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2022
Rider, L. G., C. G. Parks, J. Wilkerson, A. I. Schiffenbauer, R. K. Kwok, P. Noroozi Farhadi, S. Nazir, R. Ritter, E. Sirotich, K. Kennedy, et al., "Baseline Factors Associated with Self-reported Disease Flares Following COVID-19 Vaccination among Adults with Systemic Rheumatic Disease: Results from the COVID-19 Global Rheumatology Alliance Vaccine Survey.", Rheumatology (Oxford, England), 2022. Abstract

OBJECTIVE: To examine the frequency of, and risk factors for, disease flare following COVID-19 vaccination in patients with systemic rheumatic disease (SRD).

METHODS: An international study was conducted from April 2 to August 16, 2021, using an online survey of 5619 adults with SRD for adverse events following COVID-19 vaccination, including flares of disease requiring a change in treatment. We examined risk factors identified a priori based on published associations with SRD activity and SARS-CoV-2 severity, including demographics, SRD type, comorbidities, vaccine type, cessation of immunosuppressive medications around vaccination, and history of reactions to non-COVID-19 vaccines, using multivariable logistic regression.

RESULTS: Flares requiring a change in treatment following COVID-19 vaccination were reported by 4.9% of patients. Compared with rheumatoid arthritis, certain SRD, including systemic lupus erythematosus (OR 1.51, 95%CI 1.03, 2.20), psoriatic arthritis (OR 1.95, 95%CI 1.20, 3.18), and polymyalgia rheumatica (OR 1.94, 95%CI 1.08, 2.48) were associated with higher odds of flare, while idiopathic inflammatory myopathies were associated with lower odds for flare (OR 0.54, 95%CI 0.31-0.96). The Oxford-AstraZeneca vaccine was associated with higher odds of flare relative to the Pfizer-BioNTech vaccine (OR 1.44, 95%CI 1.07, 1.95), as were a prior reaction to a non-COVID-19 vaccine (OR 2.50, 95%CI 1.76, 3.54) and female sex (OR 2.71, 95%CI 1.55, 4.72).

CONCLUSION: SRD flares requiring changes in treatment following COVID-19 vaccination were uncommon in this large international study. Several potential risk factors, as well as differences by disease type, warrant further examination in prospective cohorts.

Senosi, M. R., H. M. Fathi, N. A. M. Baki, O. Zaki, A. M. Magdy, and T. A. Gheita, "Bone mineral density, vitamin D receptor (VDR) gene polymorphisms, fracture risk assessment (FRAX), and trabecular bone score (TBS) in rheumatoid arthritis patients: connecting pieces of the puzzle.", Clinical rheumatology, 2022. Abstract

PURPOSE: To assess vitamin D receptor (VDR) gene polymorphisms and bone mineral density and to investigate the possible risk factors of osteoporosis and fracture in rheumatoid arthritis (RA).

METHODS: A total of 97 RA patients and 45 matched controls were enrolled. Serum vitamin D level, VDR genotyping, dual-energy X-ray absorptiometry (DEXA) scan, trabecular bone score (TBS), and fracture risk assessment (FRAX) in 10 years were assessed. Disease activity score (DAS28) and modified health assessment questionnaire (MHAQ) were measured.

RESULTS: The mean age of the patients was 47.9 ± 8.9 years; 85 females, 12 males (F:M 7.1:1) and mean disease duration 9.4 ± 6.2 years. DAS28 was 4.52 ± 1.04 and MHAQ 0.6 ± 0.4. There was a significant difference between cases and controls as regards DEXA and FRAX (p < 0.0001) but the TBS and VDR genotyping were comparable (p = 0.29 and p = 0.12, respectively). The vitamin D level was comparable with the control (9.3 ± 6.5 vs 10.4 ± 7.5 ng/mL, p = 0.4). None of the patients was receiving anti-osteoporotic therapy or biologic therapy. There was a significant association between the presence of osteoporosis and age, disease duration, menopause, and rheumatoid factor (RF) positivity. The TBS was significantly lower and FRAX higher in patients with positive RF and anti-CCP. FRAX was significantly related and the TBS inversely with the age, disease duration, serum uric acid, alkaline phosphatase, and MHAQ.

