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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., and N. N. Easa, "Rheumatology in Egypt: back to the future.", Rheumatology International , vol. 39, issue 1, pp. 1-12, 2019.
Gheita, T. A., E. A. El-Latif, I. I. El-Gazzar, N. Samy, N. Hammam, R. A. Abdel Noor, E. El-Shebeiny, A. R. El-Najjar, N. N. Eesa, M. N. Salem, et al., "Behçet's disease in Egypt: a multicenter nationwide study on 1526 adult patients and review of the literature.", Clinical rheumatology, vol. 38, issue 9, pp. 2565-2575, 2019. Abstract

OBJECTIVES: The present work was conducted to estimate the prevalence of adult Behçet's disease (BD) in adult Egyptian and to study the clinical pattern and influence of age at-onset and sex on disease phenotype. Also, we investigated the spectrum of presentation and frequencies along the north-to-south gradient of the country.

PATIENTS AND METHOD: The population-based, multicenter, cross-sectional study included 1526 adult BD patients from 26 specialized Egyptian rheumatology centers. Demographic, clinical, and therapeutic data are assessed for all patients.

RESULTS: The mean age of patients was 35.7 ± 9.84 years, disease duration 6.58 ± 5.25 years, and age at onset 29.37 ± 8.6 years; 91 were juvenile-onset (JoBD). There were 1102 males and 424 females (M:F 2.6:1). Regarding co-morbidities, 19.92% were diabetic, and 26.05% were hypertensive. The mean body mass index was 27.57 ± 5.24 (43.1% overweight; 25.9% obese). The mean BD current activity form was 4.48 ± 4.28. Regarding the medications use, systemic steroid and colchicine were the most common drugs used (947 (90.2%) and 611 (82.7%), respectively). The overall estimated prevalence of BD in Egypt was 3.6/100,000 population being highest in the two main cities: Alexandria (15.27) and Cairo (8.72). Pathergy test was positive in 43.4%. 90.2% were receiving systemic steroids and 8.3%, biologics. Disease characteristics were comparable between JoBD and adult-onset BD cases. Central nervous system (CNS), deep venous thrombosis (DVT), and gastrointestinal (GIT) involvement were significantly higher in males (p = 0.01, p = 0.001, and p = 0.001 respectively) while joint affection (p = 0.001) and disease activity (p = 0.011) were increased in females.

CONCLUSIONS: This study provides current prevalence of BD in Egypt; 3.6/100,000 with no remarkable north-to-south gradient. The sex influences the disease phenotype with the CNS, DVT, and GIT involvement are higher in males, while the joint affection and disease activity were increased in females.

KEY POINTS: • The prevalence and phenotype of Behçet's disease across Egypt is presented in a multicenter nationwide study. • The potential influence of the age at onset and sex on disease phenotype is highlightened. • A review of the literature worldwide is presented allowing comparisons with studies from other nations.

Retamozo, S., N. Acar-Denizli, A. Rasmussen, I. F. Horváth, C. Baldini, R. Priori, P. Sandhya, G. Hernandez-Molina, B. Armagan, S. PRAPROTNIK, et al., "Systemic manifestations of primary Sjögren's syndrome out of the ESSDAI classification: prevalence and clinical relevance in a large international, multi-ethnic cohort of patients.", Clinical and experimental rheumatology, vol. 37 Suppl 118, issue 3, pp. 97-106, 2019. Abstract

OBJECTIVES: To analyse the frequency and characterise the systemic presentation of primary Sjögren's syndrome (SS) out of the ESSDAI classification in a large international, multi-ethnic cohort of patients.

METHODS: The Big Data Sjögren Project Consortium is an international, multicentre registry based on world-wide data-sharing and cooperative merging of pre-existing clinical SS databases from leading centres in clinical research in SS from the five continents. A list of 26 organ-by-organ systemic features not currently included in the ESSDAI classification was defined according to previous studies; these features were retrospectively recorded.

RESULTS: Information about non-ESSDAI features was available in 6331 patients [5,917 female, mean age at diagnosis 52 years, mainly White (86.3%)]. A total of 1641 (26%) patients had at least one of the ESSDAI systemic features. Cardiovascular manifestations were the most frequent organ-specific group of non-ESSDAI features reported in our patients (17% of the total cohort), with Raynaud's phenomenon being reported in 15%. Patients with systemic disease due to non-ESSDAI features had a lower frequency of dry mouth (90.7% vs. 94.1%, p<0.001) and positive minor salivary gland biopsy (86.7% vs. 89%, p=0.033), a higher frequency of anti-Ro/SSA (74.7% vs. 68.7%, p<0.001), anti-La/SSB antibodies (44.5% vs. 40.4%, p=0.004), ANA (82.7% vs. 79.5%, p=0.006), low C3 levels (17.4% vs. 9.7%, p<0.001), low C4 levels (14.4% vs. 9.6%, p<0.001), and positive serum cryoglobulins (8.6% vs. 5.5%, p=0.001). Systemic activity measured by the ESSDAI, clinESSDAI and DAS was higher in patients with systemic disease out of the ESSDAI in comparison with those without these features (p<0.001 for all comparisons).

