Synonym(s)
Familial Mediterranean fever; FMF
History
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Osler, 1895; Janeway and Mosenthal, 1908
Definition
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Hereditary fever syndrome with periodic fever, seizure-like serositis (abdominal cavity, pleura), arthritis, orchitis and possibly volatile, erysipelas-like exanthema.
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Occurrence/Epidemiology
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- More than 10,000 patients are affected worldwide. The disease occurs mainly in the Mediterranean region (e.g. Armenian, Turkish, Arab and Jewish population). Due to immigration, however, this clinical picture is also of differential diagnostic importance in Western countries.
- Depending on the study and the collective, the frequency of heterozygous gene carriers is 1:26 to 1:52. The disease manifests itself when a homozygous (both alleles carry the same mutation) or compound heterozygous (both alleles carry different mutations) status is present. For heterozygous parents, this means that the risk of producing a homozygous or compound heterozygous (diseased) child is 25%.
Etiopathogenesis
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Autosomal recessive mutations of the MEFV gene (Mediterranean fever gene; gene locus: 16p13.3). The resulting functional impairment of the protein encoded by this gene, pyrin (cryopyrin) or also called marenostrin (lat.: mare nostrum for Mediterranean), leads to the triggering of a systemic inflammatory reaction.
Manifestation
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In most cases occurring in childhood and adolescence; in about 90% of patients before the age of 20 LJ.
Clinical features
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Recurrent febrile attacks (in 96% of patients) of irregular periodicity, usually accompanied by acute peritonitis (91%), often also pleuritis (57%), arthritis or sacroiliitis (45%), as well as a volatile, erysipelas-like, 10-15 cm in diameter, macular exanthema with pruritus occurring on one or both sides, especially below the knee (13%). 2% of patients develop amyloidosis.
- Phenotype 1: Beginning with fever attacks.
- Phenotype 2: Amyloidosis as the first manifestation.
Laboratory
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BSG elevated, rarely leukocytosis. Elevated serum amyloid A is only observed in manifest amyloidosis, which is a complication of FMF and not a primary diagnosis. Regular (collective!) urine tests should therefore be an integral part of patient care.
Diagnosis
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Clinical (main criteria: peritonitis, pleuritis, monarthritis, fever, skin symptoms) is diagnostic; signs of inflammation are pronounced in relapses. Diagnosis is confirmed by molecular genetic analysis of the MEFV gene located on the short arm of chromosome 16.
Differential diagnosis
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Differentiation from other forms of periodic fever such as PFAPA syndrome; Muckle-Wells syndrome; Tumor Necrosis Factor Receptor Associated Periodic Syndrome (TRAPS); Hyper-IgD syndrome (HID); Familial cold urticaria. Exclusion of urticaria or urticarial vasculitis.
Complication(s)
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- Consequential damage such as kidney failure due to systemic amyloidosis.
- Infertility in about 30% of women with the disease. 20-30% of pregnancies in patients end in premature abortion.
Therapy
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Colchicine (e.g. Colchicum-Dispert) 0.03 ± 0.02 mg/kg bw/day in 2 ED p.o. or in children under 5 years 0.07 mg/kg bw/day in 2 ED p.o. is well effective in 70-90% of patients. In about 10% of the children, however, colchicine does not have any effect on fever spikes, although a lack of compliance is often the cause. Lifelong colchicine intake leads to a positive influence on fever spikes and prevents complications.
Literature
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- Aldea A et al (2004) A severe autosomal-dominant periodic inflammatory disorder with renal AA amyloidosis and colchicine resistance associated to the MEFV H478Y variant in a Spanish kindred: An unusual familial Mediterranean fever phenotype or another MEFV-associated periodic inflammatory disorder? On J Med Genet 124A: 67-73
- Gershoni-Baruch R et al (2003) Prevalence and significance of mutations in the familial Mediterranean fever gene in Henoch-Schonlein purpura. J Pediatr 143: 658-661
- Janeway TC, Mosenthal HO (1908) An unusual paroxysmal syndrome, probably allied to recurrent vomiting, with a study of the nitrogen metabolism. Trans Ass Am Phys 23: 504-518
- Osler W (1895) On the visceral manifestations of erythema multiforme. On J Med Sci 110: 629
- Panossian A et al (2003) Plasma nitric oxide level in familial Mediterranean fever and its modulations by Immuno-Guard. Nitric oxide 9: 103-110
- Sayarlioglu M et al (2003) Colchicine-induced myopathy in a teenager with familial Mediterranean fever. Ann Pharmacother 37: 1821-1824
- Timmann C et al (2003) Familial Mediterranean fever with amyloidosis associated with novel exon 2 mutation (S1791) of the MEFV gene. Blood Cells Mol Dis 31: 320-323
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Disclaimer
Please ask your physician for a reliable diagnosis. This website is only meant as a reference.
Prof. Dr. med. Peter Altmeyer