# Concomitant Systemic Autoinflammatory Diseases: Diagnostic and therapeutic challenges

## TL;DR

A 3-month-old infant had overlapping symptoms of two rare inflammatory diseases, requiring advanced genetic testing and combined treatment for effective management.

## Contribution

Highlights the diagnostic and therapeutic challenges of coexisting systemic autoinflammatory diseases and the role of somatic mosaicism.

## Key findings

- The infant had NOMID confirmed by NLRP3 somatic mosaicism despite initial negative genetic tests.
- Coexisting FMF was identified through MEFV gene mutations, requiring combined treatment with anakinra and colchicine.
- The case underscores the importance of considering somatic mosaicism in atypical or unresolved SAID cases.

## 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.