الفهرس 
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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
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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
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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
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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 .