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A
Abaza, N. A., E. M. Abdel-Latif, and T. A. Gheita, "Clinical Significance of Neutrophil/lymphocyte Ratio in Patients With Granulomatosis With Polyangiitis.", Reumatologia Clinica, 2018.
Acar-Denizli, N., I. - F. Horváth, T. Mandl, R. Priori, A. Vissink, G. Hernandez-Molina, B. Armagan, S. PRAPROTNIK, A. Sebastian, E. Bartoloni, et al., "Systemic phenotype related to primary Sjögren's syndrome in 279 patients carrying isolated anti-La/SSB antibodies.", Clinical and experimental rheumatology, vol. 38 Suppl 126, issue 4, pp. 85-94, 2020. Abstract

OBJECTIVES: To evaluate the systemic phenotype associated with the presence of isolated anti-La/SSB antibodies in a large international registry of patients with primary Sjögren's syndrome (pSS) fulfilling the 2002 classification criteria.

METHODS: The Big Data Sjögren Project Consortium is an international, multicentre registry created in 2014. Baseline clinical information from leading centres on clinical research in SS of the 5 continents was collected. Combination patterns of anti-Ro/SSA-La/SSB antibodies at the time of diagnosis defined the following four immunological phenotypes: double positive (combined Ro/SSA and La/SSB,) isolated anti-Ro/SSA, isolated anti-La/SSB, and immunonegative.

RESULTS: The cohort included 12,084 patients (11,293 females, mean 52.4 years) with recorded ESSDAI scores available. Among them, 279 (2.3%) had isolated anti-La/SSB antibodies. The mean total ESSDAI score at diagnosis of patients with pSS carrying isolated anti-La/SSB was 6.0, and 80.4% of patients had systemic activity (global ESSDAI score ≥1) at diagnosis. The domains with the highest frequency of active patients were the biological (42.8%), glandular (36.8%) and articular (31.2%) domains. Patients with isolated anti-La/SSB showed a higher frequency of active patients in all ESSDAI domains but two (articular and peripheral nerve) in comparison with immune-negative patients, and even a higher absolute frequency in six clinical ESSDAI domains in comparison with patients with isolated anti-Ro/SSA. In addition, patients with isolated anti-La/SSB showed a higher frequency of active patients in two ESSDAI domains (pulmonary and glandular) with respect to the most active immunological subset (double-positive antibodies). Meanwhile, systemic activity detected in patients with isolated anti-La/SSB was overwhelmingly low. Even in ESSDAI domains where patients with isolated anti-La/SSB had the highest frequencies of systemic activity (lymphadenopathy and muscular), the percentage of patients with moderate or high activity was lower in comparison with the combined Ro/SSA and La/SSB group.

CONCLUSIONS: Patients carrying isolated La/SSB antibodies represent a very small subset of patients with a systemic SS phenotype characterised by a significant frequency of active patients in most clinical ESSDAI domains but with a relative low frequency of the highest severe organ-specific involvements. Primary SS still remains the best clinical diagnosis for this subset of patients.

Alfadl, E. A., F. Ismail, R. E. R. Shereef, E. Hassan, S. Tharwat, E. F. Mohamed, E. A. Abda, A. R. Radwan, R. M. Fawzy, A. H. Moshrif, et al., "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.", Rheumatology international, vol. 41, issue 2, pp. 345-353, 2021. Abstract

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.

Ayeldeen, G., O. Shaker, and T. Gheita, "Possible use of miRNAs-146a and -499 expression and their polymorphisms as diagnostic markers for rheumatoid arthritis.", Mol Cel Biochem, vol. 449, issue 1-2, pp. 145-156, 2018.
B
Bassyouni, I. H., S. Fawzy, and T. A. Gheita, "Clinical Association of a Soluble Triggering Receptor Expressed on Myeloid Cells-1 (sTREM-1) in Patients with Systemic Lupus Erythematosus.", Immunol Invest, vol. 46, issue 1, pp. 38-47, 2017.
Brito-Zerón, P., N. Acar-Denizli, W. - F. Ng, I. F. Horváth, A. Rasmussen, R. Seror, X. Li, C. Baldini, J. - E. Gottenberg, D. Danda, et al., "Epidemiological profile and north-south gradient driving baseline systemic involvement of primary Sjögren's syndrome.", Rheumatology (Oxford, England), vol. 59, issue 9, pp. 2350-2359, 2020. Abstract

OBJECTIVE: To characterize the systemic phenotype of primary Sjögren's syndrome at diagnosis by analysing the EULAR-SS disease activity index (ESSDAI) scores.

