Table 2 Summary of all reported cases of Henoch-Schönlein Purpura with lung involvement in children

Weiss et al. 1979, USA [23]

M, 8 years

Earache and sore throat (3 days prior to admission), painful swollen joints (2 days prior to admission), skin rash, arthralgia, abdominal pain (1 day prior to admission)

The day of admission to hospital, 2 days after HSP onset

Dyspnea, hemoptysis, tachypnea, nasal flaring, retractions, bilateral basilar rales, anemia

CXR: increased heart size, increased perihilar bronchovascular markings, right pleural effusion.

BAL: not performed.

FR and ANA negative. Kidney biopsy not performed.

Oral Steroid and supportive therapy.

Not reported mechanical ventilation.

Death.

Leatherman et al. 1982, USA [29]

F, 10 years

Skin rash, arthralgia, abdominal pain, nephritis

Not reported

No respiratory symptoms

Lung biopsy: Alveolar hemorrhage, immunofluorescent-negative, with focal chronic alveolar septal inflammation, no vasculitis.

BAL: not performed.

C3, C4 normal, Kidney biopsy: granular deposits of IgG, IgM and C3 along glomerular capillary walls.

Oral Steroid + immunosuppressive therapy.

Not reported mechanical ventilation.

Resolution (after 4 reactivations in 6 months)

Payton et al. 1987, UK [30]

F, 17 years

Skin rash, arthralgia, sore throat and dry cough, proteinuria, hematuria, serum creatinine elevation

2 weeks after clinical manifestation of HSP

Hemoptysis, chest pain, dyspnea, anemia

CXR: bilateral fluffy opacities, consistent with intra-alveolar hemorrhage.

BAL: not performed.

Complement screen normal, ANA and anti-GBM negative. Kidney biopsy: patchy tubular loss, no arterial damage, some glomeruli with focal segmental proliferation with foci of necrosis and 4 glomeruli showed crescent. C1, C3, IgA, IgG, fibrin deposits

Oral steroid + immunosuppressive therapy.

Resolution.

Olson et al. 1992, USA [10]

F, 14 years

Arthralgia, abdominal pain for 3 months, then skin rash

3 weeks after skin rash

Fatigue, chest pain, cough and rales, hypoxemia, hemoptysis, anemia

CXR: marked fluffy alveolar infiltrates.

BAL: Diffuse bleeding.

ANA, ANCA, Anti- GBM negative, C3, C4, IgG, IgA, IgM normal. Kidney biopsy: Focal segmental glomerulonephritis with mild mesangial proliferation;

No deposition of IgG, IgM, IgA, C3.

Methylprednisolone iv followed by oral steroid.

Red blood cell transfusion.

Resolution (only one mild episode of purpura within a few weeks of the pulmonary hemorrhage).

F, 4½ years

Skin rash, abdominal pain, arthralgia, hematuria

Seven months after onset of HSP but during a fourth discrete episode of reactivation

Fatigue, pallor, cough, chest pain, shortness of breath, hemoptysis, anemia

CXR: reticulo-nodular interstitial pattern.

BAL: not performed.

ANA, Anti-GBM negative, C3 decreased, C4, IgG, IgA, IgM normal. Kidney biopsy: Mesangial proliferative glomerulonephrtis with crescenteric lesions (60% glomeruli) No deposition of IgG, IgM, IgA, C3.

Oral steroid + immunosuppressive therapy.

Resolution (mild transient recurrence of arthralgia and abdominal pain 16 months after the pulmonary hemorrhage).

M, 15 years

Skin rash, arthralgia, myalgia, abdominal pain, blood in stools, sore throat, hypertension

5 days after HSP onset

Acute respiratory distress and anemia

CXR: extensive interstitial and alveolar changes.

BAL: not performed.

C3, C4 normal.

Oral steroid then methylprednisolone iv.

Mechanical ventilation.

Red blood cell transfusion.

Death.

M, 16 years

Skin rash, arthralgia, abdominal pain, acute abdomen, hypertension, ARF, weakness and hyperreflexia, fever

3 weeks after onset of HSP

Dyspnea, cough, anemia

CXR: cardiomegaly, pleural effusion, increased pulmonary vascularity

CT-scan of lungs: interstitial infiltrates.

