Insight into the Epidemiology of the Adult-onset Systemic Autoimmune Rheumatic Diseases in Egypt: A Descriptive Study of 8690 Patients.

BACKGROUND/OBJECTIVE: Although systemic autoimmune rheumatic diseases (SARDs) seem to be ubiquitous, Africa and the Middle East seem to be a remarkable exception with scarcity of data compared with the developed countries. Furthermore, most of the studies addressed a particular disease. This work aimed to shed light on the relative frequency and epidemiology of the different adult-onset SARDs in Egypt. METHODS: This is a retrospective hospital-based study including six university hospitals providing free health care services: Cairo, Alexandria, Tanta, Ismailia, Beni-Suef and Assiut University Hospitals. All available files for patients attending the outpatient clinics or admitted to the inpatient departments between January 2000 and December 2021 were retrospectively reviewed. Data about the patient's diagnosis, gender, age at disease onset, year of disease onset and residence were collected. RESULTS: The study included 8690 patients. Rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Behçet's disease (BD) and spondyloarthropathies (SPA) represented the main SARDs in Egypt. They mainly affect young patients below the age of 40 years. RA and SLE mainly affect females; males are mainly affected by axial SPA and BD. There is an increasing incidence of SARDs during the study period. CONCLUSION: The study revealed the high burden of SARDs in Egypt, helping better allocation of economic resources for the management of diseases of the highest prevalence and those affecting the young reproductive age groups. Increased public and medical staff awareness about SARDs is recommended to help early referral of patients to rheumatologists and, hence, better estimation of their epidemiology.

Association of IL-8-251T/A (rs4073) gene polymorphism with Systemic lupus erythematosus in a cohort of Egyptian patients.

OBJECTIVE: Systemic lupus erythematosus (SLE) susceptibility was found to be correlated with genetic polymorphisms. Therefore, the current study aimed to investigate the association of the IL-8-251 T/A polymorphism with the risk of SLE. METHODS: A total of 135 SLE patients and 75 controls were enrolled in our study. The IL-8-251 T/A polymorphism was analysed by PCR-RFLP. Also, the serum concentration of IL-8 was measured using ELISA. Finally, investigate possible IL-8 pathways in SLE pathogenesis by using the STRING database. RESULTS: Our results revealed that the risk of having SLE in AA genotype carriers was significantly increased (OR = 1.92, 95 % CI = 1.23-3.10, p = 0.006) when compared with TT genotype carriers. Patients with SLE had a significantly higher frequency of the A allele (OR = 1.37, 95 % CI = 1.09-1.7; P = 0.01) than controls. Serum IL-8 levels were significantly increased in SLE patients (77.81 ± 21.27; p < 0.001) when compared to healthy controls (48.85 ± 7.89). Also, it was found that the serum IL-8 level had significant positive correlations with proteinuria, ESR, ANA, urea and SELADI, and significant negative correlations with RBCs count, C3 and hemoglobin. According to ROC curve analysis, serum IL-8 levels are a good biomarker for the detection of SLE disease, with 87.5 % sensitivity and 85 % specificity. STRING analysis revealed that IL-8 interacts with key SLE signaling pathway members such as TNF-α, IL-1ß, IL-6, and IL-10. CONCLUSIONS: There was a correlation between the IL-8-251 T/A polymorphism and the risk of SLE. Our findings also suggest that the IL8-251 A allele may be an important risk factor for the development of SLE.

Ultrasound abnormalities of the major salivary glands in Egyptian patients with systemic sclerosis.

