THEMAIN FACTORS INTHEORIGIN OFFAMILIAL MEDITERRANEAN FEVER DISEASE Muminova KimsanxonToxtasinovna

Аннотация

Familial Mediterranean fever is an autosomal recessive disorder characterized by recurrent bouts of fever and peritonitis, sometimes with pleuritis, erysipelas-like erythema, arthritis, and, rarely, pericarditis. Amyloidosis may develop, sometimes leading to renal failure. People with genetic origins in the Mediterranean basin are more frequently affected than other ethnic groups. Diagnosis is based on clinical suspicion and genetic testing. Treatment with prophylactic colchicine prevents acute attacks as well as amyloidosis in almost all patients. Patients who are colchicine-resistant or - intolerant may be treated with interleukin-1 inhibitors (anakinra, canakinumab, rilonacept). Prognosis is excellent with treatment. Key words Fever, disease, autosomal recesseve, pericarditis, familial mediterranean fever. Familial Mediterranean fever (FMF) is a disease of people with genetic origins in the Mediterranean basin, predominantly people who have Sephardic Jewish, North African Arab, Armenian, Turkish, Greek, or Italian ancestry. However, cases have occurred among enough other groups (eg, people who have Ashkenazi Jewish, Cuban, or Japanese ancestry), so the diagnosis should not be excluded solely onthebasis ofancestry. FMF is caused by  MutationsintheMEFV gene ontheshort arm ofchromosome 16 The mutation is classically inherited in an autosomal recessive manner, but heterozygotes may manifest a clinical phenotype. FMF mutations are gain-of-function, that is, they confer new or enhanced activity on a protein, with a gene dosage effect (ie, more copies of the abnormal gene convey a greater effect). The MEFV gene normally codes a protein named pyrin, which is expressed incirculating neutrophils. Pyrin plays a role in innate immunity. It senses modifications in the activity of the small GTPase RhoA, a molecular switch that regulates a variety of signal transduction pathways including cytoskeletal organization. Pathogen virulence toxins (such as Clostridioides difficile, Burkholderia cenocepacia, and Vibrio cholera) downregulate RhoA activity and cause an assembly pyrin along with other proteins into a pyrin inflammasome, which eventually results in the production of the proinflammatory cytokine interleukin-1 beta (IL-1 beta). MEFV pathogenic variants favor the active state of pyrin and give rise to cell membrane rupture (pyroptosis) and the release of proinflammatory cytokines. 62 IMPACT FACTOR (RESEARCHBIB) – 7,245 VOLUME 7, ISSUE 2, 2023 There is strong evidence that Yersinia pestis, the cause of bubonic plague, led to the positive selection of FMF-associated MEFV mutations. These mutations confer a survival advantage to certain peoplewho harbor Yersiniapestis. Onset of FMF is usually between the ages of 5 and 15 years but may be much later or earlier, even during infancy. Attacks have no regular pattern of recurrence. They usually last 12 to 72 hours but may last longer. Frequency ranges from 2 attacks/week to 1 attack/year (most commonly, once every 2 to 6 weeks). Physical and emotional stressors (eg, physical trauma, infection, menstruation) may trigger attacks (1). Severity and frequency tend to decrease during pregnancy and in patients with amyloidosis.Spontaneous remissions may last years. Fever as high as 40° C, usually accompanied by peritonitis, is the major manifestation. Abdominal pain (usually starting in one quadrant and spreading to the whole abdomen) occurs in about 95% of patients and can vary in severity with each attack. Decreased bowel sounds, distention, guarding, and rebound tenderness are likely to occur at the peak of an attack and cannot be differentiated from a perforated viscus by physical examination. Consequently, some patients undergo urgent laparotomy before the correct diagnosis is made. With pleural involvement, dyspnea due to pleuritic pain may occur. Other manifestations of FMF include arthritis (in 25%), usually involving the knee, ankle, and hip; an erysipelas-like rash of the lower leg; and scrotal swelling and pain caused by inflammation of the tunica vaginalis ofthe testis.Pericarditis occurs rarely. The pleural, synovial, and skin manifestations ofFMF vary in frequency among different populations (2). Despite the severity of symptoms during acute attacks, most patients recover swiftly and remain free ofillness untiltheirnextattack. 63 IMPACT FACTOR (RESEARCHBIB) – 7,245 VOLUME 7, ISSUE 2, 2023 Pict ure1.Autoinflammatory PeriodicFeverDisorders CAPS = cryopyrin-associated periodic syndromes; FMF = familial Mediterranean fever; NOMID = neonatal-onset multisystem inflammatory disease; PFAPA =periodic fevers with aphthous stomatitis, pharyngitis, and adenitis; TRAPS=tumor necrosis factorreceptor–associated periodicsyndrome. Complicationsoffamilial Mediterranean fever Themost significant long-term complication of FMF is  Chronicrenal failure caused bydeposition ofamyloid protein in thekidneys Amyloid may also bedeposited in thegastrointestinal tract, liver, spleen, heart, test