CONCLUSIONS: Reduced BMD and increased tendency to fractures are remarkable in RA patients. Vitamin D level was decreased in patients and control, and VDR gene polymorphisms were not linked to RA. TBS and FRAX are effective tools to assess osteoporotic fractures in RA. Key Points • Reduced bone mineral density (BMD) and increased tendency to fractures are remarkable in rheumatoid arthritis (RA) patients. • Vitamin D level was decreased in patients and control, and VDR gene polymorphisms were not linked to RA. • Trabecular bone score (TBS) and fracture risk assessment (FRAX) in 10 years are effective tools to assess osteoporotic fractures in RA.

Hernández-Molina, G., B. Kostov, P. Brito-Zerón, A. Vissink, T. Mandl, A. C. Hinrichs, L. Quartuccio, C. Baldini, R. Seror, A. Szántó, et al., "Characterization and outcomes of 414 patients with primary SS who developed hematological malignancies.", Rheumatology (Oxford, England), 2022. Abstract

OBJECTIVE: To characterize 414 patients with primary SS who developed hematological malignancies and to analyze how the main SS- and lymphoma-related features can modify the presentation patterns and outcomes.

METHODS: By January 2021, the Big Data Sjögren Project Consortium database included 11 966 patients fulfilling the 2002/2016 classification criteria. Hematological malignancies diagnosed according to the World Health Organization (WHO) classification were retrospectively identified.

RESULTS: There were 414 patients (355 women, mean age 57 years) with hematological malignancies (in 43, malignancy preceded at least one year the SS diagnosis). 376 (91%) patients had mature B cell malignancy, nearly half MALT lymphoma (n = 197), followed by DLBCL (n = 67), nodal MZL lymphoma (n = 29), CLL/SLL (n = 19) and follicular lymphoma (n = 17). Rates of complete response, relapses and death were 80%, 34% and 13%, respectively, with a 5-year survival rate of 86.5% after a mean follow-up of 8 years. There were significant differences in age at diagnosis (younger in MALT, older in CLL/SLL), predominant clinical presentation (glandular enlargement in MALT lymphoma, peripheral lymphadenopathy in nodal MZL and FL, constitutional symptoms in DLBCL, incidental diagnosis in CLL/SLL), therapeutic response (higher in MALT lymphoma, lower in DLBCL) and survival (better in MALT, nodal MZL and FL, worse in DLBCL).

CONCLUSION: In the largest reported study of hematological malignancies complicating primary SS, we confirm the overwhelming predominance of B cell lymphomas, especially MALT, with the salivary glands being the primary site of involvement. This highly-specific histopathological scenario is linked with the overall good prognosis with a 5-year survival rate of nearly 90%.

Tharwat, S., S. S. ElAdle, A. H. Moshrif, F. Ismail, R. El-Shereef, E. A. Talaat, S. Hassanein, Y. Hisham, and T. A. Gheita, "Computed tomography pulmonary angiography (CTPA) in Behçet's disease patients: a remarkable gender gap and time to refine the treatment strategy.", Clinical rheumatology, vol. 41, issue 1, pp. 195-201, 2022. Abstract

OBJECTIVE: The aim of the work was to delineate the computed tomography pulmonary angiography (CTPA) findings in Behçet's disease (BD) patients with and without chest manifestations.

PATIENTS AND METHODS: The study included 122 BD adults recruited from 5 Teaching University Hospitals in Egypt of those who agreed to perform a CTPA. The Arabic version of BD current activity form (BDCAF) and BD damage index (BDI) were assessed. Detailed pulmonary manifestations, examination, plain radiology chest, and CTPA findings were recorded.

RESULTS: The mean age of patients was 36.9 ± 11.3 years, male:female was 1.8:1, disease duration 9.6 ± 8.2 years, and age at onset 28.3 ± 8.6 years. Their mean BDCAF was 4.4 ± 2.2 and BDI 3.4 ± 1.8. There were chest manifestations in 51 (41.8%) and plain chest x-ray findings in 13 (10.7%) and CTPA findings in 31 (25.4%) in the form of pulmonary thromboembolism in 15 (12.3%), pulmonary aneurysms in 7 (5.7%), pneumonia in 5 (4.1%), interstitial lung disease in 4 (3.3%) and pleural effusion in 3 (2.5%). Patients with chest manifestations had significantly higher frequency of cardiac manifestations (15.7%) compared to those without (2.8%; p = 0.023); chest x-ray findings tended to be higher (17.6% vs 5.6%; p = 0.05) while CTPA findings were significantly detected (51% vs 7%; p < 0.0001). Higher frequency of CTPA findings were in females (p < 0.0001). Yet the rate of serious pulmonary embolisms, aneurysms, and thrombosis was exclusive in males.

