Safe and effective canakinumab-treatment of neonatal onset multisystem inflammatory disease (NOMID)/ chronic infantile neurologic cutaneous and articular (CINCA)

Introduction

NOMID/CINCA is the most severe phenotype of cryopyrin-associated periodic syndrome (CAPS), characterized by persistence of inflammation-mediated symptoms and overproduction of interleukin (IL)-1β, associated with significant morbidity, if untreated. In CAPS-patients early initiation of anti-IL1β-treatment appears to prevent severe disease sequelae. However, canakinumab as a 1^st-line treatment in young infants suffering from NOMID has been scarcely reported.

Objectives

To report the effects of early-onset canakinumab-treatment in NOMID/CINCA.

Patients and methods

Case presentation.

Results

A late-preterm (37-weeks- gestational-age) girl presented fever, urticarial-like rash, perilimbal redness, meningitis, elevation of WBC/neutrophils, ESR, CRP on 20 hours of life and severe anemia necessitating RBC-transfusion in the 5^th day of life. NOMID/CINCA was suspected on the basis of persistence of elevated inflammatory (including SAA) markers in the absence of infection-causative organisms in blood, CSF and urine, of non-responsiveness to antibiotics, of persistent CNS inflammation (CSF pleiocytosis and elevated protein) and of neutrophilic infiltration (revealed by skin biopsy) in the areas of urticarial-like rash. The detection of the c.1792A>T (p.Ile598Phe) mutation (de-novo as it was no detected in parents) in exon 3 of the NLRP3-gene, causative for NOMID/CINCA according to the infevers-database, confirmed the diagnosis. Brain-MRI was normal despite persistent CNS-inflammation represented by pleiocytosis and elevated protein and IL-6 and IL-8-levels in CSF (lumbar puncture performed on the 1^st-day and 3^rd-month of life). In peripheral blood IL-1β, IL-6 and IL-8 were undetectable. Opthalmoscopy/fundoscopy, and auditory-evoked-potentials were normal. After providing immunizations anti-IL1β-treatment with canakinumab 4mg/kg/8 weeks was initiated in the age of 4-months. Fever and rash remitted in 24h. Inflammatory markers normalized after 5-days. On 16-months of age the disease remains into remission. The only sign that persists is perilimbal redness. Mental and motor development is normal. No sensorineural or skeletal manifestations developed. Self-limited, 24h-duration, scarce urticarial-rash appeared in the age of 6 and 15 months with concomitant mild elevation of WBC/ neutrophils and SAA but normal CRP and ESR levels. Repeat MRI revealed absence of CNS involvement and lumbar puncture was not repeated. No adverse reactions presented apart from 1 URI after 12-months of canakinumab treatment.

Conclusion

Early initiation of canakinumab-treatment in CINCA leads to disease-remission and appears to prevent the development severe disease-sequelae such as CNS, sensorineural and skeletal manifestations. The patient presented no severe adverse reactions.

Consent to publish

Written informated consent for publication of their clinical details was obtained from the patient/parent/guardian/relative of the patient.