Familial Mediterranean Fever and Accompanying Inflammatory Diseases: Effects On The Disease Severity Score

Öz

Objective: Familial Mediterranean Fever (FMF) stands as the most prevalent autoinflammatory disorder in childhood. It is well-established that certain inflammatory conditions may coexist with FMF. Within the scope of our investigation, we examined the inflammatory diseases accompanying FMF in diagnosed pediatric patients, as well as their potential impact on the disease progression. Materials and Methods: We retrospectively reviewed the medical records of 349 patients diagnosed with FMF based on the Yalçınkaya diagnostic criteria, who were followed between January 1, 2015, and December 31, 2020. The potential impact of inflammatory diseases coexisting with FMF on the Pras disease severity score was investigated. Results: Among the patients included in the study, 45.8% exhibited mild disease, 43.2% had moderate disease, and 10.8% had severe disease. Among the study participants, 14.8% were found to have coexisting inflammatory diseases. Specifically, IgA vasculitis was present in 5.7% of cases, sacroiliitis in 3.7%, prolonged febrile myalgia in 2.0%, acute rheumatic fever in 1.7%. Some cases showed the coexistence of multiple inflammatory conditions alongside FMF. It was observed that the disease severity score was higher in patients with coexisting inflammatory diseases. Additionally, the rate of severe disease was found to be increased in patients with coexisting inflammatory diseases (17.3%). Conclusion: Our study demonstrated that coexisting inflammatory diseases elevate the disease severity score and increase the intensity of FMF. Furthermore, patients with coexisting inflammatory diseases showed higher erythrocyte sedimentation rate values during attack-free periods and an increased use of biological agents.

Anahtar Kelimeler

• Familial Mediterranean Fever
• Inflammatory Diseases
• Disease Severity Score
• Biological Agent

Ailevi Akdeniz Ateşine Eşlik Eden İnflamatuar Hastalıklar Ve Hastalık Ağırlık Skoruna Etkisinin Değerlendirilmesi

Öz

Giriş ve Amaç: Ailevi Akdeniz Ateşi (AAA), çocukluk döneminde en sık görülen otoinflamatuar hastalıktır. Bazı inflamatuar hastalıkların AAA’ya eşlik edebildiği bilinmektedir. Çalışmamızda AAA tanılı hastalarda eşlik eden inflamatuar hastalıkları ve hastalık seyrine etkilerini inceledik. Gereç ve Yöntem: Çalışmamızda, 1 Ocak 2015-31 Aralık 2020 tarihleri arasında Yalçınkaya tanı kriterlerine göre AAA tanısı ile takip edilen 349 hastanın tıbbi kayıtları geriye dönük incelendi. AAA ile birliktelik gösteren inflamatuar hastalıkların Pras hastalık ağırlık skoruna etkisi araştırıldı. Bulgular: Çalışmaya dâhil edilen hastaların %45.8’inde hafif, %43.2’sinde orta ve %10.8’inde ağır hastalık mevcuttu. Çalışmaya dâhil edilen hastaların %14.8’inde eşlik eden inflamatuar bir hastalık tespit edildi (%5.7 IgA vasküliti, %3.7 sakroileit, %2.0 uzamış febril miyalji, %1.7 akut romatizmal ateş, %0.9). AAA’ya eşlik eden birden fazla inflamatuar hastalığın olduğu durumlar mevcuttu. Hastalık ağırlık skorunun, eşlik eden inflamatuar hastalığı olanlarda olmayanlara göre yüksek olduğu bulundu. Ek olarak eşlik eden inflamatuar hastalığı olan hastalarda ağır hastalık görülme oranının (%17.3) arttığı görüldü. Sonuç: Çalışmamızda eşlik eden inflamatuar hastalıkların AAA hastalığı ağırlık skorunu yükselttiği, ağırlık şiddetini artırdığı, bu hastalarda ataksız dönemdeki eritrosit sedimentasyon hızı değerlerinin yüksek seyrettiği ve biyolojik ajan kullanımının arttığı gösterilmiştir.

