Severe Thrombocytopenia in COVID-19: A Conundrum in Dengue-endemic Areas.

Thrombocytopenia in coronavirus disease-2019 (COVID-19) can be attributed to multiple factors. Most often it is disease related. It is usually mild and if severe often associated with severe COVID-19 disease. It can also be due to drugs (Remdesivir, Tocilizumab) or coinfection with other viruses. Here we report two cases of severe thrombocytopenia in COVID-19 due to dengue coinfection. Most often the thrombocytopenia in dengue is self-resolving, and a careful "wait and watch" should suffice unlike COVID-19, where steroids can help if the cytopenia is due to cytokine storm or immune-mediated effects. HOW TO CITE THIS ARTICLE: Adarsh MB, Abraham A, Kavitha P, Nandakumar MM, Vaman RS. Severe Thrombocytopenia in COVID-19: A Conundrum in Dengue-endemic Areas. Indian J Crit Care Med 2021;25(4):465-466.

Tuberculosis in Children with Rheumatic Diseases Treated with Biologic Disease-Modifying Anti-Rheumatic Drugs.

Chronic rheumatic diseases entail the use of biologics in children. Immunosuppressive effects of drug therapy put children at risk of various infections including tuberculosis (TB). Even though TB is a major concern among individuals on biological DMARDs, the incidence and distribution among children on these drugs is not known. Hence, we performed a literature search to ascertain the prevalence of tuberculosis amongst children with rheumatic disorders treated with biological agents. Articles available on MEDLINE and SCOPUS published on or after January 1, 2010 to 1 October 2019 were reviewed and collated. We found that published data on TB infections in children with rheumatic disorders on biologics is scant even from regions with highest TB burden. Tuberculosis was reported on occasion (0-5 cases per country) in the developed world with most reports being from Turkey. While most of the retrospective studies suggest that TB risk is minimal in the paediatric rheumatology patients, prospective studies suffer from a short observation period. Most registries focus on response to therapy rather than complications. In this review we have then discussed about the variation in screening strategies for latent TB and the role of bacille Calmette-Guerin (BCG) vaccination. Based on the dearth of data and inconsistency in data collection, we propose a way forward in the form of establishing well-designed long-term prospective national registries from countries with high background prevalence of TB with focus not only on treatment efficacy but also on adverse events and infections.

Cultural adaptation, translation and validation of Cochin Hand Function Scale and evaluation of hand dysfunction in systemic sclerosis.

OBJECTIVES: Hand dysfunction causes significant reduction in quality of life in systemic sclerosis. We assessed the validity and reliability of the culturally adapted Indian version of Cochin Hand Function Scale (I-CHFS). We determined the factors contributing to hand dysfunction and its burden on quality of life. METHOD: I-CHFS was formulated by replacing five questions (questions 7, 9, 10, 14 and 15) in CHFS which were determined as unsuitable in an Indian setting. The instrument was assessed for acceptability, reliability, reproducibility and validity measures. A total of 87 patients were assessed for various demographic and disease parameters, hand disability and quality of life. RESULTS: The median I-CHFS score was 22(5-54) and 04 (0.5-17.5) among diffuse (dcSSc) and limited cutaneous systemic sclerosis (lcSSc). I-CHFS showed good reproducibility (interclass correlation coefficient = 0.92) and a strong correlation with I-HAQ (rs = 0.832), usual activities EQ-5D-5L (rs = 0.744), self-care EQ-5D-5L (rs = 0.734) and anxiety/depression EQ-5D-5L (rs = 0.729). It had moderate correlation with pain/discomfort EQ-5D-5L (rs = 0.661) and hand HAQ (rs = 0.576) and poor correlation with HAQ-DI (rs = 0.396) and modified Rodnan skin score (rs = 0.390). Finger to table distance, finger to palm distance in extension and limited hand modified Rodnan skin score were significantly associated with higher values of I-CHFS. CONCLUSIONS: Hand dysfunction in systemic sclerosis is substantial and contributes significantly to poor quality of life. The culturally adapted I-CHFS is a valid and reliable tool to assess it and correlated well with the overall disease burden. Key Points • Hand dysfunction is common among systemic sclerosis patients. • Hand dysfunction contributes to the poor quality of life and more disease burden. • Culturally adapted Cochin Hand function Scale helps assess hand dysfunction among Indian scleroderma patients.