BAL: not performed.

ANA, ANCA, Anti- GBM negative, C3, C4 normal, IgG, IgA increased, IgM decreased. Kidney biopsy: Diffuse proliferative glomerulonephritis with focal segmental necrosis.

Deposition of IgG, IgA, IgM, C3, fibrinogen.

Methylprednisolone iv followed by oral steroid + immunosuppressive therapy.

Red blood cell transfusion.

Resolution.

Wright et al. 1994, USA [26]

F, 14 years

Skin rash, arthralgia, abdominal pain, melena, hematuria, proteinuria, serum creatinine elevation, ARF

3 weeks after onset of HSP

Hemoptysis, decrease in hematocrit

CXR: bilateral pulmonary infiltrates consistent with hemorrhage Lung biopsy: intra-alveolar hemorrhage with transmural neutrophilic infiltration of small arterioles, capillaries and postcapillary venules, intravascular and intra-alveolar fibrin, IgM, C3 and fibrinogen deposits were present in the small vessels and alveolar capillaries

BAL: not performed.

ANCA, ANA, anti-GBM, FR, IgA fibronectin complexes negative. Kidney biopsy: diffuse proliferative endocapillary glomerulonephritis with segmental necrosis and intracapillary fibrin deposition. IgA, IgM, C3 deposits.

Methylprednisolone iv followed by oral steroid. Mechanical ventilation,

Peritoneal dialysis.

Resolution.

Carter et al. 1996, USA [31]

M, 15 years

Skin rash, abdominal pain, arthralgia, blood in stools, hematuria and proteinuria, hypertension, serum creatinine elevation, fever, sore throat

2 days after admission, 4 days after onset of HSP

Pleural effusion (which was drained), dyspnea, acute respiratory failure, anemia

CXR: infiltrates in the left upper and lower lung fields.

BAL: not performed.

C3 normal, C4 low, ANA negative. Kidney biopsy not performed.

Methylprednisolone iv followed by oral steroid.

Mechanical ventilation.

Red blood cell transfusion.

Resolution.

Paller et al. 1997, USA [8]

M, 12 years

Epistaxis, arthralgia, myalgia, skin rash, hypertension, nephritis with ARF

5 days after hospital admission, 12 days after onset of HSP

Tachypnea, cough, hemoptysis

CXR: bilateral fluffy alveolar infiltrates.

BAL: not performed.

ANA, ANCA negative, C3, C4, cryoglobulins, IgG, IgA, IgM normal. Kidney biopsy: necrotizing glomerulonephritis.

Methylprednisolone iv followed by oral steroid + immunosuppressive therapy.

Mechanical

Ventilation.

Resolution.

F, 21 month

Skin rash in the previous months during upper and lower respiratory infections

One week after the onset of an HSP flare (cough, irritability, lethargy)

Pallor and dyspnea, hematuria, anemia

CXR: enlarged heart, extensive bilateral lung infiltrates.

BAL: not performed.

Not performed.

Mechanical ventilation.

Death.

Vats et al. 1999, USA [32]

M, 7 years

Abdominal pain, vomiting, fever, and 4 days later: skin rash, edema, bloody diarrhea, nephritis (proteinuria and hematuria, serum creatinine elevation)

3 days after the onset of HSP symptoms, 7 days after hospital admission

Respiratory distress (tachypnea, intercostal reactions, chest rales, hypoxemia), anemia

CXR: bilateral pleural effusion with basal pulmonary infiltrates.

BAL: not performed.

ANA, ANCA negative, C3 and C4 decreased, IgG decreased, IgA normal. Kidney biopsy: focal and segmental endothelial and mesangial proliferation with no crescents; IgA, C3, and properdin in the mesangium and along the glomerular basement membrane in a peripheral lobular distribution.

Methylprednisolone iv followed by oral steroid. Mechanical

Ventilation.

Resolution.

