What is Armenian periodic disease? How to treat periodic illness.

Periodic disease (synonyms: familial Mediterranean fever, benign paroxysmal peritonitis, recurrent polyserositis, Jewish disease, Armenian disease) is a hereditary autosomal recessive disease common among representatives of the ancient peoples of the Mediterranean. Most often, periodic disease (PD) occurs among Sephardic Jews, Armenians, Arabs, Greeks, Turks, peoples of the Caucasus, etc., hence the other names of the disease. The occurrence of PB among Sephardi Jews, according to various sources, ranges from 1:250 to 1:2000 (carriage frequency of the mutant gene is from 1:16 to 1:8), among Armenians - from 1:100 to 1:1000 (carriage frequency is from 1 :7 to 1:4).

Among 15 children with BE observed at the Russian Children's Clinical Hospital (RCCH) over the past years, 8 were Armenians, 4 were Dagestanis, 1 was Greek, 1 was of Chechen and Jewish roots, 1 was Russian.

Etiology and pathogenesis

PB is based on a point mutation in the pyrin protein gene, located on the short arm of chromosome 16 (16q) next to the genes for autosomal dominant polycystic kidney disease and tuberous sclerosis. Pyrin is a protein of the primary granules of neutrophils, actively involved in the regulation of inflammatory processes. It is believed that pyrin stimulates the production of anti-inflammatory mediators, controls chemotaxis, and stabilizes the granulocyte membrane. Disruption of the structure of this protein, which occurs in BE, leads to increased production of pro-inflammatory mediators in leukocytes, activation of the microtubular apparatus and spontaneous degranulation of primary granules of leukocytes, activation of adhesion molecules and enhanced chemotaxis of leukocytes, resulting in inflammation.

To date, 8 types of mutations in the C-terminal region of the pyrin gene are known, in which a point amino acid substitution occurs. The three most common mutations, which account for more than 90% of cases of PD: M680I (replacement of isoleucine with methionine), M694V (replacement of valine with methionine), V726A (replacement of alanine with valine). All three mutations date back 2000-2500 years, so they are sometimes called “biblical”, and therefore they were predominantly distributed among representatives of the ancient peoples who inhabited the lands around the Mediterranean Sea. The M680I mutation is found mainly in Armenians, M694V and V726A - in all ethnic groups.

BE occurs in the form of attacks, the basis of which is spontaneous or provoked degranulation of neutrophils with the release of mediators and the development of aseptic inflammation mainly on the serous and synovial membranes. In the peripheral blood, the number of neutrophils and acute-phase proteins (CRP - C-reactive protein, SAA - serum amyloid A protein, etc.) increases. Irritation of receptors by inflammatory mediators leads to the development of pain, and the effect of a large number of endogenous pyrogens on the thermoregulation center leads to the development of fever.

Clinical picture and course

Clinically, BE manifests itself as stereotypical attacks of fever occurring at certain intervals (days - weeks - months). Fever may be accompanied by pain syndromes associated with the development of nonspecific inflammation in the serous and synovial tissues. Depending on the penetrance of genes, these syndromes can be isolated or combined, but each of them maintains its own rhythm. Any attack is accompanied by leukocytosis, an increase in ESR and other inflammatory proteins, an increase in the a- and b-fraction of globulins, and a decrease in the activity of neutrophil myeloperoxidase. Outside the attack, the children feel well, laboratory parameters gradually return to normal.

Fever is the most common and persistent symptom of BE, occurring in 96-100% of cases. A feature of fever in BE is that it is “not controlled” by antibiotics and antipyretics. Isolated fever during BE, as a rule, leads to diagnostic errors and is regarded as a manifestation of ARVI.

The second most common symptom of BE is abdominal pain syndrome (aseptic peritonitis), which occurs in 91% of cases, and in isolation - in 55%. Clinically, aseptic peritonitis differs little from septic peritonitis with all the symptom complex characteristic of the latter: temperature up to 40°, severe abdominalgia, nausea, vomiting, inhibition of intestinal motility. After a few days, peritonitis subsides, peristalsis is restored. Such a clinic is often the cause of diagnostic errors, and patients are operated on for acute appendicitis, peritonitis, cholecystitis, intestinal obstruction, etc. Among the children we observed, 6 were previously operated on, and 2 patients were operated on twice: 4 for acute appendicitis, 2 for for intestinal obstruction, 1 for peritonitis, 1 for acute cholecystitis. As a rule, the medical documentation of such patients notes the presence of “catarrhal appendicitis” and the need for surgical intervention is beyond doubt. It is quite typical that, according to the parents, the doctors who operated on the child in private conversations denied the actual presence of appendicitis or peritonitis.

