Effectiveness of generic tofacitinib in idiopathic inflammatory myositis (IIM)-a retrospective analysis from Indian Myositis Registry (MyoIN).

OBJECTIVES: Determine domain-based-outcomes and steroid-sparing efficacy of generic tofacitinib in IIM. METHODS: 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). RESULTS: Forty-two patients of IIM with mean age 38.7 ± 16 years; (76.2% (N = 32) women), median duration of illness 48 (19;88) months were included. Commonest indication for initiating tofacitinib was either for refractory or as steroid sparing for cutaneous domain (N = 25/42, 59.5%) followed by calcinosis (N = 16/42, 38%). Overall complete and/or partial remission was achieved in 23/37 (64.8%), 30/35 (85.7%), and 29/30 (96.6%) patients at 3, 6, and 12 months, respectively. At 12-month follow-up, there was a reduction in prednisolone dose, with absolute decrease from a daily dose of 17.5 mg (IQR 5;50) to 2.5 mg (IQR 0;5) (p < 0.001). Individual domain assessments revealed improvement in cutaneous domain [16/25 (64%)] and calcinosis [6/15 (40%)]. Adverse effects included herpes zoster (N = 2/42, 4.8%) and dyslipidemia (N = 4/42, 9.5%). CONCLUSIONS: Treatment with generic tofacitinib significantly reduces the daily dose of corticosteroids and is effective in cutaneous domain including calcinosis in IIM. KEY POINTS: • This multicenter retrospective study is the first real-world data from India, elucidating steroid sparing efficacy of generic tofacitinib in patients with inflammatory myositis. • Domain-based outcome assessment suggests good clinical improvement especially in cutaneous domain, even those with refractory disease. • Modest benefits were evident in calcinosis, but its effect on the muscle and pulmonary domain appears limited.

16s RNA-based metagenomics reveal previously unreported gut microbiota associated with reactive arthritis and undifferentiated peripheral spondyloarthritis.

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.

SARS-CoV-2 seroprevalence in patients with autoimmune rheumatic diseases versus family controls: a multi-city cross-sectional survey.

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.

RNAseq-based transcriptomics of treatment-naïve multi-inflammatory syndrome in children (MIS-C) demonstrates predominant activation of matrisome, innate and humoral immune pathways.

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.

Long-standing and poorly controlled disease in juvenile dermatomyositis is associated with calcinosis: a real-world experience from a low-middle income country.

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% (8.5% at presentation). Younger age at presentation, longer follow-up, heliotrope rash [Odds Ratio (95% confidence interval), 11.4 (1.4-92.12)], chronic or polycyclic course [4.4 (1.2-15.5)] and cyclophosphamide use [8.2 (1.6-41.9)] were associated with calcinosis. Dysphagia [0.14 (0.02-1.2)] and elevated muscle enzymes [0.14 (0.04-0.5)] were negatively associated with calcinosis. Treatment with pamidronate had a good to moderate response to calcinosis in five of seven children. Calcinosis in JDM is associated with long-standing, poorly controlled disease, and the use of bisphosphonates like pamidronate offer promise in the future for its treatment.

Assessment of cutaneous disease activity in early lupus and its correlation with quality of life: a cross-sectional study.

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% females) with a median disease duration of 1 month (1-3.7). The median age was 27.5 years (IQR: 20-41). Median Mex-SLEDAI and SLICC damage index were 8(IQR: 4.5-11) and 0 (0-1), respectively. The median CLASI activity and damage scores were 3 (1-5) and 1 (0-1), respectively. Overall, there was no correlation between SLEQoL with CLASI or CLASI damage. Only the self-image domain of SLEQoL correlated with total CLASI (ρ = 0.32; p = 0.01) and CLASI-D (ρ = 0.35; p = 0.02). There was a weak correlation of CLASI with the Mexican-SLEDAI score (ρ = 0.30; p = 0.03) but not with the SLICC damage index. In this cohort of early lupus, cutaneous disease activity in lupus had a weak correlation with systemic disease. Cutaneous features did not appear to influence the quality of life except in the self-image domain.

