Fibromyalgia and mental health in rheumatoid arthritis: a cross-sectional prevalence study from the COVID-19 pandemic.

OBJECTIVES: This study evaluated the prevalence of fibromyalgia (FM), anxiety and depression in patients with rheumatoid arthritis (RA) and their effects on the clinical parameters of RA during the COVID-19 pandemic. DESIGN: Cross-sectional, outpatient clinic, observational, non-interventional. SETTING: Single-centre, tertiary care, multispecialty, service and research hospital, north-central India. PARTICIPANTS: Adult patients with RA, controls. RESULTS: This cross-sectional study included 200 patients with RA diagnosed with the American College of Rheumatology/European League Against Rheumatism 2010 (ACR) criteria and 200 controls. FM was diagnosed using the revised 2016 ACR FM Criteria. Disease activity, quality of life and functional disability in patients with RA were assessed using multiple Disease Activity Scores. The presence of depression and anxiety was determined using the Hospital Anxiety and Depression Scale. FM was present in 31% of patients with RA compared with 4% of controls in our study. Patients with RA with FM were older, predominantly females with longer disease duration, and more likely to be on steroids. Patients with RA with FM had a higher disease activity, and none of our RA with FM patients were in remission. The multivariable analysis found FM to be an independent predictor of the Simplified Disease Activity Index for RA. Patients with RA with FM had worse functional ability and poorer quality of life. The prevalence of anxiety and depression was 12.5% and 30%, significantly higher in RA with FM patients. CONCLUSION: During the COVID-19 pandemic, around one-third of our study patients had FM and depression, significantly higher than pre-COVID-19 times. Thus, mental health assessment should be incorporated into the routine management of patients with RA.

Management of Connective Tissue Disease-related Interstitial Lung Disease.

Purpose of Review: This review aims to collate current evidence on the screening, diagnosis, and treatment of various connective tissue disease (CTD)-associated interstitial lung diseases (CTD-ILD) and present a contemporary framework for the management of such patients. It also seeks to summarize treatment outcomes including efficacy and safety of immunosuppressants, anti-fibrotics, and stem cell transplantation in CTD-ILD. Recent Findings: Screening for ILD has been augmented by the use of artificial intelligence, ultra-low dose computerized tomography (CT) of the chest, and the use of chest ultrasound. Serum biomarkers have not found their way into clinical practice as yet. Identifying patients who need treatment and choosing the appropriate therapy is important to minimize the risk of therapy-related toxicity. The first-line drugs for systemic sclerosis (SSc) ILD include mycophenolate and cyclophosphamide. Nintedanib, an anti-fibrotic tyrosine kinase inhibitor, is approved for use in SSc-ILD. The US Food and Drug Administration (FDA) has recently approved tocilizumab subcutaneous injection for slowing the rate of decline in pulmonary function in adult patients with SSc-ILD. Autologous stem cell transplantation may have a role in select cases of SSc-ILD. Summary: CTD-ILD is a challenging area with diverse entities and variable outcomes. High-resolution CT is the investigative modality of choice. Treatment decisions need to be individualized and are based on patient symptoms, lung function, radiologic abnormalities, and the risk of disease progression. Precision medicine may play an important role in determining the optimal therapy for an individual patient in the future.

Validation of Hindi version of the Pittsburg Sleep Quality Index.

BACKGROUND: Sleep quality is poorly understood in the Indian population. Lack of a suitable tool to assess sleep quality in Hindi language is the main reason behind this. Pittsburg sleep quality index (PSQI) is widely used in different population groups to assess subjective sleep quality over last one month. OBJECTIVES: To assess the reliability and validity of the Hindi translated version of Pittsburgh Sleep Quality Index (PSQI-H). gt;Methods: The PSQI-H was developed from PSQI according to following steps: (a) translation, (b) back-translation, (c) comparison between translation and back-translation performed by a group of experts, and (d) pre-pilot test in intended population. The PSQI-H was applied to 105 bilingual individuals knowing Hindi and English. The internal consistency of PSQI-H was assessed by Cronbach's alpha. For test-retest reliability assessment intraclass correlation coefficient (ICC) was measured between PSQI-H at baseline and PSQI after 4 weeks. The Pearson's coefficient was used to assess the correlation between the score of the questions and the PSQI-H scores. RESULTS: The seven components of PSQI-H shows acceptable level of internal consistency with Cronbach's alpha of 0.776. There is good test-retest reliability between PSQI-H and PSQI as measured by ICC of 0.979. The score of individual items and global scores of PSQI-H were highly correlated with each other (p< 0.001). The mean of the seven individual components score and global scores of PSQI-H at baseline and original PSQI after 4 weeks did not differ significantly. CONCLUSION: This study results demonstrate that the PSQI-H is a valid and reliable instrument for the assessment of sleep quality. PSQI-H can be used for the assessment of sleep quality in the predominantly Hindi speaking population.

Updated APLAR consensus statements on care for patients with rheumatic diseases during the COVID-19 pandemic.