The duration of febrile and abdominal variants of BE usually ranges from 1 to 3 days, less often it extends to 1-2 weeks.

Peritonitis, like articular syndrome, is most common in childhood.

Joint syndrome is characterized by arthralgia, inflammation of large joints. Arthritis and arthralgia, according to various sources, are observed in 35-80% of cases, and in 17-30% they are the first signs of the disease. At the time of the attack, sudden joint pain appears in one or more joints, which may be accompanied by swelling, hyperemia and hyperthermia of the joints. The duration of the articular version of the attack of BE is 4-7 days, sometimes extending to 1 month. Unlike isolated fever or paroxysmal peritonitis, with this variant of BE, arthralgia often persists after the attack, gradually subsiding over several months. The non-specificity of the clinical picture in the articular variant of BE leads to the fact that patients are diagnosed with rheumatoid arthritis, rheumatism, systemic lupus erythematosus, etc. The father of one of our patients, an Armenian by nationality, was observed for many years with a diagnosis of rheumatoid arthritis, and only when diagnosed We genetically established the same diagnosis for the child with BE.

The thoracic variant with pleural syndrome is less common - about 40% of cases, isolated - in 8%, in combination with abdominal syndrome - in 30%. In the thoracic variant, unilateral or bilateral pleurisy with sterile effusion develops. The duration of this syndrome is 3-7 days. As a rule, such patients are mistakenly diagnosed with pleurisy or pleuropneumonia.

Skin changes during an attack of BE occur in 20-30% of cases. The most typical is an erysipelas-like rash, but purpuric rashes, vesicles, nodules, and angioedema may occur. Sometimes clinically, BE proceeds like an allergic reaction, including angioedema and urticaria.

Other manifestations of BE may be headache, aseptic meningitis, pericarditis, myalgia, hepatolienal syndrome, acute orchitis.

Among our patients, 12 BE had an abdominal variant, and 3 had an abdominal-articular variant. 11 of them were admitted to the Russian Children's Clinical Hospital with other diagnoses: chronic cholecystitis, pancreatitis, gastroduodenitis, Crohn's disease, colitis of unknown etiology, rheumatoid arthritis, SLE (systemic lupus erythematosus), chronic glomerulonephritis, and only 4 with a referral diagnosis of “periodic disease”. Most patients are admitted to the gastroenterology department with complaints of recurrent abdominal pain, with kidney involvement with the development of proteinuria and nephrotic syndrome - to the nephrology department, with unmotivated recurrent fever - to the infectious and diagnostic departments.

The manifestation of the disease can occur at different ages. Cases of rather late manifestation of BE have been described, after 20-25 years. According to our observations, in most patients the first attack of BE was observed at the age of 2-3 years (9 patients), in 1 - from birth, in 2 - at 0.5-1.5 years, in 2 - at 4-5 years, in 1 - at 11-12 years.

The frequency and frequency of attacks vary widely among different patients: from several times a week to 1-2 times every few years. In most patients, attacks have a fairly stable rhythm. However, the literature describes cases where attacks could stop for several years or, conversely, resume after a long break under the influence of external factors (change of residence, marriage, birth of a child, military service, etc.). In our patients, the frequency of attacks was quite constant: in 1 - 2 times a week, in 4 - 1 time per week, in 5 - once every 2-3 weeks, in 2 - 1 time per week. month, for 1 - once every 2-3 months, for 1 - once every 6-12 months.

After some time from the onset of manifestation, most patients experience hepatomegaly, which, according to our observations, can vary from +1 to +5 cm. Splenomegaly gradually develops, the value of which in some patients reached +7 cm. However, enlargement of the liver and spleen is not detected in all patients. Obviously, these processes depend on the frequency and number of attacks suffered and the development of amyloidosis.

