Familial Mediterranean fever

Overview Of Familial Mediterranean fever

Familial Mediterranean Fever (FMF) is a rare, inherited autoinflammatory disorder characterized by recurrent episodes of fever and inflammation in the abdomen, chest, or joints. It primarily affects populations of Mediterranean descent, including individuals of Armenian, Arab, Turkish, and Jewish ancestry. FMF is caused by mutations in the MEFV gene, which encodes a protein called pyrin that plays a role in regulating inflammation. When the MEFV gene is mutated, the body’s inflammatory response becomes dysregulated, leading to spontaneous and excessive inflammation. Episodes, also known as attacks, typically last 1 to 3 days and resolve spontaneously. If left untreated, FMF can lead to a serious complication called amyloidosis, where abnormal protein deposits damage organs, particularly the kidneys. Early diagnosis and treatment are essential to prevent long-term complications and improve quality of life.

Causes of Familial Mediterranean fever

• Familial Mediterranean Fever is caused by mutations in the MEFV gene, which is inherited in an autosomal recessive pattern. This means that an individual must inherit two copies of the mutated gene (one from each parent) to develop the condition. The MEFV gene provides instructions for producing pyrin, a protein that helps regulate inflammation by controlling the activity of the immune system. Mutations in this gene lead to abnormal pyrin function, resulting in uncontrolled inflammation. While the exact triggers of FMF attacks are not fully understood, factors such as stress, physical exertion, infections, or menstruation may precipitate episodes. The condition is most prevalent in populations with Mediterranean ancestry, but cases have been reported in other ethnic groups as well.

Risk Factors of Familial Mediterranean fever

• Several factors increase the risk of developing Familial Mediterranean Fever:
• Ethnicity: Individuals of Mediterranean descent, including Armenians, Arabs, Turks, and Sephardic Jews, are at higher risk.
• Family History: A family history of FMF or consanguineous marriages increases the likelihood of inheriting the condition.
• Genetic Mutations: Carrying two copies of the mutated MEFV gene is necessary for the disease to manifest.
• Age: Symptoms often appear in childhood or adolescence, with most cases diagnosed before the age of
• Environmental Triggers: Stress, infections, physical exertion, or hormonal changes (e.g., menstruation) may precipitate attacks.

Prevention of Familial Mediterranean fever

• Preventing Familial Mediterranean Fever attacks and complications primarily involves lifelong adherence to colchicine therapy. Patients should take their medication as prescribed, even during symptom-free periods, to prevent flares and amyloidosis. Avoiding known triggers, such as stress, infections, and physical overexertion, may also help reduce the frequency of attacks. Regular follow-up with a healthcare provider is essential to monitor treatment efficacy and adjust dosages as needed. Genetic counseling is recommended for individuals with a family history of FMF to assess the risk of passing the condition to their children. Early intervention and patient education are key to preventing long-term complications and improving outcomes.

Prognosis of Familial Mediterranean fever

• With appropriate treatment, the prognosis for individuals with Familial Mediterranean Fever is generally favorable. Colchicine therapy effectively prevents attacks and reduces the risk of complications, particularly amyloidosis. Most patients experience a significant improvement in their quality of life and can lead normal, active lives. However, untreated or poorly managed FMF can lead to chronic complications, including kidney damage and organ failure due to amyloidosis. Early diagnosis and lifelong adherence to treatment are crucial for achieving optimal outcomes. In rare cases, individuals who do not respond to colchicine may require more aggressive therapies, but advances in biologic treatments have improved the prognosis for these patients as well.

Complications of Familial Mediterranean fever

• The most serious complication of Familial Mediterranean Fever is amyloidosis, a condition characterized by the deposition of abnormal protein (amyloid) in organs, particularly the kidneys. Amyloidosis can lead to kidney failure, requiring dialysis or transplantation. Other potential complications include chronic arthritis, infertility due to inflammation of the reproductive organs, and pericarditis (inflammation of the lining around the heart). Recurrent episodes of inflammation can also cause long-term damage to affected tissues and organs. Early and consistent treatment with colchicine is the most effective way to prevent these complications and preserve organ function.

Related Diseases of Familial Mediterranean fever

• Familial Mediterranean Fever is part of a group of conditions known as autoinflammatory disorders, which are characterized by recurrent episodes of inflammation without an apparent trigger. Related diseases include:
• Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS): Another hereditary autoinflammatory disorder causing recurrent fever and inflammation.
• Cryopyrin-Associated Periodic Syndromes (CAPS): A group of conditions caused by mutations in the NLRP3 gene, leading to excessive inflammation.
• Behçet’s Disease: A condition characterized by recurrent oral and genital ulcers, uveitis, and skin lesions, often seen in Mediterranean and Middle Eastern populations.
• Amyloidosis: A complication of untreated FMF, where amyloid protein deposits damage organs.
• Rheumatoid Arthritis: An autoimmune condition that shares some clinical features with FMF, such as joint inflammation. Understanding these related conditions is important for differential diagnosis and comprehensive management of patients with autoinflammatory disorders.

Treatment of Familial Mediterranean fever

The primary treatment for Familial Mediterranean Fever is daily colchicine, a medication that reduces inflammation and prevents attacks. Colchicine is highly effective in controlling symptoms and preventing complications in most patients. For individuals who do not respond to colchicine or cannot tolerate its side effects, biologic agents such as anakinra or canakinumab may be prescribed. These medications target specific components of the immune system to reduce inflammation. During acute attacks, additional pain relief or anti-inflammatory medications may be used. Adherence to treatment is essential, as discontinuation can lead to recurrent attacks and complications. Regular follow-up with a healthcare provider is necessary to monitor treatment efficacy and adjust dosages as needed.