Multi-ancestry genome-wide association analyses identify novel genetic mechanisms in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a highly heritable complex disease with unknown etiology. Multi-ancestry genetic research of RA promises to improve power to detect genetic signals, fine-mapping resolution and performances of polygenic risk scores (PRS). Here, we present a large-scale genome-wide association study (GWAS) of RA, which includes 276,020 samples from five ancestral groups. We conducted a multi-ancestry meta-analysis and identified 124 loci (P < 5 × 10-8), of which 34 are novel. Candidate genes at the novel loci suggest essential roles of the immune system (for example, TNIP2 and TNFRSF11A) and joint tissues (for example, WISP1) in RA etiology. Multi-ancestry fine-mapping identified putatively causal variants with biological insights (for example, LEF1). Moreover, PRS based on multi-ancestry GWAS outperformed PRS based on single-ancestry GWAS and had comparable performance between populations of European and East Asian ancestries. Our study provides several insights into the etiology of RA and improves the genetic predictability of RA.

Prevalence of coronavirus disease 2019 in a multiethnic cohort of patients with autoimmune rheumatic diseases in Qatar.

BACKGROUND: Autoimmune rheumatic diseases (ARDs) are characterized by immune dysfunction and associated with an increased risk of infections, which were of significant concern during the coronavirus disease 2019 (COVID-19) pandemic. Variable rates of COVID-19 incidence have been reported in patients with ARDs; however, the true effect of this infection on this patient population is still unclear. We, therefore, aimed to evaluate the COVID-19 prevalence among a multiethnic cohort of patients with ARDs in Qatar. MATERIAL AND METHODS: We used telephonic surveys to collect demographic and clinical information of patients with ARD in Qatar between April 1 and July 31, 2020, including any close contact with a COVID-19 case at home or work and polymerase chain reaction (PCR)-confirmed COVID-19 diagnosis. An electronic medical records review was conducted to verify pertinent data collected through the surveys. Prevalence with 95% confidence interval (CI), Student's t-tests, and chi-square/Fisher's exact tests were used for univariate analyses, whereas multivariate logistic regression was used to identify factors associated with COVID-19. RESULTS: The study included 700 patients with ARD (mean age, 43.2 ± 12.3 years), and 73% were female. Until July 2020, 75 (11%, 95% CI 9%-13%) patients had COVID-19. Factors associated with COVID-19 included being a man (adjusted odds ratio [aOR] 2.56, 95% CI 1.35-4.88, p = 0.01) and having close contact with a COVID-19 case (aOR 27.89, 95% CI 14.85-52.38, p = 0.01). Disease severity and rheumatic medications had no significant association with the odds of contracting COVID-19. In the 86 patients with ARD having close contact, the frequency of hydroxychloroquine utilization was lower in patients who contracted COVID-19 than in those who did not (35% vs 72.5%, p = 0.01). CONCLUSIONS: In Qatar, patients with ARDs had an overall higher prevalence of COVID-19 than global estimates. Being male and having close contact with a COVID-19 case were strongly associated with COVID-19 as reported globally. The presence of comorbid conditions, disease-specific factors, and rheumatic medications had no significant effect on the risk of COVID-19 in our study suggesting alternative mechanisms to the increased prevalence.

Development of an Educational Video for Self-Assessment of Patients with RA: Steps, Challenges, and Responses.

OBJECTIVES: The primary objective was to develop an educational video to teach patients with rheumatoid arthritis (RA) self-assessment of their disease activity. Secondary objectives were to validate the video, identify the challenges in producing it, and the responses to these challenges. METHODS: Rheumatologists from 7 Middle Eastern Arab countries (MEAC) discussed unmet needs in the education of patients with RA. They reviewed pre-existing educational audiovisual material and drafted the script for a new video in Arabic. The video was produced in collaboration with a technical team, then validated by patients using a standardized interview. At each step of production, challenges were identified. RESULTS: Twenty-three rheumatologists from MEAC identified unmet needs in patients' education. A video was produced, explaining the concepts of treat-to-target and showing a patient performing self-assessment using DAS-28. Sixty-two patients were interviewed for validation and found the video to be useful and easy to understand, albeit not replacing the physician's visit. Most common challenges encountered included acceptance of patient empowerment, agreement on DAS-28 as composite measure, production of a comprehensible written Arabic text, and addressing the population cultural mix. CONCLUSION: Despite challenges, the video was well accepted among patients and can be used for clinical and research purposes. It is particularly useful in pandemic periods where social distancing is recommended.

