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PFAPA SENDROMUNDA MEFV MUTASYONLARININ HASTALIK ÜZERİNE ETKİSİ

Year 2020, Volume: 14 Issue: 3, 258 - 263, 29.05.2020

Semanur Özdel , Esra Bağlan Mehmet Bülbül

https://doi.org/10.12956/tchd.679712

Abstract

ÖZ
Amaç: Kalıtsal olmayan otoinflamatuvar hastalıklardan biri olarak sınıflandırılan PFAPA (Periodic fever, apthous stomatitis, pharyngitis and cervical adenitis) sendromu; periyodik ateş, farenjit, servikal lenfadenit ve stomatit ile seyretmektedir. PFAPA sendromunun tanısı bir dışlama tanısıdır. Hastalığa tanı koydurucu özgül bir laboratuvar belirteci bulunmamaktadır. Ülkemiz 1/1000 tahmini prevalans ve 1/5 taşıyıcılık oranı ile dünya üzerinde ailesel Akdeniz ateşi yoğunluğunun en fazla olduğu toplumlardan biridir. Bu genetik yatkınlığın çeşitli romatizmal hastalıkların şiddetini arttırdığı iyi bilinmektedir. Bu çalışmada MEFV mutasyonlarının PFAPA sendromlu çocuklarda klinik ve laboratuvar bulguları, hastalık seyri ve şiddeti üzerindeki etkisini araştırmak amaçlanmıştır.

Gereç ve Yöntem: Çalışmaya PFAPA sendromu tanısı konulmuş ve MEFV gen analizi gönderilmiş 70 hasta dahil edilmiştir. Hastaların demografik verileri, klinik bulguları, atak sayısı ve şiddeti, atakta laboratuvar değerleri (lökosit sayısı, eritrosit sedimentasyon hızı, C reaktif protein), MEFV gen analiz sonuçları önceden hazırlanmış formlara kaydedilmiştir. MEFV mutasyonu pozitif olan 33 hasta ile MEFV mutasyonu negatif olan 37 hasta demografik veriler, klinik özellikler ve hastalık seyri açısından karşılaştırılmıştır.

Bulgular: MEFV mutasyonu taşıyan PFAPA’lı hastalarda atak süresi ve sıklığı mutasyon taşımayan hastalara göre daha fazlaydı (p <0,05). Ayrıca atakta laboratuvar değerleri (lökosit sayısı, eritrosit sedimentasyon hızı, C reaktif protein) MEFV mutasyonu taşıyanlarda taşımayanlara göre daha yüksekti (p <0,05). Klinik bulgular ve cinsiyet açısından fark gözlenmedi.

Sonuç: PFAPA sendromunda MEFV geni artan hastalık şiddeti ile ilişkili bir değiştirici gendir.

