Background: This multicentre prospective observational study assessed the clinical characteristics, treatment modalities and short-term outcomes of patients diagnosed with early axial spondyloarthritis (axSpA) in India. Methods: Fourteen rheumatology outpatient clinics in India enrolled patients aged >= 18 years with axial symptoms of <2 years who met the 2009 Assessment of SpondyloArthritis International Society (ASAS) classification criteria for axSpA. Disease activity indices (Ankylosing Spondylitis Disease Activity Score [ASDAS] and Bath Ankylosing Spondylitis Disease Activity Index [BASDAI]), functional index (Bath Ankylosing Spondylitis Functional Index [BASFI]), non-steroidal anti-inflammatory drug (NSAID) intake scores, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were assessed at baseline, 3 months and 6 months. Correlation analysis was conducted between the study results and comparable international early axSpA inception cohorts. Results: A total of 155 patients (81% men, mean age 28 years) were included in the study. Eighty-five percent of patients were human leukocyte antigen B27 (HLA-B27) positive. Peripheral arthritis (31%), enthesitis (32%) and uveitis (14%) were common. At baseline, the mean (standard deviation (SD), 95% confidence interval) of the ASDAS-CRP, BASDAI and BASFI indices was 3.5 (1.1, 3.3-3.7), 4.2 (1.7, 3.9-4.5) and 3.8 (1.8, 3.5-4.2), respectively. After 6 months, these indices decreased to 1.7 (0.8, 1.5-1.8; P < .01), 2.0 (1.5, 1.7-2.2; P < .01) and 1.6 (1.2, 1.3-1.8; P < .01), respectively. The median NSAID intake score decreased from 50 to 10 (P < .01). Radiographic sacroiliitis was observed in 54% of patients and magnetic resonance imaging (MRI) sacroiliitis was observed in 97% of patients. Conclusion: This study demonstrates that early diagnosis and treatment of axSpA significantly improved clinical outcomes and reduced NSAID use in the study participants. The genetic and clinical profiles of Indian patients with early axSpA are comparable to those of patients worldwide. The high radiographic sacroiliitis observed in this study suggests a delayed diagnosis of axSpA in Indian patients.
BACKGROUND:Reactive arthritis (ReA) is a lower-limb predominant oligoarthritis that follows genitourinary or gastrointestinal infection with a 2-4 week latency. Up to 40% can progress to chronicity. There is no approved disease-modifying anti-rheumatic drug for ReA yet. METHODS:Fifty consecutive patients of ReA, defined by Braun criteria, refractory to NSAIDs were included, with 25 in each group (Sulfasalazine group, tofacitinib group). Forty-six patients completed the study. The primary endpoint was DAREA (Disease Activity Index for the Assessment of Reactive Arthritis) at week 12 between the two groups. Complete response (CR), partial response (PR) and no response (NR) were defined based on DAREA of ≤ 5, 6-10, and > 10, respectively. Secondary endpoints were pain VAS, ESR, CRP, BASFI, MASES, and ASDAS-CRP. RESULTS:Of the 46 patients who completed the study, 70% were males, with HLA-B27 positivity in 65%. Twenty-one received sulfasalazine and 25, tofacitinib. The median DAREA at 12 weeks [3.35 (IQR: 2.77-9.18) vs. 3.05 (IQR: 2.69, 8.45), respectively)] was comparable between the two groups (p = 0.545). The decline in CRP, ESR, and DAREA was quicker in the tofacitinib group (by week 4). Change from baseline to 12 weeks in DAREA and the secondary endpoints was statistically significant within both groups (p < 0.001). 25% of patients in the tofacitinib group and 18.2% in the sulfasalazine group had NR. There were no serious adverse events in either group by week 12. CONCLUSION:Sulfasalazine and tofacitinib showed comparable effectiveness and safety in NSAID-refractory ReA at 12 weeks, with tofacitinib exhibiting a more rapid onset of therapeutic response.