CONCLUSION: Meticulous investigation of the chest manifestations is warranted in BD patients to undermine the actual magnitude of pulmonary impact. CTPA provides a realistic estimate of the extent of involvement even in asymptomatic cases. Key Points • Meticulous chest assessment is warranted in Behçet's disease patients to undermine the actual magnitude of pulmonary impact • CTPA provides a realistic estimate of the extent of involvement even in asymptomatic cases.

Sen, P., L. Gupta, J. B. Lilleker, V. Aggarwal, S. Kardes, M. Milchert, T. Gheita, B. Salim, T. Velikova, A. E. Gracia-Ramos, et al., "COVID-19 vaccination in autoimmune disease (COVAD) survey protocol.", Rheumatology international, vol. 42, issue 1, pp. 23-29, 2022. Abstract

The coronavirus disease-2019 (COVID-19) pandemic continues to be a cause of unprecedented global morbidity and mortality. Whilst COVID-19 vaccination has emerged as the only tangible solution to reducing poor clinical outcomes, vaccine hesitancy continues to be an obstacle to achieving high levels of vaccine uptake. This represents particular risk to patients with autoimmune diseases, a group already at increased risk of hospitalization and poor clinical outcomes related to COVID-19 infection. Whilst there is a paucity of long-term safety and efficacy data of COVID-19 vaccination in patients with autoimmune diseases, the current evidence strongly suggests that the benefits of vaccination outweigh the risks of adverse effects and disease flares. Herein, we report the protocol of the COVID-19 Vaccination in Autoimmune Diseases (COVAD) study, an ongoing international collaborative study involving 29 countries and over 110 investigators.

Putman, M., K. Kennedy, E. Sirotich, J. W. Liew, S. E. Sattui, T. T. Moni, A. A. Akpabio, D. Alpizar-Rodriguez, S. Angevare, R. P. Beesley, et al., "COVID-19 vaccine perceptions and uptake: results from the COVID-19 Global Rheumatology Alliance Vaccine Survey.", The Lancet. Rheumatology, vol. 4, issue 4, pp. e237-e240, 2022.
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.

Medhat, E., G. Ayeldeen, H. H. Ahmed, O. Shaker, T. Gheita, and S. S. Ashour, "HOTAIR and THRIL Long Non Coding RNAs and Their Target Genes in Rheumatoid Arthritis patients.", Reports of biochemistry & molecular biology, vol. 10, issue 4, pp. 614-621, 2022. Abstract

Background: Rheumatoid arthtritis (RA) is a chronic systemic inflammatory autoimmune disease characterized by irreversible joint damage and deformity. The aim of this study is to investigate THRIL and HOTAIR serum expression and their target genes in Egyptian RA patients and to evaluate their relationship to the clinico-pathological data.

Methods: The present study included fifty-two RA patients and fifty-six healthy controls. RA patients were classified according to DAS28 score. All subjects were subjected to full history taking and clinical examination. Quantitative real time PCR was done to estimate the expression levels of serum THRIL and HOTAIR as well as their target genes tumor necrosis factor alpha (TNF-α) and metalloproteinase 2 (MMP-2) were estimated by ELISA techniques.

Results: Results revealed that both THRIL and HOTAIR were statistically over expressed in RA patients compared to healthy group with p-value< 0.05. Results showed as well that the target genes for those long-non coding RNAs, TNF-α and MMP-2, were also significantly higher in RA patients compared to healthy controls.

Conclusion: Both THRIL and HOTAIR associated with their target genes, can be considered as diagnostic markers for RA.

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.

2021
Gheita, T. A., R. A. Noor, E. A. Alfadl, O. S. Abousehly, I. I. El-Gazzar, R. R. El Shereef, S. Senara, A. M. Abdalla, N. M. Khalil, A. M. Elsaman, et al., "Adult systemic lupus erythematosus in Egypt: The nation-wide spectrum of 3661 patients and world-wide standpoint.", Lupus, vol. 30, issue 9, pp. 1526-1535, 2021. Abstract

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.

Ramos-Casals, M., N. Acar-Denizli, A. Vissink, P. Brito-Zerón, X. Li, F. Carubbi, R. Priori, N. Toplak, C. Baldini, E. Faugier-Fuentes, et al., "Childhood-onset of primary Sjögren's syndrome: phenotypic characterization at diagnosis of 158 children.", Rheumatology (Oxford, England), vol. 60, issue 10, pp. 4558-4567, 2021. Abstract

OBJECTIVES: To characterize the phenotypic presentation at diagnosis of childhood-onset primary SS.

