Rheumatoid arthritis study of the Egyptian College of Rheumatology (ECR): nationwide presentation and worldwide stance.

To depict the spectrum of rheumatoid arthritis (RA) in Egypt in relation to other universal studies to provide broad-based characteristics to this particular population. This work included 10,364 adult RA patients from 26 specialized Egyptian rheumatology centers representing 22 major cities all over the country. The demographic and clinical features as well as therapeutic data were assessed. The mean age of the patients was 44.8 ± 11.7 years, disease duration 6.4 ± 6 years, and age at onset 38.4 ± 11.6 years; 209 (2%) were juvenile-onset. They were 8750 females and 1614 males (F:M 5.4:1). 8% were diabetic and 11.5% hypertensive. Their disease activity score (DAS28) was 4.4 ± 1.4 and health assessment questionnaire (HAQ) 0.95 ± 0.64. The rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) were positive in 73.7% and 66.7% respectively. Methotrexate was the most used treatment (78%) followed by hydroxychloroquine (73.7%) and steroids (71.3%). Biologic therapy was received by 11.6% with a significantly higher frequency by males vs females (15.7% vs 10.9%, p = 0.001). The least age at onset, F:M, RF and anti-CCP positivity were present in Upper Egypt (p < 0.0001), while the highest DAS28 was reported in Canal cities and Sinai (p < 0.0001). The HAQ was significantly increased in Upper Egypt with the least disability in Canal cities and Sinai (p = 0.001). Biologic therapy intake was higher in Lower Egypt followed by the Capital (p < 0.0001). The spectrum of RA phenotype in Egypt is variable across the country with an increasing shift in the F:M ratio. The age at onset was lower than in other countries.

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.

Impact of COVID-19 pandemic on rheumatoid arthritis from a Multi-Centre patient-reported questionnaire survey: influence of gender, rural-urban gap and north-south gradient.

During the coronavirus disease-2019 (COVID-19) pandemic there were several barriers to treatment access and medication adherence in rheumatoid arthritis (RA) patients. There is no information regarding the RA patient health status in Egypt during the COVID-19. Thus,the aim of this work was to study the impact of the pandemic on RA patients through a patient-reported questionnaire and to determine the influence of gender, geographic regions. This multi-centre study initiated by the Egyptian College of Rheumatology (ECR) was conducted on 1037 RA patients attending rheumatology clinics from 10 governorates. The questionnaire provided covered socio-demographic data, health/disease status, information/knowledge about COVID-19 and medical/family history of the infection. Patients mean age was 44.2 ± 12.3 years;855 females and 182 males; 539(52%) from rural and 497(48%) from urban areas. 41.8% reported a striking difficulty to obtain hydroxychloroquine during the pandemic. The majority (70%) considered maintaining a regular visit to the rheumatologist in addition to remote contact mainly by phone (44.4%) or via WhatsApp (33.1%), in particular among male and urban patients. Urban patients were more likely to be infected by COVID-19 (12.9% vs 6.2%; p < 0.0001) than rural. Northern cities had more patients with suspected COVID-19 (13.9% vs 6.1%; p < 0.0001); was significantly associated with more disease flares (30.8% vs 5.8%) with subsequent change in the RA treatment (20.9% vs 6.4%; p < 0.0001). Patients with RA faced remarkable difficulty to obtain their medications with subsequent change in their disease status. The challenges of the pandemic have hastened changes in the way we deliver health care.

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.

Rheumatologists' practice during the Coronavirus disease 2019 (COVID-19) pandemic: a survey in Egypt.

The aim of this work is to trace how rheumatologists all over Egypt are approaching the COVID-19 pandemic and what changes it has brought about in the patients' care with special attention to its effect on vulnerable rheumatic disease (RD) patients. This survey further aims to help inform the rheumatology community about the changes in practice during the COVID-19 pandemic. The survey included 26 questions distributed to University staff members across Egypt members of the Egyptian College of Rheumatology (ECR). It takes 5-10 min to fill out. The practice setting of participating rheumatologists included University Teaching Hospitals that are the main rheumatology and clinical immunology service providers for adults and children RD patients. There was an overall agreement across the country in the responses to the survey that took a median time of 7 min to fill in. Potential changes in rheumatology outpatient practice by staff members evolved since the COVID-19 pandemic. None of the university rheumatology staff members has prescribed chloroquine or HCQ to prevent or treat COVID-19 in a non-hospitalized patient who was not previously on it. Twenty-three recommended decrease/avoid NSAIDs if the RD patient had confirmed COVID-19 or symptoms. There is an agreement to the key emerging frontline role of rheumatologists in treating COVID-19. During the pandemic, RD cases requiring admission were dealt with by several modified strategies. The overall agreement among the different university rheumatology departments during such critical situation has provoked the ECR to consider providing provisional guidelines for dealing with RD patients during this global catastrophe.

Development of an Arabic version of the Behçet's Disease Current Activity Form (Ar-BDCAF): cross-cultural adaptation and validation initiative in Egypt.

