Nouran Abaza

OBJECTIVES This study aims to present the manifestations of juvenile systemic lupus erythematosus (JSLE) across Egypt, to focus on age at onset and gender-driven influence on disease characteristics, and to compare findings to other countries. METHODS The study included 404 Egyptian children with systemic lupus erythematosus (SLE) presenting to one of the specialized rheumatology centers corresponding to 13 major governorates. Juvenile cases age was ≤ 16°years at the time of recruitment. The SLE Disease Activity Index (SLEDAI) and damage index (DI) were assessed. RESULTS The mean age was 13.2 ± 2.4°years; 355 females and 49 males (7.2:1), and the disease duration was 2.3 ± 1.6 years, while age at disease onset was 11.1 ± 2.5°years. Their SLEDAI was 13.5 ± 12.3, and DI, 0.36 ± 0.78. The overall estimated prevalence of childhood-SLE patients in the recruited cohort in Egypt was 1/100,000 population (0.24/100000 males and 1.8/100000 females). 7.4% developed pre-pubertal SLE (≤ 7 years)...

Objective The aim of this study was to present the epidemiology, clinical manifestations and treatment pattern of systemic lupus erythematosus (SLE) in Egyptian patients over the country and compare the findings to large cohorts worldwide. Objectives were extended to focus on the age at onset and gender driven influence on the disease characteristics. Patients and method This population-based, multicenter, cross-sectional study included 3661 adult SLE patients from Egyptian rheumatology departments across the nation. Demographic, clinical, and therapeutic data were assessed for all patients. Results The study included 3661 patients; 3296 females and 365 males (9.03:1) and the median age was 30 years (17–79 years), disease duration 4 years (0–75 years) while the median age at disease onset was 25 years (4–75 years). The overall estimated prevalence of adult SLE in Egypt was 6.1/100,000 population (1.2/100,000 males and 11.3/100,000 females).There were 316 (8.6%) juvenile-onset (Jo-SL...

OBJECTIVE To gain consensus on the Outcome Measures in Rheumatology (OMERACT) core domain set for rheumatology trials of shared decision making (SDM) interventions. METHODS The process followed the OMERACT Filter 2.1 methodology, and used consensus-building methods, with patients involved since the inception. After developing the draft core domain set in previous research, we conducted five steps: (i) improving the draft core domain set; (ii) developing and disseminating white-board videos to promote its understanding; (iii) conducting an electronic survey to gather feedback on the draft core domain set; (iv) finalizing the core domain set and developing summaries, a plenary session video and discussion boards to promote its understanding; and (v) conducting virtual workshops with voting to endorse the core domain set. RESULTS A total of 167 participants from 28 countries answered the survey (62% were patients/caregivers). Most participants rated domains as relevant (81%-95%) and clear (82%-93%). A total of 149 participants (n = 48 patients/caregivers, 101 clinicians/researchers) participated in virtual workshops and voted on the proposed core domain set which received endorsement by 95%. Endorsed domains are: 1- Knowledge of options, their potential benefits and harms; 2- Chosen option aligned with each patient's values and preferences; 3- Confidence in the chosen option; 4- Satisfaction with the decision-making process; 5- Adherence to the chosen option and 6- Potential negative consequences of the SDM intervention. CONCLUSION We achieved consensus among an international group of stakeholders on the OMERACT core domain set for rheumatology trials of SDM interventions. Future research will develop the Core Outcome Measurement Set. CLINICAL SIGNIFICANCE Prior to this study, there had been no consensus on the OMERACT core domain set for SDM interventions. The current study shows that the OMERACT core domain set achieved a high level of endorsement by key stakeholders, including patients/caregivers, clinicians and researchers.

