Familial Mediterranean fever in Armenian children with inflammatory bowel disease

Gayane Amaryan; Tamara Sarkisian; Artashes Tadevosyan; Christian Braegger

doi:10.3389/fped.2023.1288523

Familial Mediterranean fever in Armenian children with inflammatory bowel disease

Front Pediatr. 2024 Feb 12:11:1288523. doi: 10.3389/fped.2023.1288523. eCollection 2023.

Authors

Gayane Amaryan^{1

2}, Tamara Sarkisian^{3

4}, Artashes Tadevosyan⁵, Christian Braegger⁶

Affiliations

¹ National Pediatrics Center for Familial Mediterranean Fever, "Arabkir" Medical Complex-Institute of Child and Adolescent Health, Yerevan, Armenia.
² Department of Pediatrics, Yerevan State Medical University, Yerevan, Armenia.
³ Center of Medical Genetics and Primary Health Care, Yerevan, Armenia.
⁴ Department of Medical Genetics, Yerevan State Medical University, Yerevan, Armenia.
⁵ Department of Public Health and Health Care Organization, Yerevan State Medical University, Yerevan, Armenia.
⁶ Nutrition Research Unit, Children's University Hospital in Zürich, Zürich, Switzerland.

Abstract

Inflammatory bowel disease (IBD) and familial Mediterranean fever (FMF) are inflammatory diseases with complex interactions among genetic, immune, and environmental factors. FMF is a monogenic autoinflammatory disease, characterized by recurrent febrile attacks and polyserositis, and is manifested mainly in childhood. FMF is widespread in Armenia. There are reports on the concurrent occurrence of FMF and IBD. MEFV gene mutations may have a disease-modifying effect on IBD. We have investigated the frequency of MEFV mutations and FMF in Armenian children with IBD and their influence on the clinical course. A total of 69 untreated IBD patients under 18 years of age were enrolled: 52.1% (36) had ulcerative colitis (UC), 21.7% (15) had Crohn's disease (CD), and 26.0% (18) had unclassified colitis (IBD-U). The frequency of FMF among them was 36.2% (25/69), and MEFV mutations were identified in 53.6% (37/69). The highest rate of MEFV mutations and FMF was in UC patients (61.1% and 41.6% respectively). In all, 56.7% (21/37) of IBD patients with MEFV mutations had M694V mutated alleles, mainly in compound heterozygous and heterozygous states. There were no associations in the group of IBD patients with coexisting FMF (25), either between any MEFV mutation and type of IBD or coexistence of FMF. Overall, 36.0% (9/25) of them developed VEO IBD and carried mainly the M694V mutation. We concluded that the carrier frequency of MEFV mutations among Armenian pediatric IBD patients was rather high (53.6%), especially for UC. It was suggested that the MEFV gene is not necessarily a susceptibility gene but most likely modifies the course of IBD. MEFV genetic testing was recommended for Armenian pediatric IBD patients, especially for VEO UC and IBD-U, atypical IBD course, or resistance to the conventional treatment. They should also be asked for isolated febrile attacks, recurrent arthritis, and family history, even in the absence of FMF typical symptoms, to rule out FMF and its complications.

Keywords: children; clinical characteristics; familial Mediterranean fever; genetic characteristics; inflammatory bowel disease.

Grants and funding

The author(s) declare that no financial support was received for the research, authorship, and/or publication of this article.