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Factors Affecting Diagnostic Delay in Familial Mediterranean Fever Patients in Childhood

Year 2021, Volume: 23 Issue: 2, 370 - 377, 31.08.2021
https://doi.org/10.24938/kutfd.933866

Abstract

Objective: The aim of this study was to assess the factors that cause delay in diagnosis of familial Mediterranean fever (FMF), which is a common disease in our country.
Material and Methods: The data of 101 patients diagnosed with FMF in our pediatric rheumatology center between 2010 and 2021 were retrospectively analyzed. The time elapsed from the onset of the patients' symptoms to the time of diagnosis was defined as the delay in diagnosis. Pras disease severity score was used to determine disease severity.
Results: Fifty-nine of 101 patients were girls (58.4%). The median age at onset of symptoms was 5 (min-max: 2-8) years. The median age at diagnosis of the patients was 6 (min-max: 4-9) years. Delay in diagnosis was <1 year in 41 patients, <1-3 years in 40 patients, and >3 years in 20 patients. There were 39 (38.6%) M694V homozygous, 34 (33.7%) M694V heterozygous, 13 (12.9%) non-M694V mutations, 2 (2%) patients with a single mutation except M694V, and 13 (%13) patients with no mutation. According to the Pras disease severity score, disease severity was classified as mild in 22.8%, moderate in 43.6%, and severe in 33.7% of the patients. There was no relationship between family history of FMF, consanguineous marriage, clinical findings, mutations, and delay in diagnosis. A statistically significant relationship was found between the delay in diagnosis of more than 3 years and the age of onset of symptoms of the patients (p<0.001). A statistically significant correlation was observed between mild disease and delay in diagnosis of more than 3 years according to Pras disease severity score (p=0.026).
Conclusion: Diagnosis of FMF may be delayed if symptoms begin in infancy and are compatible with mild disease. FMF should be kept in mind in children with symptoms such as recurrent fever and abdominal pain in early childhood.

