Armenian genetic disease. Symptoms of Mediterranean fever

– a genetic pathology characterized by dysregulation of inflammatory processes, especially in the serous (peritoneum, pleura) and synovial membranes. The manifestations of this disease are varied, most often abdominal pain is recorded (picture acute peritonitis), violations by pleural cavity, attacks of fever, pain and swelling of the joints. Diagnosis is made on the basis of the clinical picture, the study of hereditary history and molecular genetic tests; a supporting role is played by determining the patient’s nationality. Treatment of periodic illness is only symptomatic and supportive, specific therapy does not currently exist.

Diagnosis and treatment of periodic illness

In some cases, the diagnosis of periodic disease can be associated with significant difficulties due to the severity and, at the same time, non-specificity of its manifestations. This feature of the disease can cause diagnostic errors with far-reaching consequences - for example, with the picture “ acute abdomen» unnecessary operations are often performed on patients; for aseptic pleurisy and meningitis, they are prescribed high doses antibiotics. In case of arthralgia and staging misdiagnosis(for example, rheumatoid arthritis), a patient with periodic illness may be prescribed potent immunosuppressive drugs. Therefore, in the presence of such symptoms in patients who are natives of the Mediterranean region, the possibility of the presence of this genetic disease should be taken into account.

In the process of diagnosing periodic disease, data from studying the hereditary history of patients and molecular genetic tests are used. As a rule, the hereditary history in such patients is burdened (sporadic forms are extremely rare); similar manifestations are detected in ancestors or relatives. A geneticist can finally confirm or refute the presence of a periodic disease through genetic research. There is a common method for searching for the most common MEFV gene mutations in this disease – M694V and V726A, which cause more than 75% of all cases of this pathology. However, more rare MEFV defects may go undetected and are identified by sequencing the entire gene sequence.

Treatment of periodic illness is mainly symptomatic. For severe pain in the abdomen, chest, joints, non-steroidal anti-inflammatory drugs and other analgesics are used, in in rare cases(for pain accompanying abdominal shape diseases) narcotic painkillers may be prescribed. Hydrothorax with pleurisy is eliminated by puncture and the administration of diuretics. To prevent attacks, reduce the severity of symptoms and generally improve the condition of patients, long-term use of colchicine is prescribed. During development renal failure Due to amyloidosis, regular hemodialysis is recommended for patients with periodic illness.

Forecast and prevention of periodic illness

Prognosis of periodic illness in to a large extent depends on the presence or absence of amyloidosis. If he is not there, despite severe attacks disease, the prognosis is favorable, since in interictal period patients feel satisfactory, life expectancy is practically not reduced. In the case of amyloidosis developing against the background of periodic illness, patient survival is sharply reduced due to kidney damage. The risk of amyloidosis decreases with early diagnosis Mediterranean familial fever and timely initiation of treatment with colchicine. Prevention of periodic illness is possible only through prenatal diagnosis, which is recommended in cases where both parents are suspected of carrying a defective form of the MEFV gene.

Periodic illness is a disease that is often found among Greeks, Jews, Turks and peoples of the Caucasus. Its synonyms are Mediterranean fever, recurrent polyserositis.

In Armenia, this pathology is called “Yerevanyan ivandutyun” (“Yerevan disease”). Until now, the disease has not been fully studied; scientists and doctors are trying to find effective treatment methods.

This hereditary disease, which is manifested by attacks of pain in the abdomen and joints, changes in blood tests. This is one of the most mysterious diseases. Patients with this pathology are often operated on, suspecting surgical disease V abdominal cavity until an accurate diagnosis is established.

The danger of the disease lies in the development of renal amyloidosis over the years.

Reasons

At the core Armenian disease there is a mutation in the pyrin protein gene, located on chromosome 16. Due to impaired pyrin production, the patient’s body cannot adequately fight the inflammatory process. As a result, uncontrolled foci of inflammation appear in the abdominal cavity, chest, joints and other places.

The dependence of exacerbations of the disease between the seasons spring-summer and summer-autumn was revealed. Mediterranean fever is exacerbated by the following factors: infectious diseases, climate change, alcohol, poisoning.