Background Musculoskeletal ultrasound can be now considered a complement to physical examination in rheumatoid arthritis. This study evaluates the role of musculoskeletal ultrasound in assessment of rheumatoid hand function and underlying functional defects and disabilities in order to find out a possibly better tool for assessment. Results Hand grip weakness was significantly associated with metacarpophalangeal joints synovitis of ulnar 4 fingers (p = 0.045), wrist joint synovitis (p = 0.009), flexor tendons tenosynovitis of the ulnar 4 fingers (p = 0.001), flexor pollicis longus tendon tenosynovitis (p = 0.013). Hand function impairment by grip ability test was significantly associated with metacarpophalangeal joints synovitis of ulnar 4 fingers (p = 0.009), wrist joint synovitis (p = 0.004), and flexor tendons tenosynovitis of the ulnar 4 fingers (p = 0.042). Multiple linear regression analysis showed that the most influencing factor affecting grip ability test and hand grip stre...

The objective of this study is to assess toll-like receptor-9 (TLR9) expression in CD3-positive T lymphocytes and CD19-positive B lymphocytes in systemic sclerosis (SSc) patients and to study their relation to the extent of skin fibrosis, disease characteristics, and severity as well as the functional status. Fifty-five female SSc patients and 30 matched controls were included. Skin thickness was scored according to the modified Rodnan skin score (mRss). The severity of major organ involvement was assessed using the Medsger severity score (MSS). Scleroderma health assessment questionnaire (SHAQ) was measured to evaluate patients’ functional status. Expression of TLR9 in CD3-positive T lymphocytes and CD19-positive B lymphocytes was studied using flow cytometry. The mean age of the patients was 40.5 ± 9.1 years, and their disease duration was 6.7 ± 3.3 years. There were 21 (38.2%) with diffuse (dcSSc) and 34 (61.8%) with limited cutaneous (lcSSc) subtypes. There was a significant increase in the expression of TLR9/CD3 and TLR9/CD19 in the SSc patients (44.9 ± 18.1 and 24.1 ± 9.6) compared to that in the control (1.4 ± 0.97 and 1.3 ± 0.94; p < 0.0001 for both, respectively) being higher in those with dcSSc. TLR9/CD3 expression was significantly increased in SSc patients with arthralgia/arthritis and digital resorption compared to those without. The TLR9/CD3 significantly correlated with the mRss and MSS (r = 0.37, p = 0.006 and r = 0.31, p = 0.02; respectively). Both the TLR9/CD3 and TLR9/CD19 expressions were significantly correlating (r = 0.53, p < 0.0001). On regression analysis, only TLR9/CD3 was a significant risk factor of the mRss and MSS (β = 0.43, p = 0.009 and β = 0.33, p = 0.015, respectively). TLR9, especially TLR9/CD3, is highly expressed in SSc patients particularly those with dcSSc subtype and could form a potential marker for skin fibrosis and disease severity.

