Abstract
Familial Mediterranean fever (FMF) is A common periodic fever syndrome. The causative gene of the FMF is named Mediterranean Fever gene (MEFV). Increased inflammation in FMF may play a role as a trigger for the development of some diseases. The objective of the study is to evaluate the frequency of comorbid disorders in children followed up with diagnosis of FMF. Additionally, we aimed to assess the association between FMF and other inflammatory conditions in a large pediatric FMF cohort. A total of 686 FMF patients were included in the cross-sectional study. A questionnaire including questions about characteristics of fever episodes, presence of arthralgia, arthritis, abdominal pain, chest pain during and co-existence of any other disease diagnosed by a physician was filled out by face-to-face interviews with patients or their parents. Female–male ratio was 0.85. Median age at the time of study, age at disease onset and at the time of diagnosis were 12.9 (1.7–22.3), 3 (0.08–17), and 6 (0.75–17) years, respectively. In 130 (18.9%) FMF patients we detected co-existing inflammatory condition. The most common co-existing diseases were: juvenile idiopathic arthritis 42 (6.1%), asthma/reactive airway disease 29 (4.2%), Henoch–Schönlein purpura 20 (2.9%), uveitis 12 (1.7%) and inflammatory bowel disease 10 (1.4%). Except for asthma/reactive airway disease and inflammatory bowel disease, there was no significant difference regarding the type of MEFV gene mutation. We have reported increased frequencies of various inflammatory conditions and decreased frequency of asthma in patients with FMF.
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References
Barut K, Sahin S, Adrovic A et al (2018) Familial Mediterranean fever in childhood: a single-center experience. Rheumatol Int 38(1):67–74
Ozen S, Karaaslan Y, Ozdemir O et al (1998) Prevalence of juvenile chronic arthritis and familial Mediterranean fever in Turkey: a field study. J Rheumatol 25(12):2445–2449
Bernot A, Clepet C, Dasilva C et al (1997) A candidate gene for familial Mediterranean fever. Nat Genet 17(1):25–31
Gangemi S, Manti S, Procopio V et al (2018) Lack of clear and univocal genotype–phenotype correlation in familial Mediterranean fever patients: a systematic review. Clin Genet 94(1):81–94
Ozdogan H, Arısoy N, Kasapcopur O et al (1997) Vasculitis in familial Mediterranean fever. J Rheumatol 24(2):323–330
Tunca M, Ozdogan H, Kasapcopur O et al (2005) Familial Mediterranean Fever (FMF) in Turkey: results of a nationwide multicenter study. Medicine (Baltimore) 84(1):1–11
Barut K, Guler M, Sezen M, Kasapcopur O (2016) Increased frequency of psoriasis in the families of the children with familial Mediterranean fever. Clin Exp Rheumatol 34:137
Erden A, Batu ED, Seyhoglu E et al (2018) Increased psoriasis frequency in patients with familial Mediterranean fever. Ups J Med Sci 123(1):57–61
Ozer E, Seker D, Taner E et al (2018) The frequency of juvenile spondyloarthropathies in childhood familial Mediterranean fever. Clin Exp Rheumatol 36(Suppl. 115):141–145
Yalcinkaya F, Ozen S, Ozcakar ZB et al (2009) A new set of criteria for the diagnosis of familial Mediterranean fever in childhood. Rheumatology 48(4):395–398
Petty RE, Southwood TR, Manners P et al (2004) International League of Associations for Rheumatology Classification of Juvenile Idiopathic Arthritis: second revision, Edmonton, 2001. J Rheumatol 31(2):390–392
Ozen S, Pistorio A, Iusan SM et al (2010) EULAR/PRINTO/PRES criteria for Henoch–Schonlein purpura, childhood polyarteritis nodosa, childhood Wegener granulomatosis and childhood Takayasu arteritis: Ankara 2008. Part II: Final classification criteria. Ann Rheum Dis 69:798–806
