What is Familial Mediterranean Fever (FMF)? Symptoms, Causes and Treatment

Familial Mediterranean Fever (FMF) Disease

Familial Mediterranean Fever is a genetic disorder characterized by painful inflammation in certain parts of the body and recurrent fever. Pain frequently occurs in the joints, chest, and abdomen. Since it is an autoinflammatory disorder, the body's immune cells attack other tissues, causing damage. This clinical picture stems from mutations occurring in the MEFV gene. FMF can develop due to genes inherited from only one parent or both.

The disease FMF gets its name from the Mediterranean and Middle East geography where it is most commonly seen. Approximately 75% of cases are seen in children under the age of 10. Additionally, about 90% of disease attacks tend to begin before the age of 20. There is currently no cure for Familial Mediterranean Fever, but treatment plans aimed at alleviating symptoms can be implemented. Controlling inflammation in tissues may require lifelong treatment, which can help prevent damage to healthy organs.

What is Familial Mediterranean Fever (FMF) Disease?

Familial Mediterranean Fever, or "Reimann syndrome / Wolff periodic disease," is a hereditary health problem characterized by recurrent fever, severe pain, and inflammation. The initial attacks and diagnosis usually occur in childhood. FMF attacks can develop within two to four hours. Attacks can last from six hours up to four days. Attacks generally may not occur due to specific causes. However, in some cases, there are factors defined as triggers. Traumas, stress, intense physical activity, the onset of the menstrual cycle, and infections can be among these triggers.

Attacks can resolve spontaneously, but preventing attacks helps avoid a number of life-threatening issues. Attacks can lead to consequences such as kidney damage and subsequent kidney failure, etc. These health problems may occur in some individuals, particularly with the accumulation of amyloid compounds in the kidneys. FMF frequently involves acute inflammation of the joint, abdominal, and lung membranes. Less frequently, it can affect the heart, brain, and spinal cord membranes. Depending on the tissue and organs affected, mild or severe symptoms may appear.

What Are the Symptoms of Familial Mediterranean Fever?

Familial Mediterranean Fever symptoms can be specific symptoms that vary from person to person. However, commonly seen and recorded FMF disease symptoms include:

Recurrent fever in early childhood,

Sudden pain, stiffness, and tension affecting the entire abdominal region,

Decreased digestive system and bowel sounds,

Painful and swollen joints (hips, knees, ankles, shoulders, jaw joint, etc.),

Acute and unilateral inflammation in the lungs,

Difficult breathing and decreased breath sounds,

Skin rashes on the lower legs,

Amyloidosis, nephropathy, and kidney failure,

Pericarditis (inflammation of the heart membrane),

Emotional and neuropsychological complaints.

Less common symptoms include diarrhea, myalgia, erythema, vasculitis, and urticaria.

How Does Familial Mediterranean Fever Occur?

FMF is primarily caused by disease-causing variants on the MEFV gene. Although more than 400 variants have been identified in the MEFV gene, only four variants lead to FMF disease. The MEFV gene is a gene active in the production of the pyrin protein. Variants on the gene can be held responsible for the insufficient production of pyrin. In this case, the regulation or prevention of the inflammatory response in the body can be disrupted. At the same time, the pathogenic variant can lead to the excessive release of the IL-1B cytokine, which stimulates immune system cells.

Excessively released cytokines can overstimulate the immune system and trigger the body to attack its own cells. Individuals who do not develop FMF may be at risk for certain inflammatory diseases even if they do not have the disease because they carry the recessive gene. Crohn's disease, Behçet's disease, etc. can be counted among these diseases. FMF attacks, on the other hand, can occur due to multiple factors. Certain illnesses, injuries, physical and emotional stress, the menstrual period, and exposure to cold can trigger the onset of attacks.

How is Familial Mediterranean Fever Diagnosed?

There is no single specific method for diagnosing FMF. Diagnosis can usually be established through medical history, family history, physical examination, and various laboratory tests. Certain genetic tests may be necessary to support the clinical diagnosis. Methods used to diagnose Familial Mediterranean Fever disease may include:

Physical examination: Evaluation of signs and symptoms, identification of at least three attack episodes, and examination of the family history of FMF may be necessary. Additionally, keeping a diary describing how and when attacks occur may be requested.

Laboratory tests: Markers that appear in the body with inflammation during attack periods can be detected through blood and urine tests. It may be necessary to monitor leukocytes (white blood cells), which are immune system cells, and amyloids, which tend to accumulate.

Response to colchicine treatment: Familial Mediterranean Fever can be diagnosed with colchicine treatment. Children with FMF symptoms are provided with colchicine treatment for six months. If the number, intensity, and duration of attacks decrease or if attacks are not observed at all during this period, the presence of FMF can be mentioned.

Genetic tests: Genetic analyses can provide an FMF diagnosis by detecting mutations originating from both the mother and the father. However, genetic analysis may not be an accessible test for everyone.

Familial Mediterranean Fever symptoms generally consist of symptoms frequently seen in children. Therefore, diagnosing FMF can be difficult. However, delay in diagnosis and treatment can lead to a number of risks in children.

