cases of withdrawals. Reasons for withdrawals were AE in 7,32% (95%CI 4.49-11.72), inefficacy -i10.73% (95%CI 7.19-15.71), others – 11,71% (95% CI 8-16,83), basically due to organizational difficulties of biologics access in adult life. AE were developed after at mean 1.63 years (range 0.74-3,36). AE were included: etanercept – 3 cases of uveitis de novo (1.62 per 100 PY); infliximab – 6 infusion reactions (3.3 per 100 PY), 1 psoriasis de novo, 1 severe skin disorder, 1 toxic hepatitis, 2 tuberculosis; adalimumab – 2 psoriasis de novo, 1 tuberculosis. AE as a reason of Infliximab withdrawal was observed more often than under adalimumab or etanercept (18.9% vs 2.74% and 3.8% respectively, p < 0.05). Due to inefficacy Infliximab was cancelled more often than adalimumab (16.9% vs 6.85%, p < 0.05). Etanercept was rare withdrawn due to organization problem in compare to infliximab and adalimumab (6.3% vs 16.98% and 13.7%, p < 0.05). Long-term drug survival of TNF-inhibitors was 78% for ERA, 64% for JAS and 57% for JPsA. Drug survival for etanercept were 95% and 35% after 1 and 5 years, infliximab – 90% and 38%, adalimumab – 97% and 32%, respectively. The average survival rate of etanercept and adalimumab was higher in ERA vs JAS and JPsA (84% vs 68% and 67% respectively), but for infliximab it was similar in all JSpA subtypes.

Conclusion: Our experience of long-term study of TNF-inhibitors in JSpA demonstrated the best rate of drug survival for etanercept in pts with different subtype of JSpA, especially in ERA. Infliximab mostly withdrawn due to AE and inefficacy, but adalimumab cancelled more often because of organizational reasons, especially in adult life.

Disclosure of Interest: None Declared

P409 Concomitant MRI features of sacroiliitis increase specificity for diagnosis of juvenile spondyloarthritis

Lennart Jans1, Nele Herregods1, Jacob Jaremko2, Rik Joos1, Joke Dehoorne1

1Ghent University Hospital, Gent, Belgium; 2University of Alberta, Edmonton, Canada
Presenting author: Lennart Jans

This abstract is not included here as it has already been published.

P410 Is contrast necessary to detect sacroiliitis on MRI in juvenile spondyloarthritis?

Nele Herregods1, Jacob Jaremko2, Xenofon Baraliakos3, Joke Dehoorne4, Rik Joos4, Lennart Jans1

1Department of Radiology and Medical Imaging, Ghent University Hospital, Ghent, Belgium; 2Department of Radiology & Diagnostic Imaging, University of Alberta Hospital, Edmonton, Canada; 3Rheumazentrum Ruhrgebiet, Ruhr-University Bochum, Herne, Germany; 4Department of Pediatric Rheumatology, Ghent University Hospital, Ghent, Belgium
Presenting author: Nele Herregods

This abstract is not included here as it has already been published.

P411 Performance of disease activity measures in juvenile spondyloarthritis in a placebo controlled trial with infliximab

Sofia Ramiro1, Julio C. Casasola-Vargas2, Désirée van der Heijde1, Robert Landewé3, Ruben Burgos-Vargas2

1LUMC, Leiden, Netherlands; 2Hospital General de Mexico, Mexico, Mexico; 3ARC, Amsterdam, Netherlands
Presenting author: Ruben Burgos-Vargas

Introduction: Several outcome measures in trials with juvenile-onset spondyloarthritis (Jo-SpA) have been borrowed from trials in juvenile idiopathic arthritis and from adult spondyloarthritis, but a proper psychometric analysis has never been conducted in patients with Jo-SpA.

Objectives: To assess discriminatory aspects of several disease activity outcome measures and response criteria for Jo-SpA.

Methods: Data from a previously reported 12-week RCT comparing infliximab (IFX) and placebo (PBO) in patients <18 years with Jo-SpA and onset <16 years of age were analyzed. The primary endpoint of the trial was the number of active joints (both swollen and tender). Several other disease activity measures and response criteria were also tested (Table 5). Statistics to determine how well disease activity measures could discriminate between IFX and PBO included ‘standardized mean difference’ (SMD) and ‘Guyatt’s effect size. Both statistics are standardized measures to compare change from baseline per group. For categorical response criteria, the chi-square test (χ2) was used. Higher numbers indicate better discriminatory capacity.

Results: Patients were randomised to IFX (n = 12) and PBO (n = 14). Of the continuous measures, the ASDAS showed the best and very good discrimination between IFX and PBO (SMD:1.98; Guyatt: 4.28) (Table 5). The physician’s global, CRP, JADAS and JSpADA also discriminated well. The BASDAI (or its separate items), BASFI and spinal mobility measures performed worse. Of the response criteria ASAS40 (IFX 55% vs PB = 0%, χ2 10.05) and ACR Pedi 90 (IFX 67% vs PBO 7%, χ2 10.12) discriminated best between IFX and PBO. ASDAS response criteria (ASDAS-MI: IFX 63% vs PBO 0%, χ2 8.65, ASDAS-CII IFX 88% vs PBO 20%, χ2 8.10) and ACR Pedi 30-70 also performed well.

Conclusion: Of all continuous measures tested in adult axial SpA the ASDAS discriminates best between active treatment and PBO in patients with Jo-SpA. But the child specific JSpADA also performs well.

Of all response criteria tested the child-specific ACR Pedi 30 to 90, as well as the adult ASAS40 and ASDAS response criteria work well. One of these measures should be used as primary endpoint in trials with Jo-SpA.

Disclosure of Interest: None Declared
Table 5 (abstract P411).

Discrimination between patients on infliximab and placebo at week 12

 

Infliximab mean change (SD)

PBO mean change (SD)

Guyatt’s effect size

SMD

ASDAS

2.4 (1.3)

0.5 (0.6)

4.28

1.98

Physician’s global assessment, 0-10 mm VAS

5.2 (2.4)

1.6 (2.2)

2.34

1.56

JADAS27 (0-57)

12.7 (5.9)

4.3 (5.7)

2.22

1.46

JSpADA (0-8)

2.8 (1.2)

0.5 (1.4)

1.98

1.73

CRP (mg/L)

21.1 (8.4)

2.3 (10.9)

1.93

1.90

Total enthesitis (0-51)

8.5 (10.6)

1.6 (5.0)

1.71

0.85

Patient’s global assessment, 0-10 mm VAS

4.3 (3.8)

0.8 (2.8)

1.55

1.08

BASDAI total (0-10)

3.3 (3.1)

0.9 (2.3)

1.41

0.90

Active joint count (0-72)

4.4 (1.7)

2.6 (4.6)

0.96

0.51

P412 Efficacy and safety of adalimumab in pediatric patients with enthesitis related arthritis

Ruben Burgos-Vargas1, Shirley M. Tse2, Gerd Horneff3, Kristina Unnebrink4, Jaclyn K. Anderson5

1Hospital General de Mexico, Universidad Nacional Autonoma de Mexico, Mexico City, Mexico; 2University of Toronto, The Hospital for Sick Children, Ontario, Canada; 3Asklepios Klinik Sankt Augustin, Sankt Augustin, Germany; 4AbbVie Deutschland GmbH & Co. KG, Ludwigshafen, Germany; 5AbbVie Inc, North Chicago, IL, United States
Presenting author: Ruben Burgos-Vargas

This abstract is not included here as it has already been published.

P413 Evaluation of DMARDs effectiveness on ERA patients

Aysenur Paç Kisaarslan1, Betül Sözeri1, Zübeyde Gündüz1, Gökmen Zararsız2, Hakan Poyrazoğlu1, Ruhan Düşünsel1

1Pediatric Rheumatology, Erciyes University, Kayseri, Turkey; 2Bioistatistic, Erciyes University, Kayseri, Turkey
Presenting author: Aysenur Paç Kisaarslan

Introduction: Therapeutic options for Enthesitis Related Arthritis (ERA) include monotherapy or combination therapy with non-steroidal anti-inflammatory drugs, disease-modifying anti-rheumatic drugs (DMARDs), and biological agents. Until today, the approach to managing ERA is guided in large part by evidence from studies in adults with SpA and other forms of JIA.

Objectives: This study aim is determined whether effectiveness of DMARDs in ERA patients.

Methods: Fiftytwo ERA patients who satisfied ILAR criteria were enrolled in the study. The patients with psoriasis, inflammatory bowel disease, reactive arthritis and undifferentiated arthritis were exculuded. Patient information was obtained from the records. Registered data included demographic features, medical history, initial and following physical examination, initial juvenile spondyloarthritis disease activity index(JSpADA), initial laboratory tests, radiographic tests, JADI -A (Juvenil Arthritis Demage Index-articulary) and JADI-E(extraarticulary) on last admission, and all of medical treatment.

Results: We evaluated response of DMARDs in 52 patients. Twenty-seven patients (52%) achieved remission with DMARDs, while 25(48%) patients were not achived remission with DMARDs. Diagnosis of age, gender, family history of AS, inflammatory back pain, shoulder, hip, small joint involvement, sacroileitis with physical examination, enthesitis, presence of uveitis, presence of HLA-B27, initial high AFR levels, initial JSpADA score, last JADI-A score did not determinated risk factor on unresponsiveness of DMARD(HR:1, p > 0.05). Although it was not statistically significant, sacroileitis determinated with MRI increased 2.84 fold on unresponsiveness of DMARD with cox-regression analysis (p > 0.05). DMARD effectiveness decreased 50% at 20th month in this group with Kaplan-Meier analysis.

Conclusion: There are no significant differencies periferic between axial involvement treated with DMARD in our study. Therefore we believe that DMARDs kept up to date.

Disclosure of Interest: None Declared

P414 Assessment of entheseal ultrasonography in patients with juvenile fibromyalgia

Kazutaka Ouchi, Shinji Akioka, Hiroshi Kubo, Norio Nakagawa, Hajime Hosoi

Pediatrics, Kyoto Prefectural University of Medicine, Kyoto, Japan
Presenting author: Kazutaka Ouchi

Introduction: Fibro myalgia (FM) is characterized by widespread chronic musculoskeletal pain with fatigue, poor sleep, frequent psychological difficulties, and multiple tender points on physical examination. In adult cases, American College of Rheumatology 2010 (ACR2010) criteria was proposed as clinically useful tool, and the analyses of the underlying disease of FM based on this criteria demonstrated that some FM cases are complicated with SpA, one of which pathogenesis is enthesitis. Here, we examined ultrasound findings on entheses of juvenile FM patients.

Objectives: To identify the ultrasound (US) picture of peripheral entheses in juvenile patients with FM.

Methods: A single-center study was performed in 8 patients with definite juvenile FM according to suggestive symptom (a widespread pain resulting in school absenteeism). US assessment of the following four entheses was performed bilaterally by a senior rheumatologist: distal Achilles tendon, distal and proximal patellar tendon, and quadriceps tendon.

Results: The patients were 6 women and 2 men with a mean age of 14 ± 1 years. Total 64 entheses was examined. Inflammatory enthesitis was detected in 36 entheses (56.3%), and enthesopathy detected in 8 entheses (12.5%). All of patients had at least one lesion: inflammatory enthesitis was detected in 8 patients (100.0%), and enthesopathy detected in 6 patients (75.0%).

Conclusion: All juvenile FM cases were found to have enthesitis by US. Our result showed that a part of juvenile FM patients are probably complicated with enthesitis.

Disclosure of Interest: None Declared

P415 Epigenetic regulation of PTPN12 gene could influence the immunopathogenesis of juvenile spondyloarthritis and give rise to new therapeutic options

Lovro Lamot1,2, Fran Borovecki2, Sanja Kapitanovic3, Kristina Gotovac2, Mandica Vidovic1, Mirta Lamot1, Edi Paleka Bosak1, Miroslav Harjacek1

1Clinical Hospital Center Sestre Milosrdnice, Zagreb, Croatia; 2University of Zagreb School of Medicine, Zagreb, Croatia; 3Ruđer Bošković Institute, Zagreb, Croatia
Presenting author: Lovro Lamot

Introduction: Gene expression profiling of juvenile spondyloarthritis (jSpA) patients revealed aberrant expression of some genes, but the mechanism of this expression alterations remained unknown (1).

Objectives: To discover epigenetic modifications with effect on regulation of 4 genes (TLR4, NLRP3, CXCR4, PTPN12) differentially expressed in jSpA patients.

Methods: DNA methylation analysis was performed in promotor region of differentially expressed genes by methylated DNA Immunoprecipitation (meDIP). Based on literature search, 4 microRNAs (miR-150, miR-146a, miR-181a, miR-223) included in regulation of differentially expressed genes were selected and their expression was analyzed using RT-PCR with predeveloped Taqman microRNA assays. Both analysis were performed in 7 newly diagnosed untreated jSpA patients and 7 matched healthy children.

Results: Statistical analysis revealed no difference in methylation of promotor sites for examined genes, but PTPN12 showed trend towards higher methylation (p = 0,076), compared with control group. There was no statistical difference in expression of selected miRs between two groups.

PATIENTS

1

2

3

4

5

6

7

PTPN12 (fold enrichment)

0,43

1,01

0,54

1,84

1,06

5,08

0,55

0,95

0,57

1,08

0,81

0,886

1,26

0,586

CONTROLS

1

2

3

4

5

6

7

Conclusion: jSpA is a multifactorial disease in which a complex interplay occurs between the immune system and environmental factors on a predisposing genetic background. One of the most important mechanisms by which environment can influence processes inside of an organism is gene regulation via epigenetic modifications. Therefore, we investigated possible influence of DNA methylation and posttranscriptional modifications on the genes differentially expressed in jSpA patients. The results didn’t indicate any statistically significant abundance of miRs with described role in expression of examined genes, nor hypermethylation of their promotor sites, but there was a clear trend of higher methylation of PTPN12 in jSpA patients, while lack of statistical significance could be attributed to small number of study participants. This observation can easily explain decrease of PTPN12 expression in treated and untreated jSpA patients. PTPN12 expressed in dendritic cells is identified as a key regulator of dendritic cell migration as well as T cell-dependent immunity and autoimmunity (2). It is also a negative regulator of inflammation and intestinal cell migration, as well as a positive regulator of osteoclast activity, all of which are processes important for the pathophysiology of jSpA. Results of our study are in concordance with previous epigenetic studies of this gene in human breast cancer patients, which showed PTPN12 can be silenced by methylation. Interestingly, more recent study pointed to the potential of 5-Azac, a DNA hypomethylating agent, in increasing PTPN12 expression, and highlighted the therapeutic potential of this mechanism in treatment of breast cancer (6). Therefore, it is tempting to speculate the results of our study could after confirmation in larger cohorts give rise for new treatment options in jSpA patients as well.

References:

1. Lamot L, et al. Aberrant expression of shared master-key genes contributes to the immunopathogenesis in patients with juvenile spondyloarthritis. PLoS One. 2014 Dec 15;9(12):e115416.

2. Inmoo Rhee, et al. Control of dendritic Cell Migration, T Cell-Dependent Immunity, and Autoimmunity by Protein Tyrosine Phosphatase PTPN12 Expressed in Dendritic Cells. Mol Cell Biol. 2014 Mar;34(5):888-99.

3. Thummuri D, et al. Epigenetic regulation of protein tyrosine phosphatase PTPN12 in triple-negative breast cancer. Life Sci. 2015 Jun 1;130:73-80.

Disclosure of Interest: None Declared

P416 Anti-tumor necrosis factor therapy in patients with enthesitis-related arthritis

Ricardo A. Russo, María M. Katsicas

Immunology & Rheumatology, Hospital de Pediatría Garrahan, Buenos Aires, Argentina
Presenting author: Ricardo A. Russo

Introduction: Enthesitis-related arthritis (ERA) is a category of Juvenile idiopathic arthritis considered to be a form of Juvenile Spondyloarthropathy (jSpA). Tumor necrosis factor (TNF)-blocking strategies have proven effective in the treatment of jSpA1-2.

Objectives: To assess effectiveness of anti-TNF treatment in a cohort of patients with ERA; to search for associations between clinical features at treatment onset and inactive disease (ID).

Methods: Retrospective review of prospectively collected data. Patients with ERA (according to ILAR criteria) continuously treated with anti-TNF agents for ≥ 3 months were included. At visit 0 (baseline) and every 3 months thereafter Information was collected on therapeutic agents used and the following disease activity measures: joint count, pain score (0-10), presence of active enthesitis (AE), sacroiliac pain (SIP) or lumbar limitation (LL), wellbeing according to the patient using a visual analogue scale (VASp, 0-10), disease activity according to the physician (VASphy, 0-10), JADAS-102, JSpADA3, and ESR. Functional capacity was also assessed through the use of CHAQ. Occurrence of ID (defined as JADAS-10 £ 1 or as per Wallace et al4) and clinical remission (CR)4 was recorded. ANOVA and Mann-Whitney U test were used for comparisons between visits, while associations were analyzed with chi square and Sperman’s rank correlation.

Results: 30 patients fulfilled inclusion criteria. Patients were followed at a specialized clinic during the period 2002-2015.They were all male, 43% HLA-B27 positive; median age at start of TNF-blocker therapy was 13 years, disease duration 3.5 years; median observation period was 18 months. Twenty-seven (90%) children showed peripheral arthritis while 22 (73%) exhibited sacroiliitis on MRI/Xrays at start of therapy. Patients received etanercept (23, 2 were later switched to adalimumab and 1 to infliximab), adalimumab (5), or infliximab (2). At baseline patients showed (medians): active joints (AJ) 4, pain 1.5, VASp 2, VASphy 2, JADAS-10 9.75, JSpADA 2.5, ESR 16.5 mm/h, and CHAQ 0.25. AE was present in 4 (13%), SIP in 7 (23%), and LL in 12 (40%) children. All patients showed JSpADA > 0 and 29 (97%) children had JADAS > 1 at entry. At 3 months JADAS-10 decreased to 5.5 (p = 0.007) and JSpADA to 1.25 (p = 0.002); 6 (21%) patients achieved ID. At 12 months patients showed AJ 0 (p = 0.01), pain 0 (p = 0.009), VASp 0 (p = 0.0005), VASphy 0.75 (p = 0.0001), JADAS-10 3 (p = 0.0001), JSpADA 1 (p = 0.0004), ESR 6 mm/h (p = 0.02), and CHAQ 0 (p = 0.12). AE was present in 0 (p = 0.08), SIP in 0 (p = 0.01), and LL in 6 (24%) (p = 0.03) patients. ID was recorded in 22 (73%) and CR in 9 (30%) children during the observation period. Achievement of ID at 12 months was associated with baseline presence of active sacroiliitis (p = 0.02).

Conclusion: In this retrospective cohort of ERA patients on TNF-blockers a significant and progressive reduction in disease activity measures was observed. Patients with baseline axial involvement appear to benefit most from this therapy.

References

1. Hugle B, Burgos-Vargas R, Inman RD, et al. Long-term outcome of antitumor necrosis factor alpha blockade in the treatment of juvenile spondyloarthritis. Clin Exp Rheumatol 2014;32:424-31.

2. Consolaro A, Ruperto N, Bazso A, et al. Development and validation of a composite disease activity score for Juvenile Idiopathic Arthritis. Arthritis Care Res 2009;658-66.

3. Weiss P, Colbert RA, Xiao R, et al. Development and Retrospective Validation of the Juvenile Spondyloarthritis Disease Activity Index. Arthritis Care Res 2014;66:1775-82.

4. Wallace CA, Ruperto N, Giannini EH. Preliminary criteria for clinical remission for select categories of juvenile idiopathic arthritis. J Rheumatol 2004;31:2290-4.

Disclosure of Interest: None Declared

P417 An audit to determine the characteristics of axial symptoms and imaging studies in children/adolescents with juvenile-onset spondyloarthritis/enthesitis related arthritis described in the literature

Ruben Burgos Vargas1, Ana L. Ortiz-Peyegahud2

1Rheumatology, Mexico, Mexico; 2Hospital General de Mexico, Mexico, Mexico
Presenting author: Ruben Burgos Vargas

Introduction: Peripheral arthritis and enthesitis characterize the onset and course of JoSpA/ERA. Axial symptoms (ax-symp) are rare at onset and increasingly frequent in patients at risk of ankylosing spondylitis (AS). Unfortunately, most papers, including those mentioning the distinctive term “inflammatory back pain” (IBP) lacked of precision about symptoms.

Objectives: To identify the elements that define ax-symp in children and adolescents with joSpA/ERA.

Methods:

We extracted information regarding ax-symp, clinical signs, and imaging studies referring to spinal and sacroiliac joints and entheses in joSpA/ERA patients from series of cases, case-control and cohort studies appeared in PubMed from 1966 to 2016.

Results: 58/1405 articles mentioned scarce, ambiguous, and non-specific clinical and imaging data about the involvement of the spine and sacroiliac joints and entheses. Only nine studies described timing; five referred to IBP characteristics, and four to imaging data. The analysis suggests ax-symp occur within five years from onset in up to 50% of the patients; radiographic sacroiliitis is seen and AS diagnosis is made 7.5 to 15 years after onset; syndesmophytes are rare before the of 20 years. MR studies seem to add nothing new yet.