METHODS: The Big Data Sjögren Project Consortium is an international, multicentre registry using worldwide data-sharing cooperative merging of pre-existing clinical SS databases from the five continents. For this study, we selected those patients in whom the disease was diagnosed below the age of 19 years according to the fulfilment of the 2002/2016 classification criteria.

RESULTS: Among the 12 083 patients included in the Sjögren Big Data Registry, 158 (1.3%) patients had a childhood-onset diagnosis (136 girls, mean age of 14.2 years): 126 (80%) reported dry mouth, 111 (70%) dry eyes, 52 (33%) parotid enlargement, 118/122 (97%) positive minor salivary gland biopsy and 60/64 (94%) abnormal salivary US study, 140/155 (90%) positive ANA, 138/156 (89%) anti-Ro/La antibodies and 86/142 (68%) positive RF. The systemic EULAR Sjögren's syndrome disease activity index (ESSDAI) domains containing the highest frequencies of active patients included the glandular (47%), articular (26%) and lymphadenopathy (25%) domains. Patients with childhood-onset primary SS showed the highest mean ESSDAI score and the highest frequencies of systemic disease in 5 (constitutional, lymphadenopathy, glandular, cutaneous and haematological) of the 12 ESSDAI domains, and the lowest frequencies in 4 (articular, pulmonary, peripheral nerve and CNS) in comparison with patients with adult-onset disease.

CONCLUSIONS: Childhood-onset primary SS involves around 1% of patients with primary SS, with a clinical phenotype dominated by sicca features, parotid enlargement and systemic disease. Age at diagnosis plays a key role in modulating the phenotypic expression of the disease.

Salem, G. I., N. M. Gamal, E. A. Talaat, D. H. El-Hammady, N. Hammam, and T. A. Gheita, "Clinical Impact of the ABO Blood Type in Patients with Rheumatic Diseases: Is there a Link to the ABO and Rhesus?", Mediterranean journal of rheumatology, vol. 32, issue 3, pp. 237-242, 2021. Abstract

Objectives: Several studies have shown associations of ABO and Rh blood groups with various diseases; however, the relationship of ABO and Rh blood groups with rheumatic diseases are scarce. The aim of the present study was to examine whether there is an association between ABO and Rh blood groups and the types of rheumatic diseases.

Method: In this multi-centre cross-sectional study, sociodemographic data, type of rheumatic disease, and type ABO and Rh blood groups were examined for patients with different rheumatic diseases.

Results: A total of 304 patients; 207 (68.1%) were diagnosed with rheumatoid arthritis, and 40 (13.2%) had systemic lupus erythematosus. The patients were assessed for blood types; 37.8% patients had A type, 27.6% had B type, 19.1% had O type, and 15.4% had AB type. The Rh (+) blood group was more prevalent (89.1%) than Rh (-). Blood group A was more prevalent in patients with rheumatic disease, followed by B, O, and AB respectively, although there was no significant difference in the distribution of ABO groups among rheumatic diseases. Female gender, smoking, and anti-cyclic citrullinated peptide are significantly different between the blood groups within rheumatic diseases.

Conclusion: The A and Rh (+) blood groups were more commonly observed in patients with rheumatic diseases. There was lack of association between types of rheumatic diseases and ABO blood groups. The study provides knowledge for the interaction between ABO blood groups and several risk factors related to rheumatic diseases and may serve a guide for future clinical studies.

Gheita, T. A., N. Hammam, S. M. Fawzy, E. A. El-Latif, I. I. El-Gazzar, N. Samy, D. H. El-Hammady, R. A. Noor, E. El-Shebini, A. R. El-Najjar, et al., "Development and validation of a Behçet's Disease Damage Index for adults with BD: An Explicit, Composite and Rated (ECR) tool.", International journal of rheumatic diseases, vol. 24, issue 8, pp. 1071-1079, 2021. Abstract

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.

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.

Sattui, S. E., J. W. Liew, K. Kennedy, E. Sirotich, M. Putman, T. T. Moni, A. Akpabio, D. Alpízar-Rodríguez, F. Berenbaum, I. Bulina, et al., "Early experience of COVID-19 vaccination in adults with systemic rheumatic diseases: results from the COVID-19 Global Rheumatology Alliance Vaccine Survey.", RMD open, vol. 7, issue 3, 2021. Abstract

BACKGROUND: We describe the early experiences of adults with systemic rheumatic disease who received the COVID-19 vaccine.

