Publications by authors named "Debashish Danda"

146 Publications

Cotrimoxazole prophylaxis prevents major infective episodes in patients with systemic lupus erythematosus on immunosuppressants: A non-concurrent cohort study.

Lupus 2021 Feb 24:961203321995238. Epub 2021 Feb 24.

Department of Clinical Immunology and Rheumatology, Christian Medical College, Vellore, India.

Background: Prophylactic trimethoprim-sulfamethoxazole (TMP-SMX) prevents pneumocystis jirovecii infection in SLE on immunosuppression. Its role in preventing other major infections in immuno suppressed SLE patients is unknown.

Methods: A non-concurrent cohort study was conducted on patients of SLE fulfilling SLICC and/or ACR 1997 criteria, who received tapering dose of steroid starting with ≥0.5 mg/kg/day of prednisolone or equivalent dose of deflazacort and mycophenolate mofetil ≥1 g/day (or equivalent dose of mycophenolate sodium) at least for the preceding 1 year. Interviewing patients & documenting relevant data from hospital electronic Medical records (EMR), followed by comparison of Incidence densities of major infections between those on prophylactic Trimethoprim 160 mg + Sulfamethoxazole 800 mg and those not on it, was done by student 't' test. Multivariate logistic regression was performed for independent risk of any major infection between the two groups.

Results: Of 228 patients, 162 did not receive TMP-SMX prophylaxis, and 66 had received. The incidence density of major infection was found to be significantly lower in TMP-SMX group (1.25 per 100 person year) as compared to those not on TMP-SMX group (11.201 per 100 person year); P < 0.001 (95% CI 0.027 - 0.449) and odds ratio of 0.03 (CI 0 - 0.24).

Conclusion: Cotrimoxazole prophylaxis in SLE patients on immunosuppression prevents major infections.
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http://dx.doi.org/10.1177/0961203321995238DOI Listing
February 2021

Update on Post-Streptococcal Reactive Arthritis: Narrative Review of a Forgotten Disease.

Curr Rheumatol Rep 2021 Feb 10;23(3):19. Epub 2021 Feb 10.

Clinical Immunology & Rheumatology, Christian Medical College & Hospital, Vellore, India.

Purpose Of The Review: This topical review attempts to build the concepts of PSRA as an independent entity and discuss prevalent diagnostic criteria. It utilizes a search strategy to collate all clinical features of PSRA reported from across the world and also discusses laboratory and treatment options in brief.

Recent Findings: There are several immune-mediated diseases described after acute streptococcal infections. Post-streptococcal reactive arthritis (PSRA) is a sterile, self-limiting arthritis that occur as an immune sequelae to streptococcal infection. Though PSRA resembles the arthritis of acute rheumatic fever superficially, it is a separate entity in its own right. It is different from classical reactive arthritis too. It was being recognized worldwide and more frequently in the recent past, possibly due to heightened awareness amongst clinicians. However, research on this enigmatic immune phenomenon is limited. Most acceptable hypotheses suggest molecular mimicry sensitizing the immune system towards synovial peptides such as keratin, vimentin and laminin, leading to arthritis in a genetically predisposed individual. There is still much to be learnt from this unique disease about the vagaries of the immune system.
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http://dx.doi.org/10.1007/s11926-021-00982-3DOI Listing
February 2021

High expression of pro-inflammatory cytokine genes IL-1β and IL-1R2 upon TLR4 activation in Takayasu arteritis.

Rheumatol Int 2021 Feb 2. Epub 2021 Feb 2.

Department of Clinical Immunology and Rheumatology, Christian Medical College, Tamil Nadu, Vellore, 632004, India.

Toll-like receptors (TLR) 4 and its endogenous ligands are highly expressed in aorta. In the present study, we have explored the effect of TLR-4 activation by pro-inflammatory and angiogenic factors in PBMCs of patients with Takayasu Arteritis (TA). In the screening cohort, PBMCs of TA (n = 6) and healthy controls (n = 6) were stimulated with LPS and cultured. mRNA expression of 84 genes were quantitated by RT2 Profiler™ PCR Array kit in PBMCs. Validation set of additional PBMCs from TA (n = 7) and healthy controls [HC) (n = 7) were then stimulated with LPS to study expression of selected genes with delta Ct > 0.1 in the screening cohort. Significant gene expressions were correlated with Indian Takayasu arteritis activity scores (ITAS 2010). Increased expression of CCL2 was observed only in unstimulated PBMCs of patients with TA [median relative difference (RD) of 2.37] as compared to HC (RD 1.37, p < 0.03) in validation cohort, while stimulation with TLR4 ligand led to increased mRNA expression of IL-1β (RD 7.9, p < 0.028) and IL-1R2 (RD 0.08 p < 0.013) genes as compared to that of HC [RD of 5.32 for IL-1β and 0.01 for IL-1R2, respectively] in validation cohort. TLR4 activation also led to significantly higher expression of HPSE, TIMP1 and low expression of VEGFB, S1PR1, SERPINF1, ANGPLT4, ANGPT2, TIE1 and NOS3 genes in the screening cohort. But expression of VEGFB was not significant in validation cohort. The significant gene expressions, however, did not correlate with ITAS [ITAS2010 and ITAS-A (CRP)]. TLR4 activation leads to increased expression of IL-1β and IL-1R2 genes in PBMCs of patients with TA.
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http://dx.doi.org/10.1007/s00296-020-04785-0DOI Listing
February 2021

Efficacy and Safety of Turmeric Extracts for the Treatment of Knee Osteoarthritis: a Systematic Review and Meta-analysis of Randomised Controlled Trials.

Curr Rheumatol Rep 2021 Jan 28;23(2):11. Epub 2021 Jan 28.

Menzies Institute for Medical Research, University of Tasmania, Private Bag 23, Hobart, Tasmania, 7000, Australia.

Purpose Of The Review: Finding appropriate pharmacological options to treat osteoarthritis (OA) remain challenging. We aimed to determine the efficacy and safety of all types of turmeric extracts for the management of knee OA.

Recent Findings: Sixteen RCTs of up to 16 weeks duration including 1810 adults with knee OA were included. Eleven RCTs compared the efficacy of turmeric extracts with placebo and five with active comparators (NSAIDs). The overall risk bias of included RCTs was moderate. Turmeric extracts significantly reduced knee pain (SMD - 0.82, 95% CI - 1.17 to - 0.47, I = 86.23%) and improved physical function (SMD - 0.75, 95% CI - 1.18 to - 0.33, I = 90.05%) compared to placebo but had similar effects compared to NSAIDs. BMI was the major contributor to heterogeneity in the placebo-controlled studies (explained 37.68% and 67.24%, respectively, in the models) and modified the effects of the turmeric on pain and physical function with less improvement with higher BMI (SMD 0.26 95% CI 0.04 to 0.48; SMD 0.48 95% CI 0.21 to 0.74). No significant between-group differences were reported for either biochemical markers or imaging outcomes. Turmeric extracts had 12% fewer adverse events than NSAIDs and similar rates to placebo. Turmeric extract is a safe and effective option for the symptomatic management of knee OA, compared to placebo or NSAIDs. However, current evidence from short-term studies is heterogeneous and has moderate risk of bias leading to some uncertainty about the true effect.
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http://dx.doi.org/10.1007/s11926-020-00975-8DOI Listing
January 2021

Mycophenolate in idiopathic inflammatory myositis: outcome data of a large South Asian cohort.