Conclusion: Few papers describe timing and characteristics of ax-symp and radiographic sacroiliitis in children with joSpA/ERA evolving to AS. In contrast, most papers, including AS, do not present enough support to confirm ax-symp in joSpA/ERA patients, including those with AS; the effect of these factors may increase the proportion of false positives in the clinic and in clinical trials.

Disclosure of Interest: None Declared

P418 Juvenile-onset Ankylosing Spondylitis(JAS) and its bone metabolism

Zhang Pingping1, Mou Yikun1, Qi Jun2, Jiang Yutong2, Gu Jieruo2

1Pediatrics, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China; 2Rheumatology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
Presenting author: Zhang Pingping

Introduction: Ankylosing spondylitis (AS) is a chronic systemic inflammatory disease which characteristically involves the axial skeleton, enthesis regions or peripheral joints.As a chronic disease, AS generate high socioeconomic costs and AS cases require lifelong treatment. Severe pain and spine destruction causes high prevalence of work-related disabilities and a decrease in quality of life, which is a huge burden for the case, their families and the society.According to their onset age,the patients was classified to, Juvenile-nset Ankylosing Spondylitis (JAS), whose onset symptoms before the age of 16 years, and Adult-onset Ankylosing Spondylitis(AAS). Clinical phenotype and prognosis of JAS is different from AAS, but up to now scarce information about JAS was reported, especially the related bone metabolism mechanism.

Objectives: To analyse bone metabolic index(BMI) changes on patients with Juvenile-onset Ankylosing Spondylitis(JAS)and their relations with clinical index.

Methods: To collect the clinical data of JAS,such as C-reactive protein (CRP), blood sedimentation (ESR),the disease activity index (BASDAI),functional index (BASFI) and bone mineral density (BMD), detect the serum bone metabolism index,such as Wnt-3a, BMP-2, Dkk-1, 25 (OH) D and ICTP, then group these data and do statistical analysis.

Results: Osteopenia and VitD lack were widespread in JAS. Compared with controls, The elevated Wnt-3a and reduced Dkk-1 levels were not significant in JAS (P > 0.05), and there was no significant correlation between the two indexes and other BMI, course, clinical inflammation index, BASDAI and BASFI.However,the serum ICTP and BMP-2 were increased significantly in JAS, and both the CRP and BMP-2 were positive related with serum Wnt-3a(r was 0.271 and 0.250 respectively, P < 0.05).Correlation analysis shew there was positive correlation between serum 25 (OH) D and hip BMD in JAS(r = 0.383, P < 0.01), and there was negatively correlation between ICTP and BASDAI (r = -0.405 and -0.273 respectively, P < 0.05).Besides,regression analysis shew that both serum 25 (OH) D and the disease course were independent prognostic factors of patients’ hip BMD decreasing, where as CRP and ICTP were also independent prognostic factors of patients’ BASDAI. BMI in JAS with different clinical phenotypes were compared, BMP-2 level was much higher in JAS with hip joint involvement than other groups(P = 0.032), while there was no significant difference in serum 25(OH)D,ICTP,Wnt-3a and Dkk-1 level in all groups(P > 0.05).

Conclusion: Bone metabolism imbalance exists in JAS,and BMP pathway played an important role in the JAS with hip lesions and deserves further research.

Disclosure of Interest: None Declared

Poster Session: Systemic JIA II

P419 Identification of best cut-off points and clinical signs for discrimination of rheumatic mask of hematooncology disease and systemic onset of juvenile idiopathic arthritis

Mikhail M. Kostik1, Shilova Ekaterina1, Ilia Avrusin1, Yuriy Korin1, Olga Kopchak2, Eugenia Isupova1, Irina Chikova1, Panova Tatyana3, Margarita Dubko1, Vera Masalova1, Ludmila Snegireva1, Tatyana Kornishina1, Olga Kalashnikova1, Vyacheslav Chasnyk1

1Hospital Pediatry, Saint-Petersburg State Pediatric Medical University, Saint-Petersburg, Russian Federation; 2Pediatry, Kirov’s regional children’s hospital, Kirov, Russian Federation; 3Pediatry, Leningrad regional children’s clinical hospital, Saint-Petersburg, Russian Federation
Presenting author: Mikhail M. Kostik

Introduction: Systemic onset of juvenile idiopathic arthritis (SoJIA) is a diagnosis of exclusion and required a broad spectrum of differential diagnosis. Patients with malignant hematooncology diseases (HOD) can have the similar to SoJIA symptoms as fever, lymphadenopathy, hepatosplenomegaly, joints pain and arthritis, increased ESR, CRP, anemia and should be discriminated from SoJIA. Due to presence of rheumatic masks children with HOD can be admitted to rheumatologic department.

Objectives: The aim of our study was to find the best cut-off points and clinical signs allowed to discriminate patients who have the rheumatic masks of HOD from patients with SoJIA.

Methods: In the retrospective study were included 86 patients with SoJIA and 21 children with HOD who were admitted in the rheumatology department due to rheumatic masks with initial provisional diagnosis - SoJIA. The HOD group was presented with patients with acute lymphoblastic leukemia (n = 18), neuroblastoma (n = 1) and lymphomas (n = 2). We evaluated the presence of main clinical signs in both groups and detected the best cut-off points of qualitative variables with ROC-analysis and analysis of sensitivity and specificity. We calculated the diagnostic odds ratios (DOR) for identification the best cut-off parameters. For comparison of two independent groups was used Mann-Whitney test, chi-square test and Fisher’s exact test.

Results: There were no differences in onset age, presence of hepatosplenomegaly, lymphadenopathy, lung, CNS involvement, levels of hemoglobin, AST, LDH, ALP, GGTP, ferritin and sodium levels between both groups (table). The main diagnostic signs, allowed to discriminate HOD from SoJIA were: number of active joints ≤3 (DOR = 4.4 (95%CI:1.5-13.2), p = 0.005), CRPБ < 15 mg/l (DOR = 5.6 (95%CI:1.7-18.4), p = 0.002), PLT ≤ 307x109/l (DOR = 22.9 (95%CI:4.9-107.0), p = 0.0000001), WBC ≤ 8.9x109/l (DOR = 50.2 (95%CI:6.3-401.3), p = 0.0000001), albumin > 43.3% (DOR = 28.8 (95%CI:5.6-149.2), p = 0.000001), no fever (DOR = 37.3 (95%CI:7.2-192.8), p = 0.0000001), no rash (DOR = 39.8 (95%CI:8.4-188.5), p = 0.0000001), night bone pain (DOR = 2364.3 (95%CI:92.9-60169.9), p = 0.0000001), any bone and joint pain (DOR = 227.6 (95%CI: 12.5-4158), p = 0.0000001), pathologic fractures (DOR = 32.7 (95%CI:1.6-661.0), p = 0.0004).

Parameters

HOD (n = 21)

SJIA (n = 86)

p

WBC, x109/l

7.4 (5.3-8.3)

14.6 (9.3-18.5)

0.002

PLT, x109/l

175 (109.5-249)

436 (256-583)

0.00001

CRP, mg/l

12.3 (5.9-48.8)

57 (18-113)

0.005

Active joints, n

1 (1-3)

4 (2-13)

0.006

Fever, n (%)

11/21 (52.4)

82/84 (92.6)

0.0000001

Rash, n (%)

2/21 (9.5)

67/83 (80.7)

0.0000001

Night pains, n (%)

12/21 (57.1)

0/86 (0)

0.0000001

Bone pains, n (%)

20/21 (95.2)

0/86 (0)

0.0000001

Pathological fractures, n (%)

3/21 (14.3)

0/86 (0)

0.0004

Conclusion: The found diagnostic criteria can help physicians to discriminate HOD patients with “rheumatic masks” into the group of patients with suspected SoJIA.

Disclosure of Interest: None Declared

P420 The ability of tocilizumab induces the remission in systemic juvenile idiopathic arthritis: the main predictors

Mikhail M. Kostik, Irina Chikova, Eugenia Isupova, Margarita Dubko, Vera Masalova, Ludmila Snegireva, Tatyana Kornishina, Tatyana Likhacheva, Olga Kalashnikova, Vyacheslav Chasnyk

Hospital Pediatry, Saint-Petersburg State Pediatric Medical University, Saint-Petersburg, Russian Federation
Presenting author: Mikhail M. Kostik

Introduction: Systemic juvenile idiopathic arthritis (SJIA) is one of the most striking forms of juvenile arthritis, required biologic administration due to failure of corticosteroids (CS) and DMARDs. Currently there are two strategies in treatment SJIA with biologic: blockade of IL-1 and IL-6. Despite similar efficacy and safety profile in latest ACR recommendations blockade of IL-6 recognized as second-line biologic treatment after using the anakinra. The question about first line biologic treatment in SJIA is still open.

Objectives: The aim of our study was to evaluate outcomes and find predictors of remission in SJIA children, receiving TCZ therapy.

Methods: Our retrospective study was included 48 active SJIA children who fall CS, methotrexate (MTX), cyclosporine A (CsA) and their combination in whom TCZ was initiated in dosage 12 mg/kg if weight was < 30 kg and 8 mg/kg if weight ≥ 30 kg. The duration of study was limited the 1st and last TCZ infusions. We evaluated clinical and laboratorial signs, attributed to SJIA, such as presence of fever, hepatosplenomegaly, serositis, rash, lymphadenopathy, active joints, the levels of Hb, WBC, PLT, granulocytes, LDH, and macrophage activation syndrome (MAS). We check the granulocytes levels throw 1 and 2 after 1st TCZ infusion. The efficacy of TCZ was measured throw changes of SJIA attributed signs, symptoms, dynamic of concomitant treatment and achievement the remission according to C. Wallace (2004) criteria.

Results: The main demographic parameters (Me; IQR) included the age-9.9 (5.-12.7) years and delay of TCZ-27.0 (5.9-89.7) months. The treatment before TCZ included CS-38 (79.2%), MTX-40 (83.3%), CsA-18 (37.5%) and their combination. The macrophage activation syndrome (MAS) in past medical history before TCZ was in 14 (29.2%).

During the trial CS successfully discontinued 25 (65.8), CsA 8/18 (44.4%), MTX 12/40 (30.0%) patients. In 7 children TCZ was discontinued due to stable remission with median duration 640 days. After TCZ initiation 6 children have experienced MAS, but all of them had MAS before TCZ, so no “new cases” were observed on TCZ. 5 children early withdrew during the trial due to adverse events (infusion reaction, MAS) and 2 children died (1 severe uncontrolled MAS, 1 amyloidosis).

During the TCZ treatment 40 (83.3%) achieved the remission in 138.5 (56.0; 255.0) days. Patients, who achieved remission had milder disease course, presented in less frequent hepatosplenomegaly, lung, heart and CNS involvement, hemorrhagic syndrome and MAS. They had higher Hb (p = 0.02) and lower WBC (p = 0.048), granulocytes (p = 0.015), ESR (p = 0.034), CRP (p = 0.05), LDH (p = 0.0003), ferritin (p = 0.0007). The main predictors of achievement inactive disease, calculated with Cox-regression models, presented in the table.

Conclusions: We found clinical and laboratorial criteria for SoJIA remission during the tocilizumab treatment.

Parameters

OR (95% CI)

p

HR

p

CRP ≤ 82.0 mg/l**

7,9 (1,4-45,3)

0,016*

1,17

0,66

ESR ≤ 32 mm/h**

17,0 (0,9-314,3)

0,014*

0,85

0,62

Ferritin ≤ 273ng/ml**

56,5 (2,8-1124,9)

0,0001*

2,6

0,02

LDH ≤ 676 U/l**

113,6 (5,3-2451,8)

0,000014*

3,18

0,029

PLT > 335x109/l**

5,0 (0,9-28,9)

0,11*

2,54

0,007

Age of 1st TCZ infusion ≤ 11y.**

2,6 (0,6-12,4)

0,24*

1,44

0,3

Decreaed WBC in 2 weeks > 11%**

13,0 (1,4-124,3)

0,03*

6,03

0,019

Decreased Granulocytes in2 weeks > 12%**

14,0(1,1-185,5)

0,05*

4,7

0,13

MAS before TCZ

0,17 (0,04-0,87)

0,037*

0,7

0,34

Me (IQR), * Fisher’s exact test, ** AUC – area under the curve

Conclusion: We found clinical and laboratorial criteria for SoJIA remission during the tocilizumab treatment.

Disclosure of Interest: None Declared

P421 Efficacy and safety of canakinumab in patients with systemic juvenile idiopathic arthritis: results from an open-label long-term follow-up study

N. Ruperto1, H. I. Brunner2, P. Quartier3, T. Constantin1, E. Alexeeva1, R. Schneider2, I. Kone-Paut1, K. Schikler2, K. Marzan2, N. Wulffraat1, S. Padeh1, V. Chasnyk1, C. Wouters1, J. B. Kuemmerle-Deschner1, T. Kallinich1, B. Lauwerys4, E. Haddad2, E. Nasonov1, M. Trachana1, O. Vougiouka1, K. Leon5, A. Speziale6, K. Lheritier6, E. Vritzali6, A. Martini1, D. Lovell2 and PRINTO/PRCSG

1PRINTO-Istituto Gaslini, Genoa, Italy; 2PRCSG, Cincinnati, OH, United States; 3Necker-Enfants Malades Hospital, Paris, France; 4Cliniques Universitaires Saint-Luc and Université Catholique de Louvain, Brussels, Belgium; 5Novartis Pharmaceuticals Corporation, East Hanover, NJ, United States; 6Novartis Pharma AG, Basel, Switzerland
Presenting author: N. Ruperto

Introduction: Canakinumab (CAN), a highly selective human anti-IL1 β monoclonal antibody, had demonstrated its efficacy and safety in patients (pts) with active systemic juvenile idiopathic arthritis (SJIA) in a comprehensive global clinical program consisting of one phase II and two phase III trials.1,2 However, limited data was available on long-term efficacy and safety of CAN in SJIA.

Objectives: To assess long-term efficacy and safety of CAN treated SJIA pts over a 5-year (yr) follow-up observational period.

Methods: This was an open-label extension (OLE) study of SJIA pts participating in the global clinical trials of CAN.3 Pts, 2 to <20 yrs of age at the time of enrollment in study, received subcutaneous CAN 4 mg/kg every 4 weeks. Baseline was defined as the starting point of the extension trial. Efficacy assessments were done every 3 months, including adapted paediatric response criteria (aACR), clinical inactive disease and clinical remission on medication (continuous 12 months of clinical inactive disease). Safety assessments included adverse events (AEs) and serious AEs (SAEs).

Results: Overall, 147 pts to the OLE study had a median treatment duration of 3.2 yrs; total treatment exposure was approximately 365 pt-yrs. Of 147 pts, 100 (68%) completed 96 weeks of treatment, whereas 47 (32%) pts discontinued the study. Another 25 pts (17%) discontinued the study after Week 96. Of the 107 pts with an aACR 30 at entry to the OLE study, 61.7%, 79.4% and 86.0% have had aACR 100, 90 and 70 responses, respectively at last assessment. At baseline, 32.7% of patients were with inactive disease which increased up to 60% - 70% between Week 36 and Week 168. Clinical remission on medication was achieved in 43% pts. In total, 137 (93.2%) pts reported at least 1 AE during the 3.2 years median exposure in the study corresponding to 2.009 AEs/100 pt-days (733.6 AEs/100 pt-years) with infections (202.7 per 100 pt-years) being the most common AE. Overall, 47 (32.0%) pts had at least 1 SAE corresponding to 0.089 SAE/100 pt-days (32.6 SAE/100 pt-years) with the most common being JIA (14 pts) denoting disease flares or worsening of SJIA. Ten patients (6.8%) with a total of 12 MAS events were reported as SAE and 7 patients among them discontinued the study. No deaths were reported.

Conclusion: In patients previously treated with CAN in pivotal trials, response to treatment was sustained or improved during long-term treatment in the OLE study. Safety profile of CAN was consistent with safety findings from previous studies.

References:

1. Ruperto N, et al. N Engl J Med. 2012;367(25):2396-406.

2. Ringold S, et al. Arthritis & Rheum. 2013;65(10):2499-512.

3. Ruperto N, et al. Ann Rheum Dis. 2015;74(2):608.

Trial registration identifying number: NCT00891046

Disclosure of Interest: N. Ruperto Grant / Research Support from: Abbott, BMS, “Francesco Angelini”, GlaxoSmithKline (GSK), Hoffman-La Roche, Italfarmaco, Janssen, Novartis, Pfizer, Sanofi Aventis, Schwarz Biosciences, Sobi, Xoma and Wyeth, Speaker Bureau of: Abbott, AbbVie, Amgen, Biogenidec, Astellas, Alter, AstraZeneca, Boehringer, BMS, CDPharma, Celgene, CrescendoBio, EMD Serono,Hoffman-La Roche, Italfarmaco, Janssen, MedImmune, Medac, Novartis, Novo Nordisk, Pfizer, Sanofi Aventis, Servier, Takeda and Vertex, H. Brunner Consultant for: Novartis, Roche, Pfizer, UCB, Celgene, Regeneron, Amgen, Astrazeneca, GSK and BMS, Speaker Bureau of: Novartis and Roche, P. Quartier Grant / Research Support from: Abbvie, BMS, Chugai-Roche, Novartis, Pfizer and SOBI, Consultant for: Abbvie, Novartis, Servier and SOBI, Speaker Bureau of: Abbvie, BMS, Chugai-Roche, Medimmune, Novartis, Pfizer and SOBI, T. Constantin: None Declared, E. Alexeeva Grant / Research Support from: Roche, Abbott, Novartis, Pfizer, Bristol-Myers Squibb and Centocor, Speaker Bureau of: Roche, Novartis, Merck Sharp Dohme, Bristol-Myers Squibb, Medac and Pfizer, R. Schneider Consultant for: Novartis, Novimmune, Sobi and Innomar Strategies, I. Kone-Paut Grant / Research Support from: SOBI, Novartis and Roche, Consultant for: Novartis, SOBI, Pfizer, Abbvie and Roche/Chugai, K. Schikler Consultant for: Novartis, Novimmune, SOBI and Innomar Strategies, K. Marzan Grant / Research Support from: Novartis, Abbvie, N. Wulffraat Grant / Research Support from: Novartis, S. Padeh: None Declared, V. Chasnyk: None Declared, C. Wouters Grant / Research Support from: GSK, Novartis and Roche, J. Kuemmerle-Deschner Grant / Research Support from: Novartis, Consultant for: Novartis, SOBI and Baxalta, T. Kallinich Grant / Research Support from: Novartis, Speaker Bureau of: SOBI, Novartis, BMS and Roche, B. Lauwerys: None Declared, E. Haddad: None Declared, E. Nasonov: None Declared, M. Trachana Grant / Research Support from: Novartis, Abbvie, Bristol Meyers, Consultant for: Novartis, Roche and Pfizer, O. Vougiouka: None Declared, K. Leon Employee of: Novartis, A. Speziale Employee of: Novartis, K. Lheritier Shareholder of: Novartis, Employee of: Novartis, E. Vritzali Employee of: Novartis, A. Martini Grant / Research Support from: Abbott, BMS, “Francesco Angelini”, GlaxoSmithKline (GSK), Hoffman-La Roche, Italfarmaco, Janssen, Novartis, Pfizer, Sanofi Aventis, Schwarz Biosciences, Sobi, Xoma and Wyeth, Speaker Bureau of: Abbott, Abbvie, Amgen, Biogenidecm Bristol MyersSquibb, Astellas, Behringer, Italfarmaco, Janssen, MedImmune, Novartis, NovoNordisk, Pfizer, Sanofi, Roche, Servier and Takeda, D. Lovell Grant / Research Support from: National Institutes of Health, Consultant for: Astra-Zeneca, Bristol Meyers Squibb, AbbVee, Pfizer, Roche, Novartis, UCB, Forest Research Institute, Horizon, Johnson & Johnson, Biogen, Takeda, Genentech, Glaxo Smith Kline, Boehringer Ingelheim, Celgene and Jannsen, Speaker Bureau of: Genentech, Roche and Novartis

P422 Phagocyte involvement in systemic onset juvenile idiopathic arthritis

Nienke Ter Haar1,2, Rianne Scholman1, Wilco de Jager1, Tamar Tak1, Pieter Leliefeld1, Bas Vastert2, Sytze de Roock1,2

1Laboratory for Translational Immunology, University Medical Center Utrecht, Utrecht, Netherlands; 2Pediatric Rheumatology, University Medical Center Utrecht, Utrecht, Netherlands
Presenting author: Nienke Ter Haar

Introduction: Systemic onset Juvenile Idiopathic Artritis (sJIA) is a systemic autoinflammatory disease, characterized by arthritis, spiking fever and rash and elevation of serum S100-proteins and interleukin(IL)-18, reflecting IL-1 pathway activation. The exact role of monocytes and neutrophils in the inflammatory cascade of sJIA is still to be unravelled.

Objectives: To dissect the role of monocytes and neutrophils in the inflammatory cascade of sJIA.

Methods: In a prospectively followed cohort of 23 new-onset sJIA patients, we evaluated cell counts, serum levels of cytokines, chemokines and other analytes at disease onset and during inactive disease. Cytokine concentrations in supernatant and serum were determined by multiplex immunoassay. We determined neutrophil activation ex vivo (phenotype and cell membrane markers) and after stimulation (ROS-production and degranulation) of cells derived from sJIA with active disease (n = 10) or in clinically inactive disease (n = 6), compared to healthy donors (HDs, n = 16). To investigate the role of monocytes, we assessed cytokine production of peripheral blood derived mononuclear cells (PBMC) from active and remission sJIA patients and HDs (n = 6 for all groups) after stimulation with TLR-4 activating S100-proteins (+/- ATP) or other TLR-ligands.