A person’s affiliation with these ethnic groups serves as the main risk factor. Moreover, men suffer from this disease more often than women.

Types and symptoms

The attack of the disease begins suddenly. The patient, as a rule, cannot accurately describe his condition, what exactly bothers him. To the main clinical symptoms Armenian disease can be attributed to:

pain in the abdomen;
feverish condition;
joint inflammation.

Considering the localization of the process, several variants of periodic disease are distinguished:

abdominal;
thoracic;
febrile;
articular

Abdominal option manifests itself as abdominal pain that spreads throughout the body. Often, when the pain syndrome is severe, doctors suspect acute conditions, requiring surgical intervention. However, after a few days all symptoms disappear completely. Carry out differential diagnosis in acute period help instrumental methods research.

For thoracic variant Migrating chest pain and a picture of dry pleurisy appear. All symptoms disappear after a week as suddenly as they appeared.

For febrile type The patient's temperature rises sharply. It lasts from 3 to 7 days. Then the temperature indicators are normalized. At the same time, symptoms from other internal organs and no systems are observed.

Articular option characterized by recurrent synovitis. Occurs in the form of mono- and polyarthritis with pain syndrome, sometimes without a feverish reaction. For articular shape characterized by damage to large joints (knee, ankle, wrist). Joint pain can last up to 1 month.

The joint shape is determined by such changes in the joints as:

swelling;
redness;
soreness;
local increase in temperature;
restriction in movement.

Often the disease occurs as a combination of several options.

Periodic illness in children first appears between the ages of 2 and 5 years. Attacks are often accompanied by fever and serositis (pleurisy, peritonitis,).

The duration of attacks is short (from several hours to 1-3 days). The occurrence of attacks is preceded by a history of provoking factors: stress, surgery, trauma, vaccination.

Diagnostic methods

Main diagnostic criteria:

History: determine the nationality of the child, the presence similar symptoms with relatives.
Clinic: sudden attacks of fever with pain and complete improvement of the condition outside the attack.
Laboratory tests reveal nonspecific signs of inflammation.
Genetic testing to identify specific mutations.
Effect of colchicine therapy.

Treatment

There is no specific treatment for periodic illness. A diet with a 50% reduction in animal content (especially casein) and vegetable protein and an increase in foods containing starch.

The diet should be enriched with fruits, vegetables and other waste products. It is preferable to give protein daily (100 g of liver, raw or cooked). Liver has been used for years, in repeated courses of many months. Use hepatotropic drugs repeated courses: 2-4 months of Essentiale, lipoic acid.

Pain syndrome is treated symptomatically. For joint damage, use local drugs for anti-inflammatory and analgesic therapy (ointments, creams): , “Ortofen”, “ Nise gel", "Bystrumgel" and others.

Doctors developed the ability to prevent attacks in 1972, when colchicine was synthesized. The use of colchicine in small doses helps prevent attacks. It is usually prescribed at 1-2 mg per day, but the dosage can be changed by the doctor if necessary.

The essence of the drug’s action is that it:

has an anti-inflammatory effect;
reduces vascular permeability;
reduces the release of prostaglandins;
reduces the activity of releasing inflammatory activators from neutrophils;
able to inhibit the development of amyloidosis.

Colchicine, in addition to relieving symptoms, also has toxic effect on the body, so taking the drug should begin by determining its tolerability and monitoring the blood test.

Forecast

The prognosis largely depends on the development of amyloidosis, which leads to renal failure. Timely diagnosis and taking colchicine will help avoid complications and ensure a favorable outcome.

Conclusion

Now you know what Yerevan disease is, its symptoms and treatment. This is a hereditary disease that cannot be cured, but can be kept under control. Thanks to correctly prescribed treatment, the quality of life of patients is practically not reduced: they can work, play sports, and start families.

The most important thing is to apply for a qualified professional in time medical care and get the right treatment.

