From the Guidelines
Familial Mediterranean fever (FMF) is a hereditary inflammatory disorder characterized by recurrent episodes of fever and inflammation affecting the abdomen, chest, and joints, and the main treatment for FMF is colchicine, taken daily at doses of 0.5-2 mg per day (depending on age and severity) 1.
Definition and Cause of FMF
FMF is most common in people of Mediterranean descent, particularly those of Armenian, Arab, Turkish, and Jewish ancestry. It is caused by mutations in the MEFV gene, which produces a protein called pyrin that helps regulate inflammation. When this gene is mutated, it leads to uncontrolled inflammation in the body.
Symptoms of FMF
Symptoms typically begin in childhood or adolescence and include:
- Periodic fever episodes lasting 1-3 days
- Severe abdominal pain resembling appendicitis
- Chest pain
- Joint pain
- Sometimes a skin rash
Treatment of FMF
The main treatment for FMF is colchicine, which prevents attacks and reduces the risk of amyloidosis, a serious complication that can lead to kidney failure. Colchicine should be started as soon as a clinical diagnosis is made, and the dose may be increased up to a daily dose of 2 mg in children and 3 mg in adults, or the maximum tolerated dose if this cannot be appropriate 1. For patients who don't respond to colchicine, biologics like anakinra or canakinumab may be prescribed. Early diagnosis and treatment are crucial to prevent long-term complications and improve quality of life for those with this chronic condition.
Monitoring and Follow-up
Patients with FMF should be monitored regularly, with blood tests performed 3 months after dose reduction, and periodic laboratory evaluation of SAA protein or CRP and urinary protein. Dose reduction should be avoided in patients who may be unwilling to comply with these strict constraints, and should only be considered after expert consultation, and only if appropriate measures continue to be taken to identify subclinical inflammation and hence prevent the development of ‘silent’ amyloidosis 1.
From the FDA Drug Label
ILARIS is indicated for the treatment of Familial Mediterranean Fever (FMF) in adult and pediatric patients. The FDA drug label does not provide a definition or description of Familial Mediterranean Fever (FMF), it only mentions it as an indication for the use of canakinumab (ILARIS) 2.
From the Research
Definition and Prevalence of Familial Mediterranean Fever (FMF)
- FMF is a hereditary autoinflammatory disorder that predominantly affects individuals of Mediterranean and Middle Eastern descent, including those with certain heritages such as Sephardic Jewish, Armenian, Turkish, and Arab 3.
- The disorder affects up to 1 in 200 people, making it a common etiology for pain states worldwide, including serositis-mediated painful states of the chest, joint, and abdomen 3.
- FMF is characterized by recurrent episodes of fever and inflammation, which can lead to severe pain and complications such as renal amyloidosis if left untreated 3, 4, 5.
Clinical Manifestations and Diagnosis
- FMF is characterized by recurrent and self-limited episodes of fever and painful serositis, lasting 1-3 days 4.
- Diagnosis is based on clinical features, response to colchicine, and genetic analysis 4, 5.
- The MEFV gene mutations on chromosome 16p13.3 encode the abnormal pyrin (marenostrin), a protein involved in the activation of caspase-1 and the processing and release of active pro-inflammatory IL-1β 6.
Treatment and Management
- Colchicine remains the cornerstone of treatment, effectively preventing inflammatory attacks and complications 3, 4, 5, 6.
- For colchicine-resistant patients, IL-1 antagonists like anakinra and canakinumab show promise, although their long-term benefits require further investigation 3, 7.
- Anti-IL-1 agents are effective and safe in the treatment of FMF patients, particularly in reducing proteinuria in patients with GFR ≥ 60 ml/min/m2 7.
Complications and Prognosis
- The most severe long-term complication of FMF is type AA amyloidosis, principally affecting the kidney and causing chronic renal failure 5.
- Patients with M694V/M694V homozygosity are exposed to a higher risk of developing renal amyloidosis, arthritis, dermatologic and oral lesions, higher fever, and more frequent painful attacks 4.
- The prognosis of FMF is normal if AA amyloidosis is prevented, and colchicine remains the first-line therapy to treat pain and prevent amyloidosis 4.