Tuberculosis remains a leading contributor to morbidity due to serious infections in Indian patients of SLE.

INTRODUCTION: Infections are a major cause of morbidity and mortality in systemic lupus erythematosus (SLE). We assessed the incidence and risk factors for major infections in SLE in India. METHODS: A retrospective review of a cohort of 1354 patients of adult SLE (ACR 1997 criteria) seen between 2000 and 2021 at a single center was conducted. Serious infections (need for hospitalisation, prolonged intravenous antibiotics, disability, or death) were recorded. Cox regression was used to determine factors associated with serious infection and the effects of serious infection on survival and damage. RESULTS: Among the 1354 patients (1258 females, mean age of 30.3 years, follow-up of 7127.89 person-years), there were 439 serious infections in 339 patients (61.6 per 1000 person-years follow-up). Bacterial infections (N = 226) were the most common infection followed by mycobacterial infections (n = 81), viral (n = 35), and then invasive fungal infections (N = 13). Mycobacterium tuberculosis was the single most common microbiologically confirmed organism with incidence of 1136.4/100,000 person-years with 72.8% of them being extrapulmonary. Infection free survival at 1 year and 5 years was 82.9% and 73.8%. There were 119 deaths with infection attributable mortality in 65 (54.6%). On multivariable Cox regression analysis, higher baseline activity (HR 1.02, 1.01-1.05), gastrointestinal involvement (HR 2.75, 1.65-4.69), current steroid dose (HR 1.65, 1.55-1.76), and average cumulative steroid dose per year (HR 1.007, 1.005-1.009) were associated with serious infection and higher albumin (HR 0.65, 0.56-0.76) was protective. Serious infections led to greater damage accrual (median SLICC damage index of 1 vs. 0) and mortality (HR was 18.2, 32.7 and 81.6 for the first, second, and third infections). CONCLUSION: Serious infections remain a major cause of mortality and damage accrual in SLE and higher disease activity, gastrointestinal involvement, hypoalbuminemia, current steroid dose, and cumulative steroid dose are the risk factors for it.

Clinical features, severity and outcome of acute pancreatitis in systemic lupus erythematosus.

Acute pancreatitis (AP) is a rare but life threatening manifestation of Systemic Lupus Erythematosus (SLE). The current study aims to study the clinical characteristics, severity, mortality, and outcome of SLE-related AP in Indian population. We retrospectively reviewed medical records of patients with SLE who had AP in the past. Data from 13 rheumatology centers across India were compiled. All patients satisfied SLICC criteria for SLE and ATLANTA criteria for AP. AP was classified in to mild, moderate and severe using revised Atlanta classification. Patients with known risk factors like gall stone and alcohol were excluded.Sixty-six patients (six, children) were studied. Majority of patients were females (82%). The median age of presentation was 24 (11-63) years and most patients (57.5%) presented within first year of diagnosis of lupus. AP occurred mostly in the setting of active lupus (89%). Active nephritis was seen in 39% while a fourth had CNS disease. Patients with severe AP had lower C3. Ascites and sepsis were most common local and systemic complications, respectively. Mortality was 17%. Hypocalcemia, presence of sepsis and shock predicted mortality. In the multivariate analysis, only presence of shock remained as independent predictor of death (OR 63.0, 95% CI: 5.2-760.3). Pancreatitis is an early manifestation of SLE and is associated with active disease. Significant mortality is seen particularly with severe pancreatitis.

Catatonia in systemic lupus erythematosus: case based review.