Amyloidosis as a complication of periodic illness

Each attack of BE is accompanied by the release of a large number of mediators and the formation of inflammatory proteins. From tissues and serous tissues, these proteins enter the blood, where they circulate for a long time. Thus, the body is faced with the task of somehow eliminating these protein substances. The more frequent and severe the attacks of BE, the more acute the problem of utilization. One way to get rid of excess circulating protein molecules is to process them to form an insoluble protein, amyloid. Figuratively speaking, amyloid is tightly packed protein “junk.” The formation and deposition of amyloid in tissues leads to the development of amyloidosis.

Amyloidosis (from the Latin amylum - starch) is a collective concept that includes a group of diseases characterized by extracellular deposition of proteins in the form of characteristic amyloid fibrils. These insoluble fibrillar proteins may be localized in one specific location or may be distributed in various organs, including vital organs such as the kidneys, liver, heart, etc. This accumulation leads to organ dysfunction, organ failure, and ultimately death.

The structure of amyloid is identical for all its types and consists of rigid, non-branching fibrils with a diameter of about 10 nm, which have a folded β-cross conformation, due to which the effect of birefringence occurs in polarized light when stained with Congo red. Alkaline Congo red staining is the most common and accessible method for detecting amyloid.

Amyloid consists of fibrillar proteins (fibrillar component, F-component) and blood plasma glycoproteins (plasma component, P-component). The precursors of the F component differ in different types of amyloidosis (today, up to 30 precursor proteins are known; they determine the type of amyloidosis); There is one precursor of the P component, serum amyloid P component (SAP), similar to α-globulin and CRP.

Amyloid fibrils and plasma glycoproteins form complex compounds with tissue chondroitin sulfates with the participation of hematogenous additives, the main ones being fibrin and immune complexes. The bonds between the protein and polysaccharide components in the amyloid substance are particularly strong, which explains the lack of effect when amyloid is exposed to various enzymes of the body, i.e. amyloid is insoluble.

In BE, the basis for the formation of the fibrillar amyloid component is the serum acute phase protein SAA. SAA is an a-globulin, similar in its functional properties to CRP. SAA is synthesized by different types of cells (neutrophils, fibroblasts, hepatocytes), its amount increases many times during inflammatory processes and tumors. Several types of SAA have been isolated in humans, and only fragments of some of them are included in amyloid fibrils, which may explain the development of amyloidosis only in some patients, despite the increased production of SAA. From the serum SAA precursor, AA protein (amyloid A protein) is formed in tissues, which is the basis of amyloid fibrils. Therefore, the type of amyloidosis that develops in BE is called AA amyloidosis.

Thus, the basis for the development of amyloidosis in BE is the excessive formation of the SAA precursor protein. But for the formation of amyloid protein, cells are needed that will synthesize it - amyloidoblasts. This function is performed mainly by macrophages-monocytes, as well as plasma cells, fibroblasts, reticulocytes and endothelial cells. Macrophages process AA protein into full-fledged amyloid fibrils on their surface and deposit it in the interstitial tissue. Therefore, the greatest accumulation of amyloid in BE is observed in organs where macrophages occupy a fixed position: kidneys, liver, spleen. Gradually increasing amyloid deposits lead to compression and atrophy of parenchymal cells, sclerosis and organ failure.

According to various sources, amyloidosis in BE disease develops in 10-40% of patients. Some patients, despite having fairly frequent attacks, do not develop amyloidosis at all. Probably, the development of amyloidosis depends on the structural features of the precursor protein in a given patient and the genetic ability of macrophages to synthesize amyloid.

Despite the fact that amyloidosis can develop in any organ and tissue, amyloid kidney damage plays a decisive role in the prognosis and life of a patient with BE. With the development of AA amyloidosis, the kidneys are affected in 100% of cases.

In the kidneys, the role of amyloidoblasts is performed by mesangial and endothelial cells.

In the process of amyloid deposition in the kidney tissue and the damage to the organ caused by it, a certain stage can be traced. There are 4 stages of renal amyloidosis: latent (dysproteinemic), proteinuric, nephrotic (edematous) and uremic (azotemic).

During the latent stage, changes in the kidneys are insignificant. Disturbances of the glomerular filter are noted in the form of focal thickening, double-circuit membrane and aneurysms of a number of capillaries. There is no amyloid in the glomeruli or it is found in no more than 25% of the glomeruli.

