Familial Mediterranean Fever (FMF) is a rare, inherited autoinflammatory disorder characterized by recurrent episodes of fever and widespread inflammation throughout the body. These episodes often involve the lining of the abdomen, lungs, and joints. While there is no cure for FMF, effective treatments can help manage symptoms and prevent complications.
Understanding Familial Mediterranean Fever
FMF is classified as an autoinflammatory disease, which means the innate immune system mistakenly triggers inflammation without an external cause like an infection. This differs from autoimmune diseases, where the adaptive immune system attacks healthy tissues. FMF is considered the most common monogenic autoinflammatory disease.
The condition has a genetic basis, specifically involving mutations in the MEFV gene. This gene provides instructions for a protein called pyrin, which plays a role in regulating inflammation. FMF typically manifests during childhood, with symptoms often appearing before the age of 20.
The disorder is more prevalent in populations of Mediterranean origin, including those of Jewish, Arab, Armenian, Turkish, North African, Greek, or Italian ancestry. However, FMF can affect individuals from any ethnic background.
Recognizing the Symptoms
Individuals with FMF experience recurrent attacks of inflammation and fever that typically last one to three days. These episodes appear suddenly and resolve on their own, followed by periods of remission. Symptoms and their severity can vary.
Common symptoms during an FMF attack include high fever, sometimes with chills. Abdominal pain, often with swelling and rigid muscles, is a frequent complaint. This pain can be severe and may lead to constipation.
Chest pain, known as pleurisy, can also occur, making deep breathing difficult. Joint pain and swelling, usually affecting one joint, are also characteristic. A red, raised skin rash, often on the legs, is another common sign.
Genetic Origin and Diagnosis
FMF is caused by genetic changes in the MEFV gene, which is responsible for producing the pyrin protein. Pyrin is primarily expressed in neutrophils and plays a role in the innate immune response, including inflammasome assembly and sensing intracellular danger signals. In FMF patients, uninhibited pyrin activity leads to uncontrolled production of interleukin-1 (IL-1), resulting in inflammatory episodes.
The inheritance pattern for FMF is typically autosomal recessive, meaning an individual must inherit two copies of the mutated MEFV gene (one from each parent) to develop the condition. There are many known variations in the MEFV gene that can cause FMF, with some leading to more severe cases and others to milder symptoms.
Diagnosing FMF involves a combination of factors due to the episodic nature of symptoms. Healthcare providers review a patient’s symptoms, family health history, and genetic heritage. Blood tests may be conducted during an episode to check for signs of inflammation. Genetic testing for MEFV gene mutations helps confirm the diagnosis.
Treating and Living with the Condition
The primary treatment for FMF is daily medication with colchicine, an anti-inflammatory drug. Colchicine works by preventing inflammatory attacks and reducing inflammation in the body.
While colchicine helps prevent attacks, acute episodes may require pain relief. If left untreated, chronic inflammation from FMF can lead to amyloidosis. This condition involves the buildup of an abnormal protein called amyloid A in various tissues, which can cause organ damage, particularly to the kidneys, potentially leading to kidney failure.
For most individuals, daily colchicine treatment effectively prevents or reduces the frequency and severity of FMF attacks. With consistent treatment, people with FMF can typically lead normal lives, minimizing the risk of long-term complications like amyloidosis.