Results: Twenty-one of 23 patients with onset sJIA had elevated neutrophil counts, while monocyte counts were elevated in only 5/23 patients. Among the inflammatory markers that were significantly elevated in serum of onset sJIA patients, we observed multiple neutrophil specific proteins like elastase and neutrophil collagenase, indicating the importance of this cell type.

Neutrophils from active sJIA patients showed an activated phenotype, reflected by higher ex vivo cell membrane expression of FC-gamma receptors (CD32 and CD64), markers of secretory vesicles (CD35) and specific granules (CD66b). Further, on cytospins of acute onset patients, this hyperactivated state was confirmed, including granulocyte precursors, vacuolization and toxic granules. ROS production and degranulation were also enhanced in active sJIA, both with medium control and after short in vitro stimulation. This activated phenotype was most prominent in patients with a short, fever-dominant disease, while it was less prominent in patients with >1 month active disease, or with a more articular phenotype at disease onset. Neutrophil phenotype normalized when patients improved to clinically inactive disease.

In contrast to the hyperactivated status of neutrophils in active sJIA, PBMC from these patients produced less Il-1b, IL-18, IL-6 and TNF-a upon TLR-stimulation compared to PBMC from patients with clinically inactive disease or HDs, suggesting tolerance after exposure to high TLR4 stimulating S100-levels in vivo. RNA-sequencing of FACS sorted monocytes ex vivo and after LPS stimulation is currently undertaken and will reveal pathways involved in this ‘tolerance’ phenotype.

Conclusion: We show here that monocytes from active new-onset sJIA patients produce less cytokines upon TLR stimulation, while the neutrophils are hyperactivated, reflected by increased cell membrane activation markers, ROS production and degranulation. The exact role of both cell types in relation to the increased S100 protein levels and the IL-1 / IL-18 activaion is currently under investigation.

Disclosure of Interest: None Declared

P423 Biomarkers in systemic onset juvenile idiopathic arthritis: prediction of therapy response

Nienke Ter Haar1,2, Rianne Scholman1, Wilco de Jager1, Ariane de Ganck3, Nadia Ryter4, Miha Lavric5, Dirk Foell5, Sytze de Roock1,2, Bas Vastert2

1Laboratory for Translational Immunology, Utrecht, Netherlands; 2Pediatric Rheumatology, UMCU, Utrecht, Netherlands; 3Biogazelle NV, Zwijnaarde, Belgium; 4BÜHLMANN Laboratories AG, Basel, Switzerland; 5Pediatric Rheumatology and Immunology, University of Muenster, Muenster, Germany
Presenting author: Nienke Ter Haar

Introduction: Systemic onset juvenile idiopathic arthritis (sJIA) is an autoinflammatory disease, characterized by fever, rash and arthritis. The IL-1 pathway and IL-6 pathway are crucial disease mechanisms in sJIA, exemplified by the excellent responses to IL-1 and IL-6 blocking therapy. However, so far it has not been feasible to base treatment choice on the individual inflammatory characteristics of a patient. In addition, we cannot predict in which patients we can safely stop therapy when inactive disease is reached.

Objectives: We aim to find biomarkers to predict: which sJIA patients will respond to IL-1 blockade at disease onset, and which patients will maintain clinical remission when IL-1 blockade is stopped after reaching clinically inactive disease.

Methods: In our center, patients are treated with recombinant human IL-1 receptor antagonist (rhIL1RA) as first-line therapy. If the response to rhIL1RA is insufficient, either low dose corticosteroids are added or the patients are switched to alternative biologicals. If patients are in inactive disease at time point three months after start of rhIL1RA, we attempt to taper and stop rhIL1RA.

Biomarker discovery was performed in the serum of patients at onset (before start of rhIL1RA) and at time point 3 months in patients with clinically inactive disease on rhIL1RA, using cytokine analysis (Luminex multiplex assay), determination of S100A12 and Mrp8/14 (ELISA) and miRNAs (qPCR). To determine differences between the groups, we used the Mann-Whitney U test, with false discovery rate (FDR) correction by Benjamini-Hochberg methodology.

Results: In total, serum of 19 patients at disease onset and 20 patients at inactive disease was available. Fifty-five proteins and 10 miRNAs were significantly different between patients at onset and at inactive disease after FDR-correction. Proteins included known biomarkers as S100A12, Mrp8/14, IL-6 and IL-18, but also novel markers including metalloproteinases and angiogenesis-related proteins.

Within the onset patients, thirteen patients had a complete response with rhIL1RA monotherapy (GR), while five patients needed additional therapy/switch of therapy (NR) because of persistent fever (n = 2), arthritis (n = 2) or both fever and arthritis (n = 1). One patient had a partial response on rhIL1RA monotherapy. On univariate (uncorrected) testing, 3 proteins and 35 miRNAs were significantly different between GR and NR. After FDR-correction none remained significant, which can be explained by the low number of patients, especially in the NR group.

In the stop-prediction part of this study, ten patients flared during tapering or after stopping of therapy, while nine patients remained in remission. One patient preferred to continue rhIL1RA and could therefore not be categorized in a response group. The PCA of the Luminex data showed that patients that will flare cluster separately from patients that will maintain clinical remission. On univariate analysis, 16 proteins and 2 miRNAs were significantly different, however none were significant after FDR correction.

Conclusion: This study aimed to find novel biomarkers for the prediction of treatment response to rhIL1RA in new-onset sJIA patients. Although no markers were significant after FDR correction, the results still provide potentially interesting biomarkers that need further analysis and modeling. A soon-to-start prospective study on optimisation of stop-strategy of rhIL1RA, will provide the opportunity to validate the predictive value of these biomarkers.

Disclosure of Interest: None Declared

P424 Impact of systemic juvenile idiopathic arthritis/Still’s disease on adolescents as evidenced through social media posting

Renee F. Modica1, Kathleen G. Lomax2, Pamela Batzel3, Armelle Cassanas3, Melissa E. Elder1

1Department of Pediatrics, University of Florida, Gainesville, FL, United States; 2Immunology and Dermatology Medical Affairs, Novartis Pharmaceuticals Corp, East Hanover, NJ, United States; 3Treato, Princeton, NJ, United States
Presenting author: Renee F. Modica

Introduction: Systemic juvenile idiopathic arthritis (SJIA)/Still’s disease is a rare form of chronic arthritis in paediatrics. The patient perspective of living with the disease is not well understood, particularly among adolescent age patients.

Objectives: The objective was to understand the adolescent SJIA experience as shown by their own social media posts.

Methods: English posts from SJIA patients were reviewed on public social media sites.

Results: 71 posts with a date range of 2009-2015 on 15 sites were reviewed in Nov 2015. 24 unique authors were identified: 17 SJIA patients (40 posts) and 7 mothers of SJIA patients (12 posts). Patients were aged 13-20 years. Several patients posted about similar diagnostic experiences marked by 5 stages: (1) misunderstood with their pain and fatigue being overlooked until a crisis occurs, (2) dismissed as ‘fakers,’ where their initial misdiagnosis is often ‘growing pains’ or ‘fake pains’, (3) misdiagnosis, often as cancer, when the symptoms acutely worsen (4) testing stage that leads to an SJIA diagnosis, and (5) focus on the difficulties of dealing with a chronic invisible disease where they feel ashamed of their arthritis and distressed at being different from their peers. Many adolescent patients, looking back at the onset of the disease when they were children, describe themselves as a “sleeping child” rather than the typical active, playing child. Patients describe trying to hide their illness from friends, but express their concerns more openly online. Patients also describe anger directed at SJIA which is described as a powerful external enemy attacking their body, using terms like “bulldozer,” “dragon,” and “monster.” Many posters used superhero language or imagery in their social media posts to help them “fight” the disease and their struggle. Mothers of SJIA patients also used warrior-child imagery and language in their posts. Some SJIA patients also posted about the risk of death, or shared stories about other SJIA patients who died which is a distinct difference from non-SJIA patients. Many patients also have adopted the term “spoonie” to describe themselves as living with a chronic disease, a term that originated in the autoimmune community to refer to how people with chronic conditions manage their energy throughout the day. Only the older teenagers used the term Still’s.

Conclusion: Adolescent SJIA patients posted openly about the difficulties of their disease causing them to be different from their healthy friends, whereas in the real world they tried to minimise or hide the effects of their disease. They frequently used superhero words and images in posts in describing their fight for health. Physicians can use these insights when counselling adolescent SJIA patients to provide a narrative that meshes with the patients’ worldview and perhaps, by speaking a similar language, could increase treatment adherence.

Disclosure of Interest: R. Modica: None Declared, K. Lomax Employee of: Novartis, P. Batzel: None Declared, A. Cassanas: None Declared, M. Elder: None Declared

P425 Influence of tocilizumab treatment on bone mineral density in patients with systemic juvenile idiopathic arthritis

Rina Denisova1, Ekaterina Alexeeva1, Saniya Valieva1, Tatyana Bzarova1, Kseniya Isayeva1, Tatyana Sleptsova1, Olga Lomakina1, Alexandra Chomahidze1, Margarita Soloshenko1, Meyry Shingarova2, Elena Kachshenko1

1Rheumatology, Scientific Center of Children’s Health, Moscow, Russian Federation; 2I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation
Presenting author: Rina Denisova

Introduction: The progression of destructive changes in the joints and development of bone resorption in rheumatic diseases are closely pathogenetic relationship. An important factor in the risk of osteoporosis is a glucocorticosteroid therapy (GC). The issue of drug therapy in patients with these complications are still relevant.

Objectives: To investigate the influence of tocilizumab therapy on bone mineral density in patients with systemic JIA option.

Methods: A retrospective analysis of 49 medical records of patients diagnosed with systemic JIA observed in the rheumatology department in one center, 25 boys and 24 girls, mean age 14 years (7; 21), the average age of disease onset - 4 years (1; 14).

Results: The high disease activity was observed in 100% of children, lack of physical activity in 23/49 (47%), fractures in 5/59 (11%). Before tocilizumab treatment 36/49 (73%)patients received oral GC, 32/49 (65%) patients pulse therapy of methylprednisolone. Status of bone mineral density (BMD) of the lumbar spine (L1-L4) according to densitometry were observed: osteoporosis (reduction of Z-score > -2) -in 15/49 (30%) children, osteopenia (Z-score between -1 and -2) - in 14/49 (29%), normal values (Z-score, <-1) - in 20/49 (41%). After a year of tocilizumab treatment osteoporosis was registered in 8/49 (16%) children,osteopenia - in 13/49 (27%), and normal values - in 28/49 (57%). The analysis of the effect of treatment with monoclonal antibodies to IL-6 on BMD in children with systemic JIA showed significant (p <0.001) increase in indicators Z-score and BMD.

Conclusion: The analysis of the effect of treatment with monoclonal antibodies to IL-6 on BMD in children with systemic JIA showed significant (p <0.001) increase in indicators Z-score and BMD. The results indicate a decrease in the degree of severity of osteoporosis.

Disclosure of Interest: None Declared

P426 Recombinant IL-1RA restores the IL-18-NK cell axis in steroid naïve systemic juvenile idiopathic arthritis patients

Wilco De Jager, Sebastiaan J. Vastert, Gerdien Mijnheer, Berent J. Prakken, Nico M. Wulffraat

Pediatric Immunology, University Medical Center Utrecht, Utrecht, Netherlands
Presenting author: Wilco De Jager

Introduction: Systemic onset juvenile idiopathic arthritis (sJIA) is a severe, acquired IL-1 mediated auto-inflammatory disease. However, not all disease manifestations can be fully explained by IL-1 activation and other cytokines, like IL-6 and especially IL-18 are strikingly elevated at disease onset. We previously showed that NK cell activation by IL-18 is disturbed in sJIA patients due to defective phosphorylation of the IL-18 receptor beta chain. However, the exact role of IL-18 in the immune pathogenesis and disease manifestations of sJIA is still unclear.

Objectives: To evaluate both clinical and immunological effects of anakinra treatment prior to steroids in newly diagnosed SoJIA patients.

Methods: Twenty consecutive patients with newly diagnosed systemic onset JIA were included. Clinical response was evaluated using the validated core set parameters for JIA. Disease activity was given as percentages improvement compared to baseline values (ACR-Ped scores). Biochemical parameters of disease activity (ESR, CRP, Ferritin, NK cell function, sIL-2R) were collected at standardized timepoints. IL-18 interactions were studied using the IL-18 sensitive myelomonocytic cellline (KG-1) using westernblotting and immunoprecipitation. Furthermore we characterized the response to anakinra evaluating cytokine profiles, NK cell phenotype and function, Caspase 1 activity.

Results: We show that sJIA patients have increased inflammasome activation contributing to elevated IL-18 levels. Treatment with rIL-1RA effectively down-regulated IL-18 levels through suppression of inflammasome activation both in vitro and in vivo. Furthermore, in sJIA patients treated early in their disease course with rIL-1RA, we observed a restoration of the defective IL-18-NK cell axis within 3 weeks of treatment with rIL-1RA. In vitro experiments, using a human myelomonocytic IL-18 reporter cell line as well as healthy control monocytes, showed direct binding of rIL-1RA to the IL-18 receptor alpha unit.

Conclusion: rIL-1RA is able to target both the IL-1 and IL-18 pathway, explaining the complete therapy response in most sJIA patients when used early in the disease course.

Disclosure of Interest: None Declared

Poster Session: Systemic lupus erythematosus and antiphospholipid syndrome II

P427 Gastrointestinal symptoms in juvenile systemic lupus erythematosus patients

Hafize E. Sönmez1, Asuman N. Karhan2, Ezgi D. Batu1, Yelda Bilginer1, Zehra S. Arıcı1, Ersin Gümüş2, Hülya Demir2, Aysel Yüce2, Seza Özen1

1Department of Pediatrics, Division of Rheumatology, Hacettepe University Faculty Of Medicine, Ankara, Turkey; 2Department of Pediatrics, Division of Gastroenterology and Hepatology, Hacettepe University Faculty Of Medicine, Ankara, Turkey
Presenting author: Hafize E. Sönmez

Introduction: Systemic lupus erythematosus (SLE) is an autoimmune disease with multiple organ involvement. SLE is affecting 10-20% of patients in childhood or puberty. Atypical presentations may occur in the childhood such as gastrointestinal system (GIS) involvement being present in the early stages of the disease. The GIS involvement in the SLE can occur as an assosiation, as a disease manifestation or as a result of the advers effects of drugs.

Objectives: We aimed to present GIS symptoms of the juvenile SLE (jSLE) patients followed in our department.

Methods: We have reviewed the medical files of 69 children with SLE who were followed at Department of Pediatric Rheumatology in Hacettepe University between January 2011 and January 2016. All patients were fulfilling the Systemic Lupus International Collaborating Clinics criteria. All SLE patients (≤18 years of age) who had gastrointestinal system manifestations were included in study.

Results: GIS manifestations were observed in 19 (27.5%) out of 69 SLE patients and present at the time of SLE diagnosis in 13 (68.4%) patients. There was no significant difference in clinical or serological features between patients with and without GIS involvement. The median (min-max) age of SLE diagnosis was 120 (60-192) months; the age of the onset of the GIS symptoms was 156 (60-204) months. The median time from the SLE diagnosis to the onset of the GIS symptoms was 0 (0-96) months. The SLE GIS manifestations were autoimmune hepatitis (AIH) (n = 8) and lupus enteritis (n = 1). SLE associations were hepatomegaly and hypertransaminasemia associated with macrophage activation syndrome (MAS) (n = 3) and hepatic steatosis (n = 1). GIS manifestations as a result of the adverse events of drugs were as follows: toxic hepatitis (n = 3; associated with methotrexate and nonsteroidal anti-inflammatory drugs in one patient, methotrexate in another patient, and azathioprine in another patient), azathioprine induced cholestatic hepatitis (n = 1), and gastritis associated with corticosteroid (n = 1). In one patient, acute appendicitis occurred as a co-incidental manifestation. At the time of presentation with GIS symptoms, the median (min-max) erythrocyte sedimentation rate was 40 (4-81) mm/hour and SLE activity index was 8 (4-26). The median AIH score of the AIH patients was 18 (15-22).

For treatment, the drug of interest was discontinued for the patients with drug-related hepatitis. Seven out of eight patients with AIH received corticosteroids and azathioprine for treatment. One of these patients received ursodeoxycholic acid in addition to the immunosuppressive treatment. One AIH patient was treated with corticosteroid. Two patients with MAS received corticosteroid and cyclosporine treatment while one got corticosteroid and intravenous immunoglobulin. Corticosteroid was given to the patients with lupus hepatitis and lupus enteritis. Proton pump inhibitor was prescribed to the patient with gastritis. Dietary modifications and weight control were advised to the patient with hepatosteatosis. The GIS manifestations improved in all patients with treatment.

Conclusion: In this study, we have demonstrated that one out of every five JSLE patients of ours had GIS-related signs and symptoms during SLE course and GIS involvement may occur as an initial manifestation of the disease. Thus, it is important to consider SLE in the differential diagnosis of GIS manifestations in children. Furthermore, the criteria for SLE diagnosis may include GIS involvement since it is probably more common than anticipated.

Disclosure of Interest: None Declared

P428 Reference ranges for the antiphospholipid antibodies in children are different from those in adults- the North Indian experience

Jasmina Ahluwalia1, Bhavneet Bharti2, Sweta Rajpal1, Varun Uppal1, Alaknanda Walia1, Surjit S. Samlok2, Narender Kumar1

1Hematology, Chandigarh, India; 2Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India
Presenting author: Jasmina Ahluwalia

Introduction: Antiphospholipid antibody syndrome (APS) is an autoimmune disorder characterised by thrombosis and /or recurrent pregnancy losses and positivity for the lupus anticoagulant (LA), anticardiolipin (ACA) or anti beta 2 glycoprotein 1 (aβ2GP1) antibodies. Current guidelines recommend that values more than the 99th centile of the antibody levels found in the normal population be used to classify positivity for APS. APS has been reported in children. Pediatric controls subjects are difficult to obtain and laboratories may have to use the adult cut off values to report test positivity.

Objectives: We screened healthy children and adult volunteers in Chandigarh, India to compare the reference values of the 99thcentiles of ACA and aβ2GP1 antibodies.

Methods: Children aged between 1.5 months and 18 years and adults between 19 and 60 years were screened once for the IgG and IgM isotypes of ACA and aβ2GP1 antibodies by ELISA kits (Orgentec GmBh). Subjects with history of recent illness or drug intake in the preceding 15 days were excluded from sampling The pediatric samples were grouped as: Group I-aged <1year; II-1 to 5 years, III -6 to 10 years and IV- >10 years old. The 99th centiles for the two populations and 4 groups in the children were determined and compared.

Results: 129 children and 144 adults were screened. Three children and 2 adults were excluded from analysis since they were positive for more than 1 antibody. Data for 126 children (71 males, 55 females) and 142 adults (88 males, 54 females) were available for analysis. There were 27, 33, 27 and 39 children in groups I, II,III and IV respectively. The data distribution for levels of all isotypes tested was skewed. The 99th centile values in children vs adults were as follows ACA IgG-8.22 vs.15.41; for ACA IgM -3.2 vs. 6.32; aβ2GP1 IgG-18 vs. 4.39; aβ2GP1 IgM-8.75 vs. 5.94. The group wise 99th centile values for the antibodies are depicted in the table.
 

99 th Centile values

Subject group

ACA IgG

ACA IgM

2 GP1 IgG

2 GP 11 IgM

Adults

(n = 142)

15.41

6.32

4.39

5.94

Pediatric controls

n = 126)

8.22

3.2

18

8.75

Pediatric Group I (<1 year)

(n = 27)

8.78

1.53

16.6

2.57

Pediatric Group II (1-5 years)

(n = 33)

7.03

2.58

24.71

7.23

Pediatric Group III (6 -10 years)

(n = 27)

3.03

1.35

5.05

6.51

Pediatric Group IV (11-18 years)

(n = 39)

5.16

3.99

4.34

12.16

Conclusion: The 99th centile values for adults and children differed significantly, with adults exhibiting higher cut offs for ACA isotypes, whereas for aβ2GP1 antibodies the cut off was higher among children. The IgG isotype cut off levels were higher than the IgM isotypes for ACA, though such a pattern was not seen with aβ2GP1. The IgG isotypes of both ACA and aβ2GP1 antibodies were highest in infants and showed a decreasing trend with increasing age. A variable pattern was observed for IgM isotype of aβ2GP1 antibodies. Despite the limitations of single determinations and using only one commercial kit, the data support the fact that determining reference ranges for the APS antibodies in children is important to avoid potential misclassification of APS. With the widespread use of commercial ELISA kits for establishing APS in children, provision of pediatric reference ranges by the kit manufacturers would be invaluable for small laboratories with limited access to pediatric controls.