The leading factor in the pathogenesis of this stage of amyloidosis is a significant synthesis and increase in the concentration of amyloidosis precursor proteins in the blood plasma, i.e., dysproteinemia. Clinically, children may develop hypochromic iron deficiency anemia, hyperproteinemia, dysproteinemia with an increase in globulins α 2, β and γ against the background of attacks of BE, and a high content of fibrinogen and sialoproteins is noted. Characterized by enlargement and hardening of the liver and spleen.

Changes in urine are initially absent or transient, but over time, proteinuria becomes constant and more pronounced, microhematuria and cylindruria are often observed. The appearance of constant proteinuria characterizes the transition to the second, proteinuric, stage.

In the proteinuric stage, amyloid appears not only in the pyramids, but also in half of the glomeruli of the kidneys in the form of small deposits in the mesangium, individual capillary loops, and arterioles. Severe sclerosis and amyloidosis of the stroma, vessels, pyramids and intermediary zone are noted, which leads to atrophy of many deep-lying nephrons.

The duration of this stage, like the previous one, ranges from several months to many years. As the severity of amyloidosis increases, laboratory indicators of the pronounced activity of the process worsen: significant proteinuria and dysproteinemia, hyperfibrinogenemia, CRP, hypercoagulation. Further deposition of amyloid in the renal tissue and increasing proteinuria lead to the development of edematous syndrome, the appearance of which indicates the transition of the disease to the third, edematous stage.

During the edematous (nephrotic) stage of amyloidosis, the amount of amyloid in the kidneys increases. More than 75% of glomeruli are affected. Sclerosis of the interstitium and blood vessels progresses; in the pyramids and intramedian zone, sclerosis and amyloidosis are of a pronounced diffuse nature.

Clinically, this stage of amyloidosis is represented by complete nephrotic syndrome, although incomplete (edemaless) nephrotic syndrome can sometimes be observed. Proteinuria becomes massive and, as a rule, non-selective; cylinders grow. Hematuria is rare and usually minor. Hepatosplenomegaly, hypoproteinemia increase, dysproteinemia increases with a further increase in the level of α 1 -, α 2 -, and γ-globulins, hyperfibrinogenemia, hyperlipemia. Over time, arterial hypertension appears, azotemia increases, and renal failure progresses.

The uremic (azotemic) stage develops at the end of the disease. Due to increasing amyloidosis and sclerosis, the death of most nephrons is observed, their replacement by connective tissue, and CRF (chronic renal failure) develops.

Clinical features of chronic renal failure in amyloidosis, which distinguish it from chronic renal failure due to other diseases, are the persistence of nephrotic syndrome with massive proteinuria, large kidney sizes are often detected, and the development of hypotension is characteristic.

DIC syndrome (disseminated intravascular coagulation syndrome) is often expressed in the form of purpura, nasal, gastric and intestinal bleeding. Thrombosis of the renal vessels with the development of ischemic or hemorrhagic infarctions is possible.

We observed the development of amyloidosis in 4 children with BE (26% of observed patients). Transient proteinuria appeared in them 7-8 years after the manifestation of the disease, after 2-3 years it became permanent. In 2 children, 1.5-2 years after the establishment of constant proteinuria, nephrotic syndrome developed, which in one child developed into chronic renal failure.

Since the development of nephrotic syndrome, the children were diagnosed with chronic glomerulonephritis and prescribed appropriate treatment with glucocorticoids, which had no effect. Subsequently, the disease was regarded as SLE and a hormone-resistant variant of glomerulonephritis; the children received cytostatic therapy, also without effect. The diagnosis of “periodic disease, renal amyloidosis” in both cases was first established at the Russian Children's Clinical Hospital.

The development of amyloidosis to a certain extent depends on the number of attacks of pulmonary hypertension suffered by the child. Among our patients, renal amyloidosis was detected in those who suffered more than 130-150 attacks, while in children with fewer attacks there were no signs of amyloidosis and kidney damage. Moreover, children with nephrotic syndrome suffered the largest number of attacks - about 240 and 260. It should be noted that this pattern is not absolute and amyloidosis can develop with fewer attacks of nephrotic syndrome.

Diagnosis of periodic disease and amyloidosis

In the typical course of periodic illness, its diagnosis is not difficult. The biggest problem is the ignorance of most doctors about this pathology, which leads to poor detection even in the presence of symptoms.

Diagnosis of BE is based on 5 points.

