Identifying distinct phenotypes of patients with juvenile systemic lupus erythematosus: results from a cluster analysis by the Egyptian college of rheumatology (ECR) study group.

PURPOSE: Juvenile systemic lupus erythematosus (J-SLE) is a complex, heterogeneous disease affecting multiple organs. However, the classification of its subgroups is still debated. Therefore, we investigated the aggregated clinical features in patients with J-SLE using cluster analysis. METHODS: Patients (≤ 16 years) diagnosed using the Systemic Lupus International Collaborating Clinics (SLICC) classification criteria were identified from the clinical database of the Egyptian College of Rheumatology (ECR) SLE study group. Demographic data, clinical characteristics, laboratory features, and current therapies were selected. A cluster analysis was performed to identify different clinical phenotypes. RESULTS: Overall, 404 patients, of whom 355 (87.9%) were female, had a mean age at diagnosis of 11.2 years and a mean disease duration of 2.3 years. We identified four distinct subsets of patients. Patients in cluster 1 (n = 103, 25.5%) were characterized predominantly by mucocutaneous and neurologic manifestations. Patients in cluster 2 (n = 101, 25%) were more likely to have arthritis and pulmonary manifestations. Cluster 3 (n = 71, 17.6%) had the lowest prevalence of arthritis and lupus nephritis (LN), indicative of mild disease intensity. Patients in cluster 4 (n = 129, 31.9%) have the highest frequency of arthritis, vasculitis, and LN. Cluster 1 and 4 patients had the highest disease activity index score and were less likely to use low-dose aspirin (LDA). The SLE damage index was comparable across clusters. CONCLUSIONS: Four identified J-SLE clusters express distinct clinical phenotypes. Attention should be paid to including LDA in the therapeutic regimen for J-SLE. Further work is needed to replicate and clarify the phenotype patterns in J-SLE.

Development of machine learning models for detection of vision threatening Behçet's disease (BD) using Egyptian College of Rheumatology (ECR)-BD cohort.

BACKGROUND: Eye lesions, occur in nearly half of patients with Behçet's Disease (BD), can lead to irreversible damage and vision loss; however, limited studies are available on identifying risk factors for the development of vision-threatening BD (VTBD). Using an Egyptian college of rheumatology (ECR)-BD, a national cohort of BD patients, we examined the performance of machine-learning (ML) models in predicting VTBD compared to logistic regression (LR) analysis. We identified the risk factors for the development of VTBD. METHODS: Patients with complete ocular data were included. VTBD was determined by the presence of any retinal disease, optic nerve involvement, or occurrence of blindness. Various ML-models were developed and examined for VTBD prediction. The Shapley additive explanation value was used for the interpretability of the predictors. RESULTS: A total of 1094 BD patients [71.5% were men, mean ± SD age 36.1 ± 10 years] were included. 549 (50.2%) individuals had VTBD. Extreme Gradient Boosting was the best-performing ML model (AUROC 0.85, 95% CI 0.81, 0.90) compared with logistic regression (AUROC 0.64, 95%CI 0.58, 0.71). Higher disease activity, thrombocytosis, ever smoking, and daily steroid dose were the top factors associated with VTBD. CONCLUSIONS: Using information obtained in the clinical settings, the Extreme Gradient Boosting identified patients at higher risk of VTBD better than the conventional statistical method. Further longitudinal studies to evaluate the clinical utility of the proposed prediction model are needed.

Adult systemic lupus erythematosus in Egypt: The nation-wide spectrum of 3661 patients and world-wide standpoint.

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-SLE) and 3345 adult-onset (Ao-SLE). Age at onset was highest in South and lowest in Cairo (p < 0.0001). CONCLUSION: SLE in Egypt had a wide variety of clinical and immunological manifestations, with some similarities with that in other nations and differences within the same country. The clinical characteristics, autoantibodies and comorbidities are comparable between Ao-SLE and Jo-SLE. The frequency of various clinical and immunological manifestations varied between gender. Additional studies are needed to determine the underlying factors contributing to gender and age of onset differences.

Systemic lupus erythematosus children in Egypt: Homeland spectrum amid the global situation.

