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Aktuelle Rheumatologie 2017; 42(01): 46-52
DOI: 10.1055/s-0042-118880
Übersichtsarbeit
© Georg Thieme Verlag KG Stuttgart · New York

Familiäres Mittelmeerfieber- aktuelle Empfehlungen zu Diagnostik und Therapie gemäß der EULAR- und SHARE-Initiativen

Familial Mediterranean Fever: Current Recommendations for Diagnostics and Treatment Based on the EULAR and SHARE Initiatives
Anna Hitzegrad
1   Klinik für Pädiatrie mit Schwerpunkt Pneumologie und Immunologie, Campus Virchow-Klinikum, Charité Universitätsmedizin Berlin, Berlin
,
Tilmann Kallinich
1   Klinik für Pädiatrie mit Schwerpunkt Pneumologie und Immunologie, Campus Virchow-Klinikum, Charité Universitätsmedizin Berlin, Berlin
› Author Affiliations
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Publication History

Publication Date:
06 February 2017 (online)

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Zusammenfassung

Die Diagnose des Familiären Mittelmeerfiebers (FMF) wird anhand der Klinik gestellt. Seit der Entdeckung des MEFV-Gen (MEditerranean FeVer) kann eine genetische Untersuchung die Diagnostik ergänzen, wobei die Interpretation des genetischen Befunds oftmals eine Herausforderung darstellt. Darüberhinaus wurden Fragen zur Dosierung des Colchizins, zum Management von Nebenwirkungen, zum Einsatz unter speziellen Bedingungen und zur Definition eines Therapieversagens in der Vergangenheit häufig wenig klar formuliert. Im folgenden Artikel werden daher aktuelle Empfehlungen von Konsensusprozessen der SHARE-Initiative aus dem Jahr 2015 und der EULAR-Initiative aus dem Jahr 2016 zum Management des FMF präsentiert und erläutert, die den aktuellen Kenntnisstand bei der Erkrankung widerspiegeln und helfen die Versorgung der Patienten zu vereinheitlichen und zu verbessern.

Abstract

The diagnosis of Familial Mediterranean Fever (FMF) is based on clinical findings. Since the discovery of the MEFV-gene (MEditerranean FeVer), a genetic test can aid the diagnostic process, but the interpretation of the genetic findings can be difficult. Furthermore, questions regarding the dose of colchicine, the management of side-effects, application under special circumstances and the definition of treatment failure were often not clearly expressed in the past. The article at hand presents and explains the latest recommendations resulting from consensus procedures of the SHARE initiative from the year 2015 and the EULAR initiative from the year 2016 regarding the management of FMF, which reflect the latest state of scientific knowledge and may help to standardise and improve patient care.

