Concomitant Systemic Autoinflammatory Diseases: Diagnostic and therapeutic challenges.

Abstract

Neonatal-onset multisystem inflammatory disease (NOMID) and familial Mediterranean fever (FMF) are distinct entities within the expanding spectrum of systemic autoinflammatory diseases (SAIDs). We report a 3-month-old infant who presented with recurrent fever, urticarial rash, and polyarthritis. After excluding other causes, anakinra was initiated based on clinical suspicion of NOMID. Despite treatment optimisation, she continued to experience disease flares. An initial autoinflammatory panel and subsequent whole-exome sequencing revealed heterozygous MEFV (M694V and V726A) gene mutations, which did not explain the clinical picture. Further deep sequencing identified NLRP3 (p.Asp305Glu) somatic mosaicism, confirming NOMID. The coexistence of NOMID and FMF presented significant diagnostic and therapeutic challenges. Disease activity stabilised after colchicine was added. Clinicians should consider somatic mosaicism in mutation-negative NOMID cases. In coexisting SAIDs, treatment should address both diseases to optimise outcomes.