FMF
; It is an autoinflammatory disease with autosomal recessive inheritance, self-limiting, recurring at irregular intervals, and characterized by attacks of fever and serositis (peritonitis, pleuritis, pericarditis).
• It is the most common hereditary autoinflammatory disease.
• It mostly occurs in childhood and young adulthood (< 20 years).
Pathogenesis
• Mutations in the MEFV (MEditerranean FeVer) gene on chromosome 16 cause FMF.
• The product of the MEFV gene is pyrin (marenostrin). Pyrin; It prevents the formation of IL-1 (anti-inflammatory).
• With the MEFV gene mutation, the amount of pyrin decreases, inflammation cannot be suppressed and FMF attacks occur.
• The most common mutation in FMF cases is M694V.
Acute attack
• Characteristics of FMF attacks;
o Usually characterized by fever (most common finding) and serositis / synovitis.
o It often goes away on its own within a few days.
o Attacks can be triggered by nonspecific stimuli such as exercise, menstruation, and emotional stress.
• Peritonitis (most common attack type)
o The clinical spectrum may range from mild abdominal pain to severe peritonitis.
o It can mimic acute abdomen, so many patients have a history of appendectomy.
• Pleuritis
o It usually presents with unilateral, pleuritic chest pain.
• Arthritis/ arthralgia
o In general, it affects the large joints of the lower extremities such as knees, ankles and hips more frequently.
• Erysipelas-like erythema
o Characteristic skin finding (pathognomonic) in FMF.
o It happens on the back of the foot, ankle and tibia.
• Other findings
o Frequency of IgA vasculitis and PAN is increased in FMF patients.
Amyloidosis
• Serum amyloid A is high in FMF, even during the attack period. Therefore, the risk of amyloidosis (AA type) is high.
• Renal amyloidosis is dominant in the clinic. The first finding is proteinuria, if left untreated, end-stage renal disease may develop.
• Risk factors for amyloidosis; Late diagnosis of FMF, early onset of the disease, noncompliance with colchicine treatment, male gender, family history of amyloidosis related to FMF, M694V homozygous mutation.
laboratory findings
• During FMF attacks, there is a non-specific acute phase response (increased leukocyte, ESR, CRP, serum amyloid A, fibrinogen, etc.).
Diagnosis
• The diagnosis is made by combining the history and clinical findings.
• Clues in the history and clinical findings:
o Recurrent episodes of fever accompanied by peritonitis, pleuritis or synovitis
o AA amyloidosis not related to any disease
o Response to continued colchicine therapy
o Erysipelas-like erythema
o History of FMF in first degree relatives
• MEFV gene analysis should be requested in cases where clinical suspicion is high but in between.
Treatment
• The first choice in treatment is colchicine.
o Colchicine is a microtubule inhibitor; inhibits leukocyte functions such as movement, lysosomal degranulation, and chemotaxis.
o Colchicine is effective in ending and preventing attacks.
o It prevents the development of amyloidosis and can stop the progression of advanced amyloidosis nephropathy.
o Side effects;
The most common side effects are GI intolerance and diarrhea.
Bone marrow suppression, peripheral neuropathy, myopathy may develop.
o Colchicine does not cause sterility. It is safe in pregnancy and lactation.
• IL-1 antagonists (anakinra, rilonacept and canakinumab) can be given in cases unresponsive to colchicine.