<\/span><\/h2>\nFamilial Mediterranean fever is hereditary autoinflammatory<\/span> syndrome<\/span> characterized by recurrent<\/span> short episodes of high fever associated with abdominal pain, inflammation<\/span> of joints and other sites of the body and skin eruption<\/span>. If left untreated, amyloidosis commonly develops and can be fatal. Familial Mediterranean fever is the most common periodic fever syndrome.<\/p>\nIn familial Mediterranean fever type 2, amyloidosis is the presenting feature without a history of typical symptoms. febrile<\/span> episodes<\/p>\n<\/span>Who gets familial Mediterranean fever and why?<\/span><\/h2>\nFamilial Mediterranean fever primarily affects specific racial groups originating throughout the eastern Mediterranean Sea. These include:<\/p>\n
\n- Arabs<\/li>\n
- Armenians<\/li>\n
- Italians (mild form)<\/li>\n
- Jews<\/li>\n
- Turks<\/li>\n<\/ul>\n
In these groups, 1 in 25 to 1 in 2,000 people are affected. In comparison, in Western Europeans, the predominance<\/span> is 2.5 per 100,000 (1 in 40,000) people. the carrier<\/span> the rate can be as high as 1 in 3 in some groups. Although previously believed to only affect Sephardic Jews, it has recently been recognized that Ashkenazi Jews suffer from a mild form of the syndrome. Two-thirds of patients develop symptoms before the age of 5 years and 90% within 20 years.<\/p>\nFamilial Mediterranean fever is usually inherited as a autosomal<\/span> recessive condition, meaning both parents must carry the defect gene<\/span> and there is a one in four chance that a child will be affected (MIM 249100). There is a less common autosomal dominant<\/span> form (MIM 134610).<\/p>\n<\/span>\nMolecular<\/span> biology and genetics<\/span><\/h3>\nFamilial Mediterranean fever is usually due to mutations<\/span> in Mediterranean feverMEFV<\/em>) or pyrin gene located in chromosome<\/span> 16 (16p13.3). Mutations in the MEFV<\/em> gene have been found in the 80% of typical cases. More than 100 different mutations related to the disease have been identified. The most commonly reported mutation<\/span>, M694V<\/em>, is associated with severe disease and the development of secondary amyloidosis. Other common mutations are M680I and V726A. 20% of the Ashkenazy Jews carry the E148Q MEFV<\/em> mutation.<\/p>\nthe MEFV<\/em> genetic codes for a protein called pyrin (also known as marenostrin) expressed primarily by inflammatory<\/span> white blood cells like neutrophils<\/span><\/span> and eosinophils<\/span>. The normal form of pyrin suppresses inflammation by downregulating pro-inflammatories. cytokines<\/span> (cellular messenger proteins), positive regulation of anti-inflammatory<\/span> cytokines and the prevention of the production of interleukin<\/span> 1beta (IL-1\u03b2) by inflammasomes. Lack of functional pyrin releases the inflammatory cascade.<\/p>\nThere are also environmental effects on the manifestations of familial Mediterranean fever. For example, Armenians with familial Mediterranean fever residing in Armenia have a incidence<\/span> of amyloidosis from 25 to 48%, while Armenians residing in the US have an incidence of amyloidosis from 0%.<\/p>\n\n
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<\/span>What are the clinical characteristics of familial Mediterranean fever?<\/span><\/h2>\nThe most common clinical characteristics of familial Mediterranean fever are:<\/p>\n
\n- febrile attacks that last 1 to 3 days<\/li>\n
- severe abdominal, chest and\/or joint pain<\/li>\n
- Erysipelas-like changes in the lower legs.<\/li>\n<\/ul>\n