Background: Rheumatoid arthritis (RA) is a polyarthritis classically affecting bilateral and symmetrical joints. Although a progressive disease, RA patients experience high and low disease activity phases, which are reflected in symptoms and functional ability. Any worsening of the illness results in permanent changes to the joints. This study was conducted to assess the functional disability among patients with RA, to elicit its association with selected sociodemographic and clinical variables and with disease activity.Methods: A cross-sectional study was conducted by a convenience sampling method, amongst 400 consenting RA patients, visiting the rheumatology outpatient department (OPD) of the hospital. Sociodemographic and clinical data were taken and their functional disability.Background: RA is a polyarthritis classically affecting bilateral and symmetrical joints. Although a progressive disease, RA patients experience high and low disease activity phases, which are reflected in symptoms and functional ability. Any worsening of the illness results in permanent changes to the joints. This study was conducted to assess the functional disability among patients with RA, to elicit its association with selected sociodemographic and clinical variables and with disease activity.Methods: A cross-sectional study was conducted by convenience sampling method, amongst 400 consenting RA patients, visiting the rheumatology OPD of the hospital. Sociodemographic and clinical data were taken and their functional disability assessed using Health Assessment Questionnaire Disability Index (HAQ-DI) score and its association with the variables of disease activity studied using the Disease Activity Score 28 (DAS28) scale, from June 2022 to July 2024.Results: The mean age of the study participants was 50.2 +/- 10.48 years; 86.4% of them were females. The mean HAQ-DI score was 0.70 +/- 0.83. The eating and hygiene component of the eight domains studied in HAQ-DI was most affected in RA patients in this study. Functional disability was found to be significantly associated with a higher total cholesterol/high density lipoprotein (TC/HDL) ratio and measures of disease activity.Conclusion: This study found functional limitations in all domains with eating and personal hygiene being the most prevalent; similarly, higher TC/HDL ratio and disease severity were also associated with higher functional disability. These domains and risk factors being modifiable, can help physicians in early identification and prevention of disability.
OBJECTIVES:This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the effect and safety of yoga as an adjunctive therapy for rheumatoid arthritis.
Determine domain-based-outcomes and steroid-sparing efficacy of generic tofacitinib in IIM. This is a multicenter retrospective study wherein clinical phenotype, autoantibody profile, prior immunosuppressives, and outcomes at 3, 6, and 12 months were retrieved for IIM patients prescribed tofacitinib. Overall clinical response was assessed as complete or partial remission as per physician judgment. Changes in cutaneous and calcinosis domain were recorded as per physician global assessment (PGA), lung domain as per medical research council (MRC) dyspnea scale, and muscle strength by Manual Muscle Testing-8 (MMT-8). Forty-two patients of IIM with mean age 38.7 ± 16 years; (76.2
During the onset of the pandemic, a common research question was asked by the hospital staff, and family members who were handling COVID-19-infected cadavers, "does COVID-19-positive dead body harbor SARS-CoV-2 viral RNA?" Several research findings were reported but due to the lack of proper research findings, the question remained unanswered. The present study was planned to observe the virus transmission risk from cadavers to the handlers. A pilot study was conducted on 54 cadavers who died in COVID-ICU (SARS-CoV-2-positive diagnosed by RT-PCR) during 2021-2022. Skin swab sample from 54 dead bodies and 54 glove samples of handlers were taken within 1 hour of death for the RT-PCR test. Viability results from RT-PCR show that the infection risk was 50% in cadavers, whereas the transmission risk to handlers while handling was 7%, which is minimal. The SARS-CoV-2 viability was high in cases of those died after a long time of infection. Based on the RT-PCR result and data analysis the interpretation of the study was that the SARS-CoV-2 transmission risk from dead bodies to the handlers is minimal but the SARS-CoV-2 viability persists in the cadavers. This fact is helpful for the people who will conduct funeral activities, autopsy staff, and hospital staff handling dead bodies.
