D3.246 - A Novel Mutation in a Case of Deficiency of Interleukin-1 Receptor Antagonist in a Filipino Male Child

Introduction: Autoinflammatory conditions are rare genetic diseases that cause innate immune system activation. These should be considered in patients who present with recurrent fevers, rash, elevated inflammatory markers, and where other common causes like infection have been ruled out.

Case report: We report the case of a 7-year-old male born to consanguineous parents who was initially well until 3 months old when he began presenting with a chronic relapsing pustulosis that would usually be accompanied by fever. Initial laboratories showed a persistent leukocytosis with neutrophilic predominance, and immunologic work-up was remarkable only for a low NBT hence he was initially managed as chronic granulomatous disease and severe atopic dermatitis. The pustulosis persisted, however, and it was only at 5 years of age when a biopsy was done showing pustular psoriasis that he was subsequently started on acitretin, an oral retinoid. Fair response to this treatment led to his consult at our institution that same year. Our work-up revealed also leukocytosis with neutrophilic predominance and elevated ESR and CRP, but a negative DHR assay. We then considered an autoinflammatory condition that presents with pustular psoriasis such as deficiency of either interleukin-1 receptor antagonist (DIRA) or interleukin-36 receptor antagonist (DITRA) hence we sent for genetic testing, which revealed a homozygous missense variant in the IL1RN gene, confirming the diagnosis of DIRA. His mutation appears novel as it does not appear in any of the published case reports on DIRA. Since then, he continued to be managed with acitretin 10 mg daily, as anakinra and rilonacept are unavailable in our country, with methotrexate eventually added at 6 years old. At around this time, he also started having bilateral thigh pain with x-rays documenting lesions suspicious for osteomyelitis, and an x-ray taken when he had right knee pain showed arthritis hence colchicine was also added to his regimen.

Conclusion: This case highlights the challenges in diagnosing DIRA—pustulosis was initially attributed to infection and atopic dermatitis, and despite the diagnosis of pustular psoriasis, it took quite some time before a genetic cause was explored. Lack of access in low- and middle-income countries to biological treatment—standard of care in such cases—remains a significant hurdle to optimal management.