BACKGROUND: Behçet's disease (BD), commonly seen in the Silk road countries, is a variable vessel vasculitis with no specific investigation that reflects disease activity. The Behçet's Disease Current Activity Form (BDCAF) is the most famous and acceptable clinical activity score. PURPOSE: To develop a cross-cultural adaptation of the BDCAF to the Arabic language (Ar-BDCAF)-Egyptian dialect-across the country and to consider preliminary evaluation of its reliability in assessment of BD activity. PATIENTS AND METHODS: The score was translated to Arabic language and revised by 3 rheumatology consultants. Reliability of Ar-BDCAF was tested among 88 BD patients from 9 Egyptian main city centers. Patients were questioned by two specialists at 30 min interval to evaluate inter-observer rating and twice by the same physician within 24 h to assess the intra-observer rating. RESULTS: Patients were 64 males and 24 females (2.7:1) with a mean age of 35 ± 10.3 years. The average time required by the consultant to fill in the form was 5.1 ± 2.2 min (1.5-15 min). The mean Ar-BDCAF scores were 9.81 ± 6.22 (0-25) and 9.53 ± 6.13 (0-28) with an intra-observer concordance (p = 0.28) and was 9.95 ± 6.47 (0-29) for the inter-observer rating (p = 0.89 and p = 0.66, respectively). CONCLUSION: The Ar-BDCAF is a measurable, easy to calculate, and reliable index for assessing disease activity in Egyptian BD. The Ar-BDCAF score can be used in daily clinical practice to assess BD activity and its use can be extended to other Arab countries for possible regional validation and adaptations. Key Points • The Arabic version of the BDCAF can be extended to other Arab countries for development of a Pan-Arab score. • This is the first study to provide a reliable and valid Arabic version of the BDCAF-Egyptian dialect for measuring current disease activity in BD patients.

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.

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].

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.

Human Parvovirus B19 Infection in Rheumatoid Arthritis Patients: Screening and Clinical Significance.

Rheumatoid arthritis (RA) is a common chronic inflammatory disease, affecting about 1% of the general population. Conflicting data are available regarding the etiologic association of human parvovirus B19 (B19) infection with RA. This study aimed to determine the prevalence of B19 infection in patients with RA compared to healthy controls and to assess its possible association with disease activity or severity. The study included 40 RA patients and 40 age and sex matched apparently healthy controls. Detection of B19 DNA by nested PCR and the detection of anti-B19 IgM and IgG by ELISA) were performed for patients and controls. It was found that B19 infection is more prevalent in patients with RA than healthy controls as the frequency of detection of B19 DNA and anti-B19 IgG was significantly higher in RA patients than healthy controls (P=0.003 and P=0.04, respectively) but not IgM. It was concluded that B19 infection may have a role in the etiopathogenesis of RA but not involved in disease activity or severity.

Clinical significance of Matrilin-3 gene polymorphism in Egyptian patients with primary knee osteoarthritis.

OBJECTIVE: Osteoarthritis (OA) is a multifactorial, degenerative, and inflammatory disorder of joints causing damage of the articular cartilage, formation of osteophytes, and eburination of the subchondral bone. Matrilin-3 (MATN-3) is a non-collagenous oligomeric extracellular matrix protein (ECM), which is the smallest member of the matrilin family. This study was conducted to identify the potential association and clinical significance of MATN-3 rs8176070 (SNP6) polymorphism in a series of Egyptian patients with primary knee OA. MATERIAL AND METHODS: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to determine genotypes of MATN-3 SNP6 for 50 primary knee OA patients in addition to 50 healthy subjects of the same sex and age range. Full history was obtained from OA patients, followed by clinical examination, together with clinical assessment of the severity of knee OA using Lequesne Algofunctional Index score and radiological grading using the Kellgren-Lawrence grade scale (KL). RESULTS: With regard to genotypes of MATN-3 gene SNP6 (rs8176070), a statistically significant difference between OA patients and healthy control subjects was found for the B\b genotype and b allele (p=0.046 and 0.042 respectively), with the prevalence being higher in OA patients with a high risk to develop OA (Odds Ratio [OR]=2.250, 95% CI=1.011-5.008). Patients with the B\b genotype had worse clinical and radiological findings than those with B\B and b\b genotypes. CONCLUSION: The investigated polymorphism in the MATN-3 gene may reflect the risk and severity of knee OA in Egyptian patients, particularly with the B\b genotype.

Expression of CD64 on Surface of Circulating Monocytes in Systemic Lupus Erythematosus Patients: Relation to Disease Activity and Lupus Nephritis.

