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Objective: To compare the clinical and angiographic responses of mycophenolate mofetil (MMF) versus methotrexate (MTX) in Takayasu arteritis (TAK). Methods: This was an open-label, outcome assessor–blinded trial. Adult patients with active TAK were randomized 1:1 to MMF 1 g twice daily or MTX 20 mg once weekly by a computer-generated program. All patients were started on 0.5 mg/kg of steroids with a predetermined tapering protocol. The primary outcome was the treatment response as defined by Indian Takayasu arteritis score at 9 months. The secondary end points included the time to first failure and angiographic progression. Results: A total of 52 patients (26 in each arm) were recruited. The rate of responders was 71.43% (15/21) in the MMF arm and 63.64% (14/22) in the MTX arm (P = .58). The median time to the first failure was 9 months (range: 3–9) and 4.5 months (range: 3–9) in the MMF and MTX arms, respectively (P = .052). In both groups, 15% of patients (n = 3) had a progressive disease in angiography. Conclusions: The results showed numerically better outcomes favouring MMF, with a longer time to the first failure than MTX (9 months versus 4.5 months, P = .052). No significant difference was seen in the angiographic outcomes. [ABSTRACT FROM AUTHOR]

There are not many studies looking at psychological impact of physical morbidities amongst patients with systemic sclerosis. Our aim was to describe the prevalence of common mental disorders (CMD) in systemic sclerosis patients, as against the population prevalence of CMDs. We also wanted to assess the utility of revised clinical interview schedule (CIS-R), a standardised interview technique for screening CMDs in systemic sclerosis (SSc). We prospectively recruited 93 consecutive patients fulfilling the 2013 ACR/EULAR criteria for systemic sclerosis from our single tertiary care centre. They were interviewed using CIS-R interviewing technique. These patients were assessed for the presence of psychiatric symptoms and presence of common mental disorders. Various associations of documented mental health issues and ICD-10-based psychiatric diagnosis were also analysed. A total of 29 (31%) out of 93 individuals with systemic sclerosis had a common mental disorder as per the earlier defined CIS-R cut off score of 12 and above. Fatigue (50.5%) and sleep issues (43%) were the commonest symptoms. Thirty-four patients (33.6%) fulfilled a total of 39 ICD-10 psychiatric diagnoses. Total CIS-R score is significantly associated with duration of Scleroderma in univariate analysis (p = 0.019), but there was no significant association on a multivariate analysis. Depression [18.3% as against 5% in Asian Indian general population], followed by obsessive compulsive disorder (OCD) [15.1% as against 0.7% in general population in India] were the top two ICD-10 psychiatric diagnosis in SSc. The occurrence of both depression and OCD, therefore, are far in excess compared to community prevalence. Additionally, modified CIS-R cut off of 10 instead of 12 can also improve the sensitivity (94%) of this screening interviewing tool for an ICD-10 psychiatric diagnosis. Depression is 3.4 times and OCD is 20 times commoner in our cohort of SSc than general population in India. A modified CIS-R cut-off score of 10 may further help in early recognition of these mental disorders in SSc and their referral to a psychiatrist. [ABSTRACT FROM AUTHOR]

Globally, rheumatic musculoskeletal diseases constitute the most common causes of disability, related morbidity and economic loss worldwide. A shortage of rheumatologists warrants education of primary care doctors in primary care rheumatology, public awareness initiatives and advocacy for rheumatic musculoskeletal health. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 (162mg/week) versus matching placebo in 36 patients with TAK was included. The relapsefree 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]; p=.0345), while non-significant in the intention-to-treat population (HR 0.41 [95.41% CI, 0.15-1.10]; p=.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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The article looks at the characteristic features of primary Sjögren's syndrome (pSS) in Asia. Topics covered include incidence and prevalence rates of pSS among Asians, paucity of sicca symptoms at initial presentation observed in Asian populations, and higher frequency of antibody positivity in Asian patients.