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

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.

Immunological biomarkers in neuropsychiatric systemic lupus erythematosus: a comparative cross-sectional study from a tertiary care center in South India.

INTRODUCTION: The prevalence of various immunological biomarkers in neuropsychiatric systemic lupus erythematosus (NPSLE) differs among various patients with varied neuropsychiatric manifestations and different populations. We studied the prevalence of these biomarkers; especially the neuron specific autoantibodies in patients with systemic lupus erythematosus (SLE) and compared them among patients with and without neuropsychiatric involvement. METHODOLOGY: This is a comparative cross-sectional study conducted in a tertiary care hospital in South India. The prevalence of immunological biomarkers including complement levels, systemic and brain specific autoantibodies (anti-myelin antibody, anti-myelin oligodendrocyte glycoprotein and anti-myelin-associated glycoprotein antibody) were assessed and compared among those with and without NPSLE and with different NPSLE manifestations. RESULTS: A total of 522 SLE patients were enrolled in the study. The mean age of the study participants was 28.5 ± 8.8 years and 93.5% were women. Neuropsychiatric manifestations were seen in 167 (32%) patients. Seizure was the most common neuropsychiatric manifestation seen in 41.3%, followed by psychosis (18.6%), mood disorder (16.8%), stroke (10.8%), mononeuropathy (10.2%), headache (9.6%), acute confusional state (6.6%) and aseptic meningitis (5.4%). Patients with NPSLE had a higher SLE disease activity index score. Most of the autoantibodies, that is anticardiolipin antibody (aCL), anti-ß2 glycoprotein 1 antibody (ß2GP1), lupus anticoagulant (LA), anti-nucleosome, anti-ribosomal P, anti-Ro52, anti-Ro60 and anti-La, were seen in higher proportion in the NPSLE group, although the difference failed to reach statistical significance. On subgroup analysis, psychosis was significantly higher in patients with anti-ribosomal P positivity than without (11.8% versus 4.1%, p.0.007; odds ratio (OR) 3.1, confidence interval (CI) 1.4-6.8), while stroke had a higher proportion among those with positive b2GP1 IgG (6.3% versus 1.8%, p.0.03; OR 3.6, CI 1.2-11.0). A higher proportion of demyelination was seen among the LA positive than the negative (10.3% versus 0.2%, p.0.03; OR 5.39, CI 1.15-24.17) and anti-myelin oligodendrocyte glycoprotein in mood disorder (14.3% versus 3.4%, p = 0.03; OR 4.66, CI 1.13-19.13). CONCLUSION: No single biomarker correlated with NPSLE. Among different NPSLE manifestations, the prevalence of IgG ß2GP1 in stroke, LA in demyelination, anti-ribosomal P in psychosis and anti-myelin oligodendrocyte glycoprotein in mood disorder were higher. Further studies on the pathogenic mechanisms underlying NPSLE and its different manifestations may help us to identify better biomarkers.

Effect of mycophenolate mofetil (MMF) on systemic sclerosis-related interstitial lung disease with mildly impaired lung function: a double-blind, placebo-controlled, randomized trial.

The efficacy and safety of mycophenolate mofetil (MMF) has been studied in patients with systemic sclerosis (SSc)-related interstitial lung disease (ILD) with moderate-severe impairment. There is no study on its use in patients with mildly impaired lung function. The objective of this study is to determine the efficacy and safety of MMF for treating mild SSc-ILD (forced vital capacity (FVC) ≥ 70% predicted). This was a double-blind, randomized, placebo-controlled pilot trial. The subjects with SSc-ILD with FVC ≥ 70% were randomized to receive either MMF (2 g/day) or placebo for 6 months. FVC, diffusing capacity of lungs for carbon monoxide (DLCO), modified Rodnan skin score (mRSS), Short Form-36 (SF36v2), Mahler's Dyspnoea Index (MDI), and 6-min walk distance (6MWD) were recorded at baseline and at 6 months. Forty-one subjects were included in the study (MMF: 20, placebo: 21). FVC decreased by a median of 2.7% (range - 21 to 9) in MMF arm and increased by 1% (range - 6 to 10) in placebo arm (p = 0.131). SF36v2 scores improved in both the groups. Median change in MDI (3 vs 3), DLCO (1% vs 1.5%), and 6MWD (0 m vs 0 m) was similar between the study groups. MMF was effective in improving mRSS (- 5 vs - 1, p = 0.045) compared to placebo. Adverse events occurred with similar frequency in both the study groups. In this pilot study, MMF did not result in significant improvement in lung function in SSc-ILD with minimally impaired lung function, but was effective in reducing the skin tightness. Larger studies are needed to confirm these findings. This study was registered at ClinicalTrials.gov (NCT02896205).