The onset is almost always before 30 years of age. Children younger than 2 years often present with fever alone and progress to more typical attacks by the age of 5 years.<\/p>\n
The characteristics of the recurring acute<\/span> Familial Mediterranean fever episodes are described in the table below.<\/p>\n\n\n\n| Symptom<\/span><\/th>\n | Characteristics<\/th>\n<\/tr>\n |
\n| Fever<\/td>\n | \n\n- high, sharp<\/li>\n
- lasts 1-3 days<\/li>\n<\/ul>\n<\/td>\n<\/tr>\n
\n| Abdominal pain<\/td>\n | \n\n- affects 95%<\/li>\n
- due to inflammation of the linings of the abdominal cavity (peritonitis)<\/li>\n
- severe muscle stiffness, board-like, rebound tenderness<\/li>\n
- associated constipation or diarrhea<\/li>\n
- can mimic symptoms and signs of appendicitis<\/li>\n<\/ul>\n<\/td>\n<\/tr>\n
\n| Chest pain<\/td>\n | \n\n- affects 33-50%<\/li>\n
- due to inflammation of the lining around the lungs (pleuritis)<\/li>\n
- associated with shortness of breath or shallow breathing<\/li>\n
- less commonly due to the inflamed sac around the heart (pericarditis<\/span>, 1%)<\/li>\n<\/ul>\n<\/td>\n<\/tr>\n
\n| Pain and swelling in the joints (arthralgia<\/span>, arthritis<\/span>)<\/td>\n | \n\n- affect up to 75%<\/li>\n
- due to inflammation of the joint lining (synovitis) with neutrophils<\/li>\n
- Arthralgia is common, arthritis is seen in younger patients.<\/li>\n
- Three patterns of arthritis are recognized:\n
\n- \nasymmetric<\/span> non-destructive arthritis presenting as swelling of 1-2 large joints, most commonly ankles, knees or wrists<\/li>\n
- \nchronic<\/span> destructive arthritis<\/li>\n
- migratory polyarthritis<\/span>\n<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<\/td>\n<\/tr>\n
\n| Skin rash<\/td>\n | \n\n- affect 40%<\/li>\n
- various presentations (see below)<\/li>\n<\/ul>\n<\/td>\n<\/tr>\n
\n| Scrotal painorchitis<\/span>)<\/td>\n | \n\n- affects 5%<\/li>\n
- especially young children<\/li>\n<\/ul>\n<\/td>\n<\/tr>\n
\n| Enlarged spleen (splenomegaly)<\/td>\n | \n\n- especially in children<\/li>\n<\/ul>\n<\/td>\n<\/tr>\n
\n| Muscle pain (myalgia<\/span>)<\/td>\n | \n\n- most commonly muscle pain in the legs after exercise<\/li>\n
- Rarely, pain and weakness can last for weeks, resulting in an inability to walk (\u201cprolonged febrile myalgia\u201d).<\/li>\n<\/ul>\n<\/td>\n<\/tr>\n
\n| Neurological symptoms<\/td>\n | \n\n- affect 10-15%<\/li>\n
- due to inflammation of the linings around the brain (aseptic meningitis<\/span>)<\/li>\n
- headache: one series reported 45% in association with febrile episodes<\/li>\n
- abdominal epilepsy<\/li>\n
- Feverish convulsions<\/li>\n<\/ul>\n<\/td>\n<\/tr>\n
\n| Amyloidosis<\/td>\n | \n\n- The biggest complication of FMF<\/li>\n
- can cause kidney or liver failure and death<\/li>\n
- can also result in a peripheral<\/span> neuropathy<\/span>\n<\/li>\n<\/ul>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n
<\/span>What are the characteristics of the skin rash?<\/span><\/h3>\n\n\n\nCutaneous<\/span> characteristics of familial Mediterranean fever<\/caption>\n<\/tbody>\n\n\n| \n Erysipelas-type lesions<\/td>\n | \n\n- the most distinctive of skin changes<\/li>\n
- occur in 15-20% of children<\/li>\n
- good-demarcated<\/span>, warm, red and painful plates<\/span>\n<\/li>\n
- commonly on the front of the legs between the ankle and knee, but characteristically the top of the foot or over the medium<\/span> ankle malleoli<\/li>\n
- up to 15 cm in diameter<\/li>\n
- often associated with joint pain<\/li>\n