Background Emerging role of vitamin D in immunology and autoimmune disorders has been a worldwide interest in the last decade. Systemic lupus erythematosus (SLE) patients are particularly at a delicate position predisposing them to suffer from vitamin D deficiency due to the multiple risk factors accompanying the disease. Whether vitamin D deficiency is also involved as a risk factor for developing SLE and affecting its course is a considerable concern. Objectives To estimate prevalence of vitamin D deficiency in SLE and its relation to disease activity and severity. Methods In our observational cross-sectional study, serum levels of vitamin D from 60 SLE patients and 30 age & sex matched healthy controls (HC) were assessed and estimated for deficiency or insufficiency at 10 and 30ng/ml respectively. Disease activity was evaluated by SLEDAI, irreversible organ damage by SLICC/ACR index and severity by Lupus SDI. Fatigue was measured by visual analogue scale (VAS). Results Significantly lower levels of 25(OH)D were found in SLE patients (17.6±6.9 ng/ml) in comparison to controls (79.0±28.7 ng/ml)with statistically high significant difference (t=-11.2, p<0.001).High prevalence of vitamin D insufficiency and deficiency was detected 73.3% & 23.3% respectively. Vitamin D had a highly significant negative correlation with SLEDAI (r =-0.495, p<0.001), see figure 1a, SLICC (r =- 0.431, p<0.05) as well as fatigue (r =- 0.436, p<0.05), see figure 1b. After standardization of all clinical variants, regression analysis study showed that there is significantly inverse correlated between vit D and VAS (standardized regression coefficient β=-0.443, p=0.024) and a highly significant correlation between vit D and SLEDAI score (β=-0.940, p=0.012). Figure 1. a. Correlation between serum vitamin D and SLEDAI. b. Correlation between serum vitamin D and VAS of fatigue. Conclusions Vitamin D deficiency & insufficiency were found to be prevalent in SLE patients in our study and related to disease activity & fatigue. Routine screening and consequent repletion of vitamin D if needed is recommended in SLE. Restoring adequate vitamin D level in SLE should be more explored as a potential and simple yet valuable measure to be added to their usual management to alleviate their condition. References Kamen DL, Cooper GS, Bouali H, Shaftman SR, Hollis BW, Gilkeson GS. Vitamin D deficiency in systemic lupus erythematosus. Autoimmun Rev 2006; 5: 114–117. Ruiz-Irastorza G, Egurbide MV, Olivares N, Martinez-Berriotxoa A, Aguirre C. Vitamin D deficiency in systemic lupus erythematosus: prevalence, predictors and clinical consequences. Rheumatology (Oxford) 2008;47:920–3. Fragoso TS, Dantas AT, Marques CD, Rocha Junior LF, Melo JH, Costa AJ, Duarte AL. 25-Hydroxyivitamin D3 levels in patients with systemic lupus erythematosus and its association with clinical parameters and laboratory tests. Rev Bras Reumatol. 2012 Jan-Feb;52(1):60-5 Disclosure of Interest None declared

Background The emerging role of vitamin D in immunology and autoimmune disorders has been a worldwide interest in the last decade. Systemic lupus erythematosus (SLE) patients are particularly at a delicate position predisposing them to suffer from vitamin D deficiency due to the multiple risk factors accompanying the disease. Whether vitamin D deficiency is also involved as a risk factor for developing SLE and affecting its course is a considerable concern. Objectives The objective of this study was to estimate the prevalence of vitamin D deficiency in SLE patients and its relation to disease. MATERIALS AND METHODS: In our observational cross-sectional study, serum levels of vitamin D [25(OH)D] in 60 SLE patients and 30 age- and sex-matched healthy controls were assessed and estimated for deficiency and insufficiency at 10 and 30 ng/mL, respectively. Disease activity was evaluated by SLE disease activity index (SLEDAI), irreversible organ damage by Systemic Lupus International Colla...

To compare serum 25 OH vitamin D (25 (OH) D) levels between medial femoro-tibial knee osteoarthritis (OA) patients and controls, and to detect structural progression in patients with mild to moderate knee osteoarthritis in relation to baseline 25(OH) D levels in a one-year longitudinal prospective cohort study. Thirty eight patients with medial femoro-tibial knee OA according to the ACR criteria and no knee malalignement, and 20 age, sex and BMI-matched pain free controls were included in the vitamin D study. All included OA patients had radiographic Kellgren and Lawrence grades 2 or 3. Baseline serum levels of 25(OH) D, and the "Benefiting from ultraviolet index "(BFUI) score were determined; serum parathormone, total alkaline phosphatase, calcium and phosphorus were measured. In the OA progression study, OA patients were divided into 2 groups according to 25 (OH) D level using a cutoff of 10 ng/ml to identify their status. MRIs were done at baseline and repeated after 12 months with scoring system according to Boston Leeds osteoarthritis knee score (BLOKS). During the study period, the patients were not supplemented with 25(OH)D. The mean values of Vitamin D were statistically lower in the OA patient group than in controls (8.64 ± 6.42 vs 14.84±0.87 pg/mL, P =0.0295). The BFUI score overall correlated with 25 (OH) D status. Eight patients did not complete the study so only thirty OA patients underwent the 2 MRIs. Of those, 21 had 25(OH) D levels <10 ng/ml, while 9 had levels >10 ng/ml. A significant progression of the medial meniscal grading from baseline to 1 year was seen in the patients with 25(OH)D levels <10 ng/ml as compared to the others (Wilcoxon Z= -3.556 P<0.001). 25 (OH) D levels were significantly decreased in knee OA patients. Significant deterioration of the medial menisci was observed in OA patients with 25 (OH)D levels <10 ng/ml suggesting that Vit D deficiency may play a role in the progression of medial femoro-tibial OA.