Clin Rheumatol 2021 Jan 27. Epub 2021 Jan 27.

Department of Clinical Immunology and Rheumatology, Christian Medical College and Hospital (CMCH), Vellore, Tamil Nadu, 632002, India.

Background: Consensus on treatment of idiopathic inflammatory myositis (IIM), particularly with regard to flares and interstitial lung disease (ILD), does not exist. We studied the long-term outcome and treatment response in our large, retrospective cohort of adult South-Asian patients exclusively with IIM.

Methodology: Electronic records of IIM patients satisfying inclusion and exclusion criteria were studied longitudinally at presentation, at 3, 6, 12, 18 and 24 months and thereafter yearly till their last follow up (F/u) visit. Depending on clinical, imaging, and muscle enzyme profile during the F/u period, patients were categorised as complete (CR) and partial responders (PRs). Parameters favouring CR were assessed using multivariate logistic regression analysis. Outcome parameters and flares on immunosuppressants (IS) were then assessed in patients with/without ILD.

Results: Two hundred thirty-two patients with median F/u duration of 44.5 months (25-80.25) were included. ILD was seen in 40.1%. Patients with non-Jo1 anti-synthetase antibodies (n=26) were numerically more than those with Jo-1 antibody (n=24). CR status was attained by 50.9% patients. Absence of pericardial effusion (p=0.042, OR 4.223, 95% CI: 1.05-16.9) and presence of Gottron's rash (p=0.044, OR 1.78, 95% CI 1.017-3.121) at baseline predicted CR by multivariate regression. Majority received mycophenolate during the entire F/u period. Discontinuation of steroids was feasible in 51.7% after a median duration of 24 months (18-42). After excluding patients with ILD, flares were numerically lesser in patients only on mycophenolate compared with those only on methotrexate (p=0.06). Further flares were curtailed when switched from other agents to mycophenolate.

Conclusion: Mycophenolate is an effective treatment option in IIM patients with and without co-existing ILD. Presence of Gottron's rash and absence of pericardial effusion were found to be predictors of favourable clinical outcome in this largest single-centre study.
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http://dx.doi.org/10.1007/s10067-021-05590-1DOI Listing
January 2021

Severe COVID-19, multisystem inflammatory syndrome in children, and Kawasaki disease: immunological mechanisms, clinical manifestations and management.

Rheumatol Int 2021 01 21;41(1):19-32. Epub 2020 Nov 21.

Allergy Immunology Unit, Department of Pediatrics and Chief, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, 160012, India.

Multisystem inflammatory syndrome (MIS-C) is a pediatric hyperinflammation disorder caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). It has now been reported from several countries the world over. Some of the clinical manifestations of MIS-C mimic Kawasaki disease (KD) shock syndrome. MIS-C develops 4-6 weeks following SARS-CoV-2 infection, and is presumably initiated by adaptive immune response. Though it has multisystem involvement, it is the cardiovascular manifestations that are most prominent. High titres of anti-SARS-CoV-2 antibodies are seen in these patients. As this is a new disease entity, its immunopathogenesis is not fully elucidated. Whether it has some overlap with KD is still unclear. Current treatment guidelines recommend use of intravenous immunoglobulin and high-dose corticosteroids as first-line treatment. Mortality rates of MIS-C are lower compared to adult forms of severe COVID-19 disease.
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http://dx.doi.org/10.1007/s00296-020-04749-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7680080PMC
January 2021

Clinical course of 602 patients with Takayasu's arteritis: comparison between Childhood-onset versus adult onset disease.

Rheumatology (Oxford) 2020 Nov 12. Epub 2020 Nov 12.

Systemic Autoimmunity Branch/NIAMS, National Institutes of Health, Bethesda, MD, USA.

Objectives: To describe the clinical profile of Asian Indian patients with Takayasu's arteritis (TAK) and to compare clinical features and outcome of childhood-onset Takayasu's arteritis (cTAK) with adult-onset TAK (aTAK).

Methods: Data related to clinical features and response to treatment of patients with cTAK (age of onset <16 years) and aTAK from a large observational cohort in our tertiary care teaching hospital were noted and compared.

Results: Altogether, 602 patients (cTAK = 119; aTAK = 483) were studied. Patients with cTAK had a blunted female: male ratio; but fever, elevated acute phase reactants, involvement of abdominal aorta or its branches, hypertension, abdominal pain, elevated serum creatinine and cardiomyopathy were more common in cTAK as compared with aTAK. Patients with aTAK were more likely to have aortic-arch disease and claudication than cTAK. During follow-up, complete remission was more common in cTAK (87% vs 66%; P < 0.01), but subsequent relapses were equally common (30% vs 27%; P = 0.63). Independent associations of disease duration at presentation with disease extent [Disease Extent Index in TAK (DEI.Tak)] and damage [TAK Damage Score (TADS)] were observed (P ≤ 0.01). Moreover, 54% of patients with symptom duration of >5 years at presentation still continued to have elevated CRP suggesting continued and active inflammation warranting escalation or inititation of immunosuppression.

Conclusion: Patients with cTAK are more likely to have arterial disease below the diaphragm, systemic inflammation and achieve remission. Disease of the aortic arch is more common in patients with aTAK. Longer duration of symptoms prior to initiation of immunosuppression, thereby leading to extensive disease and damage, reflects ongoing disease activity as the rule rather than exception in untreated TAK.
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http://dx.doi.org/10.1093/rheumatology/keaa569DOI Listing
November 2020

Combination of methotrexate and sulfasalazine is an efficacious option for axial spondyloarthritis in a resource-limited, real-world clinical setting: a prospective cohort study.

Clin Rheumatol 2020 Oct 14. Epub 2020 Oct 14.

Department of Clinical Immunology and Rheumatology, Christian Medical College & Hospital, Ida Scudder Road, Vellore, Tamil Nadu, 632004, India.

Objective: Evaluation of response to combination conventional synthetic DMARD (csDMARD) therapy with methotrexate (MTX) and sulfasalazine (SSZ) in active axial spondyloarthritis (axSpA) patients without peripheral arthritis (group 1) as compared to active axSpA with peripheral arthritis (group 2), who are economically constrained for biologicals.

Methods: A prospective, observational, single-centre, cohort study on 150 consecutive active axSpA patients who were already initiated on the above mentioned combination csDMARD therapy and satisfying the other pre-defined eligibility criteria, was conducted between July 2016 and July 2017 using ASAS20 response as primary outcome measure at 3 and 6 months post treatment.