Background: Animal models studies show the role of interleukin-22 (IL-22) in the pathogenesis of enthesitis. We analysed an association of IL-22 levels with enthesitis in Enthesitis-related juvenile idiopathic arthritis (JIA-ERA) patients. Methods: Patients with JIA-ERA, polyarticular JIA (Poly-JIA), and healthy controls (HC) were enrolled. The frequencies of Th1, Th17 and Th22 cells in peripheral blood (PB) and synovial fluid (SF) were determined by flow cytometry, and IL-22 levels in SF by ELISA. Data is shown as median with interquartile range. Results: T-cell frequency was determined in 40 JIA-ERA (33 boys, 16 [3.3] years), 10 Poly-JIA (3 boys, 14.5 [6] years), and 10 HC (9 boys, 18 [2] years). Among 40 JIA-ERA patients, 28 had enthesitis. In JIA-ERA, Th1 cell frequency was significantly higher in SF (8.6 [4.5]) than in PB (2.9 [0.55]; P = 0.007). Th22 cell frequency in PB was higher in active JIA-ERA patients as (0.2 [0.1]; JSpADA >2.5) compared to the inactive disease (0.15 [0.18]; P = 0.02). No association was observed between Th22 cell frequency and enthesitis. No difference in serum IL-22 levels of 85 JIA-ERA (78 boys, 16 [4] years), 13 Poly-JIA (4 boys, 12 [7.5] years), and 31 HC (27 boys, 25 [8] years) was observed. SF showed higher IL-22 levels than corresponding serum samples (P = 0.04). Conclusion: High SF levels of IL-22 suggests its role in inflammation in JIA-ERA patients. The lack of association of PB Th22 cell frequency with enthesitis suggests that immune abnormalities at local site may not be reflected in PB.
Background: Infections are a major cause of morbidity and mortality in juvenile systemic lupus erythematosus (SLE). We assessed the incidence and risk factors for major infections in juvenile SLE. Methods: A retrospective review of 225 patients of juvenile SLE (ACR 1997 criteria) with age <18 years visiting the rheumatology clinic at a single centre between 2000 to 2020 was done from case records and the hospital electronic health records. Serious infection was defined as the need for hospitalization, or infection resulting in disability or death. Cox regression was used to determine factors associated with a serious infection and the effect of serious infection on overall survival. Results: We reviewed 225 children (197 girls, mean age 13.89 +/- 3.42 years) with a cumulative follow up of 1153.45 person-years. Eighty serious infections occurred in 63 (28% of the cohort) children at a rate of 69.35 serious infections per 1000 person-years. A second serious infection occurred in 12 children and 5 of them developed three infections. Among the cases with known etiology (78.75% of cases), bacterial infections were most common (N = 33) including S. Aureus (11), E. Coli (7), K. Pneumoniae (3), E. Fecalis (3), S. Pneumoniae (2), Acinetobacter spp. (2), Citrobacter (2), Salmonella (2) and P. Aeruginosa (1). Twenty six (32.5%) opportunistic infections occurred: Mycobacterium tuberculosis (18), Cytomegalovirus (3), disseminated Herpes zoster (4) and invasive candidiasis (1) with 15 (83.3%) of the tuberculosis cases being extrapulmonary. On multivariate analysis, fever (HR 8.51, 1.17-61.44), gastrointestinal involvement (HR 4.73, 1.13-19.94), current steroid dose (HR 1.36,1.14-1.62), average cumulative steroid dose per year (HR 1.004, 1.002-1.005) and cyclophosphamide (HR 2.22, 1.11-4.46) were associated with serious infection. Hospitalization rates were significantly higher in those with any serious infection (Rate-ratio 2.79, 1.81-3.77) as was damage accrual (SLICC damage index 1.04 vs 0.22). Serious infection-free survival at 1 year and 5 years was 84% (79.1-89.2) and 72% (65.4-79.2). There were 19 deaths with infection attributable mortality in 10 (52.6%). Serious infection predisposed to higher overall mortality with recurrent infections conferring a hazard ratio of 36.02 (8.07-160.62). Conclusion: Serious infections are a major cause of mortality and damage in SLE. Constitutional symptoms, gastrointestinal involvement, current and cumulative steroid dose and cyclophosphamide predict serious infections. TB prophylaxis in patients with SLE should be considered in endemic areas, especially when using high-dose steroid therapy.
