A mild form of Familial Mediterranean Fever associated with a polymorphisms C.NT 1588,-69G>

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

Download Full-text

AB0419 THE COEXISTENCE OF FAMILIAL MEDITERRANEAN FEVER (FMF) IN SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) PATIENTS - A CROSS SECTIONAL STUDY

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.2305 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1509.1-1510

Author(s):

T. Klein ◽

S. Tiosano ◽

A. Chohen ◽

H. Amital

Keyword(s):

Systemic Lupus Erythematosus ◽

Familial Mediterranean Fever ◽

Lupus Erythematosus ◽

Cross Sectional Study ◽

Review Of The Literature ◽

Sectional Study ◽

Systemic Lupus ◽

Cross Sectional ◽

Mediterranean Fever ◽

Age And Sex

Background:Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease characterized by multisystem inflammatory lesions affecting many organ systems in the body. Familial Mediterranean fever (FMF) is an autosomal recessive disease of chronic autoimmune inflammation characterized by frequently relapsing self-limiting fever and inflammation that may be localized in peritoneum, pleura, joint or skin.1Previous studies have described the similarity of clinical symptoms of FMF among SLE patients. However, the literature on this topic is inconsistent and based mostly on case reports.2-4Objectives:To examine the proportions of coexistence of FMF among SLE patients compared to the general population. We hypothesized that the proportion of FMF among SLE patients is higher than the general population.Methods:This cross-sectional study used the Clalit Health Services database, the largest Health Maintenance Organization in Israel, serving 4,400,000 members. SLE patients were compared to age- and sex-matched controls. Chi- was used for univariate analysis.Results:The study included4886 SLEpatients and 24430 age- and sex-matched controls. The SLE group had a significantly higher proportion of FMF patients compared to non-SLE controls (0.68% and 0.21% respectively; p < 0.001).Table 1. All study populationTable 1.SLE patients and matched controls basic characteristicsNo SLESLEp.overallN=24430N=4886Age51.2±16.551.2±16.51.000Gender: Female20100 (82.3%)4020 (82.3%)1.000FMF52 (0.21%)33 (0.68%)<0.001Table 2. StratificationTable 2.comparison of FMF patients with and without SLEFMF without SLEFMF with SLEp.overallN=52N=33Age44.6±13.750.5±17.70.106Gender: Female45 (86.5%)26 (78.8%)0.523Conclusion:FMF was found to be more common amongst SLE patients compared to matched controls.The current study results suggest that the occurrence of SLE turn patients with an appropriate genetic and environmental setting to develop also FMF. This cross-sectional study sheds light on the coexistence of these two diseases, autoimmune and autoinflammatory.References:[1]Kucuk A, Gezer IA, Ucar R, Karahan AY. Familial mediterranean fever.Acta Medica (Hradec Kralove). 2014;57(3):97-104.[2]Lidar M, Zandman-Goddard G, Shinar Y, Zaks N, Livneh A, Langevitz P. SLE and FMF: A possible negative association between the two disease entities–report of four cases and review of the literature.Lupus. 2008;17(7):663-669.[3]Erten S, Taskaldiran I, Yakut ZI. Are systemic lupus erythematosus patients carrying MEFV gene less prone to renal involvement? report of three cases and review of the literature.Ren Fail. 2013;35(7):1013-1016.[4]Shinar Y, Kosach E, Langevitz P, et al. Familial mediterranean Fever gene (MEFV) mutations as a modifier of systemic lupus erythematosus.Lupus. 2012;21(9):993-998.Disclosure of Interests: :None declared

Download Full-text

SAT0541 THE SEVERITY OF FMF MAY BE ASSOCIATED WITH CO-MORBIDITIES

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.801 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1227.3-1228

Author(s):

M. E. Tezcan ◽

N. Şen ◽

M. Yilmaz ◽

Ö. Volkan ◽

E. Tükel ◽

...

Keyword(s):