Objectives To assess genetic association between single nucleotide polymorphisms (SNPs) in genes encoding T-helper cytokines and Takayasu Arteritis (TA) susceptibility in Asian Indian population. Methods In Phase-1, the genomic DNA of 120 TA patients and 119 healthy controls were genotyped for SNPs rs1800795 (interleukin (IL)-6), rs763780 (IL-17F), rs1800871, rs1800872, rs1800896 (IL-10) and rs1800468, rs1800469, rs1800470 (transforming growth factor-β). Allele frequencies between cases and controls were compared using chi-squared test and also reassessed empirically (p e ) by 10,000 permutations. In Phase-2, additional 98 TA patients and 101 controls were genotyped for replicating the significant associations noted in Phase-1 of the study. Results All 8 SNPs in Phase 1 were in Hardy-Weinberg proportions. The G allele at rs763780 (IL-17F) was significantly associated with TA (p = 0.014). We also found that rs1800795 (IL-6) was associated with tuberculosis (p = 0.001) under a dominant model. In Phase-2 replication part of the study, the rs763780 showed a trend towards association with TA (p = 0.08), and the magnitude and direction of the odds ratio (OR) also were consistent with results of Phase-1. In the combined analysis, protective association of the G allele of rs763780 with TA was again significant [OR (95% CI) = 0.44 (0.25–0.77); p = 0.0029]. The G allele was also significantly associated (p < 0.05) with underlying tuberculosis (TB) and occurrence of syncope in TA. Conclusion G allele of rs763780 in IL-17F gene was protectively associated against susceptibility to TA. GG genotypes of rs1800795 in IL-6 was also associated with occurrence of tuberculosis in our patients with TA. [ABSTRACT FROM AUTHOR]

An introduction is presented in which the editor discusses various reports within the issue on topics including metabolic disorders, systemic lupus erythematosus, and rheumatoid arthritis.

The human body is an environmental niche which is home to diverse co-habiting microbes collectively referred as the human microbiome. Recent years have seen the in-depth characterization of the human microbiome and associations with diseases. Linking of the composition or number of the human microbiota with diseases and traits date back to the original work of Elie Metchnikoff. Recent advances in genomic technologies have opened up finer details and dynamics of this new science with higher precision. Microbe-rheumatoid arthritis connection, largely related to the gut and oral microbiomes, has showed up as a result - apart from several other earlier, well-studied candidate autoimmune diseases. Although evidence favouring roles of specific microbial species, including Porphyromonas, Prevotella and Leptotricha, has become clearer , mechanistic insights still continue to be enigmatic. Manipulating the microbes by traditional dietary modifications, probiotics, and antibiotics and by currently employed disease-modifying agents seems to modulate the disease process and its progression. In the present review, we appraise the existing information as well as the gaps in knowledge in this challenging field. We also discuss the future directions for potential clinical applications, including prevention and management of rheumatoid arthritis using microbial modifications. [ABSTRACT FROM AUTHOR]

Background & objectives: Paucity of growth retardation has been observed by us in patients with juvenile-onset ankylosing spondylitis (JAS) in a tertiary care health centre in south India. We, therefore, undertook this pilot study to assess and compare anthropometry of patients with JAS who were 15 yr and older with that of adult onset ankylosing spondylitis (AAS) and matching Indian reference population. Methods: Consecutive male patients (December 2009-October 2012) with JAS and AAS fulfilling Modified New York Criteria were selected after applying inclusion and exclusion criteria. Demography and anthropometry were noted. Height of both patient groups as well as their parents and siblings were compared with that of the reference population. Mid-parental height and delta height were derived. Those with delta height of >8.5 cm were compared with the remaining. Multivariate logistic regression was done for variables that were found to be significant by chi-square in bivariate analysis. Similar analysis was done for BMI also. Results: There was no significant difference in anthropometric variables between JAS and AAS groups. Twenty eight of the 30 (93.33%) JAS patients were taller as compared to the reference population. Twenty six (86.67%) AAS patients were taller than the reference population. The mean heights of JAS (170.67 ± 6.94 cm) and AAS (168.2 ± 5.94 cm) patients were significantly higher than the reference value of 163.11 cm; both p<0.001. Logistic regression revealed that tallness in JAS was associated positively with hypermobility (OR=23.46,95%CI 1.2-447.2, p=0.036). No significant association was detected for height in AAS and for BMI in both JAS and AAS groups. Interpretation & conclusions: No growth retardation was seen in patients with JAS in our study. Majority of patients with JAS and AAS were taller than reference population. The difference between mean height of JAS and AAS was not significant. Larger studies involving different populations are required to confirm these findings. [ABSTRACT FROM AUTHOR]

The author discusses the developments and treatment of ankylosing spondylitis (AS). Topics discussed by the author include the classification of spondyloarthritis (SpA), the use of anti-inflammatory medications called NSAIDs), and the approval of the U.S. Food and Drug Administration (FDA) on five tumor necrosis factor inhibitors (TNFi) for the treatment of AS.