Schlüsselwörter

Familiäres Mittelmeerfieber (FMF) - MEFV-Gen - Colchizintherapie

Key words

familial mediterranean fever (FMF) - MEFV-gene - colchicine therapy
 

  • Literatur

  • 1 Toplak N, Frenzel J, Ozen S. et al. An international registry on autoinflammatory diseases: the Eurofever experience. Ann Rheum Dis 2012; 71: 1177-1182
    CrossrefPubMedGoogle Scholar
  • 2 Ter Haar N, Lachmann H, Ozen S. et al. Treatment of autoinflammatory diseases: results from the Eurofever Registry and a literature review. Ann Rheum Dis 2013; 72: 678-685
    CrossrefPubMedGoogle Scholar
  • 3 The International FMF Consortium. Ancient missense mutations in a new member of the RoRet gene family are likely to cause familial Mediterranean fever. Cell 1997; 90: 797-807
    CrossrefPubMedGoogle Scholar
  • 4 The French FMF Consortium. A candidate gene for familial Mediterranean fever. Nat Genet 1997; 17: 25-31
    CrossrefPubMedGoogle Scholar
  • 5 Masters SL, Simon A, Aksentijevich I. et al. Horror autoinflammaticus: the molecular pathophysiology of autoinflammatory disease. Ann Rev Immunol 2009; 27: 621-668
    CrossrefPubMedGoogle Scholar
  • 6 Chae JJ, Cho YH, Lee GS. et al. Gain-of-function pyrin mutations induce NLRP3 protein-independent Interleukin-1ß activation and severe autoinflammation in mice. Immunity 2011; 34: 755-768
    CrossrefPubMedGoogle Scholar
  • 7 Sohar E, Gafni J, Pras M. et al. Familial Mediterranean fever. A survey of 470 cases and review of the literature. Am J Med 1967; 43: 227-253
    CrossrefPubMedGoogle Scholar
  • 8 Kallinich T. Natürlicher Krankheitsverlauf und klinische Manifestation. In: Kallinich T, Wittkowski H. Familiäres Mittelmeerfieber. 1. Aufl Bremen: UNI-MED; 2014
    Google Scholar
  • 9 Sneh E, Pras M, Michaeli D. et al. Protracted arthritis in familial Mediterranean fever. Rheumatol Rehabil 1977; 16: 102-106
    CrossrefPubMedGoogle Scholar
  • 10 Kaushansky K, Finerman GA, Schwabe AD. Chronic destructive arthritis in familial Mediterranean fever: the predominance of hip involvement and its management. Clin Orthop Relat Res 1981; 155: 156-161
    PubMedGoogle Scholar
  • 11 Kasifoglu T, Calisir C, Cansu DÜ. et al. The frequency of sacroiliitis in familial Mediterranean fever and the role of HLA-B27 and MEFV mutations in the development of sacroiliitis. Clin Rheumatol 2009; 28: 41-46
    CrossrefPubMedGoogle Scholar
  • 12 Cabili S, Zemer D, Pras M. et al. The prevention of amyloidosis in familial Mediterranean fever with colchicine. Proc Eur Dial Transplant Assoc Eur Ren Assoc 1985; 21: 709-711
    PubMedGoogle Scholar
  • 13 Zemer D, Pras M, Sohar E. et al. Colchicine in the prevention and treatment of the amyloidosis of familial Mediterranean fever. N Engl J Med 1986; 314: 1001-1005
    CrossrefPubMedGoogle Scholar
  • 14 Korkmaz C, Özdogan H, Kasapcopur Ö. et al. Acute phase response in familial Mediterranean fever. Ann Rheum Dis 2002; 61: 79-81
    CrossrefPubMedGoogle Scholar
  • 15 Lachmann HJ, Sengül B, Yavuzsen TU. et al. Clinical and subclinical inflammation in patients with familial Mediterranean fever and in heterozygous carriers of MEFV mutations. Rheumatology 2006; 45: 746-750
    CrossrefPubMedGoogle Scholar
  • 16 Samuels J, Aksentijevich I, Torosyan Y. et al. Familial Mediterranean fever at the millenium. Clinical spectrum, ancient mutations and the survey of 100 American referrals to the National Institute of Health. Medicine 1998; 77: 268-297
    CrossrefPubMedGoogle Scholar
  • 17 Schwabe AD, Peters RS. FMF in Armenians. Analysis of 100 cases. Medicine 1974; 53: 453-462
    PubMedGoogle Scholar
  • 18 Ben-Chetrit E, Levy M. Familial Mediterranean fever. Lancet 1998; 351: 659-664
    Google Scholar
  • 19 Kallinich T. Neues zum familiären Mittelmeerfieber. Arthritis+rheuma 2013; 33: 379-385
    PubMedGoogle Scholar
  • 20 Tunca M, Kirkali G, Soytürk M. et al. Acute phase response and evolution of familial Mediterranean fever. Lancet 1999; 353: 1415