Catatonia is a rare psychomotor syndrome characterized by stupor, posturing and echophenomena. It can be associated with schizophrenia, infections, drugs and autoimmune causes like anti N-methyl D-aspartate (NMDA) receptor encephalitis and systemic lupus erythematosus (SLE). Here we report two cases of systemic lupus erythematosus with catatonia, who improved with immunosuppressive treatment and review the cases described in the literature. The first case presented with fever, pancytopenia, toxic epidermal necrolysis (TEN)-like rash and later developed catatonia and macrophage activation syndrome (MAS). The second case presented with acute cutaneous lupus erythematosus (ACLE), fever, alopecia, polyarthralgias, nephritis, cytopenias along with catatonia. Successful management of this syndrome requires prompt recognition and treatment with immunosuppression as well as benzodiazepines with or without electroconvulsive therapy (ECT).

Services provided for axial spondyloarthritis patients by rheumatologists in India: a survey.

Objective: We sought to evaluate the current knowledge and attitudes of Indian rheumatologists concerning axial spondyloarthritis (axSpA) with respect to recent terminology for diagnosis, management strategies and additional services. Methods: The survey was designed for spondyloarthritis care given by rheumatologists in the Indian health-care context. The structured survey consisted of a combination of multiple-choice and open-ended questions. An anonymous Web-based questionnaire was sent to 710 members of the Indian Rheumatology Association, and descriptive analysis of responses was done. Results: The survey respondents were from government and private health-care facilities and gave a response rate of 19% (133 of 710). About 49% of respondents were using the terminology axSpA for a new diagnosis of spondyloarthritis (SpA). BASDAI was used routinely as the main disease monitoring tool by most respondents (76.2%). Same-day MRI was available to 42.9% (51 of 119) respondents. Selective cyclooxygenase-2 inhibitors were the preferred first NSAID for 50% of respondents, and SSZ was the most preferred DMARD for peripheral arthritis. Financial constraints were the most common factor that affected the initiation of biologics and also the most common reason for stopping biological therapies. Nearly 65% (80 of 122) of respondents did not have a multidisciplinary team available in clinical practice, and only 15% of respondents had access to patient support groups. Conclusion: For a new diagnosis, the terminology of axSpA is not fully accepted by Indian rheumatologists. The axSpA management given by Indian rheumatologists is in agreement with recent guidelines, however, there is a significant lack of accessibility to multidisciplinary care and patient support groups in India.

NMR-Based Metabolomics Revealed the Underlying Inflammatory Pathology in Reactive Arthritis Synovial Joints.

Reactive arthritis (ReA) is an aseptic synovitis condition that often develops 2-4 weeks after a distant (extra-articular) infection with Chlamydia, Salmonella, Shigella, Campylobacter, and Yersinia species. The metabolic changes in the synovial fluid (SF) may serve as indicative markers to both improve the diagnostic accuracy and understand the underlying inflammatory pathology of ReA. With this aim, the metabolic profiles of SF collected from ReA (n = 58) and non-ReA, i.e., rheumatoid arthritis (RA, n = 21) and osteoarthritis (OA, n = 20) patients, respectively, were measured using NMR spectroscopy and compared using orthogonal partial least-squares discriminant analysis (OPLS-DA). The discriminatory metabolic features were further evaluated for their diagnostic potential using the receiver operating characteristic (ROC) curve analysis. Compared to RA, two (alanine and carnitine), and compared to OA, six (NAG, glutamate, glycerol, isoleucine, alanine, and glucose) metabolic features were identified as diagnostic biomarkers. We further demonstrated the impact of ReA synovitis condition on the serum metabolic profiles through performing a correlation analysis. The Pearson rank coefficient (r) was estimated for 38 metabolites (profiled in both SF and serum samples obtained in pair from ReA patients) and was found significantly positive for 71% of the metabolites (r ranging from 0.17 to 0.87).

Corrigendum to: Services provided for axial spondyloarthritis patients by rheumatologists in India: a survey.

[This corrects the article DOI: 10.1093/rap/rkab048.][This corrects the article DOI: 10.1093/rap/rkab048.].