CONCLUSIONS: More than a quarter of patients with primary SS may have systemic manifestations not currently included in the ESSDAI classification, with a wide variety of cardiovascular, digestive, pulmonary, neurological, ocular, ENT (ear, nose, and throat), cutaneous and urological features that increase the scope of the systemic phenotype of the disease. However, the individual frequency of each of these non-ESSDAI features was very low, except for Raynaud's phenomenon.

Gheita, T. A., B. R. Sakr, R. E. Rabea, and S. M. Abdel Hamid, "Value of hematological indices versus VEGF as biomarkers of activity in Behçet's disease.", Clinical rheumatology, vol. 38, issue 8, pp. 2201-2210, 2019. Abstract

OBJECTIVE: The aim of this study is to investigate the value of several hematological indices, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), red blood cell distribution width (RDW), and mean platelet volume (MPV), versus vascular endothelial growth factor (VEGF) as biomarkers of activity in Behçet's disease (BD).

METHODS: This study included 96 adult BD patients recruited from the Rheumatology Outpatient Clinic, Kasr Al-Ainy Hospital, Cairo University, and 60 healthy subjects as controls. Assessment of BD activity was done using the Behçet's Disease Current Activity Form (BDCAF). The CBC was measured by COULTER LH 750 assay analyzer with special consideration to the NLR, PLR, MPV, and RDW. Serum VEGF level was measured by enzyme-linked immunosorbent assay (ELISA) technique.

RESULTS: The NLR, RDW, and PLR were significantly higher in BD patients when compared with healthy controls (p = 0.011, < 0.001, < 0.001, respectively), while there was no statistical difference in MPV or VEGF between patients and controls (p = 0.82, 0.46). NLR and PLR were significantly higher in BD patients with vascular activity (p = 0.03, 0.01). RDW was significantly higher, while MPV was significantly lower in patients with vascular manifestations (p = 0.04, 0.004). NLR and PLR were the most valuable predictors of vascular activity (p = 0.033, 0.018). PLR was more powerful as a predictor of vascular activity, but it had a lower specificity than NLR.

CONCLUSION: The NLR, PLR, and RDW are significantly higher in BD patients, suggesting their value as promising inflammatory biomarkers in BD. NLR and PLR are the most valuable predictors of vascular activity, while RDW and MPV were not valuable predictors of BD activity, rather implicated in the ongoing vascular inflammatory process in BD. The VEGF was neither a surrogate biomarker of BD activity nor reflecting the ongoing inflammatory process in BD.

Bassyouni, I. H., S. Fawzy, and T. A. Gheita, "Clinical Association of a Soluble Triggering Receptor Expressed on Myeloid Cells-1 (sTREM-1) in Patients with Systemic Lupus Erythematosus.", Immunol Invest, vol. 46, issue 1, pp. 38-47, 2017.
Khalil, H. M., H. A. El-Gendy, H. A. Raafat, and T. A. Gheita, "The Effectiveness of Pre- and Postoperative Infliximab in Controlling Behçet's Disease Posterior Uveitis in Patients Undergoing Vitrectomy: A Preliminary Study.", J Ophthalmol, vol. 2017, issue 8168369, pp. 1-10, 2017.
Gheita, T. A., S. M. El-Rabbat, and N. K. Mahmoud, "Fibromyalgia and Rheumatic Diseases. ", Fibrom Open Access, vol. 2, issue 1, pp. 1-5, 2017.
Gheita, T. A., and H. M. Fathi, "Hearing loss in systemic sclerosis – Clinically important, potentially treatable and often overlooked", Int. J. Clin. Rheumatol. , vol. 12, issue 6, pp. 151-153, 2017.
Hammam, N. H., and T. A. Gheita, "Impact of secondhand smoking on disease activity in women with rheumatoid arthritis.", Clin Rheumatol, vol. 36, issue 11, pp. 2415-2420, 2017.
Gheith, R. E., I. I. El-Gazzar, H. S. El-Fishawy, and T. A. Gheita, "Juvenile and juvenile-onset systemic lupus erythematosus patients: Clinical characteristics, disease activity and damage", Egyptian Pediatric Association Gazette, vol. 65, issue 2, pp. 49-53, 2017.