INTRODUCTION/OBJECTIVES: systemic sclerosis (SSc) is an autoimmune disorder with multiple organs destruction. This study aimed to identify the ultrasonographic changes of major salivary glands in Egyptian scleroderma patients and to detect their association to different disease manifestations. METHODS: Forty-seven SSc patients and 43 apparent healthy volunteers were enrolled. Demographics, inflammatory markers, and autoimmune status were recorded. Ultrasound evaluation of salivary glands was performed. Salivary gland changes' associations were statistically examined with SSc susceptibility and disease manifestations. RESULTS: Thirty-one SSc patients exhibited glandular pathology (p < 0.0001), compared to controls. Of these abnormalities, SSc patients showed a total parotid gray scale of 2, total submandibular gray scale of 2, total glandular gray scale of 4, and total glandular Doppler signal of 1 at p < 0.0001, compared to the control group. Patients with SSc and glandular pathology had a higher prevalence of arthritis (p = 0.029) and ESR (p = 0.002) than those with normal glandular ultrasound. Significant associations were reported between gray scale ultrasound (GSUS) of total parotid (odds ratio "OR" = 0.4), total submandibular (OR = 0.36), and total glandular (OR = 0.53) with susceptibility to SSc at p < 0.0001. Total glandular GSUS (p = 0.039) and total submandibular power Doppler (p = 0.044) correlated with the SSc duration. Total parotid GSUS (p = 0.008) and total glandular GSUS (p < 0.0001) correlated with Schirmer's test. CONCLUSIONS: Major salivary glands are affected in SSc. Hence, scanning these glands with ultrasound is an additive tool besides the current practice. Key Points • Major salivary gland changes, observed by ultrasonography, are new findings in Egyptian SSc patients. • Ultrasound changes of major salivary glands are associated with inflammatory markers and clinical manifestations of SSc. • Scleroderma ultrasonography scans of the main salivary glands could be added to the routine work.

Aging and entheses: An ultrasonographic probing of degenerative enthesopathy in a cohort of 147 healthy subjects.

AIM: To investigate the prevalence and features of degenerative enthesopathic changes in a large cohort of healthy individuals by musculoskeletal ultrasound (MSUS) and their relation to age and other demographic features. METHODS: In this cross-sectional study, 147 healthy subjects (1470 entheses) were examined by MSUS according to the Outcome Measures in Rheumatology guidelines: Achilles tendon, plantar fascia, patellar, and quadriceps insertions of both lower limbs. RESULTS: The mean age (±SD) of the participants was 43.68 (±14.53) years and 57.1% were female. Enthesopathy has been detected in at least 1 area in 113 subjects (76.87%). Thickening (21.6%) and hypoechogenicity (15.3%) were the most frequent inflammatory findings while enthesophyte (10.13%) was the most prevalent structural one. Age and male gender were significantly correlating with inflammatory (rs  = .341, P = .001/r = .310, P = .001), structural (rs  = .354, P = .001/r = .166, P = .04) and total scores (rs  = .406, P = .001/r = .302, P = .001). More inflammatory changes were noticed in the age group 36-55 years. Body mass index had a positive correlation with inflammatory (rs  = .290, P = .001) and total scores (rs  = 0.298, P = .001) but not with structural lesions (rs  = .154, P = .062). CONCLUSIONS: Thickening, hypoechogenicity, cortical irregularities, and enthesophytes are frequent degenerative features of enthesopathy. These findings need to be redefined to be more specific for spondyloarthritides. Enthesopathy should be interpreted with caution in the light of the clinical picture, especially in elderly and obese male patients.

Assessment of the Role of Urinary Heparanase in Lupus Nephritis Patients and Its Correlation with Disease Activity.

Assessing the activity of lupus nephritis (LN) with novel biomarkers is a promising noninvasive diagnostic tool for managing systemic lupus erythematosus (SLE). We assessed the ability of urinary heparanase to identify LN and its relation to the disease's activity. This crosssectional study had 90 subjects: 70 patients with SLE and 20 healthy controls. A full medical history, clinical examination, and routine investigations were carried out for the patients and controls. Immunological assays and assessments of the disease's activity with the SLE Disease Activity Index (SLEDAI) and the renal SLEDAI (r-SLEDAI) were carried out for LN groups. Urinary heparanase levels were measured using an enzyme-linked immunosorbent assay for all subjects. Of our patients, 20 had active LN, 17 had nonactive LN, 18 had active lupus without renal involvement, and 15 had nonactive lupus without renal involvement. The level of urinary heparanase was significantly higher in the LN groups than in the non-LN groups and the controls and was significantly higher in those with active LN than in those with nonactive LN. There were significant positive correlations between urinary heparanase and 24-h urinary protein, total SLEDAI, and r-SLEDAI, and significant negative correlations between urinary heparanase and Complements 3 and 4. Urinary heparanase predicted the activity of LN with a sensitivity of 80% and a specificity of 91.43%. Urinary heparanase levels were higher in patients with active LN and correlated with the markers of disease activity, indicating that it can serve as a useful new biomarker for the activity of LN.

Urinary Tumor Necrosis Factor-Like Weak Inducer of Apoptosis (uTWEAK) and Urinary Monocyte Chemo-attractant Protein-1 (uMCP-1): Promising Biomarkers of Lupus Nephritis Activity?