Patterns of T and B cell responses to Mycobacterium tuberculosis membrane-associated antigens and their relationship with disease activity in rheumatoid arthritis patients with latent tuberculosis infection.

This study was aimed at exploring whether latent tuberculosis infection (LTBI) contributes to the pathogenesis of immune-mediated inflammatory diseases in a TB endemic setting. We screened 198 rheumatoid arthritis (RA) patients with tuberculin skin test (TST) and studied 61 (median DAS28-ESR = 6.3) who were positive. Whole blood T cell proliferative responses to Mycobacterium tuberculosis (Mtb) membrane (MtM) antigens, including the latency-induced protein alpha crystallin (Acr), were determined by flow cytometry using Ki67 expression as the marker for nuclear proliferation. Serum antibody levels were determined by ELISA. Follow-up investigations (at 3-6, 9-12 and 15-18 months after baseline) were performed in 41 patients who were classified empirically as 'high' (HR-T/HR-B) or 'low' (LR-T/LR-B) responders based on their dynamic T cell or antibody responses. Significant correlations were seen between baseline T cell responses to MtM and Acr, and between IgG, IgA and IgM antibody responses to MtM. However, no correlation was seen between T and B cell responses. At all time points during the follow-up, T cell responses to both antigens (except for MtM at one point) were significantly higher in HR-T (n = 25) than LR-T (n = 16) patients. Levels of IgA and IgM (but not IgG) antibodies to MtM were also significantly higher in HR-B (n = 13) than LR-B (n = 28) at all time points. Importantly, HR-T patients exhibited significantly higher baseline and follow-up DAS28 scores than LR-T. Ten (of 61) patients had a history of TB and developed RA 6 years (median) after contracting TB. Three new TB cases (1 from TST-positive and 2 from TST-negative groups) emerged during the follow-up. Our results suggest that persistently elevated T cell responses to Mtb antigens may contribute to disease activity in RA.

Spectrum of Myelitis in Systemic Lupus Erythematosus: Experience from a Single Tertiary Care Centre over 25 Years.

BACKGROUND: Inflammatory myelitis rarely occurs in Systemic Lupus Erythematosus (SLE). METHODS: Medical records from a tertiary care centre in India (1989-2018) were reviewed to identify patients with myelitis in SLE and their clinical characteristics and outcomes were compared with two matching comparators drawn from adjacent hospital registration numbers in the SLE database. RESULTS: Ten patients had myelitis from a cohort of 1768 patients with SLE. Myelitis was the first manifestation of lupus in 7 (70%). Cervicothoracic cord was most frequent site of involvement. ANA was negative at onset in 2 cases. One of 4 was positive for Anti-Aquaporin 4 antibody. Four had relapsing disease (16 events) with a median time to relapse of 0.65 years (0.3- 7 years). All cases received steroid sparing agents over the follow-up duration (78.5 patient years). Lupus nephritis (20% vs. 75%, p=0.004) and haematologic manifestations (0 vs. 25%, p=0.02) were less common. Higher frequency of anti-Ro antibodies was noted in the group with myelitis (p=0.05). CONCLUSION: Myelitis can be a presenting feature of SLE with lupus nephritis and hematologic involvement being rare. Relapses are common that mandate long-term immunosuppression.

High Prevalence of Active Tuberculosis in Adults and Children with Idiopathic Inflammatory Myositis as Compared with Systemic Lupus Erythematosus in a Tuberculosis Endemic Country: Retrospective Data Review from a Tertiary Care Centre in India.