Disclosure of Interest: None Declared

P429 Anti-ribosomal P antibody: a multicenter study of 228 childhood-onset systemic lupus erythematousus patients

Clarissa C. Valões1, Beatriz C. Molinari1, Ana Claudia G. Pitta1, Natali W. Gormezano2, Sylvia C. Farhat1, Kátia Kozu1, Adriana M. Sallum1, Simone Appenzeller3, Ana Paula Sakamoto4, Maria T. Terreri4, Rosa M. Pereira2, Claudia S. Magalhães5, Cássia Maria Barbosa6, Francisco Hugo Gomes7, Eloisa Bonfá2, Clovis A. Silva1

1Pediatric Rheumatology Unit, Faculdade de Medicina d Universidade de São Paulo, São Paulo – SP, Brazil; 2Pediatric Rheumatology Division, Faculdade de Medicina d Universidade de São Paulo, São Paulo – SP, Brazil; 3Pediatric Rheumatology Unit, UNICAMP, Campinas-SP, Brazil; 4Pediatric Rheumatology Unit, UNIFESP, São Paulo – SP, Brazil; 5Pediatric Rheumatology Unit, UNESP, Botucatu-SP, Brazil; 6Pediatric Rheumatology Unit, Hospital Darcy Vargas, São Paulo – SP, Brazil; 7Pediatric Rheumatology Unit, USP-Ribeirão Preto, Ribeirão Preto, SP, Brazil
Presenting author: Kátia Kozu

Introduction: Anti-ribosomal P (anti-P) antibody is highly specific for systemic lupus erythematosus (SLE) and recognizes three ribosomal phosphoproteins. Evaluation of this autoantibody in childhood-onset SLE (cSLE) populations is limited to few small series hampering the interpretation of the diverse standardized 19 neuropsychiatric syndromes case definition for this specificity.

Objectives: The objective of this multicenter cohort study was to evaluate demographic, clinical and laboratorial features in cSLE patients with and without the presence of anti-P antibody.

Methods: This is a retrospective multicenter study performed in 10 Pediatric Rheumatology services of São Paulo state, Brazil. Anti-P antibody was measured by enzyme-linked immunosorbent assay (ELISA) in 228 cSLE patients. Demographic data, cumulative clinical and laboratorial features and disease damage (SLICC/ACR-DI) at last visit were evaluated.

Results: Anti-P antibody was observed in 61/228 (27%) cSLE patients. Frequencies of cumulative lymphadenopathy (29% vs. 15%,p = 0.013), acute confusional state (13% vs. 5%,p = 0.041), mood disorder (18% vs. 8%, p = 0.041), autoimmune hemolytic anemia (34% vs. 15%,p = 0.001), as well as anti-Sm (67% vs. 40%,p = 0.001), anti-RNP (39% vs. 21%,p = 0.012) and anti-Ro/SSA antibodies (43% vs. 25%,p = 0.016) were significantly higher in cSLE patients with anti-P antibodies compared to those without this autoantibody. Multiple regression model revealed that anti-P antibody was associated with autoimmune hemolytic anemia (OR = 2.719, 95%IC:1.365-5.418,p = 0.004) and anti-Sm antibody (OR = 2.758, 95%IC:1.304-5.833,p = 0.008). SLICC/ACR-DI was comparable in patients with and without anti-P antibodies (p = 0.780).

Conclusion: We describe a novel association of anti-P antibody and autoimmune hemolytic anemia in childhood onset SLE. The additional observation of an association of anti-P and anti-Sm antibodies is further supported by the same finding in lupus animal model.

Disclosure of Interest: None Declared

P430 Fresh frozen plasma treatment for Systemic Lupus Eritematozus cases associated with complement deficiency

Kubra Ozturk, Zelal Ekinci

Department of Pediatrics Rheumatology, Kocaeli University Faculty of Medicine, Kocaeli, Turkey
Presenting author: Kubra Ozturk

Introduction: Systemic Lupus Eritematozus (SLE) is a multifactorial autoimmune disease whose etiology is unknown. Genetic background, immunological abnormalities and environmental factors are included in the pathogenesis. In case of hereditary deficiency of early complement components, SLE frequently develops in the early childhood.

Objectives: The aim of this report is to share our experiences gained during the course of five cases diagnosed as SLE with hereditary deficiency of early complement components.

Methods: Five cases from three different families diagnosed as SLE with hereditary deficiency of early complement components and treated successfully by fresh frozen plasma (FFP) are presented in this paper. All patients have been followed up in the Kocaeli University School of Medicine Department of Pediatric Rheumatology.

Results: Three female and two male patients are included in this report. Parents of all patients had consanguinity. There was no other individual diagnosed as SLE in the families mentioned. Initial complaint of all cases were skin findings while one had mucosal involvement and two had joint involvement. They did not have any other organ involvement. While antinuclear antibody was detected positive in all cases, low titer anti ds DNA positivity was detected in only one case. Prior to refering our hospital, four patients had been treated with steroids and hydroxychloroquine. In addition, two patients had been treated with methotrexate while two patients had been treated with azathioprine whereas one patient had not been treated previously. It was learned that a few patients have responded only partially to these treatments, while some have not at all. Thus, hereditary deficiency of early complement components was taken into consideration. While one patient had complement C1q deficiency, other four were considered to have deficiency of early complement component of classical pathway due to low CH50 level. All symptoms of all cases improved by FFP infusion, with a frequency of three days in a week at first, but once skin findings got calmed, the infusion was arranged with a frequency that would prevent the exacerbation of symptoms. Laboratory features and treatment modalities of the patients are presented in Table 6.

Conclusion: In early onset SLE cases in which skin findings are significant, hereditary deficiency of early complement components must be considered. It is known that in such cases, severe skin findings can not be controlled with conventional immunosuppressive treatment. For the present, regular FFP infusions seem to be a good option for remission. However, the duration of this treatment and its complications that may arise in the long term are debatable.

Disclosure of Interest: None Declared
Table 6 (abstract P430).

Laboratory features and treatment modalities of the patients

 

A

B1

B2

C1

C2

CH50

35% (70-140)

29% (40-130)

27% (40-130)

<3 U/ml (30-75)

<3 U/ml (30-75)

C1q

<6 mg/L (118-238)

126% (70-130)

150% (70-130)

Not evaluated

25 mg/dl (12-22)

C2

Not evaluated

Not evaluated

40 mg/L (14-25)

Not evaluated

3.1 mg/dl (1.13)

C3

175 mg/dl (90-180)

104 mg/dl (90-180)

152 mg/dl (90-180)

119 mg/dl (90-180)

95 mg/dl (90-180)

C4

37 mg/dl (10-40)

31 mg/dl (10-40)

38 mg/L (10-40)

30.4 mg/dl (10-40)

26mg/dl (10-40)

Prior treatment

Steroid

Steroid

Steroid

Steroid

No treatment

Azathioprine

Methotrexate

Methotrexate

Azathioprine

Hydroxychloroquine

Hydroxychloroquine

Hydroxychloroquine

Hydroxychloroquine

Present treatment

Hydroxychloroquine

Hydroxychloroquine

Hydroxychloroquine

Hydroxychloroquine

Hydroxychloroquine

FFP

FFP

FFP

FFP

FFP

Time of FFP treatment

37 months

28 months

30 months

7 months

7 months

Frequency of FFP

3 weekly

4 weekly

3 weekly

Once a week

Once a week

P431 Clinical value of 24-hour protein in urine for Nephritis activity in pediatric patients with SLE in comparison to anti-dsDNA

Maie Helal

Alexandria University, Alexandria, Egypt

Introduction: Systemic lupus erythematosus (SLE) is a prototypic multisystem autoimmune disorder. Lupus Nephritis(LN) is the most common form of affection in SLE. Clinical and laboratory monitoring of cases with LN is crucial to avoid relapse and ensure proper adjustment of therapy. While monitoring has been the corner stone for assessing disease activity, laboratory tests are helpful in systems that cannot be assessed clinically. Antibodies to (ds) DNA are found at some point during the course of the disease while, 24-hour protein in urine is widely regarded as the gold standard for laboratory assessment of proteinuria in LN.

Objectives: To evaluate 24-hour protein in urine in pediatric systemic lupus erythromatosus (pSLE) and determine its clinical and statistical association in nephritis activity in comparison to anti-dsDNA

Methods: 44 pSLE patients with LN and 30 healthy individuals were enrolled. Patient records were evaluated for clinical and laboratory associations. Disease activity assessment was performed using SLEDAI, Anti-dsDNA,renal biopsies and 24-hour protein in urine.

Results: Proteinuria correlated significantly with renal biopsies and decreased complement levels (p < 0.05). Proteinuria were significantly elevated in patients with class III/IV nephritis compared II/V nephritis. pSLE patients with active nephritis at the time of sample collection demonstrated significant proteinuria compared to those without active nephritis. 24-hour protein in urine was more sensitive and specific than anti-dsDNA in monitoring disease activity pSLE with LN.

24-hour protein in urine

SLEDAI

Test of sig.

p

OR

95% CI (LL-UL)

 

≤4 (n = 36)

>4 (n = 28)

    
 

No.

%

No.

%

    

Abnormal ≥500

Normal

22

14

61.1

38.9

1

27

3.6

96.4

r = 0.65

<0.001*

42.429*

5.168-348.357

Conclusion: This study indicates the importance of monitoring 24-hour protein in urine in follow up visits of pSLE patients with LN. Elevated 24-hour protein in urine may be more indicative and specific for detecting disease activity, showing significant active nephritis than anti-DNA antibodies.

Disclosure of Interest: None Declared

P432 Serum calprotectin is not associated with renal flare in juvenile systemic lupus erythematosus

Natalia Cabrera1, Alexandre Belot1, Jean Christophe Lega2, Jocelyne Drai3, Rene Ecochard4

1Hôpital Femme Mère Enfant, Bron, Lyon, France; 2Internal Medicine and Vascular Department, CHU Lyon Sud, Lyon, France; 3Laboratory of Biochemistry and Molecular Biology, Lyon Sud, Lyon, France; 4Biostatistics Health Laboratory. “Claude Bernard” University of Lyon 1, UCBL1, Lyon, France
Presenting author: Natalia Cabrera

Introduction: Systemic lupus erythematosus (SLE) is characterized by a deregulation of the innate and adaptive immune system. SLE is the paradigm of tolerance breakthrough and underlying mechanisms are multiple, including defects in apoptosis, production of autoantibodies and formation of immune complexes within tissues (particularly renal parenchyma). Juvenile SLE (jSLE) is a rare disease that is more severe that in adult’s onset, mainly because of the more frequent kidney and neurological involvement. In the pathogenesis of SLE, the neutrophils have been recently identified as key players participating in a special active process of cellular death so called NETosis by releasing outside the cell DNA, histones and pro-inflammatory proteins such as MRP8/14 (named also calprotectin). Calprotectin is a key protein in the perpetuation of the inflammatory response by participation in the activation of intracellular signaling pathways; with DAMP role (damage-associated molecular patterns) in binding to TLR4 receptors granulocytes, involved in the production of interferon alpha (IFNα).

Objectives: Increased serum calprotectin levels have been reported increased in chronic rheumatic diseases including SLE, and could represent a biomarker of renal flare.

Methods: We retrospectively collected clinical and biological data from 30 patients with jSLE. This study was set up in a single academic center (Pediatric Nephrology and Rheumatology Department of University Hospital of Lyon). Forty frozen samples were analyzed for studying correlation of renal involvement.

Results: All 30 patients with jSLE from the retrospective cohort participated in the study. The average age at diagnosis was 13.4 (±4) years, with a sex ratio of 1/6. The Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score in jSLE was increased, mean 12 ± 8.6 (2 – 34). Twenty-two patients displayed a lupus nephritis (LN) in the course of the disease. LN is inaugural in half of cases. Delay of serum calprotectin measure was, in mean, 5 ± 5.2 years after beginning of jSLE; values varies from 0 to 18 years. We did not find any correlation with the title of anti-DNA antibodies (measured by Farr assay test), complement proteins (C3, C4 and CH50) and creatinine levels. The correlation analysis between serum calprotectin and the glomerular filtration rate (GFR calculated by Schwartz 2009 formula) was not significant (p = 0.6). Calprotectin is not different in patients with kidney disease (8.8 ± 12.2 mg/ml) compared to patients without renal involvement (7.4 ± 7.6 mg/ml).

Conclusion: We found no association between serum calprotectin dosage and clinic-biological parameters including: SLEDAI score, C3, and C4, creatinine levels, proteinuria and GFR. Serum calprotectin values were not significantly different between children with and without proteinuria. The calprotectin does not seem a biomarker of renal involvement in jSLE.

Disclosure of Interest: None Declared

P433 Thrombosis in children with systemic lupus erythematosus

O. V. Shpitonkova, N. S. Podchernyaeva, Y.O. Kostina, N. G. Dashkova, M. K. Osminina

Pediatric Department, I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation
Presenting author: O. V. Shpitonkova

This abstract is not included here as it has already been published.

P434 Preliminary validation of the Turkish Simple Measure of Impact of Lupus Erythematosus in Youngsters (SMILEY) in a single center

Gozde Yucel1, Sezgin Sahin1, Amra Adrovic1, Kenan Barut1, Ela Tarakci1, Ahmet Arvas2, Nandini Moorthy3, Ozgur Kasapcopur1

1Pediatric Rheumatology, Istanbul University, Cerrahpasa Medical Faculty, Istanbul, Turkey; 2Pediatrics, Istanbul University, Cerrahpasa Medical Faculty, Istanbul, Turkey; 3Pediatric Rheumatology, Rutgers University, Robert Wood Johnson Medical School, Liverpool, United Kingdom
Presenting author: Ozgur Kasapcopur

Introduction: Juvenile systemic lupus erythematosus (SLE) is a chronic multisystemic disease with an episodic course which is prevalent in all cultures with wide-ranging effects on their health-related quality of life (HRQOL). In order to detect the effect of SLE on pediatric population and their parents; a disease specific HRQOL tool, called Simple Measure of Impact of Lupus Erythematosus in Youngsters (SMILEY), was developed, translated into different languages and validated in several languages.

Objectives: To determine the validity and reliability of the Turkish SMILEY in our center. Here we are presenting the preliminary data of our single-center research.

Methods: In our cross-sectional study, Turkish children and adolescents 8–18 years of age with SLE and their parents were enrolled. Pediatric SLE patients and parents completed child and parent reports of Turkish SMILEY and Turkish Pediatric Quality of Life Inventory (PedsQLTM) Generic module. Disease activity was estimated by examining physicians with usage of the SLE disease activity index (SLEDAI) and Physician’s Global Assessment of disease activity (PGA); chronic damage with the Systemic Lupus Erythematosus International Collaborating Clinics ACR Damage Index (SDI). Test-retest reliability, agreement between child and parent reports of the Turkish SMILEY and validity modalities were examined.

Results: 70 children with SLE (Male/Female 11/59; mean age at investigation 15.4 ± 2.8 years, mean disease duration 41.4 ± 29.4 months) were recruited into the study. Our patients have a median SLEDAI of 4 (range 0-23), and median SDI of 0 (0-5), and median PGA was 1 (0-4) and 80% of these were active (SLEDAI > 0).

Out of 70 children, only one child didn’t complete the child report SMILEY scale; but all of seventy parents were able to fulfill their corresponding report of the Turkish SMILEY. 59 child subjects and 60 parent subjects solved the Turkish SMILEY again 14 days later. The ICC for all domains and total scores of child report (0.7-0.9, P < 0.001) and parent report (0.6-0.9, P < 0.001) was significant, thus confirming excellent test-retest reliability.

Agreement between children and their parents was found to be favoring. For the existing child-parent pairs (n = 69), moderate rho (0.4-0.6, P < 0.001) and significant ICC (0.6 - 0.8, P < 0.001) values were seen between the child and parent SMILEY total and domain scores.

For children; the mean SMILEY total score was 70.3 ± 13.4 and the mean PedsQLTM Generic module score was 78 ± 15.7. For the parents they were calculated as 70.1 ± 13.4 and 77 ± 16.5 respectively. There was a significant correlation between these scores both for the children (r = 0.5, P < 0.001) and the parents (r = 0.4, P < 0.001).

In our study; important Spearman’s correlations were found between child report of Turkish SMILEY and factors affecting morbidity, mortality. The child SMILEY total score (n = 69) correlated remarkably with the PGA (r = 0.7, P < 0.001), SLEDAI (r = 0.4, P < 0.001), and SDI (r = 0.5, P < 0.001).

The children with lower disease activity and damage were discovered to have higher scores in their corresponding SMILEY report, hereby emphasizing better QOL. This relationship was especially noticeable in total score and the limitation domain of SMILEY.

Conclusion: This first validation study about HRQOL of pediatric SLE patients in Turkey showed that; Turkish SMILEY is a useful, valid and a reliable disease-specific questionnaire which can be further used as a beneficial research tool in our country.

Disclosure of Interest: None Declared

P435 Juvenile-onset lupus nephritis and local kidney involvement: gaining insight into the role of the glomerular endothelial cells in urinary biomarker production

Paraskevi Dimou1, Angela Midgley1, Matthew Peak1,2, Simon C. Satchell3, Rachael D. Wright1, Michael W. Beresford1,2

1Women’s and Children’s Health, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom; 2Alder Hey Children’s Hospital, Liverpool, United Kingdom; 3Academic Renal Unit, University of Bristol, Bristol, United Kingdom
Presenting author: Paraskevi Dimou

Introduction: Lupus nephritis (LN) is a serious clinical manifestation of juvenile systemic lupus erythematosus (JSLE) causing chronic renal inflammation and the loss of high amounts of proteins in the urine (proteinuria), which can prove to be useful biomarkers for non-invasive renal disease monitoring.

Objectives: Our study aimed to investigate whether the glomerular endothelial cells (GEnCs), which are essential for the processes of blood filtration and urine production, are capable of producing Monocyte Chemoattractant Protein-1 (MCP-1) and Vascular Cell Adhesion Molecule-1 (VCAM-1); two candidate novel urinary protein biomarkers.

Methods: Conditionally immortalized human GEnCs (ciGEnCs) were treated for 48 hours at 37°C with 5% sera from JSLE patients with a history of renal involvement (n = 5) and age- and sex-matched healthy controls (n = 5). ciGEnCs in culture medium with 5% FBS were used as negative controls. ciGEnCs were also stimulated with 10ng/ml interferon-alpha (IFNα), a cytokine central to JSLE pathogenesis. After 48 hours, culture media were collected and total RNA was isolated. Quantitative real-time PCR (qRT-PCR) for MCP-1 and VCAM-1 mRNA and ELISA’s for MCP-1 and soluble VCAM-1 (sVCAM-1) proteins were performed. JSLE and healthy control serum samples were included in the ELISA assays in order to determine whether MCP-1 and sVCAM-1 were secreted by the ciGEnCs or already present in the sera. Data analysis was performed using Friedman’s test with Dunn’s post-hoc test.

Results: All treatment groups including negative controls expressed the MCP-1 and VCAM-1 mRNAs. However, qRT-PCR analysis did not reveal any statistically significant differences in mRNA expression. MCP-1 protein was secreted exclusively by the ciGEnCs whereas no detectable levels were found in the serum samples. JSLE sera augmented MCP-1 secretion (552.8 pg/ml; 197.4-1186) compared to healthy control sera (271.8 pg/ml; 258.4-1524) but this increase did not reach statistical significance. On the contrary, sVCAM-1 was mainly detected in JSLE and healthy control sera whereas the ciGEnCs secreted only minor amounts of sVCAM-1.

Conclusion: The ciGEnCs have the ability to express MCP-1 and VCAM-1. As there are not significant differences in mRNA and protein amounts for MCP-1, the ciGEnCs might not be the sole source of this biomarker in the kidney; other resident renal cells could be also activated to produce MCP-1. Furthermore, MCP-1 production might be secondary to other contributors to renal inflammation in LN. The fact that the ciGEnCs do not secrete significant amounts of sVCAM-1 highlights a potentially important role for the membrane-bound VCAM-1 in LN. The highly inflammatory environment of the lupus kidney could activate the GEnCs to express VCAM-1 on their surface and secrete MCP-1; membrane VCAM-1 and MCP-1 could in turn promote immune cell infiltration into the glomerulus, resulting in sustained renal inflammation. sVCAM-1 could be an indicator of systemic JSLE disease activity but not specific for LN. Finally, MCP-1 in combination with other candidate novel urinary biomarkers could prove to be a potentially important indicator of local kidney involvement in LN.

Disclosure of Interest: None Declared

P436 Working towards a clinical trial of urine biomarker led monitoring in lupus nephritis: can patients send their urine to hospital through the post?

Rachel Corkhill, Eve M. Smith, Michael W. Beresford

Woman and Childrens Health, Liverpool University, Liverpool, United Kingdom
Presenting author: Rachel Corkhill

Introduction: Lupus nephritis (LN) affects up to 80% of Juvenile-onset Systemic Lupus Erythematosus (JSLE) patients. Conventional markers of JSLE disease activity are poor at adequately detecting LN flares and the role of renal biopsy in LN monitoring is limited by it’s invasive nature. A urine ‘biomarker panel’ comprising of vascular cell adhesion molecule-1 (VCAM-1), monocyte chemoattractant protein 1 (MCP-1), lipocalin like prostaglandin D synthase (LPGDS), transferrin, ceruloplasmin and alpha-1-acid glycoprotein (AGP) has been shown to perform to a ‘excellent’ level for identification of active LN on a cross sectional basis within the UK JSLE Cohort Study. The ability of this panel to predict flare, remission, treatment response and prognosis has not been fully elucidated. To this end, a prospective study collecting serial, frequent JSLE patient urine samples is warranted. To reduce the impact of such a study on patients lives, these samples would ideally be sent to hospital through the post.