References

  • 1. Ozdogan H, Ugurlu S. Familial Mediterranean Fever. Presse Med. 2019;48(1 Pt 2):e61-e76.
  • 2. Ozen S, Karaaslan Y, Ozdemir O, Saatci U, Bakkaloglu A, Koroglu E et al. Prevalence of juvenile chronic arthritis and familial Mediterranean fever in Turkey: a field study. J Rheumatol. 1998;25(12):2445-9.
  • 3. Özen S. Update on the epidemiology and disease outcome of Familial Mediterranean fever. Best Pract Res Clin Rheumatol. 2018;32(2):254-60.
  • 4. Alghamdi M. Familial Mediterranean fever, review of the literature. Clin Rheumatol. 2017;36:1707-1713.
  • 5. Özen S, Batu ED, Demir S. Familial Mediterranean Fever: Recent developments in pathogenesis and new recommendations for management. Front Immunol. 2017;23(8):253.
  • 6. Yalçinkaya F, Özen S, Özçakar ZB, Aktay N, Çakar N, Düzova A et al. A new set of criteria for the diagnosis of familial Mediterranean fever in childhood. Rheumatology (Oxford). 2009;48(4):395–8.
  • 7. Pras E, Livneh A, Balow JE, Pras E, Kastner DL, Pras M et al. Clinical differences between North African and Iraqi Jews with familial Mediterranean fever. Am J Med Genet. 1998;75(2):216-9.
  • 8. Ozen S, Demirkaya E, Amaryan G, Koné-Paut I, Polat A, Woo P et al. Paediatric Rheumatology International Trials Organisation; Eurofever Project. 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(4):662-7.
  • 9. Turkish FMF Study Group. Familial Mediterranean fever (FMF) in Turkey: results of a nationwide multicenter study. Medicine (Baltimore). 2005;84(1):1-11.
  • 10. Barut K, Sahin S, Adrovic A, Sinoplu AB, Yucel G, Pamuk G et al. Familial Mediterranean fever in childhood: a single-center experience. Rheumatol Int. 2018;38(1):67-74.
  • 11. Ben-Chetrit E, Yazici H. Familial Mediterranean fever: different faces around the world. Clin Exp Rheumatol. 2019;37Suppl 121(6):18-22.
  • 12. Kallinich T, Gattorno M, Grattan CE, De Koning HD, Traidl Hoffmann C, Feist E et al. Unexplained recurrent fever: when is autoinflammation the explanation? Allergy. 2013 68(3):285-96.
  • 13. Mor A, Gal R, Livneh A. Abdominal and digestive system associations of familial Mediterranean fever. Am J Gastroenterol. 2003;98(12):2594-604.
  • 14. Battal F, Aylanc H, Yildirim S, Ekim Y, Silan F, Ozdemir O. Macular and choroidal thickness of children with Familial Mediterranean Fever gene mutation. Fam Pract Palliat Care. 2018;3(1):23-27.
  • 15. Battal F, Binnetoglu FK, Aylanc H, Yildirim S, Kaymaz N, Ozdemir O. Delayed time of atrial conduction in children with Familial Mediterranean Fever. Fam Pract Palliat Care. 2021;6(2):92-97.
  • 16. Giancane G, Ter Haar N, Wulffraat N, Vastert B, Barron K, Hentgen V et al. Evidence based recommendations for genetic diagnosis of familial Mediterranean fever. Ann Rheum Dis. 2015;74(4):635-41.
  • 17. Ben-Chetrit E, Lerer I, Malamud E, Domingo C, Abeliovich D. The E148Q mutation in the MEFV gene: is it a disease-causing mutation or a sequence variant? Hum Mutat. 2000;15(4):385-6.
  • 18. Topaloglu R, Batu ED, Yildiz C, Korkmaz E, Ozen S, Besbas N et al. Familial Mediterranean fever patients homozygous for E148Q variant may have milder disease. Int J Rheum Dis. 2018;21(10):1857-62.
  • 19. Battal F , Silan F , Topaloğlu N , Aylanç H , Yıldırım Ş, Binnetoğlu FK et al. The MEFV gene pathogenic variants and phenotype-genotype correlation in children with familial Mediterranean fever in the Çanakkale population. Balkan J Med Genet. 2017;19(2):23-28.
  • 20. Yasar Bilge NŞ, Bodakçi E, Bilgin M, Kaşifoğlu T. Comparison of clinical features in FMF patients according to severity scores: An analysis with the ISSF scoring system. Eur J Rheumatol. 2020;7(2):68-70.
  • 21. Yasar Bilge NS, Sari I, Solmaz D, Senel S, Emmungil H, Kilic L, et al. Comparison of early versus late onset familial Mediterranean fever. Int J Rheum Dis. 2018 (4);21:880-4.

ÇOCUKLUKTA AİLEVİ AKDENİZ ATEŞİ HASTALARINDA TANI GECİKMESİNİ ETKİLEYEN FAKTÖRLER

Year 2021, Volume: 23 Issue: 2, 370 - 377, 31.08.2021
https://doi.org/10.24938/kutfd.933866

