Familial Mediterranean fever (FMF) is a hereditary disease that occurs particularly in the eastern Mediterranean region. It is a rare disease but more common in some populations. The disease, with sporadic episodes of fever, can cause amyloidosis.
Familial Mediterranean fever (FMF).
Particularly in the eastern Mediterranean region, so-called familial Mediterranean fever sometimes occurs. As the name suggests, multiple cases of the disease occur more frequently within the family. Normally, this disease is very rare. However, it occurs more frequently in the eastern Mediterranean region. This already suggests a genetic background. Thus, mainly North African Jews, Armenian ethnic groups and parts of the Turkish population are affected by this disease. In total, approximately 0.1 to 0.2 percent of these population groups suffer from this disease. Familial Mediterranean fever is a chronic disease characterized by sporadic episodes of fever and inflammation of the tunica serosa. In approximately 30 to 60 percent of patients, amyloidosis may develop. This can reduce the life expectancy of those affected by the development of organ damage, especially to the kidneys. If amyloidosis can be prevented, life expectancy is within the normal range. There is evidence that it is not a uniform disease.
Causes
The cause of familial Mediterranean fever has been identified as a genetic alteration on a gene of chromosome 16 with gene locus 16p13.3 (MEFV gene). This gene encodes a protein known as pyrin or marenostrin. The exact function of this protein is not yet known. It can only be speculated here. In any case, it consists of 781 amino acids. Moreover, it is only produced in blood cells. Although it migrates into the cell nucleus, it does not have any special binding domains to the DNA. Thus, it is thought to play a role in regulating inflammatory (inflammatory) processes by activating certain transcription factors. In this regard, the protein is also thought to have a promoting effect on the production of interleukin-1β. Interleukin-1β is an important factor in inflammatory responses. Since interleukin-1β is probably produced more by the influence of pyrin, there is an increased influx of granulocytes with the increase of inflammatory reactions. That interleukin-1β plays a role was recognized by the improvement of symptoms after treatment with Il-1β antagonists. However, this is not a uniform disease process. Many mutations of the MEFV gene can lead to similar symptoms. There are cases of disease with autosomal recessive inheritance. However, cases of FMF with autosomal dominant inheritance have also been found.
Symptoms, complaints, and signs
Familial Mediterranean fever (FMF) is a disease that is relapsing. The intervals between relapses can last days, months, or even years. The less frequently an episode occurs, the more favorable the prognosis becomes with regard to the development of amyloidosis. During a relapse, inflammation of the tunica serosa occurs. The tunica serosa represents the lining of the thoracic cavity, the peritoneal cavity, the pericardium and the joint capsules. Accordingly, in the acute phase, the disease manifests as chest, abdominal, and joint pain. These inflammations are accompanied by fever. Usually, the first relapses occur before the age of 20. The attacks last a few days. Between the individual attacks, the affected persons feel healthy. During the inflammatory processes, so-called acute phase proteins are formed, which are subsequently deposited in the intercellular space. These can then no longer be reached by immune cells and accumulate. The more relapses occur during the chronic disease, the more proteins are deposited. This process is called amyloidosis. Due to the deposits, the structure of the organs is slowly damaged. The main complication is the development of severe renal failure, which can lead to death.
Diagnosis
Diagnostically, inflammatory parameters are determined during a fever attack. However, this examination is initially nonspecific because many inflammatory diseases show these results. More definitive is genetic testing of the corresponding MEFV gene.However, even a negative result cannot necessarily exclude familial Mediterranean fever, because other mutations may also play a role. The drug metaraminol can be used to provoke an inflammatory episode in the presence of FMF. This differentiates the disease from other possible syndromes.
When should you see a doctor?
This condition should be evaluated by a physician. Although it rarely leads to complications or a serious course, in the worst case it can lead to renal insufficiency and thus to the death of the affected person. A doctor should be consulted if the affected person suffers from regular episodes of fever. This often includes reddening of the skin and pain in the abdomen or chest. Likewise, the affected person often suffers from a general fatigue and exhaustion and furthermore also from pain in the joints. Complications may arise, especially in the case of regular or frequently occurring complaints, so that an examination by a physician is necessary. If the blood values show abnormalities in the kidneys during another examination, the kidneys should be examined. Diagnosis of the disease can usually be made by an internist or by a general practitioner. However, patients are dependent on taking medication for treatment. Furthermore, regular checkups and examinations are also advisable to detect and prevent damage to the internal organs at an early stage.