Results: ASAS20 response at 3 months was achieved in 31/58 (53.4%) and in 24/36 (66.6%) in groups 1 and 2, respectively (p = 0.2); at 6 months, these figures were 45/76 (59.2%) and 28/44 (63.6%), respectively (p = 0.6). Similarly, there was significant reduction in mean ASAS NSAID index from 29.6 to 14 over 6 months from baseline (p = 0.001), and it was similar in both groups. Using BASDAI ≥ 4 to define active disease, a 34% reduction in requirement of biologicals was also observed.

Conclusion: In resource-limited population, treatment with combination of methotrexate and sulphasalazine over a period of 6 months is equally efficacious in patients with active axSpA with and without peripheral arthritis, as evidenced by improved ASAS20 response rates, reduction in NSAID use and fewer patients switching to biologicals. Key Points • Combination of MTX+SSZ was efficacious and safe in active axSpA patients who had economic hardships to use biologicals. • This benefit in axSpA patients was similar between those without any peripheral arthritis and those with. • MTX+SSZ combination therapy also demonstrated NSAID sparing action. • Combination of MTX and SSZ prevented escalation to biological therapy as per a BASDAI score driven policy.
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http://dx.doi.org/10.1007/s10067-020-05433-5DOI Listing
October 2020

Revisiting cardiac safety of hydroxychloroquine in rheumatological diseases during COVID-19 era: Facts and myths.

Eur J Rheumatol 2020 Oct 8. Epub 2020 Oct 8.

Department of Clinical Immunology and Rheumatology, Christian Medical College, Vellore, India.

Severe acute respiratory syndrome coronavirus 2 has spread across the globe affecting more than 10 million people as of August 2020. With the pandemic spreading at such an alarming rate, a lot of efforts are in the process of identification of an effective treatment at it's earliest. Hydroxychloroquine (HCQ) is such a drug that is being studied as a repurposed agent, although the early results are still inconclusive. However, an important adverse effect that has raised concerns in the recent times is its possible cardiac toxicity, mainly the 'QT,' prolongation in electro-cardiogram, which has created a sense of apprehension for its use in traditional indications like rheumatological conditions. In decades of HCQ use by rheumatologists, this cardiac toxicity was rarely ever seen. So, what is different in the current coronavirus disease 2019 (COVID-19) era? This review outlines various studies on HCQ reporting cardiac adverse events in patients with rheumatic diseases as well as, in patients with COVID-19 infection. In addition, two important observations were noticed; first, the doses that have been used in the current COVID-19 scenario are much higher than what are used in rheumatology. Second, COVID-19 infection may by itself lead to intrinsic cardiac abnormalities, which is probably acting as a confounder. Most of the available and credible data suggest that HCQ is a safe drug, including the RECOVERY trial stating no cardiotoxicity by HCQ. This review reinforces the safety profile of HCQ in a data-driven manner and addresses the concerns of the physicians. However, its cautious use in those with pre-existing cardiac abnormalities cannot be overemphasized.
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http://dx.doi.org/10.5152/eurjrheum.2020.20174DOI Listing
October 2020

Impact of the COVID-19 pandemic on patients with systemic lupus erythematosus: Observations from an Indian inception cohort.

Lupus 2021 Jan 6;30(1):158-164. Epub 2020 Oct 6.

Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.

Introduction: The ongoing pandemic of COVID-19 has led to severe disruption of healthcare services worldwide. We conducted this study to assess the impact of COVID-19 pandemic on the management of Systemic Lupus Erythematosus (SLE) patients who were enrolled in the nation-wide inception cohort.

Methods: A questionnaire was administered to the SLE patients enrolled in the inception cohort. Questions related to the effect on disease activity, preventive measures adopted against COVID-19, the incidence of COVID-19, hardships faced in getting access to health care professionals and availability of medicines, adherence, fear of COVID-19 and the potential benefits of being part of the registry.

Results: A total of 1040 (90% females) patients completed the questionnaire. The mean age was 27.5 ± 19.1 years and the mean disease duration was 1.25 years. Twenty-Four (2.3%) patients had developed fever (>1 day) during this period, including one patient with additional symptoms of diarrhoea and anosmia, however, none of the patients developed COVID-19 infection. 262 patients (25.2%) reported financial difficulty during this period and patients reported an average excess expenditure of at least 2255.45 INR ($30) per month. 378 patients (36%) reported problems in getting their prescribed medicines due to lockdown. Of these, 167 (40%) patients needed to change their medication schedule due to this non-availability. Almost 54% of patients missed their scheduled follow up visits during the lockdown period and 37% of patients were unable to get their investigations done due to closure of laboratories and hospitals. 266 patients (25.5%) reported worsening of various symptoms of SLE during this period. Almost 61% patients felt confident that being associated with the inception cohort had helped them in managing their disease better during this period of lockdown as they received help in the form of timely and frequent telephonic consults, assistance in making the medicines available, and regular counselling resulting in abetment of their fears and anxieties.

Conclusion: The current COVID-19 pandemic has made a huge impact on our SLE patients. Patients faced difficulty in the availability of medicines, missed the doses of medicines, had financial constraints, and spent more money on health during the pandemic.
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http://dx.doi.org/10.1177/0961203320962855DOI Listing
January 2021

Understanding immunopathological fallout of human coronavirus infections including COVID-19: Will they cross the path of rheumatologists?

Int J Rheum Dis 2020 Aug 10;23(8):998-1008. Epub 2020 Aug 10.

Department of Clinical Immunology and Rheumatology, Christian Medical College, Vellore, India.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causing coronavirus disease 2019 (COVID-19) is the biggest pandemic of our lifetime to date. No effective treatment is yet in sight for this catastrophic illness. Several antiviral agents and vaccines are in clinical trials, and drug repurposings as immediate and alternative choices are also under consideration. Immunomodulatory agents like hydroxychloroquine (HCQ) as well as biological disease-modifying anti-rheumatic drugs (bDMARDs) such as tocilizumab and anakinra received worldwide attention for treatment of critical patients with COVID-19. This is of interest to rheumatologists, who are well versed with rational use of these agents. This brief review addresses the understandings of some of the common immunopathogenetic mechanisms in the context of autoimmune rheumatic diseases like systemic lupus erythematosus (SLE) and COVID-19. Apart from demographic comparisons, the role of type I interferons (IFN), presence of antiphospholipid antibodies and finally mechanism of action of HCQ in both the scenarios are discussed here. High risks for fatal disease in COVID-19 include older age, metabolic syndrome, male gender, and individuals who develop delayed type I IFN response. HCQ acts by different mechanisms including prevention of cellular entry of SARS-CoV-2 and inhibition of type I IFN signaling. Recent controversies regarding efficacy of HCQ in management of COVID-19 warrant more studies in that direction. Autoantibodies were also reported in severe acute respiratory syndrome (SARS) as well as in COVID-19. Rheumatologists need to wait and see whether SARS-CoV-2 infection triggers development of autoimmunity in patients with COVID-19 infection in the long run.
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http://dx.doi.org/10.1111/1756-185X.13909DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7436450PMC
August 2020

Autoimmune and rheumatic musculoskeletal diseases as a consequence of SARS-CoV-2 infection and its treatment.