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); 73.3%, peri-pubertal; and 19.3% during early adolescence. The differences according to age group were equal for gender and clinical manifestations except skin lesions present in 59.3% of pre-pubertal onset, 74.6% of peri-pubertal, and 84.2% of adolescents (p = 0.029), and renal involvement in 73.8% of peripubertal, 62.1% of pre-pubertal and 58.9% of adolescents (p = 0.03). Laboratory investigations, SLEDAI, and DI were similar among age categories. Lupus nephritis was more common in Egypt compared to JSLE from other countries. CONCLUSION: Our large multicenter study identified that female gender influenced disease characteristics with more frequent skin involvement. Skin lesions were significantly higher in adolescents, while renal involvement in peri-pubertal children.

Rheumatology university faculty opinion on coronavirus disease-19 (COVID-19) vaccines: the vaXurvey study from Egypt.

OBJECTIVES: The aim of the present work was to explore the perspectives of Egyptian Rheumatology staff members as regards the coronavirus disease-19 (COVID-19) vaccine. METHODS: The survey is composed of 25 questions. Some questions were adapted from the global rheumatology alliance COVID-19 survey for patients. RESULTS: 187 rheumatology staff members across Egypt from 18 universities and authorizations actively participated with a valid response. The mean time needed to complete the survey was 17.7 ± 13 min. Participants were 159 (85%) females (F:M 5.7:1). One-third agreed that they will be vaccinated once available, 24.6% have already received at least one dose, 29.4% are unsure while 16% will not take it. Furthermore, 70.1% agreed that they will recommend it to the rheumatic diseases (RD) patients once available, 24.1% are not sure while 5.9% will not recommend it. RD priority to be vaccinated against COVID-19 in descending order include SLE (82.9%), RA (55.1%), vasculitis (51.3%), systemic sclerosis (39.6%), MCTD (31.6%), Behcet's disease (28.3%). The most common drugs to be avoided before vaccination included biologics (71.7%), DMARDs (44.4%), biosimilars (26.7%), IVIg (17.1%) and NSAIDs (9.1%). CONCLUSIONS: The results of the study and specifically the low rate of acceptability are alarming to Egyptian health authorities and should stir further interventions to reduce the levels of vaccine hesitancy. As rheumatic disease patients in Egypt were not systematically provided with the vaccine till present, making the vaccine available could as well enhance vaccine acceptance. Further studies to investigate any possible side effects, on a large scale of RD patients are warranted.

Therapeutic Potential of Digital Nerve Block in Rheumatoid Arthritis Patients: A Clinical and Sonographic Prospective Study.

BACKGROUND: This study attempted to test the effectiveness of digital nerve block (DNB) in active rheumatoid arthritis (RA) joints with respect to local disease control. METHODS: The study included 83 RA patients aged 18 years or above and diagnosed, after American College of Rheumatology/European League Against Rheumatism criteria 2010, with bilateral proximal interphalangeal (PIP) arthritis. PIPs were examined by European League Against Rheumatism-outcome measures in rheumatoid arthritis clinical trials scoring system at 0, 2, and 8 weeks. Visual analog scales for each hand were also done at the same intervals. DNBs of the second and third PIPs were performed to the dominant hand in 50% of participants. The other hand was used as a control, and saline was injected in the same level at the control side. RESULTS: At 2 weeks and 8 weeks intervals, the active side showed significantly less clinical and ultrasound scores when compared to the control side and the baseline values. The mean OMERACT score for the active hand dropped from 3.37±1.43 at 0 time to 2.31±1.66 after 2 weeks and 2.55±1.43 at 8 weeks (P<0.001). Also, visual analog scale decreased from 59 at 0 time to 41 at 2 weeks and 43 at 8 weeks (P<0.001). The amelioration was greater when the active side was the dominant one. The injected PIPs showed maximum improvement at 2 weeks. Improvement was more significant in the second PIP. Early patients achieved better outcomes. CONCLUSION: DNB is a new promising therapy for RA. It can control pain and inflammation of the PIPs. It has relatively short-term effect, yet it could limit escalation of systemic treatment plans.