Anamnesis. Of greatest importance are the child’s nationality, heredity (LP in parents or relatives; diseases in the family similar to BP), the characteristic history of the child’s life and illness (frequent “colds” with fever, frequent pain in the abdomen and joints, previous surgical interventions, etc. ).

Clinical picture. Attacks of fever with pain, ineffectiveness of antibiotics and antipyretics, good health during the non-attack period.

Laboratory data. Leukocytosis with neutrophyllosis, acceleration of ESR, decreased activity of neutrophil myeloperoxidase and increased its activity in the blood at the time of attack; normalization of indicators outside of an attack.

Genetic research. The most reliable diagnostic sign of BE. Detection of homozygous carriage of the M680I, M694V, V726A mutations makes the diagnosis of periodic disease 100%. However, certain difficulties are also possible here when a typical clinical picture and medical history reveals a heterozygous carriage of mutations. A similar situation can occur when one of the above mutations is detected in one of the alleles of the pyrin gene, and a rarer one that is not detected by standard typing is detected in the other.

Effect of colchicine therapy. Trial therapy with colchicine as a diagnostic criterion is necessary when it is not possible to conduct a genetic study or when its results do not fully confirm the diagnosis of BE (heterozygous carriers of the M680I, M694V, V726A mutations or carriers of rarer mutations). The presence of an effect from therapy confirms the diagnosis of BE.

Diagnosis of AA amyloidosis is very difficult. In most cases, AA amyloidosis is not diagnosed in a timely manner, even when clinical signs of the disease are present. The reason for this is, on the one hand, the nonspecificity of the symptoms of the disease, and on the other, the lack of alertness among most doctors regarding amyloidosis, which is also due to its low prevalence in children. However, our understanding of the frequency of amyloidosis in children is erroneous, and the detected cases represent only the “tip of the iceberg.” As recent studies conducted in adult patients show, amyloidosis is not diagnosed during life in 83% of patients.

When diagnosing BE, in most cases the doctor becomes wary of amyloidosis. But often the first suspicion of AA amyloidosis may arise from a pediatrician when treating patients with nephrotic syndrome who are resistant to standard glucocorticoid therapy.

Only the study of biopsy materials with mandatory Congo red staining and polarizing microscopy allows a final diagnosis of AA amyloidosis to be made. In addition, specific antibodies to AA fibrils can be used for diagnosis. The most reliable is a kidney biopsy. The detection rate of AA amyloidosis in this case reaches 90-100%. The more widespread the process, the greater the likelihood of detecting AA amyloid in other places (gastrointestinal tract (GIT) - mucosa and submucosa, gingival mucosa, rectum, fat biopsy). The most informative among non-renal biopsies is a biopsy of the wall of the gastrointestinal tract and rectum, in which the probability of detecting amyloid is 50-70%.

Treatment

For periodic illness, the mainstay of therapy is the administration of colchicine. Colchicine has an antimitotic effect against amyloidoblasts in periodic disease - macrophages and stabilizes the neutrophil membrane, preventing the release of pyrin. Colchicine is prescribed for life at a dose of 1-2 mg/day. It is well tolerated, sometimes dyspeptic symptoms occur that do not require complete discontinuation of the drug. Colchicine in most cases completely prevents the occurrence of attacks of kidney stones or significantly reduces their frequency and severity, prevents the development of renal amyloidosis, and reduces the severity of its manifestations. In case of renal failure, the dose is reduced based on the degree of decrease in glomerular filtration. The drug may be temporarily discontinued in case of acute infections in a child.

We observed a boy who was sent to the Russian Children's Clinical Hospital with a genetically established diagnosis of periodic disease at the age of 16 years. He had attacks of BE from the age of 4, occurring once every 2-3 weeks in the form of fever with abdominal pain, 1-2 times vomiting, headache and severe weakness. The attacks lasted about a day, then for 1-2 days there was such pronounced weakness that the boy could not get out of bed and did not attend school. There were no signs of amyloidosis.

At the Russian Children's Clinical Hospital, the child was prescribed colchicine at a dose of 2 mg/day. Over the next 2 years of observation, the number of attacks sharply decreased to 1-2 times a year, and during the last 10 months there were none. Now the young man is successfully studying at a university, lives in a hostel in another city, and feels good.