Treatment and therapy
Because familial Mediterranean fever is a genetic disease, it can only be treated symptomatically. Causative therapy is not currently available. During acute attacks, either opioids such as morphine or anti-inflammatory drugs such as acetylsalicylic acid or diclofenac are administered as analgesics. To prevent the development of amyloidosis, the number of relapses must be reduced. This can be achieved by the administration of colchicine. Colchicine inhibits neutrophil granulocytes and thus helps to prevent the inflammatory processes. Thus, the intervals between attacks can be drastically prolonged. Successes have also been achieved recently with the administration of the drug anakinra. Anakinra is an antagonist of interleukin-1 by binding to its receptor.
Prospect and prognosis
Gene disease is treated symptomatically by physicians. Alteration of the mutated genes is not permitted for legal reasons. Although the disease occurs mainly in people from the Mediterranean region, German physicians cannot perform gene therapy because of legal regulations. Therefore, according to the current state of science, there is no prospect of a cure for the patient. The symptoms, which occur in episodes, are managed symptomatically by the attending physician. By administering medication, the existing irregularities can be well controlled and contained. Relief of the symptoms occurs within a short period of time until they have completely subsided after a few days or weeks. The aim of therapy is also to reduce the number of episodes that occur over a lifetime. Since there are always symptom-free phases in the course of life, the patient experiences periods of recovery. This improves well-being and promotes quality of life. Nevertheless, long-term therapy must be adhered to, otherwise symptoms will return. If medical care is refused, the prognosis is worse. The relapses occur at shorter intervals. In addition, the individual phases last longer or become more intense. Because damage to the organs can occur, the average life expectancy is lowered in this disease.
Prevention
Human genetic testing can be performed to prevent onward transmission to offspring. If cases of familial Mediterranean fever have occurred within the family or relatives, there is some risk of onward transmission. If FMF is present, amyloidosis should be prevented. This can be achieved by continuous treatment with colchicine. Another option is treatment with anakinra.
Follow-up
In most cases of Mediterranean fever, no special measures or options for follow-up are necessary.As a rule, the focus is on the rapid detection and subsequent treatment of the disease, so that there are no particular complications or worsening of the symptoms. The earlier Mediterranean fever is detected, the better the further course of the disease usually is. Therefore, a doctor should be consulted at the first symptoms and signs of the disease. Mediterranean fever is usually treated with the help of medication. The affected persons are dependent on a regular and above all correct taking of the medicines, in order to relieve the complaints durably, since an independent healing cannot occur thereby. In most cases, the symptoms can be completely resolved by taking the medication. If there is any uncertainty, a doctor should always be contacted. In general, those affected by Mediterranean fever should rest and take it easy on the body. Efforts or stressful activities should be refrained from. The trigger of Mediterranean fever should of course continue to be avoided, so that it does not come again to the outbreak of the disease.
This is what you can do yourself
Hereditary familial Mediterranean fever belongs to the group of periodic fever syndromes. The disorder is clustered among residents of the eastern Mediterranean region. There are currently neither conventional nor alternative methods that treat the disease causally. Self-help measures can at best be directed toward prevention or treatment of the symptoms. Since the disease can be accompanied by dangerous complications if it is not treated professionally, a specialist in this rather rare disease should be consulted at the first signs. Couples in whose relatives familial Mediterranean fever has occurred may seek humangentic counseling. During this counseling, young couples planning a family learn about the risk of their offspring contracting the disorder and the burdens they will then face. The best self-help measure for individuals who discover symptoms of familial Mediterranean fever in themselves is to consult a physician promptly. Administration of the drug colchicine can significantly prolong the interval between fever episodes, which significantly reduces the risk of amyloidosis. Acetylsalicylic acid is regularly used to combat inflammatory processes during acute fever attacks. This substance is also found in willow bark. Patients who prefer naturopathic therapy can, after consultation with their physician, take preparations based on willow bark instead of or in addition to allopathic medications.