The pathogenesis of scleroderma

Systemic sclerosis (SSc) results from the complex interplay between the immune system, vasculature and tissue-repair mechanisms. Endothelial injury is the prime event; environmental triggers in the susceptible individual trigger the pathologic process, which translates into fibrosis. The outcome of SSc is not as bleak as it looked a couple of decades ago. With a greater understanding of older pathways, as well as elucidation of newer ones, the potential targets to block and even reverse fibrosis bring around a revolution in the way we look at this once dreaded disease

Recent evidence comparing combination of conventional synthetic disease-modifying antirheumatic drugs with biologic disease-modifying antirheumatic drugs in rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic, disabling inflammatory arthritis often treated with a variety of disease-modifying antirheumatic drugs (DMARDs), whether conventional synthetic DMARDs (csDMARDs), targeted synthetic DMARDs (tsDMARDs), or biological DMARDs (bDMARDs). Most patients with RA are seropositive, have significant disease activity at presentation to the Rheumatologist and may have erosions at the time of diagnosis, all of which are poor prognostic factors. Patients with RA are often initially started on methotrexate (MTX), with addition of other DMARDs, the usual practice in the event of failure of/suboptimal response to MTX monotherapy. Since the recent guidelines by the European League against Rheumatism favor the use of bDMARDs over the combination of csDMARDs following the failure of MTX monotherapy in patients with such poor prognostic factors, we decided to review the recent literature comparing combination csDMARDs with bDMARDs. Long-term follow-up of landmark trials such as the Behandel-Strategieëen study (10 years) and NEO-RACo study (5 years) as well as other trials supports similar efficacy of both strategies in terms of clinical and functional outcomes. Whereas some studies have shown a minor but statistically significant progression of radiographic damage in those receiving combination of csDMARDs versus those on bDMARDs, others have not, further confirmed in a recent meta-analysis. Thus, keeping in mind, the similar efficacy and better cost-effectiveness of combination of csDMARDs, this should be the preferred strategy following failure of MTX monotherapy. bDMARDs should be reserved when combination csDMARDs fail, especially in an Indian scenario where most patients are poor and a majority of healthcare is not government-sponsored

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

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

Dihydropyrimidine dehydrogenase mutation in neoadjuvant chemotherapy in head and neck cancers: Myth or reality?

Purpose: The docetaxel, 5-fluorouracil (5-FU), and cisplatin (TPF) regimen in India is associated with high percentages of Grade 3-4 toxicity. This analysis was planned to evaluate the incidence of dihydropyrimidine dehydrogenase (DPD) mutation in patients with severe gastrointestinal toxicity, to assess whether the mutation could be predicted by a set of clinical criteria and whether it has any impact on postneoadjuvant chemotherapy response. Methods: All consecutive patients who received TPF regimen in head and neck cancers between January 2015 and April 2015 were selected. Patients who had predefined set of toxicities in Cycle 1 were selected for DPD mutation testing. Depending on the results, C2 doses were modified. Postcompletion of two cycles, patients underwent radiological response assessment. Descriptive statistics has been performed. The normally distributed continuous variables were compared by unpaired Student′s t-test, whereas variables which were not normally distributed by Wilcoxon sum rank test. For noncontinuous variables, comparison was performed by Fisher′s exact test. Results: Out of 34 patients, who received TPF, 12 were selected for DPD testing, and 11 (32.4%, 95% confidence interval [95% CI]: 19.1-49.3%) had DPD mutation. The predictive accuracy of the criteria for the tested DPD mutations was 81.3% (95% CI: 62.1-100%). Of the 11 DPD mutation positive patients, except for one patient, all others received the second cycle of TPF. The dose adjustments done in 5-FU were 50% dose reduction in 9 patients and no dose reduction in one patient. The response rate in DPD mutated patients was 27.3% (3/11) and that in DPD nonmutated/nontested was 39.1% (9/23) (P = 0.70). Conclusion: In this small study, it seems that the incidence of DPD mutation is more common in Indian then it′s in the Caucasian population. Clinical toxicity criteria can accurately predict for DPD mutation. Postdose adjustments of 5-FU from C2 onward, TPF can safely be delivered in the majority of patients with DPD heterozygous mutations without decrement in efficacy

Juvenile Reactive Arthritis and other Spondyloarthritides of Childhood:A 28-year Experience from India

OBJECTIVES: Understanding of Juvenile reactive arthritis (jReA) and other spondyloarthritides of childhood (jSpA) is limited to small case series. Since most of them have speculated pathogenic origins in the gut, we compared and contrasted jReA with other jSpA -Enthesitis-related arthritis (ERA) and undifferentiated SpA (jUSpA). METHODS: A record-based medical data review of jReA, and jUSpA was compared with cohort data of ERA collected for other studies. Data are presented as median (interquartile range) and non-parametric tests used for analysis. RESULTS: Of 179 juvenile SpA (61 jReA; 101 ERA; and 17 jUSpA), 61 had jReA [M:F-52:9; 15.5 (12–18) years] with a disease duration of 2.75(1–36) months. Inflammatory backache IBP (32%), dactylitis (21%) and enthesitis (29%) were common. A significant proportion (14 of 17, 82.3% at >6 months follow-up) had a chronic course. 101 ERA [M:F-93:7; age-16(14–20) years] had a longer disease duration (45 vs 2.75 months, p<0.001), as compared with jReA. Enthesitis and IBP was more common in ERA (OR-2.3 and 3.4 respectively). jUSpA (n=17) had a similar clinico-laboratory profile and exhibited significant (7 of 17, 58.3%) chronicity over 9.5(4.8–37) months follow-up. CONCLUSION: jReA and jSpA exhibit similar features apart from varying disease duration, suggesting that jspA may form a continuum with similar clinico-laboratory profiles plausibly due to shared pathogenesis