Tamer Atef Gheita

Objective: The aim of this work was to identify disease-related factors associated with a history of spontaneous abortion in adult female patients with systemic sclerosis (SSc), and to further analyze the distinguishing features of SSc patients with recurrent versus single abortion episodes. Materials and Methods: This multicenter case-control study was extracted from a nationwide SSc cohort of 1,080 patients. Ninety-one female adult SSc patients (8.4%) with a history of spontaneous abortion before 20 completed weeks of gestation were compared with 91 age-matched female SSc patients without a history of spontaneous abortion. Clinical characteristics, comorbidities, organ involvement, medications, and laboratory parameters were analyzed. Results: Patients with spontaneous abortion had significantly longer disease duration (6.4±4.7 vs . 4.6±4.2 years; p =0.007), a higher prevalence of comorbidities (29.7% vs . 15.4%; p =0.03), more frequent telangiectasia (28.6% vs . 12.1%; p =0.009) and a higher frequency of mycophenolate mofetil use (29.7% vs . 15.4%; p =0.03) compared with patients without a history of spontaneous abortion. Recurrent spontaneous abortion occurred in 30 patients (33.0%). Compared with those with a single spontaneous abortion, patients with recurrent spontaneous abortion had significantly higher frequencies of Raynaud’s phenomenon ( p p =0.047), hypo-/hyperpigmentation ( p =0.03), cardiovascular involvement ( p =0.046), anti-Scl-70 positivity ( p =0.01), double autoantibody positivity ( p =0.017), and higher serum triglyceride levels ( p =0.006). Discussion: Patients with SSc have a higher risk of spontaneous abortion than the general population; this risk is likely driven by decidual vasculopathy and fibrosis. Factors contributing to spontaneous abortion were variable in previous reports, with hypertension and long disease duration among the most contributing factors. Conclusion: In women with SSc, spontaneous abortion is associated with longer disease duration, telangiectasia, higher serum creatinine levels, the presence of comorbidities, and the use of MMF. Recurrent spontaneous abortion is associated with anti-Scl-70 positivity, double autoantibody positivity, and hypertriglyceridemia.

Background and Aims: The “quantity” of bone can be evaluated by dual-energy X-ray absorptiometry (DXA) scans, but not its “quality. We aim to study the clinical relevance of urinary-N-terminal telopeptide (NTx) in a retrospective exploratory study. Patients and Methods: The medical records of patients with osteoporosis, osteopenia with or without fractures, and with available urinary NTx were retrospectively reviewed; those on anti-osteoporotic medication before the start of the study were excluded. In all NTx levels, bone-specific alkaline phosphatase (BSAP), parathormone, serum calcium, and vitamin D were measured. In all cases, a recent DXA scan and fracture risk assessment (FRAX) had been performed. Appropriate statistics were applied using SPSS. 15. Results: Included were 93 patients (17.2% males); thirty-one (33.33%) had osteoporosis, 56 (60.21%) osteopenia, whereas 36 (38.7%) had prior or existing fractures. Older participants had lower NTx levels, and females had higher NTx levels, albeit NS. A negative correlation was found between the T-score of the left hip and NTx levels (p = 0.015) but not of the right hip or lumbar spine. In multivariate analysis, NTx levels (p = 0.013) and FRAX (p = 0.001) were significantly associated with fractures. Patients with osteoporosis had higher NTx levels when compared to patients with osteopenia (p = 0.015). NTx at a cut-off value of 207.4 showed a sensitivity of 80.6% and a specificity of 56.1% for the diagnosis of previous fracture with an area under the curve (AUC) of 0.72 (95% CI: 0.61, 0.83). Conclusions: Elevated NTx levels were significantly associated with existing or prior fractures. Combining DXA scan and FRAX, with NTx testing, may provide a comprehensive approach to osteoporosis assessment and treatment. Further prospective studies are warranted to validate its clinical utility.

Background: Systemic lupus erythematosus (SLE), an autoimmune disease, predominantly affects women and is associated with an increased risk of spontaneous abortion (SA). However, traditional analytical methods found a modest relationship between some factors and SLE-SA and were limited to a small sample size, frequently associated with poor predictive performance. Objectives: This study aimed to apply and evaluate an Extreme Gradient Boosting (XGBoost) model using routinely collected clinical data to identify patterns associated with spontaneous abortion in women with SLE and to identify the key variables associated with this outcome. Methods: The study included adult SLE women from the Egyptian College of Rheumatology (ECR)-SLE cohort, a national multicenter study, which had available SA data. SA was defined as unexplained pregnancy loss up to 20 weeks of gestation. Patients’ demographics, clinical manifestations, SLE disease activity index (SLEDAI), therapeutic and laboratory data were used as input variables for the logistic regression (LR) and XGBoost models. We evaluated the performance of both the XGBoost and LR models by calculating the area under the receiver operating characteristic curve (AUC) for each model, and then compared these AUC values to assess which model better distinguished between patients with and without SA. The importance and direction of each variable contributing to the risk of SA were evaluated using SHapley Additive exPlanation (SHAP). Results: A total of 3296 SLE women (mean ± SD age: 32.5 ± 10.1 years; median disease duration: 48 months) were included. The mean SLEDAI score was 11.3 ± 9.5. About 13.9% of the patients included had at least one abortion. Optimized XGBoost performed better (AUC 0.99) compared with LR (AUC 0.78). Positive antiphospholipid antibodies, low complement 3, longer disease duration, hypertension and the presence of mucocutaneous ulcers, as well as anticoagulants and steroid use, were among the important factors associated with SA in SLE patients. Conclusion: Using information obtained in the clinical settings, the XGBoost identified variables associated with SA in women with SLE, including positive antiphospholipid antibodies, low complement 3 levels and longer disease duration. Further, longitudinal studies are necessary to evaluate the clinical utility of the proposed classification model.