    PubMedGoogle Scholar
  • 21 Tamir N, Langevitz P, Zemer D. et al. Late-onset familial Mediterranean fever (FMF): a subset with distinct clinical, demografic, and molecular genetic characteristics. Am J Genet 1999; 87: 30-35
    CrossrefPubMedGoogle Scholar
  • 22 Demirkaya E, Saglam C, Turker T. et al. Performance of different diagnostic criteria for familial Mediterranean fever in children with periodic fevers: results from a multicenter international registry. J Rheumatol 2016; 43: 154-160
    CrossrefPubMedGoogle Scholar
  • 23 Tunca M, Akar S, Onen F. et al. Familial Mediterranean fever (FMF) in Turkey. Results of a nationwide multicenter study. Medicine 2005; 84: 1-11
    CrossrefPubMedGoogle Scholar
  • 24 Zemer D, Livneh A, Danon YL. et al. Long-term colchicine treatment in children with familial Mediterranean fever. Arthritis Rheum 1991; 34: 973-977
    CrossrefPubMedGoogle Scholar
  • 25 Federici S, Sormani MP, Ozen S. et al. Evidence- based provisional clinical classification criteria for autoinflammatory periodic fevers. Ann Rheum Dis 2015; 74: 799-805
    CrossrefPubMedGoogle Scholar
  • 26 Giancane G, ter Haar NM, Wulffraat N. et al. Evidence-based recommendations for genetic diagnosis of familial Mediterranean fever. Ann Rheum Dis 2015; 74: 635-641
    CrossrefPubMedGoogle Scholar
  • 27 Ozen S, Demirkaya E, Erer B. et al. EULAR recommendations for the management of familial Mediterranean fever. Ann Rheum Dis 2016; 75: 644-651
    CrossrefPubMedGoogle Scholar
  • 28 Padeh S, Livneh A, Pras E. et al. Familial Mediterranean fever in the first two years of life: A unique phenotype of disease in evolution. J Pediatr 2010; 156: 985-989
    CrossrefPubMedGoogle Scholar
  • 29 Padeh S, Livneh A, Pras E. et al. Familial Mediterranean fever in children presenting with attacks of fever alone. J Rheumatol 2010; 37: 865-869
    CrossrefPubMedGoogle Scholar
  • 30 Ben-Chetrit E, Touitou I. Familial Mediterranean fever in the world. Arthritis Rheum 2009; 61: 1447-1453
    CrossrefPubMedGoogle Scholar
  • 31 Ozen S, Demirkaya E, Amaryan G. et al. Results from a multicentre international registry of familial Mediterranean fever: impact of environment on the expression of a monogenic disease in children. Ann Rheum Dis 2014; 73: 662-667
    PubMedGoogle Scholar
  • 32 Padeh S, Shinar Y, Pras E. et al. Clinical and diagnostic value of genetic testing in 216 Israeli children with familial Mediterranean fever. J Rheumatol 2003; 30: 185-190
    PubMedGoogle Scholar
  • 33 Kogan A, Shinar Y, Lidar M. et al. Common MEFV mutations among Jewish ethnic groups in Israel: high frequency of carrier and phenotyp III states and absence of a perceptible biological advantage for the carrier state. Am J Med Genet 2001; 102: 272-276
    CrossrefPubMedGoogle Scholar
  • 34 Koné-Paut I, Hentgen V, Guillaume-Czitrom S. et al. The clinical spectrum of 94 patients carrying a single mutated MEFV allele. Rheumatology 2009; 48: 840-842
    CrossrefPubMedGoogle Scholar
  • 35 Touitou I. The spectrum of familial Mediterranean fever (FMF) mutations. Eur J Hum Genet 2001; 9: 473-483
    CrossrefPubMedGoogle Scholar
  • 36 Bernot A, da Silva C, Petit JL. et al. Non-founder mutations in the MEFV Gene establish this gene as the cause of familial Mediterranean fever (FMF). Hum Mol Genet 1998; 7: 1317-1325
    CrossrefPubMedGoogle Scholar
  • 37 Ben-Chetrit E, Lerer I, Malamud E. et al. The E148Q mutation in the MEFV Gene: is it a disease-causing mutation or a sequence variant?. Hum Mutat 2000; 15: 385-386
    PubMedGoogle Scholar
  • 38 Marek-Yagel D, Bar-Joseph I, Pras E. et al. Is E148Q a benign polymorphism or a disease causing mutation?. J Rheumatol 2009; 36: 2372
    CrossrefPubMedGoogle Scholar
  • 39 Soriano A, Pras E. Familial Mediterranean fever: genetic update. IMAJ 2014; 16: 274-276
    PubMedGoogle Scholar
  • 40 Ben-Chetrit E, Backenroth R. Amyloidosis induced, end stage renal disease in patients with familial Mediterranean fever is highly associated with point mutations in the MEFV gene. Ann Rheum Dis 2001; 60: 146-149
