Abstract
Familial Mediterranean fever (FMF) is inherited autosomal recessively; however, heterozygotes may express FMF phenotype. We aimed to define the characteristics of FMF patients heterozygous for MEFV (MEditerranean FeVer) mutations in whom colchicine was stopped after a period of treatment, with close follow-up. We reviewed the charts of 182 children who were heterozygous for MEFV variants. We excluded the patients (n = 34) heterozygous for MEFV variants of unknown significance and patients with typical periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis syndrome (n = 2). All patients were followed up with their routine analysis and serum amyloid A levels every 6 months while on colchicine treatment and every 3–6 months thereafter. MEFV gene variant analysis was performed with Sanger sequencing. Twenty-two out of 146 heterozygotes initially had FMF phenotype, but colchicine was discontinued after a treatment period. The most common MEFV variant was M694V (86.3 %). The median age at diagnosis/initiation of colchicine was 76 (24–144) months. The median duration of colchicine treatment was 36 (24–110) months. The median age at colchicine cessation was 120 (55–172) months. At the time of colchicine cessation, the median attack- and inflammation-free period was 27 (24–84) months. The median follow-up after colchicine cessation was 22.5 (6–102) months. We re-started colchicine in only two patients because of recurrence of symptoms. Individuals with one mutation only can display FMF phenotype and require colchicine for the clinical and laboratory inflammation. However, in some of these patients, colchicine may be discontinued with very careful follow-up.
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References
Ozen S, Batu ED (2015) The myths we believed in familial Mediterranean fever: what have we learned in the past years? Semin Immunopathol 37(4):363–369. doi:10.1007/s00281-015-0484-6
The International FMF Consortium (1997) Ancient missense mutations in a new member of the RoRet gene family are likely to cause familial Mediterranean fever. Cell 90(4):797–807
French FMF Consortium (1997) A candidate gene for familial Mediterranean fever. Nat Genet 17(1):25–31
Chae JJ, Wood G, Masters SL, Richard K, Park G, Smith BJ, Kastner DL (2006) The B30.2 domain of pyrin, the familial Mediterranean fever protein, interacts directly with caspase-1 to modulate IL-1beta production. Proc Natl Acad Sci U S A 103(26):9982–9987
Goldfinger SE (1972) Colchicine for familial Mediterranean fever. N Engl J Med 287(25):1302
Ozen S, Demirkaya E, Erer B et al (2016) EULAR recommendations for the management of familial Mediterranean fever. Ann Rheum Dis 75(4):644–651. doi:10.1136/annrheumdis-2015-208690
Hentgen V, Grateau G, Kone-Paut I, Livneh A, Padeh S, Rozenbaum M, Amselem S, Gershoni-Baruch R, Touitou I, Ben-Chetrit E (2013) Evidence-based recommendations for the practical management of Familial Mediterranean Fever. Semin Arthritis Rheum 43(3):387–391. doi:10.1016/j.semarthrit.2013.04.011
Livneh A, Zemer D, Langevitz P, Shemer J, Sohar E, Pras M (1993) Colchicine in the treatment of AA and AL amyloidosis. Semin Arthritis Rheum 23(3):206–214
Lachmann HJ, Sengul B, Yavuzsen TU et al (2006) Clinical and subclinical inflammation in patients with familial Mediterranean fever and in heterozygous carriers of MEFV mutations. Rheumotology (Oxford) 45(6):746–750
Marek-Yagel D, Berkun Y, Padeh S, Abu A, Reznik-Wolf H, Livneh A, Pras M, Pras E (2009) Clinical disease among patients heterozygous for familial Mediterranean fever. Arthritis Rheum 60(6):1862–1866. doi:10.1002/art.24570
Kalyoncu M, Acar BC, Cakar N, Bakkaloglu A, Ozturk S, Dereli E, Tunca M, Kasapcopur O, Yalcinkaya F, Ozen S (2006) Are carriers for MEFV mutations “healthy”? Clin Exp Rheumatol 24(5 Suppl 42):S120–S122
Shinar Y, Obici L, Aksentijevich I et al (2012) Guidelines for the genetic diagnosis of hereditary recurrent fevers. Ann Rheum Dis 71(10):1599–1605. doi:10.1136/annrheumdis-2011-201271
Yalcinkaya F, Ozen S, Ozcakar ZB et al (2009) A new set of criteria for the diagnosis of familial Mediterranean fever in childhood. Rheumatology (Oxford) 48(4):395–398. doi:10.1093/rheumatology/ken509
Booty MG, Chae JJ, Masters SL, Remmers EF, Barham B, Le JM, Barron KS, Holland SM, Kastner DL, Aksentijevich I (2009) Familial Mediterranean fever with a single MEFV mutation: where is the second hit? Arthritis Rheum 60(6):1851–1861. doi:10.1002/art.24569
Ben-Zvi I, Krichely-Vachdi T, Feld O, Lidar M, Kivity S, Livneh A (2014) Colchicine-free remission in familial Mediterranean fever: featuring a unique subset of the disease—a case control study. Orphanet J Rare Dis 9:3. doi:10.1186/1750-1172-9-3
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The study was approved by the ethical committee of Hacettepe University.
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Hafize Emine Sönmez and Ezgi Deniz Batu contributed equally to this work.
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Sönmez, H.E., Batu, E.D., Bilginer, Y. et al. Discontinuing colchicine in symptomatic carriers for MEFV (Mediterranean FeVer) variants. Clin Rheumatol 36, 421–425 (2017). https://doi.org/10.1007/s10067-016-3421-8
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DOI: https://doi.org/10.1007/s10067-016-3421-8