Examining the clinical and radiological landscape of rhupus: navigating the challenges in disease classification.

Rhupus, in the broad sense, refers to an overlap between rheumatoid arthritis (RA) and lupus. However, there is a paucity of data on the appropriate diagnostic/classification criteria that should be used to define rhupus. Hence, we undertook this narrative review to analyze the clinical characteristics, radiology, and treatment with a focus on diagnostic challenges and defining features of rhupus. The databases of Medline/PubMed, Scopus, and DOAJ were searched for relevant articles using the following keywords: ("Rhupus"), ("lupus" AND "erosive" AND "arthritis"), and ("lupus" AND "rheumatoid arthritis" AND "overlap"). Studies have used a variety of classification criteria for rhupus of which a combination of the latest classification criteria for RA and lupus along with positive anti-cyclic citrullinated peptide, anti-Smith, and anti-dsDNA antibodies seem most relevant. The majority of rhupus cohorts report the onset of the disease as RA (two-thirds of rhupus patients) followed by the development of features of lupus at an average interval of 3-11.3 years. The radiographic features and distribution of erosions are similar to RA. However, ultrasonography and MRI reveal erosions in pure lupus related arthritis as well. This makes the reliability of radiologic tools for the evaluation of rhupus supportive at the most. Extra-articular features in rhupus are mild with major organ involvement in the form of neuropsychiatric lupus and lupus nephritis being rare. We have further discussed the fallacies of the various classification criteria and proposed a theme for classifying rhupus which needs to be tested and validated in future studies. Our current state of understanding supports rhupus as an overlap of SLE and RA with articular disease similar to RA with the extra-articular disease being milder than SLE. Developing standardized classification criteria for rhupus will help in the early diagnosis and prevention of articular damage in patients with rhupus.

Gastrointestinal Manifestations in Systemic Lupus Erythematosus: Data from an Indian Multi-institutional Inception (INSPIRE) Cohort.

OBJECTIVES: To study the prevalence, correlates, and outcomes of GI manifestations in a prospectively enrolled nationwide cohort of SLE in India (INSPIRE). METHODS: It is an observational cohort study with analysis of the baseline database of the INSPIRE cohort with early outcomes assessed till April 10, 2023. Cases with GI manifestations as per the BILAG index were selected, pertinent clinical and laboratory data were retrieved for analysis. Patients with GI manifestations were compared with the rest of the cohort and factors associated with death were determined. RESULTS: Of the 2503 patients with SLE enrolled in the INSPIRE cohort, 243(9.7%) had GI manifestations observed early in the disease course(1,0-3 months). Ascites(162,6.5%), followed by enteritis(41,1.6%), pancreatitis(35,1.4%) and hepatitis(24,0.9%) were the most prevalent manifestations.All patients received immunosuppressive therapy, and four patients required surgery. Twenty-nine patients died(11.9%), with uncontrolled disease activity(17,58.6%) and infection(6,20.7%) accounting for the majority of deaths. Low socioeconomic class[lower(Hazard Ratio (95% Confidence intervals- CI) 2.8(1.1-7.9); upper lower 7.5(2-27.7); reference as upper class] and SLEDAI 2K[1.06(1.02-1.11)] were associated with death in the GI group.GI manifestations were significantly associated with age[Odds Ratio & 95% CI 0.97(0.96-0.99)], pleural effusion[4.9(3.6-6.7)], thrombocytopenia[1.7(1.2-2.4)], myositis[1.7(1.1-2.7)], albumin[0.7(0.5-0.8)], alkaline phosphatase(ALP)[1.01(1.0-1.002)], low C3[1.9(1.3-2.5)], total bilirubin[1.2(1.03-1.3)], alopecia[0.62(0.5-0.96], elevated anti-dsDNA[0.5(0.4-0.8)], and anti-U1RNP antibody[0.8(0.5-0.7)] in model one; and age[0.97(0.96-0.99)], creatinine[1.2(1.03-1.4)], total bilirubin[1.2(1.03-1.3)], ALP[1.01(1.0-1.002)], albumin[0.6(0.5-0.7)], andanti-U1RNP antibody[0.6(0.5-0.8)] in model two in multivariate analysis compared with patients without GI features. The mortality was higher in the GI group(11.9% and 6.6%, p= 0.01) as compared with controls. CONCLUSION: GI manifestations were observed in 9.7% of the cohort and were always associated with systemic disease activity and had higher mortality.