Background: Primary Sjögren’s Syndrome (pSS) is a systemic autoimmune disease that predominantly impacts the exocrine glands. It is characterized by a diverse clinical manifestation and the existence of various autoantibodies. There is a lack of studies assessing the primary pSS phenome driven by anti-Sjögren syndrome autoantibodies in Africa, particularly in Egypt. Objective: This study aims to evaluate the clinical implications of antinuclear antibodies (ANA) and anti-Ro/anti-La autoantibodies in an Egyptian national cohort of pSS patients. Methods: We conducted a cross-sectional analysis of pSS patients, comparing clinical manifestations and disease severity based on serological profiles. Results: A total of 301 pSS patients (mean age: 45.6± 10.2 years; F:M ratio 7.4:1) were included. Patients with positive ANA (59.5%) had a higher prevalence of anti-Ro (p=0.001) and anti-La (p=0.0001) antibodies, along with lower rates of dry eyes (p=0.04) and enlarged parotid glands (p=0.001). Corticosteroid and azathioprine use was more frequent in ANA-positive patients (p=0.017, p=0.003). Double-positive anti-Ro/anti-La patients exhibited higher rates of dry mouth (p=0.045), articular manifestations (p< 0.0001), fibromyalgia (p=0.001), RF positivity (p< 0.001), and C4 consumption (p< 0.001). Conclusion: Patients with pSS exhibit distinct clinical and laboratory profiles based on their autoantibody status, emphasizing the importance of immunological assessment for disease management.

Objective: The aim of the work was to describe the characteristics of married rheumatoid arthritis (RA) female patients with history of spontaneous abortion and compare them to those without. Patients and methods: Three hundred and four female RA with history of abortion compared with another 304 RA married patients of matched age without history of abortion. Patients were subjected to full history taking and clinical examination. The routine laboratory investigations were done in addition to rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP), antinuclear antibody. Also, plain x-ray hands were performed to detect erosions. Disease activity score (DAS28) and health assessment questionnaire (HAQ) were assessed. Results: In this study 3.5 % of patients with history of abortion out of a large RA cohort (n = 8750), had a mean age of 42.8±11.4 years and disease duration of 6.2 ±5.4 years. 14 (4.6 %) were smokers. There was a significant increase in the frequency of metabolic syndrome in those with abortion (17.4%) than in those without (10.9%) (p=0.008). Methotrexate (MTX) and hydroxychloroquine (HCQ) were less frequently used among patients with a history of spontaneous abortion (67.8% and 68.8%) compared to those without (82.6% and 78%) (p =0.005 and p =0.037 respectively). Disease activity and the functional status were comparable between those with and without abortion. Conclusion: Spontaneous abortion in RA females was higher in those with metabolic syndrome. Reluctance and/or incompliance in using the basic DMARD treatment with MTX or HCQ in controlling the disease may add to the possibility of abortion.

Limited evidence on long-term COVID-19 vaccine safety in patients with idiopathic inflammatory myopathies (IIMs) continues to contribute to vaccine hesitancy. We studied delayed-onset vaccine adverse events (AEs) in patients with IIMs, other systemic autoimmune and inflammatory disorders (SAIDs), and healthy controls (HCs), using data from the second COVID-19 Vaccination in Autoimmune Diseases (COVAD) study. A validated self-reporting e-survey was circulated by the COVAD study group (157 collaborators, 106 countries) from Feb–June 2022. We collected data on demographics, comorbidities, IIM/SAID details, COVID-19 history, and vaccination details. Delayed-onset (> 7 day) AEs were analyzed using regression models. A total of 15165 respondents undertook the survey, of whom 8759 responses from vaccinated individuals [median age 46 (35–58) years, 74.4% females, 45.4% Caucasians] were analyzed. Of these, 1390 (15.9%) had IIMs, 50.6% other SAIDs, and 33.5% HCs. Among IIMs, 16.3% and 10.2% patients reported minor and major AEs, respectively, and 0.72% (n = 10) required hospitalization. Notably patients with IIMs experienced fewer minor AEs than other SAIDs, though rashes were expectedly more than HCs [OR 4.0; 95% CI 2.2–7.0, p < 0.001]. IIM patients with active disease, overlap myositis, autoimmune comorbidities, and ChadOx1 nCOV-19 (Oxford/AstraZeneca) recipients reported AEs more often, while those with inclusion body myositis, and BNT162b2 (Pfizer) recipients reported fewer AEs. Vaccination is reassuringly safe in individuals with IIMs, with AEs, hospitalizations comparable to SAIDs, and largely limited to those with autoimmune multimorbidity and active disease. These observations may inform guidelines to identify high-risk patients warranting close monitoring in the post-vaccination period.

