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.

Keywords: Anakinra; Case report; Colchicine; FMF; NOMID; Oman.

Fig. 1.

Images demonstrating disease flares manifested by fever associated with generalised urticarial rashes and irratibility.

Fig. 2.

Markers of inflammation in a neonatal-onset multisystem inflammatory diseases infant and her response to anakinra and colchicine. The x-axis is a time of disease course in months. Vertical black lines indicate the start of anakinra treatment, whereas dotted red lines represent the start of colchicine therapy. Gray shaded areas represent normal values. C reactive protein reference range is <1 mg/L. Serum Amyloid reference range is <10 mg/L. WBC = white blood cells; CRP = C-reactive protein; ALT = alanine transaminase.