Objectives: To assess the stability of urine biomarkers in samples which have been processed using accepted standard techniques compared with those that undergo delayed processing but are transported in the presence of additives (protease inhibitors or boric acid) and an ice-pack.

Methods: Participants of the UK JSLE Cohort Study, aged < 16 years at diagnosis were included. Urine samples were obtained at routine clinics. One aliquot underwent standard processing (centrifuged at 2000rpm for 5 minutes, stored at -80°C) and four more aliquots were taken and added to eppendorfs containing protease inhibitor 1 (condition 1), protease inhibitor 2 (condition 2), protease inhibitor 1 and boric acid (BA, to inhibit bacterial growth, condition 3), protease inhibitor 2 and BA (condition 4). After 48 hours, the samples were centrifuged at 2000rpm for 5 minutes and stored at -80°C. Novel urinary biomarkers VCAM-1, MCP-1, LPGDS, transferrin, ceruloplasmin and AGP were quantified by enzyme-linked immunosorbent assays. Biomarker levels in samples exposed to conditions 1-4 were compared to those processed in the standard fashion. The study had full ethical approval in place.

Results: Six JSLE patients and two healthy controls were included, 7 female / 1 male, median age 15.6 years (IQR 12.1-16.6) and length of disease 1.8 years (IQR 13.2-16.2). Condition 1, including protease inhibitor 1 and ice proved to be better than other conditions for maintaining biomarker levels. Compared with standard processing, biomarkers in the presence of condition 1 were as follows; VCAM-1 111%, AGP 87%, CP 120%, TF 99%, LPGDS 108%, MCP-1 106%. With condition 1, all biomarker levels were within 20% of the standard urine processing levels. The second best condition was condition 3, which included protease inhibitor 1 & BA & ice (see Table below).

Urine processing conditions

% of Standard Processing

VCAM-1

AGP

CP

TF

LPGDS

MCP-1

Protease inhibitor 1 + ice

111

87

120

99

108

106

Protease inhibitor 2 + ice

114

95

122

85

116

62

Boric acid + protease inhibitor 1 + ice

114

104

116

106

106

78

Boric acid + protease inhibitor 2 + ice

116

121

113

171

117

426

Conclusion: Use of protease inhibitor 1 and ice-packs with samples being transported through the post provides an opportunity for a clinical study which will provide very close monitoring of urine biomarker levels without having to bring the patient to hospital very frequently, reducing the impact of the study on their lives. Such a study will be able to accurately identify if such markers are able to predict flare, remission, treatment response, informing a study of urine biomarker led monitoring.

Disclosure of Interest: None Declared

P437 Complement deficiency in early-onset lupus: experience from a tertiary care centre in North India

Sagar Bhattad1, Amit Rawat1, Surjit Singh1, Anju Gupta1, Deepti Suri1, Martin de Boer2, Taco Kuijpers2

1Pediatrics, PGIMER, Chandigarh, India, Chandigarh, India; 2Blood lab, Sanquin Blood Supply Foundation, Amsterdam, Netherlands
Presenting author: Sagar Bhattad

Introduction: Inherited deficiencies of early complement components of the classical pathway (C1q, C4 and C2) are the strongest risk factors for monogenic forms of lupus. This form of lupus characteristically has a young age at onset (1), predominant cutaneous manifestations and unique management strategies (2).

Objectives: To assay complement C1q, C2, C3 and C4 and CH50 in children with early-onset lupus (onset below 5 years).

Methods: Children with systemic lupus erythematosus (SLE) attending the Pediatric Rheumatology Clinic at our institute were enrolled after written informed consent. Records of those who had an onset of SLE below 5 years of age were analyzed in detail. Complement components C1q and C2 levels were estimated by enzyme-linked immunosorbent assay (ELISA) whereas C3 and C4 were measured by end-point nephelometry. Functional assay for the classical pathway (CH50) was carried out by ELISA. Mutation analysis of the classical complement pathway proteins was carried out in children with depressed complement levels.

Results: Five children with onset of SLE below 5 years were noted. Male:female ratio was 3:2. Mean age of onset was 1.9 years. Mean duration of illness at the time of enrollment was 4.6 years (0.2 to 9.5 years). Rash was noted in 80%, renal involvement in one and neurological involvement was documented in one. Anti-nuclear antibodies were detected in all and they were of speckled pattern on indirect immunofluorescence (IIF). Anti-dsDNA antibodies were negative in all, except one.

All children had markedly reduced CH50, 3 had low C1q, while 2 had low C4. Amongst children with low C1q, mutation analysis of C1qA gene revealed a homozygous nonsense mutation: C1QA (NM_015991) c.622C > T, p.Q208X in Patient 1. A homozygous acceptor splice site mutation at the −2 position of intron 2 of C1QA (c.164-2A > C) was detected in Patient 2. In the third child with C1q deficiency, anti-C1q antibodies were absent.

Patient 1 had lost a sibling due to probable lupus. On screening of family members, younger brother was noted to have markedly reduced CH50, low C1q and mutation analysis revealed homozygous mutation in the same gene. He, however, is asymptomatic at present. Details have been tabulated below:

Conclusion: Children with C1q deficiency developed SLE at a young age and presented predominantly with cutaneous manifestations. Immunological investigations revealed negative anti-dsDNA and low CH50. Mutations in C1QA gene were noted in 2 children with early onset SLE. One child with C1QA gene mutation is asymptomatic and is under close follow-up.

References:

1. Stegert M, Bock M, Trendelenburg M. Clinical presentation of human C1q deficiency: how much of a lupus? Mol Immunol 2015;67(1):3–11

2. Arkwright PD, Riley P, Hughes SM, Alachkar H, Wynn RF. Successful cure of C1q deficiency in human subjects treated with hematopoietic stem cell transplantation. J Allergy Clin Immunol 2014 ;133(1):265-7

Disclosure of Interest: None Declared
Table 7 (abstract P437).

Details of children with early onset lupus

Sl. No

Age at onset

Predominant clinical manifestations

ANA

Anti- dsDNA (IU/ml)

C1q

C3

C4

CH 50

Mutation analysis

1

2.5

Cutaneous, CNS

4+ (s)

1.5

0.24

1610

420

0

C1QA (NM_015991) c.622C > T, p.Q208X

Brother of 1

a

Asymptomatic

3+ (s)

1.0

0.27

1970

400

0

C1QA (NM_015991) c.622C > T, p.Q208X

2

1.5

Cutaneous

3+ (s)

7.7

0.37

2500

500

0.09

C1QA (c.164-2A > C)

3

2

Muco-cutaneous

4+ (s)

6

3.3

156

36

0.1

-

4

3

Renal

4+ (s)

16

30

47

<3

0.33

-

5

0.7

Cutaneous

3+ (s)

109

164

86

10

1.6

-

a Asymptomatic, s- speckled pattern on IIF

P438 Neuropsychiatric lupus with hepatitis in a child with CMV co-infection: chicken first or the egg?

Sagar Bhattad, Amit Rawat, Anju Gupta, Deepti Suri, Vignesh Pandiarajan, Surjit Singh

Pediatrics, PGIMER, Chandigarh, India, Chandigarh, India
Presenting author: Sagar Bhattad

Introduction: Systemic lupus erythematosus (SLE) is a multi-systemic disease with multifactorial etiology. Cytomegalovirus (CMV) infection at first presentation in pediatric SLE (pSLE) is a rare phenomenon. In a study of 670 patients with pSLE (1), CMV infection at the time of diagnosis was noted in 7 patients (incidence: 1.04%). This is the largest series reporting CMV in pSLE.

Objectives: To report an adolescent girl with SLE presenting with neurological and hepatic manifestations and CMV co-infection.

Methods: 12-year old girl presented to our department with history of low grade intermittent fever for 7 months, maculopapular rash over trunk and photosensitive malar rash for 5 months and jaundice for 1 month. She had altered behavior with agitation, disorientation, fluctuating consciousness, hallucinations and altered sleep. There was no significant past history and her development was age-appropriate. On examination, she had a small head, malar rash, icterus and hepatosplenomegaly. She also had catatonia, mutism, would stare intermittently, had low speech output and psychomotor retardation with rigidity. There was no focal deficit. Investigations revealed pancytopenia, transaminitis, conjugated hyperbilirubinemia, normal renal functions. Immunological tests: anti-nuclear antibody (ANA) - strongly positive (homogenous pattern on IIF), high anti-dsDNA with hypocomplementemia. Tests have been tabulated.

She was evaluated extensively for cause of hepatitis (Table 8). Liver biopsy revealed steatosis with hepatitis. Screen for infections was negative, except CMV. Very high levels of CMV DNA in blood were noted on PCR. It was a clinical dilemma as to whether CMV was causative, co-infection or a re-activation due to immunosuppression.

For neuropsychiatric manifestations, CSF analysis was performed which was normal. Magnetic resonance imaging (MRI) of brain showed cortical atrophy. There was no evidence of any vascular involvement.

Results: Child was treated with intravenous (IV) methylprednisolone, IV cyclophosphamide pulses and ganciclovir. CMV hyper-immune globulin could not be administered due to financial constraints. Over next 6 weeks, she had improvement in neurological status. Hallucinations, agitation and rigidity had become passive, while there was mild improvement in psychomotor retardation. Transaminitis gradually recovered, bilirubin normalized and on repeat testing, CMV was undetectable. She is now doing well on maintenance immunosuppression and oral valganciclovir.

Conclusion: We present a challenging case of SLE with neuropsychiatric and hepatic manifestations along with CMV co-infection. Whether CMV came first or SLE remains unresolved. The ideal strategy of managing such patients is yet to be defined.

References

1. Rozenblyum EV, Levy DM, Allen U, Harvey E, Hebert D, Silverman ED. Cytomegalovirus in pediatric systemic lupus erythematosus: prevalence and clinical manifestations. Lupus 2015;24(7):730-5

Disclosure of Interest: None Declared
Table 8 (abstract P438).

Investigations in the index child

Investigation

Result

Investigation

Result

Hemoglobin (g/L)

87

ANA

3+ (homogenous)

Leucocyte counts (x 109/L)

6

Anti-dsDNA

733 IU/ml (<40)

Platelet counts (X 109/L)

20

C3       C4

68 (50-150) 6 (20-50)

Urea/creatinine

15/0.6

DCT

Anti-IgG +, C3d -

Serum protein/albumin

5.8/2.8

APL work up

negative

Total bilirubin/ direct

13/12

Serologies for HAV, HCV, HEV, HIV, EBV

negative

AST/ALT/ALP

1650/120/455

CMV PCR

8160 copies/ml

PTI

50%

Anti-LKM/ SMA/ PCA

negative

apTT

57 (<28)

MRI Brain

Cerebral atrophy

DCT Direct Coombs test, APL anti-phospholipid, HAV Hepatitis A, HCV Hepatitis C, HEV Hepatitis E, HIV Human Immunodeficiency Virus, EBV Epstein Barr Virus

P439 Soluble Receptor Activator of Nuclear Factor κ B ligand (s RANK-L) levels in pediatric onset SLE

Sapna Sandal, Amit Rawat, Anju Gupta, Surjit Singh

Pediatrics, PGIMER, Chandigarh, Chandigarh, India
Presenting author: Sapna Sandal

Introduction: Receptor Activator of Nuclear Factor κ B (RANK), its ligand (RANKL) and osteoprotegerin are the key mediators of bone remodeling and the final effector pathway in osteoclast development and differentiation. The data on RANKL axis in pediatric Systemic Lupus Erythematosus (SLE) is lacking.

Objectives: To estimate serum sRANKL levels in pediatric SLE and to evaluate the correlation of sRANKL levels with the SLE disease activity.

Methods: Consecutive children with SLE attending Pediatric Rheumatology Clinic of Advanced Pediatrics Centre, PGIMER, Chandigarh were enrolled. The study group was divided into active (with ongoing disease activity) and inactive (no disease activity) subgroups based on SLE disease activity index (SLEDAI) scores. The sRANKL ligand levels were measured using an enzyme- linked immunosorbent assay (sRANKL – ELISA MyBioSource@, USA).

Results: Thirty-one children (12 boys) with a mean age of 13.4 ± 3.2 years were included. The median (interquartile range) sRANKL level of the cohort was 52.3 (24.1, 66.4) pg/mL. Serum RANKL levels were not significantly different in active and inactive disease subgroups [median (interquartile range): 55.2 (21.3, 66.4) pg/mL versus 53.3 (29.3, 64.9) pg/mL, respectively] (p = 0.89). There was no statistically significant correlation between sRANKL levels and SLEDAI scores, Spearman correlation coefficient rs = 0.083, p = 0.65.

Conclusion: There was no statistically significant difference in sRANKL levels between the inactive and active disease group which is further reflected in a lack of correlation between sRANKL and SLEDAI scores.

Disclosure of Interest: None Declared

P440 Heart valve damage in patients with lupus and antiphospholipid syndrome

Sebastian Giraldo1,2, Roy Sanguino3, Adriana S. Diaz4,5

1Rheumatology and Inmunology, Hospital Militar Central, Bogota, Colombia; 2School of Medicine, Universidad Militar Nueva Granada, Bogota, Colombia; 3Cardiology Department, Hospital de La Misericordia, Bogota, Colombia; 4Rheumatology, Hospital de La Misericordia, Bogota, Colombia; 5Rheumatology, Care for Kids, Bogota, Colombia
Presenting author: Sebastian Giraldo

Introduction: Heart valve disease is the most common manifestation in systemic lupus erythematosus (SLE), even more so when the association with antiphospholipid syndrome (APS) is present, showing a prevalence of valvular commitment to 50%, which is a common cause for morbidity and mortality in these patients. Manifestations include thickening, stenosis or aseptic thrombus on the surface of the valve (Libman-Sacks endocarditis). The mitral valve is involved in 24% of cases, and the aortic valve and the tricuspid valve or pulmonary up to 5%. It is more common in female.

Objectives: Valvular heart disease is common in systemic lupus erythematosus (SLE) associated with antiphospholipid syndrome (APS) in children. Important entity in the initiation of immune pathogenesis. Information on the role of antiphospholipid antibodies has been inconsistent, particularly with regard to valvular lesions and associated SLE. Although the diagnosis by echocardiography on time is essential to prevent progression of this type of injury, still it remains a real challenge to the therapeutic approach to this entity given the risk of valve replacement and / or chronic anticoagulation therapy.

Methods: Three cases of valve disease are related in the context of SLE and APS association with different presentation and management of symptoms, who were diagnosis and followed at the Hospital La Misericordia, Bogota-Colombia.

Results: Two female patients 12 and 11 years old with positive immunological profile for SLE and APS, commitment largest organ kidney and heart involvement. In one clinical improvement of their valvular involvement (severe tricuspid regurgitation, pulmonary hypertension and right heart failure) once management is done with systemic steroids (methylprednisolone), and cyclophosphamide, in maintenance therapy with prednisolone, Azathioprine, Chloroquine, Enalapril and spironolactone. The second case, despite stabilization of autoimmune disease therapy Methylprednisolone and Cyclophosphamide continued progression of their cardiac involvement (aortic and mitral insufficiency) and therefore requires surgery. The third case, a man seven years old with a diagnosis of SLE and associated APS, who makes kidney and central nervous system involvement. It requires pulses of intravenous steroid, cyclophosphamide, mycophenolate mofetil, plasmaferisis and renal replacement therapy. Cardiac involvement (tricuspid regurgitation) is documented, who does two episodes of disease activity occurring in less than two years. Severe tricuspid valvular commitment and refractory heart failure without achieving stabilization and death finally.

Conclusion: The treatment of valvular manifestation in SLE associated with APS depends on the type and severity of involvement. The important valvular dysfunction can influence hemodynamic compromise so the treatment is initially aimed at conservative therapy including ACE inhibitor, beta blocker, diuretic, immunosuppression, anticoagulation therapy and prophylaxis of endocarditis) in some patients undergoing chronic anticoagulation therapy until the need for surgical approach with possible complications with biological and mechanical valve replacement.

Disclosure of Interest: None Declared

P441 The impact of Juvenile Systemic Lupus Erythematosus on psycho-social status

Selcuk Uzuner1, Sezgin Sahin2, Gizem Durcan3, Amra Adrovic2, Kenan Barut2, Ali Guven Kilicoglu4, Ayhan Bilgic5, Kayhan Bahali4, Ozgur Kasapcopur2

1Pediatrics, Bezmialem University, Istanbul, Turkey; 2Pediatric Rheumatology, Istanbul University, Cerrahpasa Medical School, Istanbul, Turkey; 3Child and Adolescent Psychiatry, Istanbul University, Cerrahpasa Medical School, Istanbul, Turkey; 4Child and Adolescent Psychiatry, Bakirkoy Research and Training Hospital for Psychiatry, Neurology and Neurosurgery, Istanbul, Turkey; 5Child and Adolescent Psychiatry, Necmettin Erbakan University, Meram Medical Faculty, Konya, Turkey
Presenting author: Selcuk Uzuner

Introduction: There is very little documentation about the association between peer victimization, psychological status, and quality of life (QOL) in adolescents with Juvenile Systemic Lupus Erythematosus (JSLE).

Objectives: Adolescent studies have generally reported that chronic conditions can negatively affect psychosocial status. The aim of this study was to evaluate the association between peer victimization, psychological symptoms and QOL in a cohort of adolescents with JSLE.

Methods: 31 patients participated in this study. The inclusion criteria were as follows: 12–18 years of age, no psychotropic drug treatments for at least three months prior to the study, and no other chronic diseases. The control group (n = 39) was composed of healthy adolescents from the local community. Questionnaires were used to evaluate the peer victimization, psychological status and QOL of children with JSLE and without JSLE.

Results: The mean (± SD) age of the sample was 15.7 (±1.6) years, and consisted of 6 (19.3%) males and 25 (80.7%) females. The mean (± SD) age of the control group was 15.6 (±1.4) years, and 31 (79.5%) of the adolescents in this group were females. No significant difference was found between study and control group for peer victimization, depression, state and trait anxiety, self-esteem, and QOL scores.

Conclusion: To the best of our knowledge, this is the first report on peer victimization, psychological status, and QOL data, especially focused on adolescents with JSLE, compared with a control group. The present study revealed that peer victimization, depression, anxiety, self-esteem, and QOL levels of the patients with JSLE were not worse than the control group.

Disclosure of Interest: None Declared

P442 Pentraxin-3 level predicts vasculitis and mucocutaneous involvement in childhood-onset systemic lupus erythematosus

Sezgin Sahin1, Amra Adrovic1, Kenan Barut1, Sinem Durmus2, Hafize Uzun2, Ozgur Kasapcopur1

1Department of Pediatric Rheumatology, Istanbul University, Cerrahpasa Medical School, Istanbul, Turkey; 2Department of Biochemistry, Istanbul University, Cerrahpasa Medical School, Istanbul, Turkey
Presenting author: Sezgin Sahin

Introduction: Systemic lupus erythematosus (SLE) is a persistent or remitting-relapsing autoimmune disease that handled in the context of connective tissue diseases and also vasculitides. Although there are commonly used biomarkers of active kidney disease and central nervous system disease, there is not a specific marker for vasculitic involvement.

Pentraxin-3 (PTX3) is derived primarily from vascular endothelium and innate immunity cells in response to local inflammation and plays an important role locally at the site of inflammation. Thus PTX3 seems to be a useful biomarker directly reflecting local inflammation and local vasculitis.

However, there are conflicting results about the role of PTX3 in SLE. Moreover, to the best of our knowledge PTX-3 was not studied in children with SLE.

Objectives: In the present study, we aimed to compare the concentrations of plasma PTX-3 among childhood-onset SLE (cSLE) patients and control groups and to assess the association of PTX-3 levels with SLEDAI-2K, clinical manifestations and laboratory results.

Methods: From October 2015 to May 2016, 82 cSLE patients were examined at our outpatient clinic of pediatric rheumatology department. One patient and also her parents did not give consent for participation so she was not enrolled to the study. Since bacterial and viral infections could interfere with pentraxin levels, 5 patients were not recruited due to signs and symptoms of active infection. Moreover, the procalcitonin level was also measured to rule out bacterial and viral infection. Finally, a total of 76 c-SLE patients without active infection sign and symptom were eligible for this cross-sectional single center study. We have also measured pentraxin-3 level in 41 healthy and age-matched controls.

Both the cumulative and current organ involvement and manifestations were recorded from patient records and from the last examination at that moment, respectively. All of the laboratory analyses were studied concurrently with PTX-3 levels. PedSDI and SLEDAI-2K scores at disease onset, at the most severe flare and at the last examination were calculated.

Serum pentraxin-3 levels were measured by a commercially available enzyme-linked immunosorbent assay kit.

Results: Plasma PTX3 concentrations were measured in 76 patients with c-SLE and 41 control subjects. Plasma PTX3 concentration of the SLE patients was significantly higher than that of the healthy controls (mean 10.6 ± 8.2 vs. 2.7 ± 1.3 ng/mL, p < 0.001).

The ratio of females to males with cSLE was 5.3:1. The mean SLEDAI scores decreased from 10.3 ± 4.8 (at disease onset) to 5.2 ± 5.3 (at last examination). Additionally, only 10.5% (n = 8) and 3.9% (n = 3) of the cohort were displaying the signs of active nephritis and active neuropsychiatric disease at last examination.

