An unusual presentation of familial Mediterranean fever with co-existing polyarteritis nodosa and acute post-streptococcal glomerulonephritis

The homozygous M694V mutation in the MEFV gene may cause an augmented response to the streptococcal infection that plays a role in the development of APSGN and PAN. Both clinical manifestations may occur simultaneously after streptococcal infection in a child who is previously healthy but carries a MEFV mutation.

Serum amyloid A1 genotype associates with adult-onset familial Mediterranean fever in patients homozygous for mutation M694V

Objectives FMF shows considerable variability in severity and type of clinical manifestations by geographic region, which are attributed to Mediterranean fever (MEFV) gene allelic heterogeneity, additional genetic modifiers and environmental factors. Considering the severe impact of MEFV mutation M694V on the FMF phenotype, this work aimed at investigating a possible disease modifying role of the serum amyloid A1 (SAA1) genotype in a cohort of 386 Armenian FMF patients homozygous for MEFV mutation M694V. Methods A cohort of 386 Armenian patients diagnosed with FMF based on the Tel-Hashomer criteria and carrying two MEFV M694V mutant alleles were included in this study. Fifty-two (13.40%) of these patients experienced their first attack at the age of ≥20 years (i.e. adult-onset FMF). MEFV and SAA1 analyses were performed by a commercial reverse-hybridization assay, and resulting genotypes were matched against the patients’ clinicodemographic profiles. Results Genotypic distribution of SAA1 alleles was significantly different between patients with an age of onset <20 and ≥20 years. SAA1 genotypes α/α, α/β and β/β could be identified in 8 (15.38%), 12 (23.08%) and 32 (61.54%) adult-onset patients while this was the case for 47 (14.07%), 172 (51.50%) and 115 (34.43%) patients with a disease onset <20 years, respectively (P < 0.001). Furthermore, adult-onset disease was associated with a less severe FMF phenotype (P < 0.001). Conclusion We have identified a significant relationship between the SAA1β/β genotype and the age of disease onset in M694V homozygous FMF patients.

A HYPOTHETICAL ROLE FOR PLAGUE IN THE SELECTION OF MEFV MUTATION CARRIERS IN THE MEDITERRANEAN AREA

Familial Mediterranean fever (FMF) is the most common autoinflammatory disease associated with mutations in the MEFV gene encoding Pyrin. MEFV mutations are frequent in the Mediterranean region. Increased resistance to an infection endemic to this area could have caused a selective advantage for individuals with MEFV mutations. Recent studies have shown that Pyrin is a part of host defense against microorganisms and it gets activated after sensing Rho GTPase inactivation by bacteria such as Clostridium difficile or Yersinia pestis. However, Yersinia species have another effector molecule, YopM which inhibits Pyrin in addition to RhoA modifiers YopE and YopT. Continuously overactive Pyrin in individuals with MEFV mutations could be a good host defense against Yersinia infections. Y. pestis causes plague, which led to a devastating pandemic in the Mediterranean basin. Thus, plague could be the infection which caused a selective biologic advantage for MEFV mutation carriers in this area.

AB0730 ASSOCIATION OF SPONDYLOARTHRITIS AND FAMILIAL MEDITERRANEAN FEVER AND IMPACT ON DISEASE PHENOTYPE: A SYSTEMATIC REVIEW OF THE LITERATURE

