A small group of genetic conditions cause recurrent episodes of unexplained fever — often with rashes, abdominal pain, joint pain, or eye inflammation. These are not infections. They are caused by inappropriate activation of the innate immune system. Identifying the syndrome allows for targeted treatments that prevent attacks.
Hereditary periodic fever syndromes are a family of autoinflammatory disorders in which patients experience recurrent episodes of fever and inflammation that are not caused by infection. The episodes occur because the innate immune system — the part of the immune system that responds to threats without needing to be specifically targeted — fires inappropriately.
The major syndromes include Familial Mediterranean Fever (FMF), TNF Receptor-Associated Periodic Syndrome (TRAPS), Hyper-IgD Syndrome (HIDS, also called Mevalonate Kinase Deficiency or MKD), and the Cryopyrin-Associated Periodic Syndromes (CAPS). Each has a characteristic clinical pattern, age of onset, and underlying genetic cause. Many patients have lived with episodes for years before diagnosis.
Diagnosis combines documentation of the attack pattern, laboratory inflammation markers (CRP, SAA, ESR) measured both during and between attacks, IgD level, and confirmatory genetic testing for the specific syndromes on the differential.
The pattern of attack — duration, frequency, associated features such as rash or eye inflammation, and family history — narrows the differential significantly before genetic testing is sent.
Treatment is disease-specific. Familial Mediterranean Fever responds well to colchicine. Several syndromes including CAPS and TRAPS respond to IL-1 blockade with anakinra, canakinumab, or rilonacept. Coordination with rheumatology is common for ongoing management. With proper diagnosis and treatment, attack frequency is substantially reduced for most patients, helping to prevent long-term complications such as amyloidosis.
A first visit takes a detailed history of attack pattern, family history, and any prior workup. Inflammatory markers and genetic testing are ordered as appropriate. Coordination with rheumatology is arranged for ongoing management once diagnosis is confirmed.
Donald L. McNeil, MD · Board Certified in Allergy & Immunology and Internal Medicine
This page is provided for educational purposes and does not substitute for clinical judgment or direct medical advice. Treatment decisions are individualized based on your full history, examination, and laboratory findings. If you have an emergency, call 911.