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Familial mediterranean fever: assessment of clinical manifestations, pregnancy, genetic mutational analyses, and disease severity in a national cohort

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Abstract

The aims of this study were to investigate the main clinical and laboratory features, including pregnancy and genetic analysis, of Turkish Familial Mediterranean Fever (FMF) patients and to analyze the relationships between genotypic features, age of disease onset, clinical findings, and disease severity. A study was planned within a national network of 22 different centers. Demographics, clinical and laboratory findings, attack characteristics, drugs, pregnancy and birth history, disease severity, and gene mutation analyses were evaluated. Disease severity, assessed using a scoring system developed by Pras et al., was evaluated in relation to gene mutations and age of disease onset. A total of 979 patients (643 females and 336 males; mean age: 35.92 ± 11.97 years) with FMF were included in the study. Of a total of 585 pregnancies, 7% of them resulted in preterm birth and 18.1% resulted in abortions. During pregnancy, there was no FMF attack in 61.4% of patients. Of the MEditerranean FeVer (MEFV) mutations, 150 (24.3%) cases were homozygous, 292 (47.3%) cases were heterozygous, and 175 (28.4%) were compound heterozygous. Patients with homozygous gene mutations had more severe disease activity, earlier age of disease onset, higher rates of joint and skin involvement, sacroiliitis, and amyloidosis. Patients with compound heterozygous genotype displayed severe disease activity in close resemblance to patients with homozygous mutation. In addition, patients with compound heterozygous mutations had higher rates of protracted febrile myalgia and elevated fibrinogen levels. In 63.9% of compound heterozygous patients, age of onset was < 20 years, with greater disease severity, and high rates of attack frequency and colchicine resistance. Our results suggest that indicators for disease severity include early onset of disease and homozygous gene mutations. Furthermore, patients with compound heterozygous mutations displayed significant presentations of severe disease activity.

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Acknowledgements

The authors would like to thank Enago (www.enago.com) for English language review.

Funding

This study was not funded.

Author information

Authors and Affiliations

  1. Department of Physical Medicine and Rehabilitation, Ankara Numune Training and Research Hospital, Ankara, Turkey

    Hatice Bodur & Fatma Gül Yurdakul

  2. Department of Physical Medicine and Rehabilitation, Rheumatology Clinic, Antalya Training and Research Hospital, Antalya, Turkey

    Hasan Fatih Çay & Ülkü Uçar

  3. Department of Physical Medicine and Rehabilitation, Rheumatology Clinic, Bozyaka Training and Research Hospital, İzmir, Turkey

    Ülkü Uçar

  4. Faculty of Medicine, Department of Physical Medicine and Rehabilitation, Bezmialem Vakıf University, Istanbul, Turkey

    Yaşar Keskin & Ozan Volkan Yurdakul

  5. Faculty of Medicine, Department of Physical Medicine and Rehabilitation Rheumatology Clinic, Adnan Menderes University, Aydin, Turkey

    Betül Sargın & Gülcan Gürer

  6. Department of Rheumatology, Aydın State Hospital, Aydin, Turkey

    Betül Sargın

  7. Faculty of Medicine, Department of Physical Medicine and Rehabilitation, Erciyes University, Kayseri, Turkey

    Mustafa Çalış & Hüseyin Kaplan

  8. Faculty of Medicine, Department of Physical Medicine and Rehabilitation, Gaziosmanpaşa University, Tokat, Turkey

    Hülya Deveci

  9. Department of Physical Medicine and Rehabilitation, Training and Research Hospital, Sakarya University, Sakarya, Turkey

    Yıldıray Aydın

  10. Faculty of Medicine, Department of Physical Medicine and Rehabilitation Rheumatology Clinic, Cumhuriyet University, Sivas, Turkey

    Sami Hizmetli & Gökhan Çağlayan

  11. Faculty of Medicine, Department of Physical Medicine and Rehabilitation, Dicle University, Diyarbakır, Turkey

    Remzi Çevik

  12. Faculty of Medicine, Department of Physical Medicine and Rehabilitation, Uşak University, Uşak, Turkey

    Ali Yavuz Karahan

  13. Faculty of Medicine, Department of Physical Medicine and Rehabilitation Rheumatology Clinic, Ankara University, Ankara, Turkey