There is no single biomarker to detect lupus nephritis (LN) activity. Renal biopsy is still the gold standard method but it is invasive and mainly used in the initial assessment of the patients. Urinary tumor necrosis factor-like weak inducer of apoptosis (uTWEAK) and urinary monocyte chemo-attractant protein-1 (uMCP-1) can be secreted in the urine of active LN. The aim of the study is to assess the potential role of uTWEAK and uMCP-1 in lupus patients and to determine their correlation with disease activity. This is a case-control study conducted on a total of 114 subjects; 92 systemic lupus erythematosus (SLE) patients and 22 healthy volunteers. The patients were recruited from the rheumatology unit at the internal medicine department, Tanta University Hospital, Tanta, Egypt. The patients and controls were subjected to full history taking, complete clinical examination, routine laboratory tests, uTWEAK and uMCP-1 measurement, assessment of the disease activity using SLE Disease Activity Index (SLEDAI), and renal SLEDAI (rSLEDAI) scores. uTWEAK and uMCP-1 levels were higher in SLE with active nephritis group than those of other SLE groups and controls. There was a significant positive correlation between uTWEAK and uMCP-1 levels in lupus patients with proteinuria, anti-dsDNA, SLEDAI and r-SLEDAI and a negative correlation with C3 and C4. TWEAK showed a sensitivity of 80.43% and 100% and specificity of 50% and 100% in detecting lupus activity and LN activity, respectively. Furthermore, uMCP-1 showed a sensitivity of 82.6% and 100% and specificity of 50% and 100% in detecting lupus activity and LN activity, respectively. uTWEAK and uMCP-1 are new, easily obtained, accurate markers with high sensitivity and specificity in the detection of LN activity.

Characteristics, evolution, and outcome of patients with non-infectious uveitis referred for rheumatologic assessment and management: an Egyptian multicenter retrospective study.

OBJECTIVE: To investigate the characteristics, evolution, and visual outcome of non-infectious uveitis. METHODOLOGY: Records of 201 patients with non-infectious uveitis (136 (67.7%) males and 84 (41.8%) juvenile-onset (≤ 16 years)) were retrospectively reviewed. Data were analyzed through Kruskal-Wallis and Mann-Whitney, chi-square (χ2) tests, and logistic regression. RESULTS: The median disease and follow-up durations were 36 (interquartile range (IQR) 24-70) and 24 (IQR 10-36) months, respectively. Fifty-eight (28.9%) patients had persistently idiopathic uveitis, and 143 (71.1%) were associated with rheumatic diseases, of whom uveitis heralded, coincided with, and succeeded the rheumatic manifestation(s) in 62/143 (43.4%), 37/143 (25.9%), and 44/143 (30.7%) patients, respectively. Established rheumatic diseases were Behçet's disease (103/201 (51.2%)), juvenile idiopathic arthritis (13/201 (6.5%)), sarcoidosis (8/201 (4%)), seronegative spondyloarthropathy (7/201 (3.5%)), and Vogt-Koyanagi-Harada (7/201 (3.5%)), and other diagnoses were present in 5/201 (2.5%) patients. Patients with idiopathic uveitis were characterized by a juvenile-onset (p < 0.001), lower male predominance (p = 0.01), prevalent granulomatous (p < 0.001), and anterior (p = 0.001) uveitis. The median visual acuity at last visit was 0.3 (IQR 0.05-0.6). Visual loss was present in 45/201 (22.3%) patients (36/201 (17.9%) unilateral and 9/201 (4.4%) bilateral). Apart from a longer disease duration (p = 0.002), lower educational level (p = 0.03), and prevalent panuveitis (p < 0.001), visual loss was not associated with any other studied ocular or extra-ocular characteristics. CONCLUSION: Behçet's disease (51.2%) and idiopathic uveitis (28.9%) were the most prevalent causes of non-infectious uveitis in our study. Visual loss (22.3%) was associated with a longer disease duration, lower education level, and prevalent panuveitis. Key Points • Most common causes of uveitis referred to rheumatologists were Behçet's disease and idiopathic uveitis. • Several rheumatic diseases initially presented only with uveitis, more commonly in adult and male patients. • Panuveitis was more frequent among patients with an established rheumatic disease, whereas granulomatous uveitis was uncommon. • Longer disease duration and presence of panuveitis were independently associated with visual loss.

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.

