autoinflammatory

Autoinflammatory refers to diseases driven by dysregulation of the innate immune system that cause recurrent or continuous episodes of systemic inflammation. Unlike autoimmune diseases, autoinflammatory conditions typically lack high-titer autoantibodies or antigen-specific T cells, and inflammation often occurs without an obvious external trigger.

Most autoinflammatory conditions are linked to genetic mutations affecting innate immune pathways, including inflammasomes. Mutations in genes such as NLRP3, MEFV, MVK, and TNFRSF1A can lead to overproduction of inflammatory cytokines, particularly interleukin-1 beta and interleukin-18, driving fever and organ inflammation. Some disorders are multifactorial or acquired.

Common features include recurrent fever, rash, serositis, arthritis, abdominal pain, lymphadenopathy, and elevated inflammatory markers during flares. Episodes range from days to weeks and may begin in infancy or childhood; chronic inflammation can occur in certain syndromes.

Diagnosis relies on clinical assessment, family history, and targeted genetic testing for known autoinflammatory genes. Laboratory findings often show elevated C-reactive protein, erythrocyte sedimentation rate, and serum amyloid A during flares, while infections and autoimmune diseases are excluded.

Treatment varies by syndrome but often centers on controlling inflammation with cytokine inhibitors. Interleukin-1 blockers such as anakinra, canakinumab, and rilonacept are effective in many conditions. Colchicine is used in familial Mediterranean fever; corticosteroids or other immunosuppressants may be employed in some cases. Long-term management aims to prevent complications such as amyloidosis.

The term autoinflammatory was introduced to distinguish these innate-immune–driven disorders from autoimmune diseases, and ongoing research continues to identify additional conditions and improve therapies.