Genetic disease of Armenians and Jews. What does a doctor do

– genetic pathology characterized by dysregulation inflammatory processes, especially in the area of ​​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 based on clinical picture, studying hereditary history and molecular genetic analyses, 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 a picture of an “acute abdomen”, patients often undergo unnecessary operations; 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, they are prescribed long-term use colchicine. 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 (familial Mediterranean fever, benign familial paroxysmal peritonitis, Armenian disease) is a disease inherited in an autosomal recessive manner and characterized by irregular attacks of fever in the presence of one or more inflammatory foci.

The disease occurs mainly among residents of the Mediterranean basin (Arabs, Jews, Turks, Armenians) and usually begins in childhood and adolescence. Men are more often affected; familial cases of the disease are possible.

Etiology and pathogenesis

It is assumed that pathological process is explained by a congenital metabolic defect, but the pathogenesis of acute attacks and the factors that provoke inflammation have not been established. It is assumed that neutrophilic leukocytes play a major role in the development of attacks.

Clinic

The disease debuts mainly before the age of 30 years. At the core clinical manifestations periodic disease lies benign aseptic inflammation serous membranes. The disease manifests itself periodic attacks acute pain in the abdomen, simulating peritonitis, or in the chest, fever (up to 39-40 ° C), arthralgia or arthritis, sometimes early development amyloidosis, which is often the only phenotypic trait diseases. Crises usually last 1-2 days and often cause erroneous surgical interventions.

Basic clinical manifestations of periodic illnessoccur with a fairly high frequency: fever - 100%, peritonitis - 85-97%, arthritis - 50-77%, pleurisy - 33-66%, erysipelas - 46%, splenomegaly - 33%, lymphadenopathy - 1-6%. In some cases, aseptic meningitis develops.

Joint syndrome characterized sharp pains, sharp pain on palpation and severe dysfunction of the joint, not corresponding to the degree of swelling of the joint. There is also no skin hyperemia or increased local temperature in the area of ​​the affected joint. The most typical are transient attacks of mono- or oligoarthritis, more often large joints(knee, hip, ankle, shoulder, elbow). 20% of patients have polyarthritis. Joint attacks last slightly longer than other manifestations of the disease (4-7 days), and in some cases their duration is several weeks and months. During the period between attacks, the function of the affected joint is completely restored, and its destruction is rare.

During an acute attack, leukocytosis, an increase in ESR, and an increase in the level of fibrinogen in the blood are noted.

In 25-40% of patients, the disease is combined with amyloidosis, mainly of the kidneys, the failure of which leads to fatal outcome often before the age of 40.

The development of amyloidosis does not depend on the frequency and nature of acute attacks diseases.

Based on the predominance of clinical manifestations, several variants of periodic disease are distinguished.

The abdominal variant is the most common, accompanied by symptoms of an “acute abdomen” with partial intestinal obstruction, serous peritonitis with moderate adhesions. Unlike acute surgical abdominal pathology, all signs disappear spontaneously after 2-4 hours.

The thoracic variant is observed less frequently. It is based on inflammation of the pleural layers. Characterized by an increase in body temperature (no more than 1 day), the development of dry pleurisy (sometimes with minor effusion). All symptoms disappear after 3-7 days.

The articular variant is characterized by recurrent synovitis. It occurs in the form of arthralgia, mono- and polyarthritis, sometimes without a febrile reaction, spontaneously disappears after 4-7 days, but sometimes lasts longer.

The febrile variant should be distinguished from the fever that accompanies all variants of the disease. In this case, the disease resembles malarial paroxysms: chills are accompanied by an increase in body temperature to 40 °C, which decreases during the day. Attacks develop infrequently, occurring mainly in childhood. This variant of periodic disease, like articular and thoracic, can disappear, giving way to abdominalgia.

Often, periodic disease occurs as a combination of several clinical variants.

Treatment

The use of colchicine in small doses helps prevent attacks of periodic illness. In 50% of cases, complete remission is observed with constant use of colchicine. daily dose 1-2 mg.

Treatment with colchamine (colchicine) should begin with determining the tolerability of the drug: patients take the drug for 10 days after meals under the control of a blood test, including leukocytes and platelets. In this case, the optimal daily dose (no more than 2 mg) is selected, taking into account the frequency of attacks. In those rare cases where colchamine is not effective, replacing it with colchicine at the same or even lower dose may be helpful.

During acute attacks, treatment of periodic illness involves the administration of NSAIDs. Hormone therapy is ineffective, which can serve as a differential diagnostic sign.


"Rheumatology"
T.N. Onboard

Manifested by periodically recurrent serositis and frequent development amyloidosis. It is found mainly among representatives of nationalities whose ancestors lived in the basin Mediterranean Sea, especially among Armenians, Jews (usually Sephardim), Arabs, regardless of their place of residence. begins, as a rule, in childhood and adolescence with equal frequency in males and females.

Etiology insufficiently studied. It is assumed that patients have a congenital metabolic, enzymatic defect, which entails a violation of the immune and endocrine systems, protein synthesis, proteolysis. Autosomal recessive inheritance of the disease has been established.

