FRI0455 IS THERE AN INCREASE IN THE FREQUENCY OF INFLAMMATORY DISEASES IN THE FAMILIES OF PATIENTS WITH FMF?
Authors: S. Yildirim, M. Yildiz, A. Aliyeva, F. Haslak, O. Koker, A. Adrovic, S. Sahin, K. Barut, O. Kasapcopur
Journal: Annals of the Rheumatic Diseases (2020)

Background: Familial Mediterranean Fever (FMF) is the most common periodic fever syndrome in childhood with an autosomal recessive inheritance pattern and is characterized by unprovoked fever attacks, serositis episodes. The causative gene of the disease is MEFV that encodes pyrin protein. The pyrin protein takes a role in pathways related to inflammation, and mutations of it lead to increased inflammation. It is already shown that frequencies of some certain diseases like PAN, HSP increase in patients with FMF. Nevertheless, frequencies of inflammatory diseases in families of patient with FMF haven’t been investigated. Objectives: In this study, we have aimed to evaluate the comorbid disorders in a large cohort of families of patients with FMF. Methods: Four hundred and ninety-eight children with FMF, one hundred and forty patients with JIA and ninety-two healthy children were interviewed between December 2019 and January 2020. In JIA group and healthy control group, patients who have family history for FMF were excluded from the study. Patients were asked about characteristics of their disease attacks and if there is a relative with any inflammatory diseases who does not have FMF in patient’s 1 st and 2th degree relatives. Results: Demographic features of study group have shown in Table 1. The most common MEFV mutations in patients with FMF were: M694V homozygotes (13.2 %), M694V heterozygotes (12 %), M694V homozygotes and R202Q homozygotes (6,8 %). Type II diabetes, asthma and hypothyroidism were the most commonly detected diseases in all cohorts. Frequency of Behçet’s disease, allergic rhinitis and type II diabetes were significantly higher in families of patients with FMF than other groups (p&lt;0.05) (Table 2). Table 1. Demographic features of study population. FMF † JIA †† Healthy Control n: 498 (% ) mean +/- SD n: 140 (% ) mean +/- SD n: 92 (% ) mean +/- SD Female 284 (57) 91 (65) 55 (59.8) Age (years) 12.9 ± 8.2 11.7 ± 5.1 7.4 ± 4.6 Age at Onset (years) 4.3 ± 3.3 5.4 ± 4.1 - Age at Diagnosis (years) 6.3 ± 3.6 6.3 ± 4.5 - Delay in Diagnosis (months) 23.8 ± 29.2 11.3 ± 28.2 - Follow-up Duration (years) 6.9 ± 8.3 5.3 ± 4.0 - Consanguinity 100 (20) 25 (17.8) 8 (8.6) Family History of FMF 282 (56.6) 0 (0) 0 (0) JIA subgroup - - Oligoarticular 72 (51.4) Polyarticular (RF negative ) 16 (11.4) Polyarticular (RF positive ) 3 (2.1) Enthesitis Related Arthritis 14 (10) Psoriatic Arthritis 7 (5) Systemic 23 (16.4) Other 5 (3.5) Clinical Findings - - Fever 392 (78.1) Abdominal Pain 429 (86.1) Chest Pain 102 (20.5) Arthralgia 334 (67.1) Arthritis 157 (31.5) Extremity Pain 64 (12.8) Heel Pain 44 (8.8) Myalgia 43 (8.6) *ELE 13(2.6) Serositis 10 (2) † Familial Mediterranean Fever †† Juvenile Idiopathic Arthritis *Erysipelas like erythema Table 2. Comparison of frequencies of diseases detected among families of patient groups (shortened). Diseases FMF JIA Healthy Control p 1 Type II Diabetes 284 (57) 64(45.7) 44 (47.8) 0.02 Asthma 139 (27.9) 30 (21.4) 20 (21.7) 0.19 Hypothyroidism 122 (24.4) 27 (19.2) 14 (15.2) 0.09 Eczema 68 (13.6) 14 (10) 5 (5.4) 0.06 Psoriasis 49 (9.8) 6 (4.2) 7 (7.6) 0.10 Allergic Rhinitis 49 (9.8) 3 (2.1) 1 (1) 0.001 Hyperthyroidism 40 (8) 9 (6.4) 3 (3.2) 0.24 Behçet’s Disease 31 (6.2) 1 (1) 2 (2.1) 0.01 Rheumatic Fever 30 (6) 10 (7.1) 2 (2.1) 0.25 Conclusion: In this study, we have reported increased frequencies of Behçet’s disease, allergic rhinitis and type II diabetes in families of patients with FMF. Our results suggest that possible increased mutation load among families of patients with FMF may cause increased inflammatory diseases. References: [1]Yildiz M, Adrovic A, Tasdemir E, et al. Evaluation of co-existing diseases in children with familial Mediterranean fever. Rheumatol Int . 2020;40(1):57–64. doi:10.1007/s00296-019-04391-9 Disclosure of Interests: None declared