Diagnostic accuracy of antineutrophil cytoplasmic antibodies (ANCA) in predicting relapses of ANCA-associated vasculitis: systematic review and meta-analysis.

Relapse in antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) is associated with significant morbidity and mortality. Utility of ANCA for prediction of relapses is still controversial. PubMed/MEDLINE, Scopus, and WebOfScience were searched, screened and confirmed for inclusion [PROSPERO No: CRD42020220308]. Studies measuring serial ANCA by ELISA or indirect immunofluorescence (IF), reporting relapses with sufficient data to calculate sensitivity and specificity were included. Diagnostic odds ratio (OR), sensitivity, specificity and likelihood ratios (LR) were synthesized using a bivariate mixed-effect regression model. Sub-group analysis included a comparison between ELISA and IIF, anti-myeloperoxidase (MPO) and -proteinase 3(PR3), and type of rise in ANCA. For meta-analysis of survival outcomes, hazard ratios were synthesized using a random-effect model. QUADAS-2 was used for assessing quality of studies, I2 statistic for heterogeneity Begg's test for publication bias. 2946 abstracts and 43 full-texts were reviewed to identify 26 eligible studies that included 2623 patients with AAV and 848 relapses. Overall heterogeneity was high [I2 = 99%] and the overall risk of bias was low to moderate. ANCA positivity by either ELISA or immunofluorescence for predicting relapse of AAV had a sensitivity of 0.70(95% CI 0.58-0.81), specificity of 0.66(0.55-0.76), positive LR of 2.1(1.6-42.7) and negative LR of 0.44(0.30-0.60). ELISA performed marginally better [OR: 5(3-7)] than IIF [OR: 4(2-9)] with similar sensitivity, specificity, PLR and NLR. The area under the curve for PR3 was 0.74(0.7-0.77), while that for MPO was not computed as the number of eligible studies was only three. In the survival analysis, the hazard ratio for relapse was 3.11(1.7-5.65). The meta-analysis shows modest accuracy of ANCA in predicting relapses of ANCA vasculitis and supports the use of serial ANCA monitoring as a biomarker for relapse.

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

To study the prevalence and predictors of calcinosis in Juvenile Dermatomyositis (JDM). Medical records over 20 years at a tertiary care rheumatology center in Northern India were reviewed to identify patients with JDM and clinical details were recorded. The frequency of calcinosis, predictors, specific treatment, and its outcomes were studied. Data are expressed as median and interquartile range. In eighty-six patients (median age 10) of JDM, the frequency of calcinosis was 18.2% (8.5% at presentation). Younger age at presentation, longer follow-up, heliotrope rash [Odds Ratio (95% confidence interval), 11.4 (1.4-92.12)], chronic or polycyclic course [4.4 (1.2-15.5)] and cyclophosphamide use [8.2 (1.6-41.9)] were associated with calcinosis. Dysphagia [0.14 (0.02-1.2)] and elevated muscle enzymes [0.14 (0.04-0.5)] were negatively associated with calcinosis. Treatment with pamidronate had a good to moderate response to calcinosis in five of seven children. Calcinosis in JDM is associated with long-standing, poorly controlled disease, and the use of bisphosphonates like pamidronate offer promise in the future for its treatment.

Effects of the second dose of COVID-19 vaccines in patients with autoimmune rheumatic diseases with hybrid immunity.