Is Hepatitis B Surface Antigen (HB s Ag) Enough Alone as a Screening Test for HBV Infection in Rheumatic Disease Patients Before Starting Immunosuppressive Therapies? A Cross-sectional Study.

BACKGROUND & OBJECTIVES: Prevalence of hepatitis B virus in patients with rheumatic diseases has been reported differently among studies. The loss of immune control in these patients may result in the reactivation of HBV replication within hepatocytes. Considering the lifelong use of multiple anti-rheumatic drugs, screening for HBV is recommended before starting immunosuppressive or immunomodulatory therapy. The aim of this study was to select the best and simplest test for screening of HBV in rheumatic patients. METHODS: This study was carried out in 102 patients with different rheumatic diseases. Screening to all patients for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibodies and human immune deficiency virus antibodies (HIV) was done. HBV core antibodies and real time PCR to detect HBV DNA were done. RESULTS: The mean age of the patients was 37.18 ± 12.37 years, 3.9% of them were males and 96.1% were females. HBsAg had 100% Sensitivity, 100% Specificity, 100% PPV, 100% NPV and 99.0% accuracy. While, anti-HBc had 100% Sensitivity, 78% Specificity, 8% PPV, 100% NPV and 78% accuracy in the screening of HBV. CONCLUSIONS: HBs Ag was found to be superior to antiHBc for screening for HBV infection in rheumatic patients.

Shedding light on vasculitis in Egypt: a multicenter retrospective cohort study of characteristics, management, and outcome.

OBJECTIVES: The frequency of different vasculitides and their characteristics vary among different regions. The identification of geographic disparities of disease phenotypes helps the development of international criteria, allowing the classification of patients of different ethnicities. This study aimed to describe the frequency, characteristics, course, response to treatment, and outcome of the different adulthood vasculitides in Egypt. METHODS: This was a multicenter study in which the medical records of adult Egyptian patients diagnosed with vasculitis between 2002 and 2018 were retrospectively reviewed. RESULTS: The most frequent vasculitides in Egypt were Behçet's disease (76%), hepatitis C virus vasculitis (13.9%), and granulomatosis with polyangiitis (3.9%). Most patients (73.8%) had a major event at the time of diagnosis. Generalized granulomatosis with polyangiitis was more common than the localized type (90% versus 10%, respectively). The aortic arch and its branches were the most common affected sites of Takayasu arteritis. Of vasculitides, Behçet's disease and giant cell arteritis were associated with the greatest rates of relapse (62.7% and 33.3%, respectively). Delayed diagnosis and permanent organ damage were reported in 69.9% and 68.9% of patients, respectively. A low mortality rate was noted (1.3%). CONCLUSIONS: The most common types of adulthood vasculitides in Egypt are Behçet's disease, hepatitis C virus vasculitis, and granulomatosis with polyangiitis. Major organ involvement is frequent. Delayed diagnosis and permanent organ damage are common.

The Importance of Log Ferritin and Transferrin /Log Ferritin in Differentiating Iron Deficiency Anemia from Anemia of Chronic Disease in Rheumatoid Arthritis Patients.

The most common types of anemia in rheumatoid arthritis (RA) are iron deficiency anemia (IDA) and anemia of chronic disease (ACD).The differentiation between both is important and challenging. Our objective is to select the most accurate method that differentiates IDA from ACD in RA patients. This case control study was carried out on 80 RA patients. 40 RA patients with anemia and 40 RA patients without anemia, complete blood count, assessment of disease activity using DAS 28 score, serum iron, transferrin level, transferrin saturation (TSAT), serum ferritin, log ferritin and transferrin /log ferritin were tested, anemic patients were divided into 2 subgroups according to TSAT: group Ia (with low TSAT) and group Ib (with normal TSAT). There was a statistically significant difference between anemic and non-anemic RA patients as regard serum iron level and transferrin saturation. Among the anemic group 67.5% had low TSAT (IDA) and 32.5% had normal TSAT (ACD). In these 2 subgroups there was no significant differences as regard DAS28 score, blood indices, serum ferritin and transferrin /log ferritin) and there was a positive correlation between TSAT and ferritin and log ferritin and a significant negative correlation between TSAT and transferrin/log ferritin. In conclusions, Iron deficiency anemia is prevalent in RA patients. A combination of serum ferritin and TSAT is simple and accurate parameter to differentiate both. Log ferritin and transferrin /log ferritin may be promising new parameters in diagnosis of IDA in general population but their use in inflammatory diseases like RA still has a limitation.

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.