Journal Article
. 2015 Jun; 49(3):198-202.
doi: 10.5152/tpa.2014.1998.

Association of familial Mediterranean fever in Turkish children with inflammatory bowel disease

Ömer Faruk Beşer 1 Fügen Çullu Çokuğraş 1 Tufan Kutlu 1 Ethem Erginöz 2 Didem Gülcü 1 Özgür Kasapçopur 3 Tülay Erkan 1 
Affiliations
  • PMID: 26078663
  •     17 References
  •     6 citations

Abstract

Aim: Familial Mediterranean fever (FMF) and inflammatory bowel disease (IBD) carry similar clinical and biological properties. Both are characterized with chronic inflammation attacks and neutrophil migration and impaired apoptosis mechanism are present in the areas of damage in both conditions. In our study, we aimed to determine the frequency of association of FMF in patients with IBD, to compare the demographic, clinical, laboratory and treatment response properties in these patients with the ones in other IBD patients and to determine association of FMF especially in treatment-resistant patients.

Material And Methods: Fifty-three patients who were being followed up with a diagnosis of IBD aged between 0 and 18 years were included in the study. The patient group included the patients who were diagnosed with IBD according to clinical, serological, endoscopic and histopathological criteria, who were being followed up and whose therapies were continuing. Genetic analysis in terms of MEFV gene mutations was performed in all patients with a diagnosis of IBD. Acute phase reactants, complete blood count, immunoglobulin levels, stool analysis, "perinuclear anti-neutrophil cytoplasmic antibodies" (pANCA) and "anti-Saccharomyces cerevisiae antibodies" (ASCA) were studied at the time of diagnosis. The diagnosis of FMF was made according to detailed history, physical examination findings, laboratory tests and the results of genetic analyses in terms of MEFV gene mutations in accordance with the criteria defined in 2009.

Results: We found that FMF accompanied in 14 (26.4%) of the patients who had a diagnosis of IBD. 3 of these 14 patients in whom FMF accompanied were being followed up with a diagnosis of Crohn disease and 11 were being followed up with a diagnosis of ulcerative colitis. All of these patients had MEFV gene mutation. These mutations included M694V (50%), K695R (21.4%), M680I (14.3%) and R202Q (14.3%) in order of frequency. When the laboratory data were compared between the patients who had a diagnosis of IBD alone and who had a diagnosis of IBD plus FMF, it was observed that the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) values were statistically significantly higher in the IBD+FMF group.

Conclusions: FMF is a common condition in the Turkish population and M694V mutation is found most commonly. In our study, this status did not change in cases where FMF accompanied IBD, but K695R mutation was found more frequently compared to FMF alone. We think that it should be kept in mind that other inflammatory conditions including mainly FMF may accompany IBD, if a case of IBD does not have an expected course or is resistant to treatment.

Keywords: Familial Mediterranean fever; MEFV; inflammatory bowel disease.