Development and validation of a Behçet's Disease Damage Index for adults with BD: An Explicit, Composite and Rated (ECR) tool.

BACKGROUND: Behçet's disease (BD) is a chronic multisystem variable vessel vasculitis. Disease damage is irreversible and permanent. Validated tools evaluating damage are limited. Enhancements in the clinical treatment of vasculitis will take place from the development of refined and exclusive indices for individual vasculitic syndromes including BD and attempting their international validation. OBJECTIVES: This aim was to develop and validate a simple BD Damage Index (BDI). METHODS: This was a nationwide study including 1252 BD patients. The work consisted of 3 stages. Stage 1: items generation for score content. Stage 2: items selection for the draft score was performed by an expert rheumatologist. Stage 3: the content validity of the draft score was assessed and BDI, Vasculitis Damage Index (VDI), Antineutrophil cytoplasmic antibody-associated Vasculitis Index of Damage (AVID) and Combined Damage Assessment Index (CDAI) were calculated and compared. RESULTS: The mean age of the BD patients was 36.1 ± 9.9 years. Stages 1 and 2 resulted in a BDI instrument containing 73 items with a maximum score of 100. Stage 3, the VDI, CDAI, AVID, and BDI were 2.9 ± 2.2, 3.1 ± 2.3, 3.1 ± 2.3 and 5.1 ± 2.9, respectively. High correlations (r = .9) between comparable damage scores assured acceptable concurrent validity. CONCLUSION: The proposed BDI represents a new robust and potentially useful tool when dealing with BD chronic status.

Behçet's disease in Egypt: a multicenter nationwide study on 1526 adult patients and review of the literature.

OBJECTIVES: The present work was conducted to estimate the prevalence of adult Behçet's disease (BD) in adult Egyptian and to study the clinical pattern and influence of age at-onset and sex on disease phenotype. Also, we investigated the spectrum of presentation and frequencies along the north-to-south gradient of the country. PATIENTS AND METHOD: The population-based, multicenter, cross-sectional study included 1526 adult BD patients from 26 specialized Egyptian rheumatology centers. Demographic, clinical, and therapeutic data are assessed for all patients. RESULTS: The mean age of patients was 35.7 ± 9.84 years, disease duration 6.58 ± 5.25 years, and age at onset 29.37 ± 8.6 years; 91 were juvenile-onset (JoBD). There were 1102 males and 424 females (M:F 2.6:1). Regarding co-morbidities, 19.92% were diabetic, and 26.05% were hypertensive. The mean body mass index was 27.57 ± 5.24 (43.1% overweight; 25.9% obese). The mean BD current activity form was 4.48 ± 4.28. Regarding the medications use, systemic steroid and colchicine were the most common drugs used (947 (90.2%) and 611 (82.7%), respectively). The overall estimated prevalence of BD in Egypt was 3.6/100,000 population being highest in the two main cities: Alexandria (15.27) and Cairo (8.72). Pathergy test was positive in 43.4%. 90.2% were receiving systemic steroids and 8.3%, biologics. Disease characteristics were comparable between JoBD and adult-onset BD cases. Central nervous system (CNS), deep venous thrombosis (DVT), and gastrointestinal (GIT) involvement were significantly higher in males (p = 0.01, p = 0.001, and p = 0.001 respectively) while joint affection (p = 0.001) and disease activity (p = 0.011) were increased in females. CONCLUSIONS: This study provides current prevalence of BD in Egypt; 3.6/100,000 with no remarkable north-to-south gradient. The sex influences the disease phenotype with the CNS, DVT, and GIT involvement are higher in males, while the joint affection and disease activity were increased in females. KEY POINTS: • The prevalence and phenotype of Behçet's disease across Egypt is presented in a multicenter nationwide study. • The potential influence of the age at onset and sex on disease phenotype is highlightened. • A review of the literature worldwide is presented allowing comparisons with studies from other nations.

Correction to: Behçet's disease in Egypt: a multicenter nationwide study on 1526 adult patients and review of the literature.

The author wishes to correct the record and clarify that in the original version of this article in the Discussion section under "Prevalence over the country governorates" inadvertently presented incorrect data cited in the reference [30].