Familial Mediterranean Fever ◽

Scoring System ◽

Disease Duration ◽

Severe Disease ◽

Smoking History ◽

Disease Group ◽

Severity Scoring ◽

Mild Disease ◽

Co Morbidity ◽

Mediterranean Fever

Background:Familial Mediterranean fever (FMF) is an auto inflammatory disease with recurrent attacks of serositis. Frequent attacks and disease related sequels may be associated with co-morbidities in FMF patients.Objectives:One of the tools for evaluating the FMF severity is the international severity scoring system for FMF (ISSF)1. This score includes disease related sequels, acute phase measurements, attack features and exertional leg pain. Therefore, more severe disease may be link with subclinical inflammation, amyloidosis and frequent, prolonged and widespread attacks. All these components may augment the frequency of non-disease related co-morbidities.Methods:We enrolled 158 FMF patients who fulfilled modifiedTel-HashomerDiagnosisCriteria2. The patients dichotomized based upon disease severity (mild disease or severe disease). Patients with ISSF scores lower or equal to 2 were accepted to have mild disease. Then, we compared frequency of non-disease related co-morbidities between the groups. These co-morbidities arehypertension, hypothyroidism, hyperthyroidism cardiovascular diseases, coronary artery diseases, cerebrovascular diseases, chronic renal disease (non-FMF related), chronic obstructive pulmonary diseases, and diabetes mellitus. This study was approved by the Local Research Ethics Committee and carried out in compliance with the Helsinki Declaration. All the patients gave written informed consent. P-value lower than 0.05 was considered as statistically significant.Results:Demographic features, disease duration, smoking history and body mass index (BMI) were similar between the groups. Frequency of co-morbidity in severe disease group was statistically higher than mild disease group (p=0.02). Most frequent co-morbidity was hypertension in both groups.Table.Features of mild and severe FMF groupsMild (n=135)Severe (n=23)pGender (M/F)47/8811/120.23Age36.4±11.336.5±14.30.68Smoking (%)38 (28.1)5 (21.7)0.52BMI (kg/m2)24.3±9.224.0±8.90.34Disease duration (year)7.7±11.38.6±14.30.09Amyloidosis (%)2 (1.4)3 (13.0)0.02Exon 10 homozygote (%)35 (25.9)9 (39.1)0.19Colchicine dosage (mg/day)1.2±0.41.4±0.50.02ISSF scores0.7 ±0.73.4±0.5<0.001Co-morbidity (%)25 (18.5)9 (39.1)0.02Conclusion:In our FMF patient cohort, we found that severity of the disease may be associated with higher frequency of co-morbidities. Therefore, clinicians should be aware of the high possibility of co-morbidities in patients with more severe FMF and addressed these co-morbidities timely and properly.References:[1]Demirkaya E, et al. Development and initial validation of international severity scoring system for familial Mediterranean fever (ISSF). Ann Rheum Dis 2016;75:1051-6.[2]Berkun Y, et al. Diagnostic criteria of familial Mediterranean fever. Autoimmun Rev 2014;13:388-90.Acknowledgments:NoneDisclosure of Interests:None declared

Download Full-text

Toll-like receptor-4 gene variations in Egyptian children with familial Mediterranean fever

Egyptian Rheumatology and Rehabilitation ◽

10.1186/s43166-020-00053-y ◽

2021 ◽

Vol 48 (1) ◽

Author(s):

Yomna Farag ◽

Samia Salah ◽

Hanan Tawfik ◽

Mai Hamed ◽

Huda Marzouk

Keyword(s):

Familial Mediterranean Fever ◽

Disease Severity ◽

Gene Mutation ◽

Rflp Analysis ◽

Gene Variants ◽

Gene Variant ◽

Toll Like Receptor ◽

Toll Like Receptor 4 ◽

Egyptian Children ◽

Mediterranean Fever

Abstract Background Familial Mediterranean fever (FMF) is an autosomal recessive disorder affecting people in the region of the Mediterranean Sea. It is usually associated with mutation in Mediterranean fever (MEFV) gene that encodes the pyrin protein, which affects the innate inflammatory response. Toll-like receptors (TLR) are a family of pattern recognition receptors that recognize pathogenic microbes and activate antimicrobial defense mechanisms. Toll-like receptor 4 (TLR-4) is concerned with recognition of gram-negative organisms. There is growing clinical evidence suggesting a role for expression of TLRs in the immune pathogenesis of FMF. Thus, the aim of the current study was to evaluate the presence of TLR-4 (p.Asp299Gly) and TLR-4 (p.Thr399Ile) gene variants in association with Egyptian children having FMF, furthermore, its effect on disease course and severity. Results Seventy Egyptian children diagnosed as having FMF, together with 50 age and gender-matched controls were enrolled in the study. The TLR-4 (p.Asp299Gly) and (Thr399Ile) gene variants were determined by PCR-RFLP analysis for all studied patients and controls. TLR-4 p.Asp299Gly gene variant was detected in 1 (1.4%) of the patients and p.Thr399Ile gene variant was detected in 2 (2%). None of the controls had any of the two tested gene variants. All found variations were heterozygous. We could not find a statistically significant association with disease severity in cases with or without TLR-4 gene variants (P = 0.568). Patients with M694V gene mutation showed a higher disease severity (P = 0.035). Conclusion TLR-4 (p.Asp299Gly) and (p.Thr399Ile) gene variants were not found to have a link with the occurrence, the clinical picture of FMF, its severity, and response to colchicine treatment in Egyptian children. M694V gene mutation seems to be associated with higher disease severity. Further larger studies are needed to verify these results.

Download Full-text