Is the IL-6 -174G/C Gene Polymorphism Related to the Disease Severity Score in Turkish Children with Familial Mediterranean Fever?

Introduction: Nonalcoholic fatty liver disease (NAFLD) is closely associated with metabolic syndrome (MetS), insulin resistance (IR) and chronic inflammation. Although familial Mediterranean fever (FMF) patients have no symptoms in the periods between attacks, their subclinical inflammation continues. The aim of the present study was to determine the NAFLD frequency in FMF patients and to evaluate their MetS, IR and lipid profiles. Methods: The study included 54 FMF patients and 54 control subjects. The clinical and demographic characteristics of the subjects were recorded, and the patients’ Pras disease severity score was calculated. IR was determined using the homeostasis model assessment (HOMA) index. MetS was diagnosed using the revised National Cholesterol Education Program Adult Treatment Panel III criteria (NCEP ATP III). Hepatic ultrasonography was used to diagnose NAFLD. Results: NAFLD was observed in 15 FMF patients (27.8%) and 14 controls (25.9%). The difference between the groups was not significant (p=0.828). Similarly, no significant difference was found between the two groups for MetS frequency and HOMA index levels. Fasting plasma glucose was significantly higher in FMF patients, whereas differences between the two groups were not significant for lipid levels and other parameters. When FMF patients with and without NAFLD were compared, no significant difference was found in Pras disease severity score, duration of the disease and daily colchicine dose. Conclusion: The present study showed that NAFLD frequency was not increased in FMF patients, and that patients’ MetS frequency, IR and lipid profiles were not different from control subjects.

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Disease severity in children and adolescents with familial Mediterranean fever: a comparative study to explore environmental effects on a monogenic disease

Annals of the Rheumatic Diseases ◽

10.1136/ard.2008.092031 ◽

2008 ◽

Vol 68 (2) ◽

pp. 246-248 ◽

Cited By ~ 59

Author(s):

S Ozen ◽

N Aktay ◽

E Lainka ◽

A Duzova ◽

A Bakkaloglu ◽

...

Keyword(s):

Familial Mediterranean Fever ◽

Disease Severity ◽

Group Living ◽

Scoring Systems ◽

Monogenic Disease ◽

Secondary Amyloidosis ◽

Turkish Children ◽

Severity Scores ◽

Significant Difference ◽

Mediterranean Fever

Background:Worldwide, familial Mediterranean fever (FMF) is the most common autoinflammatory disease. It has been suggested that environmental factors affect the phenotype as some patients do not develop the complication of secondary amyloidosis.Objective:To analyse whether disease severity in Turkish children with FMF, living in Turkey and Germany is different.Patients and methods:A total of 55 Turkish children living in Turkey were compared with 45 Turkish children born and raised in Germany. Mean age among the group from Turkey and Germany was 42.2 and 44.29 months, respectively. M694V was the leading mutation in both groups. The severity scores were compared with two scoring systems, modified according to published paediatric data for dosage.Results:There was no significant difference between the mean C-reactive protein and erythrocyte sedimentation rate levels of the two groups. According to the modified Sheba Center score, 78.2% of patients from the group living in Turkey had a severe course compared with 34.1% from the group living in Germany. The modified score of Pras et al also showed more severe disease in the patients from Turkey. The difference between the two groups for both scoring systems were significant (both p<0.05).Conclusions:We believe the modified scores that we introduce can be widely used for children. Our results suggest that the environment affects the phenotype of a monogenic disease of the innate inflammatory pathway.

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Development and initial validation of international severity scoring system for familial Mediterranean fever (ISSF)

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2015-208671 ◽

2016 ◽

Vol 75 (6) ◽

pp. 1051-1056 ◽

Cited By ~ 32

Author(s):

Erkan Demirkaya ◽

Cengizhan Acikel ◽

Philip Hashkes ◽

Marco Gattorno ◽

Ahmet Gul ◽

...