Patients with autoimmune rheumatic diseases with a previous infection by the SARS-CoV-2 virus have exaggerated responses to a single dose of COVID-19 vaccination as compared to fully vaccinated infection naive patients. The second dose is currently recommended at an extended gap after the infection, but the information available regarding response to the second dose in this subgroup is limited. Patients with AIRDs previously infected with COVID-19, who have received at least one dose of AZD1222/ChAdOx1 (n = 200) were included and stratified based on vaccine doses (V), and infection (I) into I + V, I + V + V, V + I, V + V + I. Anti-RBD (receptor binding domain) antibodies were compared across the four groups. In 49 patients of the I + V + V group (AZD12222), paired sera were compared for antibody levels and neutralization after each vaccine dose. Thirty patients with hybrid immunity after BBV152 and 25 with complete vaccination without infection were included as controls. The highest anti-RBD antibody levels were observed in the V + V + I group (18,219 ± 7702 IU/ml) with statistically similar titers in the I + V + V (10,392 ± 8514 IU/ml) and the I + V (8801 ± 8122 IU/ml). This was confirmed in the 49 paired samples that paradoxically showed a lowering of antibody titers after the second dose [9626 (IQR: 4575-18,785)-5781 (2484-11,906); p < 0.001]. Neutralization of the Delta variant was unaffected but Omicron neutralization was significantly reduced after the second dose [45.7 (5.3-86.53)-35% (7.3-70.9); p = 0.028]. Ancillary analyses showed that only the hybrid immune sera could neutralize the Omicron variant and AZD1222 hybrids performed better than BBV152 hybrids. The second dose of AZD1222 did not boost antibody titers in patients with RD who had COVID-19 previously. In the analysis of paired sera, the second dose led to a statistically significant reduction in antibody titers and also reduced neutralization of the Omicron variant.

Correlates of breakthrough Omicron (B.1.1.529) infections in a prospective cohort of vaccinated patients with rheumatic diseases.

BACKGROUND: Data on the effectiveness of SARS-CoV-2 vaccines and the durability of protection against the prevalent Omicron variant are scarce, especially in patients with autoimmune rheumatic diseases (AIRDs). Hence, we prospectively studied Omicron breakthrough infections in patients with AIRDs and attempted to isolate associated risk factors. METHODS: Patients with AIRDs who had completed primary vaccination with either AZD1222 or BBV152 vaccines were included and prospectively followed up from January 2022 onwards for the development of breakthrough Omicron infections. The time interval from the last event [2nd dose of vaccination (V) or past COVID-19 infection (I) whichever was later] to Omicron infection was recorded. Patients were divided based on the events and their order of occurrence into V + V, V + I, I + V, V + I + V, and V + V + I groups. The incidence of breakthrough infections and their predictors were studied with a focus on the vaccine type and hybrid (H) immunity (vaccinated individuals with a history of COVID-19 infection). RESULTS: We included 907 patients with AIRDs (53.5 ± 11.7 years and a male-to-female ratio of 1:5.1), and the majority of patients had received AZD1222 (755, 83.2%). Breakthrough infections were observed in 158 of 907(17.4%) of which 97 (10.4%) were confirmed by RT-PCR. Breakthrough infections were significantly greater in the V versus the H group (15.7% and 3.5%, log-rank test, p = < 0.01). Among the hybrid group, the order of infection and vaccination had no bearing on the risk of breakthrough infections. On multivariate analysis, breakthrough infections were significantly lesser in the H versus the V group [HR: 0.2(0.1-0.4); p = 0.01]. CONCLUSION: The risk of breakthrough Omicron infections in fully vaccinated patients with AIRDs was 17.4% with a significantly lower risk in patients with hybrid immunity.

Efficacy and safety of curcumin in maintaining remission during disease-modifying antirheumatic drug withdrawal in rheumatoid arthritis at 52 weeks: a phase III double-blind, randomized placebo-controlled trial.

Curcumin has anti-inflammatory properties but current evidence is limited to advocate its use in rheumatoid arthritis (RA). We explored whether curcumin could maintain remission in patients with RA while tapering conventional synthetic Disease-Modifying Antirheumatic Drugs (csDMARD). In this patient-and investigator-blinded trial, adults with RA in sustained remission for more than six months were randomized to oral curcumin (1 g) with piperine (5 mg) twice daily or matching placebo. Patients who had received biological DMARDs or curcumin supplements in the last 6 months were excluded. csDMARD were tapered and stopped sequentially as per a fixed protocol. The primary outcome was flare-free survival at 52 weeks. The secondary outcomes were flare rate, correlation of serum curcuminoid levels with flares and safety. 200 patients (100 per arm) entered the trial with comparable baseline characteristics. Per protocol analysis included 92 and 93 participants in the curcumin and the placebo group, respectively. Flare-free survival at week 52 was similar between both groups (60% versus 64%; p = 0.76). The median time to flare was similar [Curcumin: 219 days (IQR: 123) versus placebo: 214 days (95.8); p = 0.067]. Cox proportionate regression modelling showed that the flare-free survival was independent of serum curcuminoid levels [adjusted HR = 0.99 (95% CI: 0.97-1.0)]. The model showed that flare-free survival was not associated with age, gender, seropositivity, or csDMARD used at baseline. No serious adverse effects were noted. Curcumin did not impact the flare-free survival in patients with RA in remission during the tapering of csDMARDs despite achieving adequate serum levels.Trial registration: CTRI/2018/04/013279.