An introduction is presented in which the authors discuss various reports within the issue on topics including the management and prevention of Asian lupus nephritis, the crescentic lupus nephritis treatment, and the development in treatment of lupus nephritis in Asian countries.

Aim: To assess outcome of 10 'difficult to treat' patients with Takayasu arteritis (TA) treated with tocilizumab. Methods: Records of 10 patients with TA who received at least six infusions of tocilizumab were studied and data related to demography, medications, investigations, angiography and outcome were analyzed. Results: Median age, disease duration and Indian Takayasu Arteritis Score (ITAS) of 10 patients were 24.5 (13- 53) years, 25.5 (1.5-60) months and 4.5 (0-13), respectively. All patients had active disease with ITAS of ≥ 1 and/or they were angiographically active in spite of treatment with steroids and second line agents for a median duration of 27 (15-60) months. Tocilizumab led to a clinical response with ITAS of 0 and reduction in acute phase reactants (APR) in 100% of patients by the fourth infusion. Six patients (60%) maintained clinical response with radiologically stable disease and normal APR up to the sixth infusion. Two out of three patients (66%) with normal APR at baseline achieved and maintained stable disease state up to the last infusion, in contrast to 49.2% (4/7) responders in those with baseline high APR. Tocilizumab facilitated rapid reduction in steroid dose from 24 ± 15 to 5.4 ± 4.9 mg/day (P = 0.003). However, following discontinuation of toclizumab therapy after six infusions, only two patients maintained stable disease state and the majority of them needed rescue therapy. There was no major adverse event or fatality. Conclusion: Tocilizumab may be an effective steroid-sparing option for rapid control of refractory disease activity in patients of TA. However, the benefit is not sustained after its withdrawal. [ABSTRACT FROM AUTHOR]

Objectives. There are no valid instruments to measure disease activity in Takayasu arteritis (TA). We aim to provide a valid measure to assess clinical disease activity with or without incorporating acute phase reactants.Methods. The Indian Takayasu Clinical Activity Score (ITAS) was initially derived from disease manifestations scored in the Disease Extent Index (DEI.Tak). The ITAS was validated by a group of physicians scoring both live and paper cases for inter-rater reliability (IRR), convergence with BVAS, correlation with the Physician’s Global Assessment (PGA) and ESR/CRP. It was further validated at a single centre in 177 patients for its ability to discriminate between active and inactive disease state at first visit and sensitivity to change in 132 active patients measured serially at two follow-up visits. ITAS-A also included graded scores for ESR/CRP.Results. The final ITAS2010 contains 44 items with 33 features arising from the cardiovascular system. Seven key items are weighted to score 2 and all others score 1 only. Inter-observer variability was highly satisfactory (IRR 0.97). The ITAS showed superior inter-rater agreement compared with the BVAS (IRR 0.9) and PGA (IRR 0.82). In the single-centre study, median ITAS scores at first visit were significantly higher in active disease (5.62 ± 3.14) compared with grumbling (3.36 ± 1.96) and inactive disease (1.27 ± 1.26, P < 0.0001). The therapy induced a significant decrease in the ITAS2010 but the higher ITAS-A scores remained elevated.Conclusion. The ITAS2010, validated in over 300 TA patients and sensitive to change, is a useful measure of clinical disease activity for patient monitoring. Higher ITAS-A scores suggest poor control of active disease by current therapy. [ABSTRACT FROM AUTHOR]