METHODS: From 2 April to 30 April 2021, we conducted an online, international survey of adults with systemic rheumatic disease who received COVID-19 vaccination. We collected patient-reported data on clinician communication, beliefs and intent about discontinuing disease-modifying antirheumatic drugs (DMARDs) around the time of vaccination, and patient-reported adverse events after vaccination.

RESULTS: We analysed 2860 adults with systemic rheumatic diseases who received COVID-19 vaccination (mean age 55.3 years, 86.7% female, 86.3% white). Types of COVID-19 vaccines were Pfizer-BioNTech (53.2%), Oxford/AstraZeneca (22.6%), Moderna (21.3%), Janssen/Johnson & Johnson (1.7%) and others (1.2%). The most common rheumatic disease was rheumatoid arthritis (42.3%), and 81.2% of respondents were on a DMARD. The majority (81.9%) reported communicating with clinicians about vaccination. Most (66.9%) were willing to temporarily discontinue DMARDs to improve vaccine efficacy, although many (44.3%) were concerned about rheumatic disease flares. After vaccination, the most reported patient-reported adverse events were fatigue/somnolence (33.4%), headache (27.7%), muscle/joint pains (22.8%) and fever/chills (19.9%). Rheumatic disease flares that required medication changes occurred in 4.6%.

CONCLUSION: Among adults with systemic rheumatic disease who received COVID-19 vaccination, patient-reported adverse events were typical of those reported in the general population. Most patients were willing to temporarily discontinue DMARDs to improve vaccine efficacy. The relatively low frequency of rheumatic disease flare requiring medications was reassuring.

T, G., and K. S, "Emerging value of stem cell therapy in rheumatic diseases", African Journal of Rheumatology, vol. 9, issue 1, 2021.
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.

Retamozo, S., N. Acar-Denizli, I. F. Horváth, W. - F. Ng, A. Rasmussen, X. Dong, X. Li, C. Baldini, P. Olsson, R. Priori, et al., "Influence of the age at diagnosis in the disease expression of primary Sjögren syndrome. Analysis of 12,753 patients from the Sjögren Big Data Consortium.", Clinical and experimental rheumatology, vol. 39 Suppl 133, issue 6, pp. 166-174, 2021. Abstract

OBJECTIVES: To analyse how the main components of the disease phenotype (sicca symptoms, diagnostic tests, immunological markers and systemic disease) can be driven by the age at diagnosis of primary Sjögren's syndrome (pSS).

METHODS: By January 2021, the participant centres had included 12,753 patients from 25 countries that fulfilled the 2002/2016 classification criteria for pSS. The age at diagnosis was defined as the time when the attending physician confirmed fulfilment of the criteria. Patients were clustered according to age at diagnosis. 50 clusters with more than 100 observations (from 27 to 76 years) were used to study the influence of the age at diagnosis in the disease expression.

RESULTS: There was a consistent increase in the frequency of oral dryness according to the age at diagnosis, with a frequency of <90% in patients diagnosed at the youngest ages and >95% in those diagnosed at the oldest ages. The smooth curves that best fitted a linear model were the frequency of dry mouth (adjusted R2 0.87) and the frequency of abnormal oral tests (adjusted R2 0.72). Therefore, for each 1-year increase in the age at diagnosis, the frequency of dry mouth increased by 0.13%, and the frequency of abnormal oral diagnostic tests by 0.11%. There was a consistent year-by-year decrease in the frequency of all autoantibodies and immunological markers except for cryoglobulins. According to the linear models, for each 1-year increase in the age at diagnosis, the frequency of a positive result decreased by 0.57% (for anti-Ro antibodies), 0.47% (for RF) and 0.42% (for anti-La antibodies). The ESSDAI domains which showed a more consistent decrease were glandular and lymph node involvement (for each 1-year increase in the age at diagnosis, the frequency of activity decreased by 0.18%), and constitutional, cutaneous, and haematological involvements (the frequency decreased by 0.09% for each 1-year increase). In contrast, other domains showed an ascending pattern, especially pulmonary involvement (for each 1-year increase in the age at diagnosis, the frequency of activity increased by 0.22%), and peripheral nerve involvement (the frequency increased by 0.09% for each 1-year increase).

CONCLUSIONS: The influence of the age at diagnosis on the key phenotypic features of pSS is strong, and should be considered critical not only for designing a personalised diagnostic approach, but also to be carefully considered when analysing the results of diagnostic tests and immunological parameters, and when internal organ involvement is suspected at diagnosis.