Background:Spondyloarthritis (SpA) and Familial Meditaerranean fever (FMF) may co-exist in certain populations, and have some overlapping manifestations (oligo-arthritis, hip involvement). Their association may impact disease phenotype and may affect disease management.Objectives:To evaluate the association of SpA and FMF and its impact on disease phenotype and management.Methods:A systematic literature search was conducted with the keywords spondyloarthritis and familial mediterranean fever from Janurary 1990 to January 2020 in PubMed and using manual cross-reference methods.Results:The search retrieved 74 articles, out of which 37 articles were relevant to the study question; most of the articles were case reports, with some large cohort studies of FMF and SpA (Flowchart in Figure 1).In large FMF cohorts, the prevalence of SpA was higher compared to the general population (7.5-13%, OR around 10). M694V was a risk factor for SpA. These FMF-SpA patients were older at diagnosis, had lower fever attacks, and higher disease duration, inflammatory back pain, chronic arthritis, enthesopathy, persistent inflammation and higher resistance to Colchicine. In case series, they were responsive to anti-TNF therapy.In large SpA cohorts, MEFV mutation, particularly M694V, was found in 15-35% (even without associated FMF). In most cohorts, MEFV mutation carriers didn’t have any distinct disease phenotype, except for some reports of higher ESR, more hip involvement, higher BASFI and higher BASDAI. Genome-wide association studies and case reports suggest an implication for IL-1 and thus a role for Anakinra therapy in these patients.Conclusion:In FMF or SpA patients with resistance to conventional therapy, the evaluation of disease association should be performed as it may have significant impact on disease management.References:[1]Li et al, Plos Genetics 2019. Watad et al, Frontiers Immunol 2019. Atas et al, Rheumatol Int 2019. Cherqaoui et al, JBS 2017. Zhong et al. Plos One 2017. Ornek et al, Arch Rheumatol 2016. Cinar et al, Rheumatol Int 2008. Durmur et al, JBS 2007.Figure 1.Flowchart of the systematic literature search (Spondyloarthritis, Familial Mediterranean Fever; January 1990-2020).Disclosure of Interests:Nelly Ziade Speakers bureau: Abbvie, Janssen, Lilly, Novartis, Pfizer, Roche, Sanofi, Aref Nassar: None declared

P733 The influence of concomitant familial Mediterranean fewer on Crohn’s disease course: Data from an FMF endemic area

Background Crohn’s disease (CD) and Familial Mediterranean fever (FMF) are both inflammatory disorders characterised by recurrent abdominal pain and fever attacks. Mutations of Mediterranean (MEFV) gene appear to be associated with stricturing behaviour and extraintestinal manifestations of CD. Further clinical studies regarding progression of CD in coexistence with FMF is still required. The aim of this study was to evaluate the influence of concomitant FMF in CD patients on the course of the CD in FMF endemic area. Methods Total 210 adult patients who had diagnosed with CD with or without FMF between November 2006 and April 2019 were respectively examined. FMF diagnoses were based on Tel-Hashomer criteria. The Montreal classification was used to define location and behaviour of CD. CD patients were divided into two groups FMF positive and FMF negative. Severity of CD was assessed by the need for hospitalisation related to CD, whether biological therapy was received and/or whether surgery was undergone due to CD. All demographic features, MEFV mutations, location/behaviour of disease, and extraintestinal manifestations were analysed retrospectively. Results In the present study, 8 (3.8%) of the total 210 CD patients have concomitant FMF. Mean follow-up time in CD-FMF was 59.55 months and CD-non-FMF was 60.98 months. CD patients with or without FMF showed similar demographic features including age, sex, smoking behaviour, disease location, behaviour, and treatment regimen in maintenance of the remission. Regarding extraintestinal manifestations, only peripheral arthritis was found significantly higher in CD-FMF patients (n = 3, 37.5%) compared CD-non-FMF patients (n = 21, 10.4%). In the CD-FMF patients, a result of MEFV mutation gene analysis was found in medical records 6 patients. Of those, 2 had homozygote MEFV mutation, 2 had heterozygote MEFV mutation and 2 without any MEFV mutations. In CD-FMF group, percentage of patients on biological therapy (n = 4, 50%) was significantly higher than CD-non FMF group (n = 24, 11.9%) (p = 0.012). Steroid dependence and hospitalisation in CD-FMF (n = 3, 37.5% and n = 5, 62.5%) group were relatively higher than CD-non-FMF (n = 83, 41.1%) group, but not statistically significant. The percentage of CD-FMF patients who underwent intestinal surgery (n = 1, 12.5%) was similar to that of CD-non-FMF (n = 33, 16.3%). Conclusion In the current study, the prevalence of FMF in CD patients was detected 3.8% in FMF endemic area. The group of patients on biological therapy in CD-FMF patients was significantly higher than CD-non-FMF patients. Frequency of hospitalisation in CD-FMF patients was relatively higher than CD-non-FMF patients. Our findings indicate that concomitant FMF in CD patients may have a negative effect on the course of CD.