Familial Mediterranean fever (FMF) is a genetic disorder that is caused by a gene mutation.
How does FMF present?
FMF typically starts with repeated bouts of fever with abdominal, chest or joint pain. It gets its name from the fact that the most commonly affected are people of Middle Eastern or Mediterranean descent. However, with more knowledge of how the disease is actually caused, testing has revealed its presence in other populations as well, such as Italians, Asians and Greeks.
The disease usually manifests in childhood, with nine of ten patients being diagnosed before the age of 20 years. The typical presentation is as episodic fever beginning before the age of ten years.
In most patients, the fever subsides in about three days or less, without specific treatment. In between febrile episodes, the child appears quite healthy, unless the bouts are so close together that recovery is difficult or growth is affected.
However, the appearance of pain varies from mild to severe. Sometimes the abdominal pain may mimic appendicitis, or the chest pain may restrict breathing.
With joint pain, typically monoarticular, the joint may be tender and swollen, limiting movement. In one of three patients, a red rash may be observed over the legs and feet.
Sometimes, joint inflammation is the only presenting symptom, and this may be diagnosed mistakenly as acute rheumatic fever or juvenile idiopathic arthritis. Joint symptoms last for 5-14 days, though in some cases they may persist for much longer.
Another presentation is of muscle pain following exercise, and uncommonly, with repeated bouts of chest pain due to inflammation of the heart sac (pericarditis), inflammation of the muscles (myositis), of the brain coverings (meningitis) or of the testes (orchitis).
What causes FMF?
This inherited condition is often caused by a mutation in both copies of a gene called the MEFV gene, one copy each from the mother and the father. This is called autosomal recessive inheritance.
Typically the parents are unaffected, though one or more siblings may have the same condition. Recently, however, it has been shown that almost one in three patients with FMF do not have two copies or even one, of the mutated gene.
Conventional thinking is that the MEFV gene encodes the pyrin protein, which regulates the process of inflammation. Thus mutations here cause dysregulation and uncontrolled inflammation, leading to fever and pain.
The condition may be triggered by trauma, over-vigorous exercise, infections, menstruation or stress.
How is FMF managed?
When the presence of FMF is suspected, genetic testing is recommended to detect gene mutations. While this will help confirm the clinical diagnosis in 70% of patients, the history and examination are still the only clues in the remaining 30%.
The family history is important, as is the ethnic origin, in suggesting the diagnosis. Laboratory tests for inflammation may also help, if carried out during febrile episodes.
At present, FMF cannot be cured. However, some cases may be treated using a specific anti-inflammatory drug as a preventive that reduces the frequency of fever and pain episodes. However, it must be taken regularly to avoid the return of the episodes, and must be continued lifelong. It is not useful in an acute attack.
This medicine can cause potentially serious adverse effects, so careful monitoring of the dose is necessary until the patient is stabilized. Some side effects mimic the symptoms of the condition itself, while others occur as a result of drug interactions.
Another newer option being explored is interleukin inhibitors, which benefit most patients with FMF.
What complications does FMF cause?
FMF may lead to the presence of amyloid in blood, eventually causing its accumulation within multiple organs, damaging them. Renal damage, infertility in women and arthritis are also common.