Hammam, N., S. Tharwat, R. E. R. Shereef, A. M. Elsaman, N. M. Khalil, H. M. Fathi, M. N. Salem, H. M. El-Saadany, N. Samy, A. S. El-Bahnasawy, et al., "Rheumatology university faculty opinion on coronavirus disease-19 (COVID-19) vaccines: the vaXurvey study from Egypt.", Rheumatology international, vol. 41, issue 9, pp. 1607-1616, 2021. Abstract

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.

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.

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.

2020
Niazy, M. H., W. Gaber, S. Sayed, O. G. Shaker, and T. A. Gheita, "The anti-aging protein alpha-Klotho in systemic sclerosis patients: does a relationship to telangiectasia exist?", Zeitschrift fur Rheumatologie, vol. 79, issue 4, pp. 404-409, 2020. Abstract

OBJECTIVE: The anti-aging protein alpha-Klotho has been reported to have an emerging role in the pathogenesis of systemic sclerosis (SSc). More studies are needed to approach this issue. This study aimed to assess the serum levels of α‑Klotho in SSc patients compared to healthy controls, and to correlate them with the disease parameters.

METHODS: Forty-two SSc patients were included in this study. History taking, clinical examination, and related investigations were performed. The modified Rodnan skin score (mRss) was used to assess skin tightness in SSc patients. Twenty-seven age- and sex-matched healthy participants served as controls. Serum α‑Klotho was assessed in the two groups.

RESULTS: SSc patients comprised 39 females and 3 males; mean age was 42.2 ± 12.1 years and mean disease duration 8.5 ± 6.3 years. Serum α‑Klotho levels were decreased in scleroderma patients in comparison to healthy controls (p < 0.001). Scleroderma patients who had higher frequencies of telangiectasias and digital ischemic lesions had higher serum α‑Klotho levels (p = 0.01 and p = 0.04, respectively). By simple regression, only telangiectasias were significantly associated with higher α‑Klotho levels (p = 0.01). No other significant relationships were found between serum α‑Klotho and SSc disease parameters.

CONCLUSION: Scleroderma patients had significantly lower serum α‑Klotho levels than healthy controls. Higher α‑Klotho levels were significantly associated with telangiectasias. An imbalance in serum α‑Klotho levels may be involved in systemic sclerosis. Further longitudinal studies in a larger population of systemic sclerosis patients may provide a clearer clue for its role.

Hammam, N., N. Abdel-Wahab, and T. A. Gheita, "Atherogenic Index of Plasma in Women with Rheumatoid Arthritis and Systemic Lupus Erythematosus: a 10-Year Potential Predictor of Cardiovascular Disease.", Current rheumatology reviews, 2020. Abstract

BACKGROUND: Women with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are at high risk of cardiovascular diseases (CVD). The atherogenic index of plasma (AIP) is a new marker for the assessment of CVD.

OBJECTIVE: This study aimed to determine the predictive value of AIP with long term CVD risk among women with RA and SLE.

METHODS: This is a cross-sectional study of 99 RA and 59 SLE women. Demographic, clinical, and biochemical data were obtained, and disease activities were calculated. For each patient, the long-term risk of CVD was calculated using the Framingham risk score (FRS); AIP was derived according to the logarithmic (triglycerides/high-density lipoproteins cholesterol).

RESULTS: The mean age of the RA and SLE patients was 47.97 ± 8.78 and 36.75 ± 9.09 years, respectively. The median (interquartile range) of AIP values in RA and SLE patients were 0.34 (-0.15, 1.02) and 0.33 (-0.53, 0.96), respectively, while FRS values of RA patients and SLE patients were 6.38 ± 5.58 and 4.86 ± 4.5, respectively (p >0.05). There was a moderate correlation between AIP and FRS in RA and SLE patients (r=0.42, p=0.002 and r=0.33, p=0.007, respectively). According to the multivariate regression analyses, we found that AIP value is an independent factor for FRS in RA (β: 4.13, 95% confidence interval; 1.71, 6.18; p=0.008) and in SLE patients (β: 6.19, 95% confidence interval; 2.58, 9.81; p<0.001).

CONCLUSIONS: We reported that AIP can be used as an independent indicator for long-term CVD risk in RA and SLE patients.

Gheita, T. A., and S. A. Kenawy, "Egypt's groundwork blessing during the COVID-19 pandemic curse: Rheumatologic experience.", European journal of rheumatology, vol. 7, issue Suppl 2, pp. S134-S136, 2020.
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