Ethics Committees: Structure, Roles, and Issues.

An Ethics Committee (EC) is an independent body composed of members with expertise in both scientific and nonscientific arenas which functions to ensure the protection of human rights and the well-being of research subjects based on six basic principles of autonomy, justice, beneficence, nonmaleficence, confidentiality, and honesty. MEDLINE, Scopus, and Directory of Open Access Journals were searched for studies relevant to this topic. This review is focused on the types of research articles that need EC approval, the submission process, and exemptions. It further highlights the constitution of ECs, their duties, the review process, and the assessment of the risk-benefit of the proposed research including privacy issues. It's pertinent for academicians and researchers to abide by the rules and regulations put forth by ECs for upholding of human rights and protecting research subjects primarily, as well as avoiding other issues like retraction of publications. Despite various issues of cost, backlogs, lack of expertise, lesser representation of laypersons, need for multiple approvals for multisite projects, conflicts of interest, and monitoring of ongoing research for the continued safety of participants, the ECs form the central force in regulating research and participant safety. Data safety and monitoring boards complement the ECs for carrying out continuous monitoring for better protection of research subjects. The establishment of ECs has ensured safe study designs, the safety of human subjects along with the protection of researchers from before the initiation until the completion of a study.

Postvaccination antibody titres predict protection against COVID-19 in patients with autoimmune diseases: survival analysis in a prospective cohort.

INTRODUCTION: To assess the incidence and risk factors for breakthrough COVID-19 infection in a vaccinated cohort of patients with autoimmune rheumatic diseases (AIRDs) and determine whether antibodies to receptor binding domain of spike protein (anti-RBD) serve as a reliable predictor of susceptibility to such infections. METHODS: Patients with AIRDs who had completed two doses of SARS-CoV2 vaccines were included and anti-RBD antibodies were determined 4-6 weeks post the second vaccine dose and stratified into good responders (GR) (>212 IU), inadequate responders (IR) (0.8-212 IU) and non-responders (NR) (<0.8 IU). Patients who had completed a minimum of 8 weeks interval after the second dose of vaccine were followed up every 2 months to identify breakthrough infections. All sero converted patients who had contact with COVID-19 were also analysed for neutralising antibodies. RESULTS: We studied 630 patients of AIRDs (mean age 55.2 (±11.6) years, male to female ratio of 1:5.2). The majority of patients had received AZD1222 (495, 78.6%) while the remaining received the BBV152 vaccine. The mean antibody titre was 854.1 (±951.9), and 380 (60.3%) were GR, 143 (22.7%) IR and 107 (16.9%) NR.Breakthrough infections occurred in 47 patients (7.4%) at a mean follow-up of 147.3 (±53.7) days and were proportionately highest in the NR group (19; 17.75%), followed by the IR group (13; 9.09%) and least in the GR group (15; 3.95%). On log-rank analysis, antibody response (p<0.00001), vaccine(p=0.003) and mycophenolate mofetil (p=0.007) were significant predictors of breakthrough infections. On multivariate Cox regression, only NR were significantly associated with breakthrough infections (HR: 3.6, 95% CI 1.58 to 8.0, p=0.002). In sero converted patients with contact with COVID-19, neutralisation levels were different between those who developed and did not develop an infection. CONCLUSION: Breakthrough infections occurred in 7.4% of patients and were associated with seronegativity following vaccination. This provides a basis for exploring postvaccination antibody titres as a biomarker in patients with AIRD.

Serum and urinary galectin-9 and C-X-C motif chemokine ligand 10.