Hochberg MC (1997) Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 40(9):1725–1734
Marshall GS, Edwards KM, Lawton AR (1989) Pfapa syndrome. Pediatr Infect Dis J 8:658–659
Gewitz MH, Baltimore RS, Tani LY et al (2015) Revision of the Jones criteria for the diagnosis of acute rheumatic fever in the era of Doppler echocardiography a scientific statement from the American heart association. Circulation 131(20):1806–1818
Newburger JW, Takahashi M, Gerber MA et al (2004) Diagnosis, treatment, and long-term management of Kawasaki disease: a statement for health professionals from the Committee on Rheumatic Fever, Endocarditis and Kawasaki Disease, Council on Cardiovascular Disease in the Young, American Heart Association. Circulation 110:2747–2771
Koné-Paut I, Shahram F, Darce-bello M et al (2016) Consensus classification criteria for paediatric Behçet’s disease from a prospective observational cohort: PEDBD. Ann Rheum Dis 75:958–964
Hentgen V, Grateau G, Kone-Paut I et al (2013) Evidence-based recommendations for the practical management of familial Mediterranean fever. Semin Arthritis Rheum 43:387–391
Kisla Ekinci RM, Balci S, Altintas DU et al (2019) The influence of concomitant disorders on disease severity of familial Mediterranean fever in children. Arch Rheumatol 33(3):282–287
Ozcakar ZB, Cakar N, Uncu N et al (2017) Familial Mediterranean fever-associated diseases in children. QJM 110(5):287–290
Pehlivan E, Adrovic A, Sahin S et al (2018) PFAPA syndrome in a population with endemic familial Mediterranean fever. J Pediatr 192:253–255
Beser OF, Cokugras FC, Kutlu T et al (2014) Association of familial Mediterranean fever in Turkish children with inflammatory bowel disease. Turk Pediatri Ars 49:198–202
Berkun Y, Levy R, Hurwitz A et al (2011) The familial Mediterranean fever gene as a modifier of periodic fever, aphthous stomatitis, pharyngitis, and adenopathy syndrome. Semin Arthritis Rheum 40(5):467–472
Cakir N, Pamuk ON, Dervis E et al (2012) The prevalences of some rheumatic diseases in western Turkey: Havsa study. Rheumatol Int 32:895–908
Tozun N, Atug O, Imeryuz N et al (2009) Clinical characteristics of inflammatory bowel disease in Turkey: a multicenter epidemiologic survey. J Clin Gastroenterol 43:51–57
Can G, Posul E, Yilmaz B et al (2018) Epidemiologic features of ınflammatory bowel disease in Western Blacksea region of Turkey for the last 10 years: retrospective cohort study. Korean J Intern Med 34:519–529
Aksu K, Keser G (2011) Coexistence of vasculitides with Familial Mediterranean Fever. Rheumatol Int 31:1263–1274
Yalçınkaya F, Ozcakar ZB, Kasapcopur O et al (2007) Prevalence of the MEFV gene mutations in childhood polyarteritis nodosa. J Pediatr 151(6):675–678
Can E, Yaprak ZK, Hamilcikan S, Erol M, Gayret OB, Yigit O (2018) MEFV gene mutations and clinical course in pediatric patients with Henoch–Schönlein purpura. Arch Argent Pediatr 116(3):e385–e391
Mahr A, Guillevin L, Poissonnet M, Aymé S (2004) Prevalences of polyarteritis nodosa, microscopic polyangiitis, Wegener’s granulomatosis, and Churg–Strauss syndrome in a French urban multiethnic population in 2000: a capture–recapture estimate. Arthritis Care Res (Hoboken) 51:92–99
Kasifoglu T, Calisir C, Cansu DU, Korkmaz C (2009) The frequency of sacroiliitis in familial Mediterranean fever and the role of HLA-B27 and MEFV mutations in the development of sacroiliitis. Clin Rheumatol 28(1):41–46
