2023 Management Recommendations of Bangladesh Rheumatology Society on Pharmacological Treatment of Rheumatoid Arthritis With Synthetic and Biologic Disease-Modifying Drugs.

Rheumatoid arthritis (RA) is the most common inflammatory polyarthritis in Bangladesh. Bangladesh Rheumatology Society (BRS) proposes these management recommendations to treat the considerable burden of RA in the resource-constrained situation based on the best current evidence combined with societal challenges and opportunities. BRS formed a task force (TF) comprising four rheumatologists. The TF searched for all available literature, including updated American College of Rheumatology (ACR), European Alliance of Associations for Rheumatology (EULAR), and Asia-Pacific League of Associations for Rheumatology (APLAR) and several other guidelines, and systematic literature reviews until October 2023, and then a steering committee was formed, which included rheumatologists and internists. We followed the EULAR standard operating procedures to categorize levels of evidence and grading of recommendations. This recommendation has two parts -- general (diagnosis of RA, nomenclature of disease-modifying anti-rheumatic drugs [DMARDs], disease activity indices) and management portion. The TF agreed on four overarching principles and 12 recommendations. Overarching principles deal with early diagnosis and disease activity monitoring. Recommendations 1-5 discuss using glucocorticoids, NSAIDs, and conventional synthetic DMARDs (csDMARD). Recommendations 6-9 stretch the use of targeted synthetic DMARDs (tsDMARDs) and biological DMARDs (bDMARDs). The suggested DMARD therapy includes initiation with methotrexate (MTX) or another csDMARD (in case of contraindication to MTX) in the first phase and the addition of a tsDMARD in the second phase, switching to an alternative tsDMARDs or bDMARDs in the subsequent phases. The TF included the Padua prediction score for the thromboembolism risk estimation. Recommendations 10-12 cover infection screening, vaccination, and DMARD tapering. Bangladesh has a higher prevalence of RA. This recommendation will serve as a tool to treat this high burden of patients with RA scientifically and more effectively.

Cross-cultural adaptation and validation of a Bengali version of the modified fibromyalgia impact questionnaire.

BACKGROUND: Currently, no validated instruments are available to measure the health status of Bangladeshi patients with fibromyalgia (FM). The aims of this study were to cross-culturally adapt the modified Fibromyalgia Impact Questionnaire (FIQ) into Bengali (B-FIQ) and to test its validity and reliability in Bangladeshi patients with FM. METHODS: The FIQ was translated following cross-cultural adaptation guidelines and pretested in 30 female patients with FM. Next, the adapted B-FIQ was physician-administered to 102 consecutive female FM patients together with the Health Assessment Questionnaire (HAQ), selected subscales of the SF-36, and visual analog scales for current clinical symptoms. A tender point count (TPC) was performed by an experienced rheumatologist. Forty randomly selected patients completed the B-FIQ again after 7 days. Two control groups of 50 healthy people and 50 rheumatoid arthritis (RA) patients also completed the B-FIQ. RESULTS: For the final B-FIQ, five physical function sub-items were replaced with culturally appropriate equivalents. Internal consistency was adequate for both the 11-item physical function subscale (α = 0.73) and the total scale (α = 0.83). With exception of the physical function subscale, expected correlations were generally observed between the B-FIQ items and selected subscales of the SF-36, HAQ, clinical symptoms, and TPC. The B-FIQ was able to discriminate between FM patients and healthy controls and between FM patients and RA patients. Test-retest reliability was adequate for the physical function subscale (r = 0.86) and individual items (r = 0.73-0.86), except anxiety (r = 0.27) and morning tiredness (r = 0.64). CONCLUSION: This study supports the reliability and validity of the B-FIQ as a measure of functional disability and health status in Bangladeshi women with FM.

Health systems strengthening to arrest the global disability burden: empirical development of prioritised components for a global strategy for improving musculoskeletal health.

INTRODUCTION: Despite the profound burden of disease, a strategic global response to optimise musculoskeletal (MSK) health and guide national-level health systems strengthening priorities remains absent. Auspiced by the Global Alliance for Musculoskeletal Health (G-MUSC), we aimed to empirically derive requisite priorities and components of a strategic response to guide global and national-level action on MSK health. METHODS: Design: mixed-methods, three-phase design.Phase 1: qualitative study with international key informants (KIs), including patient representatives and people with lived experience. KIs characterised the contemporary landscape for MSK health and priorities for a global strategic response.Phase 2: scoping review of national health policies to identify contemporary MSK policy trends and foci.Phase 3: informed by phases 1-2, was a global eDelphi where multisectoral panellists rated and iterated a framework of priorities and detailed components/actions. RESULTS: Phase 1: 31 KIs representing 25 organisations were sampled from 20 countries (40% low and middle income (LMIC)). Inductively derived themes were used to construct a logic model to underpin latter phases, consisting of five guiding principles, eight strategic priority areas and seven accelerators for action.Phase 2: of the 165 documents identified, 41 (24.8%) from 22 countries (88% high-income countries) and 2 regions met the inclusion criteria. Eight overarching policy themes, supported by 47 subthemes, were derived, aligning closely with the logic model.Phase 3: 674 panellists from 72 countries (46% LMICs) participated in round 1 and 439 (65%) in round 2 of the eDelphi. Fifty-nine components were retained with 10 (17%) identified as essential for health systems. 97.6% and 94.8% agreed or strongly agreed the framework was valuable and credible, respectively, for health systems strengthening. CONCLUSION: An empirically derived framework, co-designed and strongly supported by multisectoral stakeholders, can now be used as a blueprint for global and country-level responses to improve MSK health and prioritise system strengthening initiatives.