AIM: Infections are the leading cause of morbidity and mortality in idiopathic inflammatory myositis (IIM) with India being endemic for Tuberculosis (TB). We compared and contrasted the prevalence, clinical profile and outcomes of active TB in IIM with systemic lupus erythematosus (SLE). METHODS: Medical records were reviewed for adults and children with IIM (Bohan and Peter criteria) and SLE (ACR criteria) at a tertiary care hospital in India from January 2015 to October 2017. Follow-up was recorded until February 2020 for all those who had developed active TB. RESULTS: Of 167 (132 adults and 35 juvenile) IIM and 280 (131 adults and 149 juvenile) SLE, active TB occurred in 24 (14.4%) IIM (22 (16.7% of 132) adults; 2 (5.71% of 35) juvenile) and 18 (6.4%) SLE [(8 (6.1% of 131) adults; 10 (6.7% of 149) juvenile, p-value < 0.01]. Patients with IIM had higher odds of developing TB as compared with SLE [OR 2.24 (CI 1.5-5.5), p=0.007]. The risk of developing active TB was 68-fold and 30.4-fold higher in patients with IIM and SLE, respectively, as compared with the general population. Extrapulmonary forms were more common (14/24). Nearly half developed TB during active IIM, at a glucocorticoid dose of 0.25 (0-1.5) mg/kg/day. Over a follow-up duration of 27 months (8-184), all were cured of TB, though prolonged course of anti-tuberculous treatment was required in 25%, and five IIM relapsed during treatment. CONCLUSION: Patients with IIM have increased risk of active TB, with common extrapulmonary forms, slow response, and relapses during treatment.

Prevalence and Clinical Correlates of Myositis Specific Autoantibodies in Idiopathic Immune-Mediated Inflammatory Myositis - Results from a Multicentric Cohort (MyoIN) from India.

There is a need to understand the clinical and antibody associations in patients with IIM in various ethnicities and geographical areas. Patients who fulfilled Bohan's and Peter criteria of IIM and seen between October 2017 through Jan 2020 were enrolled in this study at 3 centres. Clinical and relevant laboratory parameters were recorded in a pre designed case record form. MSA and MAA to 16 antigens were performed by line blot assay using Euroimmun (Luebec, Germany) as per manufacturer's instruction. Of the 150 patients, 13 were juvenile onset. Ninety sera had either one MSA or MAA. Sixty sera had neither MSA/MAA. anti-Ro 52 were the commonest antibody and anti-Mi-2α and b the commonest MSA. Novel associations identified were severe myositis with anti-Ro 52, cutaneous ulcerations with anti-MDA5 and anti-PM-Scl and calcinosis with anti-PM-Scl. One-third sera had no MSA or MAA. Larger sample size and use of antibody assays together with muscle biopsy will improve subtyping and phenotype associations in IIM.

Reactive arthritis and undifferentiated peripheral spondyloarthritis share human leucocyte antigen B27 subtypes and serum and synovial fluid cytokine profiles.

OBJECTIVES: Peripheral SpA (pSpA) is comprised of ReA, PsA, enteritis-associated arthritis and undifferentiated pSpA (upSpA). ReA and upSpA share T cell oligotypes and metabolomics in serum and SF. We investigated HLA-B27 subtypes and cytokines in serum and SF that were compared between ReA and upSpA. METHODS: ReA and upSpA were compared in two cohorts. In cohort I (44 ReA and 56 upSpA), HLA-B27 subtyping was carried out. In cohort II (17 ReA and 21 upSpA), serum and SF cytokines were compared using a multiplex cytokine bead assay (27 cytokines). A total of 28 healthy controls with similar age and sex to cohort II were included for comparison of serum cytokine levels. RESULTS: In cohort I, HLA-B27 was positive in 81.8% (36/44) of ReA and 85.71% (48/56) of upSpA patients. HLA-B27 typing was successful in 70 patients (30 ReA and 40 uSpA). HLA-B*2705 was the most common, followed by HLA-B*2704 and HLA-B*2707. Frequencies were the same between ReA and upSpA. In cohort II, 14 cytokines were detectable in the serum of patients. The levels of eight cytokines were higher than in the controls. The cytokine levels of ReA and upSpA were similar. Sixteen cytokines were detectable in the SF of patients. There was no statistical difference in the levels between ReA and upSpA. The cytokine profiles in sera and SF were also similar among HLA-B27-positive and negative patients. CONCLUSION: ReA and upSpA have similar HLA-B27 subtype associations and similar cytokine profiles. They should be considered as a single entity during studies as well as clinical management.