Keywords

PFAPA senrdomu ailesel Akdeniz ateşi Ateş

References

  • KAYNAKLAR 1- Marshall GS, Edwards KM, Lawton AR. PFAPA syndrome. Pediatr Infect Dis J 1989; 8:658-659
  • 2- Theodoropoulou K, Vanoni F, Hofer M. Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis (PFAPA) Syndrome: a Review of the Pathogenesis. Curr Rheumatol Rep 2016; 18:18
  • 3- Adrovic A, Sahin S, Barut K, Kasapcopur O. Familial Mediterranean fever and periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome: shared features and main differences. Rheumatol Int 2019; 39:29–36
  • 4- Padeh S, Brezniak N, Zemer D, Pras E, Livneh A, Langevitz P, Migdal A, Pras M, Passwell JH. Periodic fever, aphthous stomatitis, pharyngitis, and adenopathy syndrome: clinical characteristics and outcome. J Pediatr 1999; 135:98–101.
  • 5- Hofer M, Pillet P, Cochard MM, Berg S, Krol P, Kone-Paut I, Rigante D, Hentgen V, Anton J, Brik R, Neven B, Touitou I, Kaiser D, Duquesne A, Wouters C, Gattorno M. International periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis syndrome cohort: description of distinct phenotypes in 301 patients. Rheumatology (Oxford) 2014; 53:1125–1129
  • 6- Pehlivan E, Adrovic A, Sahin S, Barut K, Kul Cinar O, Kasapcopur O. PFAPA syndrome in a population with endemic familial Mediterranean fever. J Pediatr 2018; 192:253–255
  • 7- Barut K, Sahin S, Adrovic A, Sinoplu AB, Yucel G, Pamuk G, Aydın AK, Dasdemir S, Turanlı ET, Buyru N, Kasapcopur O. Familial Mediterranean fever in childhood: a single-center experience. Rheumatol Int 2018; 38:67–74
  • 8- Özen S, Batu ED, Demir S. Familial Mediterranean fever: recent developments in pathogenesis and new recommendations for management. Front Immunol 2017; 8:253
  • 9- Tunca M, Akar S, Onen F, Ozdogan H, Kasapcopur O, Yalcinkaya F, Tutar E, Ozen S, Topaloglu R, Yılmaz E, Arici M, Bakkaloglu A, Besbas N, Akpolat T, Dinc A, Erken E; Turkish FMF Study Group. Familial Mediterranean fever (FMF) in Turkey: Results of a nationwide multicenter study. Medicine (Baltimore) 2005; 84: 1-11.
  • 10- French FMF Consortium. A candidate gene for familial Mediterranean fever. Nat Genet 1997; 17: 25-31. 25.
  • 11- Ancient missense mutations in a new member of the RoRet gene family are likely to cause familial Mediterranean fever. The International FMF Consortium. Cell 1997; 90: 797-807.
  • 12- Chae JJ, Wood G, Richard K, Jaffe H, Colburn NT, Masters SL, Gumucio DL, Shoham NG, Kastner DL. The familial Mediterranean fever protein, pyrin, is cleaved by caspase-1 and activates NF-kappaB through its N-terminal fragment. Blood 2008; 112:1794-803.
  • 13- Berkun Y, Ben-Chetrit E. Pyrin and cryopyrin—similar domain sequence but opposite inflammatory consequence. Clin Exp Rheumatol 2007;25(4 Suppl 45): S6-8.
  • 14- Rabinovich E, Livneh A, Langevitz P, Brezniak N, Shinar E, Pras M, Shinar Y. Severe disease in patients with rheumatoid arthritis carrying a mutation in the Mediterranean fever gene. Ann Rheum Dis 2005; 64:1009-1014
  • 15- Fidder H, Chowers Y, Ackerman Z, Pollak RD, Crusius JB, Livneh A, Bar-Meir S, Avidan B, Shinhar Y. The familial Mediterranean fever (MEVF) gene as a modifier of Crohn’s disease. Am J Gastroenterol 2005;100: 338-43
