What is Familial Mediterranean Fever?
Familial Mediterranean Fever (FMF) is a rare inherited autoinflammatory disease characterised by recurrent, self-limited episodes of fever and serositis — inflammation of the membranes lining the abdomen, chest, and joints. The episodes typically last 1 to 3 days and resolve on their own, only to return weeks or months later.
It is the most common of the monogenic autoinflammatory disorders, and although it is described as rare globally, it is decidedly less rare around the eastern Mediterranean: among populations of Armenian, Turkish, Arab, Sephardi Jewish and (less commonly) Greek and Cypriot ancestry, carrier frequencies can reach 1 in 5.
The cause
FMF is caused by mutations in the MEFV gene, which encodes a protein called pyrin, a key regulator of the inflammatory response. Faulty pyrin allows inflammation to fire off without an obvious trigger.
The condition is usually inherited in an autosomal recessive pattern: a child must inherit a mutated MEFV gene from both parents to develop classic disease. Carriers (one mutated gene) are typically healthy, although some develop milder symptoms.
Typical attack
A textbook FMF attack includes:
- Sudden high fever (38–40°C)
- Sharp abdominal pain (peritonitis), often mistaken for appendicitis
- Chest pain with breathing (pleuritis)
- Monoarthritis — one painful, swollen joint, usually in the lower limb
- An erysipelas-like rash on the lower legs in some patients
Attacks resolve in 1 to 3 days. Between attacks, patients usually feel well.
Why early diagnosis matters
Repeated bouts of inflammation, untreated, can cause AA amyloidosis — the deposition of an abnormal protein in organs, most damagingly in the kidneys. Amyloidosis was historically the leading cause of premature death in untreated FMF; today, with treatment, it is largely preventable.
Diagnosis
Diagnosis is clinical — based on the pattern of recurring attacks, ethnic background, and exclusion of other causes. MEFV gene testing supports the diagnosis but a negative result does not rule it out, since not all mutations are detected by routine panels.
Inflammation markers (CRP, SAA, ferritin) are typically very high during attacks and normalise between them.
Treatment
The cornerstone of treatment is colchicine, an old, inexpensive drug that, in this disease, is transformative. Daily lifelong colchicine:
- Prevents most or all attacks in around two-thirds of patients
- Dramatically reduces the risk of amyloidosis even in patients whose attacks are not fully controlled
For colchicine-resistant cases, biologic IL-1 inhibitors (anakinra, canakinumab) are now the standard second-line therapy.
Living with FMF
With proper treatment, most people with FMF live full and active lives. Practical considerations include:
- Sticking with daily colchicine, even when feeling well
- Routine monitoring of kidney function and urinalysis
- Genetic counselling when planning a family
- Carrying a brief medical summary in case an attack is mistaken for a surgical abdomen
A rheumatologist with experience in autoinflammatory disease is the right specialist to manage this condition long-term.