Background Cyclo-oxygenase ( COX)-2 inhibitors have been the target of severe criticism, more so following the withdrawal of Rofecoxib. Post-marketing surveillance of Celecoxib in Asian Indians, who are predisposed to premature athero-thrombotic events, has not been studied. Aims To study the adverse effects of Celecoxib and compare them with those of other non-steroidal anti-inflammatory drugs ( NSAIDs) in an Asian Indian cohort. Materials and methods This is a retrospective chart review with convenience sampling of patients on NSAIDs (at least five tablets a week, for at least 3 months prior to the study), attending the Rheumatology clinic of a tertiary care institution in south India between June 2004 and November 2004. Those with pre-existing heart disease, hypertension, thrombo-embolic disease, peptic ulcer and patients on corticosteroids were excluded. All the recorded adverse events were noted and compared between the Celecoxib and non-selective NSAID users. Univariate analysis using Chi-square test was performed. Results Of the 1387 patients included, 915 were on Celecoxib. In the NSAID group, 204 had used multiple NSAIDs in sequence. Of the Celecoxib users, 164 had switched over to an NSAID during the study period. New onset of hypertension was significantly higher in the Celecoxib users as compared to non-selective NSAID users (3.06% vs. 1.27%, P = 0.04). However, those who had switched over to NSAIDs did not show this trend. NSAID users, on the other hand, had significant gastrointestinal ( GI) toxicity (2.54% vs. 0.327%, P = 0.001). A significant number of Celecoxib users who switched over to NSAIDs also developed GI toxicity (6.1% vs. 1.21%, P = 0.018) over a shorter time span, as compared to the continuous NSAID users. Multiple NSAID users had higher adverse events (6.37% vs. 2.23%, P = 0.023) as compared to single NSAID users. Conclusion Celecoxib significantly increased the incidence of new onset hypertension in this cohort of Indian patients with rheumatic diseases. No thromboembolic events were documented. [ABSTRACT FROM AUTHOR]

Aim: 1,25 dihydroxy vitamin D3 has immunomodulatory functions in rheumatoid arthritis (RA) and is an anti-osteoporotic agent. No studies exist to assess its pain-relieving action in RA. Methods: An open-labeled randomized trial comparing triple disease-modifying anti-rheumatic drug (DMARD) therapy and 500 IU 1,25 dihydroxy vitamin D3 + calcium combination versus triple DMARD and calcium alone was conducted. The primary outcome was the time to pain relief by patients' visual analogue scale (VAS). Changes in VAS after first achievement of pain relief and after 3 months were noted. 25 hydroxy-vitamin D levels were correlated with disease activity scor (DAS-28), adjusting for sun exposure. Comparisons between the groups were done by Mann-Whitney test and independent samples test. Results: Patients on the vitamin D group ( n = 59) had higher pain relief than the control group ( n = 62) (50% vs. 30%, P = 0.006). There was no significant difference in the time taken for initial pain relief between the two groups. Occurrence of hypovitaminosis D in RA patients (68.1%) is comparable to published normal Indian prevalence. There was no correlation between 25 hydroxy vitamin D levels and disease activity. Conclusions: Supplementation of 500 IU of 1,25 dihydroxy vitamin D3 daily to previously DMARD-naïve patients with early RA along with triple DMARD therapy results in a significantly higher pain relief at the end of 3 months. The number needed to treat for this additional pain relief was 5. The prevalence of vitamin D deficiency in the study population was 68.1%. [ABSTRACT FROM AUTHOR]

The objective of the study is to evaluate the outcome of patients with seronegative spondyloarthritis continuing on sulphasalazine (SSZ) and methotrexate (MTX) after a short course of infliximab. Patients with seronegative spondyloarthritis on MTX and SSZ were given short course of infliximab therapy at 0, 2, 6 and 14 weeks. Outcome of these patients while continuing on MTX and SSZ was assessed. Clinical features, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were noted at baseline (pre-infliximab), 1 month, 3 months and last follow-up after last dose of infliximab infusion. Twenty-four patients were included in this study. The mean duration of follow-up was 9.1 months. Statistically significant reduction in tender and swollen joint count was noted at all the three visits as compared to baseline. Fall in ESR and CRP was statistically significant at 1 and 3 months, but not at last follow-up. Mean reduction in BASDAI at 1 month ,3 month and last follow-up after last infliximab dose were 3.907 (95% CI 2.98-4.83; p < 0.001), 4.53 (95% CI 3.56-5.49; p < 0.001) and 2.48 (95% CI 1.12-3.84; p = 0.002), respectively. Mean reduction in BASFI at 1 month, 3 months and last follow-up after last infliximab dose were 4.13 (95% CI 3.23-5.04; p < 0.001), 4.34 (95% CI 2.8-5.88; p < 0.001) and 2.38 (95% CI 0.86-3.90; p = 0.005), respectively. Continuing SSZ and MTX after short course of infliximab results in sustained improvement in our patients with seronegative spondyloarthritis in India. [ABSTRACT FROM AUTHOR]