METHODS: The Sjögren Big Data Consortium is an international, multicentre registry based on worldwide data-sharing cooperative merging of pre-existing databases from leading centres in clinical research in Sjögren's syndrome from the five continents.

RESULTS: The cohort included 10 007 patients (9352 female, mean 53 years) with recorded ESSDAI scores available. At diagnosis, the mean total ESSDAI score was 6.1; 81.8% of patients had systemic activity (ESSDAI score ≥1). Males had a higher mean ESSDAI (8.1 vs 6.0, P < 0.001) compared with females, as did patients diagnosed at <35 years (6.7 vs 5.6 in patients diagnosed at >65 years, P < 0.001). The highest global ESSDAI score was reported in Black/African Americans, followed by White, Asian and Hispanic patients (6.7, 6.5, 5.4 and 4.8, respectively; P < 0.001). The frequency of involvement of each systemic organ also differed between ethnic groups, with Black/African American patients showing the highest frequencies in the lymphadenopathy, articular, peripheral nervous system, CNS and biological domains, White patients in the glandular, cutaneous and muscular domains, Asian patients in the pulmonary, renal and haematological domains and Hispanic patients in the constitutional domain. Systemic activity measured by the ESSDAI, clinical ESSDAI (clinESSDAI) and disease activity states was higher in patients from southern countries (P < 0.001).

CONCLUSION: The systemic phenotype of primary Sjögren's syndrome is strongly influenced by personal determinants such as age, gender, ethnicity and place of residence, which are key geoepidemiological players in driving the expression of systemic disease at diagnosis.

E
Eesa, N. N., H. Abdel Nabi, R. E. Owaidy, I. Khalifa, A. R. Radwan, A. M. NourEl-Din, M. A. Amer, R. R. El Shereef, E. Hassan, F. Ismail, et al., "Systemic lupus erythematosus children in Egypt: Homeland spectrum amid the global situation.", Lupus, vol. 30, issue 13, pp. 2135-2143, 2021. Abstract

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 ( = 0.029), and renal involvement in 73.8% of peripubertal, 62.1% of pre-pubertal and 58.9% of adolescents ( = 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.

El-Gazzar, I. I., H. M. Fathy, T. A. Gheita, and S. A. Kenawy, "Tumor necrosis factor-α -308 A/G gene polymorphism in children with juvenile idiopathic arthritis: relation to disease activity, damage, and functional status.", Clin Rheumatol, vol. 36, issue 8, pp. 1757-1763, 2017.
Eldefrawy, A., T. Gheita, H. Raslan, and M. El-Ansary-etal, "Serum and synovial cartilage oligomeric matrix protein levels in early and established rheumatoid arthritis", Z Rheumatol, vol. 75, issue 9, pp. 917-923, 2016.
Elessawi, D. F., H. Gabr, M. M. M. Badawy, and T. A. Gheita, "Therapeutic potential of mesenchymal stem cells for scleroderma induced in mouse model.", Tissue & cell, vol. 73, pp. 101671, 2021. Abstract

OBJECTIVE: To examine the potential therapeutic effect of mesenchymal stem cells (MSCs) for experimental scleroderma.

MATERIALS AND METHODS: Fifty-four mice six-week-old (30-35 g) were studied. Hypochlorous acid (HOCl) induced scleroderma was considered. Mice were divided into 3 groups: (I) Control: Six mice did not receive any treatment and were sacrificed at the end of the experiment; (II) HOCl mice (induced scleroderma as a positive control): (III) MSCs-treated HOCl mice: Thirty six HOCl-induced mice were injected with MSCs (7.5 × 105) intravenous every week for 3 weeks. Skin pieces were taken from the backs of mice and lung tissue pieces. a smooth muscle actin (α-SMA) and transforming growth factor-β (TGF-β1) were analysed or fixed in 10 % formalin for skin and lung tissue histopathological analysis. Plasma nitric oxide (NO) was also assayed.

RESULTS: There was a significant rise in the NO level and of the cutaneous and lung tissue α-SMA and TGF-β1 in untreated scleroderma-induced mice. The values significantly normalized after MSC therapy over the 7 weeks duration of the study. The altered histopathology of the skin and lung tissues in the scleroderma-induced mice showed a remarkable tendency to normalization of the skin and lung parenchyma and vasculature.

