Publications

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Book
Gheita, T. A., S. A. Kenawy, and R. W. El-Sisi, Behçet's disease and subclinical atherosclerosis: An overlooked association, , Berlin, Germany, LAP Lambert, 2013.
Book Chapter
Gheita, T. A., and S. A. Kenawy, "Measurement of malondialdehyde, glutathione and glutathione peroxidase in systemic lupus erythematosus patients.", Systemic Lupus Erythematosus Methods and Protocols - Methods in Molecular Biology, NewYork, Springer - Humana Press, 2014.
Conference Paper
Gheita, T. A., S. A. Kenawy, and H. A. Gheita, "BAFF in postmenopausal RA patients with low bone mass: A possible protective role of HCQ. ", Ann Rheum Dis. Supplement Paris, France, ‘EULAR’, 2014.
Gheita, T. A., S. Sayed, W. Hammam, and G. A. Hegazy, "Subclinical hypovitaminosis D and osteoporosis in breast cancer patients. ", 7th Int’l Conf. on Osteoporosis and Bone Research (COBR), , Xiamen, China, 2014.
Journal Article
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.

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.

Gheita, T. A., R. W. El-Sisi, H. A. Raafat, and et al, "Anti-Annexin V Antibodies in Primary Fibromyalgia Syndrome: Relation to Associated Sjögren's Syndrome. ", J Clin Immunol., vol. 33, issue 2, pp. 311-3-12, 2013.
Gheita, T. A., N. M. Abaza, and N. H. Hammam, "Anti-dsDNA titre in female systemic lupus erythematosus patients: relation to disease manifestations, damage and antiphospholipid antibodies.", Lupus, vol. 27, issue 7, pp. 1081-1087, 2018.
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.

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.

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.

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.

Gheita, T. A., GS Azkalany, S. A. Kenawy, and A. A. Kandeel, "Bone scintigraphy in axial seronegative spondyloarthritis patients: role in detection of subclinical peripheral arthritis and disease activity.", Int J Rheum Dis., issue doi: 10.1111/1756-185X.12527. [Epub ahead of print], 2015.
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%.

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.

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.
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., D. M. Abd-El-Rehim, S. A. Kenawy, and H. A. Gheita, "Clinical significance of MMP-3 in SLE patients: a potential biomarker for disease activity and damage.", Acta Reumatológica Portuguesa, issue Online First: 2015-01-12, 2015.
Abaza, N. A., E. M. Abdel-Latif, and T. A. Gheita, "Clinical Significance of Neutrophil/lymphocyte Ratio in Patients With Granulomatosis With Polyangiitis.", Reumatologia Clinica, 2018.
Gheita, T. A., S. M. Gamal, I. Shaker, and et al, "Clinical significance of serum interleukin-23 and A/G gene (rs17375018) polymorphism in Behçets disease: Relation to neuro-Behçet, uveitis and disease activity.", Joint Bone Spine, vol. 82, issue 3, pp. 213-215, 2015.
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