In the treatment of BE and the prevention of amyloidosis, it is necessary to organize proper nutrition for the child. Increasing the total amount of protein in the diet stimulates amyloidogenesis, while liver protein and cardiac muscle inhibit it. A diet with a 50% reduction in animal (especially casein) and plant proteins and an increase in starch-containing foods is recommended. The diet should be sufficiently 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. Hepatotropic drugs are used in repeated courses: 2-4 months of Essentiale, Lipoic acid.

Forecast

With timely diagnosis and prescription of colchicine, the prognosis for BE is favorable.

In the absence of therapy, the greatest danger is the development of renal amyloidosis, which, in fact, is the only cause of death in patients with BE. Analysis of morbidity in adults and children shows that during the natural course of periodic disease, in approximately 50% of patients, end-stage renal failure develops within 5 years from the onset of proteinuria, in 75% - within 10 years.

For questions about literature, please contact the editor.

A. V. Malkoch, Candidate of Medical Sciences
RGMU, Moscow

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 predominantly among representatives of nationalities whose ancestors lived in the Mediterranean basin, especially among Armenians, Jews (usually Sephardim), Arabs, and only in 6% of all cases among people of other nationalities.

It was established that there is no influence of geographical latitude on the spread of the disease. The disease begins predominantly in childhood and adolescence, regardless of gender.

Etiology insufficiently 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 disruption of the immune and endocrine systems, protein synthesis, and proteolysis.

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

A violation of cellular metabolism is evidenced by the frequent development of 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., gross anatomical changes are not formed. In the interictal period, a small number of tender adhesions are found in the area of ​​recurrent inflammation. During an acute attack of 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 reveals only signs of superficial serous peritonitis and moderate adhesions. Unlike acute surgical diseases of the abdominal cavity, all symptoms disappear spontaneously after 2-4 days. In rare cases, usually after repeated surgical interventions, mechanical intestinal obstruction, intussusception or volvulus may develop, which is facilitated by pronounced dyskinetic processes in the gastrointestinal tract. tract and bile ducts, caused by P. b. and clearly detected by rentgenol, examination of patients, especially carried out during acute abdominal pain. 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. It is observed less frequently; it is characterized by inflammation of the pleura, which occurs in one or the other half of the 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. Large joints are most often affected, especially ankles and knees. Attacks of the disease in its articular variant are tolerated more easily than in other variants, they recur less frequently, sometimes occur at normal temperatures, 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, reaches various levels and decreases to normal levels 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 parameters during each exacerbation reflect only the degree of the inflammatory reaction and normalize as the acute phase of the disease subsides.

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 reaction 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 of 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 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. characterized by good health of 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 in a daily dose of 0.6 to 2 mg. Subsequently, the preventive effectiveness of colchicine was confirmed, as well as the absence of side effects with long-term use of the 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 or marriage. Very frequent attacks of the disease can cause disability, and the development of amyloidosis in some patients (usually before the age of 40) 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.

Periodic illness is one of the strangest and most difficult to diagnose problems in human health. As a rule, the patient manages to undergo treatment from doctors of almost all specializations, which does not give any positive results, until he eventually learns about the diagnosis, which causes unbearable suffering.

Description of the pathology

Periodic disease is known to humanity under various names, such as recurrent polyserositis, Mediterranean fever or Armenian disease. is related to hereditary autosomal recessive dysfunctions and is widespread mainly among residents of the Mediterranean region of the planet. Therefore, the disease can often be found among Greeks, Armenians, Sephardic Jews, Turks and among the numerous peoples of the Caucasus.

Clinical picture of periodic Armenian disease

The following types of periodic disease are distinguished, which depend on their location:

• Thoracic.
• Feverish.
• Abdominal.
• Articular.

Thoracic type

The thoracic type is accompanied by a process of inflammation of the pleura, which seems to wander to various parts of the chest. The results of research and the patient’s complaints, as a rule, indicate dry pleurisy, which, of course, cannot correspond to reality. Exacerbations may disappear spontaneously after a week.

Abdominal option

Against the background of the abdominal variant of Armenian periodic disease, doctors may suspect appendicitis, since the patient suffers from severe, even acute pain in the abdominal area. It appears as if we are talking about obstruction of the small intestine or cholecystitis. Often, such symptoms mysteriously disappear after two to four days. Periodic disease is usually diagnosed by resorting to an X-ray examination of the affected organs in the abdominal region.