CONCLUSION: There was a significant rise in the level of NO and skin and lung tissue α-SMA and TGF-β1 in untreated scleroderma-induced mice and values were significantly normalized after MSC therapy over the 7 weeks duration of the study. Altered histopathology of the skin and lung appeared nearly normal after MSC therapy.

Elgengehy, F. T., S. M. Gamal, N. Sobhy, I. Siam, A. M. Soliman, G. W. Elhady, and T. A. Gheita, "Vasculitis damage index in Behçet's disease.", Advances in rheumatology (London, England), vol. 61, issue 1, pp. 33, 2021. Abstract

BACKGROUND: Vasculitis damage index (VDI) is a validated damage index for systemic vasculitis, and as Behçet's disease is considered one of systemic vascular disease we aimed to study the relationship of the vasculitis damage index to clinical manifestations and comorbidity in patients with Behçet's disease (BD) to determine if VDI could be used to assess damage in patients with BD.

METHODS: A total of 109 patients with BD were recruited from the Rheumatology Department (outpatient and inpatient clinic), Cairo University Hospitals. All patients were subjected to full history taking, clinical examination, and routine laboratory investigations. Disease activity was assessed by the BD current activity form, and the VDI was calculated in all patients. The relationship of the VDI to the disease clinical manifestations was studied. Mann-Whitney and Kruskal Wallis tests were used to estimate differences in quantitative variables. Spearman correlation test was used to test for correlation between quantitative variables.

RESULTS: In the current study, the VDI ranged from 1 to 10, with a mean of 3.5 ± 1.8. It was significantly associated with total thrombosis (P = 0.022); total neurological manifestations (P = 0.000), especially stroke and cranial nerve affection; uveitis (P = 0.005); avascular necrosis (AVN) (P = 0.015); osteoporosis (P = 0.01); impaired vision (P < 0.0001); cataract (P < 0.0001); and diabetes (P = 0.012). Generally, immunosuppressive treatment was significantly associated with VDI (P = 0.039), especially cyclophosphamide (P < 0.0001), biological agent (P = 0.008), chlorambucil (P = 0.003), and anticoagulant (P = 0.02). VDI was also significantly correlated with age (P = 0.033), disease duration (P = 0.029), and duration of eye involvement (P = 0.003).

CONCLUSION: VDI is significantly associated with most disease parameters of BD, except for parameters such as mucocutaneous manifestations and uncomplicated venous thrombosis; however, further studies may be needed to establish BD-specific damage index.

F
Fathi, H. M., I. E. I. Gazzar, M. A. I. Elazeem, E. AboulKheir, N. M. Gamal, F. Ismail, R. E. R. Shereef, S. Tharwat, S. Elwan, N. Samy, et al., "Rheumatologists' knowledge and perception of COVID-19 and related vaccines: the vaXurvey2 online survey.", Rheumatology international, 2022. Abstract

The study aimed to explore the experience of coronavirus disease-2019 (COVID-19) infection and vaccine adverse events (AEs) among rheumatologists. A validated questionnaire was distributed as a Google form to rheumatologists across the country via social networking sites from late December 2021 till early January 2022. The questionnaire included questions regarding participants' socio-demographic details, COVID-19 infection and vaccination details with special emphasis on AEs. Out of 246 responses, 228 were valid. 200 (81.3%) responders had received the vaccine. The mean age of the 228 participants was 37.9 ± 8.5 years, 196 were females and 32 males (F:M 6.1:1) from 18 governorates across the country. Comorbidities were present in 54 subjects (27%). There was a history of highly suspicious or confirmed COVID-19 infection in 66.7% that were all managed at home. The COVID-19 vaccine was received by 200 and a booster dose of 18.5%. Obesity and musculoskeletal involvement co-morbidities were present only in those with AEs (9.1% and 5.5% respectively). AEs were present in 82%; 66.7% had injection-site tenderness, 50% fatigue, 35.5% fever, 15% chills, 42.5% myalgia, 14.5% arthralgia, 8% low back pain, headache 31%, dizziness 10%, sleepliness 16% and 15% developed post-vaccine. There were no differences according to the geolocation regarding the occurrence of COVID-19 infection (p = 0.19) or AEs post-vaccine (p = 0.58). The adverse events were mostly mild to moderate and tolerable which makes this work in agreement with other studies that support the broad safety of the vaccine in favor of the global benefit from mass vaccination.