Rheumatol Int 2020 10 14;40(10):1539-1554. Epub 2020 Jul 14.

Department of Clinical Immunology, Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry, India.

The coronavirus disease-2019 (COVID-19) pandemic is likely to pose new challenges to the rheumatology community in the near and distant future. Some of the challenges, like the severity of COVID-19 among patients on immunosuppressive agents, are predictable and are being evaluated with great care and effort across the globe. A few others, such as atypical manifestations of COVID-19 mimicking rheumatic musculoskeletal diseases (RMDs) are being reported. Like in many other viral infections, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection can potentially lead to an array of rheumatological and autoimmune manifestations by molecular mimicry (cross-reacting epitope between the virus and the host), bystander killing (virus-specific CD8 + T cells migrating to the target tissues and exerting cytotoxicity), epitope spreading, viral persistence (polyclonal activation due to the constant presence of viral antigens driving immune-mediated injury) and formation of neutrophil extracellular traps. In addition, the myriad of antiviral drugs presently being tried in the treatment of COVID-19 can result in several rheumatic musculoskeletal adverse effects. In this review, we have addressed the possible spectrum and mechanisms of various autoimmune and rheumatic musculoskeletal manifestations that can be precipitated by COVID-19 infection, its therapy, and the preventive strategies to contain the infection.
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http://dx.doi.org/10.1007/s00296-020-04639-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7360125PMC
October 2020

Comparison of safety, efficacy and cost between oral pulse cyclophosphamide versus intravenous cyclophosphamide pulse therapy in severe systemic lupus erythematosus.

Int J Rheum Dis 2020 Jun 25;23(6):800-804. Epub 2020 May 25.

Department of Clinical Immunology and Rheumatology, Christian Medical College, Vellore, India.

Objectives: The aim of this study is to compare efficacy, toxicity and cost between oral and intravenous cyclophosphamide (CYC) pulse therapy in inducing remission (Systemic Lupus Erythematosus Disease Activity Index [SLEDAI] <3) in severe SLE.

Methods: We retrospectively checked the hospital records of patients between the years 2000 and 2018, who had been administered oral cyclophosphamide pulse and intravenous (IV) cyclophosphamide pulse. SLEDAI at baseline and after 6 months of therapy were noted. The statistical analysis was done using Mann-Whitney U test. The cost was also calculated.

Results: We included 45 patients in this study, 21 in the oral pulse group and 24 in the IV group. The median age of patients in the oral and IV groups were 29 (interquartile range [IQR] 22-37) and 26 (IQR 19.25-0.75) years respectively. Median SLEDAI at baseline was comparable between the 2 groups (oral 18.0 [IQR 15.0-26.0]; IV 14.5 [IQR 11.0-20.0] P = .151). At the end of 6 months of treatment, it was 0.0 (IQR 0.0-4.0) in the oral group, as against 2.0 (IQR 0.0-5.5) in IV group (P = .676). There was no major adverse event in either group. Oral cyclophosphamide pulse therapy was more economical as compared to IV cyclophosphamide [630 Indian National rupees( INR)/ 8.85 US dollars(USD) in the IV arm and 50 INR/0.7 USD in the oral arm] (P < .001).

Conclusion: This study concludes that oral cyclophosphamide pulse therapy is an economical option and there was no difference in efficacy and safety between oral cyclophosphamide pulse therapy and IV pulse cyclophosphamide therapy.
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http://dx.doi.org/10.1111/1756-185X.13823DOI Listing
June 2020

Founder effects of the homogentisate 1,2-dioxygenase (HGD) gene in a gypsy population and mutation spectrum in the gene among alkaptonuria patients from India.

Clin Rheumatol 2020 Sep 24;39(9):2743-2749. Epub 2020 Mar 24.

Department of Orthopedics, Christian Medical College Vellore and Hospital, Vellore, Tamil Nadu, India.

Introduction: Alkaptonuria (AKU) is a rare metabolic disease. The global incidence is 1:100,000 to 1:250,000. However, identification of a founder mutation in a gypsy population from India prompted us to study the prevalence of AKU in this population and to do molecular typing in referred cases of AKU from the rest of India.

Objective: To determine the prevalence of AKU in the gypsy population predominantly residing in the seven districts of Tamil Nadu. To determine the molecular characteristic of AKU cases referred to our clinic from various parts of India.

Method: Urine spot test to detect homogentisic acid followed by quantitative estimation using high-performance liquid chromatography in 499 participants from the gypsy population and confirming the founder mutation in those with high levels by sequencing. Sequence the homogentisate 1,2-dioxygenase (HGD) gene to identify mutations and variants in 29 AKU non-gypsy cases.

Results: The founder mutation was detected in homozygous state in 41/499 AKU-affected individuals of the gypsy community giving a high prevalence of 8.4%. Low back pain, knee pain, and eye and ear pigmentation were the most common symptoms and signs respectively. The commonest mutation identified in the non-gypsy AKU cases was p.Ala122Val.

Conclusion: High prevalence of AKU in the inbred gypsy population at 8.4% was detected confirming the founder effect. Urine screening provided a cost-effective method to detect the disease early. Mutation spectrum is varied in the rest of the Indian population. This study identified maximum number of mutations in exon 6 of the HGD gene. Key Points • High prevalence (8.4%) of alkaptonuria (AKU) in the gypsy population due to founder mutation in the HGD gene. • Inbreeding exemplifies the founder effects of this rare genetic disorder. • Urinary screening is a cost-effective method in this community for early detection of AKU and intervention. • The mutation spectrum causing AKU is diverse in the rest of the Indian population.
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http://dx.doi.org/10.1007/s10067-020-05020-8DOI Listing
September 2020

Efficacy and safety of tocilizumab in treatment of Takayasu arteritis: A systematic review of randomized controlled trials.

Mod Rheumatol 2021 Jan 13;31(1):197-204. Epub 2020 Feb 13.

Menzies Institute for Medical Research, University of Tasmania, Tasmania, Australia.

Background: Takayasu arteritis (TAK) is a chronic immune vasculitis in which Interleukin-6 (IL-6) receptors play a key role in pathogenesis. Tocilizumab (TCZ), an IL-6 receptor antagonist with a favorable safety and efficacy profile, has been tried as an option for patients with TAK. This systematic review analyzed the evidence from randomized control trials (RCT) assessing the safety and efficacy of TCZ in patients with TAK.

Methods: MEDLINE, Embase, the Cochrane Library, and clinical trial registries were searched from inception to July 2018. We included RCT assessing the efficacy and safety of TCZ versus placebo/other comparators for the treatment of patients with TAK. The risk of bias (RoB) was assessed using Cochrane RoB tool.