Takayasu arteritis is an uncommon systemic inflammatory large vessel vasculitis affecting women in their third and fourth decades frequently. The disease poses considerable morbidity and mortality owing to the involvement of the aorta and its major branches. Treatment comprises medical and vascular interventions, tailored to each patient. We review the high-impact publications of the year 2023 up to April 2024, which provide great insight into clinical, biomarker, imaging, pathogenetic, and therapeutic updates.
Background: Methotrexate (MTX) at a dose of ≤25 mg/week is one of the most prescribed disease-modifying anti-rheumatic drugs (DMARDs) in a variety of rheumatic diseases. It can potentially cause life-threatening neutropenic sepsis, and acute renal and hepatotoxicity when taken inadvertently at high doses. We aim to analyse the clinical profile and risk factors of patients who presented with acute MTX toxicity. Methods: All patients presenting to the Rheumatology department with a history of inadvertent consumption of higher doses of MTX (>25 mg/week), from July 2021 to May 2023 were included. Additional data was extracted from hospital electronic medical health records. The clinical profile, risk factors, and outcome of patients with MTX toxicity were analysed. Results: The median age of the patients in our cohort was 52 IQR (40–62.5) years, with 80% females. The median cumulative dose of MTX was 120 mg (IQR 95–150). The reason for overdose in our cohort was medication error in comprehending once-weekly dosing. The most common major adverse event was neutropenia (80%). All our patients had stomatitis, with half of them having oral bleeding. Gastrointestinal adverse events like vomiting and diarrhoea were seen in 60% and 13% of the patients, respectively. Our cohort had two patients who succumbed to the complications due to neutropenic sepsis. The dose of MTX did not correlate with the severity of the disease or duration of hospital stay; however, the latter was significantly influenced by lower absolute neutrophil count (ANC). Conclusion: Acute MTX toxicity is one of the severe rheumatological emergencies and the toxicity profile includes haematological, gastrointestinal, hepatic, and renal adverse events. Severe neutropenia leading to sepsis can be fatal if not intervened early.
Objectives Reactive arthritis (ReA) provides a unique opportunity to comprehend how a mucosal infection leads to inflammatory arthritis at a distant site without the apparent invasion of the pathogen. Unfortunately, conventional stool cultures after ReA provide limited information, and there is a dearth of metagenomic studies in ReA. The objective of this study was to identify gut microbiota associated with the development of ReA.Methods Patients with ReA or undifferentiated peripheral spondyloarthritis (UpSpA) were included if they presented within 4 weeks of the onset of the current episode of arthritis. Metagenomic DNA was extracted from the stools of these patients and of 36 age- and sex-similar controls. Sequencing and analysis were done using a standard 16S ribosomal pipeline.Results Of 55 patients, there was no difference between the gut microbiota of postdiarrheal ReA (n = 20) and of upSpA (n = 35). Comparing the gut microbiota of patients vs healthy controls, the patients had significantly higher alpha and beta diversity measures. After stringency filters, Proteobacteria had high abundance while Firmicutes had lesser as compared with the controls. Six families were overexpressed in patients, while another five were overexpressed in controls. Sixteen genera and 18 species were significantly different between patients and controls. At the species level there was strong association of Staphylococcus aureus, Clostridium septicum Klebsiella pneumoniae, Escherichia coli, Empedobacter brevis, Roseburia hominis, Bacillus velezensis and Crassaminicella with ReA.Conclusion The microbiota of classical gut-associated ReA and upSpA is similar. Patients have higher diversities in their gut microbiota compared with healthy controls. Both known and previously unreported species associated with ReA/upSpA were identified.