BACKGROUND: Systemic lupus erythematosus (SLE) is characterized by a type I interferon (IFN) signature, and traditional methods for its measurement like gene expression analysis are cumbersome for routine use. Thus, we aimed to study galectin-9 as a biomarker and compared it with a validated marker, C-X-C motifchemokine ligand 10(CXCL-10). METHODS: Ninety-seven patients with SLE (26 years; 89 females) were included and stratified based on renal involvement and activity into - active (SLEDAI > 4) renal (35), active non-renal (32) and inactive renal subgroups (30) along with 20 healthy controls (HC, 25 years; 15 females). The median disease duration was 24 months (6-48), and SLEDAI 2K was 9 (2-15). Serum and urine galectin-9 and CXCL-10 levels were measured by ELISA. Urine levels were normalized with spot urine creatinine values. Follow-up serum and urine galectin-9 levels were measured for those in the active renal group at 6 months. RESULTS: Patients with SLE had higher serum galectin-9 (5.6 vs 1.7 µg/mL, p = .0001) but not urine galectin-9 (0.52 vs 0.32 µg, p = .7) levels as compared to HC. Serum galectin-9 but not urine galectin-9 was higher in patients with active as compared to inactive lupus (12.9 - active renal, 16.7 - active non-renal vs 3.57 µg/mL, p = .04 and .005). Serum CXCL-10 (0.16 vs 0.05, p = .01) and urine CXCL-10 (0 vs 0, p = .01) were both significantly higher in the SLE group as compared with HC. Serum but not urine CXCL-10 was higher in the active as compared to inactive lupus (0.2 - active renal, 0.3 - active non-renal vs 0.08 µg/mL, p = .9 and .02). Serum galectin-9 showed a modest correlation with CXCL-10 0.4 (0.2-0.6), whereas none was found between their urine levels.Serum galectin-9 and CXCL-10 showed a moderate positive correlation with SLEDAI 2K. Serum galectin-9 showed a greater AUC than CXCL-10 (0.77 vs 0.67) in differentiating active from inactive SLE, and both tested together had the best AUC of 0.82. However, urinary levels had no association with SLEDAI 2K or renal SLEDAI. In a subset of patients with active renal disease, serum galectin-9 but not urine levels declined significantly after 6 months. CONCLUSION: Serum galectin-9 is a good marker of lupus activity; however, it does not differentiate between active renal and active non-renal disease. It performs slightly better than CXCL-10. Urinary galectin-9 does not reflect renal activity.

Differentiating flare and infection in febrile lupus patients: Derivation and validation of a calculator for resource constrained settings.

Background: Patients with Systemic Lupus Erythematous (SLE) are at an increased risk of infection and it is often difficult to differentiate between infection and disease activity in a febrile patient with SLE. Methods: Patients with SLE (SLICC criteria) presenting with fever between December 2018 and August 2021 were included. Neutrophil to lymphocyte ratio (NLR), NEUT-x, -y, -z indices, Erythrocyte sedimentation rate (ESR), C-reactive protein(CRP), C3, C4, anti-dsDNA antibodies, and procalcitonin(PCT) were tested in addition to investigations as per the treating physician's discretion. Based on the clinical assessment and laboratory data, the febrile episode was classified into infection, disease flare, or both. Statistical analysis was done using GraphPad prism v8.4.2. A novel composite score was devised and validated with a calculator incorporated is a spreadsheet. The performance of a previously proposed model of duration of fever, CRP, and dsDNA (Beca et al) was evaluated and other models using PCT and NEUT-Z were explored. Results: Among 168 febrile episodes in 166 patients with SLE (25 (19-32) years), 46 were due to infection, 77 due to flare, 43 due to both, and two due to other causes. High SLEDAI 2K (0.001), anti-dsDNA (p = 0.004), and low complements(C3, p = 0.001 and C4, p = 0.001) were characteristic of disease flare, whereas high total leukocyte count (TLC) (p = 0.008), NLR (p = 0.008), NEUT-x (p = 0.001), -y (p = 0.03), -z (p = 0.002), CRP (p = 0.001), and PCT (p = 0.03) were observed with infection. A model using age, TLC, and CRP was devised using 80% of the cohort with an AUC of 0.88 (0.78-0.97) which was validated in the remaining 20% to have an AUC of 0.83(0.60-1.0). The model devised by Beca et al yielded an AUC of 0.74. Use of PCT did not improve the discrimination between flare and infection. A Model of C4 and NEUT-z analyzed in a subset performed well and needs further exploration. Conclusion: A composite score of low cost and routinely available parameters like age, TLC, and CRP gives a good discrimination between infection and flare in a febrile patient with SLE.

