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Abstract Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease and characterized by recurrent selflimited febrile attacks and polyserositis, it is caused by mutations in the MEFV gene. Continuous subclinical inflammation is expected to be present during attack-free periods as well as during attacks. It is suggested that based on this ongoing inflammatory process development of endothelial dysfunction (ED) and atherosclerosis along with increased risk of cardiovascular disease (CVD) may occur. There are many blood markers which can give idea about vascular endothelial dysfunction such as endocan and assymetric dimethyl arginine. We aimed to assess the value of serum endocan and asymmetric dimethyl arginine as being markers of vascular endothelial dysfunction in Egyptian children and adolescents with FMF for early detection of any vascular complications. So, we conducted a prospective case control study at Pediatric Immunology and Rheumatology Clinics of Menoufia University Hospitals. It was carried out on 50 children diagnosed with Familial Mediterranean fever and 50 age and sex matched apparently healthy children as a control group. Inclusion criteria Children of both sexes who were diagnosed with Familial Mediterranean Fever according to Tel Hashomer criteria. Summary - 98 - Exclusion criteria Patients previously diagnosed with any cardiovascular disease, hepatic, or renal impairment, chronic autoinflammatory disease other than FMF, malignancies, hypothyroidism, hyperlipidemia, those using drugs other than colchicine were excluded from the study. All patients and control children were subjected to the following: Detailed history taking, measurements of Vital signs, Anthropometric measurements, general and local examinations, routine Laboratory investigations (CBC. Kidney function tests, Lipid profile, CRP and Serum amyloid A), Specific investigations Estimation of the serum levels of endocan and asymmetric dimethyl arginine (ADMA) by ELISA. The results of the current study showed: 1. Demographic data of the studied groups showed no statistically significant difference between patients and controls groups regarding age, sex and presence of consanguinity. 2. Anthropometric measurements showed no statistically significant difference regarding mean or centiles of weight, height, and BMI between the studied groups 3. Clinical data in patients showed that mean age at diagnosis in patients was 4.37 ± 1.49 years with mean duration of disease was 3.66 ± 2.21 years. fever was the major documented symptom in 90% of patients followed by abdominal pain in 40 % of patients then arthritis in 4 % of them, Classification of the patients according to Tel Hashomer criteria of diagnosis showed that 28 patients have typical criteria (56٪), 11 patients have atypical with heterozygous genetic affection (22٪), 7 patients were with no genetic affection (14٪) and 4 patients have atypical criteria with homozygous genetic affection (8٪). Summary - 99 - 4. Familial Mediterranean fever gene mutations distribution among patients showed that M694I and E148Q are the most common mutations observed in our patients (both 23.3٪) followed by A744s mutation (20.9٪) 5 .Laboratory data of the studied groups showed that : I. CRP levels of patients group during attack period was statistically significantly higher compared to controls, while during attack free period there was no statistically significant difference between both groups II. No statistically significant differences were observed between patients and controls regarding Hemoglobin, %WBC, platelets, serum urea or creatinine levels. III. LDL-C, TG, Castelli’s risk index II and Atherogenic index of plasma were statistically significantly higher in patients compared to controls. IV. CRP and serum amyloid A were statistically significantly higher in patients during the attack compared to attack free period. V. Serum endocan and asymmetric dimethyl arginine showed high statistically significant difference in patients compared to controls. VI. There was statistically positive significant correlation between ADMA and serum total cholesterol, non HDL –cholesterol, Castelli risk index I, atherogenic index of plasma (AIP) and atherogenic coefficient. Summary - 100 - VII. LDL cholesterol and serum triglycerides showed statistically significant difference in those with homozygous gene mutation compared to those with heterozygous gene mutation. VIII. ROC curve analysis for diagnostic performance of serum endocan and ADMA in FMF patients demonstrated a high significance in FMF patients, endocan with AUC꞊ 0.99 at a cut-off >80pg/ml showed 94% sensitivity, 88% specificity, 88.7% positive predictive value (PPV) and 93.6% negative predictive value (NPV). In addition AUC for ADMA was 0.99 with cut-off value >150ng/ml showed 92% sensitivity, 84% specificity, 85.2% PPV and 91.3% NPV. Conclusion Serum endocan and ADMA could be used as reliable markers of early detection of endothelial dysfunction of children and adolescents with familial Mediterranean fever. Recommendation We recommend early measurement of serum endocan and ADMA for early diagnosis of endothelial dysfunction in patients with familial Mediterranean fever . |