Feverish and articular types

Due to fever, the patient's temperature rises sharply, and the course of the disease itself is more reminiscent of malarial fever.

But the most unpleasant is the articular variant, which manifests itself in the form of recurrent synovitis, and in addition, monoarthritis and arthralgia. When arthritis lingers, there is a possibility of transient osteoporosis.

Causes and features of occurrence

The main cause of Armenian disease lies in the heredity of metabolic disorders, which can be accompanied by an increase in vascular permeability, the development of connective tissue, as well as a tendency to exudation or, to put it in a more understandable language, to swelling. For a long time, the disease can proceed unsystematically, without causing any exacerbations. But due to the influence of an as yet unstudied complex of internal and external prerequisites, a benign tumor is formed in relation to the serous membranes in Mediterranean fever (Armenian disease).

The onset of fever is accompanied by pain. There is a deposition of protein - amyloid in tissues and organs, mainly in the kidneys. The attack can last for several days, after which the patient’s condition noticeably improves until the next attack occurs. Typically, remission lasts approximately three to seven days.

The deposition of amyloid substance after each attack causes increasing renal depression. Chronic renal failure subsequently occurs in twenty-five to forty percent of patients.

Manifestations and signs of periodic illness

Diagnosis of Armenian disease, as a rule, causes great difficulties. But nevertheless, this illness can still be outlined:

• Fever usually accompanies the main stages of exacerbations. It is identical in its typology to malaria and is determined by a sudden temperature jump to the forty-degree mark.
• Peritonitis occurs in ninety-five percent of cases. Due to inflammation of the peritoneum, patients are hospitalized and sent to surgical departments.
• Arthritis acts as an articular type of disease, which is observed in eighty percent of cases.
• The thoracic form includes various breathing problems, bronchitis and pleurisy, which occurs in sixty percent of situations.
• Combined forms, characterized by a significant enlargement of the spleen, damage to the lymph nodes, as well as a skin rash that vaguely resembles erysipelas, occur among fifty percent. Rarely, but it happens that aseptic meningitis occurs.

Diagnosis of periodic illness

The symptoms of the Armenian disease (we explained what it is) are quite unpleasant.

When diagnosing this disease, you should pay attention to the following criteria:

• Periods of short attacks that are not associated with a provoking factor and are stereotypical.
• It is noteworthy that the disease affects representatives of specific ethnic groups. However, in children and adolescents it occurs quite early.
• Similar diseases occur in close relatives.
• Kidney amyloidosis occurs, against the background of which the specific laboratory parameters are extremely difficult to determine.

The Armenian genetic disease is absolutely incompatible with pregnancy. Be that as it may, the frequency of seizures in expectant mothers is noticeably reduced.

Treatment

The main therapeutic agent in the fight against this disease is Colchicine. The dosage of this medication is one to two milligrams per day. It has a stabilizing effect on the neutrophil membrane. In most situations, the drug at its root prevents the formation of attacks of periodic disease, while reducing their severity and frequency, and it also prevents renal amyloidosis. The symptoms and treatment of Armenian disease are interrelated.

Initially, treatment for this disease was predominantly symptomatic. Doctors began using methods to prevent attacks in 1972, when the drug Colchicine was developed. In practice, it turns out that therapy extends for the rest of the patients’ lives. The mechanism of action of the drug remains unclear. It works by inhibiting prostaglandins and has anti-inflammatory properties, markedly reducing vascular permeability.

As for prognosis, the disease may lead to temporary disability. With stable strengthening of amyloidosis, the onset of renal failure is likely, which will most likely inevitably lead to disability. A positive effect, as a rule, occurs when treatment is started in a timely manner. For this reason, it is welcomed and therefore doctors strongly recommend it to suffering patients.

There is a cure for the Armenian disease. More on this later.

Human genes and the drug "Colchicine"

An attack of a periodic illness often begins suddenly and disappears just as suddenly. Sometimes it happens that the disease goes away for a long time, and sometimes even forever. But most often, in the absence of serious therapeutic measures, this disease can acquire irreversible consequences. Against the background of all sorts of clinical manifestations, the disease goes by many names, which were mentioned at the beginning of the article. For a long time, doctors believed that it was purely genetic. Most often, it was diagnosed among Armenians, Jews, Greeks and Arabs, which, among other things, gave it another unofficial name - “disease of the old blood.” Experts to this day believe that the main reason for the manifestation of the Armenian disease, according to patients, is a certain genetic mutation that can form in old nations.