Mycophenolate mofetil (MMf) has recently been reported as a useful alternative immunosuppressive drug in autoimmune diseases. There is paucity of literature on its use in Takayasu's arteritis (TA). The aim of this study was to assess the safety and efficacy of MMf in Asian Indian patients with Takayasu's arteritis. Records of 21 consecutive patients with TA on treatment with oral MMF attending our centre from January 2005 to August 2008 were studied. The clinical, laboratory and angiography findings were noted and disease activity assessment was done using Indian Takayasu's arteritis activity score (ITAS) and physician's global observation score at baseline and last follow-up. Eleven patients were on steroids alone at baseline while ten patients had received azathioprine prior to administration of mycophenolate. The mean duration of follow-up on mycophenolate was 9.6 (±6.4) months. Nineteen patients (90%) received mycophenolate due to active disease, while in the other two patients, it was given to facilitate steroid tapering. Mycophenolate had to be discontinued in one patient due to skin rash. At the last visit, all the remaining 20 patients who continued mycophenolate had improvement in disease activity as evident by the drop in median ITAS [7 (range 0–19) versus 1 (range 0–7); p = 0.001]. A similar trend was noted in laboratory markers of inflammation with a reduction in mean Erythrocyte Sedimentation Rate (ESR) (68 ± 36.5 versus 43.2 ± 34 mm/first hour; p = 0.003) and mean C - Reactive protein (CRP) (31 ± 46.7 versus 17.3 ± 23.9 mg/L; p = 1.00). All patients received concomitant steroids, but there was a significant decrease in steroid dosage from 36 (±16) mg/day at baseline to 19 (±14) mg/day at last follow-up ( p < 0.001). This study is the largest series till date establishing the use of mycophenolate as a safe and effective steroid-sparing immunosuppressant in Takayasu's arteritis. [ABSTRACT FROM AUTHOR]

Ankylosing spondylitis (AS) is a chronic inflammatory disorder, characterized by an inflammatory enthesopathy progressing to ossification and ankylosis. Osteoporosis is a well-reported complication of AS. Bone loss begins early in the disease at the spine, and later progresses to the hip. This reduction in bone density leads to an increased risk of fractures. However, there is a lack of awareness regarding this common complication, thus adding to the morbidity associated with AS. Early recognition, appropriate assessment and timely treatment of this complication will help reduce the attendant fracture risk due to decreased bone mass. [ABSTRACT FROM AUTHOR]

The author discusses the potential of curcumin analogues and curcumin as alternative medicine in rheumatology. Topics include the use of curcumin-like diarypentanoid analog BDMC33 to overcome curcumin's poor pharmacokinetic properties, the benefits of curcumin in human rheumatoid arthritis, and the structural modifications made by curcumin analogs on curcumin's structural motif.

The authors reflect on the use of biological agents in people with rheumatoid arthritis (RA). They describe the advantages of taking this drug by RA patients. The authors cite a literature review which evaluates the effect of dose optimization on clinical response in infliximab treated RA patients. They note that some studies showed a potential role of biologics as induction therapy to achieve clinical remission in early RA patients.

The COVID-19 pandemic has put pressure on researchers around the world. In this Viewpoint, six rheumatology researchers at different career stages and from different regions discuss the difficulty of conducting research during the pandemic, and also reflect on how the pandemic has changed their attitudes towards research and their plans for the future. [ABSTRACT FROM AUTHOR]

The author reflects on the role of vitamin D in human nutrition. The author discusses the molecule of vitamin D which belongs to the class of secosteroids and its role as an immunomodulatory, anti-inflammatory, and antineoplastic agent. Meanwhile, the author highlights the emergence of studies about the role of vitamin D receptor (VDR) in the cause and effects of autoimmune diseases.

An introduction is presented in which the editor discusses articles in the issue on topics including vasculitis, Kawasaki's disease.

The article shares the experience of outgoing and incoming editor in chief of the journal including their role in the journal, efficiency and efficacy of publication processes, and focus on the work and scholarship.

The authors discuss genetic aspects of rheumatoid arthritis (RA), focusing on role of transcriptions and translations of genes in predisposition of the disease. They state significance of genome wide association studies (GWAS) related to RA, and mention risks associated with the insulin receptor substrate (IRS). They note role of single nucleotide polymorphisms as risk factor of the disease, and cite that promoter polymorphisms related mRNA expression may cause RA.