Results: 2799 identified articles were screened as per abstract and title; 42 selected full-texts articles were assessed for the potential inclusion. One trial, reported in two publications, comparing subcutaneous TCZ (162 mg/week) versus matching placebo in 36 patients with TAK was included. The relapse-free rate at 24 weeks was 50.6% and 22.9% in TCZ and placebo arm, respectively. The hazard ratio (HR) for time to first relapse was statistically significant in the per-protocol population (HR 0.34 [95.41% CI, 0.11-1.00];  = .0345), while non-significant in the intention-to-treat population (HR 0.41 [95.41% CI, 0.15-1.10];  = .0596). The serious adverse events were higher in the placebo arm.

Conclusions: This systematic review finds the existing evidence from RCT on efficacy and safety profile of TCZ in TAK to be promising but limited. Additional evidence is required to draw a stronger conclusion.
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http://dx.doi.org/10.1080/14397595.2020.1724671DOI Listing
January 2021

Comment on: Derivation of an angiographically based classification system in Takayasu's arteritis: reply.

Rheumatology (Oxford) 2020 05;59(5):1184-1185

Systemic Autoimmunity Branch, NIAMS, National Institutes of Health, Bethesda, MD.

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http://dx.doi.org/10.1093/rheumatology/kez659DOI Listing
May 2020

Circulatory Glutamine/Glucose ratio for evaluating disease activity in Takayasu arteritis: A NMR based serum metabolomics study.

J Pharm Biomed Anal 2020 Feb 24;180:113080. Epub 2019 Dec 24.

Centre of Biomedical Research, Lucknow-226014, Uttar Pradesh, India. Electronic address:

Quantitative assessment of disease activity is important for effective care of patients with Takayasu arteritis (TA). Activated glutaminolysis and reduced glycolytic flux is the hallmark of active inflammation. Based on this, we hypothesize that the circulatory Glutamine/Glucose ratio (QGR) can serve as an indicant of active inflammation in TA. To probe this hypothesis, the serum samples were collected from 45 active and 53 inactive TA patients fulfilling American College of Rheumatology (ACR) criteria and assessed for disease activity according to Indian Takayasu Clinical Activity Score (ITAS) using acute phase reactant-erythrocyte sedimentation rate [ITAS-A (ESR)]. The quantitative profiles of circulatory metabolites implicated in glutaminolysis (Glutamine and Glutamate) and those which estimate glycolytic flux (i.e. glucose and lactate) were measured using high field (800 MHz) NMR spectroscopy. The recorded spectra were analyzed using CHENOMX NMR Suite and the estimated concentration profiles were compared and evaluated for their diagnostic potential using Metaboanalyst. Compared to inactive-TA patients, the sera of active-TA patients were characterized by significantly decreased serum levels of glutamine and lactate suggesting that these patients exhibit activated glutaminolysis and reduced glycolytic activity. This is further supported by significantly decreased QGR and lactate to glucose ratio (LGR) levels in active compared to inactive TA patients. The receiver operating characteristic (ROC) curve analysis revealed satisfactory accuracy, sensitivity and specificity for QGR [with area under ROC curve (AUROC) = 0.76 and 95% confidence interval (CI) = 0.66-0.84) compared to that for LGR (with AUROC = 0.67 and CI = 0.561-0.77). Therefore, we believe that the circulatory QGR has the potential to serve as surrogate marker for the assessment of disease activity in TA patients. However, the use of this ratio in clinical settings will require future studies on large patient cohorts and procedural optimization as well to improve accuracy.
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http://dx.doi.org/10.1016/j.jpba.2019.113080DOI Listing
February 2020

Epidemiological profile and north-south gradient driving baseline systemic involvement of primary Sjögren's syndrome.

Rheumatology (Oxford) 2020 09;59(9):2350-2359

Sjögren Syndrome Research Group (AGAUR), Laboratory of Autoimmune Diseases Josep Font, IDIBAPS-CELLEX, Department of Autoimmune Diseases, ICMiD, University of Barcelona, Hospital Clínic, Barcelona, Spain.

Objective: To characterize the systemic phenotype of primary Sjögren's syndrome at diagnosis by analysing the EULAR-SS disease activity index (ESSDAI) scores.

Methods: The Sjögren Big Data Consortium is an international, multicentre registry based on worldwide data-sharing cooperative merging of pre-existing databases from leading centres in clinical research in Sjögren's syndrome from the five continents.

Results: The cohort included 10 007 patients (9352 female, mean 53 years) with recorded ESSDAI scores available. At diagnosis, the mean total ESSDAI score was 6.1; 81.8% of patients had systemic activity (ESSDAI score ≥1). Males had a higher mean ESSDAI (8.1 vs 6.0, P < 0.001) compared with females, as did patients diagnosed at <35 years (6.7 vs 5.6 in patients diagnosed at >65 years, P < 0.001). The highest global ESSDAI score was reported in Black/African Americans, followed by White, Asian and Hispanic patients (6.7, 6.5, 5.4 and 4.8, respectively; P < 0.001). The frequency of involvement of each systemic organ also differed between ethnic groups, with Black/African American patients showing the highest frequencies in the lymphadenopathy, articular, peripheral nervous system, CNS and biological domains, White patients in the glandular, cutaneous and muscular domains, Asian patients in the pulmonary, renal and haematological domains and Hispanic patients in the constitutional domain. Systemic activity measured by the ESSDAI, clinical ESSDAI (clinESSDAI) and disease activity states was higher in patients from southern countries (P < 0.001).

Conclusion: The systemic phenotype of primary Sjögren's syndrome is strongly influenced by personal determinants such as age, gender, ethnicity and place of residence, which are key geoepidemiological players in driving the expression of systemic disease at diagnosis.
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http://dx.doi.org/10.1093/rheumatology/kez578DOI Listing
September 2020

Validation of new classification criteria of rheumatoid arthritis in an international multicentre study.

Clin Exp Rheumatol 2020 Sep-Oct;38(5):841-847. Epub 2019 Dec 9.

Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing Key Laboratory for Rheumatism and Immune Diagnosis (BZ0135) and Peking-Tsinghua Center for Life Sciences, Beijing, China.

Objectives: Early identification of patients with rheumatoid arthritis (RA) is essential to allow prompt therapy. In this study, we aimed to evaluate the performance of the newly proposed ERA criteria, compared to the 1987 ACR and 2010 ACR/EULAR criteria in an international multicentre study.

Methods: A total of 606 patients with disease duration ≤2 years and age ≥16 years who were diagnosed as RA or non-RA were enrolled from China, Sweden and India. The clinical and laboratory parameters were recorded. We compared the sensitivity, specificity, predictive value, likelihood ratio (LR), and the area under the ROC curve (AUC) of three criteria in these cohorts. Concordance between the three criteria was calculated with the Kappa coefficient.

Results: Three hundred and twelve RA and 294 non-RA patients were included. The Early Rheumatoid Arthritis (ERA) criteria had significantly higher specificity compared to the 2010 ACR/ EULAR criteria (83.7% vs. 78.2%, p=0.02) and sensitivity were similar (79.2% vs. 78.5%, p=0.883). In comparison with the 1987 ACR criteria, the ERA criteria had higher sensitivity (79.2% vs. 54.5%, p<0.001) but lower specificity (83.7% vs. 89.1%, p<0.001), and the AUC of the ERA criteria (0.878) was comparable to the 2010 ACR/EULAR criteria (0.849) and higher than the 1987 ACR criteria (0.791, p<0.0001). Patients from the three countries, seronegative and very early arthritis cohorts yielded consistent results.