Pathogenesis recurrent inflammation, which characterizes P.'s attacks, is associated with cell degranulation. A genetically determined disorder of cellular metabolism is evidenced by the frequent development of P. b. Amyloidosis a, regardless of the duration and severity of P. b. The existence of two genotypic manifestations is allowed. With the first genotype, the disease manifests itself for a long time with attacks of serositis, then it can join. With the second genotype, amyloidosis develops first, and subsequently attacks of P. b. Along with this, there are cases of P. b. without amyloidosis and cases where amyloidosis is the only manifestation of the disease.

Pathological anatomy in the absence of amyloidosis, it has no specific features. Despite chronic course P.b., rude anatomical changes none. During P.'s attack b. there are all the signs of aseptic inflammation of the serous membranes, mainly the peritoneum, pleura, synovial membranes, in some cases a small serous is detected. It is also possible increased blood vessels, nonspecific cellular. Amyloidosis, if present, primarily affects the kidneys; in terms of histoimmunochemical properties it is close to secondary amyloidosis.

Clinical picture and course. Depending on the predominant localization of manifestations, four variants of P. b. are distinguished: thoracic, articular and febrile. option occurs most often and, when fully developed, is characterized by symptoms of an acute abdomen (Acute abdomen), which often serves as a reason for surgical intervention due to suspected acute, acute or obstruction small intestine. During the operation, 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 operations, mechanical may develop, which is facilitated by pronounced gastrointestinal tract And biliary tract, caused by P. b. itself. and detectable when x-ray examination abdominal organs during an attack of illness.

Thoracic variant of P. b., observed less frequently. 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 are the same as for pleurisy - dry or with slight effusion. All signs of exacerbation of the disease spontaneously disappear after 3-7 days.

The articular variant in the form of recurrent synovitis is manifested by arthralgia, mono- and polyarthritis. The ankles and knees are most often affected. Joint attacks are more easily tolerated than attacks of the abdominal and thoracic variants of P. b.; they often occur with normal temperature bodies. With prolonged arthritis, lasting more than 2-3 weeks, transient symptoms may occur.

Feverish variant of P. b. characterized by sudden increases in body temperature; attacks of the disease resemble those of malaria. They occur rarely, usually at the beginning of the disease, then, like articular and thoracic attacks, they can disappear completely. febrile variant as an independent clinical form P. b. it is necessary to distinguish the fever that accompanies P.'s attacks. with other manifestations of the disease. In the latter case, it increases soon or simultaneously with the appearance of pain, sometimes accompanied by chills, reaches various levels and decreases to normal numbers after 6-12, less often 24 h.

The course of the disease is chronic, relapsing, usually benign. Exacerbations occur in a stereotypical manner, differing only in severity and duration. Regardless of the frequency and severity of P.'s attacks. 30-40% of patients develop amyloidosis, which leads to kidney failure (renal failure).

Diagnosis diagnosed based on the following criteria: 1) periodically occurring short attacks of the disease (abdominal, thoracic, articular, febrile), not associated with a specific provoking factor, characterized by stereotypicality; 2) onset of the disease in childhood or adolescence, mainly among certain ethnic groups; 3) frequent detection of the disease in relatives; 4) frequent development of renal amyloidosis; laboratory values ​​are mostly nonspecific and reflect the severity of inflammatory reaction or degree of kidney failure. At the first manifestations of P. b. differential can be difficult and is based on careful exclusion of diseases with similar symptoms. In case of repeated relapses of the disease, the above criteria and the fact that for P. b. typical wellness patients during the interictal period and to any therapy, incl. antibiotics and glucocorticoids.

Treatment until the 70s was only symptomatic. In 1972, information appeared about the possibility of preventing attacks of P. b. taking colchicine orally in a daily dose of 1 to 2 mg. Subsequently, the preventive effectiveness of colchicine was confirmed, as well as its good effectiveness with long-term (almost all) use of the indicated doses in both adults and children. The mechanism of action of the drug is not completely clear. In small doses, it has an anti-inflammatory effect, influencing each of the successive steps leading to degranulation of leukocytes, reduces vascular permeability, inhibits prostaglandins, and also inhibits the development of amyloidosis, acting on the intracellular and exocytosis of amyloid precursors, on the assembly of amyloid fibrils.

Forecast for life in patients with P. b. without amyloidosis, favorable. Frequent attacks Illnesses can cause temporary disability. The development of amyloidosis leads to disability due to renal failure (usually before the age of 40). Before the use of colchicine, the 5- and 10-year survival rate of patients with P. b. with amyloidosis (from the onset of proteinuria) was 48 and 24%, respectively. With treatment with colchicine, it increased to 100%, and the average survival rate increased to 16 years. Colchicine is effective regardless of the stage of amyloid nephropathy. However, the earlier it starts, the faster it comes positive result. Therefore, it is very important for patients with P. b. For early detection persons requiring treatment with colchicine primarily for the purpose of preventing amyloidosis.

Bibliography: Ayvazyan A.A Periodic disease, Yerevan, 1982; Vinogradova O.M. Periodic illness. M., 1973.