Infection-associated vasculitides.

Vasculitides are disorders characterized by inflammation of the vessel walls, often caused by autoimmunity, but sometimes as a result of microbial invasion. Almost all types of microbes including bacteria, viruses, protozoa and fungi have been incriminated in the pathogenesis of vasculitis. Accurate etiological diagnosis is important since immunosuppressive treatment may lead to further deterioration if infection is the cause of vasculitis. Clinical features sometimes provide clues to the etiology. Further evaluation requires a focused and cost-effective plan of laboratory investigation. The investigations aim at establishing the diagnosis of vasculitis and identify the causative organism. An accurate diagnosis of vasculitis optimally requires histological examination and imaging. For infection-associated vasculitis, the identification of the organism requires studies of stained specimens, cultures, and/or detection of antigens and antibodies. Ideally, the treatment involves administration of an appropriate antimicrobial. In non-self-limiting types of vasculitides, glucocorticoids are needed when the symptoms are progressive, with vital organs involvement, and sometimes, when there is no antimicrobial agent of proven efficacy against the incriminated agent. Additional immunosuppressive agents or interventions must be considered when the disease is severe and/or post-infective immune mechanisms are involved in the pathogenesis, e.g., severe HBV- or HCV-associated vasculitides. Available preventative vaccinations are also crucial. The incidence of HBV-associated vasculitides dramatically decreased following HBV vaccination campaigns, and other infection-associated vasculitides may as well in the future.

Study on association of human leukocyte antigen-DRB1 alleles amongst Bangladeshi patients with rheumatoid arthritis.

INTRODUCTION: Rheumatoid arthritis (RA) is a chronic, systemic and autoimmune disease affecting 0.5-1% of the world population. Genetic and environmental factors are already established as being involved in the development of RA. Different human leukocyte antigen (HLA)-DRB1 alleles have major pathogenic effects to the development of RA. OBJECTIVE: To determine the HLA-DRB1 allelic frequency of RA in one Bangladeshi tertiary care center. METHODS: This case-control study was conducted at the Microbiology and Rheumatology Department of Bangabandhu Sheikh Mujib Medical University (BSMMU). Fifty-two patients diagnosed as having RA and 52 healthy controls were enrolled. Buccal swabs were collected from all subjects and HLA-DRB1 typing was carried out with polymerase chain reaction with sequence-specific primers (PCR-SSP) of low resolution. Blood was also collected for auto-antibodies (rheumatoid factor [RF] and anti-cyclic citrullinated peptide [anti-CCP]) detection from all subjects. RF was detected by nephelometry and anti-CCP was detected by using the enzyme-linked immunosorbent assay method. Statistical associations of HLA antigen between the groups were determined by chi-square test. RESULTS: In RA patients DR*04 and DR*10 were found at the DRB1 locus at higher frequencies (20.5%, P = 0.0035 and 18.3%, P = 0.0045, respectively). However, the frequency of DR*15 was significantly lower (P = 0.005) in RA cases (18.3%) than the control group (35.6%). The frequencies of autoantibodies (anti-CCP and RF) were compared between approximate shared epitope (SE) positive and SE negative patients, and no significant association was found. CONCLUSIONS: In this study DRB1*04 and DRB1*10 alleles were significantly associated with RA patients while DRB1*15 was found more in the control group.

Idiopathic inflammatory myopathies: from immunopathogenesis to new therapeutic targets.

