Vitamin D and miRNA-155 in Behçet's Disease: Possible Association with the Disease and Disease Activity.

Background: Vitamin D (vit D) controls inflammation and immunity. In Behçet's disease (BD), microRNA-155 is recognized as a significant immune response regulator. We aimed to investigate the role of vit D on immunomodulation and downregulation of inflammatory pathways associated with BD and detect the role of miRNA-155 in BD. Methods: miRNA-155 expression by Real Time -Polymerase Chain Reaction (RT-PCR), and vit D, nuclear factor Kappa-light-chain-enhancer of activated B cells (NF-κB), and Tumor necrosis fact of TNF-α) expression by Enzyme Linked Immunosorbent Assay (ELISA) were assessed. Results: BD patients had a significantly higher relative expression of microRNA-155 (P< 0.001), it was significantly related to vascular manifestations (P< 0.001). Vit D relative expression was significantly low in BD (P< 0.001). There was a significant rise in miRNA-155 in the active group compared to the inactive group (P< 0.001). A significant decrease in vit D levels (IU) was found in inactive and active individuals suffering from BD when compared to controls (P< 0.001). A significant rise was found in vit D levels in inactive BD cases (P< 0.001). A significant positive correlations were found between miRNA-155, NF-κB, TNF-α, and negative correlations with vit D relative expression in BD patients. Conclusions: miRNA-155 relative expression is higher in BD is significantly related to vascular manifestations. It may have a relationship to disease activity. Vitamin D relative expression is significantly low in BD patients, which can significantly influence immunomodulatory BD therapy. Vitamin D deficiency linked to active BD.

Psoriatic arthritis among Egyptian patients with psoriasis attending the dermatology clinic: prevalence, comorbidities, and clinical predictors.

OBJECTIVES: Early diagnosis and treatment of psoriatic arthritis (PsA) help to prevent progressive joint involvement and disabilities. There is a problem in the early diagnosis of PsA worldwide, which may be attributed to the dermatologists missing PsA symptoms and signs and a lack of effective screening tools. AIM OF THE STUDY: The current study was designed to assess the prevalence, comorbidities, and clinical predictors associated with the development of PsA in psoriasis patients. MATERIAL AND METHODS: A cross-sectional observational study was performed. Screening questionnaires - the Psoriasis Epidemiology Screening Tool (PEST) and Early Arthritis for Psoriatic Patients (EARP) - were applied to 200 psoriasis patients; among them n = 22 (11% of all tested patients) were in developmental age. Those with positive questionnaires were classified as having PsA or not according to the classification for psoriatic arthritis criteria. Body surface area, psoriasis area and severity index, and psoriasis disability index tools were used for assessing psoriasis patients. A full rheumatological and dermatological evaluation were carried out for PsA patients. RESULTS: The prevalence of PsA was found to be 30%, with a mean age of 45.48 ±10.79 years. Further, psoriasis preceded the onset of PsA in 46 patients (76.6%), arthritis began before psoriasis in 6 individuals (10%), and both psoriasis and arthritis coincided in 8 (13.3%) patients. Obesity (OR 7.0, 95% CI: 2.61-18.85), nail psoriasis (OR 5.02, 95% CI: 2.02-12.476), and intergluteal cleft site (OR 12.659, 95% CI: 4.302-37.255) were associated with increased risk of PsA. However, classic plaque psoriasis (OR 0.149, 95% CI: 0.051-0.433) and flexure site (OR 0.238, 95% CI: 0.076-0.746) were linked with a decreased risk of PsA development. CONCLUSIONS: Screening for PsA in patients with psoriasis revealed a significant number of undiagnosed cases of PsA that should be treated early. Obesity, nail psoriasis, and psoriasis at the intergluteal sites can help predict the PsA development.

Influence of glutathione S transferase A1 gene polymorphism (-69C > T, rs3957356) on intravenous cyclophosphamide efficacy and side effects: a case-control study in Egyptian patients with lupus nephritis.