Idiopathic inflammatory myopathies (IIMs) confer a significant risk of disability and poor quality of life, though fatigue, an important contributing factor, remains under-reported in these individuals. We aimed to compare and analyze differences in visual analog scale (VAS) scores (0–10 cm) for fatigue (VAS-F) in patients with IIMs, non-IIM systemic autoimmune diseases (SAIDs), and healthy controls (HCs). We performed a cross-sectional analysis of the data from the COVID-19 Vaccination in Autoimmune Diseases (COVAD) international patient self-reported e-survey. The COVAD survey was circulated from December 2020 to August 2021, and details including demographics, COVID-19 history, vaccination details, SAID details, global health, and functional status were collected from adult patients having received at least one COVID-19 vaccine dose. Fatigue experienced 1 week prior to survey completion was assessed using a single-item 10 cm VAS. Determinants of fatigue were analyzed in regression models. Six thousand nine hundred and eighty-eight respondents (mean age 43.8 years, 72% female; 55% White) were included in the analysis. The overall VAS-F score was 3 (IQR 1–6). Patients with IIMs had similar fatigue scores (5, IQR 3–7) to non-IIM SAIDs [5 (IQR 2–7)], but higher compared to HCs (2, IQR 1–5; P < 0.001), regardless of disease activity. In adjusted analysis, higher VAS-F scores were seen in females (reference female; coefficient −0.17; 95%CI −0.21 to −13; P < 0.001) and Caucasians (reference Caucasians; coefficient −0.22; 95%CI −0.30 to −0.14; P < 0.001 for Asians and coefficient −0.08; 95%CI −0.13 to 0.30; P = 0.003 for Hispanics) in our cohort. Our study found that patients with IIMs exhibit considerable fatigue, similar to other SAIDs and higher than healthy individuals. Women and Caucasians experience greater fatigue scores, allowing identification of stratified groups for optimized multidisciplinary care and improve outcomes such as quality of life.

Background: Metabolic syndrome (MetS) is characterized by insulin resistance, high blood pres-sure/sugar, dyslipidemia, and obesity. Whether MetS and its components affect the development of Behçet's Disease (BD) remains unclear. Aims: The aim was to determine the frequency of MetS among BD patients and to study its relationship with disease characteristics. Methods: The study included 1028 adult BD patients recruited from 18 specialized rheumatology centers. 51 healthy matched control were considered. Behçet Disease Current Activity Form (BDCAF) and the BD damage index (BDI) were estimated. Adult Treatment Panel-III criteria were used to define MetS. Results: The mean age of patients was 36.8 ± 10.1 years, M:F 2.7:1 and disease duration 7.01 ± 5.2 years. Their mean BDCAF was 5.1 ± 4.6 and BDI 5.5 ± 2.8. MetS was present in 22.8% of patients and in 5.9% of control (3.9 fold higher-risk). Patients with MetS had a significantly increased age at onset (31.8 ± 9.2 vs. 29 ± 8.5 years) and higher frequency of genital ulcers (96.2% vs. 79.7%), skin involvement (73.1% vs. 50.4%), arthritis (48.3% vs. 29.1%) (p<0.0001) and CNS manifestations (18.8% vs. 13%) (p=0.042) compared to those without it. Eye involvement was significantly increased in those with MetS (82.1% vs. 74.2%) (p=0.003) with increased frequency of posterior uveitis (67.1% vs. 43.5%), retinal vessel occlusion (35.9% vs. 21.3%), retinal vasculitis (41.9% vs. 26.4%) (p<0.0001) and vitritis (37.2% vs. 24%) (p=0.001). BDCAF was significantly lower (3.9 ± 4.3 vs. 5.6 ± 4.6) and BDI higher (7.4 ± 2.7vs5 ± 2.6) (p<0.0001). Conclusion: BD patients with MetS are predisposed to mucocutaneous, musculoskeletal, neuropsychiatric and ocular manifestations with consequently increased damage. The involvement of the deeper structures of the eye should alarm rheumatologists to keep in mind that all patients should have an eye examination, especially those with MetS.