What's familial Mediterranean fever?
Familial Mediterranean fever (FMF) is the most common inherited autoinflammatory disease. Caused by mutations in the MEFV gene (which encodes the protein pyrin) and inherited in an autosomal recessive pattern, it causes recurrent, self-limited attacks of fever and inflammation of the membranes lining the abdomen, chest, and joints. It is most common in populations around the Mediterranean.
| Also indexed as | ORPHA:342, MONDO:0018088 |
|---|---|
| Features mapped | 15 |
| Treatments mapped | 3 |
| Published sources | 12 |
| Last reviewed | 2026-08-04 |
Signs and symptoms
Proteinuria
Proteinuria means protein leaking into the urine, a sign of kidney involvement from amyloidosis. In a rare, severe form called amyloid storm it can appear suddenly and severely alongside rapidly worsening kidney function.
Fever
Recurring fever is one of the usual features of familial Mediterranean fever, coming with abdominal pain and joint involvement. The attacks typically last 12 to 72 hours.
Elevated erythrocyte sedimentation rate
During and between attacks, blood markers of inflammation such as the ESR and serum amyloid A are often raised, and tracking them helps gauge disease activity.
Amyloid deposition
Over the long term, the most important complication of familial Mediterranean fever is AA amyloidosis, a build-up of a protein called amyloid in the body, including in the kidneys.
Erysipelas
An erysipelas-like erythema, a red, raised, tender patch usually on the lower leg or foot, is a skin sign fairly specific to FMF.
Splenomegaly
Ongoing low-grade inflammation between attacks in FMF can enlarge the spleen (splenomegaly), along with anemia. This persistent inflammation is also what drives the most serious long-term complication, amyloidosis.
Nephropathy
Amyloid nephropathy is kidney damage from amyloid build-up. In familial Mediterranean fever it typically develops slowly over time.
Pleuritis
Pleurisy is inflammation of the lining around the lungs, which can cause chest pain. It is one of the forms of serositis seen during the relapsing fever attacks of familial Mediterranean fever.
Peritonitis
Peritonitis is inflammation of the lining of the abdomen. It is one of the forms of serositis seen during the relapsing fever attacks of familial Mediterranean fever.
Abdominal pain
Abdominal pain is one of the usual features of familial Mediterranean fever, occurring during attacks alongside recurrent fever and joint involvement.
Arthritis
Arthritis, meaning joint inflammation, is one of the features that can come with the relapsing fever attacks of familial Mediterranean fever.
Chest pain
Attacks of familial Mediterranean fever can cause sharp chest pain from inflammation of the lining around the lungs (pleuritis). The pain is usually one-sided and worse with breathing, and it resolves as the attack passes.
Arthralgia
Joint pain and arthritis are common during FMF attacks, usually affecting a single large joint of the leg and settling on their own as the attack passes.
Myalgia
Myalgia means muscle pain. It appears in a rare form of familial Mediterranean fever called protracted febrile myalgia syndrome, where muscle pain, fever, and raised inflammation markers can last for several weeks.
Recurrent febrile attacks
Familial Mediterranean fever runs in relapsing episodes, or attacks. The key feature is repeated bouts of fever along with inflammation of the membranes that line the belly, the lungs, and the joints.
How it is diagnosed
Familial Mediterranean fever
Diagnosed using: MEFV gene testing.
“Diagnosis relies on clinical criteria and is supported by genetic testing.”
Familial Mediterranean fever
Diagnosed using: Tel-Hashomer criteria.
“Tel-Hashomer criteria were the first set of criteria primarily designed for adults.”
Familial Mediterranean fever
Diagnosed using: Eurofever/PRINTO classification criteria.
“Recently, the Eurofever/PRINTO group has validated a new set of classification criteria for FMF, including clinical and genetic variables.”
Treatment and management
What the research describes, not a recommendation. Treatment decisions belong with your clinician.
This covers treatments that appear in the published research mapped here. Investigational and experimental therapies are not included, so their absence is a boundary of this map, not a sign they do not exist.
Colchicine
Colchicine is the mainstay treatment for familial Mediterranean fever. It lowers the number of attacks and, over time, helps prevent amyloidosis, the most worrisome complication of uncontrolled disease.
Used to help with: Familial Mediterranean fever.
“Colchicine is an essential component of familial Mediterranean fever (FMF) treatment.”
anakinra
Anakinra is an interleukin-1 (IL-1) inhibitor. IL-1 inhibitors have known beneficial effects in familial Mediterranean fever that does not respond to colchicine.
Used to help with: Familial Mediterranean fever.
“Anti-interleukin-1 agents have known beneficial effects in the treatment of colchicine-resistant familial Mediterranean fever…”
canakinumab
Canakinumab is an interleukin-1 (IL-1) inhibitor. IL-1 inhibitors have known beneficial effects in familial Mediterranean fever that does not respond to colchicine.
Used to help with: Familial Mediterranean fever.
“Anti-interleukin-1 agents have known beneficial effects in the treatment of colchicine-resistant familial Mediterranean fever…”
What changes how it shows up
The diagnosis is not the whole story. The factors and open questions below are described in the research mapped here as shaping whether, or how strongly, the condition shows up, or as points the field has not yet settled. They are not, on their own, its cause or its cure.
MEFV
Familial Mediterranean fever is caused by mutations in the MEFV gene. These mutations disrupt the pyrin inflammasome, leading to excessive production of inflammatory signals called cytokines.
Described as modulating: Familial Mediterranean fever.
“Mutations in the MEFV gene result in the dysregulation of the pyrin inflammasome, leading to excessive production of inflammatory cytokines.”
How to read the evidence labels
Where this comes from
This guide is built from 12 published source(s). Every claim above links back to one of them. Click any source ID to read the original on PubMed.
Take it further
Printed, source-linked documents built from this condition's graph — ready to bring to an appointment or attach to a coverage request. Every claim carries its published source, the same as this guide.