PERIODIC ILLNESS(syn.: Armenian disease, Janeway - Mosenthal paroxysmal syndrome, periodic peritonitis, Reimann syndrome, Segal-Mamou disease, familial Mediterranean fever) is a relatively rare genetically determined disease, manifested by periodically recurrent serositis and the relatively frequent development of amyloidosis.

The first description of the disease dates back to the 17th century, but only in 1949 did Sh. Siegal describe in detail and systematize its wedge, symptoms, and draw attention to the ethnic selectivity and hereditary nature of the pathology. In domestic honey. literature P. b. first described in 1959. E. M. Tareev and V. A. Nasonova. Nosological form of P. b. was recognized only in the 70s. The disease occurs mainly in representatives of ethnic groups whose ancestors lived in the basin Mediterranean Sea, especially among Armenians, Jews (usually Sephardim), Arabs, and only in 6% of all cases among people of other nationalities.

No influence found geographical latitudes to the spread of the disease. The disease begins predominantly in childhood and adolescence, regardless of gender.

Etiology has not been sufficiently studied. An autosomal recessive type of inheritance of P. b. has been established. It is assumed that patients have a congenital metabolic and enzymatic defect, which entails a violation of the immune and endocrine systems, protein synthesis, proteolysis.

Pathogenesis in many respects has not yet been clarified. The basis of the wedge, relapses of the disease is benign superficial aseptic inflammation serous membranes, ch. arr. peritoneum, pleura, synovial tissue. The inflammatory response begins with cell degranulation.

Indicates a violation of cellular metabolism frequent development with P. b. amyloidosis (see) regardless of the severity of P. b., which suggests its genetic cause. The existence of two genotypic manifestations is allowed. With genotype I, attacks of P. b. occur primarily, and then amyloidosis can occur. With genotype II, amyloidosis develops first, and then attacks of P. b. appear. Along with this, there are cases of P. b. without amyloidosis and cases where amyloidosis is the only manifestation of the disease.

Pathological anatomy. Despite hron, the course of P. b., rough anatomical changes not formed. In the interictal period, a small number of tender adhesions are found in the area of recurrent inflammation. During acute attack P. b. there are all signs of superficial aseptic inflammation of the serous tissues. Possible small serous effusion, injection and increased vascular permeability, nonspecific cellular reaction, less often moderate hyperplasia of lymph nodes. Amyloidosis, if present, is generalized with primary damage to the kidneys. According to histoimmunochemical properties of amyloidosis in P. b. close to secondary amyloidosis.

Clinical manifestations and course. Depending on the predominant manifestations, there are four wedges, variants of P. b.: abdominal, thoracic, articular and febrile.

The abdominal variant occurs most often and, with a detailed picture, is characterized by symptoms of an acute abdomen (see) with symptoms of partial intestinal obstruction (see. Intestinal obstruction), which is confirmed by x-ray, and peritonitis (see) During surgery for suspected acute appendicitis, acute cholecystitis or small intestinal obstruction show only signs of superficial serous peritonitis and moderate adhesive process. Unlike acute surgical diseases abdominal cavity, all symptoms disappear spontaneously after 2-4 days. In rare cases, usually after repeated surgical interventions, mechanical damage may develop intestinal obstruction, intussusception or volvulus, which is facilitated by pronounced dyskinetic processes in the gastrointestinal tract. tract and biliary tract, caused by P. b. itself. and clearly detectable during X-ray examination of patients, especially those carried out during acute pain in the stomach. Abdominal attacks, once they appear, accompany the patient throughout his life and tend to decrease with increasing age and with the development of amyloidosis.

Thoracic version of P. b. observed less frequently, it is characterized by inflammation of the pleura, which occurs in one or the other half chest, rarely in both. The patient's complaints and examination data correspond to the wedge, the picture of pleurisy (see), dry or with slight effusion. All signs of exacerbation of the disease spontaneously disappear after 3 to 7 days.

The joint variant occurs less frequently than others in the form of recurrent synovitis (see). It manifests itself as arthralgia, mono- and polyarthritis. More often affected large joints, especially ankles, knees. Attacks of the disease with its articular variant are tolerated more easily than with other variants, are less likely to recur, and sometimes occur with normal temperature and only with prolonged arthritis, lasting more than 2-3 days, can transient osteoporosis be observed.