- whether it's unilateral<\/span> or symmetrical<\/span>\n<\/li>\n<\/ul>\n<\/td>\n<\/tr>\n
\n| Henoch-Sch\u00f6nlein purple<\/span><\/td>\n | \n\n- reported in 5% of children<\/li>\n<\/ul>\n<\/td>\n<\/tr>\n
\n| Non-specific purple\n<\/td>\n | \n\n- reported in 5% of children<\/li>\n
- seen on the face, trunk and extremities<\/li>\n
- a common finding in children<\/li>\n<\/ul>\n<\/td>\n<\/tr>\n
\n| Polyarteritis nodosa<\/td>\n | \n\n- queer<\/li>\n
- tends to occur at an early age<\/li>\n
- associated with peri-renal<\/span> hematoma<\/span>\n<\/li>\n<\/ul>\n<\/td>\n<\/tr>\n
\n| Angioedema<\/span><\/td>\n | \n\n- rarely reported<\/li>\n<\/ul>\n<\/td>\n<\/tr>\n
\n| Redness of the palms<\/td>\n | \n\n- rarely reported<\/li>\n<\/ul>\n<\/td>\n<\/tr>\n
\n| Raynaud's phenomenon<\/span><\/td>\n | \n\n- rarely reported<\/li>\n<\/ul>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n
<\/span>What triggers the attacks?<\/span><\/h2>\nThe frequency of episodes is variable, from weekly to every few years. Attacks can be caused by:<\/p>\n \n- Exercise<\/li>\n
- Infection<\/span><\/li>\n
- Menstruation<\/li>\n
- Stress.<\/li>\n<\/ul>\n
Acute attacks occur spontaneously. Between episodes, health is normal.<\/p>\n <\/span>How is familial Mediterranean fever diagnosed?<\/span><\/h2>\nThe diagnosis of familial Mediterranean fever is made using the Tel-Hashomer criteria:<\/p>\n \n- The diagnosis is definitive if 2 major criteria or 1 major + 2 minor criteria are met.<\/li>\n
- The diagnosis is probable if 1 major + 1 minor criterion are met.<\/li>\n<\/ul>\n
<\/span>Main criteria<\/span><\/h3>\n\n- Recurrent febrile episodes associated with peritonitis, pleuritis or synovitis.<\/li>\n
- Type AA amyloidosis without a predisposing disease<\/li>\n
- Favorable response to daily colchicine.\n<\/li>\n<\/ol>\n
<\/span>Minor criteria<\/span><\/h3>\n\n- Recurrent febrile episodes<\/li>\n
- \n
Erysipelas erythema<\/span>\n<\/li>\n- A positive history of familial Mediterranean fever in a first-degree relative<\/li>\n<\/ol>\n
\n \n \n \n<\/div><\/div><\/div><\/div>\n <\/span>Research on familial Mediterranean fever.<\/span><\/h2>\nBlood tests during an attack can show:<\/p>\n \n- Increased white blood cell count (leukocytosis<\/span>), erythrocytes<\/span> sedimentation rate (ESR<\/span>), serum<\/span> fibrinogen<\/span>, C-reactive protein<\/span> (CRP<\/span>)<\/li>\n
- Increased serum IgD in 10%.<\/li>\n<\/ul>\n
X-rays of the abdomen often reveal multiple levels of fluid suggesting an \u201cacute abdomen.\u201d<\/p>\n A skin biopsy<\/span> erysipelas type injury<\/span> can show a heavy infiltrate<\/span> of neutrophils (white blood cells). Leukocytoclastic<\/span> vasculitis<\/span> it's seen in biopsies<\/span> of Henoch-Sch\u00f6nlein purpura or polyarteritis nodosa type lesions.<\/p>\nInvestigations for myalgia (muscle pain) reveal normal muscle enzymes<\/span>, electromyography (EMG) and muscle biopsy.<\/p>\nLa amiloidosis se presenta con mayor frecuencia como proteinuria sin gl\u00f3bulos rojos o presi\u00f3n arterial elevada.<\/p>\n La secuenciaci\u00f3n de genes puede ser realizada por laboratorios especializados como an\u00e1lisis de mutaciones espec\u00edficas (buscando las mutaciones m\u00e1s comunes) o an\u00e1lisis de secuencia de exones seleccionados (observando el ex\u00f3n 10 y posiblemente otros). Una vez que se han identificado las mutaciones gen\u00e9ticas en el paciente, el estado de portador de los padres, la detecci\u00f3n de otros parientes consangu\u00edneos de primer grado, incluso si asymptomatic<\/span>and | | | | | | | | | | | | | | | | |