Anahtar Kelimeler

• Ailevi Akdeniz Ateşi
• İnflamatuar Hastalık
• Hastalık Ağırlık Skoru
• Biyolojik Ajan

Kaynakça

1. 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;38:67–74.
2. Onen F. Familial Mediterranean fever. Rheumatol Int 2006;26:489–96.
3. Tunca M, Ozdogan H, Kasapcopur O, Yalcinkaya F, Ozen S, Topaloglu R, et al. Familial Mediterranean Fever (FMF) in Turkey: Results of a nationwide multicenter study. Medicine (Baltimore) 2005;84:1–11.
4. Yilmaz E, Ozen S, Balci B, Duzova A, Topaloglu R, Besbas N, et al. Mutation frequency of Familial Mediterranean Fever and evidence for a high carrier rate in the Turkish population. Eur J Hum Genet 2001;9:553–5.
5. 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 2009;48:395–8.
6. Ozen S, Demirkaya E, Erer B, Livneh A, Ben-Chetrit E, Giancane G, et al. EULAR recommendations for the management of familial Mediterranean fever. Ann Rheum Dis 2016;75:644–51.
7. Ben-Chetrit E, Levy M. Familial Mediterranean fever. Lancet 1998;351:659–64.
8. Yildiz M, Adrovic A, Tasdemir E, Baba K. Evaluation of co-existing diseases in children with familial. Rheumatol Int 2020;40:57-64.

9. Ozen S, Aktay N, Lainka E, Duzova A, Bakkaloglu A, Kallinich T. Disease severity in children and adolescents with familial Mediterranean fever: A comparative study to explore environmental effects on a monogenic disease. Ann Rheum Dis 2009;68:246–8.
10. Pras E, Livneh A, Balow JE Jr, Pras E, Kastner DL, Pras M, Langevitz P. Clinical differences between North African and Iraqi Jews with familial Mediterranean fever. Am J Med Genet 1998;75:216-9.
11. Ozcakar ZB, Cakar N, Uncu N, Celikel BA, Yalcinkaya F. Familial Mediterranean Fever Associated Diseases in Children. QJM An int J of Medicine 2017;110:287–90.
12. Ozdogan H, Arisoy N, Kasapçapur O. Vasculitis in familial Mediterranean fever. J Rheumatol 1997;24:323–7.
13. Cattan D. MEFV mutation carriers and diseases other than familial Mediterranean fever: Proved and non-proved associations; putative biological advantage. Curr Drug Targets Inflamm. Allergy 2005;4:105–12.
14. Watts RA, Scott DGI. Epidemiology of the vasculitides. Semin Respir Crit Care Med 2004;25:455–64.
15. Langevitz P, Zemer D, Livneh A, Shemer J, Pras M. Protracted febrile myalgia in patients with familial Mediterranean fever. J Rheumatol 1994;21:1708–9.
16. Ayaz NA, Tanatar A, Karadağ ŞG, Çakan M, Keskindemirci G, Sönmez HE.Comorbidities and phenotype–genotype correlation in children with familial Mediterranean fever. Rheumatol Int 2021;41:113-10.
17. Schwartz T, Langevitz P, Zemer D, Gazit E, Pras M, Livneh A. Behcet’s disease in Familial Mediterranean fever: Characterization of the association between the two diseases. Semin Arthritis Rheum 2000;29:286–95.
18. Birlik M, Tunca M, Hizli N, Soytürk M, Yeniçerioǧlu Y, Özcan MA, et al. Coexistence of familial mediterranean fever with sacroiliitis and Behcet’s disease: A rare occurrence. Clin Rheumatol 1998;17:397–9.
19. Yıldırım DG, Fidan HK, Gönen S, Söylemezoğlu O. Sacroiliitis associated with familial mediterranean fever in childhood: A case series and review of literature. Turk J Pediatr 2020;62:175–81.
20. Beşer ÖF, Çokuğraş FÇ, Kutlu T, Erginöz E, Gülcü D, Kasapçopur Ö, et al. Association of familial mediterranean fever in Turkish children with inflammatory bowel disease. Turk Pediatr Ars 2014;49:198–202.
21. Balcı-Peynircioǧlu B, Kaya-Akça Ü, Arıcı ZS, Avcı E, Akkaya UlumY Z, Karadaǧ Ö, et al. Comorbidities in familial Mediterranean fever: Analysis of 2000 genetically confirmed patients. Rheumatol (United Kingdom) 2020;59:1372–80.
22. Örün UA, Ceylan Ö, Bilici M, Karademir S, Öcal B, Şenocak F, et al. Acute rheumatic fever in the Central Anatolia Region of Turkey: A 30-year experience in a single center. Eur J Pediatr 2012;171:361–8.
23. Korkmaz C, Özdogan H, Kasapçopur O, Yazici H. Acute phase response in familial Mediterranean fever. Ann Rheum Dis 2002;61:79–81.