    İsmihan Sunar

  14. Faculty of Medicine, Department of Physical Medicine and Rehabilitation Rheumatology Clinic, Marmara University, Istanbul, Turkey

    Mehmet Tuncay Duruöz

  15. Faculty of Medicine, Department of Physical Medicine and Rehabilitation Rheumatology Clinic, Necmettin Erbakan University, Konya, Turkey

    Hilal Ecesoy

  16. Faculty of Medicine, Department of Physical Medicine and Rehabilitation Rheumatology Clinic, Gazi University, Ankara, Turkey

    Zafer Günendi

  17. Faculty of Medicine, Department of Physical Medicine and Rehabilitation, Van Yüzüncü Yıl University, Van, Turkey

    Murat Toprak

  18. Rheumatology Clinic, Kartal Dr. Lütfi Kırdar Training and Research Hospital, İstanbul, Turkey

    Nesrin Şen

  19. Faculty of Medicine, Department of Physical Medicine and Rehabilitation Rheumatology Clinic, Atatürk University, Erzurum, Turkey

    Duygu Altıntaş & Meltem Alkan Melikoğlu

  20. Department of Physical Medicine and Rehabilitation Rheumatology Clinic, Sivas Numune Training and Research Hospital, Sivas, Turkey

    Ahmet Kıvanç Cengiz

  21. Faculty of Medicine, Department of Physical Medicine and Rehabilitation, 19 Mayıs University, Samsun, Turkey

    Ahmet Kıvanç Cengiz

  22. Faculty of Medicine, Department of Physical Medicine and Rehabilitation Rheumatology Clinic, Akdeniz University, Antalya, Turkey

    Ali Nail Demir & İlhan Sezer

  23. Department of Physical Medicine and Rehabilitation, Aksaray University Training and Research Hospital, Aksaray, Turkey

    Hüseyin Kaplan

  24. Faculty of Medicine, Department of Physical Medicine and Rehabilitation Rheumatology Clinic, Giresun University, Giresun, Turkey

    Sertaç Ketenci

  25. Faculty of Medicine, Department of Physical Medicine and Rehabilitation, Namık Kemal University, Tekirdağ, Turkey

    Mehmet Nayimoğlu & Ayşe Banu Sarıfakıoğlu

  26. Faculty of Medicine, Department of Physical Medicine and Rehabilitation Immunology Clinic, Sakarya University, Sakarya, Turkey

    Kemal Nas

Authors
  1. Hatice Bodur
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  2. Fatma Gül Yurdakul
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  28. Mehmet Nayimoğlu
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  30. Ayşe Banu Sarıfakıoğlu
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  31. İlhan Sezer
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Corresponding author

Correspondence to Fatma Gül Yurdakul.

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Conflict of interest

Author Hatice Bodur, Fatma Gül Yurdakul Hasan Fatih Çay Ülkü Uçar Yaşar Keskin Betül Sargınn Gülcan Gürer Ozan Volkan Yurdakul Mustafa Çalış Hülya Deveci Yıldıray Aydın Sami Hizmetli Remzi Çevik Ali Yavuz Karahan İsmihan Sunar Mehmet Tuncay Duruöz Hilal Ecesoy Zafer Günendi Murat Toprak Nesrin Şen Duygu Altıntaş Ahmet Kıvanç Cengiz Gökhan Çağlayan Ali Nail Demir Hüseyin Kaplan Sertaç Ketenci Meltem Alkan Melikoğlu Mehmet Nayimoğlu Kemal Nas Ayşe Banu Sarıfakıoğlu and İlhan Sezer declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards (ethic committee approval date/no:22.11.2107/E-17-1626).

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Bodur, H., Yurdakul, F.G., Çay, H.F. et al. Familial mediterranean fever: assessment of clinical manifestations, pregnancy, genetic mutational analyses, and disease severity in a national cohort. Rheumatol Int 40, 29–40 (2020). https://doi.org/10.1007/s00296-019-04443-0

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