What Is Familial Mediterranean Fever?

Familial Mediterranean Fever (FMF) is a spontaneous autosomal recessive genetic disease of unknown etiology. It occurs mostly in people of Mediterranean origin, especially non-Central European Jews, Armenians, Turks, Levant Arab . Mostly onset in children. The related gene, named after the Mediterranean fever, is called the MEFV gene, and it encodes a protein that works to down-regulate the inflammatory response. If the gene is mutated, this regulation cannot be exerted, and the patient is characterized by repeated fever and peritonitis.

Basic Information

English name: familial Mediterranean fever
Visiting department: Division of Rheumatology

Multiple groups: Races of Mediterranean origin
Common symptoms: Recurrent fever and peritonitis

Causes of familial Mediterranean fever

This disease is a spontaneous autosomal recessive disease of unknown etiology (not related to gender). In this genetic method, two mutant copies are needed to get sick, one copy from the mother and the other copy from the father. Therefore, both parents should be carriers (the carrier has only one mutated copy and is not sick) and not the patient. If in a large family, familial Mediterranean fever can usually be seen among siblings, cousins, uncles or distant relatives. However, in a small number of cases, it can be seen that one of the parents is a familial Mediterranean fever patient and the other is a carrier. The child's disease may be 50%, and one child may be sick.

Clinical manifestations of familial Mediterranean fever

It is characterized by recurrent fever and peritonitis, with fewer cases manifesting as pleurisy, arthritis, skin lesions, and pericarditis.

The main symptom of familial Mediterranean fever is periodic fever with abdominal, chest, or joint pain. Fever usually lasts 1 to 3 days, and may show peritonitis, constipation more than diarrhea, pleurisy is common, if not diagnosed in time, familial Mediterranean fever peritonitis often leads to unnecessary acute abdominal surgery. Symptoms usually resolve spontaneously within a few days. Arthralgia is a common symptom of familial Mediterranean fever. Arthritis usually involves a single large joint with acute pain and swelling, which usually subsides after 2 to 3 days. Although it also lasts for a long time, especially if the hip joint is involved, the swelling is mild, but The pain can be severe. Compared to most other periodic arthritis syndromes, permanent joint damage does not occur. Pericarditis is rare. 3% of adolescent boys have scrotal pain and occasional skin manifestations, mainly erysipelas-like erythema, 10-25 cm in diameter, mostly below the waist, and scattered tenderness purple spots. 10% to 50% have splenomegaly, AA type (protein-derived amyloid) amyloidosis is more common, the highest incidence among Jews, proteinuria, nephrotic syndrome can occur.

Familial Mediterranean Fever

1. Erythrocyte sedimentation rate (ESR), CRP and fibrinogen

Erythrocyte sedimentation rate (ESR), CRP and fibrinogen increased during the seizure period. About one third of the patients returned to normal during the seizure period, and the other two thirds of the patients' parameters were significantly higher but normal.

2. Urine test

The main test is for protein or red blood cells. During the onset, there may be a transient abnormality in urine. However, in patients with amyloidosis, urine protein will persist.

3. Genetic testing

Helps diagnose the disease.

4. Rectal biopsy or kidney biopsy

Helps diagnose amyloidosis.

Familial Mediterranean fever diagnosis

Diagnosis can be based on clinical manifestations and laboratory-stained monoclonal antibody staining. There is no specific way to diagnose FMF. Generally based on the following aspects:

1. The disease may only be considered when the child has at least 3 episodes. Attention should be paid to a detailed history of ethnic background, relatives with similar symptoms, or renal insufficiency. Parents should also be required to give a detailed description of their previous illness.

2. Children with suspected FMF should be followed closely before a diagnosis is established. As much as possible during the follow-up visits, a full physical and blood test should be performed during the episode to detect the presence of inflammation.

3. Children with high suspicion of FMF through clinical and laboratory tests will receive colchicine treatment for approximately 6 months to evaluate response to treatment. If the child has FMF, it may no longer occur, or the frequency, severity, and duration of the attack will decrease significantly.

4. In the past two years, genetic analysis of patients can determine the presence of mutant genes associated with the occurrence of FMF. If the child carries two mutated genes from each parent, the clinical diagnosis of FMF can be determined. But so far, only 70% to 80% of children with FMF have found this mutation. This means that some patients with FMF may be free of genetic mutations. Therefore, the diagnosis of FMF mainly depends on clinical judgment.

Familial Mediterranean fever treatment

Glucocorticoids are not effective in preventing or treating familial Mediterranean fever. Currently, colchicine is the only drug used to treat familial Mediterranean fever. After the diagnosis of this disease, the child must take medicine for life. Proper medication can reduce the onset by about 60%, 30% of patients can get partial results, and 5% to 10% of patients are ineffective. Not only can colchicine treatment control the onset, but it can also reduce the risk of amyloidosis.

Colchicine is a safe drug with only minor side effects, and usually improves after reduction. The most common side effect is diarrhea. Other side effects include nausea, vomiting, and abdominal cramps. Occasionally, patients can cause muscle weakness. Peripheral blood cells (white blood cells, red blood cells, and platelets) may occasionally decrease, and they may recover as the dose decreases. At therapeutic doses, rare sperm counts decrease. Female patients do not have to stop taking colchicine during pregnancy and lactation.

Familial Mediterranean fever prevention

Children's illness is due to the presence of familial Mediterranean fever-causing genes. It's important to understand that marriage between close relatives will increase the likelihood of the two carriers joining together. About one-quarter of patients have parents from the same lineage (offspring of the same ancestor). Especially for those at high risk, it should be promoted not to marry close relatives.