Feverish variant of P. b. as an independent one, it should be distinguished from fever (see), accompanying any variant of the disease. In the latter case, the temperature rises soon or simultaneously with the appearance of pain, sometimes accompanied by chills, reaching various levels and decreases to normal numbers after 6-12, less often 24 hours. With the febrile variant of P. b. fever is the leading symptom of relapse of the disease; attacks resemble malarial paroxysms. They occur rarely, usually at the beginning of the disease, then, unlike attacks in the abdominal variant, just like articular and thoracic attacks, they can disappear completely. In some cases, the course of the disease may involve a combination of its various variants, which most often manifest themselves in their characteristic rhythm.

The course of the disease is chronic, relapsing, usually benign. Exacerbations occur in a stereotypical manner, differing only in severity and duration. Laboratory indicators for each exacerbation reflect only the degree inflammatory reaction and normalize as it subsides acute phase diseases.

30-40% of patients develop amyloidosis, which can lead to kidney failure. Amyloidosis occurs regardless of the wedge, P.'s manifestations, its duration, frequency and severity of attacks.

Diagnosis set taking into account the following criteria: 1) onset of the disease in childhood or adolescence, mainly among certain ethnic groups; 2) frequent detection of the disease in relatives; 3) periodically occurring short attacks of the disease (abdominal, thoracic, articular, febrile), not associated with specific provoking causes, characterized by stereotypicality; 4) frequent detection of renal amyloidosis. Laboratory indicators are mostly nonspecific and reflect the severity of the inflammatory response or the degree of renal failure.

Differential diagnosis carried out depending on the wedge, option P. b. with pneumonia (see), pleurisy of various etiologies (see Pleurisy), acute appendicitis (see), acute cholecystitis (see), various forms arthritis (see), rheumatism (see), collagenosis (see Collagen diseases), malaria (see), sepsis (see), acute inf. diseases (febrile variant). At the first manifestations of P. b. differential diagnosis can be very difficult and is based on the careful exclusion of all diseases with similar symptoms. In case of repeated relapses of the disease, the above criteria and the fact that for P. b. characteristic wellness patients during the interictal period and resistance to any therapy, including antibiotics and glucocorticoids during wedge, exacerbation.

Treatment not sufficiently developed. Until the 70s. it was only symptomatic. In 1972, information began to appear about the possibility of preventing attacks of P. b. taking colchicine orally daily dose from 0.6 to 2 mg. Subsequently, the preventive effectiveness of colchicine was confirmed, as well as the absence side effects at long-term use indicated doses in both adults and children. The mechanism of action of the drug is not yet clear. There is evidence of its effect on fibrillar intracellular structures, which consists in preventing cell degranulation, which prevents the development of inflammation.

Forecast favorable for life. Presence of P. b. usually does not interfere with physical and mental development, marriage. Very frequent attacks diseases can cause disability, and the development of amyloidosis in some patients (usually before 40 years of age) leads to renal failure and disability.

Bibliography: Vinogradova O. M. Periodic disease, M., 1973; Heller H., S o h a r E. a. P r a s M. Ethnis distribution and amyloidosis in familial Mediterranean fever, Path, et Microbiol. (Basel), y. 24, p. 718, 1961; L ehma n T. J. a. o. Long-term colchicine therapy of familial Mediterranean fever, J. Pediat., v. 93, p. 876, 1978; Siegal S. Benign paroxysmal peritonitis, Gastroenterology, v. 12, p. 234, 1949.

O. M. Vinogradova.

Armenian periodic disease- synonyms: paroxysmal Janeway-Mosenthal syndrome, Reimann syndrome, periodic peritonitis, Segal-Mamu disease, Mediterranean fever. What is it?

This is a relatively rare disease that manifests itself periodic relapses serositis and the development of amyloidosis.

The name “Armenian disease” is probably due to the fact that the disease has a predominant distribution among peoples whose ancestors lived in the Mediterranean area, especially among Jews, Armenians, and Arabs, regardless of their place of residence. The disease first appears in childhood or adolescence and is observed equally often in both men and women.