In patients with SLE, PTX3 concentrations were correlated with SLEDAI-2K (p < 0.001), active vasculitis (p < 0.001), Raynaud’s phenomenon (p = 0.006) and active mucocutaneous involvement (p < 0.001). PTX3 level was not associated with disease duration, anti-ds DNA antibody, decreased complement levels, PedSDI, active nephritis, active neuropsychiatric involvement, musculoskeletal involvement, hematological involvement, ESR,CRP, procalcitonin levels.

Conclusion: In brief, PTX3 levels were significantly correlated with SLEDAI scores in cSLE. Additionally, its levels are found to be substantially increased in the presence of Raynaud’s phenomenon and vasculitic manifestations. Thus predicting the vascular involvement early and quantitatively in a cSLE patient with presumed clinically inactive, will provide a better management of the disease. In conclusion, as in other vasculitides, PTX3 may represent a potential biomarker for vascular involvement in cSLE.

Disclosure of Interest: None Declared

P443 Age-related differences in childhood-onset systemic lupus erythematosus

Sezgin Sahin1, Amra Adrovic1, Kenan Barut1, Nur Canpolat2, Salim Caliskan2, Lale Sever2, Ozgur Kasapcopur1

1Department of Pediatric Rheumatology, Istanbul University, Cerrahpasa Medical School, Istanbul, Turkey; 2Department of Pediatric Nephrology, Istanbul University, Cerrahpasa Medical School, Istanbul, Turkey
Presenting author: Sezgin Sahin

Introduction: Only 20% of the systemic lupus erythematosus (SLE) disease emerges before 18-years old and there are conflicting conclusions about demographic characteristics, disease manifestations of this autoimmune disease based on age at disease onset.

Objectives: To compare the disease characteristics, SLEDAI-2K and PedSDI scores, medications, laboratory data between 2 different age groups of c-SLE.

Methods: This single-center cohort study is implemented in a retrospective manner by reviewing patient records and included 82 c-SLE patients from January 2003 to October 2015.

Patients were divided into two groups based on age at disease onset: group A (early onset and school-aged children that are <12 years old), group B (adolescents that are ≥12 years-old and <18 years-old).

Pearson chi-square test compared the sex differences, presence of constitutional symptoms and decrease in complement levels at disease onset, the number of ANA, anti-dsDNA and anticardiolipin antibody positivity, existence of organ involvements, Reynaud’s phenomenon, all medications that are used, and finally comorbid conditions and side effects related the drug between these groups.

Moreover, delay in diagnosis (months), the measured procalcitonin, ESR, CRP, Anti-dsDNA levels (both at disease onset and at last visit) and the other continuous variables such as number of flares, PedSDI and SLEDAI scores (at disease onset, at last examination and the peak score ever reached) were compared by means of Mann-Whitney U test.

Results: 39 patients had their disease onset before 12-years-old and 43 patients at or after 12-years-old. Age at diagnosis was 8.5 ± 2.6 (range 2-11) in group A and 14.4 ± 1.7 (range 12-18) in group B. We were following the Group A and B on an average for 5.5 years and 3.5 years, respectively. The ratio of females to males was 5.5:1 in Group A and 6.1:1 in Group B.

Delay in diagnosis of SLE in younger patients were significantly higher than that of the adolescents by means of months (median 8 vs. 1 months, p = 0.0016).

In Group A, constitutional symptoms were pronounced in 43.6% (n = 17) of the patients at disease onset. However, this percentage was 67.4% (n = 29) in Group B and it was also statistically reliable.

Groups were similar regarding female gender (84.6% vs. 86%, p = 0.855) and frequency of two major organ involvement of c-SLE: nephritis (25.6% vs. 32.5%, p = 0.549), neuropsychiatric involvement (15.4% vs. 18.6%, p = 0.699).

Additionally, other cumulative organ involvement frequencies, such as cardiovascular disease, hematologic and musculoskeletal involvement, pulmonary involvement were same between these two groups.

Procalcitonin, ESR, CRP, Anti-dsDNA levels (both at disease onset and at last visit) and the other continuous variables such as number of flares, PedSDI and SLEDAI scores (at disease onset, at last examination and the peak score ever reached) were not different between groups.

The mean SLEDAI-2K scores of Group A; at disease onset, at last examination and during the most severe flare did not differed from Group B (p > 0.05).

Although the ratio of damaged individuals in Group A (n = 12/39) were increased comparing to Group B (n = 12/43), this was not statistically significant (p > 0.05).

There was not any difference in number of patients that had positive anti-ds DNA antibody, anticardiolipin antibody, ANA and decreased complement levels among different age groups.

Conclusion: Unlike the reported data, we could not find an increased risk of disease severity and organ involvement in children less than 12-years-old. However, we conclude that diagnosing SLE seems to be more difficult in younger children.

Disclosure of Interest: None Declared

P444 Ovarian tissue cryopreservation before cyclophosphamide treatment for severe lupus nephritis; two juvenile systemic lupus erythematosus cases

Tomomi Sato1, Fuminori Kimura2

1Department of Pediatrics, Shiga University of Medical Science, Otsu, Japan; 2Department of Obstetrics and Gynecology, Shiga University of Medical Science, Otsu, Japan
Presenting author: Tomomi Sato

Introduction: Severe lupus nephritis, often a complication in pediatric cases of systemic lupus erythematosus (SLE), is often treated using cyclophosphamide, which seriously declines fertility, when mycophenolic acid cannot be used owing to its side effect. It is known that many female patients with various cancers opted for ovarian tissue cryopreservation before receiving alkylating antineoplastic agents and some of them have given birth after transplantation of their cryopreserved ovarian cortex tissue.

Objectives: Two cases of girls with severe lupus nephritis underwent ovarian tissue cryopreservation before cyclophosphamide treatment for preservation their fertility.

Methods: Case 1 was a 9-year-old girl with lupus nephritis class IV-S (a), complicated with nephrotic syndrome, anti-phospholipid syndrome and idiopathic thrombocytopenic purpura. Case 2 was a 14-year-old girl with lupus nephritis class III-G (a/c) and diffuse alveolar hemorrhage. Lupus nephritis was diagnosed on kidney biopsy at initial diagnosis of SLE in both cases. The patients were first treated with prednisolone (1 mg/kg/day) and mycophenolic acid (1500 mg/day); however they experienced severe stomachache with mycophenolic acid use and hence it was discontinued. They were determined to need cyclophosphamide therapy for remission from lupus nephritis. Before IVCY therapy, we suggested ovarian tissue cryopreservation to help preserve fertility. The patients and their parents agreed to cryopreserve their ovarian cortical tissue and provided written informed consent. They underwent laparoscopic right ovariectomy under general anesthesia before the initiation of cyclophosphamide pulse therapy for fertility preservation. Their ovarian cortical tissues were vitrified in liquid nitrogen and stored in our hospital.

Results: Laparoscopic ovariectomy was successful and cyclophosphamide pulse therapy was started two days after surgery. Pathological review of the ovarian tissue from the patient in case 1 showed stromal fibrosis, suggesting chronic ovaritis. The surgical scar was very small in both patients, and the degree of satisfaction of the patients and their parents was high. They both continue to receive oral steroid therapy and cyclophosphamide pulse therapy and are in remission.

Conclusion:

The survival rates of patients with lupus nephritis have dramatically improved recently due to development of treatment, so long-term damage to the ovary after cyclophosphamide therapy for severe lupus nephritis with girls has gained importance. SLE occurs frequently in young women; unfortunately, juvenile SLE is more often complicated by severe lupus nephritis, which may lead to end-stage renal failure, than adult SLE. Previous studies have suggested that laparoscopic ovariectomy under general anesthesia for cryopreservation is safe and that immature ovaries can restore hormonal function in prepubertal girls with cancer. Spontaneous full-term pregnancy after orthotropic cryopreserved ovarian tissue transplantation has been reported, and at least 40 live births after cryopreserved ovarian cortical tissue transplantation have been reported. Similar to female patients with cancer, patients with severe systemic lupus erythematosus should be provided with the option of ovarian tissue cryopreservation before the use of alkylating drugs to help preserve fertility.

Disclosure of Interest: None Declared

P445 Pulmonary involvement in childhood onset systemic lupus erythematosus: a multicenter cohort report of clinical patterns and outcome

Wafaa Suwairi1, Reem Abdwani2, Abdulaziz Al Rowais3, Jubran Al qanatish1, Abdulrahman Al Asiri3

1Pediatrics, King Abdullah specialized children hospital, Riyadh, Saudi Arabia; 2Pediatrics, Sultan Qaboos University Hospital, Maskat, Oman; 3Pediatrics, Prince Sultan Military Medical City, Riyadh, Saudi Arabia
Presenting author: Wafaa Suwairi

Introduction: Pulmonary manifestations may be the initial and/or life-threatening complication of childhood onset systemic lupus erythematosus (cSLE). Although pulmonary involvement is relatively frequent in adult patients; it has been infrequently reported in children with SLE.

Objectives: To describe the frequency of pleuropulmonary manifestation and outcome of Arab children with cSLE.

Methods: This is a multicenter retrospective study that included all patients diagnosed with SLE between the period of 2000 and 2015. All our patients fulfilled at least four of the 1997 revised American College of Rheumatology classification criteria. Using a standardized form, we obtained data from medical records including age of disease onset, disease duration, sex, clinical manifestations of SLE, and details of pleuropulmonary involvement, treatment and outcome

Results: A total of 110 patients with cSLE were included from 3 centers in 2 Arab countries; (n = 65)59% from Sultanate of Oman and (n = 45) 41% from Saudi Arabia. The mean range of follow up is 4.6 years (range 1-10 years). Pleuro-pulmonary involvement was observed in (n = 27) 24.5% of the cases; diffuse alveolar hemorrhage (DAH) (n = 13) 12%, serositis (n = 11) 10% pulmonary infection (n = 8) 7%, interstitial pneumonitis (n = 4) 3.6% and shrinking lung syndrome (n = 1) 0.9%. Outcome of patients included mechanical ventilation (n = 8) 7.0% and death (n = 1) 0.9% in a patient with both DAH and catastrophic anti-phsopholipid syndrome (CAPS). The demographic, clinical manifestations, disease activity treatment and outcome of patients with DAH in our patient cohort will be described in Conclusion: DAH is a rare pleuro-pulmonary manifestation in cSLE, however, in an Arab cohort it was the most common clinical manifestaion. However, despite its major impact on morbidity and mortality, our patients had an overall good outcome with aggressive treatment and supportive care. The cause of the differences in the clinical expression of SLE and outcome around the world is yet to be determined; however it can be due to interplay between genetic, environmental and ethnic factors.

Disclosure of Interest: None Declared
Table 9 (abstract P445).

See text for description

Demographics

 - · Gender (M:F)

8:5

 - · Mean age of onset

5.5 years (range 1.5 to 11 years)

 - ·  Follow up duration

4.6 years

Clinical Symptoms at presentation

 - ·  Cough

(n = 9) 70%

 - ·  Dyspnea

(n = 13) 100%

 - ·  Anemia

(n = 13) 100%

 - ·  Hemoptysis

(n = 5) 35%

 - ·  CXR infiltrates

(n = 13) 100%

Associated SLE Clinical features

 - ·  Hematological

(n = 7) 54%

 - ·  Nephritis

(n = 11) 85%

 - ·  Arthritis

(n = 11) 85%

 - ·  Mucocutanous

(n = 12) 92%

 - ·  Serositis

(n = 7) 54%

 - ·  Neuropsychiatric

(n = 5)35%

Treatment:

 - ·  IVM

(n = 13) 100%

 - ·  CYC

(n = 9) 70%

 - ·  MMF

(n = 7) 54%

 - ·  IVIG

(n = 9) 70%

 - ·  Plasmapharesis

(n = 6) 46%

 - ·  Mechanical ventilation

(n = 7) 54%

Outcome:

 - ·  Acute DAH outcome

 

Death / Survival

(n = 1) 7%

 - ·  Long term SLE outcome

(n = 11)

Remission

(n = 7) 64%

Minimal disease activity

(n = 2)18%

Lost to follow up

(n = 2) 15%

P446 Systemic lupus erythematosus and thrombotic microangiopathy, on account of two cases

Kubra Ozturk, Zelal Ekinci

Department of Pediatrics Rheumatology, Kocaeli University Faculty of Medicine, Kocaeli, Turkey
Presenting author: Zelal Ekinci

Introduction: Thrombotic microangiopathy (TMA) is the term used for diseases in which disseminated microthrombi composed of agglutinated platelets are occluding arterioles and capillaries. It can present in approximately 2% of the patients with SLE.

Objectives: In this report, it is aimed to emphasize the occurrence of TMA during diagnosis and follow up course of SLE in two children.

Methods: Case 1: A 15-year old male presented with arthralgia, weakness and fever. Physical examination was unremarkable. Laboratory workup revealed: pancytopenia (white blood cells 2.41x103/uL, platelets 163 x103/uL, haemoglobin 6.9 g/dl), increased level of serum creatinine (1.09 mg/dl) and LDH (463 IU/l). Peripheral blood smear revealed schistocytes. Due to decreased level of haptoglobin (<8mg/dl), patient was hospitalized with the diagnosis of TMA. Besides, the ADAMTS13 activation was low (<%0.2 [40–130]) and ADAMTS13 inhibitor level was high (51 U/mL [<15]). Pancytopenia, proteinuria, decreased complement C3 (32 mg/dl) and C4 (5.3 mg/dl), positive ANA and anti-dsDNA demonstrated that TMA was resulted from SLE. The kidney biopsy was consistent with class IV lupus nephritis. He was treated with 1 gr/day intravenous methylprednisolone for three days and 1 gr/m2 cyclophosphamide. Despite this treatment, microangiopathic hemolysis and trombocytopenia persisted and thus plasma exchange with fresh frozen plasma (FFP) was initiated. After 27 sessions of plasma exchange and treatment with prednisolone and mycophenolate mofetil, he improved remarkably with the normalisation of his platelet count.

Results: Case 2: A 7-year old male was admitted with the complaining of weakness, headache, arthralgia and rash in hands. He has been followed up with the diagnosis of SLE due to complement C1q deficiency for 3 years and he was treated with hydroxychloroquine and FFP infusion twice a month. Physical examination revealed discoid rashes in his face, hands and feet. Besides he had petechiae and purpura at his toe. Laboratory tests revealed: pancytopenia (white blood cells 2.11x103/uL, platelets 45.3 x103/uL, haemoglobin 7.07 g/dl) and decreased haptoglobin level (<8mg/dl). Additionally peripheral blood smear revealed schistocytes. When checking for the TMA selective diagnosis, it was seen that the ADAMTS13 activation was low (% 30 [40–130]) and ADAMTS13 inhibitor level was high (69 U/mL [<15]). As a result, it was confirmed that TMA was developed because of SLE. The treatment was started with intravenous methylprednisolone 30 mg/kg/day for 3 days and daily FFP infusion. Despite this treatment, hemolysis and trombocytopenia persisted and plasma exchange was initiated. After 6 sessions of plasma exchange, he improved remarkably. He was discharged with weekly FFP infusion, oral steroid and azathioprine.

Conclusion: SLE is a prototypic systemic autoimmune disease with heterogeneous clinical features. This report is presented to emphasize the similarities and the differences between the two cases, one of which referred with TMA symptoms and diagnosed as SLE and the other developed TMA during the course of SLE. It is important to look for laboratory findings of TMA during diagnosis and follow up course of SLE.

Disclosure of Interest: None Declared

Poster Session: Uveitis

P447 The evaluation of efficacy of adalimumab in juvenile idiopathic arthritis-associated uveitis and chronic anterior uveitis

Ekaterina Gaidar, Mikhail Kostik, Margarita Dubko, Vera Masalova, Elena Serogodskaya, Ludmila Snegireva, Tatyana Nikitina, Vyacheslav Chasnyk, Olga Kalashnikova, Evgenia Isupova

Saint-Petersburg State Pediatric Medical University, Saint-Petersburg, Russian Federation
Presenting author: Ekaterina Gaidar

Introduction: Juvenile idiopathic arthritis (JIA) - associated uveitis (JIA-U) and chronic anterior uveitis (CAU) are both immune-mediated chronic eye diseases, which can lead to severe impairment of visual function and blindness. Only about 75% of patients with JIA-U and CAU can reach the remission on methotrexate treatment. The rest require TNF-a inhibitors, especially adalimumab (ADA).

Objectives: The aim of our study was to evaluate the possibility of ADA to induce remission of uveitis, and the duration of remission and flares.

Methods: 39 children with JIA-U (n = 36) and CAU (n = 3) treated with ADA were included in the present[1] retrospective study. The diagnosis of JIA was made with ILAR criteria. Each patient was examined by an experienced ophthalmologist. The visits were scheduled depending upon the uveitis course. Patients could only be included in the study if they were under observation for at least 1 year before the ADA initiation. The reasons for ADA treatment were active uveitis or severe complicated uveitis course (n = 30) and active arthritis with inactive uveitis (n = 9). The median onset age of the disease was 2.9 (2.0-6.0) years, onset age of uveitis was 5.0 (3.2-7.7) years. According to the joint involvement, patients had oligoarthritis (59.1%), polyarthritis (23.1%), enthesitis-related arthritis (10.2) and no arthritis - CAU (7.7%). In 74.6% of patients arthritis occurred before uveitis, girls were 64.1%[2], ANA positivity was detected in 58.3% children. Three types of uveitis were detected: anterior (76.9%), peripheral (5.9%) and panuveitis (18.0%). The median involved eyes[3] were 2.0 (1.0-2.0). Patients with acute symptomatic uveitis were not included in the study.

Results: The initial uveitis remission in a patient with active uveitis was detected in 29/30 patients (96.7%) in 2.0 (2.0-12.0) weeks, only 1 still had active uveitis. Flares were experienced by 11 patients (28.2%) in the 28 (12.9-68.6) weeks: 2/11 patients were inactive before ADA and 9/11 had previously remission on ADA. The frequency of flares significantly decreased (p = 0,007) after ADA starting from 4.0 (1.0-9.0) flares/year per patient to 0.0 (0.0-1.0) and decreased the number of patients who received topical steroids from 17/28 (60.7%) to 2/28 (7.1%, p = 0.00001).

We have not found the difference in time between the start of ADA and the remission, or in the probability to achieve remission depending on gender (p = 0.22), first joint or eye involvement (p = 0.59), ANA-status (p = 0.8), type of uveitis (p = 0.5), articular course (p = 0.25), concomitant DMARD (p = 0.85) and previous biologic treatment (p = 0.18).

Conclusion: ADA can induce the fast and prolonged remission of JIA-U and CAU. ADA treatment is a good therapeutic option for patients with uveitis, refractory to non-biologic DMARD. Further randomized control trials required.

Disclosure of Interest: None Declared

P448 Retrospective study evaluating treatment decision and outcome of non-juvenile idiopathic arthritis (JIA)-associated childhood uveitis

Elham Sardar1, Perrine Dusser1, Antoine Rousseau2, Marc Labetoulle2, Emanuel Barreau2, Bahram Bodaghi3, Isabelle Kone-Paut1

1Paediatric Rheumatology, Paris-Sud University Hospital, APHP, Paris, France; 2Ophtalmology, Paris-Sud University Hospital, APHP, Paris, France; 3Ophtalmology, Pitie-Salpetriere Hospital,University of Paris VI, Paris, France
Presenting author: Elham Sardar

Introduction: Non-infectious uveitis is the most common cause of blindness in children. Most studies have evaluated diagnosis criteria and treatment of JIA-associated uveitis.

Objectives: We analyzed treatment, ocular complications and outcome of childhood uveitis related to other causes than JIA.

Methods: A retrospective chart review of pediatric uveitis in patients <16y-old seen between 2005 and 2015 at a university hospital in Paris. We excluded patients with JIA-associated uveitis. Clinical characteristics, treatment and ocular complications were collected. We used the SUN (Standardization of Uveitis Nomenclature) for the classification of uveitis, disease activity (inactive uveitis: rare cells or less) and treatment endpoints, improvement: defined as a 2-step decrease in the inflammation level or a decrease to grade 0, worsening: defined as a 2-step increase in the inflammation level or an increase from grade 3+ to 4+, or remission (inactivity without treatment for ≥ 3 months).

Results: Sixty patients (SR M/F: 0, 42; 107 eyes) were enrolled. Mean age at diagnosis was 10 ± 3.5 years (3 to 15 y). Mean follow-up was 4 ± 3 years. Uveitis was symptomatic in 90% of patients: eye redness (30%), decreased vision (30%) and eye pain (20%). Main diagnoses were: idiopathic (55%), Behçet’s disease (BD) (15%), sarcoidosis (7%), infectious (7%), Blau (3%) Vogt-Koyanagi– Harada syndrome (2%), and Tubulointerstitial nephritis and uveitis (TINU) syndrome (2%). Among idiopathic uveitis (n = 59 eyes), 31% were anterior and 31% were posterior. Thirty four eyes (58%) received systemic corticosteroid as first-line therapy, inducing inactivity for 10 eyes (29%) and remission for 1 eye (3%). DMARDs were needed for 21 eyes (62%). Methotrexate was used as second-line therapy in 18 eyes (53%) with 5% (n = 1 eye) and in 33% resulting in inactivity (n = 6 eyes). Infliximab was used as third-line treatment in 9 eyes with 80% of inactivity but no remissions. Ocular complications were present in 47% (n = 28) at diagnosis and they increased until 61% of patients during the follow-up. The most common were posterior synechiae (32%), macular edema (30%), cataract (20%), and band keratopathy (12%). In BD uveitis (n = 16 eyes), 56% had panuveitis. Twelve eyes received systemic corticosteroids therapy at first-line and all needed azathioprine as second-line. Azathioprine allowed (n = 4) 33% of inactivity and 16% (n = 2) of remission. Infliximab was used as third-line therapy in 7 eyes with 85% of inactivity. Thirty percent of BD patients presented complications at the beginning until 63% during the follow-up: posterior synechiae (31%), vitreous hemorrhage (25%), cataract (25%) ischemia macular (19%) and macular edema (19%). Sarcoidosis affected 5 eyes, 80% were panuveitis and all patients received systemic corticosteroids and became steroid dependent. All these patients received methotrexate as second-line therapy,which allowed 50% of improvement. Forty percent required infliximab as a third-line therapy with remission in 1 eye (20%) and inactivity in 3 eyes (60%). Posterior synechiae were present in 1 eye at the beginning and 3 eyes at the end of the follow up (60%).