Abstract

Amaç: Bu çalışmada ülkemizde sık görülen ailevi Akdeniz ateşinin tanısının konulmasında gecikmeye neden olan faktörlerin ortaya konulması amaçlanmıştır.
Gereç ve Yöntemler: Çocuk Romatoloji Polikliniğinde 2010-2021 yılları arasında ailevi Akdeniz ateşi tanısı alan 101 hastanın dosya kayıtları retrospektif olarak incelendi. Hastaların şikâyetlerinin başlama zamanından tanı aldıkları zamana kadar geçen süre tanı gecikmesi olarak tanımlandı. Hastalık ağırlığını belirlemek için Pras hastalık ağırlık skoru kullanıldı.
Bulgular: Yüz bir hastanın 59’u kızdı (%58.4). Şikâyetlerin ortanca başlama yaşı 5 yıl (min-maks: 2-8) olarak saptandı. Hastaların ortanca tanı alma yaşı 6 yıl (min-maks:4-9) idi. Tanı gecikmesi 41 hastada <1 yıl, 40 hastada <1-3 yıl, 20 hastada >3 yıldı. M694V homozigot olan 39 (%38.6), M694V heterozigot 34 (%33.7), M694V dışı iki mutasyon taşıyan 13 (%12.9), M694V dışında tek mutasyon olan 2 (%2), mutasyon saptanmayan 13 (%13) hasta olduğu görüldü. Pras hastalık ağırlık skoruna göre, hastalık ağırlığı hastaların %22.8’sinde hafif, %43.6’sında orta, %33.7’sinde ağır şiddetli olarak sınıflandırıldı. Tanı gecikmesi ile ailede ailevi Akdeniz ateşi öyküsü, akraba evliliği olması, klinik bulgular ve mutasyonlarla ilişki gösterilemedi. Tanı gecikmesinin >3 yıl olması ile hastaların semptomlarının başlama yaşı arasında istatistiksel olarak anlamlı ilişki saptandı (p<0.001). Pras hastalık ağırlık skoruna göre hafif hastalık ile tanı gecikmesinin >3 yıl olması arasında istatistiksel anlamlı ilişki olduğu görüldü (p=0.026).
Sonuç: Ailevi Akdeniz ateşi’nin tanısının konulması, şikâyetler süt çocukluğu döneminde başlarsa ve hafif hastalıkla uyumluysa gecikebilir. Erken çocukluk döneminde tekrarlayan ateş ve karın ağrısı gibi bulguları olan çocuklarda ailevi Akdeniz ateşi akılda tutulması gereklidir.