The familial Mediterranean fever (MEFV) gene may be a modifier factor of inflammatory bowel disease in infancy.
Sinan Sari, Odul Egritas, Buket Dalgic.
Eur J Pediatr, 2007 May 24; 167(4). PMID: 17520284
Targeted disruption of pyrin, the FMF protein, causes heightened sensitivity to endotoxin and a defect in macrophage apoptosis.
Jae Jin Chae, Hirsh D Komarow, +4 authors, Daniel L Kastner.
Mol Cell, 2003 Apr 02; 11(3). PMID: 12667444
Highly Cited.
MEFV mutations in systemic onset juvenile idiopathic arthritis.
N A Ayaz, S Ozen, +6 authors, A Bakkaloğlu.
Rheumatology (Oxford), 2008 Nov 06; 48(1). PMID: 18984609
Increased frequency of mutations in the gene responsible for familial Mediterranean fever (MEFV) in a cohort of patients with ulcerative colitis: evidence for a potential disease-modifying effect?
Stavros Giaglis, Konstantinos Mimidis, +9 authors, Konstantinos Ritis.
Dig Dis Sci, 2006 Apr 15; 51(4). PMID: 16614989
Criteria for the diagnosis of familial Mediterranean fever.
A Livneh, P Langevitz, +6 authors, M Pras.
Arthritis Rheum, 1997 Oct 23; 40(10). PMID: 9336425
Highly Cited.
Innate immunity and apoptosis in IBD.
G Scott Lichtenberger, Richard A Flavell, Lena Alexopoulou.
Inflamm Bowel Dis, 2004 Jun 01; 10 Suppl 1. PMID: 15168833
Review.
Clinical and subclinical inflammation in patients with familial Mediterranean fever and in heterozygous carriers of MEFV mutations.
H J Lachmann, B Sengül, +8 authors, P N Hawkins.
Rheumatology (Oxford), 2006 Jan 13; 45(6). PMID: 16403826
The association of inflammatory bowel disease and Mediterranean fever gene (MEFV) mutations in Turkish children.
Nuray Uslu, Aysel Yüce, +7 authors, Seza Ozen.
Dig Dis Sci, 2010 Mar 23; 55(12). PMID: 20306331
Familial Mediterranean fever and related periodic fever syndromes/autoinflammatory diseases.
Sinisa Savic, Laura J Dickie, Michele Battellino, Michael F McDermott.
Curr Opin Rheumatol, 2011 Nov 18; 24(1). PMID: 22089100
Review.
The autoinflammatory syndromes.
Michael F McDermott, Ivona Aksentijevich.
Curr Opin Allergy Clin Immunol, 2004 Jan 31; 2(6). PMID: 14752334
Review.
A new set of criteria for the diagnosis of familial Mediterranean fever in childhood.
Fatos Yalçinkaya, Seza Ozen, +10 authors, Aysin Bakkaloglu.
Rheumatology (Oxford), 2009 Feb 06; 48(4). PMID: 19193696
Association of inflammatory bowel disease with familial Mediterranean fever in Turkish children.
Omer F Beşer, Ozgür Kasapçopur, +3 authors, Tülay Erkan.
J Pediatr Gastroenterol Nutr, 2012 Nov 21; 56(5). PMID: 23164758
Detection of MEFV gene mutations in patients with inflammatory bowel disease.
Erkan Yurtcu, Hale Gokcan, Ugur Yilmaz, Feride Iffet Sahin.
Genet Test Mol Biomarkers, 2009 Mar 25; 13(1). PMID: 19309279
New concepts in the pathophysiology of inflammatory bowel disease.
Giorgos Bamias, Mark R Nyce, +3 authors, American Physiological Society.
Ann Intern Med, 2005 Dec 21; 143(12). PMID: 16365470
Review.
A common pathway in periodic fever syndromes.
Michael F McDermott.
Trends Immunol, 2004 Aug 25; 25(9). PMID: 15324736
Review.
Diagnostic significance of endoscopic biopsy in Crohn's disease.
R Pötzi, M Walgram, +2 authors, A Gangl.
Endoscopy, 1989 Mar 01; 21(2). PMID: 2707173
Association of the MEFV gene variations with inflammatory bowel disease in Turkey.
Filiz Akyuz, Fatih Besisik, +9 authors, Ahmet Gul.
J Clin Gastroenterol, 2012 Jul 20; 47(3). PMID: 22810105
Neonatal ulcerative colitis associated with Familial Mediterranean fever: a case report.
Elif Sag, Ferhat Demir, +2 authors, Murat Cakir.
Rheumatol Int, 2017 Oct 14; 38(1). PMID: 29027576
Ulcerative Colitis and Familial Mediterranean Fever: Can Anakinra Treat Both?
Lisa Kaly, Michael Rozenbaum, +6 authors, Itzhak Rosner.
ACG Case Rep J, 2019 Oct 18; 6(7). PMID: 31620540    Free PMC article.
Evaluation of co-existing diseases in children with familial Mediterranean fever.
Mehmet Yildiz, Amra Adrovic, +6 authors, Ozgur Kasapcopur.
Rheumatol Int, 2019 Jul 29; 40(1). PMID: 31352561
The Influence of Concomitant Disorders on Disease Severity of Familial Mediterranean Fever in Children.
Rabia Miray Kişla Ekinci, Sibel Balci, Derya Ufuk Altintaş, Mustafa Yilmaz.
Arch Rheumatol, 2017 Oct 30; 33(3). PMID: 30632526    Free PMC article.
Antineutrophil cytoplasmic antibody-positive familial Mediterranean fever and hyperthyroidism: A case report.
Sorato Segoe, Ken-Ei Sada, +5 authors, Jun Wada.
Medicine (Baltimore), 2018 Dec 24; 97(51). PMID: 30572542    Free PMC article.
Evolution of Our Understanding of XIAP Deficiency.
Anne C A Mudde, Claire Booth, Rebecca A Marsh.
Front Pediatr, 2021 Jul 06; 9. PMID: 34222142    Free PMC article.
Review.