Conclusion: Idiopathic uveitis is the most common cause of non-JIA uveitis in children and seems more severe at presentation. BD and Sarcoidosis appeared more difficult to treat because the complication rate increased during the follow-up despite treatment. Most patients required a DMARD in association with infliximab. Improvement and disease inactivity were frequently obtained but remission was rare.

Disclosure of Interest: None Declared

P449 Proposal for a damage index for juvenile idiopathic arthritis related uveitis from the Multinational Interdisciplinary Working Group for Uveitis in Childhood Group (MIWGUC)

Ivan Foeldvari1, Jordi Anton2, Rosa Bou2, Sheila Angeles-Han3, Regitze Bangsgaard4, Gabriele Brumm5, Tamas Constantin6, Clive Edelsten7, Jens Klotsche8, Kirsten Minden8, Elisabetta Miserocchi9, Susan Nielsen4, Gabriele Simonini10, Arnd Heiligenhaus11

1AM Schön Klinik Eilbek, Hamburg, Germany; 2Universitat de Barcelona, Hospital Sant Joan de Deu, Barcelona, Spain; 3Emory University, Atlanta, GA, United States; 4Juliane Marie Centret, Rigshospitalet, Copenhaven, Denmark; 5Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany; 6Semmelweis University, Budapest, Hungary; 7Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom; 8German Rheumatism Research Center, Berlin, Germany; 9Università Vita-Salute, Scientific Institute San Raffaele, Milano, Italy; 10Universita degli studi Firenze, Firenze, Italy; 11St. Franziskus Hospital, Muenster, Germany
Presenting author: Ivan Foeldvari

Introduction: Juvenile idiopathic arthritis (JIA) associated Uveitis is the most common extraarticulare comorbidity of juvenile idiopathic arthritis. Nowdays it occurs about 10-15% of JIA patients. As innovative effective treatment options are emerging, it is extremely important for defining validated damage index in order to assess the effectivity of drugs to preventing damage, one of the main aims of the treatment.

Objectives: To develop a proposal for the damage index, that asses the effectivity of a given drug for preventing damage in JIA associated uveitis.

Methods: Multinational Interdisciplinary Working Group for Uveitis in Childhood Group (MIWGUC) had prospectively evaluated the validity of the proposed outcome measures(1). Based on the data, we proposed a damage index using the nominal group technique in a consensus meeting in Barcelona, Spain, in November 2015.

Results:

Following items were selected for assessing damage:

Vision related permanent damage per eye /per patient - yes / no

Right eye Left eye
  1. 1.

    flare

     
  2. 2.

    synechiae

     
  3. 3.

    cataract

     
  4. 4.

    maculopathy

     
  5. 5.

    Opticopathy

     
  6. 6.

    Decreased Visual acuity

     
  7. 7.

    Ocular hypertony – >21 mmHg

     
  8. 8.

    Ocular hypotony - <6 mmHg

     
  9. 9.

    Glaucomatous field loss and /or glaucomatous optic atrophy

     
  10. 10.

    Band-keratopathy

     
  11. 11.

    Epiretinal membrane formation

     
  12. 12.

    Visual deterioration – less then 0.3 in any eye

     
  13. 13.

    Uveitis related disability VAS 0-100 by ophthlamologist

     
  14. 14.

    Uveitis related disability VAS 0-100 by pediatric rheumatologist

     

Conclusion: We proposed items for assessing the damage index of JIA associated uveitis. The damage index should be a valid instrument for assessing the effectivity of a given drug in order to preventing damage. This proposal will be evaluated from the MIWGUC group in prospective study.

References:

1. Heiligenhaus A, Foeldvari I, Edelsten C, Smith JR, Saurenmann RK, Bodaghi B, et al. Proposed outcome measures for prospective clinical trials in juvenile idiopathic arthritis-associated uveitis: a consensus effort from the multinational interdisciplinary working group for uveitis in childhood. Arthritis Care Res (Hoboken). 2012;64(9):1365-72.

Disclosure of Interest: None Declared

P450 Proposal for the definition of remission for juvenile idiopathic arthritis related uveitis from the Multinational Interdisciplinary Working Group for Uveitis in Childhood Group (MIWGUC)

Ivan Foeldvari1, Jordi Anton2, Rosa Bou2, Sheila Angeles-Han3, Regitze Bangsgaard4, Gabriele Brumm5, Tamas Constantin6, Clive Edelsten7, Jens Klotsche8, Kirsten Minden8, Elisabetta Miserocchi9, Susan Nielsen4, Gabriele Simonini10, Arnd Heiligenhaus11

1AM Schön Klinik Eilbek, Hamburg, Germany; 2Universitat de Barcelona, Hospital Sant Joan de Deu, Barcelona, Spain; 3Emory University, Atlanta, GA, United States; 4Juliane Marie Centret, Rigshospitalet, Copenhaven, Denmark; 5Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany; 6Semmelweis University, Budapest, Hungary; 7Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom; 8German Rheumatism Research Center, Berlin, Germany; 9Università Vita-Salute, Scientific Institute San Raffaele, Milano, Italy; 10Universita degli studi Firenze, Firenze, Italy; 11St. Franziskus Hospital, Muenster, Germany
Presenting author: Ivan Foeldvari

Introduction: Juvenile idiopathic arthritis (JIA) associated Uveitis is the most common extraarticulare comorbidity of juvenile idiopathic arthritis. Nowdays it occurs about 10-15% of JIA patients. As effective treatment options are emerging, validated definition criteria of of remission are warranted, which is main aim of the treatment.

Objectives: To develop a proposal for the definition of remission JIA-associated uveitis.

Methods: Multinational Interdisciplinary Working Group for Uveitis in Childhood Group (MIWGUC) had prospectively evaluated the validity of the proposed outcome measures (1). Based on the data, we proposed a definition of JIA associated uveitis remission using the nominal group technique in a consensus meeting in Barcelona, Spain, in November 2015.

Results: The following items were selected to define remission of JIA associated uveitis on medication or off medication. It is required, that in both eyes the following condition is reached and the condition last at least 6 months on medication, or inactive disease for ≥ 3 months after discontinuing all treatments.

1. Slit lamp total number of AC cells: no inflammatory cells

*In aphakic patients some cells may be present in the anterior vitreous

2. Absence of optic disc edema

*The presence of isolated optic disc edema may not be a sign of activity

3. Absence of macular edema

*The presence of isolated macular edema may not be a sign of activity

4. Absence of vitreous haze

*The presence of isolated vitreous haze may not be a sign of activity

5. VAS score of activity by the physician 0-100: must be 0

Conclusion: We proposed items to define remission of in JIA associated uveitis, which is the major goal of treatment. This proposal will be validated from the MIWGUC group in prospective study.

References:

1. Heiligenhaus A, Foeldvari I, Edelsten C, Smith JR, Saurenmann RK, Bodaghi B, et al. Proposed outcome measures for prospective clinical trials in juvenile idiopathic arthritis-associated uveitis: a consensus effort from the multinational interdisciplinary working group for uveitis in childhood. Arthritis Care Res (Hoboken). 2012;64(9):1365-72.

Disclosure of Interest: None Declared

P451 Proposal for the definition of inactivity of juvenile idiopathic arthritis related uveitis from the Multinational Interdisciplinary Working Group for Uveitis in Childhood Group (MIWGUC)

Ivan Foeldvari1, Jordi Anton2, Rosa Bou2, Sheila Angeles-Han3, Regitze Bangsgaard4, Gabriele Brumm5, Tamas Constantin6, Clive Edelsten7, Jens Klotsche8, Kirsten Minden8, Elisabetta Miserocchi9, Susan Nielsen4, Gabriele Simonini10, Arnd Heiligenhaus11

1AM Schön Klinik Eilbek, Hamburg, Germany; 2Universitat de Barcelona, Hospital Sant Joan de Deu, Barcelona, Spain; 3Emory University, Atlanta, GA, United States; 4Juliane Marie Centret, Rigshospitalet, Copenhaven, Denmark; 5Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany; 6Semmelweis University, Budapest, Hungary; 7Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom; 8German Rheumatism Research Center, Berlin, Germany; 9Università Vita-Salute, Scientific Institute San Raffaele, Milano, Italy; 10Universita degli studi Firenze, Firenze, Italy; 11St. Franziskus Hospital, Muenster, Germany
Presenting author: Ivan Foeldvari

Introduction: Juvenile idiopathic arthritis (JIA) associated uveitis is the most common extraarticulare comorbidity of juvenile idiopathic arthritis. Nowdays it occurs in about 10-15% of JIA patients. As effective treatment options are emerging, is it extremely important to propose validated definition of inactivity, which is main aim of the treatment.

Objectives: To develop a proposal for the definition of inactivity.

Methods: Multinational Interdisciplinary Working Group for Uveitis in Childhood Group (MIWGUC) had prospectively evaluated the validity of the proposed outcome measures (1). Based on these data, we proposed a definition of inacitivity using the nominal group technique in a consensus meeting in Barcelona, Spain, in November 2015.

Results: The following items were selected to define inacitivity. It is required, that in both eyes the following condition is reached:

1. Slit lamp total number of AC cells: 0 inflammatory cells

*In aphakic patients,some cells may be present, in the anterior vitreous

2. Absence of Optic disc edema

*The presence of isolated optic disc edema may not be a sign of activity

3. Absence Macular edema

*The presence of isolated macular edema may not be a sign of activity

4. Absence of Vitreous haze

*The presence of isolated vitreous haze may not be a sign of activity

5. VAS score of activity physician 0-100: must be 0

Conclusion: We proposed items to define inactivity of JIA associated uveitis, which is a major goal of treatment. This proposal will be validated from the MIWGUC group in prospective study.

References:

1. Heiligenhaus A, Foeldvari I, Edelsten C, Smith JR, Saurenmann RK, Bodaghi B, et al. Proposed outcome measures for prospective clinical trials in juvenile idiopathic arthritis-associated uveitis: a consensus effort from the multinational interdisciplinary working group for uveitis in childhood. Arthritis Care Res (Hoboken). 2012;64(9):1365-72.

Disclosure of Interest: None Declared

P452 Proposal for a response index for juvenile idiopathic arthritis related uveitis from the Multinational Interdisciplinary Working Group for Uveitis in Childhood Group (MIWGUC)

Ivan Foeldvari1, Jordi Anton2, Rosa Bou2, Sheila Angeles-Han3, Regitze Bangsgaard4, Gabriele Brumm5, Tamas Constantin6, Clive Edelsten7, Jens Klotsche8, Kirsten Minden8, Elisabetta Miserocchi9, Susan Nielsen4, Gabriele Simonini10, Arnd Heiligenhaus11

1AM Schön Klinik Eilbek, Hamburg, Germany; 2Universitat de Barcelona, Hospital Sant Joan de Deu, Barcelona, Spain; 3Emory University, Atlanta, GA, United States; 4Juliane Marie Centret, Rigshospitalet, Copenhaven, Denmark; 5Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany; 6Semmelweis University, Budapest, Hungary; 7Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom; 8German Rheumatism Research Center, Berlin, Germany; 9Università Vita-Salute, Scientific Institute San Raffaele, Milano, Italy; 10Universita degli studi Firenze, Firenze, Italy; 11St. Franziskus Hospital, Muenster, Germany
Presenting author: Ivan Foeldvari

Introduction: Juvenile idiopathic arthritis (JIA) associated Uveitis is the most common extraarticulare comorbidity of juvenile idiopathic arthritis. Nowdays it occurs in about 10-15% of the JIA patients. As inniovativ effective treatment options are emerging, therefore is it extremely important for defining a validated response index in order to assess the effectivity of a drug.

Objectives: To develop a proposal for the response index, that assesses the effectivity of a given drug for treating JIA associated uveitis.

Methods: Multinational Interdisciplinary Working Group for Uveitis in Childhood Group (MIWGUC) had prospectively evaluated the validity of the proposed outcome measures(1). Based on the data, we proposed a response index using the nominal group technique in a consensus meeting in Barcelona, Spain, in November 2015.

Results: The following items were selected for defining response to treatment:

1. Slit lamp evaluation : total number of anterior chamber cells (AC) – expressed on a VAS 0- 100

2. Slit lamp evaluation: AC cells before pupil dilatation

3. Grade of AC flare according SUN criteria

4. Change in visual acuity – without operation – (provided in logMAR, independently of the charts used)

5. Occurrence and course of structural complications:

a. occurrence new posterior synechia

b. Change of Optic disc edema

c. Change of Macular edema

d. Change of Vitreous haze

6. VAS score of 0 to 100 score for uveitis activity in the worst eye in the last 4 weeks (assessed by ophthalmologist)

7. Has your eyes caused a problems in the last 4 weeks?

expressed on a VAS score of 0-100

(assessed by patients / or under the age of 8 years by the parents)

8. How do you judge your eye disease during the last 3 months?

Lot better / something better/ stable/ something worst/ lot worst

(assessed by patients / or under the age of 8 years by the parents)

9. Change of the score of the quality of life in an Uveitis specific quality of life instrument research item

10. How did you eye improved under treatment at the last three months? Expressed VAS score of 0-100

11. Missed work/school /kindergarten days– due of the uveitis

12. Change in CHQ/PedsQl score

Conclusion: We proposed items to define a response index for JIA associated uveitis. This should be an important instrument for evaluating effectivity of the treatment. This proposal will be validated from the MIWGUC group in prospective study.

References:

1. Heiligenhaus A, Foeldvari I, Edelsten C, Smith JR, Saurenmann RK, Bodaghi B, et al. Proposed outcome measures for prospective clinical trials in juvenile idiopathic arthritis-associated uveitis: a consensus effort from the multinational interdisciplinary working group for uveitis in childhood. Arthritis Care Res (Hoboken). 2012;64(9):1365-72.

Disclosure of Interest: None Declared

P453 National prospective online registry for juvenile idiopathic arthritis associated uveitis in Spain

Juan Manuel Mosquera Angarita1, Rosa Bou1, Carmen Garcia de Vicuña1, Maria Victoria Hernandez2, Alfredo Adan2, Victor Llorens2, Rosa Alcobendas3, Susana Noval3, Juan Carlos Lopez Robledillo4, Isabel Valls4, Mari Carmen Pinedo5, Alejandro Fonollosa5, Jaime de Inocencio6, Pilar Tejada6, Beatriz Bravo7, Manuel Torribio7, María Jesús García de Yebenes8, Jordi Antón1; Uveitis Working Group of the Spanish Pediatric Rheumatology Society

1Hospital Sant Joan de Déu, Barcelona, Spain; 2Hospital Clínic, Barcelona, Spain; 3Hospital La Paz, Madrid, Spain; 4Hospital Niño Jesus, Madrid, Spain; 5Hospital Cruces, Bilbao, Spain; 6Hospital 12 de Octubre, Madrid, Spain; 7Hospital Virgen de las Nieves, Granada, Spain; 8Instituto de Salud Musculoesqueletica, Madrid, Spain
Presenting author: Juan Manuel Mosquera Angarita

Introduction: Anterior uveitis is the most frequent extraarticular manifestation of juvenile idiopathic arthritis (JIA). However, there is a lack of standardization in its follow-up and management. Disease registries are powerful tools for evaluation and feedback on medical care quality, and become the base for recommendations on disease management.

Objectives: To design an online multicentric prospective registry for JIA-uveitis in Spain, establish quality indicators and propose improvements in the follow-up and management of this disease.

Methods: Through different consensus meetings, pediatric rheumatologists and ophthalmologists members of the uveitis working group of the Spanish Pediatric Rheumatology Society (SERPE), designed a data collection sheet. A centered electronic database with intellectual property of SERPE was created following data safety regulation. The inclusion criteria for the registry were a known diagnosis of JIA and active uveitis at the moment of inclusion. The registry was open to the different centers in Spain willing to participate and a first data analysis was performed in February 2016. The project was approved by the local ethics committee and patients and families provided a signed informed consent.

Results: After a trial period, the online registry platform was launched in February 2015. 13 centers in Spain have applied to participate and in February 2016, seven centers have included a total of 91 patients from whom 331 registries were collected. Those registries correspond to: 1) Basal data (demographic, arthritis and uveitis characteristics), 2) Prospective rheumatology visits and 3) Prospective ophthalmology visits. We present the preliminary results from the basal data and first rheumatology and ophthalmology visits. Predominantly female gender (79%), caucasic origin (93%), positive ANA test (82%) and persistent oligoarticular JIA subtype (68%). Mean age at onset of arthritis symptoms is 3.3 ± 2.8 years, mean age at JIA diagnosis is 3.8 ± 3.2 years and mean age at first uveitis diagnosis is 5.8 ± 5.3 years. At first rheumatology visit the average of active arthritis was 0.4, the mean value in the global disease visual analogical scale (VAS) was 17.1 mm for the rheumatologist, 16.2 for parents and 12.2 for children; and the VAS for uveitis was 28.9 mm for the rheumatologist and 24.3 for the ophthalmologist. At first ophthalmology visit 95% were anterior uveitis and around 85% were asymptomatic. Measurement of cellularity grading was 1+ or less according SUN classification in about 70%. Mean logMAR visual acuity was 0.14 in right eye and 0.23 in left eye. Main complication was band keratopathy (21%) and methotrexate was the most frequent used medication at the first visit (50%) followed by adalimumab (32%)

Conclusion: Our group has managed to launch a prospective online multicentered registry of JIA associated uveitis obtaining a representative sample of patients of whom we present the preliminary data. Future steps will be the analysis of prospective data and the development of recommendations to achieve the best standards and quality indicators in JIA-uveitis. This registry represents a first but firm step for standardization of diagnosis, follow-up and management of the disease.

This project was partially funded by an unrestricted grant from Abbvie

Disclosure of Interest: None Declared

P454 Anti-DFS70 antibodies: new biomarkers for uveitis in juvenile idiopatic arthritis?

Lorenza Maria Argolini1, Irene Pontikaki1, Maria Orietta Borghi2, Laura Cesana2, Elisabetta Miserocchi3, Barbara Castiglioni4, Maurizio Gattinara1, Pierluigi Meroni1

1Rheumatology, Gaetano Pini Institute, Center of Pediatric Rheumatology, Chair of Rheumatology, University of Milan, Milan, Italy; 2Experimental Laboratory of ImmunoRheumatologic Researches, Department of Clinical Sciences and Community Health, University of Milan, IRCCS Istituto Auxologico Italiano, Milan, Italy; 3Ophthalmology and Visual Sciences, University Vita-Salute, Scientific Institute San Raffaele, Milan, Italy; 4Ophtometrist, Department of Rheumatology, JIA Uveitis Center, Gaetano Pini Institute, Milan, Italy
Presenting author: Lorenza Maria Argolini

Introduction: Uveitis is the most frightening extraarticular manifestation of juvenile idiopathic arthritis (JIA), if undiagnosed and untreated can lead to blindness. Historically antinuclear antibodies (ANAs) are associated with an increased risk of uveitis however as biomarkers they have a limited specificity because they are also seen in JIA without uveitis and the molecular target is still unknown. Anti-DFS70 antibodies are defined by a nuclear dense fine speckled (DFS) indirect immunofluorescence (IIF) pattern, first described in 1994. The main antigen recognized by these autoantibodies was identified as the lens epithelium-derived growth factor (LEDGF), also known as DFS70. This finding suggested that these antibodies may display a role in ocular diseases. Accordingly two recent studies described these antibodies n JIA patients with uveitis (H. Schmeling et al, J Rheumatology 2015; Vol 42, no.12; SL. Tansley et al, Rheumatology Vol 55 Suppl 1, april 2016).

Objectives: To investigate whether DFS70-like pattern may correlate with uvetis in a monocentric cohort of JIA patients.

Methods: Anti-DFS70 antibodies were investigated in 51 JIA ANA-positive patients [31 with uveitis (JIA-U) and 20 without uveitis as controls] by Nova-Lite HEp-2 Select providing a DFS70-enriched sample diluent, that allows the specific absorption of anti-DFS70 antibodies. The sera were tested by IIF before and after absorption and inhibition values higher than 30% were considered positive for the presence of anti-DFS70. Furthermore, ANA screening was also performed by QUANTA Flash CTD Screen Plus, a chemiluminescent immunoassay which includes the most relevant nuclear/cytoplasmic antigens but not DFS70 (dsDNA, Sm/RNP, Ro52, Ro60, SS-B, Scl-70, centromere, Mi-2, Ku, ThTo, RNAPol III, Pm/Scl, PCNA, Jo-1 and ribosomal-P protein).

