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Gheita, T. A., and N. N. Easa, "Rheumatology in Egypt: back to the future.", Rheumatology International , vol. 39, issue 1, pp. 1-12, 2019.
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.
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.

Ramos-Casals, M., P. Brito-Zerón, S. Bombardieri, H. Bootsma, S. De Vita, T. Dörner, B. A. Fisher, J. - E. Gottenberg, G. Hernandez-Molina, A. Kocher, et al., "EULAR recommendations for the management of Sjögren's syndrome with topical and systemic therapies.", Annals of the rheumatic diseases, vol. 79, issue 1, pp. 3-18, 2020. Abstract

The therapeutic management of Sjögren syndrome (SjS) has not changed substantially in recent decades: treatment decisions remain challenging in clinical practice, without a specific therapeutic target beyond the relief of symptoms as the most important goal. In view of this scenario, the European League Against Rheumatism (EULAR) promoted and supported an international collaborative study (EULAR SS Task Force) aimed at developing the first EULAR evidence and consensus-based recommendations for the management of patients with SjS with topical and systemic medications. The aim was to develop a rational therapeutic approach to SjS patients useful for healthcare professionals, physicians undergoing specialist training, medical students, the pharmaceutical industry and drug regulatory organisations following the 2014 EULAR standardised operating procedures. The Task Force (TF) included specialists in rheumatology, internal medicine, oral health, ophthalmology, gynaecology, dermatology and epidemiology, statisticians, general practitioners, nurses and patient representatives from 30 countries of the 5 continents. Evidence was collected from studies including primary SjS patients fulfilling the 2002/2016 criteria; when no evidence was available, evidence from studies including associated SjS or patients fulfilling previous sets of criteria was considered and extrapolated. The TF endorsed the presentation of general principles for the management of patients with SjS as three overarching, general consensus-based recommendations and 12 specific recommendations that form a logical sequence, starting with the management of the central triplet of symptoms (dryness, fatigue and pain) followed by the management of systemic disease. The recommendations address the use of topical oral (saliva substitutes) and ocular (artificial tear drops, topical non-steroidal anti-inflammatory drugs, topical corticosteroids, topical CyA, serum tear drops) therapies, oral muscarinic agonists (pilocarpine, cevimeline), hydroxychloroquine, oral glucocorticoids, synthetic immunosuppressive agents (cyclophosphamide, azathioprine, methotrexate, leflunomide and mycophenolate), and biological therapies (rituximab, abatacept and belimumab). For each recommendation, levels of evidence (mostly modest) and TF agreement (mostly very high) are provided. The 2019 EULAR recommendations are based on the evidence collected in the last 16 years in the management of primary 2002 SjS patients and on discussions between a large and broadly international TF. The recommendations synthesise current thinking on SjS treatment in a set of overarching principles and recommendations. We hope that the current recommendations will be broadly applied in clinical practice and/or serve as a template for national societies to develop local recommendations.

Gheita, A. A., T. A. Gheita, and S. A. Kenawy, "The potential role of B5: A stitch in time and switch in cytokine.", Phytotherapy research : PTR, vol. 34, issue 2, pp. 306-314, 2020. Abstract

The wound healing process is a multifaceted sequence of activities associated with tissue restoration. Novel approaches for the perfection of wound healing have been determined as a stitch in time saves nine. Dysregulation of the immune response is a key element in the pathogenesis of rheumatic diseases and serves as a potential target for novel therapeutic strategies. Vitamin B5 (VB5), also known as pantothenate or "anti-stress vitamin," is the precursor of coenzyme A, which is essential in every micro-organism. Many pantothenic acid amides acquire persuasive antimicrobial activity. Pantothenic acid improves surgical wounds healing with moisturizing and skin barrier enhancing potential. Its deficiency leads to reduced cortisol production, increased arthritic pain, myalgia, fatigue, headache, depression, insomnia, and widespread "proinflammatory" effects on the immune-system. VB5 triggers immune cells to produce cytokines and is multifunctional. The paradoxical effect of VB5 on the switch of anti-inflammatory and proinflammatory cytokines has been revealed. This review aims to present the long research journey of B5 as it is becoming a forerunner in the healing of wounds and in enhancing the immune function, thus providing potentially important therapeutic implications. As its role in healing a wound stitch is promising, amending the immune system damage too is a hopeful target.

Gheita, T. A., M. N. Salem, N. N. Eesa, N. M. Khalil, N. M. Gamal, R. A. Noor, A. H. Moshrif, R. E. Shereef, F. Ismail, N. Noshy, et al., "Rheumatologists' practice during the Coronavirus disease 2019 (COVID-19) pandemic: a survey in Egypt.", Rheumatology international, vol. 40, issue 10, pp. 1599-1611, 2020. Abstract

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

Hammam, N., N. M. Gamal, M. H. Elzohri, A. M. Elsonbaty, A. M. Rashed, Z. H. Eldaly, D. Tarik, and T. A. Gheita, "Serum 14-3-3η protein is associated with clinical and serologic features of Sjögren's syndrome in patients with systemic lupus erythematosus: a cross-sectional analysis.", Clinical rheumatology, vol. 39, issue 9, pp. 2603-2610, 2020. Abstract

INTRODUCTION/OBJECTIVES: Systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS) may coexist and carry a higher risk for future comorbidities. Although 14-3-3η protein is recently a known diagnostic marker in rheumatoid arthritis (RA), its role has not been investigated in SLE. The aim of this study was to compare serum 14-3-3η protein level in SLE and RA patients and to examine its association with clinical and laboratory features in SLE patients.

METHODS: Eighty-four SLE patients and 39 RA patients were included. Sociodemographic, SLE disease activity index (SLEDAI), and damage index were assessed for SLE patients. Data about secondary SS were collected. 14-3-3η was measured by ELISA; titres above 0.19 ng/ml were considered positive.

RESULTS: Serum 14-3-3η protein in SLE was significantly lower than in RA (0.37 ± 0.09 vs 1.5 ± 0.51; p < 0.001). 14-3-3η protein level was comparable between SLE patients with and without arthritis (0.29 ± 0.8 vs 0.15 ± 0.08 respectively; p = 0.20). Serum 14-3-3η protein level was higher in SLE with secondary SS features compared to those without (0.22 ± 0.10 IU/ml vs 0.11 ± 0.04 IU/ml; respectively, p < 0.001). There were no differences in 14-3-3η positivity for other lupus criteria or correlation of 14-3-3η titer with SLEDAI. 14-3-3η protein at 1.11 ng/mL yield a secondary SS diagnostic accuracy of 71%.

CONCLUSIONS: Serum 14-3-3η protein level is high in SLE-associated SS. The 14-3-3η protein level was able to distinguish patients with secondary SS among patients with SLE. Studying the role of 14-3-3η protein in Sjögren's syndrome would be considered in further larger scale studies to confirm the impact of any association. Key Points • Serum 14-3-3η protein level is significantly higher in systemic lupus patients with secondary Sjögren's syndrome (SS) in comparison to those without. • Serum 14-3-3η protein can be used as a useful marker to distinguish patients with secondary SS among patients with systemic lupus. • 14-3-3η protein level shows no difference between systemic lupus patients with and without arthritis.

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.

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.

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.