Effectiveness and adverse effects of the use of mirtazapine as compared to duloxetine for fibromyalgia: real-life data from a retrospective cohort.

On the background of a restricted armamentarium of drugs available for the management of fibromyalgia (FM), we aimed to compare the real-world effectiveness of two serotonin-norepinephrine reuptake inhibitors (SNRIs), mirtazapine (MTZ) and duloxetine (DLX) in FM. A medical records review was done to identify patients diagnosed with FM and prescribed a stable dose of either MTZ or DLX for more than 6 months. Their present status was determined by a telephonic interview which included a subjective assessment of improvement (Likert scale), FIQR (Revised Fibromyalgia Impact Questionnaire), adverse drug effects and compliance. One-fifty-eight patients were screened to include 81 patients [mean age 46.7 (± 13.0) years, 64 (79%) females]. Sixty (79%) had primary fibromyalgia and 66 (81.5%) were on DLX (20-40 mg) while 15(18.5%) were on MTZ (7.5 mg). In addition to the drugs, lifestyle modification was followed by 57 (70.3%). A moderate-to-good improvement was seen in 66 (81.5%), while 15 (18.5%) reported poor to no improvement overall. In the DLX group, a majority (59, 89.4%) showed moderate-to-good improvement compared to 7(46.7%) on MTZ [p = 0.001, 9.6(2.6-34)]. However, FIQR was similar for those on DLX (3.6 ± 0.9) and MTZ (3.8 ± 0.7). Adverse effects were reported for 51 (77%) of patients on DLX and all (100%) on MTZ with a poorer compliance with MTZ 5 (33.3%) compared to DLX 47 (71.2%) [p = 0.008, OR 0.1(0.03-0.4)]. On multivariate analysis, DLX use [OR 16.7 (95% CI 2.7-100); p = 0.008] and lifestyle modification [p = 0.002; OR 11.2(1.5-83.3)] were associated with better subjective outcomes. Low-dose MTZ appears to be inferior to DLX in the management of FM in this real-world cohort.

Prevalent Drug Usage Practices in Adults and Children With Idiopathic Inflammatory Myopathies: Registry-Based Analysis From the MyoCite Cohort.

BACKGROUND: Idiopathic inflammatory myopathies (IIMs) form a heterogeneous group of disorders with a deficit of quality evidence regarding its management. Therefore, we aimed to explore the prevalent treatment practices in the MyoCite cohort from India. METHODS: Drug usage patterns, their predictors, drug retention rates, efficacy, and adverse drug reactions were analyzed for adults and children newly diagnosed with IIM (2017-2020) and followed prospectively and compared with real-world data by performing a medical records review. GraphPad Prism version 8.4.2 was used for statistical analysis. RESULTS: Of 181 adults (male-to-female ratio, 1:4.6) and 30 children (M:F, 1.3:1), dermatomyositis (41% adults, 93% children) was the most common subtype. Methotrexate (MTX) was the drug of choice (67% adult, 90% children) followed by azathioprine (AZA) and mycophenolate mofetil (MMF). The MMF, AZA, cyclophosphamide, and rituximab (RTX) were preferred for those with antisynthetase syndrome (ASSD) and those with lung involvement, whereas MTX was avoided in them. Functional class and family income did not determine drug preferences. Glucocorticoids were initiated at a lower dose in overlap myositis (45% vs 80%, p = 0.001), and the time to achieve the lowest dose of glucocorticoids was longer than 24 months for ASSD (77% vs 14%, p = 0.002).Over a median of 35 months, the overall retention rate was the highest for RTX (75%) followed by MTX (58%). Relapse-free survival was the highest for RTX followed by MTX. The most common reasons for discontinuation were adverse drug reactions for MTX and MMF, inefficacy for AZA, and cost for RTX. CONCLUSIONS: In this first analysis of drug usage and retention in patients with IIM in Northern India, MTX emerged as the most preferred drug in both adults and children, with the exception of those with ASSD or lung disease. Organ involvement and subtype of IIM are key determinants of drug preference. Overall, RTX and MTX were well-tolerated with high retention rates, followed by AZA and MMF.