Keyword(s):

Familial Mediterranean Fever ◽

Disease Severity ◽

Severity Score ◽

Characteristic Curve ◽

Severe Disease ◽

Clinical Manifestations ◽

Future Research ◽

Laboratory Findings ◽

Therapeutic Decisions ◽

Mediterranean Fever

ObjectiveTo develop widely accepted international severity score for children and adult patients with familial Mediterranean fever (FMF) that can be easily applied, in research and clinical practice.MethodsCandidate severity criteria were suggested by several FMF expert physicians. After three rounds of Delphi survey, the candidate criteria, defined by the survey, were discussed by experts in a consensus meeting. Each expert brought data of clinical manifestations, laboratory findings and physician's global assessments (PGAs) of minimum 20 patients from their centres. We used the PGAs for disease severity as a gold standard. Logistic regression analysis was used to evaluate the predicting value of each item, and receiver operating characteristic curve analysis was performed to demonstrate the success of the criteria set.ResultsA total of 281 patients consist of 162 children and 119 adults with FMF were enrolled and available for validity analysis: Nine domains were included in the final core set of variables for the evaluation of disease severity in FMF. The International Severity Score for FMF (ISSF) may reach a maximum of 10 if all items are maximally scored. The threshold values to determine: severe disease ≥6, intermediate disease 3–5, mild disease ≤2. Area under the curve was calculated as 0.825 for this set in the whole group.ConclusionsThe initial validity of ISSF both in children and adult with FMF was demonstrated. We anticipate that it will provide a robust tool to objectively define disease severity for clinical trials, future research as well as for therapeutic decisions in managing patients with FMF.

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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.

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AB1065 VISIT COMPLIANCE IN PATIENTS WITH FAMILIAL MEDITERRANEAN FEVER: RESULTS FROM A GAZI UNIVERSITY FMF COHORT

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.4675 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1822.1-1822

Author(s):

R. Bilici Salman ◽

A. Avanoğlu Güler ◽

H. Satiş ◽

H. Karadeniz ◽

H. Babaoglu ◽

...

Keyword(s):

Logistic Regression ◽

Family History ◽

Familial Mediterranean Fever ◽

Predictive Factors ◽

Severity Score ◽

Comorbid Disease ◽

Rheumatology Clinic ◽

Mediterranean Fever ◽

One Year

Background:Follow-up in all rheumatologic patients is critical, particularly Familial Mediterranean Fever (FMF). Current recommendations for all experts by the EULAR state that patients with FMF should be evaluated 6-monthly intervals to monitore the character and frequency of the attacks and the acute phase response. Disease-related complications such as amyloidosis can beasymptomaticand need only a careful follow-up.Objectives:to quantify this phenomenon and to find predictive factors of visit compliance in patients with FMF.Methods:The study included 474 adult patients with a diagnosis of FMF who followed at the outpatient rheumatology clinic of tertiary university hospital, from January 2018 to December 2018. . Demographic, socioeconomic data, familiy history, comorbid disease, medication history, characteristics, the International Severity Score for FMF (ISSF),autoinflammatory disease damage index (ADDI) were recorded. Visit compliance was defined as the presence of two visits in the outpatient rheumatology clinic for FMF last one year for the purposes set out in EULAR suggestion.Those who had fewer than two visits in the last one year were considered noncompliant.Results:230 (48.5%) were compliant while 244 (51.5 %) patients were noncompliant with their rheumatology visit. Both compliant and noncompliant patients had similar median age and disease duration. Female sex and being married was increased the visit compliance.The results of the logistic regression model exploring factors associated with compliance indicated that presence of family history in parents, absence of family history in sibling, treatment with biologic agents, other drug using,presence of more than 2 attacks except fever and adequate medical care were important predictors of visit compliance.Conclusion:In conclusion, if FMF patients visit compliance increase, their functionality, medication adherence and quality of life will increase and flares and complication of disease can decrease. Thus, we highlight some recommendations for FMF specialist, patients and health care providers to improve outcomes.Table 2.Multivariate logistic regression analysis for predictive factors of visit compliance of the patients with FMF, n=430Adj. OR%95 CI**pFamily history in parents(positive history vs negative)1,81,0-3,10.03Family history in sibling(negative history vs positive)1,91,2-3,10.004Comorbid disease status1,30,7-2,50.32Treatment(anakinra&canakinumab vs colchicine)3,71,7-8,20.001Drug using(other drugs vs FMF drugs)2,21,1-4,40.01More than 2 attacks except fever2,31,2-4,00.004Chronic peripheral arthritis2,30,8-6,60.10Proteinuria2,20,7-6,70.14Adequate medical care1,91,2-3,10.003Number of index flare within last 12-month0,90,9-1,00.38ISSF severity score0,80,7-1,10,30Disclosure of Interests:None declared

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