Ankle Evaluation in Active Rheumatoid Arthritis by Ultrasound: A Cross-Sectional Study.

Ankle joint evaluation is underestimated in many clinical and sonographic scores used for evaluation and follow-up of rheumatoid arthritis (RA) patients. Agreement on examination parameters is poor among sonographic scores that include the ankle joint. More effort is needed to detect the value of ankle joint examination in RA and assessment of ultrasonographic signs according to frequency, disease duration and activity. The objective of this study was to use ultrasound (US) to detect ankle involvement in active RA and to compare findings with disease duration, disease activity and assessment of ankle bone erosion. A total of 63 RA patients with active disease and 20 controls were included in the study. The tibiotalar and talonavicular joints were examined by US for synovitis and/or effusion in gray-scale and power Doppler modes. The anterior, lateral and posterior ankle tendons were examined for tenosynovitis and tendinosis. Mean age was 35.1 ± 8.3 y, mean disease duration was 22.7 ± 9.6 mo and the mean 28-joint Disease Activity Score-erythrocyte sedimentation rate was 3.05 ± 0.66. Ankle involvement was seen in 28 patients (44.4%). The most frequent pathologies detected were tenosynovitis (30.2%), followed by synovitis (18.3%), erosion (8.7%) and tendinosis (4%). The earliest sonographic signs were tenosynovitis, followed by synovitis, erosion and tendinosis. The right ankle exhibited greater involvement than the left ankle, which was significant with respect to erosions (p = 0.009). The most common tendon affected by tenosynovitis was the tibialis anterior (22.2%), followed by the tibialis posterior (20.6%). Tenosynovitis, especially of the tibialis anterior and posterior, tibiotalar synovitis and erosions should be considered in future US ankle scores for the assessment of RA.

Sonographic Findings in Gouty Arthritis: Diagnostic Value and Association with Disease Duration.

The objective of this work was to evaluate the sonographic features of gouty arthritis and correlate findings with disease duration. The study was conducted on 100 patients in ambulatory care aged ≥40 y. Inclusion criteria included mono- or oligo-arthritis with effusion of the knee or the first metatarsophalangeal (MTP) joint and no known history of gout. A complete medical history was obtained with emphasis on the known risk factors or causes of gouty arthritis. A 12-MHz Medison linear probe was used for ultrasonography (US). Synovial fluid analysis with polarizing light microscopy was performed on all patients. Ninety-eight knee joints and 33 first MTP joints were examined. Gouty arthritis was found by US in four forms: (i) floating echogenic foci in effusion fluid or Baker cysts, (ii) deposits on the cartilage surface (double contour sign), (iii) erosions and (iv) mature tophus/tophi. These were found in 78.9%, 42.3%, 39.4% and 28.2% of patients, respectively. The overall sensitivity and specificity of US in detecting gout (as defined by the clinical gold standard, i.e., detection of urate crystals by polarizing light microscopy) were 85.9% and 86.7%, respectively. Detection of echogenic foci in effusion fluid was associated with the shortest duration of symptoms (median duration 2 y) followed by double contour sign (3.5 y), erosions (4 y) and tophus (12.5 y). Sonographic findings in gout can be assigned a temporal pattern, with echogenic foci being associated with the shortest and full tophus formation with the longest disease duration.

Low-dose Spironolactone: Treatment for Osteoarthritis-related Knee Effusion. A Prospective Clinical and Sonographic-based Study.