The article focuses on the impact of psoriasis and psoriatic arthritis on the quality of life of patients. Sleep disturbance has been found to be linked with generalized pain, anxiety, and levels of C-reactive protein and erythrocyte sedimentation rate in psoriatic arthritis patients. Biological treatments for psoriasis have caused more improvement in mental health than other therapies.

In this article, the author focuses on the need for diagnosing patients with chronic pain disorders like fibromyalgia, chronic fatigue syndrome and myofascial pain syndromes. It mentions painful disorders with anatomical lesions like inflammatory arthropathies, connective tissue diseases and osteoarthritis termed as secondary fibromyalgia. It states lack in awareness and deficiency in diagnostic skills amongst doctors including rheumatologists.

The author reflects on the heart complications cause by immune mediated inflammatory diseases (IMIDs) such as systemic autoimmune rheumatic diseases. He says that most studies show that progression of micro vascular dysfunction in IMIDs result to inflammation. He argues on the need for further studies on the prevalence and nature of heart complications.

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 18F-labeled fluoro-2-deoxyglucose (18F-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. [ABSTRACT FROM AUTHOR]

The author discusses the occurrence of lupus in Asia which are considered as common and different compared to the Western world while exploring the factors that contribute to variations in presentations and outcome of the disease.

Abstract: Anti‐Ro and anti‐La antibodies are important in pathogenesis and diagnosis of Sjögren's syndrome (SS). Ro60, Ro52 and La are RNA binding proteins of Y RNA, which were discovered more than three decades ago. Significance of Y RNA is not appreciated as much as Ro and La in SS. It can be hypothesised that 5′‐YsRNA, short fragment derived from Y RNA may be recognized by TLR7 in pDC, which induces type I interferon signature in SS. New genomics tools, namely RNA seq, enables assay of 5′‐YsRNA in blood. 5′‐YsRNA has the potential to be a novel biomarker of SS. [ABSTRACT FROM AUTHOR]

The article presents a letter from the editor-in-chief of the journal that invites volunteers to contribute in the journal's effort to bring more scientific research to readers.

The article presents a letter from the editor discussing the cost of open access publications.

The article focuses on the Asia Pacific League of Associations for Rheumatology (APLAR) which is celebrated its 50th anniversary in Bali, Indonesia in 2013. Topics discussed include the theme of the 2014 APLAR event which is sustainable rheumatology, the forming special interests groups (SIG), and collaboration of APLAR with all with all rheumatological international societies.

The article offers the author's insights on the conflict of interest in science research. Topics discussed by the author include the existence of competing ideas among science experts, the effect of the negative studies, and the rejection of high quality work in the peer review process. Other topics include the citation and the resultant impact factor as the most serious anomaly in publication.

The author emphasizes that collaboration is important for researchers in conducting studies.

The article discusses the progress and evolution of evidence-based medicine (EBM) practice. Topics include the basic science research that are driven by technology which strengthens the understanding of diseases, technological innovations, and the potential of comparative effectiveness trials (CET) as an alternative to randomized controlled trials (RCTs).

The article offers information regarding the journal including its role for Asia Pacific League of Associations for Rheumatology (APLAR), its priorities and commitment for faster review process of updated articles for rheumatology, and a preview for its upcoming issues in 2014.

Objective: Colchicine, an approved treatment for gout, has been trialed in many diseases including osteoarthritis (OA) due to its anti-inflammatory effects. However, its efficacy and safety remain unclear in OA. This systematic review and meta-analysis evaluated the efficacy and safety of colchicine for the treatment of OA. Methods: PubMed, Web of Science, Scopus, and Cochrane Central were searched from inception through September 2022. Two reviewers independently screened for randomized controlled trials (RCTs) comparing colchicine with placebo or other active comparators for the treatment of OA (knee, hand, or hip OA), extracted data, and performed Cochrane risk of bias assessments. Result: Nine RCTs for the knee OA and one for the hand OA were identified, consisting of 847 patients (429 in colchicine arms, 409 in control arms). The studies were conducted between 2002 and 2021 with follow-up periods ranging from 2 to 12 months, in India, Iran, Turkey, Australia, Singapore, and Iraq. Moderate-quality evidence showed no clinically important pain reduction with colchicine compared to control (standardized mean difference [SMD], 0.17; 95% confidence interval [CI], − 0.55, 0.22). Moderate-quality evidence showed no improvement in function with colchicine compared to control in knee OA patients (SMD, − 0.37; 95% CI, − 0.87, 0.13). Colchicine showed an acceptable safety profile with AEs/SAEs comparable to control. Conclusion: Current evidence does not suggest a benefit of colchicine in reducing pain and improving physical function in the overall cohort of hand/knee OA patients. Future trials should focus on the subgroups of OA patients with local or systemic inflammation and/or mineralization who might benefit from colchicine. Key Points •Colchicine is an approved treatment for gout that has been trialed in many diseases including osteoarthritis (OA) due to its anti-inflammatory effects. However, the benefit and harms of colchicine in OA remain unclear. • Current evidence from randomized control trials does not suggest a benefit of colchicine in reducing pain and improving physical function for the treatment of OA patients. • Future trials of colchicine in OA should focus on the subgroups of OA patients with local or systemic inflammation and/or mineralization who might benefit from colchicine. [ABSTRACT FROM AUTHOR]