Methotrexate in Early Chikungunya Arthritis: A 6 Month Randomized Controlled Open-label Trial.

OBJECTIVE: Evidence for treating chikungunya arthritis early in the course of illness is scarce. This study assesses the efficacy of Methotrexate in early Chikungunya arthritis. METHODS: It is a randomized controlled open-label assessor-blinded trial with a crossover design. Sixty patients with persistent post chikungunya arthritis with at least 3 or more tender or swollen joints (28 joint count) were recruited. MTX arm was given oral Methotrexate and NSAID arm was given NSAIDs (Naproxen 1 gm/day or Etoricoxib 120 mg/day). Patients were followed at 1, 2, 4 and 6 months. After 2 months patients in NSAID arm who have not achieved remission were given MTX. The primary endpoint was remission (no tender or swollen joints by 28 joint count) at 6 months. Secondary endpoints were change in CDAI, Indian HAQ, total steroid use, total NSAID use, and serious adverse effects. Intention to treat analysis was used. RESULTS: TJC, SJC, CDAI and HAQ were matched between two at baseline. Remission was achieved by 28 patients (93%, CI- 78%-98%) in the NSAID arm and 26 patients (86%, CI-70%- 94%) in MTX arm (p=0.18). There was no significant difference in steroid need, change in HAQ, CDAI, TJC or SJC. Those who have not achieved remission had higher disease activity at baseline. CONCLUSION: A protocol-based approach with steroid and NSAIDs helped to achieve remission in most patients with early subacute phase of post-Chikungunya arthritis and the effect was comparable to that of early initiation of methotrexate.

Esophageal manometry, esophagogastroduodenoscopy, and duodenal mucosal histopathology in systemic sclerosis.

BACKGROUND AND AIM: Systemic sclerosis (SSc) is known to involve the gastrointestinal (GI) tract, resulting in dysmotility, gastroesophageal reflux disease, and mucosal changes causing significant morbidity. The study aimed to assess esophageal motility and duodenal mucosal changes in SSc. METHODS: This is a prospective, cross-sectional, single-center study of 23 patients with SSc diagnosed on the basis of standard criteria. Clinical details including the GI symptoms were recorded. All of them underwent esophagogastroduodenoscopy with duodenal biopsy, and 21 underwent esophageal manometry. RESULTS: Regurgitation, heartburn, and dysphagia were seen in 19 (82%), 16 (69%), and 10 (43%) patients, respectively. On endoscopy, 19 patients (83%) showed changes of reflux esophagitis (4 had grade C esophagitis), and 3 had esophageal candidiasis. Of the 21 patients who underwent esophageal manometry, 13 (62%) had absent peristalsis, 6 (28%) had ineffective peristalsis, and 10 (48%) had hypotensive lower esophageal sphincter (LES). Duodenal biopsy showed partial villous atrophy in 9 (39%) patients, increased intraepithelial lymphocytes in 18 (78%), and excess of mononuclear inflammatory cells in lamina propria in 21 (91%). Partial villous atrophy was seen more commonly in those with abnormal esophageal peristalsis and a hypotensive LES. CONCLUSION: Most of the patients with SSc had esophageal dysmotility in the form of absent peristalsis, ineffective esophageal peristalsis, and hypotensive LES. Histology of descending duodenum demonstrated partial villous atrophy and chronic inflammatory infiltrates in most of the patients with SSc.

Corticosteroid-associated lupus pancreatitis: a case series and systematic review of the literature.