High early mortality in idiopathic inflammatory myopathies: results from the inception cohort at a tertiary care centre in northern India.

OBJECTIVES: We determined the mortality along with the proportion of disease related adverse events measured individually and by a composite adverse outcome (devised by including deaths, disability, relapses and minimal response) and its predictors in an inception cohort of idiopathic inflammatory myopathies (IIM). METHODS: IIM from the MyoCite cohort (December 2017-19) were reviewed for early outcomes (mortality, IMACS core set). Comparisons were drawn between those meeting the primary and secondary outcomes. RESULTS: Of 70 patients [62 adults, M:F = 1:4.8, age 43 (28.5-51) and eight children, M:F = 1:1, 14.5 (8.8-16)], dermatomyositis (DM) was the most common subset [29 (41.4%) adults; 7 (87.5%) children]. Over 10 (4-15) months, 10 (15.2%) died and four polymyositis were reclassified. One-year survival for anti-melanoma differentiation antigen 5 (MDA5) subtype was 30% and anti-synthetase syndrome (ARS) subtype was 75%. Overall, lower respiratory infections were the most common cause of death [n = 3 (30%)] followed closely by malignancy and rapidly progressive interstitial lung disease (RP-ILD). Amongst survivors, a major IMACS response was recorded in 54.5% adults and 100% children. Thirty per cent suffered from moderate to severe disability and 16.7% experienced relapses. Overall, two-thirds accrued the composite adverse outcome. On multivariate analysis, older age and anti-MDA5 predicted mortality. Arthritis, rash and positive ANA reduced and anti-MDA5 increased the risk for the composite adverse outcome. CONCLUSION: Indian patients with IIM suffer high early mortality attributable to infection, cancer and RP-ILD, calling for high vigilance post diagnosis. Autoantibodies and certain clinical features identify risk for composite adverse outcomes.

High burden of infections in Indian patients with Idiopathic Inflammatory Myopathy: validation of observations from the MyoCite dataset.

OBJECTIVE: To determine the prevalence, profile and predictors of infections in an Indian cohort with idiopathic inflammatory myopathies (IIM). METHODS: We reviewed the records of a retrospective cohort with IIM enrolled from consecutive patients being followed up in the clinic, and these constituted the observation cohort. A newly diagnosed inception cohort with IIM were followed prospectively as the validation cohort for confirmation of observations and comparison with the observation cohort. RESULTS: Among the 68 patients in the observation cohort (average age 33.4 years, female:male 4.2:1), 37 (54.4%) experienced 54 infections between them; of these 54 infections, 21 (38.8%) were major and recurrent infections and they occurred in 11 patients (16.17%) over 3.08 years. Tuberculosis was the most common infection (12, 22.2%), with a predominance of extrapulmonary forms. Serum protein [odds ratio (OR) 0.44], platelets (0.44) at disease onset and daily steroid dose (1.04) predicted major infections on multivariate analysis. A higher daily dose of steroids at first infection correlated with number of recurrent infections. The infection-free 1-year survival was 73.8%.Of the 70 patients in the validation cohort (average age 35.7 years, female:male 3.7:1), 3 had myositis attributed to an infection. A similar proportion of the cohort experienced infections (22, 33.3%) with similar number of major (10, 45.4%) and recurrent (4, 18%) infections being recorded. The most common infection was community-acquired pneumonia, followed by tuberculosis, with serum albumin (OR 0.25) at disease onset being the only predictor. The one-year infection-free survival rate was 64.7%. Those who had a major infection had increased mortality at 1 year, with a survival rate of 60%, compared with 89.09% in those without.In both cohorts, a daily prednisone dose >6.25 mg predisposed to major infections. CONCLUSION: Major and recurrent infections are common in Indian IIM patients and confer higher risk for future infections and lower survival. Respiratory and atypical bacterial infections such as tuberculosis occur throughout the disease course.

Understanding and managing anti-MDA 5 dermatomyositis, including potential COVID-19 mimicry.