OBJECTIVE: To evaluate the effectiveness of spironolactone as a treatment for osteoarthritis (OA)-related knee effusion in comparison to ibuprofen, cold compresses, and placebo. METHODS: This study was carried out on 200 patients, aged 40 years or older, attending the outpatient clinic of the Rheumatology Department of Sohag University Hospital with unilateral knee effusion related to OA based on clinical examination, musculoskeletal ultrasonography (US), and synovial fluid analysis. In group 1, 50 patients received spironolactone 25 mg daily for 2 weeks; in group 2, 50 patients took ibuprofen 1200 mg daily for 2 weeks; in group 3, 50 patients used cold compresses 2 times daily for 2 weeks; and in group 4, 50 patients received placebo for the same duration. Fluid > 4 mm was considered as effusion. Decrease in fluid to reach below 4-mm thickness was considered complete improvement, and any decrease that did not reach below 4 mm thickness was considered partial improvement. RESULTS: The mean age of the participants was 51.2 ± 8.1 years. The mean duration of effusion was 16.5 ± 3.6 days. In group 1, 66% had complete improvement, 20% partial improvement, and 14% no response. In group 2, 24% had complete improvement, 12% partial improvement, and 64% no response. In group 3, 28% had complete improvement, 14% partial improvement, and 58% no response. In group 4, only 6% had complete improvement, 10% partial improvement, and 84% no response. CONCLUSION: Low-dose spironolactone is a safe and effective medical treatment for OA-related knee effusion.

Amyloid arthropathy associated with multiple myeloma: polyarthritis without synovial infiltration of CD20+ or CD38+ cells.

OBJECTIVES: To describe histological, immunohistochemical and ultrastructural features of synovial biopsies of amyloid arthropathy associated with multiple myeloma (MM). METHODS: Synovial biopsies from affected joints of two patients with MM and amyloid arthropathy were examined with light and electron microscopy, and immunohistochemically for expression of CD3, CD8, CD20, CD38, CD68, Ki-67 and vWF. Results were compared to values from osteoarthritis (OA, n = 26), rheumatoid arthritis (RA, n = 24) and normal (n = 15) synovial membranes. RESULTS: There was no or only mild lining hyperplasia. Vascular density was not elevated, and there were few Ki-67+ proliferating cells in the stroma. The Krenn synovitis score classified one specimen as "low-grade" and one as "high-grade" synovitis. CD68+ and CD3+ cells were the predominant mononuclear inflammatory cells, whereas CD20+ and CD38+ cells were absent from both synovial membrane and synovial fluid sediment. Electron microscopy demonstrated amyloid phagocytosis by synovial macrophages. In hierarchical clustering the two amyloid arthropathy specimens were more closely related to OA than to RA or normal synovium. CONCLUSIONS: This first detailed immunohistological analysis of MM-associated amyloid arthropathy suggests that it is a chronic synovitis that evolves despite the loss of humoral immunity seen in advanced MM. Instead, amyloid phagocytosis by synovial macrophages likely triggers and perpetuates local disease.

Amyloid arthropathy associated with multiple myeloma: a systematic analysis of 101 reported cases.

OBJECTIVE: Amyloid deposition in multiple myeloma (MM) may lead to an arthropathy resembling rheumatoid arthritis (RA). Since a systematic description of its natural history is lacking, we have performed a systematic analysis of all published cases. METHODS: Literature review featuring backward and forward database searches and direct inspection of reference lists. Inclusion criteria were as follows: publication between 1931 and 2012, diagnosis of multiple myeloma, and demonstration of light chain amyloid (AL) in any organ or in synovial fluid, arthritis, or synovitis. RESULTS: Overall, 101 cases were identified. Median age was 59 years and the male-to-female ratio was 1:1. A systemic manifestation of MM was reported in 88 cases. In 53 of these, characteristic physical findings (carpal tunnel syndrome, macroglossia, shoulder pad, and soft tissue swelling/masses) were present. Arthritis manifested before the diagnosis of MM in 63 cases, with 33 cases initially misdiagnosed as RA. There were 72 cases of poly-, 17 of oligo-, and three of monoarthritis. The shoulder joint was most commonly affected, followed by knees and small hand joints. Median synovial fluid leukocyte count was 2460 cells/mm(3), and was normal in seven cases. Synovial histopathology often featured mild synovitis without plasma cell infiltration. Imaging revealed articular or periarticular inflammation in many cases and bone lesions near 22% of affected joints. Treatments varied but led to some improvement in the majority of cases. CONCLUSIONS: These results solidify previous experience that MM arthropathy tends to feature a symmetric RF-negative nonerosive polyarthritis. However, the results also highlight the diversity of its presentations and stress the importance of arthropathy as a potentially under-recognized presenting manifestation of MM.