AIM: To update previous guidance of the Asia Pacific League of Associations for Rheumatology (APLAR) on the management of patients with rheumatic and musculoskeletal diseases (RMD) during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: Research questions were formulated focusing on diagnosis and treatment of adult patients with RMD within the context of the pandemic, including the management of RMD in patients who developed COVID-19. MEDLINE was searched for eligible studies to address the questions, and the APLAR COVID-19 task force convened 2 meetings through video conferencing to discuss its findings and integrate best available evidence with expert opinion. Consensus statements were finalized using the modified Delphi process. RESULTS: Agreement was obtained around key aspects of screening for or diagnosis of COVID-19; management of patients with RMD without confirmed COVID-19; and management of patients with RMD with confirmed COVID-19. The task force achieved consensus on 25 statements covering the potential risk of acquiring COVID-19 in RMD patients, advice on RMD medication adjustment and continuation, the roles of telemedicine and vaccination, and the impact of the pandemic on quality of life and on treatment adherence. CONCLUSIONS: Available evidence primarily from descriptive research supported new recommendations for aspects of RMD care not covered in the previous document, particularly with regard to risk factors for complicated COVID-19 in RMD patients, modifications to RMD treatment regimens in the context of the pandemic, and COVID-19 vaccination in patients with RMD.

Deficiency of Adenosine Deaminase 2 in Adults and Children: Experience From India.

OBJECTIVE: Deficiency of adenosine deaminase 2 (DADA2) is a potentially fatal monogenic syndrome characterized by variable manifestations of systemic vasculitis, bone marrow failure, and immunodeficiency. Most cases are diagnosed by pediatric care providers, given the typical early age of disease onset. This study was undertaken to describe the clinical phenotypes and treatment response both in adults and in children with DADA2 in India. METHODS: A retrospective analysis of pediatric and adult patients with DADA2 diagnosed at various rheumatology centers across India was conducted. Clinical characteristics, diagnostic findings, and treatment responses were analyzed in all subjects. RESULTS: In total, 33 cases of DADA2 were confirmed in this cohort between April 2017 and March 2020. Unlike previous studies, nearly one-half of the confirmed cases presented during adulthood. All symptomatic patients exhibited features of vasculitis, whereas constitutional symptoms and anemia were more common in pediatric patients. Cutaneous and neurologic involvement were common, and 18 subjects had experienced at least one stroke. In addition, the clinical spectrum of DADA2 was expanded by recognition of novel features in these patients, including pancreatic infarction, focal myocarditis, and diffuse alveolar hemorrhage. Treatment with tumor necrosis factor inhibitors (TNFi) was initiated in 25 patients. All of the identified disease manifestations showed marked improvement after initiation of TNFi, and disease remission was achieved in 19 patients. Two cases were complicated by tuberculosis infection, and 2 deaths were reported. CONCLUSION: This report presents the first case series of patients with DADA2 from India, diagnosed by adult and pediatric care providers. The findings raise awareness of this syndrome, particularly with regard to its presentation in adults.

Screening for Hydroxychloroquine Retinal Toxicity in Indian Patients.

OBJECTIVE: Several studies have reported hydroxychloroquine (HCQ) retinal toxicity in East Asian patients. However, at present, there are limited data from Indian patients. The aim of this study was to investigate the prevalence and pattern of HCQ retinal toxicity in Indian population and to see if screening protocol for retinal toxicity in Indian patients should be any different to others. METHODS: This was a cross-sectional study involving adult patients with autoimmune rheumatic diseases who had received HCQ for at least 5 years or a cumulative dose of at least 500 g. Retinal toxicity was evaluated using fundus examination, visual fields 10-2 and 30-2 protocol, and spectral domain optical coherence tomography. RESULTS: Of 110 patients screened, retinal toxicity was found in 7 patients (6.36%). A parafoveal pattern was found in 4 patients, whereas a mixed parafoveal and perifoveal pattern was found in 3 patients. None of the patients had isolated perifoveal pattern. Except for the one patient, all the patients with retinal toxicity had more than 10 years (mean, 13 ± 4.89 years; range, 5-20 years) of HCQ usage with a mean cumulative dose of 1573.7 ± 771.5 g. The mean daily dose was 5 ± 1.6 mg/kg per day. CONCLUSIONS: Hydroxychloroquine retinal toxicity is more common than previously recognized in patients who have used the drug for more than 5 years. The toxicity manifests as a parafoveal or a mixed parafoveal and perifoveal pattern in Indian patients.

Anti-drug antibodies and low serum trough infliximab levels correlate with disease activity measures in spondyloarthritis patients on an as-needed infliximab treatment.