Objectives To correlate magnetic resonance imaging ( MRI) assessment of disease activity in patients with Takayasu's arteritis with the Indian Takayasu's activity score ( ITAS). Design, Materials and Methods We prospectively assessed 20 patients with Takayasu's arteritis from November 2010 to September 2011. Results We found a statistically significant association between MRI assessment of disease activity and ITAS with a P-value of 0.01. The MRI features suggesting active disease included wall thickening and enhancement. We also analyzed the association between MRI and clinical assessment which was also statistically significant at P = 0.037. Conclusion Our study suggests that there is an association between MRI assessment of disease activity and the ITAS. MRI evaluation of disease activity of Takayasu's arteritis therefore goes hand in hand with ITAS 2010, ITAS - A, erythrocyte sedimentation rate and C-reactive protein. However this needs further investigation from future studies using serial assessments. [ABSTRACT FROM AUTHOR]

Pulmonary hypertension ( PH) is a relatively commoner complication of systemic sclerosis ( SSc) with estimated prevalence ranging between 8% and 12% as compared to much lower figures in other connective tissue diseases ( CTD). It is a major cause of morbidity and mortality in CTDs. PH is classified into five major groups. CTD-associated PH belongs to group 1 PH, also known as pulmonary arterial hypertension ( PAH). Around 30% of scleroderma-related deaths are due to PAH. Underlying pathogenesis is related to pulmonary vasculopathy involving small vessels. The Evidence-based Detection of Pulmonary Arterial Hypertension in Systemic sclerosis ( DETECT) algorithm outperforms the current European Society of Cardiology/European Respiratory Society guidelines as a screening tool in SSc- PAH; it can, therefore, suggest when to refer a patient for right heart catheterization. CTD- PAH patients constitute at least 20% of patients included in all major trials of PH-specific therapy and the results are comparable to those of idiopathic PAH. The role of anticoagulation in CTD- PAH is associated with a high risk-benefit ratio with the caveat of its potential role in those with severe disease. There appears to be no role of immunosuppression in scleroderma- PAH; however, immunosuppressive agents, namely the combination of glucocorticoids and pulse cyclophosphamide / possibly mycophenolate, may result in clinical improvement in a subset of patients with systemic lupus erythematosus and mixed connective tissue disease-related PAH. [ABSTRACT FROM AUTHOR]

The status of vascular lesion treatment using percutaneous intervention (PI) in Takayasu arteritis (TAK) remains unresolved. This study sought to develop PI strategies appropriate for TAK. A prospectively maintained single-center database of TAK PI procedures from 1996 to 2022 was analyzed retrospectively. Obstructive lesions were treated by elective stenting (using bare or covered stents), balloon angioplasty (BA), or cutting-balloon angioplasty (CBA), with adjunctive stenting for suboptimal BA or CBA results. PIs were repeated in restenotic lesions until sustained success was obtained. Aortic or peripheral aneurysms and spontaneous aortic dissections were treated with covered stents or endografts. Immunosuppressive therapy, started before PI, was continued long term. A total of 942 patients underwent PI to treat 2,450 arterial lesions (2,365 stenoses or occlusions, 85 aneurysms or dissections) in 630 subclavian or axillary, 586 renal, 463 aortic, 333 carotid, 188 mesenteric, 116 iliac, 71 coronary, and 63 other arteries; 3,805 PIs were performed (1.55 PIs per lesion; range 1-7 PIs per lesion). Early success was obtained in 2,262 (92.3%), and late success in 1,460 (84.5%) of 1,727 lesions with a median of 39 months (IQR: 15-85 months) of follow-up. Repeated PIs increased late success in obstructive lesions from 48.6% to 83.3%. A total of 1,687 elective stenting lesions achieved 88% late success with 1.49 PIs per lesion; covered stents (1.18 PIs per lesion) restenosed less than bare stents (1.51 PIs per lesion; P < 0.001). A total of 183 (36%) of 513 BA-treated lesions had good outcomes without adjunctive stenting; 122 CBA-treated lesions had 19% dissections and 8% ruptures or pseudoaneurysm formations. Aneurysms or dissections had 91.3% late success after PI. A total of 472 complications occurred in 415 (17%) lesions; 375 (79%) were resolved. Most vascular lesions in TAK can be effectively, safely, and durably treated using predominantly stent-based PI strategies. [Display omitted] [ABSTRACT FROM AUTHOR]