Fotouh, A. A., M. O. N. A. HAMDY, F. Ali, E. F. Mohamed, A. Allam, W. A. Hassan, A. Elsaman, A. El-Najjar, M. A. Amer, D. Mosad, et al., "The Emerging Era of Interventional Imaging in Rheumatology: An Overview During the Coronavirus Disease-2019 (COVID-19) Pandemic.", Open access rheumatology : research and reviews, vol. 14, pp. 43-56, 2022. Abstract

Imaging has long been taking its place in the diagnosis, monitor, and prognosis of rheumatic diseases. It plays a vital role in the appraisal of treatment. Key progress in the clinical practice of rheumatology is the innovation of advanced imaging modalities; such as musculoskeletal ultrasound (MSUS), computerized tomography (CT) and magnetic resonance imaging (MRI). These modalities introduced a promising noninvasive method for visualizing bone and soft tissues to enable an improved diagnosis. The use of MSUS in rheumatology is considered a landmark in the evolution of the specialty and its ease of use and many applications in rheumatic diseases make it a forerunner instrument in the practice. The use of MSUS among rheumatologists must parallel the development rate of the excellence revealed in the specialty. Moreover, innovative interventional imaging in rheumatology (III-R) is gaining fame and key roles in the near future for a comprehensive management of rheumatic diseases with precision. This review article throws light on the emergence of these robust innovations that may reshape the guidelines and practice in rheumatology, in particular, efforts to enhance best practice during the coronavirus disease 2019 (COVID-19) pandemic are endorsed.

G
Gaber, W., GS Azkalany, T. A. Gheita, and et al, "Clinical significance of serum interleukin-6 and −174 G/C promoter polymorphism in Rheumatoid arthritis patients.", The Egyptian Rheumatologist,, vol. 35, issue 2, pp. 107-113, 2013.
Gheita, T. A., S. Sayed, and H. A. Gheita, "Vitamin D status in rheumatoid arthritis patients: relation to clinical manifestations, disease activity, quality of life and fibromyalgia syndrome. ", Intl J Rheum Dis, issue doi: 10.1111/1756-185X.12426. [Epub ahead of print], 2014.
Gheita, T. A., and S. A. Kenawy, "Measurement of malondialdehyde, glutathione and glutathione peroxidase in systemic lupus erythematosus patients.", Systemic Lupus Erythematosus Methods and Protocols - Methods in Molecular Biology, NewYork, Springer - Humana Press, 2014.
Gheita, T. A., S. Sayed, W. Hammam, and G. A. Hegazy, "Subclinical hypovitaminosis D and osteoporosis in breast cancer patients", Middle East J of Internal Medicine, vol. 8, issue 2, pp. 12-17, 2015.
Gheita, T. A., I. I. El-Gazzar, R. I. El-Shazly, and et al, "Elevated Serum Resistin in Juvenile IdiopathicArthritis: Relation to Categories and Disease Activity.", J Clin Immunol. , vol. 33, issue 1, pp. 297-301, 2013.
Gheita, T. A., H. M. Abdel-Samad, M. A. Mahdy, and A. B. Kamel, "Pattern of Primary Vasculitis with Peripheral Ischemic Manifestations: REPORT of a Case Series and Role of Vascular Surgery.", Curr Rheumatol Rev, vol. 10, issue 2, pp. 26-30, 2015.
Gheita, T. A., and H. M. Fathi, "Hearing loss in systemic sclerosis – Clinically important, potentially treatable and often overlooked", Int. J. Clin. Rheumatol. , vol. 12, issue 6, pp. 151-153, 2017.
Gheita, T. A., E. A. El-Latif, I. I. El-Gazzar, N. Samy, N. Hammam, R. A. Abdel Noor, E. El-Shebeiny, A. R. El-Najjar, N. N. Eesa, M. N. Salem, et al., "Behçet's disease in Egypt: a multicenter nationwide study on 1526 adult patients and review of the literature.", Clinical rheumatology, vol. 38, issue 9, pp. 2565-2575, 2019. Abstract

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.

Gheita, T. A., H. M. Fathi, N. N. Eesa, E. El-Shebini, S. Tharwat, N. Hammam, R. M. Fawzy, R. R. El-Shereef, M. H. Abd El-Samea, R. A. Abdel Noor, et al., "Development of an Arabic version of the Behçet's Disease Current Activity Form (Ar-BDCAF): cross-cultural adaptation and validation initiative in Egypt.", Clinical rheumatology, vol. 40, issue 11, pp. 4609-4618, 2021. Abstract

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.