Armenian disease- one of the most mysterious diseases, and difficult to diagnose. As a rule, a sick person manages to pass all narrow specialists unsuccessful treatment until she learns about her diagnosis, which causes unbearable suffering.

Symptoms

The disease begins sudden attack, which ends just as suddenly. The attack may never recur and go away forever, but it may... long time return. Without serious treatment, the Armenian disease will take the form of an irreversible condition.

The disease owes its many names to a variety of clinical manifestations. For a long time Mediterranean fever was believed to be a genetically determined disease. There are also names - Yerevan disease, Jewish disease, old blood etc.

Reasons

Experts called the cause of the disease a special genetic mutation which arises among old nations. Such complex explanations were convenient - they allowed medicine to put forward a worthy excuse for medical impotence: pain that could not be relieved by any strong drugs, muscle numbness, depression - everything was attributed to genetics. Nothing can be done.

Treatment

But they finally invented colchicine - miracle drug, bringing relief during an attack of fever. However, it turned out that this medicine is powerless against the most terrible complication Armenian disease - amyloidosis. , usually in the kidneys.

But recently there has been hope for serious relief and even complete healing- The doctoral dissertation of psychotherapist A. Nersesyan made a great impression in the scientific world. Nensesyan believes that the root of the Armenian disease lies in psychosomatic disorders. Exactly psychotherapy, according to the doctor, can help patients suffering from the Armenian disease and its consequences.

Familial Mediterranean fever (FMF), or periodic illness (PF)- This inflammatory disease, which causes repeated episodes of fever, painful inflammation of the abdominal organs, lungs and joints.

Familial Mediterranean fever is a hereditary disease.

It usually occurs in people from the Mediterranean and Caucasus regions - Jews, Arabs, Armenians, Turks and other peoples. This disease sometimes occurs in representatives of completely different ethnic groups.

Familial Mediterranean fever is usually diagnosed in childhood. There is no cure for this disease yet, you can only alleviate the symptoms, or even prevent their occurrence.

Causes and risk factors of the disease

Familial Mediterranean fever is caused by an abnormality in the MEFV gene on chromosome 16. This gene should code for the protein pyrin, which regulates inflammatory processes. There can be more than 50 different mutations in this gene. As a result of disruption of pyrin production, the patient’s body cannot adequately regulate inflammatory process, and it gets out of control.

Familial Mediterranean fever is inherited in an autosomal recessive manner. This means that a child whose both parents are carriers of the mutated MEFV gene can get sick.

The main risk factor for periodic illness is belonging to these ethnic groups. In addition, men get Mediterranean fever slightly more often than women.

Symptoms of Mediterranean fever

Symptoms of familial Mediterranean fever usually appear in patients during childhood. About 90% of all cases are diagnosed before the age of 20 years.

Attacks of the disease usually last several days and may include the following symptoms:

1. Sudden fever (from 37.8 to 40.2C).
2. Attacks of chest pain.
3. Abdominal pain.
4. Muscle pain.
5. Inflammation and pain in the joints.
6. Constipation, which is replaced by diarrhea.
7. Red rash on the legs, especially under the knees.
8. In men - swollen, inflamed scrotum.

Seizures occur without obvious reason. But some people note that attacks appear after severe physical activity or stress. Asymptomatic periods of illness can last from several weeks to several months.

At this time, patients usually feel normal.

Diagnosis of the disease

There are no specific tests to diagnose familial Mediterranean fever.

After ruling out other diseases, the doctor may make this diagnosis based on a combination of factors:

1. Symptoms.

Most symptoms of periodic illness are unexplained. Fever, sudden pain in the abdomen, chest and joints come and go, without any visible reasons. Abdominal pain may resemble appendicitis, which is also excluded. After some time, the symptoms recur.

2. Family history.

The presence of similar symptoms, or even a diagnosis of familial Mediterranean fever in relatives of the patient.