Introduction: Buerger’s disease is an unclassifiable vasculitis of the small and medium-sized distal arteries and superficial veins. BVAS (Birmingham Vasculitis Activity Score) is a validated disease activity index for vasculitis of different types. DEI.Tak (Disease Extent Index. Takayasu’s arteritis) scoring system is a validated disease extent Index used for Takayasu arteritis. Aim: The aim of this study was to assess outcome in patients with Buerger’s disease using various clinical features, laboratory parameters, BVAS and DEI.Tak scoring system. Materials and Methods: Case records of 136 patients diagnosed with Buerger’s disease in our hospital between August 1996 and July 2006 were studied retrospectively. Various clinical features (smoking history, claudication pain, loss of pulse), laboratory parameters, treatment modalities and outcome measures were recorded in a defined proforma. BVAS and DEI.Tak scoring was done using the data from medical records documented during the patients’ last visit to the hospital. Outcome of any patient requiring amputation was considered as bad outcome. Others, who could be managed by antiplatelet drugs, sympathectomy and revascularization procedures without any amputation were classified within the good outcome subset. Statistical analysis was done using Chi-square test and Non parametric Mann- Whitney test was performed to correlate outcome with all the recorded parameters including those embedded in BVAS and DEI.Tak scoring systems. Results: Sixty eight patients were in each group, namely the good outcome and bad outcome subsets. The mean BVAS score were 10.29±1.26 and 10.88±2.57 and mean DEI.Tak score were 5.29±1.75 and 7.93±2.43 and these scores were observed to be significantly different (p=0.038, p=0.014 respectively) among the good outcome subsets and bad outcome patients with respectively. Proportion of patients with claudication pain and absent upper limb pulse were observed significantly higher in the bad outcome group. Conclusion: Buerger’s disease with higher DEI.Tak score has significantly higher risk of bad outcome. DEI.Tak score can be used as an important predictor of outcome in Buerger’s disease. [ABSTRACT FROM AUTHOR]

Objective: To develop and validate new classification criteria for Takayasu arteritis (TAK). Methods: Patients with vasculitis or comparator diseases were recruited into an international cohort. The study proceeded in 6 phases: 1) identification of candidate criteria items, 2) collection of candidate items present at diagnosis, 3) expert panel review of cases, 4) data‐driven reduction of candidate items, 5) derivation of a points‐based classification score in a development data set, and 6) validation in an independent data set. Results: The development data set consisted of 316 cases of TAK and 323 comparators. The validation data set consisted of an additional 146 cases of TAK and 127 comparators. Age ≤60 years at diagnosis and imaging evidence of large‐vessel vasculitis were absolute requirements to classify a patient as having TAK. The final criteria items and weights were as follows: female sex (+1), angina (+2), limb claudication (+2), arterial bruit (+2), reduced upper extremity pulse (+2), reduced pulse or tenderness of a carotid artery (+2), blood pressure difference between arms of ≥20 mm Hg (+1), number of affected arterial territories (+1 to +3), paired artery involvement (+1), and abdominal aorta plus renal or mesenteric involvement (+3). A patient could be classified as having TAK with a cumulative score of ≥5 points. When these criteria were tested in the validation data set, the model area under the curve was 0.97 (95% confidence interval [95% CI] 0.94–0.99) with a sensitivity of 93.8% (95% CI 88.6–97.1%) and specificity of 99.2% (95% CI 96.7–100.0%). Conclusion: The 2022 American College of Rheumatology/EULAR classification criteria for TAK are now validated for use in research. [ABSTRACT FROM AUTHOR]