Background Musculoskeletal ultrasound (MSUS) use in Rheumatoid arthritis (RA) has been growing over the last decades mainly to monitor response to treatment and for early detection of erosions. Suggestions to involve this technique in RA diagnosis were taking place but not yet implicated (due to absence of specific sonographic criteria confined to RA). Objectives To verify a proposed combined structural and synovial scoring system's (designed by Kunkel et al., 2012) performance in discriminating RA from osteoarthritis and healthy sonographic findings in small joints of the hand. Methods Twenty RA patients, 20 hand OA patients and 10 healthy controls were subjected to MSUS to metacarpophalyngeal (MCP) and proximal interphalyngeal (PIP) joints. The novel proposed scoring system was applied characterizing each joint as either RA-supported (according to presence of synovial thickening>2mm, doppler signal and/or erosion) or RA-unsupported. Grading of synovitis as mild, moderate or severe was also applied. In RA group, disease activity was assessed by DAS28 and Anti-CCP serum levels were measured. Results Upon applying this scoring system, high statistically significant difference was found between study groups (Table 1) as regards presence of synovium>2mm, doppler signal (Figure 1) and erosions. When one or more RA-supported joints were detected, this scoring system had a sensitivity of 100.0% and specificity of 83.0% with diagnostic accuracy of 90.0% for diagnosis of RA. If two or more joints were detected, it had a sensitivity of 95.0% and specificity of 96.7.0% with diagnostic accuracy of 96.0% for diagnosis of RA. Table 1. Comparison between study groups as regards to number of RA-supported joints by US RA OA Control P^ P^ P^ RA/OA RA/Control OA/Control Erosion Median (IQR) 0.0 0.0 0.0 0.014* 0.014* 0.309 (0.0–1.8) (0.0–0.0) (0.0–0.0) Range 0.0–5.0 0.0–2.0 0.0–0.0 Doppler Median (IQR) 1.0 0.0 0.0 <0.001** 0.005* 1.000 (0.0–2.0) (0.0–0.0) (0.0–0.0) Range 0.0–3.0 0.0–0.0 0.0–0.0 Synovim >2mm Median (IQR) 3.0 0.0 0.0 <0.001** <0.001** 1.000 (2.3–4.0) (0.0–0.0) (0.0–0.0) Range 1.0–8.0 0.0–2.0 0.0–1.0 Total Median (IQR) 3.0 0.0 0.0 <0.001** <0.001** 0.476 (2.3–4.0) (0.0–0.0) (0.0–0.0) Range 1.0–8.0 0.0–2.0 0.0–1.0 IQR: Interquartile range. ^Mann Whitney test,* Significant,** Highly significant. Figure 1. Positive Doppler signal in right third MCP joint in an RA patient. Conclusions The novel suggested combined structural and synovial scoring system showed high performance in differentiating RA from OA and controls. References Kunkel GA, Canon GW and Clegg DO: Combined Structural and Synovial Assessment for Improved Ultrasound Discrimination of Rheumatoid, Osteoarthritic, and Normal Joints: A Pilot Study. The Open Rheumatology Journal 2012;6: 199-206. Scheel AK, Hermann KG, Kahler E, Pasewaldt D, Fritz J, Hamm B, Brunner E, Müller GA, Burmester GR, Backhaus M: A novel ultrasonographic synovitis scoring system suitable for analyzing finger joint inflammation in rheumatoid arthritis. Arthritis Rheum 2005; 52: 733-43.12. Disclosure of Interest None declared

Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) is a member of the TNF superfamily of structurally related cytokines and is known to induce proliferation, migration, differentiation, apoptotic cell death, inflammation, and angiogenesis. These physiological processes are induced by the binding of TWEAK to fibroblast growth factor-inducible 14 (Fn14), a highly inducible cell-surface receptor that is linked to several intracellular signaling pathways, including the nuclear factor-κB (NF-κB) pathway. This review discusses the role of the TWEAK-Fn14 axis in several rheumatic diseases and the potential therapeutic benefits of modulation of the TWEAK-Fn14 pathway.