How is Familial Mediterranean Fever Treated?

Familial Mediterranean Fever treatment primarily aims to improve and prevent attacks, and to stop the development and progression of amyloidosis. In this case, Familial Mediterranean Fever treatment is mostly protective and preventive in nature. FMF treatment involves lifelong use of colchicine. Colchicine is a proven effective medication and can provide protection against potential attacks. Therefore, discontinuing colchicine medications can lead to an increased risk of attacks and amyloidosis. Preventing both attacks and amyloidosis can halt the development of chronic kidney failure. It is important to take the regularly recommended amount of colchicine. Taking an overdose of colchicine in the treatment of Familial Mediterranean Fever attacks may not show positive results. Therefore, it should be used as a protective, not therapeutic, treatment method. Although alternative studies and medications exist for the treatment of Familial Mediterranean Fever, there is still insufficient data and evidence.

Frequently Asked Questions

FMF disease alone may not always be life-threatening. However, complications that arise if early diagnosis and treatment cannot be provided can be fatal. Amyloidosis can occur as a fatal consequence of FMF cases. Amyloidosis in Familial Mediterranean Fever can be life-threatening when it leads to kidney damage and kidney failure. FMF can lead to various complications when medical treatment is not provided. Complications that may occur if FMF progresses mainly include:

Amyloidosis,

Renal vein thrombosis,

Kidney failure,

Joint pain and arthritis,

Additionally, inflammations in the lungs, spleen, heart, brain, and blood vessels can be observed. Regarding the question "Which department handles FMF disease?", it is handled by the pediatric rheumatology department or internal medicine and rheumatology department. Rheumatology or internal medicine specialists may follow a multidisciplinary approach in some cases. In this context, a collaborative approach between parents and specialists becomes important. In FMF disease, test results can evaluate inflammatory markers such as white blood cells, erythrocyte sedimentation rate, C-reactive protein, etc. Additionally, the excessive accumulation of protein or the presence of blood in urinalysis may indicate kidney damage associated with FMF. Genetic tests may be necessary in cases where blood and urine tests are insufficient. FMF attacks tend to last 12-72 hours. Patients may exhibit symptoms of varying severity during attack periods. During these periods, anxiety, restless mood, irritability, nausea, and myalgia commonly appear. During the attack period, individuals may need to stay away from physical and emotional stress, avoid cold environments and intense exercise, and receive psychological support in the presence of depression and anxiety. Besides, individuals may feel normal during periods between attacks. Familial Mediterranean Fever acute attack treatment may require the use of pain relievers and anti-inflammatory drugs prescribed by your doctor, as well as rest. Individuals with Familial Mediterranean Fever must continue lifelong colchicine treatment. Familial Mediterranean Fever symptoms can flare up again when colchicine is discontinued. The disease can frequently cause diarrhea by altering the intestinal flora. Since diarrhea causes a significant loss of fluids and electrolytes, necessary nutrients must be taken into the body through diet. Also, when muscle weakness, nausea and vomiting, and cramps occur, the person should be rested and kept away from intense physical activity. Mediterranean fever can lead to symptoms in the lower extremities in some children. Characteristic rashes and erythema on the legs and joints, and severe pain are commonly observed findings. These findings can be uncomfortable and can be seen parallel to recurrent fevers. Leg pain and erythema can negatively affect social life. Familial Mediterranean Fever, which has an inflammatory course, can show a high response to colchicine through certain foods. Furthermore, various foods that help reduce the inflammatory burden can be consumed in FMF patients. These foods can be effective in alleviating the course of the disease. For this purpose, the diet may include:

Foods containing less saturated fat, sugar, and salt,

Fish oil containing omega-3 fatty acids,

Fresh vegetables and fruits,

Turmeric,

Green tea.

In addition to foods, taking immuno-nutrients such as vitamins C, D, E, and zinc as supplements can positively affect the course of the disease. Mediterranean fever attacks are a condition that can be triggered by fatigue and physical stress, and can cause fatigue. Especially in children experiencing severe attack periods, joint, abdominal, and chest pain, difficult breathing, recurrent fevers, rashes, and kidney problems can cause fatigue and lethargy in the individual. FMF is a medical problem that can be transmitted by recessive genes. Pathogenic variants of recessive genes found in both parents can genetically appear in the child. With the combination of the variant causing the disease and normal genes, children can be carriers. Familial Mediterranean Fever carrier state generally may not show symptoms in individuals. The risk is the same for women and men. Therefore, consanguineous marriages are a factor that increases the risk of two carriers coming together.

Familial Mediterranean Fever (FMF) can be controlled with early diagnosis and regular treatment. If you are experiencing complaints such as recurrent fever, joint, or abdominal pain, consult a rheumatology specialist without delay.

Hisar Hospital Intercontinental Department of Internal Medicine specialist physicians are by your side in the diagnosis and treatment of FMF. To get more information or to create an appointment, you can visit our contact page or create an online appointment request.