  • 16- Shinar Y, Livneh A, Villa Y, Pinhasov A, Zeitoun I, Kogan A, Achiron A. Common mutations in the familial Mediterranean fever gene associate with rapid progression to disability in non-Ashkenazi Jewish multiple sclerosis patients. Genes Immun 2003; 4:197-203.
  • 17- Yaşar Bilge Ş, Sarı İ, Solmaz D, Şenel S, Emmungil H, Kılıç L, Yılmaz Öner S, Yıldız F, Yılmaz S, Ersözlü Bozkırlı D, Aydın Tufan M, Yılmaz S, Yazısız V, Pehlivan Y, Bes C, Yıldırım Çetin G, Erten Ş, Gönüllü E, Şahin F, Akar S, Aksu K, Kalyoncu U, Direskeneli H, Erken E, Kısacık B, Sayarlıoğlu M, Çınar M, Kaşifoğlu T. The distribution of MEFV mutations in Turkish FMF patients: multicenter study representing results of Anatolia. Turk J Med Sci 2019; 49:472-477
  • 18- Thomas KT, Feder HM Jr, Lawton AR, Edwards KM. Periodic fever syndrome in children. J Pediatr 1999; 135:15–21
  • 19- Adachi M, Watanabe A, Nishiyama A, Oyazato Y, Kamioka I, Murase M, et al. Familial cases of periodic fever with aphthous stomatitis, pharyngitis, and cervical adenitis syndrome. J Pediatr 2011; 158:155-9.
  • 20- Akelma AZ, Cizmeci MN, Kanburoglu MK, Mete E, Bozkaya D, Tufan N, et al. Is PFAPA syndrome really a sporadic disorder or is it genetic? Med Hypotheses 2013; 81:279-81.
  • 21- Dagan E, Gershoni-Baruch R, Khatib I, Mori A, Brik R. MEFV, TNF1rA, CARD15 and NLRP3 mutation analysis in PFAPA. Rheumatol Int 2010: 30: 633–636
  • 22- Taniuchi S, Nishikomori R, Iharada A, Tuji S, Heike T, Kaneko K. MEFV Variants in Patients with PFAPA Syndrome in Japan. Open Rheumatol J 2013: 7: 22–25
  • 23- Gunes M, Cekic S, Kılıc SS. Is colchicine more effective to prevent periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis episodes in Mediterranean fever gene variants? Pediatr Int 2017; 59:655-660
  • 24- Berkun Y, Levy R, Hurwitz A, Meir-Harel M, Lidar M, Livneh A, Padeh S. The familial Mediterranean fever gene as a modifier of periodic fever, aphthous stomatitis, pharyngitis, and adenopathy syndrome. Semin Arhritis Rheum 2011; 40:467-472
  • 25- Harel L, Hashkes PJ, Lapidus S, Edwards KM, Padeh S, Gattorno M, Marshall GS. The first international conference on periodic fever, aphthous stomatitis, pharyngitis, adenitis syndrome. J Pediatr 2018; 193:265–274
  • 26- Celiksoy MH, Ogur G, Yaman E, Abur U, Fazla S, Sancak R, Yildiran A. Could familial Mediterranean fever gene mutations be related to PFAPA syndrome? Pediatr Allergy Immunol 2016; 27:78-82
  • 27- Batu ED, Kara Eroğlu F, Tsoukas P, Hausmann JS, Bilginer Y, Kenna MA, Licameli GR, Fuhlbrigge RC, Ozen S, Dedeoğlu F. Periodic Fever, Aphthosis, Pharyngitis, and Adenitis Syndrome: Analysis of patients from two geographis ares. Arthritis Care Res (Hoboken) 2016; 68:1859-1865
  • 28- Tasher D, Stein M, Dalal I, Somekh E. Colchicine prophylaxis for frequent periodic fever, aphthous stomatitis, pharyngitis and adenitis episodes. Acta Paediatr 2008; 97:1090-1092
  • 29- Cronstein BN, Molad Y, Reibman J, Balakhane E, Levin RI, Weissmann G. Colchicine alters the quantitative and qualitative display of selectins on endothelial cells and neutrophils. J Clin Invest 1995; 96: 994–1002.
  • 30- Ting K, Graf SW, Whittle SL. Update on the diagnosis and management of gout. Med J Aust 2015; 203:86- 88.
  • 31- Butbul Aviel Y, Tatour S, Gershoni Baruch R, Brik R. Colchicine as a therapeutic option in periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis (PFAPA) syndrome. Semin Arthritis Rheum 2016; 45:471-474

