Familial Mediterranean fever FMF is an inherited autoinflammatory disease characterized by recurrent episodes attacks of fever and acute inflammation of the membranes lining the abdomen, ts, and lungs. In some cases, affected individuals may develop skin rashes erysipelas like erythema affecting the lower legs.
Home » Decision Support in Medicine » Pediatrics. Familial Mediterranean fever FMF is the most common inherited periodic fever syndrome and predominantly affects people of Mediterranean origin. FMF is characterized by lifelong recurrent episodes of fever and illness due to seemingly unprovoked systemic inflammation in the absence of autoimmunity or infection. The diagnosis is suspected based on constellation of symptoms including fever pattern, associated symptoms, acute phase response, family history and ethnicity. Patients are asymptomatic and in generally good health between attacks.
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FMF may present initially as functional abdominal pain in children. t aspiration reveals cloudy synovial fluid with primarily neutrophils, increased protein, normal glucose.
An erysipelas-like erythema and tender, erythematous and warm areas of swelling cm in diameter on distal lower extremities is a distinctive symptom of FMF. Cutaneous vasculitis such as Henoch-Schonlein purpura and polyarteritis nodosa may occur in FMF and may precede other more typical disease manifestations. Genotyping is used to confirm diagnosis, but is also helpful for treatment decisions and assessment of long term prognosis. The diagnosis of FMF may be confirmed in symptomatic persons without identifiable MEFV mutations if a 6-month trial of daily colchicine remits attacks that recur after discontinuation of colchicine.
The diagnosis should not be excluded based solely on genetic testing forMEFV mutations if the observed clinical features are characteristic.
To screen initially for FMF, the following laboratory studies are helpful: a CBC with differential during fever episodes and when symptom-free, an ESR and CRP during fever episodes and when symptom-free, a complete metabolic panel, uric acid, LD, ferritin, fibrinogen, quantitative immunoglobulins IgG, IgA, IgM, urinalysis, blood and urine cultures, a PPD, and a 24 hr urine collection for protein and creatinine clearance.
Additional tests can be performed as clinically indicated and often include: C3, C4, haptoglobin, pleural, peritoneal, synovial fluids for culture, cell count, protein, and glucose, skin biopsy for histology, renal or rectal biopsy for histology and staining for amyloid deposition. Genotyping for FMF and other inherited periodic fever syndromes may confirm diagnosis. Imaging studies helpful in confirming FMF or a related disease include: a chest x-ray for infection, inflammatory lung disease or serositis pleuritis, pericarditisan abdominal x-ray, ultrasound or computed tomography CT to evaluate abdominal pain, rule out peritonitis or a surgical emergency, an echocardiogram to rule out pericarditis, and a t magnetic resonance imaging MRI with and without contrast can evaluate for arthritis.
Suspect the diagnosis of FMF if a patient of middle eastern ethnicity presents with recurrent fevers in a typical pattern of days every weeks in association with:. Recurrent pleuritis or chest pain A family history of FMFResolution of fever and associated symptoms when treated with colchicine, but recur when colchicine is discontinued. If serositis present, consider prednisone 0. There is controversy regarding risk versus benefit of chronic colchicine use if MEFV mutations identified by genotyping are considered:.
Alternatively, management depends on genotyping since amyloidosis is associated with particular MEFV mutations:. Patients homozygous for MV mutation or compound heterozygous for MV and another disease-causing mutation VA-EQ should start chronic daily colchicine as soon as diagnosis is confirmed.
Patients without MV or VA-EQ mutations and mild clinical symptoms may not need colchicine unless attacks severe or has amyloidosis. Treatment with colchicine should not be excluded in individuals with typical clinical symptoms who lack an identifiable MEFV mutation.
Canakinumab mg SQ q. Clinical symptoms and range of MEFV mutations in Arabs distinctly different from other ethnicities and vary by country of birth.
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MV is most common mutation, confers highest disease severity and risk of amyloidosis, and predominates in North African and Iraqi Jews, Armenians and Turks. Il-1 beta is the pleiotrophic pyrogen and alarm cytokine and its activation triggers a cascade of events resulting in inflammation and production of other proinflammatory cytokines.
Stimulation of the inflammasome by danger als activates caspase-1, which converts IL-1beta to its bioactive form. Mutations in one or more of the proteins comprising the inflammasome and subsequent effects on IL-1 activity have been shown to cause inherited periodic fever syndromes. Sequestration of the ASC by pyrin also prevents caspase-1activation, inhibiting activation of the inflammasome and production of bioactive IL-1beta.
Colchicine inhibits neutrophil chemotaxis via microtubule depolymerization and reduces production of IL-1beta and other proinflammatory cytokines through NF-kappaB inhibition.
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Secondary amyloidosis is the most serious complication of FMF, which may lead to early death and ificant morbidities. Renal failure due to amyloid-related nephropathy may be first clinical manifestation of FMF. Measurement of the serum SAA level may reflect active amyloid deposition and can help guide therapy.
Proteinuria is measured by a 24 hr urine collection for protein and creatinine clearance. Secondary amyloidosis is then confirmed by biopsy of the kidney or rectum.
Familial mediterranean fever (fmf)
Amyloid also can deposit in the liver, spleen, thyroid, and nervous system. The median survival time of untreated FMF patients with secondary amyloidosis is months from time of diagnosis. Treatment with colchicine or biologic therapy can prolong survival. Most complications of FMF are self-limited, but some do affect health and quality of life: abdominal serositis may lead to unnecessary abdominal surgery and can cause infertility in women secondary to pelvic adhesions and defective ovulation.
Treatment complications may be more common than complications from the disease and may include worsening inflammation, organ toxicity, infection and the possibility of a future malignancy. FMF cannot be prevented since it is a genetic disease.
Conditions and treatments
Genetic counseling is important if FMF is suspected. Prenatal diagnosis may be helpful for some families and requires prior identification of disease-causing mutation s in the parents. The following references provide general and historical overview of FMF and related conditions:. Brit J Hematol.
Curr Allergy Asthma Rep. Clin Exp Med. Samuels, J, Ozen, S. Curr Opin Rheumatol. Simon, A, van der Meer. Goldbach-Mansky, Kastner, DL. J Allergy Clin Immunol. Ann Rev Immunol.
Henderson, C, Goldbach-Mansky, R. Pediatr Nephrol March. Goldfinger, SE. New Engl J Med. Br J Haematol.
J Rheumatol. Use of colchicine for treatment or prophylaxis in FMF patients with one identified mutation not MV or mild presentation. All rights reserved. No sponsor or advertiser has participated in, approved or paid for the content provided by Decision Support in Medicine LLC. Show More. Register. We want you to take advantage of everything Cancer Therapy Advisor has to offer.
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Table I. What about prognosis? Major cause of mortality is renal amyloidosis. Normal lifespan without amyloidosis. MV mutation is associated with a severe phenotype and strongly affects prognosis: Early age of disease onset High frequency of arthritis and rash Increased amyloidosis.
Familial mediterranean fever
Table II gives the risks and benefits of available treatment options. Table II. Epidemiology: Most common inherited periodic fever syndrome. Predominantly affects people of Mediterranean origin. Mutation frequency: in Ashkenazi Jews. Slight male predominance All mutations decrease pyrin function.