3. Nationality of the patient.

Familial Mediterranean fever is more common in certain peoples - Jews, Arabs, Turks, Armenians, Moroccans, Egyptians, Greeks and Italians (Mediterranean peoples). As for Jews, even those whose ancestors lived for centuries outside their historical homeland - in Russia, Germany, Canada, etc. - are susceptible to the disease.

4. Blood tests.

During an attack, blood tests are taken from the patient, which can reveal increased level inflammatory markers, including increased content leukocytes.

5. Genetic analysis.

In some clinics it is possible to carry out genetic analysis, which helps identify a defect in the gene responsible for this disease. True, even in the West, doctors do not often use this analysis - it does not yet identify all possible mutations associated with Mediterranean fever.

Treatment of familial Mediterranean fever

There is no definitive treatment for this disease, but it can be effectively controlled. In the West the most effective method Treatment is considered to be the use of Colchicine. This drug is taken to prevent symptoms of the disease before it worsens.

Colchicine is a potent cytotoxic drug used orally (in tablet form). Some people with Mediterranean fever need to take Colchicine daily, while others need less frequent dosing. Doses of the drug also vary significantly. Patients who may feel a fever coming on should take Colchicine at the first sign to help stop the flare-up.

Taking Colchicine also reduces the risk of developing complications of the disease, especially amyloidosis. True, this drug causes quite a lot side effects - muscle weakness, numbness of the limbs, blood disorders, etc.

If the symptoms of Mediterranean fever cannot be relieved with Colchicine, then the following options can be used:

1. Alpha interferon.
2. Thalidomide.
3. Anakinra.
4. Infliximab.
5. Etanercept.

The last options are drugs new group, called tumor necrosis factor inhibitors (TNF-alpha or TNF-alpha). These drugs are new to use and are not available in all countries (you can buy any of them in the United States).

An interesting recent study showed the unexpected effectiveness of antidepressants in exacerbations of periodic illness. It's about about the famous drugs from the group of serotonin reuptake inhibitors (SSRIs). These drugs can be used in those patients who cannot tolerate colchicine, but with less success.

1. Accept prophylactic drugs(Colchicine) strictly as prescribed by your doctor. Compliance with the dosage regimen is necessary to achieve the effect and prevent complications of the disease. Do not use Colchicine on your own!

2. If you are pregnant or planning to become pregnant, be sure to consult your doctor. He can review the treatment regimen and discontinue medications that are unsafe for the fetus. During pregnancy, some patients notice that the frequency and severity of exacerbations decreases. It's not entirely clear why this happens. Maybe, hormonal changes influence the course of the disease.

3. Optimize your diet. Some patients with familial Mediterranean fever note that attacks depend on diet. You should switch to a diet with low content fats to relieve symptoms of the disease. In addition, one of the side effects of Colchicine is lactose intolerance, so patients should limit the amount of lactose in their diet.

Possible complications of the disease

Complications of familial Mediterranean fever usually occur if the disease is left untreated or not treated regularly.

Possible complications include:

1. Amyloidosis.

This is the most common complication a disease that was not treated in a timely manner. With amyloidosis, amyloid protein is deposited in the patient's organs, which leads to the failure of one organ after another. The disease can lead to death. There is no radical treatment for amyloidosis.

2. Nephrotic syndrome.

This severe complication usually refers to amyloidosis. With nephrotic syndrome, the filtering apparatus (glomeruli) of the kidneys is affected and cannot perform its functions. Patients develop excess protein in their urine. This condition leads to blood clots in the kidneys (renal vein thrombosis) and kidney failure.

3. Arthritis.

Chronic inflammation of the joints is common among patients with familial Mediterranean fever. In most patients, the knee, hip, elbow and some others are affected, more small joints. The arthritis usually resolves without causing joint destruction.

4. Infertility.

Uncontrolled inflammation can cause damage reproductive organs. About 30-35% of women with periodic illness suffer from infertility. About 25% of those who manage to get pregnant experience miscarriages.

5. General discomfort.

Periodic illness, in itself, can be unpleasant, painful condition, which constantly affects the daily routine and reduces the quality of life. Sometimes patients even have to take narcotic analgesics to relieve daily suffering.

Konstantin Mokanov