Results: Before absorption, 26/31 (84%) JIA-U patients showed a DFS/homogeneous pattern. After the exposure to DFS70, 9/31 (29%) sera displayed an inhibition suggestive for anti-DFS70 positivity (>30%). In the JIA control group, 14/20 (70%) sera, displayed a DFS/homogenous pattern. However, only 3 of them (15%) were inhibited by the absorption. The CTD Screen was positive in 6/31 (19%) JIA-U and in 3/20 (15%) controls. Only one of these samples was significantly reduced after exposure to DFS70.

Conclusion: DFS/homogenous is the prevalent pattern in our ANA-positive JIA cohort, mainly in JIA-U. These data are in agreement with recent studies supporting a relationship between DFS/homogenous pattern and the risk of developing uveitis. The absorption with DFS70 suggests the presence of anti-DFS70 antibodies, that seems more frequent in JIA-U. However, as the DFS70-induced reduction of fluorescence intensity is only partial, a reactivity against molecules not yet identified may be suggested, in association with a DFS-like pattern. This hypothesis is also supported by CTD Screen results. Further studies aimed to identify new antibody specificities by additional techniques are needed to deeply investigate the ANA-associated risk of uveitis in JIA.

Disclosure of Interest: None Declared

P455 Adjuvite: a double-blind, randomized, placebo-controlled trial of Adalimumab in juvenile idiopathic arthritis associated uveitis

Pierre Quartier1, Veronique Despert2, Sylvaine Poignant3, Amandine Baptiste4, Caroline Elie4, Isabelle Kone-Paut5, Alexandre Belot6, Laurent Kodjikian7, Dominique Monnet8, Michel Weber9, Bahram Bodaghi10

1Unité d’Immuno-Hématologie et Rhumatologie Pédiatrique, Hôpital Necker-Enfants Malades, Paris, France; 2Pediatrie, CHU, Rennes, France; 3Pédiatrie, CHU, Nantes, France; 4Biostatistiques, Hôpital Necker-Enfants Malades, Paris, France; 5Pédiatrie, CHU, Kremlin-Bicetre, France; 6Pédiatrie, Hopital femme-mere-enfant, Lyon, France; 7Ophtalmologie, CHU, Lyon, France; 8Ophtalmologie, CHU Cochin, Paris, France; 9Ophtalmologie, CHU, Nantes, France; 10Ophtalmologie, CHU Pitié Salpétrière, Paris, France
Presenting author: Pierre Quartier

Introduction: Patients with early-onset, oligo or polyarticular juvenile idiopathic arthritis (JIA) may develop a chronic, anterior uveitis, which treatment usually requires long-term topical steroids, sometimes systemic steroids. Methotrexate often lack of efficacy. Small series suggested that a reduction of ocular inflammation and of the risk of flare could be achieved with anti-TNF alpha antibodies

Objectives: To asses the saffecty and efficacty of Adalimumab in patients with JIA-associated uveitis with an inadequate response to topical steroids and methotrexate

Methods: Elligible patients had chronic uveitis with inadequate response to topical steroids and MTX, no previous anti-TNF antibody therapy and at least one assessable eye with inflammation quantified by laser flare photometry ≥30 photons/ms. Double-blind randomization at Day 1 (D1) into 2 equal groups, one treated with placebo and one with adalimumab (24 mg/m2 in patients aged 4 to less than 13 years, 40 mg in patients ≥ 13), every other week subcutaneous injections. The primary objective was to demonstrate a higher response rate at Month 2 (M2) in the adalimumab arm versus the placebo arm. Response was defined as a 30% reduction of inflammation on laser flare photometry in the eye with the highest flare value at D1 and improvement or a stable appearance on slit lamp examination. From M2 to M12, all patients were allowed to receive adalimumab (open phase)

Results: 34 patients were screened and 31 received at least one injection of study treatment.

Conclusion: Adalimumab was effective in reducing ocular inflammation within 2 months and well tolerated over 12 months in patients with JIA-associated chronic uveitis and an inadequate response to topical steroids and MTX. Laser flare photometry is a valuable tool to assess early response to treatment in these patients

Trial registration identifying number: NCT01385826

Disclosure of Interest: P. Quartier Grant / Research Support from: Abbvie, Novartis, Pfizer, Roche, Consultant for: Abbvie, Novartis, SOBI, Speaker Bureau of: Abbvie, BMS, Novartis, PfiZer, Roche, SOBI, V. Despert: None Declared, S. Poignant: None Declared, A. Baptiste: None Declared, C. Elie: None Declared, I. Kone-Paut Grant / Research Support from: SOBI, Novartis and Roche, Consultant for: Novartis, SOBI, Pfizer, Abbvie and Roche, A. Belot: None Declared, L. Kodjikian Consultant for: Alcom, Alimera, Allergan, Bayer, Bausch&Lomb, Novartis, Thea, Speaker Bureau of: Alcom, Alimera, Allergan, Bayer, Bausch&Lomb, Novartis, Thea, D. Monnet: None Declared, M. Weber: None Declared, B. Bodaghi Consultant for: Abbvie
Table 10 (abstract P455).

Patients characteristics at study treatment onset

 

Ada (n = 16)

Placebo (n = 15)

All (n = 31)

Female, n (%)

15 (94)

13 (87)

28 (90)

Age, median value, years [ranges

10.8 [5.0-20.3]

9.2 [4.9-29.1]

 

Active joints, median n [ranges]

0 [0-3]

0 [0-4]

0 [0-4]

Uveitis median duration, years [ranges]

4.4 [0.4-18.9]

4.8 [0.6-24.2]

 

Laser flare (ph/ms), median [ranges]

99 [23-322]

70 [36-265]

 

Bilateral uveitis, n (%)

10 (63)

14 (93)

24 (78)

Ongoing treatments at D1

 Oral steroids, patients n (%)

7 (44)

3 (20)

10 (32)

 Methotrexate, patients n (%)

15 (94)

11 (73)

26 (84)

At M2, in intention-to-treat (1ary objective), there were 9/16 responders in the adalimumab group and 3/15 in the placebo group (p = 0.038, Chi-squared test; RR = 2.81, CI95% = [0.94-8.45] with log-binomial model estimation). Among responders to adalimumab, patients with very high laser flare photometry values showed quick improvement. One patient stopped the trial at D14 (adalimumab group, uveitis worsening) and one at M9 (ocular hypertony). 29 patients reached M12 on adalimumab. There were 6 serious adverse events in 5 patients, all in the placebo group, 5 during the open-label phase, none related to study treatment (investigator assessment)

P456 Paediatric uveitis in french referral ophthalmologic/rheumatologic centers: a descriptive analysis of 61 children

Laura Moal1, Antoine Rousseau2, LuuLy Pham1, Emmanuel Barreau2, Cherif Titah3, Pascal Dureau3, Marc Labetoulle2, Bahram Bodaghi4, Severine Guillaume Czitrom5

1Paediatrics, CHU de Bicetre, Le Kremlin Bicetre Cedex, France; 2Ophthalmology, CHU de Bicetre, Le Kremlin Bicetre Cedex, France; 3Ophthalmology, Fondation Rothschild, Paris, France; 4Ophthalmology, CHU Pitie Salpetriere, Paris, France; 5Service de Medecine des Adolescents, CHU de Bicetre, Le Kremlin Bicetre Cedex, France
Presenting author: Severine Guillaume Czitrom

Introduction: Uveitis in children is rare; fortunately, knowledge about the different types of paediatric uveitis is growing. Intensive interactions between ophthalmologists and paediatric rheumatologists are needed in order to choose the best therapeutic strategies for, sometimes, deep uveitis attacks.

Objectives: To describe a cohort of 61 patients with paediatric uveitis.

Methods: Retrospective analysis of the cohort of patients followed in a tertiary care center by a paediatric rheumatologist (SGC) and members of 3 well known ophthalmologic departments (AR, EB, CT, PD, ML and BB) in Paris, during the 2006-2016 period.

Results: 61 children were diagnosed with uveitis before the age of 18 and collectively followed in 3 ophthalmologic departments specialized in uveitis care in children along with 1 paediatric rheumatologist, each time systemic treatment was to be decided. Among the 61 patients, 33 had anterior (54%, group 1), 13 had intermediate (21%, group 2), and 15 had posterior or pan-uveitis (25%, group 3). Sex ratio was equally distributed among girls and boys for groups 1 and 2, but F/M ratio was 2 in group 3. Most of the children originated from Europe but importantly, as much as 1/3 came from non-European Mediterranean countries in groups 1 and 3. JIA was the leading cause of group 1 uveitis (42%); groups 2 and 3 uveitis were idiopathic despite complete etiological work-up in 77% and 47%, respectively. In group 3, etiologies were JIA (3 with 2 SpA), Behçet (3), sarcoidosis (1) and TINU syndrome (1). At presentation, mean ages were 8.1 ± 3.6 [2-17], 9.5 ± 4.6 [4-20] and 11 ± 3.9 [4-15] years old; eyes remained white in 51%, 77%, 47%, painless in 70%, 100%, 67%, and non photophobic in 70%, 100%, 87% of group 1,2, 3, respectively. There was no correlation between the color, the pain, and the photophobia of eyes in this cohort. Bilateral eye involvement was present in 70%, 77%, 73% at onset, with a secondary bilateralisation in 9%, 8%, 13% and uveitis presentation was granulomatous in 33%, 0%, 47% in group 1, 2, 3, respectively. The mean follow-up was 4.85 ± 3.1 [0.5-16] years with no difference between groups. Complications including band keratopathy, synechiae, papillary edema, macular edema, ocular hypertension, neovascularization, chorioretinitis, neuroretinitis, retinal detachment, vitreous hemorrhage, amblyopia were observed in 58% (19/33 patients, of which 5 had more than 1 complication), 61% (8/13 patients but 4/8 had more than 1 complication), 87% (13/15 patients, of which 9 had more than 1 complication) in group 1, 2, 3, respectively. In group 1, recourse to a 3rd line therapy combining at least synthetic DMARDs (MTX, AZA) and biologic DMARDs (monoclonal anti-TNFs, TCZ) was necessary in 11/33 children (33%, group 1), in 1/13 (8%, group 2), in 8/15 (53%, group 3). Surgery mainly for cataracts but also for recurrent band keratopathy and refractory glaucoma was done in 7/33 group 1 (21%), 1/13 group 2 (8%), 3/15 group 3 (20%).

Conclusion: Paediatric posterior and pan-uveitis induce a very high-level burden in children, but anterior uveitis as well, sometimes despite optimal therapeutic management in tertiary care centers.Tight control of uveitic children is absolutely required in order to decrease the level of definitive complications.

Disclosure of Interest: None Declared

P457 Safety and efficacy of infliximab and adalimumab for refractory uveitis in juvenile idiopathic arthritis: two year follow up data from the orchidea registry

Vanessa Cecchin1,2, Maria Elisabetta Zannin1,2, Daniele Ferrari2, Francesco Comacchio2, Irene Pontikaki2, Claudia Bracaglia2, Rolando Cimaz2, Fernanda Falcini2, Antonella Petaccia2, Stefania Viola2, Luciana Breda2, Francesco La Torre2, Fabio Vittadello2, Giorgia Martini1,2, Francesco Zulian1,2

1Department of Pediatrics, University of Padua, Padua, Italy; 2ORCHIDEA Network (OculaR involvement in CHIldhood rheumatic DisEAses, Padua, Italy
Presenting author: Vanessa Cecchin

Introduction:

The anti-tumour necrosis factor α (anti-TNFα) agents has significantly changed the management of many rheumatic conditions, included Juvenile Idiopathic Arthritis-related Chronic Anterior Uveitis (JIA-CAU) but the experience, so far, is still limited. Since 2007 a National Registry (ORCHIDEA), formed by Paediatric Rheumatologists and Ophthalmologists, prospectively collected online, through a protected website, data on safety and efficacy of anti-TNF-α agents used for the treatment of CAU.

Objectives: To evaluate safety and efficacy of adalimumab (ADA) and infliximab (IFX) for the treatment of JIA-CAU) in a cohort of patients followed for at least 2 years of follow-up.

Methods:

Patients with JIA-CAU refractory to standard immunosuppressive treatment and/or corticosteroid-dependent and treated with infliximab (IFX) or adalimumab (ADA) were managed by a standard protocol and entered the Orchidea Registry. Data, recorded every 3 months, included uveitis course, number/type of ocular complications, drug-related adverse events (AE), treatment change. The diagnosis and course of JIA was based upon the ILAR criteria and the diagnosis of uveitis was made according to the SUN Working Group criteria. Uveitis flare was defined as an increase of the cells in the anterior chamber of 2+ or more as compared to the baseline. Clinical remission was defined as the absence of flares for more than 6 months on treatment, without or with minimal topical treatment (corticosteroid and/or mydriatic-cycloplegic eye drops ≤ 1/day). Data of patients treated for at least 2 years were retrieved from the Orchidea Registry and analyzed using descriptive statistics.

Results: From January 2007 to December 2014, among 236 patients included in the Orchidea database with JIA-CAU on anti-TNF agents (IFX or ADA), 154 (125 female, 29 male) reached 2 years of follow-up and entered the study. Fifty-nine patients were treated with IFX, 95 with ADA. No major AEs were recorded; 30 patients (19.5%) experienced minor AE and 11 (7.1%) multiple AEs. The total number of minor AEs amounts to 54: 22 were related to ADA, 32 to IFX. Infections were the most frequent AE for both anti-TNF agents (37.6% for IFX and 40.9% for ADA), followed by headache for ADA (25%) and local skin reactions for IFX (27.4%). During the 2-years follow-up, 84 new-onset complications (42 with ADA and 42 with IFX) were reported. Cataract was the most common complication (18.1%) followed by band keratopathy 12.1% and synechiae 12.7%. Vitreitis was significantly less frequent in the ADA group (3.2%) than in IFX group (15.3%, p 0.006). Drug switch was reported in 35 patients (22.7%): 26 IFX to ADA, 2 ADA to IFX, 6 ADA and 1 IFX to other biological agents. In general, 129 patients (83.8%) achieved clinical remission, 89.5% with ADA and 74.6% with IFX, respectively (p = 0.015).

Conclusion: IFX and ADA confirm to be effective and safe for treatment of refractory JIA-related CAU after 2 years of follow-up, a higher rate of clinical remission was reported in the ADA group that presented less frequency of adverse events and lower evidence of drug switch.

Disclosure of Interest: None Declared

P458 Rare NOD2 variants in patients with granulomatous uveitis

Caroline Galeotti1, Guillaume Sarrabay2, Olivier Fogel3, Isabelle Touitou2, Bahram Bodaghi4, Corinne Miceli-Richard3, Isabelle Koné-Paut1

1Pediatric Rheumatology, Bicêtre Hospital, Le Kremlin Bicêtre, France; 2Genetics, CHU Montpellier, Montpellier, France; 3Rheumatology, Cochin Hospital, Paris, France; 4Ophtalmology, La Pitié Salpêtrière, Paris, France
Presenting author: Caroline Galeotti

Introduction: Blau Syndrome is a rare autosomal dominant inflammatory disease characterized by early-onset granulomatous arthritis, dermatitis and recurrent uveitis (1). Mutations in the nucleotide-binding domain (NBD) of CARD15/NOD2 gene (mainly R334W, R334Q and L469F) have been identified in Blau syndrome (2). Polymorphisms in the leucine-rich repeats (LRR) of CARD15 are associated with Crohn’s Disease, and mutations in the NBD domain are observed in Blau syndrome (3).

Objectives: We describe two patients with granulomatous uveitis carrying rare genetic variants of NOD2.

Methods: The analysis of the coding exons of the NOD2/CARD15 gene was performed in our two patients because they had a granulomatous uveitis.

Results: The first patient, a 14 years old boy, had an isolated bilateral granulomatous uveitis since he was 10 years old. He was treated by steroids and methotrexate. He carried the A725G variant of NOD2 (rs5743278 MAF 0.018). The second patient, a 15 years old girl had an isolated bilateral granulomatous panuveitis since she was 5 years old. She was treated by azathioprine and steroids. She carried two other rare genetic variants of NOD2: H287Y and L682F (MAF = 0.0002).

Conclusion: NOD2 is composed of three domains: a C-terminal LRR domain involved in ligand recognition, a central NBD and an N-terminal CARD domain. Our two patients carried a rare genetic variant located between the LRR and the NBD domains (A725G and L682F). The A725G variant has been previously described in patients with Crohn disease’s (CD) phenotype by Hugot et al (3) but our first patient had no clinical symptom related to CD. The second patient carried another rare variant located in the NBD domain (H287Y), compatible with the diagnosis of Blau syndrome. According to these observations, genetic variations located between the LRR and the NBD domains of NOD2 might be associated with the occurrence of granulomatous uveitis. It should be thus recommended to screen NOD2 mutations in patients with isolated granulomatous uveitis.

References:

1. Blau EB. Familial granulomatous arthritis, iritis, and rash. The Journal of pediatrics. 1985 Nov;107(5):689-93. PubMed PMID: 4056967. Epub 1985/11/01. eng.

2. Miceli-Richard C, Lesage S, Rybojad M, Prieur AM, Manouvrier-Hanu S, Hafner R, et al. CARD15 mutations in Blau syndrome. Nature genetics. 2001 Sep;29(1):19-20. PubMed PMID: 11528384. Epub 2001/08/31. eng.

3. Hugot JP, Chamaillard M, Zouali H, Lesage S, Cezard JP, Belaiche J, et al. Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn’s disease. Nature. 2001 May 31;411(6837):599-603. PubMed PMID: 11385576. Epub 2001/06/01. eng.

Disclosure of Interest: None Declared

P459 Characteristics of children with juvenile idiopathic arthritis and JIA-associated uveitis

Hala Etayari, Hashad Soad

Pediatric rheumatology, Tripoli Children Hospital, Tripoli, Libya
Presenting author: Hala Etayari

Introduction: JIA is a group of heterogeneous diseases characterized by the presence of chronic arthritis develops before the 16th birthday after the exclusion of other causes of chronic arthritis. Uveitis is the most common extra-articular manifestation in JIA which has vision threatening complications. The well known risk factors for development of uveitis in JIA are 1) younger age at the development of JIA, 2) female sex, 3) short disease duration, 4) ANA positivity 5) RF negative disease 6) oligoarticular subtype. Since the disease is most of the times asymptomatic, regular screening by ophthalmologist is necessary for early diagnosis and treatment.(1-4)

Objectives: The Rheumatology Clinic of Tripoli Children Hospital receives JIA cases from western and southern areas of Libya. Despite adherence to the guidelines for uveitis screening, low incidence of uveitis was noticed. We studied this population to find out the reason for this low prevalence.

Methods: This case series study is performed by reviewing the medical records of the patients. Data regarding demographic characters, age at presentation and if MTX was received are collected, for those with uveitis if received before development of uveitis. Data was summarized by using percentages, mean and standard deviation where applicable. Chi square test was used to compare JIA with uveitis and JIA with no uveitis cases. Mann-Whitney test was used in comparing age at presentation. 155 JIA cases were included and followed up for a period ranged from 3 weeks to 12.5 years. Patients were included even if they were followed up for short period because tow has developed uveitis during this period.

Results: The majority of cases are of the oligoarticular type and polyarticular seronegative type representing 28.3% and 27.7% of the cases respectively. Age at presentation ranged from 10 months to 15.5 years with mean 8 ± 4years. Females represented 67.1% of the cases and female predominance was noticed in all JIA types except ERA were males and females are nearly equal (male to female ratio 1:1.2)

ANA positive cases represented 20% and rheumatoid factor positive cases represented 8.4% of total cases.

Of the 155 cases 9 (5.8%) developed uveitis. There are also 6 cases of idiopathic uveitis still following up may develop JIA not included in the analysis. 2 of the uveitis cases were males and 7 were females. By comparing uveitis and non-uveitis cases sex was not found a significant factor (p value = 0.22).The period from JIA diagnosis to development of uveitis ranged from 0 (uveitis developed at diagnosis) to 6 years with average of 2 years. The mean age at JIA diagnosis in uveitis cases is 5.6 ± 2 years. This is significantly lower than non-uveitis cases (p value (0.042)

4 cases developed in the persistent oligoarticular subtype, 2 cases in the polyarticular seronegative subtype, 1 case in the extended oligoarticular subtype, and 1 case in Enthesitis related arthritis.

All of the cases were rheumatoid factor negative and 5 of them were ANA positive. Comparing uveitis and non-uveitis cases ANA positivity was a significant factor in the development of uveitis (p value = 0.00) while rheumatoid factor result was not a significant factor (p value = 0.523)

6 of uveitis patients did not receive MTX as a treatment before the development of uveitis while 4 of them received MTX.

By comparing uveitis and non-uveitis cases MTX did not significantly affect the development of uveitis (p value = 0.47)

Conclusion: The incidence of uveitis is one of the lowest amung JIA cases and the factors found to be significant in the development of uveitis are age at presntation and ANA positivity.

References:

1. Angeles-Han ST, Pelajo CF, Vogler LB, Rouster-Stevens K, Kennedy C, Ponder L, et al. Risk Markers of Juvenile Idiopathic Arthritis-associated Uveitis in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry. J Rheumatol. 1 December, 2013;40(12):2088–96.

2. Angeles-Han ST, McCracken C, Yeh S, Jenkins K, Stryker D, Rouster-Stevens K, et al. Characteristics of a cohort of children with Juvenile