ABSTRACT Objective: The transanal mucosectomy of the aganglionic segment is a critical step in the transanal endorectal pullthrough procedure for the treatment of Hirchsprung’s disease. It exerts considerable traction on the anorectal tissue during dissection. Anal sphincter electromyography (EMG) is an indispensable parameter for the diagnosis of patients with any anorectal dysfunction. The aim of our study was to assess the integrity of the anorectal sphincter after transanal endorectal pullthrough using anal EMG. Methods: This prospective study was carried out on 25 infants and children with Hirchsprung’s disease who underwent the endorectal pullthrough (soave) procedure. Needle EMG was used to assess the sphincter preoperatively and postoperatively. Results: Preoperative EMG showed positive neuropathic changes in 28% of the patients. Postoperative EMG showed neuropathic changes in 60% of the patients, of whom 28% showed preoperative changes and 32% showed absolute postoperative findings, mostly related to difficult operative dissection. Conclusion: The functional results of the endorectal pullthrough procedure were acceptable overall. Significance: The reduced sphincter function encountered postoperatively was because of a combination of preoperative and intraoperative influences.

ABSTRACT Background Immortality, aggressiveness and tumor-like behavior of fibroblasts-like synoviocytes (FLS) are to be blamed for the joint damage in rheumatoid arthritis (RA). The lack of apoptosis is a hallmark of these FLS in RA synovium and the molecular basis responsible for such a lack involves many antiapoptotic proteins including the bcl-2 family. Named after it, this family pronounces the importance of this particular protein being crucial and pivotal in apoptosis. Objectives To estimate bcl-2 expression in RA synovium - specially FLS – in relation to disease severity, synovial hyperplasia & aggressiveness, high-lightening future therapeutic interventions. Methods Synovium from 10 RA patients, 10 Osteoarthritis (OA) patients & 6 healthy post-traumatic control were studied for histological (number of cell layers, cell types & arrangement) and ultrastructural assessment (apoptotic features and tumor-like behavior features: prominent nucleolus, dispersed chromatin and rich dilated endoplasmic reticulum with wide cysternae) using light & electron microscopy respectively. Severity of RA was assessed using Steinbrocker classification of progression of RA. Immunohistochemistry staining of bcl-2 was performed measuring its expression percent by cell analysis system (CAS 200) image analyser and correlation with disease severity. Results Area percentage of bcl-2 expression in FLS was significantly higher in RA group (17.54±12.19%) in comparison to OA (4±6.43%) and heathy post-traumatic control (0.83±1.59%) groups (p<0.01) and in lymphocytes in RA group compared to both groups (p<0.001). No statistical significant difference was detected between OA and post-traumatic groups. Our results also demonstrated a highly significant positive correlation between bcl-2 positive FLS and bcl-2 positive lymphocytes in RA (r=0.89, p<0.01) as well as between each and disease severity (r=0.88, p<0.01 and r=0.83, p<0.01 respectively) and number of cell layer in synovial hyperplasia (r=0.89, p<0.01 and r=0.97, p<0.01 respectively). Estimated percentage of FLS showing apoptotic features in RA was the lowest (19.8%) compared to the other groups. RA FLS showed tumor-like ultrastructural features. Conclusions Bcl-2 overexpression in RA synovium leads to a generation of death-resistant aggressive FLS and immortal effector cells, hence playing a pivotal role in pathogenesis and severity of RA. Potential damage control and better disease prognosis can be obtained by targeting such anti-apoptotic protein. Controlling bcl-2 expression level would be of great benefit to decelerate, minimize or prevent joint damage in RA. Disclosure of Interest None Declared

