This is general health information only and is not a substitute for advice from your GP or healthcare professional.
1. What are autoinflammatory periodic fever syndromes?
Autoinflammatory periodic fever syndromes are a group of disorders in which the innate immune system becomes inappropriately activated, causing recurrent episodes of fever and systemic inflammation without an identifiable infection. They are different from autoimmune diseases, which primarily involve an abnormal adaptive immune response. Some periodic fever syndromes are inherited, while others can occur without a clear genetic cause.
2. What are the main periodic fever syndromes?
Important inherited syndromes include Familial Mediterranean Fever (FMF), Tumour Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS), Mevalonate Kinase Deficiency (MKD/Hyper-IgD syndrome), and Cryopyrin-Associated Periodic Syndromes (CAPS). Other autoinflammatory conditions, such as PFAPA (Periodic Fever, Aphthous Stomatitis, Pharyngitis and Adenitis), are also important causes of recurrent fever, particularly in children.
3. What symptoms occur during an attack?
Episodes typically involve fever accompanied by one or more inflammatory symptoms. Depending on the syndrome, these may include abdominal pain, chest pain, joint pain or swelling, muscle pain, rash, mouth ulcers, swollen lymph nodes, headache, conjunctivitis, or marked fatigue. The pattern, duration, and associated symptoms can provide important clues to the specific syndrome.
4. How are periodic fever syndromes different from recurrent infections?
Recurrent infections usually have an identifiable infectious cause and may be associated with exposure or localising symptoms. Autoinflammatory fever episodes often occur repeatedly in a characteristic pattern, sometimes with complete recovery between attacks, and investigations demonstrate systemic inflammation without evidence of an infection. However, infection must be excluded appropriately, particularly during a first or severe episode.
5. Are periodic fever syndromes genetic?
Some are caused by inherited genetic variants. For example, FMF is commonly associated with variants in the MEFV gene, TRAPS with TNFRSF1A, MKD with MVK, and CAPS with NLRP3. However, genetic testing does not identify a causative variant in every patient, and finding a genetic variant does not automatically establish that it is responsible for the symptoms.
6. How are these conditions diagnosed?
Diagnosis is based on the pattern of recurrent fever, associated symptoms, physical findings, inflammatory markers, family and ethnic background, and exclusion of alternative diagnoses. Blood tests such as CRP, ESR, full blood count, ferritin, and serum amyloid A may be useful during attacks. Genetic testing can support the diagnosis in selected patients, but it should be interpreted in the clinical context.
7. What is the risk of complications?
Repeated uncontrolled inflammation can cause complications in some autoinflammatory syndromes. The most important long-term complication is AA amyloidosis, in which serum amyloid A deposits can accumulate in organs, particularly the kidneys, potentially causing proteinuria and progressive kidney disease. Effective control of inflammation substantially reduces this risk.
8. How are periodic fever syndromes treated?
Treatment depends on the specific syndrome. Colchicine is highly effective for preventing attacks and complications in most people with FMF. Other syndromes may respond to targeted biologic therapies that block inflammatory pathways, particularly interleukin-1 (IL-1). Medicines such as anakinra or canakinumab may be used in appropriate patients under specialist supervision.
9. Can periodic fever syndromes be cured?
Most inherited autoinflammatory syndromes are chronic conditions rather than illnesses that can simply be cured. However, modern treatments can often suppress inflammation very effectively, reduce attacks, prevent organ damage, and allow people to lead normal or near-normal lives. Treatment is generally tailored to the individual’s specific syndrome and disease severity.
10. When should someone be assessed for a periodic fever syndrome?
Medical assessment should be considered when a person has recurrent unexplained episodes of fever, particularly when they follow a recognisable pattern or are accompanied by abdominal or chest pain, arthritis, rash, mouth ulcers, swollen lymph nodes, or markedly elevated inflammatory markers. Specialist assessment is particularly important when episodes begin in childhood, there is a family history of periodic fever, or inflammation persists between attacks.