Akar S, Soysal O, Balci A et al (2013) High prevalence of spondyloarthritis and ankylosing spondylitis among familial Mediterranean fever patients and their first-degree relatives: further evidence for the connection. Arthritis Res Ther 15:R21
Päivonsalo-Hietanen T, Tuominen J, Saari KM (2000) Uveitis in children: population-based study in Finland. Acta Ophthalmol Scand 78:84–88
Köşker M, Çelikay O, Çalışkan S et al (2018) The association between uveitis and familial Mediterranean fever: coincidence or association? Turk Klin J Ophthalmol 27:249–254
Salehzadeh F, Yasrebi O, Hosseini Khotbesara M, Hosseini Khotbesara M et al (2014) Idiopathic uveitis and familial Mediterranean fever: is there any relationship? Autoimmune Dis 2014:238931
Güncan S, Bilge NS, Candu DÜ, Kaşifoğlu T, Korkmaz C (2016) The role of MEFV mutations in the concurrent disorders observed in patients with familial Mediterranean fever. Eur J Rheumatol 3:118–121
Schwartz T, Langevitz P, Zemer D, Gazit E, Pras M, Livneh A (2000) Behcet’s disease in Familial Mediterranean fever: characterization of the association between the two diseases. Semin Arthritis Rheum 29:286–295
Yurdakul S, Gunaydin I, Tuzun Y et al (1988) The prevalence of Behcet’s syndrome in a rural area in northern Turkey. J Rheumatol 15:820–822
Saraçlar Y, Sekerel BE, Kalayci O et al (1998) Prevalence of asthma symptoms in school children in Ankara, Turkey. Respir Med 92:203–207
Oneş U, Sapan N, Somer A et al (1997) Prevalence of childhood asthma in Istanbul, Turkey. Allergy Eur J Allergy Clin Immunol 52:570–575
Kalyoncu AF, Selçuk ZT, Karakoca Y et al (1994) Prevalence of childhood asthma and allergic diseases in Ankara, Turkey. Allergy 49:485–488
Sackesen C, Bakkaloglu A, Sekerel BE et al (2004) Decreased prevalence of atopy in paediatric patients with familial Mediterranean fever. Ann Rheum Dis 63:187–190
Bolat E, Arikoglu T, Sungur MA, Batmaz SB, Kuyucu S (2017) Prevalence and risk factors for wheezing and allergic diseases in preschool children: a perspective from the Mediterranean coast of Turkey. Allergol Immunopathol (Madr) 45:362–368
Brenner-Ullman A, Melzer-Ofir H, Daniels M, Shohat M (1994) Possible protection against asthma in heterozygotes for familial Mediterranean fever. Am J Med Genet 53:172–175
Aydoğmuş Ç, Ayaz NA, Çakan M et al (2017) Is there any difference regarding atopy between children with familial Mediterranean fever and healthy controls? Allergol Immunopathol (Madr) 45:549–552
Aypar E, Ozen S, Okur H, Kutluk T, Besbas N, Bakkaloglu A (2003) Th1 Polarization in familial Mediterranean fever. J Rheumatol 30:2011–2013
Simsek I, Pay S, Pekel A et al (2007) Serum proinflammatory cytokines directing T helper 1 polarization in patients with familial Mediterranean fever. Rheumatol Int 27:807–811
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MY, AA, and OK contributed to the conception and design of the study, data analysis and manuscript writing. AA had substantial contribution to conception and design of the study and to data analysis. ET, KB, and MA contributed to data collection and data input. OK contributed to data analysis and manuscript writing. SS and KB contributed to data analysis and critical revisions. OK made final manuscript to be submitted for publication. All authors read and approved the final version of the manuscript.
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Yildiz, M., Adrovic, A., Tasdemir, E. et al. Evaluation of co-existing diseases in children with familial Mediterranean fever. Rheumatol Int 40, 57–64 (2020). https://doi.org/10.1007/s00296-019-04391-9
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DOI: https://doi.org/10.1007/s00296-019-04391-9