Year 2020, Volume: 14 Issue: 3, 258 - 263, 29.05.2020

Semanur Özdel , Esra Bağlan Mehmet Bülbül

https://doi.org/10.12956/tchd.679712

Abstract

References

  • KAYNAKLAR 1- Marshall GS, Edwards KM, Lawton AR. PFAPA syndrome. Pediatr Infect Dis J 1989; 8:658-659
  • 2- Theodoropoulou K, Vanoni F, Hofer M. Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis (PFAPA) Syndrome: a Review of the Pathogenesis. Curr Rheumatol Rep 2016; 18:18
  • 3- Adrovic A, Sahin S, Barut K, Kasapcopur O. Familial Mediterranean fever and periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome: shared features and main differences. Rheumatol Int 2019; 39:29–36
  • 4- Padeh S, Brezniak N, Zemer D, Pras E, Livneh A, Langevitz P, Migdal A, Pras M, Passwell JH. Periodic fever, aphthous stomatitis, pharyngitis, and adenopathy syndrome: clinical characteristics and outcome. J Pediatr 1999; 135:98–101.
  • 5- Hofer M, Pillet P, Cochard MM, Berg S, Krol P, Kone-Paut I, Rigante D, Hentgen V, Anton J, Brik R, Neven B, Touitou I, Kaiser D, Duquesne A, Wouters C, Gattorno M. International periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis syndrome cohort: description of distinct phenotypes in 301 patients. Rheumatology (Oxford) 2014; 53:1125–1129
  • 6- Pehlivan E, Adrovic A, Sahin S, Barut K, Kul Cinar O, Kasapcopur O. PFAPA syndrome in a population with endemic familial Mediterranean fever. J Pediatr 2018; 192:253–255
  • 7- Barut K, Sahin S, Adrovic A, Sinoplu AB, Yucel G, Pamuk G, Aydın AK, Dasdemir S, Turanlı ET, Buyru N, Kasapcopur O. Familial Mediterranean fever in childhood: a single-center experience. Rheumatol Int 2018; 38:67–74
  • 8- Özen S, Batu ED, Demir S. Familial Mediterranean fever: recent developments in pathogenesis and new recommendations for management. Front Immunol 2017; 8:253
  • 9- Tunca M, Akar S, Onen F, Ozdogan H, Kasapcopur O, Yalcinkaya F, Tutar E, Ozen S, Topaloglu R, Yılmaz E, Arici M, Bakkaloglu A, Besbas N, Akpolat T, Dinc A, Erken E; Turkish FMF Study Group. Familial Mediterranean fever (FMF) in Turkey: Results of a nationwide multicenter study. Medicine (Baltimore) 2005; 84: 1-11.
  • 10- French FMF Consortium. A candidate gene for familial Mediterranean fever. Nat Genet 1997; 17: 25-31. 25.
  • 11- Ancient missense mutations in a new member of the RoRet gene family are likely to cause familial Mediterranean fever. The International FMF Consortium. Cell 1997; 90: 797-807.
  • 12- Chae JJ, Wood G, Richard K, Jaffe H, Colburn NT, Masters SL, Gumucio DL, Shoham NG, Kastner DL. The familial Mediterranean fever protein, pyrin, is cleaved by caspase-1 and activates NF-kappaB through its N-terminal fragment. Blood 2008; 112:1794-803.
  • 13- Berkun Y, Ben-Chetrit E. Pyrin and cryopyrin—similar domain sequence but opposite inflammatory consequence. Clin Exp Rheumatol 2007;25(4 Suppl 45): S6-8.
  • 14- Rabinovich E, Livneh A, Langevitz P, Brezniak N, Shinar E, Pras M, Shinar Y. Severe disease in patients with rheumatoid arthritis carrying a mutation in the Mediterranean fever gene. Ann Rheum Dis 2005; 64:1009-1014
  • 15- Fidder H, Chowers Y, Ackerman Z, Pollak RD, Crusius JB, Livneh A, Bar-Meir S, Avidan B, Shinhar Y. The familial Mediterranean fever (MEVF) gene as a modifier of Crohn’s disease. Am J Gastroenterol 2005;100: 338-43
  • 16- Shinar Y, Livneh A, Villa Y, Pinhasov A, Zeitoun I, Kogan A, Achiron A. Common mutations in the familial Mediterranean fever gene associate with rapid progression to disability in non-Ashkenazi Jewish multiple sclerosis patients. Genes Immun 2003; 4:197-203.