Objective:To differentiate the nailfold capillaroscopy (NFC) findings in patients with MCTD-ILD and SSc-ILD and correlate the NFC changes and lung functions among them. Methods:In this observational study from Oct 2020 to Oct 2022, 27 patients with MCTD-ILD and 27 patients with SSc-ILD were included. NFC was performed using Jiangsu Jiahua, JH 1004, China. Statistical analysis was conducted using IBM SPSS software, version 26, and tests including Mann-Whitney U-test, student t-test, chi-square test, or Fisher's exact test were used to compare between groups. Results:In this study, major capillaroscopic changes were more frequent in SSc-ILD group (92%) than in MCTD-ILD group (72.3%), with normal capillaries seen in 7.4% of MCTD-ILD cases. The mean FVC was higher in SSc-ILD group compared to MCTD-ILD group, and patients with capillary loss had a lower mean FVC. Loss of capillaries was more frequent in SSc-ILD group, while dilated capillaries were predominantly observed in MCTD-ILD group. A significant association was found between the severity of restriction in spirometry and NFC. Conclusion:There is an important role for NFC in detecting the severity of lung involvement, as the grading of restrictive severity in spirometry is strongly associated with capillaroscopic abnormalities.
To study the prevalence and predictors of calcinosis in Juvenile Dermatomyositis (JDM). Medical records over 20 years at a tertiary care rheumatology center in Northern India were reviewed to identify patients with JDM and clinical details were recorded. The frequency of calcinosis, predictors, specific treatment, and its outcomes were studied. Data are expressed as median and interquartile range. In eighty-six patients (median age 10) of JDM, the frequency of calcinosis was 18.2
There is uncertainty regarding the effect of the SARS-CoV-2 infection on patients with autoimmune rheumatic diseases (AIRD) who are on immunosuppressive drugs. We did a multicity cross-sectional seroprevalence study conducted in five different cities in India before COVID-19 immunization. Patients with a diagnosis of AIRD and DMARDs were included. Relatives of the patients, preferably staying in the same household with no known rheumatic diseases served as controls. Serum IgG antibodies to SARS-CoV-2 Receptor Binding Domain (RBD) of the spike protein and nucleoprotein (NP) were assayed in eight hundred and eighty nine sera (subjects with disease = 379 and in subjects without disease = 510). IgG antibodies to either RBD and/or NP were positive in 135 (36%) subjects with AIRD as compared to 196 (38%) controls. The seroprevalence of anti-RBD and anti-NP varied between different cities but was not significantly different between subjects with and without disease in Mumbai, Ahmedabad, Bengaluru and Bhubaneswar. However, the occurrence of IgG antibodies to RBD was significantly ( p < 0.05) lower in subjects with disease (28/65;43%) as compared to subjects without disease (42/65;65%) in Kolkata, where the positivity rate was lower in connective tissue disease group than in inflammatory arthritis group. Overall, patients with rheumatic diseases on DMARDs have IgG antibodies to RBD and NP of SARSCoV-2 at a comparable level with that of subjects without disease, but the level of antibodies to RBD is lower in patients with connective tissue disease on immunosuppressive drugs in one centre.
Systemic lupus erythematosus (SLE) is a multi-system autoimmune disease with varied dermatological manifestations that are almost universal. Overall, lupus disease has a major effect on the quality of life in these patients. We assessed the extent of cutaneous disease in early lupus and correlated it with the SLE quality-of-life (SLEQoL) index and disease activity measures. Patients diagnosed as SLE with the skin involved were recruited at the first presentation and were assessed for cutaneous and systemic disease activity using the cutaneous lupus erythematosus disease area and severity index (CLASI) and the Mexican-SLE disease activity index (Mex-SLEDAI), respectively. Quality of life was assessed with the SLEQoL tool while systemic damage was captured by the SLICC damage index. Fifty-two patients with SLE who had cutaneous involvement were enrolled (40, 76.9
MIS-C is a rare, highly inflammatory state resembling incomplete Kawasaki disease, temporarily associated with COVID-19. The pathogenesis is not completely known. RNAseq was carried out on whole blood of six treatment-naïve MIS-C patients. This was compared against RNAseq transcriptomics data of five healthy controls (HC), four Kawasaki Disease (KD) and seven systemic Juvenile Idiopathic Arthritis (sJIA). Using PCA, MIS-C clustered separately from HC, KD and sJIA. Amongst the top 50 significant genes in the three comparisons with HC, KD, and sJIA, common genes were: TMCC2, ITGA2B, DMTN, GFI1B, PF4, QSER1, GRAP2, TUBB1. DSEA revealed that maximum number of hits for overexpressed pathways was for NABA matrisome activation when MIS-C was compared against HC. Cytokine stimulated cellular activation pathways, specifically IL-10 were downregulated. MIS-C had more activated pathways of neutrophil degranulation and acquired immune activation but less of coagulation system or heat-shock system involvement as compared to KD. As compared to sJIA, humoral immune response and complements were activated. Matrisome activation was higher, with increased cell–cell interaction and ECM signalling. This analysis revealed novel insights into the pathogenesis of MIS-C, including the potential role of matrisomes, humoral immune system and down-regulated interleukin-10 pathways.