OBJECTIVES: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease. Cyclophosphamide (CYC) is a cytotoxic drug of a narrow therapeutic window that is commonly used in lupus nephritis (LN) treatment. However, 30-40% of patients experience CYC resistance. CYC inactivation is mediated by the glutathione S transferases (GSTs) superfamily: GST class A (GSTA) has the greatest activity and contains 5 isoenzymes. Polymorphisms of genes involved in the drug metabolism could alter the drug pharmacokinetics and effectiveness. CYC pharmacokinetics and pharmacogenomics are extensively studied in malignancies; however, scarce data are available about this issue in the autoimmune rheumatic diseases. Prediction of the drug response helps the achievement of the highest benefit-to-risk ratio. The aim of this case-control study was to address the association between GSTA1 polymorphism (-69C > T, rs3957356), and the rate of response to and side effects of intravenous CYC in LN patients. METHODS: Ninety-four patients were included and divided into matched groups: resistant and responsive. Genotyping was performed using restriction fragment length polymorphism method after amplification. RESULTS: A significant association between the TT genotype, and CYC resistance and partial response was observed. Concerning the recessive model, none of the patients within the TT group achieved complete remission. CYC side effects were more common with the polymorphism under the genotype, recessive model, and allele distributions. When patients' pre- and post-treatment characteristics were compared, patients with the TT genotype did not show any significant improvement. CONCLUSION: LN patients with GSTA1 (-69C > T, rs3957356) TT genotype have the highest risk of CYC unresponsiveness and toxicity. Key-Points • LN patients with the wild genotype of GSTA1 have the greatest probability of achieving a complete renal response to IV CYC. • The homozygous GSTA1 (-69C > T, rs3957356) TT genotype is associated with the highest risk of LN unresponsiveness to IV CYC. • The homozygous GSTA1 (-69C > T, rs3957356) TT genotype is associated with the highest risk of CYC-related side effects.

Development and initial validation of a composite disease activity score for systemic juvenile idiopathic arthritis.

OBJECTIVE: To develop a composite disease activity score for systemic JIA (sJIA) and to provide preliminary evidence of its validity. METHODS: The systemic Juvenile Arthritis Disease Activity Score (sJADAS) was constructed by adding to the four items of the original JADAS a fifth item that aimed to quantify the activity of systemic features. Validation analyses were conducted on patients with definite or probable/possible sJIA enrolled at first visit or at the time of a flare, who had active systemic manifestations, which should include fever. Patients were reassessed 2 weeks to 3 months after baseline. Three versions were examined, including ESR, CRP or no acute-phase reactant. RESULTS: A total of 163 patients were included at 30 centres in 10 countries. The sJADAS was found to be feasible and to possess face and content validity, good construct validity, satisfactory internal consistency (Cronbach's alpha 0.64-0.65), fair ability to discriminate between patients with different disease activity states and between those whose parents were satisfied or not satisfied with illness outcome (P < 0.0001 for both), and strong responsiveness to change over time (standardized response mean 2.04-2.58). Overall, these properties were found to be better than those of the original JADAS and of DAS for RA and of Puchot score for adult-onset Still's disease. CONCLUSION: The sJADAS showed good measurement properties and is therefore a valid instrument for the assessment of disease activity in children with sJIA. The performance of the new tool should be further examined in other patient cohorts that are evaluated prospectively.

Factors contributing to disability in rheumatoid arthritis patients: An Egyptian multicenter study.

OBJECTIVE: Minimizing disability and enhancing physical function to its optimal levels is still a challenge in management of rheumatoid arthritis (RA). The aim is to identify factors leading to disability in RA. METHODS: This is a cross-sectional Egyptian multicenter study carried out on 215 RA patients attending to our inpatient and outpatient rheumatology clinics during 4 months starting from April to July 2017 who agreed to participate in the study; 170 patients were from Cairo University hospitals and 45 from Zagazig University hospitals. We recorded a number of possible risk factors including demographic, clinical, serological and therapeutic factors. The assessment of patients' disability was done using Modified HAQ (MHAQ). RESULTS: A significant positive correlation was found between MHAQ and different markers of activity in addition to age and depression score (P<0.001). Illiteracy accounted for higher MHAQ scores (P=0.001). A higher MHAQ was found in patients with ischemic heart disease (P<0.05). Patients with erosions on X-rays had significantly higher MHAQ scores. Subluxations also accounted for higher MHAQ scores (P=0.000). CONCLUSION: Aging, illiteracy, disease activity, erosions, subluxations, depression and ischemic heart disease were all related to higher disability. Good control of disease activity which in turn reduces erosions and subluxations is mandatory. Screening for depression and proper use of anti-depressants is of great value. Proper screening and prophylaxis is recommended against ischemic heart disease by controlling modifiable risk factors like obesity, dyslipidaemia, hypertension, smoking and sedentary lifestyle.