Clinical spectrum of active tuberculosis in patients with systemic lupus erythematosus.

INTRODUCTION: There is paucity of data on tuberculosis in Indian patients with systemic lupus erythematosus (SLE). We retrospectively studied clinical features and outcome of tuberculosis in SLE. METHODS: Medical records of patients who developed tuberculosis simultaneous or after the diagnosis of SLE were retrospectively reviewed. All patients fulfilled 1997 ACR and/or SLICC 2012 classification criteria for SLE. A diagnosis of tuberculosis required bacteriological, histopathological or CT/MRI suggestive of tuberculosis and initiation of four drug antituberculous therapy. Baseline parameters were compared with the rest of cohort to identify predictors of tuberculosis. RESULTS: In our cohort of 1335 SLE patients, 48 (3.6%) developed tuberculosis. Incidence of tuberculosis was calculated to be 733 per 100,000 patient years and occurred after a mean disease duration of 3.0 ± 4.1 years. Extrapulmonary tuberculosis (n = 37) was commoner than pulmonary tuberculosis (n =11). Most common radiological pattern in pulmonary tuberculosis was miliary and musculoskeletal TB was most common extrapulmonary TB. A microbiological diagnosis was obtained in 52.1% patients. Male gender was associated with higher risk of tuberculosis [OR 3.30 (1.55-7.05)]. Mortality was 14.5% and all patients who died had either disseminated (n = 5) or central nervous system (CNS) tuberculosis (n = 2). CONCLUSION: Incidence of tuberculosis in SLE is higher than general population and is associated with different phenotype and higher mortality. Male gender was associated with increased risk of tuberculosis in SLE.

Polymorphism of genes involved in methotrexate pathway: Predictors of response to methotrexate therapy in Indian rheumatoid arthritis patients.

INTRODUCTION: The adenosine pathway is one of the ways through which methotrexate (MTX) ameliorates inflammation. We therefore explored an association of polymorphism of genes involved in adenosine and MTX metabolic pathways with response to MTX. METHODS: Association of polymorphism in 7 genes (rs2236225 [MTHFD1 1958G>A], rs17602729 [AMPD1 G>A], rs1127354 [ITPA C>A], rs1431131 [TGFBR2 A>T], rs2372536 [ATIC C>G], rs11188513 [ENTPD1 C>T] and rs5751876 [ADORA2A T>C]) with efficacy of MTX was studied in Indian rheumatoid arthritis (RA) patients. The patients, classified by European League Against Rheumatology (EULAR)/American College of Rheumatology (ACR) 2010 criteria, were DMARD (disease-modifying antirheumatic drug)-naïve, with Disease Activity Score (DAS28) >3.2. After 4 months of MTX monotherapy, patients were classified as responders (R) or non-responders (NR) based on EULAR response criteria. Genotyping was done by TaqMan 5' nuclease assay and association of gene polymorphisms with response to MTX was determined by Chi-squared test. RESULTS: Two hundred and twenty-six patients (86% female, median age 40 [interquartile range, IQR = 17.25] years), with disease duration of 24 (IQR = 38.25) months and DAS28-C-reactive protein score of 4.61 (IQR = 1.34) were enrolled. After therapy, 186 patients were classified as R and 40 as NR. GG genotype of ATIC (P = .01, odds ratio [OR] 2.56, 95% CI, 1.04-6.30) and CC genotype of ITPA (P = .009, OR 1.34, 95% CI 1.02-1.76) genes were found to be associated with the response. On binary logistic regression analysis, GG genotype of ATIC and CC of ITPA genes were independent predictors of the response. CONCLUSION: Polymorphisms of ATIC and ITPA genes alone or with clinical variables were associated with response to MTX therapy in Indian RA patients.