Supporting Institution

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References

  • 1. Ozdogan H, Ugurlu S. Familial Mediterranean Fever. Presse Med. 2019;48(1 Pt 2):e61-e76.
  • 2. Ozen S, Karaaslan Y, Ozdemir O, Saatci U, Bakkaloglu A, Koroglu E et al. Prevalence of juvenile chronic arthritis and familial Mediterranean fever in Turkey: a field study. J Rheumatol. 1998;25(12):2445-9.
  • 3. Özen S. Update on the epidemiology and disease outcome of Familial Mediterranean fever. Best Pract Res Clin Rheumatol. 2018;32(2):254-60.
  • 4. Alghamdi M. Familial Mediterranean fever, review of the literature. Clin Rheumatol. 2017;36:1707-1713.
  • 5. Özen S, Batu ED, Demir S. Familial Mediterranean Fever: Recent developments in pathogenesis and new recommendations for management. Front Immunol. 2017;23(8):253.
  • 6. Yalçinkaya F, Özen S, Özçakar ZB, Aktay N, Çakar N, Düzova A et al. A new set of criteria for the diagnosis of familial Mediterranean fever in childhood. Rheumatology (Oxford). 2009;48(4):395–8.
  • 7. Pras E, Livneh A, Balow JE, Pras E, Kastner DL, Pras M et al. Clinical differences between North African and Iraqi Jews with familial Mediterranean fever. Am J Med Genet. 1998;75(2):216-9.
  • 8. Ozen S, Demirkaya E, Amaryan G, Koné-Paut I, Polat A, Woo P et al. Paediatric Rheumatology International Trials Organisation; Eurofever Project. 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(4):662-7.
  • 9. Turkish FMF Study Group. Familial Mediterranean fever (FMF) in Turkey: results of a nationwide multicenter study. Medicine (Baltimore). 2005;84(1):1-11.
  • 10. Barut K, Sahin S, Adrovic A, Sinoplu AB, Yucel G, Pamuk G et al. Familial Mediterranean fever in childhood: a single-center experience. Rheumatol Int. 2018;38(1):67-74.
  • 11. Ben-Chetrit E, Yazici H. Familial Mediterranean fever: different faces around the world. Clin Exp Rheumatol. 2019;37Suppl 121(6):18-22.
  • 12. Kallinich T, Gattorno M, Grattan CE, De Koning HD, Traidl Hoffmann C, Feist E et al. Unexplained recurrent fever: when is autoinflammation the explanation? Allergy. 2013 68(3):285-96.
  • 13. Mor A, Gal R, Livneh A. Abdominal and digestive system associations of familial Mediterranean fever. Am J Gastroenterol. 2003;98(12):2594-604.
  • 14. Battal F, Aylanc H, Yildirim S, Ekim Y, Silan F, Ozdemir O. Macular and choroidal thickness of children with Familial Mediterranean Fever gene mutation. Fam Pract Palliat Care. 2018;3(1):23-27.
  • 15. Battal F, Binnetoglu FK, Aylanc H, Yildirim S, Kaymaz N, Ozdemir O. Delayed time of atrial conduction in children with Familial Mediterranean Fever. Fam Pract Palliat Care. 2021;6(2):92-97.
  • 16. Giancane G, Ter Haar N, Wulffraat N, Vastert B, Barron K, Hentgen V et al. Evidence based recommendations for genetic diagnosis of familial Mediterranean fever. Ann Rheum Dis. 2015;74(4):635-41.
  • 17. Ben-Chetrit E, Lerer I, Malamud E, Domingo C, Abeliovich D. The E148Q mutation in the MEFV gene: is it a disease-causing mutation or a sequence variant? Hum Mutat. 2000;15(4):385-6.
  • 18. Topaloglu R, Batu ED, Yildiz C, Korkmaz E, Ozen S, Besbas N et al. Familial Mediterranean fever patients homozygous for E148Q variant may have milder disease. Int J Rheum Dis. 2018;21(10):1857-62.
  • 19. Battal F , Silan F , Topaloğlu N , Aylanç H , Yıldırım Ş, Binnetoğlu FK et al. The MEFV gene pathogenic variants and phenotype-genotype correlation in children with familial Mediterranean fever in the Çanakkale population. Balkan J Med Genet. 2017;19(2):23-28.
  • 20. Yasar Bilge NŞ, Bodakçi E, Bilgin M, Kaşifoğlu T. Comparison of clinical features in FMF patients according to severity scores: An analysis with the ISSF scoring system. Eur J Rheumatol. 2020;7(2):68-70.
  • 21. Yasar Bilge NS, Sari I, Solmaz D, Senel S, Emmungil H, Kilic L, et al. Comparison of early versus late onset familial Mediterranean fever. Int J Rheum Dis. 2018 (4);21:880-4.
There are 21 citations in total.

Details

Primary Language Turkish
Subjects Health Care Administration
Journal Section Articles
Authors

Elif Çelikel 0000-0003-0129-4410

Zahide Ekici Tekin 0000-0002-5446-667X

Fatma Aydın 0000-0003-0306-7473

Müge Sezer 0000-0002-9254-9935

Tuba Kurt 0000-0003-3711-8347

Nilüfer Tekgöz 0000-0002-2235-4489

Serkan Coşkun 0000-0003-2568-9329

Melike Kaplan 0000-0002-8012-2774

Cüneyt Karagöl 0000-0002-2987-1980

Merve Tanrısever Türk This is me 0000-0001-9406-9946

Banu Acar 0000-0002-1808-3655

Publication Date August 31, 2021
Submission Date May 7, 2021
Published in Issue Year 2021 Volume: 23 Issue: 2