Large Scale Metabolic Profiling identifies Novel Steroids linked to Rheumatoid Arthritis.

Recent metabolomics studies of Rheumatoid Arthritis (RA) reported few metabolites that were associated with the disease, either due to small cohort sizes or limited coverage of metabolic pathways. Our objective is to identify metabolites associated with RA and its cofounders using a new untargeted metabolomics platform. Moreover, to investigate the pathomechanism of RA by identifying correlations between RA-associated metabolites. 132 RA patients and 104 controls were analyzed for 927 metabolites. Metabolites were tested for association with RA using linear regression. OPLS-DA was used to discriminate RA patients from controls. Gaussian Graphical Models (GGMs) were used to identify correlated metabolites. 32 metabolites are identified as significantly (Bonferroni) associated with RA, including the previously reported metabolites as DHEAS, cortisol and androstenedione and extending that to a larger set of metabolites in the steroid pathway. RA classification using metabolic profiles shows a sensitivity of 91% and specificity of 88%. Steroid levels show variation among the RA patients according to the corticosteroid treatment; lowest in those taking the treatment at the time of the study, higher in those who never took the treatment, and highest in those who took it in the past. Finally, the GGM reflects metabolite relations from the steroidogenesis pathway.

An assessment of the current treatment landscape for rheumatology patients in Qatar: Recognising unmet needs and moving towards solutions.

Objective This study assessed the mode of application (oral, intravenous or subcutaneous (SC)) currently employed in the treatment of rheumatoid arthritis (RA) in patients from Qatar in comparison with patients' individual preferences for the mode of application of their treatment. Methods This study included 294 RA patients visiting three clinics at the main referral hospital in Qatar who were interviewed using a standard questionnaire to determine their preference of mode of application for their disease-modifying antirheumatic drug (DMARD) treatment in relation to their currently employed mode of application. Results The majority of patients were female (76%), and 93% of male patients and 61% of female patients in the study clinics were of a nationality other than Qatari. The highest patient preference recorded was for an oral therapy (69%), compared with injection (23%) and intravenous (8%) therapy. In total, 85% of patients expressed a preference to remain on oral therapy compared with 63% and 58% of intravenous and SC injection patients indicating a preference to remain on their current method of administration. Conclusions This high preference for oral therapies highlights the considerable need for incorporation of new oral targeted synthetic DMARD therapies into clinical practice within the region.

Case of arthritis secondary to leprosy.

INTRODUCTION: Leprosy is a chronic granulomatous infectious disease, which is caused by Mycobacterium leprae. High numbers of people are still affected by this disease in some of the developing countries however, it is rarely seen in non-endemic regions. Cutaneous and neurological manifestations are the common and classical presentations of leprosy. Musculoskeletal involvement is the third most common manifestation but is less frequently reported. Joint involvement can present as acute symmetrical polyarthritis or chronic polyarthritis resembling rheumatoid arthritis. Leprosy can also present with tenosynovitis, either isolated or associated with arthritis. CASE PRESENTATION: We report a case of 29-year-old man who developed tenosynovitis and acute symmetrical polyarthritis including small joints of hands and feet three weeks after appearance of typical cutaneous lesion of leprosy. Patient improved with steroid and anti leprosy treatment. Patient had another acute episode with symmetrical polyarthritis four months later while on treatment. DISCUSSION AND EVALUATION: In the modern era, there is increase movement of population from developing countries to developed countries, it is likely that patient suffering from leprosy with arthritis may present to rheumatology clinic in those countries where leprosy is not endemic. Exact pathogenesis for musculoskeletal manifestations is still not fully known. Our patient presented with symmetrical polyarthritis, enthesitis and systemic involvement, which was secondary to lepra reaction. Having good knowledge of musculoskeletal manifestation of leprosy, will help narrow differential diagnosis and will prevent unnecessary diagnostic workup. CONCLUSION: Leprosy can present with different rheumatologic manifestation including tenosynovitis and acute symmetrical polyarthritis. Type 2 lepra reaction (Erythema nodosum leprosum ENL) can present with systemic manifestation and can involve skin, nerves, joints, kidneys and liver.