Such complex explanations were, to some extent, convenient, since they allowed science to find a worthy justification for its shameful impotence. The pain, which even the most powerful drugs cannot relieve, as well as the depressed state of health, accompanied by muscle numbness, were explained by genetics, and nothing could be done. But over time, Colchicine was developed - an excellent drug that can bring significant relief during fever. But it turned out that this remedy is helpless against one of the most terrible consequences of the disease - amyloidosis, which is an irreversible change in body tissues, most often occurring in the kidneys.

Risk factors for disease manifestation

The cause of this disease is often psychological trauma. In most cases, the disease can worsen in situations where a person finds himself in a life situation accompanied by a long-term depressed and depressed state, as well as a feeling of insecurity. Experienced fears have a great influence on the development of the disease. Seizures that occur at an early age can often be triggered by interruption of the child's connection with the mother. This explains why the vast majority of patients have all the signs of depression, especially of a masked nature, when they are expressed not in mental manifestations, but in pain in various parts of the body, for example, in the head, muscles, joints or abdominal cavity.

In the twentieth century, there were a huge number of factors that contributed to the spread of this disease and the increase in the number of corresponding patients. Among them: resettlement, genocide, destruction of former foundations, rallies and earthquakes, as well as the massacre in Sumgait, war and blockade.

Today, all over the world, medicine is considering a psychosomatic disorder of a man-made nature, which, as a rule, occurs in people who have suffered various disasters and horrors. The description of these factors expresses the essence of the initial formation of periodic Armenian disease. That is, if we talk about the role that heredity plays in the development of this dangerous disease, then we should remember that this disease carries a deep-seated genetic fear of a number of the mentioned peoples.

Familial Mediterranean fever (FMF), or periodic illness (PF) is an inflammatory disease that 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 the 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 for no apparent reason. But some people note that attacks appear after heavy physical exertion 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 apparent reason. 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 elevated levels of inflammatory markers, including elevated white blood cell counts.

5. Genetic analysis.

Some clinics can conduct genetic analysis, which helps identify the defect in the gene responsible for the 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 treatment method is 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 of 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 latest options are a new group of drugs 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. We are talking 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. Take preventive medications (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. It is possible that 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 low-fat diet 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 of the disease, which is 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 is usually referred to as 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 other smaller joints are affected. The arthritis usually resolves without causing joint destruction.

4. Infertility.

An uncontrolled inflammatory process can cause damage to the 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 an unpleasant, painful condition that constantly affects daily routine and reduces quality of life. Sometimes patients even have to take narcotic analgesics to alleviate daily suffering.

Konstantin Mokanov

Manifested by periodically recurrent serositis and frequent development of amyloidosis. It is found mainly among representatives of nationalities whose ancestors lived in the Mediterranean basin, 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 disruption of the immune and endocrine systems, protein synthesis, and 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 the chronic course of P. b., there are no gross anatomical changes. 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. Increased blood vessels and nonspecific cellularity are also possible. 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. the variant 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 of the small intestine. During the operation, only signs of superficial serous peritonitis and a moderate adhesive process are detected. Unlike acute surgical diseases of the abdominal cavity, all symptoms disappear spontaneously after 2-4 days. In rare cases, usually after repeated operations, mechanical inflammation may develop, which is facilitated by severe gastrointestinal and biliary tract problems caused by P. b. and detected by X-ray examination of the abdominal organs during an attack of the disease.

Thoracic variant of P. b., observed less frequently. characterized by inflammation of the pleura, which occurs in one or the other half of the 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 at normal body temperature. 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 of 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 onset of pain, sometimes accompanied by chills, reaches various levels and decreases to normal levels 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 the inflammatory reaction or the degree of renal failure. At the first manifestations of P. b. differential diagnosis 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. Patients are characterized by good health 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 of illness 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 is started, the faster the positive result comes. Therefore, it is very important for patients with P. b. for early identification of individuals in need of 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 aid. - M.: Great Russian Encyclopedia. 1994 3. Encyclopedic Dictionary of Medical Terms. - M.: Soviet Encyclopedia. - 1982-1984.

See what “Periodic disease” is in other dictionaries:

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, 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 familial, 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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