Background Infections are a major cause of morbidity and mortality in juvenile systemic lupus erythematosus (SLE). Objectives We assessed the incidence and risk factors for major infections in juvenile SLE. Methods A retrospective review of 225 patients of juvenile SLE (ACR 1997 criteria) with age <18 years visiting the rheumatology clinic at a single centre between 2000 to 2020 was done from clinical case records and data from the hospital electronic health records. Serious infection was defined as the need for hospitalization, or infection resulting in disability or death. Cox regression was used to determine factors associated with a serious infection and the effect of serious infection on overall survival. Results Among the 225 children (197 girls) with a mean age of 13.89 ±3.42 years and a cumulative follow up of 1153.45 person-years. A total of 80 serious infections occurred in 63 (28% of the cohort) individuals at a rate of 69.35 serious infections per 1000 person-years of follow-up. A second serious infection occurred in 12 children and 5 of them developed a third serious infection. Among the microbiologically confirmed cases (78.75% of cases) Bacterial infections were most common (N=33) and included S. Aureus (11), E. Coli (7), K. Pneumoniae (3), E. Fecalis (3), S. Pneumoniae (2), Acinetobacter spp. (2), Citrobacter (2), Salmonella (2) and P. Aeruginosa [1]. Twenty six (32.5%) opportunistic infections occurred: Mycobacterium tuberculosis (18), Cytomegalovirus (3), disseminated Herpes zoster (4) and invasive candidiasis (1) with 15 (83.3%) of the tuberculosis cases being extrapulmonary. On multivariate analysis fever at baseline(HR 8.51, 1.17-61.44), gastrointestinal involvement (HR 4.73, 1.13-19.94), current steroid dose (HR 1.36,1.14-1.62), average cumulative steroid dose per year (HR 1.004, 1.002-1.005) and cyclophosphamide use (HR 2.22, 1.11-4.46) were associated with serious infection (Table 1). Hospitalization rates were significantly higher in those with any serious infection (Rate ratio 2.79, 1.81-3.77). Serious infection led to more damage accrual (SLICC damage index 1.04 vs 0.22). Serious infection-free survival at 1 year, 5 years and 10 years was 84% (79.1-89.2) and 72% (65.4-79.2). There were 19 deaths with infection attributable mortality in 10 (52.6%). Serious infection predisposed to higher overall mortality (Figure 1). Conclusion Serious infections are a major cause of mortality and damage accrual in SLE. Constitutional symptoms, gastrointestinal involvement, current and cumulative steroid dose and cyclophosphamide use predict serious infections. TB prophylaxis in patients with SLE should be considered in endemic areas, especially when using high-dose steroid therapy. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests None Declared.Table 1Cox proportional hazard models for predictors of infectionCovariatesHazard ratio95% CIFever*8.511.17-61.45Serositis0.810.41-1.59Gastrointestinal involvement*4.761.94-19.94Major organ manifestation1.070.49-2.31SLEDAI-2K0.990.95-1.05Daily steroid dose (/10mg)*1.361.14-1.62Mean cumulative steroid dose*1.0041.002-1.005Albumin1.010.66-1.55Absolute lymphocyte count0.990.99-1Cyclophosphamide use*2.221.11-4.46*-significant baseline predictors of serious infection on follow up. Major organ manifestation referes to presence of nephritis or neuropsychiatric lupus.Figure 1A. The Kaplan meier survival curve depicts time to first serious infection. B. The Kaplan meier survival curve shows the overall survival difference between those with any serious infection ever compared to those with no serious infection in the disease course.