  • 17- Yaşar Bilge Ş, Sarı İ, Solmaz D, Şenel S, Emmungil H, Kılıç L, Yılmaz Öner S, Yıldız F, Yılmaz S, Ersözlü Bozkırlı D, Aydın Tufan M, Yılmaz S, Yazısız V, Pehlivan Y, Bes C, Yıldırım Çetin G, Erten Ş, Gönüllü E, Şahin F, Akar S, Aksu K, Kalyoncu U, Direskeneli H, Erken E, Kısacık B, Sayarlıoğlu M, Çınar M, Kaşifoğlu T. The distribution of MEFV mutations in Turkish FMF patients: multicenter study representing results of Anatolia. Turk J Med Sci 2019; 49:472-477
  • 18- Thomas KT, Feder HM Jr, Lawton AR, Edwards KM. Periodic fever syndrome in children. J Pediatr 1999; 135:15–21
  • 19- Adachi M, Watanabe A, Nishiyama A, Oyazato Y, Kamioka I, Murase M, et al. Familial cases of periodic fever with aphthous stomatitis, pharyngitis, and cervical adenitis syndrome. J Pediatr 2011; 158:155-9.
  • 20- Akelma AZ, Cizmeci MN, Kanburoglu MK, Mete E, Bozkaya D, Tufan N, et al. Is PFAPA syndrome really a sporadic disorder or is it genetic? Med Hypotheses 2013; 81:279-81.
  • 21- Dagan E, Gershoni-Baruch R, Khatib I, Mori A, Brik R. MEFV, TNF1rA, CARD15 and NLRP3 mutation analysis in PFAPA. Rheumatol Int 2010: 30: 633–636
  • 22- Taniuchi S, Nishikomori R, Iharada A, Tuji S, Heike T, Kaneko K. MEFV Variants in Patients with PFAPA Syndrome in Japan. Open Rheumatol J 2013: 7: 22–25
  • 23- Gunes M, Cekic S, Kılıc SS. Is colchicine more effective to prevent periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis episodes in Mediterranean fever gene variants? Pediatr Int 2017; 59:655-660
  • 24- Berkun Y, Levy R, Hurwitz A, Meir-Harel M, Lidar M, Livneh A, Padeh S. The familial Mediterranean fever gene as a modifier of periodic fever, aphthous stomatitis, pharyngitis, and adenopathy syndrome. Semin Arhritis Rheum 2011; 40:467-472
  • 25- Harel L, Hashkes PJ, Lapidus S, Edwards KM, Padeh S, Gattorno M, Marshall GS. The first international conference on periodic fever, aphthous stomatitis, pharyngitis, adenitis syndrome. J Pediatr 2018; 193:265–274
  • 26- Celiksoy MH, Ogur G, Yaman E, Abur U, Fazla S, Sancak R, Yildiran A. Could familial Mediterranean fever gene mutations be related to PFAPA syndrome? Pediatr Allergy Immunol 2016; 27:78-82
  • 27- Batu ED, Kara Eroğlu F, Tsoukas P, Hausmann JS, Bilginer Y, Kenna MA, Licameli GR, Fuhlbrigge RC, Ozen S, Dedeoğlu F. Periodic Fever, Aphthosis, Pharyngitis, and Adenitis Syndrome: Analysis of patients from two geographis ares. Arthritis Care Res (Hoboken) 2016; 68:1859-1865
  • 28- Tasher D, Stein M, Dalal I, Somekh E. Colchicine prophylaxis for frequent periodic fever, aphthous stomatitis, pharyngitis and adenitis episodes. Acta Paediatr 2008; 97:1090-1092
  • 29- Cronstein BN, Molad Y, Reibman J, Balakhane E, Levin RI, Weissmann G. Colchicine alters the quantitative and qualitative display of selectins on endothelial cells and neutrophils. J Clin Invest 1995; 96: 994–1002.
  • 30- Ting K, Graf SW, Whittle SL. Update on the diagnosis and management of gout. Med J Aust 2015; 203:86- 88.
  • 31- Butbul Aviel Y, Tatour S, Gershoni Baruch R, Brik R. Colchicine as a therapeutic option in periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis (PFAPA) syndrome. Semin Arthritis Rheum 2016; 45:471-474
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Details

Primary Language Turkish
Subjects Clinical Sciences
Journal Section ORIGINAL ARTICLES
Authors

Semanur Özdel 0000-0001-5602-4595

Esra Bağlan This is me 0000-0001-5637-8553

Mehmet Bülbül This is me 0000-0001-9007-9653

Publication Date May 29, 2020
Submission Date January 24, 2020
Published in Issue Year 2020 Volume: 14 Issue: 3

Cite

Vancouver Özdel S, Bağlan E, Bülbül M. PFAPA SENDROMUNDA MEFV MUTASYONLARININ HASTALIK ÜZERİNE ETKİSİ. Turkish J Pediatr Dis. 2020;14(3):258-63.
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