Pathogenesis of idiopathic inflammatory myositis (IIM) involves strong interactions between dendritic cells (DCs), activated Th1 and Th17 cells, B cells, muscle cells, genes and environment. Local maturation of DCs permit the activation and polarization of CD4+ T cells into T(H)1 and T(H)17 that play a key role in maintaining chronic muscle inflammation. T-cell mediated myocytotoxicity promotes the liberation of specific muscle autoantigens from regenerating muscle cells with production of myositis-specific autoantibodies. Type I interferon signature is a key characteristic of IIM. Type I IFN that can be induced by immune complexes containing myositis-specific autoantibodies is produced by scattered plasmacytoid DCs but also by muscle cells particularly regenerating muscle cells. These immature muscle precursors appear to be critical in the pathogenesis of IIM as they up-regulate muscle autoantigens, type I IFN, HLA class I antigens and TLR3-7, all together involved in maintaining chronic muscle inflammation. In addition to the role of immune and muscle cells, genome-wide association studies have confirmed the importance of several MHC and non-MHC genes in IIM. Environmental factors can contribute to the pathogenesis of IIM. In sIBM, distinct features suggest both degenerative and inflammatory processes. In addition to our better understanding of the pathogenesis, identify molecular pathway leads to consider new targeted therapies including cytokine inhibition, B-cell and T-cell costimulation blockade, type I IFN neutralization or inhibition of the ubiquitin proteasome pathway.

The Bengali Short Form-36 was acceptable, reliable, and valid in patients with rheumatoid arthritis.

OBJECTIVE: To develop a culturally adapted Bengali version of the Short Form-36 (SF-36) Health Survey and to test its acceptability, reliability, and validity in patients with rheumatoid arthritis (RA). STUDY DESIGN AND SETTING: The US English SF-36 was translated into Bengali after established cross-cultural adaptation procedures. The questionnaire was interviewer administered to 125 consecutive outpatients with RA and readministered after 2 weeks to 40 randomly selected patients. RESULTS: Most participants (86.4%) did not have any problem in understanding the Bengali SF-36 and 98.4% of the questionnaires were fully completed. Only the role-physical and role-emotional scales showed substantial floor and ceiling effects. Principal component analysis confirmed that the hypothesized two-factor structure and tests of scaling assumptions were 100% successful for all eight scales expect physical functioning (98.8%) and general health (77.5%). Cronbach's α was higher than 0.78 and the test-retest reliability was high (r>0.82) for all scales. Correlations with other disease activity parameters were generally as expected and summary scores were able to discriminate between relevant subgroups. CONCLUSION: The interviewer-administered Bengali SF-36 appears to be an acceptable, reliable, and valid instrument for measuring health-related quality of life in Bangladeshi patients with RA. The questionnaire should be further evaluated in people from the general population and in patients with different medical conditions.

Efficacy and safety of methotrexate in articular and cutaneous manifestations of systemic lupus erythematosus.

AIM: A prospective open-label study comparing the efficacy and safety of methotrexate (MTX) and chloroquine (CQ) in articular and cutaneous manifestations of systemic lupus erythematosus (SLE). METHODS: Consecutive SLE patients were randomly assigned to either 10 mg MTX weekly or 150 mg CQ daily during 24 weeks. Outcome measures were: numbers of swollen and tender joints, duration of morning stiffness, visual analog scale (VAS) for articular pain, physician global assessment index, patient global assessment index, SLE Disease Activity Index (SLEDAI), disappearance of skin rash and erythrocyte sedimentation rate (ESR). RESULTS: Forty-one patients consented to participate, 15 were allocated in the MTX group and 26 in the CQ group. Two patients on MTX dropped out due to side-effects and two in the CQ group, one due to side-effects and one due to inefficacy. Baseline demographic, clinical and laboratory parameters of the two groups were nearly identical. In both groups the clinical and laboratory parameters improved significantly over 24 weeks, except the ESR in the MTX group. The results of the outcome measures at the end of the trial did not differ significantly between the two groups, except morning stiffness (P < 0.05 in favor of the MTX group) and ESR (P < 0.01 in favor of the CQ group). Rise of serum alanine aminotransferase was observed in two cases in the MTX group and in none in the CQ group. CONCLUSION: Low-dose MTX appears to be as effective as CQ in patients with articular and cutaneous manifestations of SLE, having an acceptable toxicity profile. Results of this prospective study need to be confirmed in a larger study.

Osteoarthritis of the knees in the COPCORD world.

This paper examines and summarizes data on knee osteoarthritis (AO) in Community Oriented Program For Control Of Rheumatic Disorders (COPCORD) publications. A literature search was made through PubMed, Google, Proceedings of Asia-Pacific League of Associations for Rheumatology (APLAR) congresses, and Abstracts from APLAR congresses. Data were compiled to examine the prevalence of knee OA and knee pain, sex ratio, urban/rural differences and other risk factors. Data on knee pain and OA were available in a total of 36 COPCORD publications. The pooled prevalence of knee OA was 7.9% in adults above the age of 15 years. It was more common in women. Overweight, squatting and cycling appeared to be modifiable risk factors for knee OA. OA of the knee is the commonest rheumatic disease in studied communities. Further research is needed for identification of its modifiable risk factors and development of strategies for reduction of the community burden of this malady.