II Periodic illness

1. Small medical encyclopedia. - M.: Medical encyclopedia. 1991-96 2. First health care. - M.: Great Russian Encyclopedia. 1994 3. encyclopedic Dictionary medical terms. - M.: Soviet Encyclopedia. - 1982-1984.

See what “Periodic disease” is in other dictionaries:

Occurring predominantly in the Mediterranean region chronic illness human (genetic determination is assumed) with various manifestations, a characteristic change of exacerbations and remissions, frequent development of amyloidosis... Big Encyclopedic Dictionary

The style of this article is non-encyclopedic or violates the norms of the Russian language. The article should be corrected according to the stylistic rules of Wikipedia... Wikipedia

Benign paroxysmal peritonitis, familial Mediterranean fever, recurrent superficial aseptic inflammation of the serous membranes (peritoneum of the pleura) with a predominance of exudative (see Effusion) reaction. Overwhelmingly... Great Soviet Encyclopedia

A chronic human disease observed mainly in the Mediterranean region (suggested to be genetically determined) with various manifestations, a characteristic change of exacerbations and remissions, and frequent development of amyloidosis. * * *… … Encyclopedic Dictionary Medical Encyclopedia

- (syn.: B. Armenian, B. periodic family, Janeway Mosenthal paroxysmal syndrome, familial Mediterranean fever, six-day fever, paroxysmal peritonitis, periodic peritonitis, recurrent polyserositis, polyserositis... ... Large medical dictionary

See Periodic disease... Large medical dictionary

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Periodic disease (Familial Mediterranean fever) is an autosomal recessive disease that usually begins before age 30. More early start corresponds to a more severe phenotype. Periodic illness is divided into 2 types. Type 1 is characterized by outbreaks (usually once a week or every few years) of fever and serositis that last about 1-4 days and resolve spontaneously. Stress exposure to cold, fatty foods, infections, certain medications and monthly cycle may provoke an exacerbation. Mild symptoms (myalgia, headache, nausea, dyspnea, arthralgia, low back pain, asthenia and anxiety) herald outbreaks of the disease and last about 17 hours. Outbreaks manifest as fever (38°-40°C lasting 12-72 hours that does not respond to antibiotics), diffuse or localized pain in the abdomen (often mimicking acute stomach), constipation (diarrhea in children), arthralgia (in large joints), arthritis (in the upper/ lower limbs/ knee joints), and chest pain caused by pleurisy and/or pericarditis. 7-40% of patients also have erysipelas skin. Type AA amyloidosis is a common complication. Periodic disease type 2 is characterized by amyloidosis, which is the first and only symptom of the disease.

The disease occurs mainly in certain ethnic groups(Armenians, Turks, Sephardic Jews, Arabs), while the carrier frequency reaches 1/10. The gene responsible for the occurrence of Periodic Disease in these ethnic groups, called MEFV, located in the area 16р13.3. Gene MEFV encodes the protein marenostrin (pyrin), which is involved in the regulation of inflammatory processes.

A dominant form of the disease has also been described (OMIM#134610)

Currently, 177 mutations in the gene have been described MEFV, of which 154 are missense mutations. Most mutations, including the two most common, recorded in 75% of patients - M694V and V726A - are localized in exon 10 of the gene MEFV. The Center for Molecular Genetics performs direct DNA diagnostics based on the study of a fragment of exon 10 of the gene. The information content of such a study is 98%. In addition, it is possible to sequence all exons and adjacent intronic regions of the gene MEFV.

When conducting prenatal (prenatal) DNA diagnostics in relation to specific disease, it makes sense to use existing fetal material to diagnose common aneuploidies (Down, Edwards, Shereshevsky-Turner syndromes, etc.), paragraph 54.1. Relevance this study due to the high total frequency of aneuploidy - about 1 in 300 newborns, and the absence of the need for repeated sampling of fetal material.

Family Mediterranean fever (FMF, periodic illness) is hereditary disease characterized by recurrent episodes of fever and peritonitis, sometimes with pleurisy, skin lesions, arthritis and very rarely pericarditis. Renal amyloidosis may develop, which can lead to kidney failure. This disease most often occurs in the descendants of inhabitants of the Mediterranean Sea basin. The diagnosis is largely clinical, although it is available genetic testing. Treatment includes colchicine to prevent acute attacks as well as renal amyloidosis in most patients. The prognosis for treatment is favorable.

Familial Mediterranean fever (FMF) is a disease that occurs in people descended from the inhabitants of the Mediterranean basin, mainly Sephardic Jews, North African Arabs, Armenians, Turks, Greeks and Italians. However, cases of the disease have also been reported in other groups (eg, Ashkenazi Jews, Cubans, Belgians), which cautions against excluding a diagnosis based on origin alone. Approximately 50% of patients have a family history of the disease, usually including siblings.

The most common of the described diseases, FMF affects predominantly nationalities living in the Mediterranean region (Sephardic Jews, Turks, Armenians, North Africans and Arabs), although descriptions of cases of periodic disease can also be found in Ashkenazi Jews, Greeks, Russians, Bulgarians , Italians. The frequency of occurrence depending on nationality is 1:1000 - 1:100000. It occurs more often in men than in women (1.8:1).