AIM: In India, many centers use infliximab at lower doses of 3-5 mg/kg without the loading dose for spondyloarthritis (SpA) patients. It is then continued on an as-required basis, rather than a fixed schedule. Our study was undertaken to see if the trough drug levels and anti-drug antibodies in patients with SpA treated with as-needed infliximab dosing correlated with the disease activity measures. METHODS: Thirty-five adult SpA patients in the age group 18-70 years were recruited. They had received three or more infusions of infliximab at 3-5 mg/kg over the past 6 to 12 months. Patient's serum tumor necrosis factor-α, trough infliximab levels and anti-drug antibodies were measured by enzyme-linked immunosorbent assay technique. The disease activity was quantified by Ankylosing Spondylitis Disease Activity Score - erythrocyte sedimentation rate/ C-reactive protein (ASDAS-ESR/CRP) scores. Correlation between quantitative variables was analyzed by the Spearman's correlation assay. The difference in mean trough infliximab and ASDAS between the drug antibody positive and negative patients was assessed using the Mann-Whitney U test. RESULTS: There was a significant negative correlation between the trough infliximab levels and the ASDAS-ESR (rs = -0.57, P < 0.01) and ASDAS-CRP scores (rs = -0.53, P < 0.01). Anti-drug antibodies were positive in 68.7% of the patients and in comparison to the antibody negative patients, had significantly higher ASDAS-ESR and ASDAS-CRP scores. CONCLUSIONS: Spondyloarthritis patients on low-dose, as-needed infliximab therapy, have both the trough infliximab and anti-drug antibodies correlate significantly with the measures of disease activity. We hypothesize that trough infliximab levels and anti-drug antibodies may be used to predict a suboptimal response due to secondary resistance in SpA patients.

Tuberculosis and biologics in rheumatology: A special situation.

India has a huge patient burden of rheumatic diseases (RDs) including rheumatoid arthritis. The use of biologics has transformed the treatment paradigm for RD; however, biologic treatment-related infections (especially tuberculosis [TB]) are an area of potential concern for TB-endemic nations like India. Anti-tumor necrosis factor (TNF) therapy impairs the physiological TNF-mediated signaling and may cause reactivation and dissemination of latent TB infection (LTBI). Careful screening is, thus, crucial in RD patients who are about to commence anti-TNF treatment. To date, there is no consensus available for the screening, evaluation and treatment of LTBI as well as on the drug dosage and duration regimen (monotherapy or combination therapy) in the Indian population. An evidence-based algorithm for LTBI screening and management in RD patients undergoing biologic disease-modifying anti-rheumatic drug therapy is suggested in this review for Indian rheumatologists. The proposed algorithm guides physicians through a step-wise screening approach, including medical history, tuberculin skin test, interferon gamma release assay, chest radiograph and management of LTBI with isoniazid therapy or its combination with rifampicin. Further, the provided algorithm can aid the national bodies (such as National TB Control Program) in formulating recommendations for LTBI in this high-risk population.

Literature review of rheumatoid arthritis in India.

AIM: Rheumatoid arthritis (RA) can lead to severe disability. This literature review assessed the descriptive epidemiology, comorbidities and extra-articular manifestations, functioning abilities and quality of life, and treatment patterns of RA patients in India. METHOD: A literature review of all observational studies published from 1985 to 2012 was conducted using MEDLINE and Embase. Quantitative and qualitative findings were summarized. RESULTS: Twenty-eight studies were identified for data extraction. Seven described the descriptive epidemiology of RA, 14 described comorbidities and extra-articular manifestations, nine described the functioning abilities and quality of life among patients, and 10 provided information on treatments. CONCLUSION: This review is confined to studies with small sample sizes, cross-sectional designs, and/or clinical settings that may not be representative of the entire Indian population. There is a need for more robust studies, as conclusions for the entire Indian RA population cannot be drawn from only the current observational studies.

Rheumatology in India--quo vadis?

Rheumatology has been a neglected subspecialty in India. A staggering patient load, a severely inadequate number of trained rheumatology specialists, therapeutic nihilism and limited advocacy are some of the critical challenges that confront rheumatology care, and possibly explain the high rates of reliance on complementary and alternative medicines in India. Disease spectrum and treatment patterns are not remarkably different from those in other countries, but biologic agents have limited use and are administered for short periods only. Consequently, outcomes in India do not yet match those reported in developed countries. Furthermore, the high prevalence of infectious diseases continues to be a major contributor to mortality in patients with rheumatic disorders such as systemic lupus erythematosus. Several tropical diseases with rheumatic manifestations are relevant in India, including chikungunya, brucellosis, leptospirosis, dengue and melioidosis. To address the many problems with rheumatology care in India, curricular reforms, capacity building, patient education and political support are sorely needed.

The effect of antidrug antibodies on the sustainable efficacy of biologic therapies in rheumatoid arthritis: practical consequences.

Biologic therapies, predominantly TNF-α inhibitors, have revolutionized the treatment of rheumatoid arthritis (RA). However, their clinical utility can be limited by the development of antidrug antibodies (ADAs). Immunogenicity is a complex phenomenon related to various drug, disease, and patient characteristics, and may be more common with the monoclonal antibodies than with etanercept, a soluble TNF receptor-Fc immunoglobulin fusion protein. Neutralizing antibodies - those that hinder bioactivity by preventing drug molecules from binding to TNF - are correlated with reduced serum drug concentrations, loss of therapeutic response, adverse events, and treatment discontinuation. Cost-effective use of these agents will depend on further research into drug and ADA assays, and how they should guide dose reduction or switching strategies.