ABSTRACT Background Despite the presence of an increase in immunoregulatory cells in rheumatoid arthritis (RA), chronic inflammation persists and activity recurs. This finding has been intriguing rheumatologists and immunologists trying to justify the presence of activity daring this quarterback of cells usually aiming to fight inflammatory process. Namely the forkhead box P3 (FoxP3) transcription factor, essential for T regulatory cells (T regs) development and function is now considered their most specific marker denoting FoxP3+ cells as suppressors whereas FoxP3- effectors. Objectives To clarify the subsets distribution of peripheral blood (PB) CD4+CD25+ T regulatory cells (T regs) according to FoxP3 expression in RA (both in remission & activity) for a better understanding of RA pathogenesis highlighting future therapeutic targets. Methods In our observational cross-sectional study PB T regs from 40 RA patients & 20 age and sex matched healthy controls (HC) were characterized and quantified by flow cytometry. Disease activity was evaluated by DAS28. Patients were divided into 2 equal groups: active RA group (ARA) & remission RA group (RRA). All patients were on methotrexate MTX and folic acid. Results A significantly higher T regs subsets numbers were found on comparing RRA, ARA patients & HC as shown in table 1 Conclusions CD4+CD25+FoxP3+ & CD4+CD25+FoxP3- are both increased in RA but it is their balance that is more important; the abundance of Foxp3- cells gave the effector function the upper hand over the suppressive function represented in Foxp3+ cells. This imbalance is related to the presence of RA & to its activity. Restoring this imbalance by future targeting therapeutics might be of great benefit in RA patients. References Disclosure of Interest None Declared

ABSTRACT Background Renal involvement affects about 50% of SLE patients accounting for significant morbidity and mortality in these patients[1]. The adipokine “Visfatin” acting as a growth factor for B-lymphocyte-precursors, exerts several proinflammatory functions[2]. It was demonstrated as a marker of endothelial dysfunction (ED) in chronic kidney disease (CKD) thus could be a factor linking inflammation in SLE and kidney disease[3]. Objectives To assess serum visfatin level in patients with lupus nephritis (LN)and its correlation to disease activity in these patients. Methods The present study included 40 patients with SLE and forty age and sex matched healthy subjects served as control group.Oral consent was obtained from all patients and controls after a full explanation of the study.Clinical assessment od disease activity by SLE Disease activity index (SLEDAI)[4].Lupus nephritis was assessed clinically with the renal SLE disease activity index (renal SLEDAI).Renal biopsies were taken from the patients with LN and were classified according to the modified WHO classification [5].Serum level of visfatin were measured for the patients and controls using enzyme-linked immunosorbent assay (ELISA). Results A significantly higher serum visfatin level was found on comparing SLE patients (mean 109±180 ng/ml, median18) with controls (mean 9.4±11 ng/ml, median2.5) with statistically highly significant difference (z 5.2, P<0.001).Also there was a statistically significant difference as regards serum visfatin level between active SLE patients (mean 173±111 ng/ml, median 14) and inactive patients (mean 139±88 ng/ml, median 5) (z 2.1, p<0.05) as well as between patients with LN (mean 226±180 ng/ml, median18) and patients with no LN (mean 101±140 ng/ml, median 8 (2-229)) (z=2.1, p<0.05). Visfatin had a highly significant positive correlation with disease duration (r=0.48, p<0.001), SLEDAI (r=0.62, p<0.001) as well as ESR, CRP and, renal score (r=0.45, 0.35, and 0.65 respectively) while inverse correlation with estimated GFR (r=-0.614) and C3 & C4 titre (r=-0.26, r=-0.35 respectively) was recorded. Visfatin showed high sensitivity in detecting active SLE & LN 83% and 85% respectively. Conclusions Serum visfatin is strongly associated with LN in SLE patients and is a promising biomarker for prediction of renal involvement in these patients. It reflects SLE activity specially LN activity namely renal score & GFR decline. Disclosure of Interest None Declared