BACKGROUND: Acute pancreatitis is an uncommon complication that occurs in 0.85% to 4% of patients with systemic lupus erythematosus (SLE). In some patients, it occurs within days to weeks of starting medium-to-high dose corticosteroids. The authors have used the term 'corticosteroid-associated lupus pancreatitis' for these patients, and they report a case series and perform a systematic review of previously published reports. METHODS: For the purpose of this study, corticosteroid-associated lupus pancreatitis was defined as occurrence of acute pancreatitis in patients with SLE (fulfilling the 1997 ACR), within 3 weeks of starting therapy with medium-to-high dose corticosteroids - either newly initiated or escalated from a lower dose. All patients with SLE admitted in the last 2.5 years in a North Indian university hospital were reviewed, and those with pancreatitis who fulfilled the above criteria were included in the case series. For the systematic review, a PUBMED search using the keywords 'lupus' and 'pancreatitis' was performed, and reports in English were reviewed for an association with corticosteroids. RESULTS: Among 420 admissions of SLE patients, six patients (1.4%) fulfilled criteria for corticosteroid-associated lupus pancreatitis. All were female, with mean age and disease duration of 19.7 ± 3.3 and 3.8 ± 2.5 years respectively. All had active disease and developed acute pancreatitis within 48-72 hours of newly initiating medium-to-high dose corticosteroids (in three patients) or escalating them to medium-high dose (in three patients). After the development of pancreatitis, corticosteroids were continued in all except one patient. In addition, two patients received pulse methylprednisolone, two received pulse cyclophosphamide and one was started on azathioprine. Three patients died during hospitalization, all with severe pancreatitis. On systematic review, among 451 cases of lupus pancreatitis reported, 23 (5%) fulfilled criteria for 'corticosteroid-associated lupus pancreatitis'. A majority of them had pancreatitis within 3 days of starting treatment with medium-to-high dose corticosteroids. The mortality in these patients was 37.5%. CONCLUSION: In a small but substantial proportion of patients with lupus who develop pancreatitis, it occurs within days to weeks of starting medium-to-high dose corticosteroids. Many of these patients continue to receive corticosteroids, and some receive more aggressive immunosuppression. However, they have significant mortality, and further studies are required to identify appropriate treatment in this subgroup of patients.

Gastrointestinal Dysmotility and Infections in Systemic Sclerosis- An Indian Scenario.

INTRODUCTION: Systemic Sclerosis is known to involve the gastrointestinal system and can lead to multitude of problems predominantly affecting the GI motility. METHODS: It was a prospective, observational, single centre study of fifty consecutive patients with SSc who presented to rheumatology clinic. Gut score was assessed using UCLA SCTC GIT 2.0 questionnaire. 35 patients underwent esophago- gastro duodenoscopy(UGIE), 31 underwent esophageal manometry, 37 underwent lactulose breath test to assess orocaecal transit time (OCTT) and glucose breath test for detecting small intestinal bacterial overgrowth (SIBO) and 36 underwent gastric emptying scintigraphy to measure gastric emptying time. RESULTS: GI involvement was seen in 98% of patients, with most common symptom being regurgitation (78%). Mean T score of the GUT score was 0.60±0.27. In UGIE, esophagitis was seen in 30, of which 3 had candidiasis and 1 had HSV esophagitis. Hiatus hernia was noted in 10 patients. Mean lower esophageal sphincter pressure was 16.1± 12.7 mmHg with hypotensive sphincture in twelve patients. Esophageal peristaltic abnormalities were observed in 28(90%) patients. Gastric emptying was delayed in10/36 patients. OCTT was prolonged in 23/ 37 patients whereas SIBO was noted in 7/37. CONCLUSION: GI involvement is common in SSc with esophagus being most commonly affected. Motility abnormalities make them prone for super added infections especially infectious esophagitis and SIBO and should be investigated for early detection and treatment.

Not all febrile critical illness with rash is infective: Drug reaction may be a mimic.

We report a case of ciprofloxacin-related drug rash with eosinophilia and systemic symptoms (DRESS) which was initially diagnosed and managed on the line of tropical fever. Later, a diagnosis of definite case of DRESS was made according to the RegiSCAR scoring system and the patient was managed with the removal of ciprofloxacin along with steroids. DRESS is a great masquerader. The diagnosis should be highly suspected in the presence of fever, skin rash, liver involvement, and hypereosinophilia.