Besbas et al. 2001, Turkey [33]

M, 6 years

Skin rash, ARF (edema, hypertension, oliguria and proteinuria)

9 days after skin rash, 2 days after ARF

Dyspnea and anemia

CXR: diffuse pulmonary infiltrates.

BAL: not performed.

C3, C4, IgA, IgG, ANA, anti-dsDNA, ANCA, anti-GBM, anti-cardiolipin negative. Kidney biopsy: diffuse proliferation, segmental scars and epithelial-fibroepitelial crescent formation, IgA and mild C3 and IgM staining.

Methylprednisolone iv followed by oral steroid + immunosuppressive therapy.

Hemodialysis and Mechanical ventilation.

Resolution.

Al Harbi et al. 2002, Kingdom of Saudi Arabia [34]

F, 9 years

Skin rash, knee joint pain, 2 days later abdominal pain and bloody stools and then nephritis with ARF (anuria, edema and hypertension)

10 days after onset of HSP

Respiratory distress, bleeding

CXR: moderate bilateral lung infiltrate and opacities.

BAL: not performed.

C3 1.17 g/l, C4 0.22 g/l, ANA 1:320, anti-dsDNA e ANCA negative. Kidney biopsy not performed.

Oral steroid followed by methylprednisolone + immunosuppressive therapy. Then oral steroid + immunosuppressive therapy. Hemodialysis, Mechanical ventilation.

Resolution.

Kalyoncu et al. 2006, Turkey [25]

M, 13 years

A one-week history of skin rash and arthralgia followed by abdominal pain and severe mitral insufficiency leading to hospital admission, ARF

3 weeks after the onset of skin rash and arthralgia, 2 weeks after hospital admission

Respiratory distress, severe anemia followed by anuria

CXR: bilaterally diffuse pulmonary opacities.

BAL: not performed.

C3 and C4 normal, ANA, anti-dsDNA, LE cell and other rheumatologic markers negative. Kidney biopsy not performed.

Oral steroid, then methylprednisolone iv + immunosuppressive therapy. Mechanical ventilation, Hemodialysis,

Red blood cell transfusion.

Death.

Matsubayashi et al. 2008 [15]

M, 6 years

Skin rash, 3 days later arthralgia, abdominal pain, blood in stools, microhematuria and then proteinuria

17 days after HSP flare

Dyspnea, polypnea, anemia

CXR: consolidation in the right lung fields.

Lung CT scan: diffuse consolidation and patchy opacities mainly in the right lung without interstitial thickening and fibrosis.

BAL: not performed.

ANA, ANCA, anti-GBM undetectable. Kidney biopsy: mesangial proliferative glomerulonephritis with crescent formation and IgA deposition in the mesangium.

Oral steroid then methylprednisolone iv + immunosuppressive therapy, then oral steroid + mizoribine.

Red blood cell transfusion.

Resolution.

Boyer et al. 2011, USA [35]

F, 9 years

Skin rash, arthralgia, abdominal pain, nephritis for 10 days, followed by clinical improvement and the same week, by a flare characterised by rash, arthralgia, abdominal pain, ARF, seizures

20 days after HSP onset

Dyspnea, hypoxemia, and respiratory failure

CXR: diffuse patchy infiltrates.

BAL: Gross pulmonary hemorrhage with fresh blood and hemosiderin-laden macrophages

Kidney biopsy: sclerosing lesions and abundant IgA deposits in more than half of the glomeruly. No data about Auto-Antibody.

Methylprednisolone iv followed by oral steroid, then methylprednisolone iv + immunosuppressive therapy.

Plasmapheresis, Intravenous gamma globulin, Mechanical ventilation.

Resolution (progressive decrease in renal function and 14 months after HSP onset, successful kidney transplant)

Chen et al. 2011, Taiwan [14]

F, 11 years

Skin rash, abdominal pain, vomiting for 3 days then hematuria and nephrotic proteinuria, ARF

3 days after hospital admission, 6 days after HSP onset

Cough, general malaise, anemia

CXR: bilateral infiltration and consolidation

Lung CT scan: multiple patches with ground-glass appearance.

