CINCA syndrome

Chronic Infantile Neurological Cutaneous and Articular (CINCA) syndrome, also known as Neonatal-Onset Multisystem Inflammatory Disease (NOMID), is the most severe form of the cryopyrin-associated periodic syndromes (CAPS). It is caused by mutations in the NLRP3 (CIAS1) gene, which encodes the protein cryopyrin, a key regulator of the inflammatory response. The disease is characterized by excessive production of interleukin-1β (IL-1β), leading to chronic systemic inflammation that begins in the neonatal period. CINCA/NOMID affects multiple organ systems. The hallmark features include a persistent urticaria-like skin rash that is typically present from birth or the first weeks of life, chronic aseptic meningitis causing progressive neurological complications (including headaches, papilledema, sensorineural hearing loss, and intellectual disability), and a distinctive overgrowth arthropathy particularly affecting the knees and other large joints. Patients also experience recurrent fevers, hepatosplenomegaly, lymphadenopathy, and chronic inflammation of the eyes (uveitis, papillitis) that can lead to vision loss. Secondary amyloidosis (AA amyloidosis, corresponding to ICD-10 code E85.0) is a serious long-term complication that can result in renal failure if the disease is left untreated. The treatment landscape has been transformed by the availability of IL-1 inhibitors. Anakinra (an IL-1 receptor antagonist), canakinumab (a monoclonal antibody targeting IL-1β), and rilonacept (an IL-1 trap) have demonstrated significant efficacy in controlling inflammation, preventing organ damage, and improving quality of life. Early and sustained treatment is critical to prevent irreversible neurological damage, hearing loss, joint destruction, and amyloidosis. Prior to the advent of IL-1-targeted therapies, the prognosis was poor, with significant morbidity and early mortality.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

Common questions about CINCA syndrome