Conclusions: The ERA criteria demonstrate a better performance across ethnics in early RA diagnosis, and is more feasible in daily practice.
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October 2020

Derivation of an angiographically based classification system in Takayasu's arteritis: an observational study from India and North America.

Rheumatology (Oxford) 2020 05;59(5):1118-1127

Systemic Autoimmunity Branch, NIAMS, National Institutes of Health, Bethesda, MD, USA.

Objectives: To develop and replicate, using data-driven methods, a novel classification system in Takayasu's arteritis based on distribution of arterial lesions.

Methods: Patients were included from four international cohorts at major academic centres: India (Christian Medical College Vellore); North America (National Institutes of Health, Vasculitis Clinical Research Consortium and Cleveland Clinic Foundation). All patients underwent whole-body angiography of the aorta and branch vessels, with categorization of arterial damage (stenosis, occlusion or aneurysm) in 13 territories. K-means cluster analysis was performed to identify subgroups of patients based on pattern of angiographic involvement. Cluster groups were identified in the Indian cohort and independently replicated in the North American cohorts.

Results: A total of 806 patients with Takayasu's arteritis from India (n = 581) and North America (n = 225) were included. Three distinct clusters defined by arterial damage were identified in the Indian cohort and replicated in each of the North American cohorts. Patients in cluster one had significantly more disease in the abdominal aorta, renal and mesenteric arteries (P < 0.01). Patients in cluster two had significantly more bilateral disease in the carotid and subclavian arteries (P < 0.01). Compared with clusters one and two, patients in cluster three had asymmetric disease with fewer involved territories (P < 0.01). Demographics, clinical symptoms and clinical outcomes differed by cluster.

Conclusion: This large study in Takayasu's arteritis identified and replicated three novel subsets of patients based on patterns of arterial damage. Angiographic-based disease classification requires validation by demonstrating potential aetiological or prognostic implications.
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http://dx.doi.org/10.1093/rheumatology/kez421DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7850097PMC
May 2020

Obstetric and perinatal outcomes in pregnant women with Takayasu’s arteritis: single centre experience over five years

J Turk Ger Gynecol Assoc 2020 03 30;21(1):15-23. Epub 2019 Sep 30.

Clinic of Obstetrics and Gynaecology, Christian Medical College and Hospital, Vellore, India

Objective: To study obstetric and perinatal outcomes among pregnant women with Takayasu arteritis (TA), attending our hospital for pregnancy and childbirth between January 2011 to December 2016.

Material And Methods: Retrospective study was carried out by abstracting clinical charts on all pregnant women with TA who underwent antenatal care and/or delivery in our hospital during this period. American College of Rheumatology criteria was used for diagnosis of TA. Sixteen women with TA were included in the study. Maternal demographic data, stage of disease, complications related to disease, details of treatment taken prior to pregnancy, pregnancy outcomes, and neonatal outcomes were studied.

Results: Forty-four percentage (7/16) belonged to type 5 angiographic type, however the same proportion (7/16) had undergone surgical corrections prior to pregnancy and the majority (15/16) were on medical management. Only three women (19%) were diagnosed during pregnancy. Most did not have active disease measured by Kerr’s criteria (n=12; 75%), and Indıan Takayasu clinical activity scores A. Chronic hypertension was the commonest antenatal complication (56.2%), nearly one-third had growth restricted babies and 25% had preterm labour. There were no cardiovascular events, no maternal deaths, nor fetal or neonatal deaths. Two-thirds of our women were delivered by caesarean section.

Conclusion: Preconceptional counselling is of paramount importance in women with TA. Good maternal and fetal outcomes are observed with close antenatal surveillance and multidisciplinary care. Pregnancy should be planned during disease remission, with good antenatal care, close monitoring of clinical symptoms, early diagnosis and treatment of complications.
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http://dx.doi.org/10.4274/jtgga.galenos.2019.2019.0115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7075400PMC
March 2020

Saliva microbiome in primary Sjögren's syndrome reveals distinct set of disease-associated microbes.

Oral Dis 2020 Mar 10;26(2):295-301. Epub 2020 Jan 10.

Informatics and Big Data, CSIR Institute of Genomics and Integrative Biology (CSIR-IGIB), New Delhi, India.

Objective: This study systematically aims to evaluate the salivary microbiome in patients with primary Sjögren's syndrome (pSS) using 16S rRNA sequencing approach.

Methods: DNA isolation and 16S rRNA sequencing was performed on saliva of 37 pSS and 35 control (CC) samples on HiSeq 2500 platform. 16S rRNA sequence analysis was performed independently using two popular computational pipelines, QIIME and less operational taxonomic units scripts (LoTuS).

Results: There were no significant changes in the alpha diversity between saliva of patients and controls. However, four genera including Bifidobacterium, Lactobacillus, Dialister and Leptotrichia were found to be differential between the two sets, and common between both QIIME and LoTuS analysis pipelines (Fold change of 2 and p < .05). Bifidobacterium, Dialister and Lactobacillus were found to be enriched, while Leptotrichia was significantly depleted in pSS compared to the controls. Exploration of microbial diversity measures (Chao1, observed species and Shannon index) revealed a significant increase in the diversity in patients with renal tubular acidosis. An opposite trend was noted, with depletion of diversity in patients with steroids.

Conclusion: Our analysis suggests that while no significant changes in the diversity of the salivary microbiome could be observed in Sjögren's syndrome compared to the controls, a set of four genera were significantly and consistently differential in the saliva of patients with pSS. Additionally, a difference in alpha diversity in patients with renal tubular acidosis and those on steroids was observed.
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http://dx.doi.org/10.1111/odi.13191DOI Listing
March 2020

Systemic manifestations of primary Sjögren's syndrome out of the ESSDAI classification: prevalence and clinical relevance in a large international, multi-ethnic cohort of patients.

Clin Exp Rheumatol 2019 May-Jun;37 Suppl 118(3):97-106. Epub 2019 Aug 28.

Sjögren's Syndrome Res. Group (AGAUR), Lab. of Autoimmune Diseases Josep Font, IDIBAPS-CELLEX, Dept. of Autoimmune Diseases, ICMiD, Univ. of Barcelona, Hospital Clínic, and Autoimmune Diseases Unit, Dept. of Medicine, Hosp. CIMA-Sanitas, Barcelona, Spain.

Objectives: To analyse the frequency and characterise the systemic presentation of primary Sjögren's syndrome (SS) out of the ESSDAI classification in a large international, multi-ethnic cohort of patients.

Methods: The Big Data Sjögren Project Consortium is an international, multicentre registry based on world-wide data-sharing and cooperative merging of pre-existing clinical SS databases from leading centres in clinical research in SS from the five continents. A list of 26 organ-by-organ systemic features not currently included in the ESSDAI classification was defined according to previous studies; these features were retrospectively recorded.