CD64 is a type of integral membrane glycoprotein known as FC receptor that binds monomeric IgG-type antibodies with high affinity. It is more commonly known as FC gamma receptor 1 (FC?R1) and it is expressed on monocytes surface. The goal of this study was to investigate the association of CD64 expression on the surface of peripheral blood monocytes of systemic lupus erythematosus patients with disease activity, and lupus nephritis. 30 SLE patients were enrolled into this study. They were subdivided into: 15 SLE patients with lupus nephritis and 15 SLE patients without lupus nephritis. In addition,Together with 25 age and sex matched healthy volunteers were enrolled as controls group. Disease activity was defined by SLE Disease Activity Index (SLEDAI) score and the renal Systemic Lupus Erythematosus Disease Activity Index (rSLEDAI) score. Surface expression of CD64 on peripheral blood monocytes was evaluated by Flowcytometry. Renal biopsies of Lupus nephritis patients was obtained and evaluated using the International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification scheme. There was a statistically significant difference in surface expression of CD64 on circulating monocytes (P > 0.001) in SLE patients with nephritis especially those with class II/III as compared to SLE without nephritis and healthy controls. The mean fluorescent intensity of CD64 staining correlated positively with markers of systemic inflammation, lupus nephritis, SLEDAI and rSLEDAI scores. In conclusions, surface expression of CD64 on circulating monocytes reflects systemic inflammation, renal injury and could be used as a rapid approach and good biomarker for disease activity and lupus nephritis in SLE patients.

Serum Level of Interleukin-37 and Expression of Its mRNA in Ankylosing Spondylitis Patients: Possible Role in Osteoporosis.

Ankylosing spondylitis (AS) is a chronic inflammatory disease of the axial skeleton.Interleukin-37 (IL-37) is a member of IL-1 family cytokines, that downregulate expression of pro-inflammatory cytokines in chronic inflammatory diseases. The aim of the work is to investigate role of IL-37 in AS disease activity and osteoporosis. Twenty-five patients with AS and 25 controls were enrolled into this study. They were subjected to full clinical examination including assessment of disease activity according to the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Serum IL-37 levels and IL-37 mRNA relative concentration were measured by enzyme-linked immunosorbent assay (ELISA) and quantitative reverse transcriptase- polymerase chain reaction (RT-PCR) respectively. Bone mineral density (BMD) was determined using dual energy X-ray absorptiometry (DEXA). Spine radiographs were scored using the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Mean serum IL-37 level was significantly higher in AS patients compared with the controls (P < 0.001) and significantly elevated in AS patients with osteoporosis (P < 0.05). IL-37 mRNA gene expression showed a significant increase expression in active AS patient (25 folds) as well as in inactive patient (12 folds) as compared to controls . In conclusion, serum IL-37 and its mRNA expression is increased in AS patients with special consideration in patient with Osteoporosis and correlates with disease activity and BMD which indicate that IL-37 may provide a novel research target for pathogenesis and therapy of AS. .

Serum Interleukin-33 in Behcet's Disease: Its Relation to Disease Activity and Clinical Manifestations.

Behcet's disease (BD) is a chronic systemic inflammatory disorder characterized by a course of remissions and exacerbations of unpredictable frequency and duration . Pro- inflammatory cytokines seem to be responsible for the enhanced inflammatory response in BD. AIM OF THE WORK: This study aimed to investigate serum levels of IL-33 in patients with Behcet's disease (BD) and their relationship to disease activity and clinical manifestations. Thirty patients with BD were enrolled and subjected to assessment of disease activity according to Behcet's Disease Current Activity Form (BDCAF) score. Serum IL-33 levels were determined using Enzyme-Linked-Immunosorbent Assay (ELISA). Thirty age and sex matched rheumatoid arthritis patients and thirty healthy volunteers were included in this study as control groups. Serum IL-33 level was 132.5±19 pg\ml, 101.2±20.1 pg\ml and 31.5±10.5 pg\ml in RA, BD and healthy control groups respectively. IL-33 was significantly higher in BD patients (101.2±20.1pg/ml) as compared to healthy controls (31.5±10.5 pg/ml) but lower than rheumatoid arthritis patients (132.5±19.1 pg/ml). Levels of IL-33 were significantly increased in BD patients with skin lesions (Erythema nodosum & Acneiform lesions) and ocular lesions (retinal vasculitis) (P<0.05), and a positive correlation was found between BDCAF score and IL-33serum levels (r=0.9, P<0.001). In conclusions, serum IL-33 level is elevated in active BD patients with skin and ocular affection and correlates with disease activity.

Role of anti-nucleosome antibodies in the diagnosis of systemic lupus erythematosus and as a marker for lupus nephropathy.

SLE is a heterogeneous disease, characterized by variation in clinical and serological manifestations. This study intended to verify the role of anti-nucleosome (anti-NCS) antibodies in diagnosis of SLE and lupus nephritis and to establish the correlation between antibody reactivity and disease activity. Study subjects included 35 patients diagnosed as SLE and two control groups. While the first is a group with other collagen diseases (n = 80), the second included 50 matched apparently healthy subjects. Serum IgG anti-NCS antibodies in all subjects were detected by ELISA. Serum anti-NCS were higher in SLE than in the two control groups (P < 0.001). Serum anti-NCS antibody levels were higher in SLE patients with renal affection (P < 0.001), malar rash and with hematological disorders (P < 0.05). Anti-NCS antibodies showed a higher diagnostic sensitivity (74.7%) and specificity (96%) than anti-dsDNA. Combining data of anti-NCS and anti-dsDNA antibodies increased the diagnostic specificity to 97.3%. In conclusion, serum anti-NCS antibodies have diagnostic value and play role in the assessment of disease activity especially active renal disease and may predict disease outcome.