Cite

APA Çelikel, E., Ekici Tekin, Z., Aydın, F., Sezer, M., et al. (2021). ÇOCUKLUKTA AİLEVİ AKDENİZ ATEŞİ HASTALARINDA TANI GECİKMESİNİ ETKİLEYEN FAKTÖRLER. Kırıkkale Üniversitesi Tıp Fakültesi Dergisi, 23(2), 370-377. https://doi.org/10.24938/kutfd.933866
AMA Çelikel E, Ekici Tekin Z, Aydın F, Sezer M, Kurt T, Tekgöz N, Coşkun S, Kaplan M, Karagöl C, Tanrısever Türk M, Acar B. ÇOCUKLUKTA AİLEVİ AKDENİZ ATEŞİ HASTALARINDA TANI GECİKMESİNİ ETKİLEYEN FAKTÖRLER. Kırıkkale Uni Med J. August 2021;23(2):370-377. doi:10.24938/kutfd.933866
Chicago Çelikel, Elif, Zahide Ekici Tekin, Fatma Aydın, Müge Sezer, Tuba Kurt, Nilüfer Tekgöz, Serkan Coşkun, Melike Kaplan, Cüneyt Karagöl, Merve Tanrısever Türk, and Banu Acar. “ÇOCUKLUKTA AİLEVİ AKDENİZ ATEŞİ HASTALARINDA TANI GECİKMESİNİ ETKİLEYEN FAKTÖRLER”. Kırıkkale Üniversitesi Tıp Fakültesi Dergisi 23, no. 2 (August 2021): 370-77. https://doi.org/10.24938/kutfd.933866.
EndNote Çelikel E, Ekici Tekin Z, Aydın F, Sezer M, Kurt T, Tekgöz N, Coşkun S, Kaplan M, Karagöl C, Tanrısever Türk M, Acar B (August 1, 2021) ÇOCUKLUKTA AİLEVİ AKDENİZ ATEŞİ HASTALARINDA TANI GECİKMESİNİ ETKİLEYEN FAKTÖRLER. Kırıkkale Üniversitesi Tıp Fakültesi Dergisi 23 2 370–377.
IEEE E. Çelikel, “ÇOCUKLUKTA AİLEVİ AKDENİZ ATEŞİ HASTALARINDA TANI GECİKMESİNİ ETKİLEYEN FAKTÖRLER”, Kırıkkale Uni Med J, vol. 23, no. 2, pp. 370–377, 2021, doi: 10.24938/kutfd.933866.
ISNAD Çelikel, Elif et al. “ÇOCUKLUKTA AİLEVİ AKDENİZ ATEŞİ HASTALARINDA TANI GECİKMESİNİ ETKİLEYEN FAKTÖRLER”. Kırıkkale Üniversitesi Tıp Fakültesi Dergisi 23/2 (August 2021), 370-377. https://doi.org/10.24938/kutfd.933866.
JAMA Çelikel E, Ekici Tekin Z, Aydın F, Sezer M, Kurt T, Tekgöz N, Coşkun S, Kaplan M, Karagöl C, Tanrısever Türk M, Acar B. ÇOCUKLUKTA AİLEVİ AKDENİZ ATEŞİ HASTALARINDA TANI GECİKMESİNİ ETKİLEYEN FAKTÖRLER. Kırıkkale Uni Med J. 2021;23:370–377.
MLA Çelikel, Elif et al. “ÇOCUKLUKTA AİLEVİ AKDENİZ ATEŞİ HASTALARINDA TANI GECİKMESİNİ ETKİLEYEN FAKTÖRLER”. Kırıkkale Üniversitesi Tıp Fakültesi Dergisi, vol. 23, no. 2, 2021, pp. 370-7, doi:10.24938/kutfd.933866.
Vancouver Çelikel E, Ekici Tekin Z, Aydın F, Sezer M, Kurt T, Tekgöz N, Coşkun S, Kaplan M, Karagöl C, Tanrısever Türk M, Acar B. ÇOCUKLUKTA AİLEVİ AKDENİZ ATEŞİ HASTALARINDA TANI GECİKMESİNİ ETKİLEYEN FAKTÖRLER. Kırıkkale Uni Med J. 2021;23(2):370-7.

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