Results: Information about non-ESSDAI features was available in 6331 patients [5,917 female, mean age at diagnosis 52 years, mainly White (86.3%)]. A total of 1641 (26%) patients had at least one of the ESSDAI systemic features. Cardiovascular manifestations were the most frequent organ-specific group of non-ESSDAI features reported in our patients (17% of the total cohort), with Raynaud's phenomenon being reported in 15%. Patients with systemic disease due to non-ESSDAI features had a lower frequency of dry mouth (90.7% vs. 94.1%, p<0.001) and positive minor salivary gland biopsy (86.7% vs. 89%, p=0.033), a higher frequency of anti-Ro/SSA (74.7% vs. 68.7%, p<0.001), anti-La/SSB antibodies (44.5% vs. 40.4%, p=0.004), ANA (82.7% vs. 79.5%, p=0.006), low C3 levels (17.4% vs. 9.7%, p<0.001), low C4 levels (14.4% vs. 9.6%, p<0.001), and positive serum cryoglobulins (8.6% vs. 5.5%, p=0.001). Systemic activity measured by the ESSDAI, clinESSDAI and DAS was higher in patients with systemic disease out of the ESSDAI in comparison with those without these features (p<0.001 for all comparisons).

Conclusions: More than a quarter of patients with primary SS may have systemic manifestations not currently included in the ESSDAI classification, with a wide variety of cardiovascular, digestive, pulmonary, neurological, ocular, ENT (ear, nose, and throat), cutaneous and urological features that increase the scope of the systemic phenotype of the disease. However, the individual frequency of each of these non-ESSDAI features was very low, except for Raynaud's phenomenon.
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October 2019

Determinants of diagnosis and disease course in primary Sjögren's syndrome: Results from datamining of electronic health records.

Int J Rheum Dis 2019 Sep 21;22(9):1768-1774. Epub 2019 Jul 21.

Department of Clinical Immunology and Rheumatology, Christian Medical College and Hospital, Vellore, Tamil Nadu, India.

Background: Determinants of diagnosis in primary Sjögren's syndrome (pSS) in tertiary care settings is not well understood.

Methods: Patients were screened by tracing reports of anti-SSA (anti-Ro) antibody assays between January 2008 and October 2015. Electronic health records (EHR) were reviewed. Patients fulfilling the 2016 American College of Rheumatology/European League Against Rheumatism (EULAR) classification criteria were included. Variables including the specialties of first consultation, initial clinical presentations, investigations ordered at first consultation, number of hospital visits prior to reaching the final diagnosis of pSS and the baseline EULAR SS Disease Activity Index (ESSDAI) were noted.

Results: A total of 275 patients with pSS consulted 24 different specialties at first visit. Rheumatology accounted for 128 (46.55%) patients. At first consultation, initial suspicion for pSS was 48.4% for all specialties together and 64.84% for the rheumatologist. Median number of visits prior to arriving at the final diagnosis was 1 (1-6), when the initial impression was pSS and 3 (1-14), if the initial clinical impression was a non-SS differential (P < 0.001). A first impression of pSS, enquiry about sicca symptoms and ordering anti-SSA (anti-Ro) antibody test at first consultation were strong predictors of early diagnosis with odds (95% CI) of 5.01 (1.72-14.55) P < 0.001, 4.79 (1.16-19.84) P = 0.03 and 9.60 (3.0-30.67) P < 0.0001, respectively. None of the clinical variables proved to be useful predictors of early diagnosis.

Conclusions: Diagnosis of pSS is challenging even in tertiary care centers as patients present with myriad features to several specialties. Initial suspicion was limited to 48.4% for all specialties together and 64.84% for the rheumatologist. High suspicion of pSS along with ordering anti-SSA (anti-Ro) antibody could hasten diagnosis.
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http://dx.doi.org/10.1111/1756-185X.13641DOI Listing
September 2019

Unique clinical and autoantibody profile of a large Asian Indian cohort of scleroderma-do South Asians have a more aggressive disease?

Clin Rheumatol 2019 Nov 15;38(11):3179-3187. Epub 2019 Jul 15.

Department of Clinical Immunology and Rheumatology, Christian Medical College, Vellore, 632004, India.

Aim And Methods: A single-centre retrospective study was conducted using electronic medical records (EMR) of inpatients and outpatients with the diagnosis of "scleroderma" or "systemic sclerosis" visiting our clinic over the preceding 5 years.

Results: A total of 327 patients' charts met our selection criteria; 301 were females. The median (IQR (inter quartile range)) age at onset of first non-Raynaud's symptom was 34.67 (27-43) years and median (IQR) disease duration prior to presentation to our department was 2.5 (1-5) years. Of these, 310 (94.8%) belonged to diffuse systemic sclerosis variety, 13 (4%) had limited systemic sclerosis, and 4 (1.2%) were of sine scleroderma type. A total of 289/302 (95.7%) patients were positive for ANA; of them, 245/327 (74.9%) were Scl-70 antibody-positive and 4% were CENP antibody-positive. Interstitial lung disease (ILD) was present in 288/327 (88.1%) patients. Among patients with available baseline forced vital capacity (FVC) data, 20% had a normal lung function and 28.4% had severe restriction. Pulmonary hypertension as assessed by echocardiography was present in 8.1% of patients. A significant association of Scl-70 antibody positivity with the presence of interstitial lung disease (ILD) (p = 0.000) and pulmonary hypertension (p = 0.035) was seen. On the other hand, presence of CENP antibody showed a protective trend against muscle weakness and/or muscle enzyme elevation (p = 0.052). Presence of arthritis was protective against development of digital ulceration (p = 0.021) and PAH (0.004). Patients younger than 40 years of age had significantly higher frequency of Scl-70 positivity (p = 0.038), whereas CENP antibody positivity was more likely in those aged > 40 years (p = 0.002).

Conclusion: Younger age of onset and high prevalence of Scl-70 antibody are unique South Asian features common with large Indian, Thai, and Chinese series. High prevalence of ILD is a feature common to Indian and Chinese series. Strong correlation of Scl-70 antibody with younger age and pulmonary hypertension were unique features of our cohort.

Key Points: • Asian Indian scleroderma patients are younger by 2 decades compared to Caucasian series. • Higher prevalence of Scl-70 antibody, its association with young age, interstitial lung disease and pulmonary hypertension are features of our cohort. • High prevalence of interstitial lung disease (88.1%) was noted ; among those with baseline spirometry data (141/327), two thirds(66%) had moderate to severe restriction. • Younger age at onset, higher prevalence of Scl-70 antibody are features common to other Indian, Thai and Chinese series.
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http://dx.doi.org/10.1007/s10067-019-04659-2DOI Listing
November 2019

Study of familial aggregation of autoimmune rheumatic diseases in Asian Indian patients with systemic lupus erythematosus.

Rheumatol Int 2019 Dec 1;39(12):2053-2060. Epub 2019 Jul 1.

Department of Clinical Immunology and Rheumatology, Christian Medical College Hospital, Vellore, India.