    CrossrefPubMedGoogle Scholar
  • 41 Ozturk C, Halicioglu O, Coker I. et al. Association of clinical and genetical features in familial Mediterranean fever with focus on MEFV strip assay sensitivity in 452 children from western Anatolia, Turkey. Clin Rheumatol 2012; 31: 493-501
    CrossrefPubMedGoogle Scholar
  • 42 Mansour I, Delague V, Cazeneuve C. et al. Familial Mediterranean Fever in Lebanon: mutation spectrum, evidence for cases in Maronites, Greek orthodoxes, Greek catholics, Syriacs and Chiites and for an a association between amyloidosis and M694V and M694I mutations. Eur J Hum Genet 2001; 9: 51-55
    CrossrefPubMedGoogle Scholar
  • 43 Cattan D, Dervichian M, Thomas M. et al. MEFV mutations and phenotype-genotype correlations in North African jews and Armenians with familial Mediterranean fever. IMAJ 2001; 3: 803-804
    PubMedGoogle Scholar
  • 44 Melikoglu M, Özdogan H, Korkmaz C. et al. A survey of phenotyp II in familial Mediterranean fever. Ann Rheum Dis 2000; 59: 910-913
    CrossrefPubMedGoogle Scholar
  • 45 Touitou I, Sarkisian T, Medley-Hashim M. et al. Country as the primary risk factor for renal amyloidosis in familial Mediterranean fever. Arthritis Rheum 2007; 56: 1706-1712
    CrossrefPubMedGoogle Scholar
  • 46 Saatci U, Ozen S, Ozdemir S. et al. Familial Mediterranean fever in children: report of a large series and discussion of the risk and prognostic factors of amyloidosis. Eur J Pediatr 1997; 156: 619-623
    CrossrefPubMedGoogle Scholar
  • 47 Akpolat T, Özkaya O, Ozen S. Homozygous M694V as a risk factor for amyloidosis in Turkish FMF patients. Gene 2012; 492: 285-289
    CrossrefPubMedGoogle Scholar
  • 48 Bilginer Y, Akpolat T, Ozen S. Renal amyloidosis in children. Pediatr Nephrol 2011; 26: 215-1227
    PubMedGoogle Scholar
  • 49 Zemer D, Revach M, Pras M. et al. A controlled trial of colchicine in preventing attacks of familial Mediterranean fever. N Engl J Med 1974; 291: 932-934
    CrossrefPubMedGoogle Scholar
  • 50 Dinarello CA, Wolfe SM, Goldfinger SE. et al. Colchicine therapy for familial Mediterranean fever – a double blind trial. N Engl J Med 1974; 291: 934-937
    CrossrefPubMedGoogle Scholar
  • 51 Kallinich T, Wittkowski H, Keitzer R. et al. Neutrophil-derived S100A12 as a novel biomarker of inflammation in familial Mediterranean fever. Ann Rheum Dis 2010; 69: 677-682
    CrossrefPubMedGoogle Scholar
  • 52 Celkan T, Celik M, Kasapcopur Ö. et al. The anemia of familial Mediterranean fever disease. Pediatr Hematol Oncol 2005; 22: 657-665
    CrossrefPubMedGoogle Scholar
  • 53 Duzova A, Ozaltin F, Ozon A. et al. Bone mineral density in children with familial Mediterranean fever. Clin Rheumatol 2004; 23: 230-234
    CrossrefPubMedGoogle Scholar
  • 54 De Beer FC, Mallya RK, Fagan EA. et al. Serum Amyloid-A protein concentrations in inflammatory disease and its relationship to the incidence of reative systemic amyloidosis. Lancet 1982; 2: 231-234
    PubMedGoogle Scholar
  • 55 Kallinich T, Haffner D, Niehues T. et al. Colchicine use in children and adolescents with familial Mediterranean fever: literature review and consensus statement. Pediatrics 2007; 119: 474-483
    CrossrefPubMedGoogle Scholar
  • 56 Hentgen V, Grateau G, Koné-Paut I. et al. Evidence-based recommendations for the practical management of familial Mediterranean fever. Semin Arthritis Rheum 2013; 43: 387-391
    CrossrefPubMedGoogle Scholar
  • 57 Padeh S, Gerstein M, Berkun Y. Colchicine is a safe drug in children with familial Mediterranean fever. J Pediatr 2012; 161: 1142-1146
    CrossrefPubMedGoogle Scholar
  • 58 Ben-Chetrit E, Levy M. Colchicine: 1998 update. Semin Arthritis Rheum 1998; 28: 48-59
    CrossrefPubMedGoogle Scholar
  • 59 Fradkin A, Yahar J, Zemer D. et al. Colchicine-induced lactose malabsorption in patients with familial Mediterranean fever. Isr J Med Sci 1995; 31: 616-620