BAL: Macrophages with hemosiderin-laden particles and numerous red blood cells

C3 167 mg/dl, C4 43.2 mg/dl, ANA 1:40, anti-dsDNA, ENA, anti-GBM, anti-cardiolipin, cryoglobulin, cANCA negative, pANCA positive. Kidney biopsy: crescentic glomerulonephritis with diffuse mesangial proliferation and focal necrosis, IgA deposition.

Oral steroid then methylprednisolone iv followed by oral steroid + immunosuppressive therapy, plasma exchange

Red blood cell transfusion.

Resolution.

Ren et al. 2013, China [36]

F, 11 years

Skin rash for 2 weeks and urine test abnormality for 3 days, hospitalised with skin rash, joint pain, abdominal pain, and 10 days later nephritis

Not reported

No signs

CXR and Lung CT scan compatible with hemorrhage.

BAL: not performed.

C3, C4 normal. ANA, ENA negative. Kidney biopsy: mesenteric and endothelial cell proliferation and lobulation; three segments mild mesenteric proliferation and focal segmental hypertrophy of podocytes, and two segments presented endothelial cell swelling. Deposit of IgA and C3.

Oral steroid.

Resolution.

Ngobia et al. 2014, USA [27]

M, 18 years

Skin rash, arthralgia, abdominal pain, dark urine for 5 days, followed by hospital admission with finding of hematuria and proteinuria, treated with prednisolone and discharged after 4 days.

15 days after HSP onset, 6 days after discharge

Shortness of breath, hemoptysis, epistaxis and anemia, associated with worsening of HSP symptoms and hematuria, nephrotic proteinuria and serum creatinine elevation

CXR: right lower lobe opacity

Lung CT scan: mixed ground glass appearance Lung Function Tests: normal.

BAL: Low inflammatory profile and 30% hemosiderin-laden macrophages

C3, C4 normal. ANA, anti-GBM, ANCA negative. Kidney biopsy: necrotizing segmental glomerulonephritis with strong positive IgA and C3 staining.

Oral steroid, followed by methylprednisolone iv, then oral steroid + immunosuppressive therapy.

Resolution.

Aeschlimann et al. 2017, Canada [37]

M, 26 months

Skin rash, arthralgia, swelling, microhematuria and then proteinuria with hypertension

A few days after onset of HSP

Tachypnea, shortness of breath, severe respiratory distress, anemia

CXR and CT scan of the lungs showed extensive bilateral patchy opacities.

BAL: Diffusely blood-tinged mucus, no hemosiderin-laden macrophages

Normal C3, ANA, ANCA, Anti-GBM negative. Kidney biopsy: involvement of 10% of 23 glomeruli with segmental granular staining of mesangial regions with some capillary loops for IgG, IgA and C3 (IgAV nephritis).

Methylprednisolone iv then oral steroid + immunosuppressive therapy. Mechanical ventilation Red blood cell transfusion.

Resolution.

James et al. 2017, USA [38]

F, 10 years

Skin rash, arthralgia, fever, dry cough and then severe mitral regurgitation/ diastolic dysfunction/ increase in size of left atrium

10 days after HSP onset

Shortness of breath, tachypnea, anemia

CXR: patchy bibasilar opacities

Lung CT scan: bibasilar airspace disease.

BAL: not performed.

Kidney biopsy not performed.

Methylprednisolone iv then oral steroid. Mechanical ventilation, Intravenous gamma globulin.

Resolution (mild to moderate mitral regurgitation persisted after 1 year).

Clarke et al. 2018, UK [39]

M, 5 years

Purpuric rash, swollen extremities, arthralgia, fever, abdominal pain and rectal bleeding, proteinuria and hematuria (through to deterioration in renal function)

3 weeks after HSP onset

Respiratory deterioration, anemia

CXR: bilateral focal abnormalities.

BAL: not performed.

C3, C4, ANA, ANCA, anti-dsDNA negative. Kidney biopsy: diffuse proliferative glomerulonephritis with strong deposition of IgA.

Methylprednisolone iv, then immunosuppressive therapy + plasmapheresis followed by oral steroid and enalapril. Mechanical ventilation, Red blood cell transfusion.

Resolution.