Systemic lupus erythematosus (SLE) and other autoimmune rheumatic diseases (AIRD) tend to co-aggregate in families, making positive familial history a risk factor. We aimed to estimate familial aggregation of AIRD in SLE patients and to compare between ones having a positive and negative family history of autoimmunity in our cohort. We included families of 157 consecutive SLE patients in a hospital-based, cross-sectional design for a three-generation pedigree study. Clinical and laboratory parameters of these patients were recorded. AIRD was seen in families of 39 SLE patients amounting to a familial prevalence of 24.8% [95% confidence interval (CI) 18.1, 31.6] with a relative risk (λ) of 4.3 for first-degree relatives (FDRs) and 1.1 for second-degree relatives (SDRs). SLE was the commonest AIRD seen in families of 19 patients with a familial prevalence of 12.1% (95% CI 7.0, 17.2) and λ of 78.2 for FDRs and 18.1 for SDRs. AIRD as a whole and SLE alone were seen more commonly with parental consanguinity (p < 0.05). Familial aggregation in SLE patients also showed a relatively higher percentage of affected males and lesser presentation with constitutional features (p < 0.05) than sporadic SLE patients. Rheumatoid arthritis (RA) was the second most common AIRD seen in 16/39 (41%) families with a RR of 3.1 in FDRs of SLE patients. In conclusion, Asian Indian SLE patients seem to have a high familial aggregation of AIRD, which is more pronounced in the background of parental consanguinity. SLE is the commonest AIRD seen amongst FDRs and SDRs of SLE patients, followed by RA, with FDRs being at highest risk.
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http://dx.doi.org/10.1007/s00296-019-04355-zDOI Listing
December 2019

A descriptive pilot study of mitochondrial mutations & clinical phenotype in fibromyalgia syndrome.

Indian J Med Res 2019 Jan;149(1):47-50

Department of Clinical Immunology & Rheumatology, Christian Medical College & Hospital, Vellore, India.

Background & Objectives: : Fibromyalgia syndrome (FMS) is one of the most common chronic pain conditions of unknown aetiology. Mitochondrial dysfunction has been reported in FMS with some studies reporting the presence of mitochondrial mutation namely A3243G, which also causes mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes. This pilot study was conducted to assess this mutation and also detect large deletions in mitochondrial DNA (mtDNA) in patients with FMS.

Methods: : Thirty female patients with FMS participated and 30 matched controls were included. Genomic DNA was subjected to polymerase chain reaction (PCR) amplification using specific primers followed by restriction digestion with Apa I enzyme to detect the specific A3243G mtDNA mutation. Long-range PCR was done in two sets to detect the large deletions in the mtDNA. Biochemical parameters including thyroid-stimulating hormone and vitamin D levels were also looked at.

Results: : None of the patients were found to carry the common mutation or large deletions. Low vitamin D level was a common finding. Hypothyroidism was found in a few patients.

Interpretation & Conclusions: : Although the common mutation or large mtDNA deletions were not detected in blood mtDNA in the FMS patients, mutations in the muscle and sequence variation in mtDNA remained a possibility. Future studies in both blood and muscle tissue including mtDNA sequencing are warranted in such patients to determine if a subset of FMS patients have mitochondrial myopathy.
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http://dx.doi.org/10.4103/ijmr.IJMR_1977_16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6507534PMC
January 2019

Childhood-Onset Takayasu Arteritis (c-TA): Current and Future Drug Therapy.

Paediatr Drugs 2019 Apr;21(2):81-93

Department of Clinical Immunology and Rheumatology, Christian Medical College, Vellore, India.

Childhood-onset Takayasu arteritis (c-TA) is the third most common systemic vasculitic disorder in children. Vascular stenosis is the main complication, and aneurysms are reported in 19-65% of cases, often in combination with stenotic lesions. Management of patients with c-TA is largely based on studies involving predominantly patients with adult-onset TA (a-TA). More widely used criteria for patients with c-TA have been devised by the joint European League Against Rheumatism, Pediatric Rheumatology International Trials Organization, and Pediatric Rheumatology European Society. Of the available imaging modalities, those that do not use radiation (color Doppler ultrasound and magnetic resonance angiogram) are preferred over F-labeled fluoro-2-deoxyglucose (F-FDG) positron-emission tomography, computed tomography (CT), and CT angiogram in children. Remission rates have been reported to be lower in c-TA than in a-TA, and published mortality rates in c-TA range from 16 to 40%, which is much higher than reported in patients with a-TA. The usual drug therapy options include steroids plus steroid-sparing second-line immunosuppressants, such as mycophenolate, azathioprine, methotrexate, cyclophosphamide, and cyclosporine, along with antiplatelet agents. Interleukin-6 inhibitors such as tocilizumab, as well as the tumor necrosis factor inhibitors, are other aggressive therapeutic options. As yet, no randomized controlled trials have been conducted in c-TA.
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http://dx.doi.org/10.1007/s40272-019-00327-9DOI Listing
April 2019

Progress towards universal health coverage in the context of rheumatic diseases in India.

Int J Rheum Dis 2019 May 4;22(5):880-889. Epub 2019 Apr 4.

Department of Clinical Immunology & Rheumatology, Christian Medical College and Hospital, Vellore, India.

Aim: This study aims to measure current situation with regard to access and financial protection towards healthcare for rheumatic diseases (RDs) in India.

Method: The first part of this study is quantitative, and uses the data generated by the 71st Round of National Sample Survey 2014, which measured self-reported morbidity, choice of provider and utilization of services and out of pocket expenditure (OOPE) incurred on healthcare services in a sample of 65 932 households and 333 104 individuals from all across India. The second qualitative part of the study was done in one sample district to understand the barriers to access and financial protection.

Results: 3.5% of all hospitalizations in the preceding one year and 9.9% of all ambulatory care in the preceding 15 days of this study period were due to RDs. Cost of care for RDs was three times higher in private sector. Cost on medicines comprised the largest share in both sectors. 54% of the households faced catastrophic health expenditure at 10% threshold (CHE-10) and this was nine times higher in private provisioning (OR: 8.8, CI: 6.8-11.4). 24% of the households had to borrow or sell household assets to meet the hospitalization expenditure. Insurance had marginal impact and it did not help in preventing household from facing CHE-10 for the lowermost three economic quintiles. There was significant unmet health care needs and lack of continuity of care of RDs in India.

Conclusion: Addressing the gaps in access and financial protection for patients with RDs need greater emphasis in policy as well as implementation, if the country has to achieve Universal Health Coverage.
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http://dx.doi.org/10.1111/1756-185X.13488DOI Listing
May 2019

Clinical spectrum of post-streptococcal reactive arthritis (PSRA) revisited: Juvenile versus adult-onset disease.

Int J Rheum Dis 2019 Apr 3;22(4):750-751. Epub 2019 Apr 3.

Department of Clinical Immunology and Rheumatology, Christian Medical College & Hospital, Vellore, India.

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http://dx.doi.org/10.1111/1756-185X.13524DOI Listing
April 2019