Familial Mediterranean Fever (FMF) in Turkey: Results of a nationwide multicenter study

Mehmet Tunca, Huri Ozdogan, Ozgur Kasapcopur, Fatos Yalcinkaya, Ercan Tutar, Rezan Topaloglu, Engin Yilmaz, Mustafa Arici, Aysin Bakkaloglu, Nesrin Besbas, Tekin Akpolat, Ayhan Dinc, Eren Erken, Kazim Tirpan, Huseyin T.E. Ozer, Mujde Soyturk, Taskin Senturk, Banu Balci, Meral Ozguc, Munis DundarEce Akar, Duygu Ozel, Munis Dundar, Ramazan Gunesacar, David R. Booth, Philip N. Hawkins, Isabelle Touitou, Ivona Aksentijevich, Yakov Matzner, Serap Arslan, Yasemin Balaban, Figen Batman, Yusuf Bayraktar, Sule Apras, Meral Calguneri, Ali Duzova, Taylan Kav, Fatih Ozaltin, Halis Simsek, Bulent Sivri, Gonca Tatar, Nurullah Akkoc, Salih Kavukcu, Alper Soylu, Mehmet Turkmen, Erbil Unsal, Nil Arisoy, Salim Caliskan, Feride Gogus, Seval Masatlioglu, Lale Sever, Nermin Akkok, Nilgun Cakar, Nazli Kara, Hulusi Kocak, Sila Ozalp, Ilmay Bilge, Emre Sevinc, Ahmet Gul, Sevil Kamali, Banu Sadikoglu, Fatih Selcukbiricik, Aydan Sirin, Aysegul Sucu, Kenan Bek, Mehmet Bulbul, Ali Delibas, Gulay Demircin, Ozlem Erdogan, Ayse Oner, Ekim Mesiha, Nuray Ozkaya, Mustafa Tekin, Erkan Demirkaya, Hakan Erdem, Faysal Gok, Salih Pay, Ismail Islek, Yasemin Kabasakal, Gokhan Keser, Mustafa Ozmen, Emel Akoglu, Pamir Atagunduz, Haner Direskeneli, Musa Temel, Serhan Tuglular, Necla Buyan, Sevcan Bakkaloglu, Ulver Derici, Berna Goker, Suleyman Kalman, Ozan Ozkaya, Ruhan Dusunsel, Zubeyde Gunduz, M. Hakan Poyrazoglu, Cengiz Korkmaz, Esra Baskin, Hamide Kart Koseoglu, Umit Saatci, Eftal Yucel, Erkan Coban, Gulsen Yakupoglu, Faruk Oktem, Ercan Tunc, Veli Cobankara

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Abstract

Familial Mediterranean fever (FMF) is an autosomal recessive disease that is prevalent among eastern Mediterranean populations, mainly non-Ashkenazi Jews, Armenians, Turks, and Arabs. Since a large proportion of all the FMF patients in the world live in Turkey, the Turkish FMF Study Group (FMF-TR) was founded to develop a patient registry database and analyze demographic, clinical, and genetic features. The cohort was composed of 2838 patients (mean age, 23.0 ± 13.33 yr; range, 2-87 yr), with a male:female ratio of 1.2:1. There was a mean period of 6.9 ± 7.65 years from disease onset to diagnosis; the period was about 2 years shorter for each decade since 1981. Ninety-four percent of patients were living in the central-western parts of the country; however, their familial origins (70% from the central-eastern and Black Sea regions) reflected not only the ongoing east to west migration, but also the historical roots of FMF in Turkey. Patients' clinical features included peritonitis (93.7%), fever (92.5%), arthritis (47.4%), pleuritis (31.2%), myalgia (39.6%), and erysipelas-like erythema (20.9%). Arthritis, arthralgia, myalgia, and erysipelas-like erythema were significantly more frequent (p < 0.001) among patients with disease onset before the age of 18 years. Genetic analysis of 1090 patients revealed that M694V was the most frequent mutation (51.4%), followed by M680I (14.4%) and V726A (8.6%). Patients with the M694V/M694V genotype were found to have an earlier age of onset and higher frequencies of arthritis and arthralgia compared with the other groups (both p < 0.001). In contrast to other reported studies, there was no correlation between amyloidosis and M694V homozygosity in this cohort. However, amyloidosis was still remarkably frequent in our patients (12.9%), and it was prevalent (27.8%) even among the 18 patients with a disease onset after age 40 years. Twenty-two patients (0.8%) had nonamyloid glomerular diseases. The high prevalence of vasculitides (0.9% for polyarteritis nodosa and 2.7% for Henoch-Schönlein purpura) and high frequency of pericarditis (1.4%) were striking findings in the cohort. Phenotype II cases (those patients with amyloidosis as the presenting or only manifestation of disease) were rare (0.3% or less). There was a high rate of a past diagnosis of acute rheumatic fever, which suggested a possible misdiagnosis in children with FMF presenting with recurrent arthritis. To our knowledge, this is the largest series of patients with FMF reported from 1 country. We describe the features of the disease in the Turkish population and show that amyloidosis is still a substantial problem.

Original languageEnglish (US)
Pages (from-to)1-11
Number of pages11
JournalMedicine
Volume84
Issue number1
DOIs
StatePublished - Jan 1 2005

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  • Medicine(all)

Cite this

Tunca, M., Ozdogan, H., Kasapcopur, O., Yalcinkaya, F., Tutar, E., Topaloglu, R., Yilmaz, E., Arici, M., Bakkaloglu, A., Besbas, N., Akpolat, T., Dinc, A., Erken, E., Tirpan, K., Ozer, H. T. E., Soyturk, M., Senturk, T., Balci, B., Ozguc, M., ... Cobankara, V. (2005). Familial Mediterranean Fever (FMF) in Turkey: Results of a nationwide multicenter study. Medicine, 84(1), 1-11. https://doi.org/10.1097/01.md.0000152370.84628.0c