    PubMedGoogle Scholar
  • 60 Lieber M. Prophylaxe der Schübe und der Langzeitfolgen mit Colchizin. In: Kallinich T, Wittkowski H. Familiäres Mittelmeerfieber. 1. Aufl. Bremen: UNI-MED; 2014
    Google Scholar
  • 61 Van der Hilst JC, Moutschen M, Messiaen PE. et al. Efficacy of anti-IL-1 treatment in familial Mediterranean fever: a systematic review of the literature. Biologics 2016; 10: 75-80
    PubMedGoogle Scholar
  • 62 Yilmaz S, Cinar M, Simsek I. et al. Tocilizumab in the treatment of patients with AA amyloidosis secondary to familial Mediterranean fever. Rheumatology 2015; 54: 564-565
    CrossrefPubMedGoogle Scholar
  • 63 Koga T, Migita K, Kawakami A. Biologic therapy in familial Mediterranean fever. Mod Rheumatol 2016; 1-5
    PubMedGoogle Scholar
  • 64 Yenokyan G, Armenian HK. Triggers for attacks in familial Mediterranean fever: application of the case-crossover design. Am J Epidemiol 2012; 175: 1054-1061
    CrossrefPubMedGoogle Scholar
  • 65 Ben-Chetrit E, Scherrmann JM, Zylber-Katz E. et al. Colchicine disposition in patients with familial Mediterranean fever with renal impairment. J Rheumatol 1994; 21: 710-713
    PubMedGoogle Scholar
  • 66 Niel E, Scherrmann JM. Colchicine today. Joint Bone Spine 2006; 73: 672-678
    CrossrefPubMedGoogle Scholar
  • 67 Ben-Chetrit E, Levy M. Reproductive system in familial Mediterranean fever: an overview. Ann Rheum Dis 2003; 62: 916-919
    CrossrefPubMedGoogle Scholar
  • 68 Ben-Chetrit E, Ben-Chetrit A, Levy M. et al. Pregnancy outcomes in women with familial Mediterranean fever receiving colchicine: is amniocentesis justified?. Arthritis Care Res 2010; 62: 143-148
    PubMedGoogle Scholar
  • 69 Ehrenfeld M, Brzezinski A, Levy M. et al. Fertility and obstetric history in patients with familial Mediterranean fever on long-term colchicine therapy. Br J Obstet Gynaecol 1987; 94: 1186-1191
    CrossrefPubMedGoogle Scholar
  • 70 Yasar O, Iskender C, Kaymak O. et al. Retrospective evaluation of pregnancy outcomes in women with familial Mediterranean fever. J Matern Fetal Neonatal Med 2014; 27: 733-736
    CrossrefPubMedGoogle Scholar
  • 71 Ben-Chetrit E, Scherrmann JM, Levy M. Colchicine in breast milk of patients with familial Mediterranean fever. Arthritis Rheum 1996; 39: 1213-1217
    CrossrefPubMedGoogle Scholar
  • 72 Ben-Chetrit E, Berkun Y, Ben-Chetrit E. et al. The outcome of pregnancy in the wives of men with familial Mediterranean fever treated with colchicine. Semin Arthritis Rheum 2004; 34: 549-552
    CrossrefPubMedGoogle Scholar
  • 73 Yanmaz MN, Özcan AJ, Savan K. The impact of familial Mediterranean fever on the reproductive system. Clin Rheumatol 2014; 33: 1385-1388
    CrossrefPubMedGoogle Scholar
  • 74 Sakallioglu O, Duzova A, Ozen S. Etanercept in the treatment of arthritis in a patient with familial Mediterranean fever. Clin Exp Rheumatol 2006; 24: 435-437
    PubMedGoogle Scholar
  • 75 Kaplan E, Mukamel M, Barash J. et al. Protracted febrile myalgia in children and young adults with familial Mediterranean fever: analysis of 15 patients and suggested criteria for working diagnosis. Clin Exp Rheumatol 2007; 25: 114-117
    PubMedGoogle Scholar
  • 76 Langevitz P, Zemer D, Livneh A. et al. Protracted febrile myalgia in patients with familial Mediterranean fever. J Rheumatol 1994; 21: 1708-1709
    PubMedGoogle Scholar
  • 77 Mercan R, Turcan A, Bitik B. et al. Rapid resolution of protracted febrile myalgia syndrome with anakinra: report of two cases. Mod Rheumatol 2016; 26: 458-459
    CrossrefPubMedGoogle Scholar
  • 78 Ben-Zvi I, Krichely-Vachdi T, Feld O. et al. Colchicine-free remission in familial Mediterranean fever: featuring a unique subset of the disease- a case control study. Orphanet J Rare Dis 2014; 9: 3
    CrossrefPubMedGoogle Scholar
  • 79 Hentgen V, Grateau G, Stankovic-Stojanovic K. et al. Familial Mediterranean fever in heterozygotes. Arthritis Rheum 2013; 65: 1654-1662
    CrossrefPubMedGoogle Scholar