Anti-Melanoma Differentiation-Associated gene 5 (MDA-5) Dermatomyositis (MDA5, DM) is a recently identified subtype of myositis characteristically associated with Rapidly Progressive Interstitial Lung Disease (RP-ILD) and unique cutaneous features. We reviewed PubMed, SCOPUS and Web of Science databases and selected 87 relevant articles after screening 1485 search results, aiming to gain a better understanding of the pathophysiology, clinical features, diagnosis, and treatment approaches of anti-MDA-5 DM described in the literature. The etiopathogenesis is speculatively linked to an unidentified viral trigger on the background of genetic predisposition culminating in an acquired type I interferonopathy. The clinical phenotype is highly varied in different ethnicities, with new clinical features having been recently described, expanding the spectrum of cases that should raise the suspicion of anti-MDA-5 DM. Unfortunately, the diagnosis is frequently missed despite excessive mortality, calling for wider awareness of suspect symptoms. RP ILD is the major determinant of survival, treatment being largely based on observational studies with recent insights into aggressive combined immunosuppression at the outset.

Glucose-6-Phosphate Dehydrogenase Deficiency Unveiled by Diabetic Ketoacidosis: A Dual Dilemma.

An 18 year old male, known case of Type 1 Diabetes Mellitus was admitted in view of diabetic ketoacidosis. With normalization of blood sugars patient developed gross reddish discoloration of urine. Urine routine microscopy did not reveal RBCs or RBC casts. Peripheral blood smear revealed bite cells, Heinz bodies and spherocytes. Thus a diagnosis of hemolytic anemia with hemoglobinuria was made. Patient's glucose-6-phosphate dehydrogenase (G6PD) levels were below the normal range. G6PD, an enzyme of the HMP shunt, is the most common enzyme defect causing hemolytic anemia. G6PD deficiency related hemolytic crisis is most commonly precipitated by infection, drugs or fava beans. Its association with DKA has been seldom reported.

Boosting Vaccine Response in Autoimmune Rheumatic Disease Patients With Inadequate Seroconversion: An Analysis of the Immunogenicity of Vector-Based and Inactivated Vaccines.

BACKGROUND: An additional dose of COVID-19 vaccine is being offered to vaccinated people, especially those immunocompromised. The most widely available vaccines in India are the adenoviral vector-based AZD1222 (ChAdOx1 nCoV-19) and the heat-inactivated (BBV152). This study investigated the efficacy of both vaccines in patients with autoimmune rheumatic diseases (AIRD). OBJECTIVES:  To compare final anti-SARS-CoV-2 antibody titers, neutralization of pseudovirions by these antibodies, and T cell responses between patients of AIRD who had received the third dose of AZD1222 and BBV152 vaccines. METHODS: Patients with stable AIRD who had completed two doses of COVID-19 vaccination but had a suboptimal response (anti-receptor binding domain (RBD) antibody<212) were randomized (1:1) to receive either AZD1222 or BBV152 as a booster dose. Patients with previous hybrid immunity or those who developed COVID-19 during the trial were excluded. Antibody titers, neutralization of Wuhan and Omicron pseudovirions, and interferon release by T cells (enzyme-linked immunosorbent spot (ELISpot)) in response to the Spike antigen were measured four weeks after this booster dose. RESULTS: 146 were screened, 91 were randomized, and 67 were analyzed per protocol. The third dose improved antibody titers (p<0.001), neutralization of the Wuhan strain (p<0.001), and T cell interferon release (p<0.001) but not neutralization of the Omicron strain (p=0.24). Antibody titers were higher (p<0.005) after ADZ1222 boost (2,414 IU (interquartile range (IQR): 330-10,315)) than BBV1222 (347.7 IU (0.4-973)). Neutralization of the Wuhan stain was better (AZD1222: 76.6%(23.0-95.45) versus BBV152 (32.7% (0-78.9), p=0.03 by ANCOVA). Neutralization of Omicron (0 (0-28.4) vs 0 (0-4.8)) and T cell interferon release (57.0 IU (23.5-95) vs 50.5 IU (13.2-139)) were similar. CONCLUSION: The third dose improved all parameters of immunogenicity in AIRD patients with previous inadequate responses except Omicron neutralization. The vector-based vaccine exhibits notable efficacy, particularly in antibody titers and neutralizing the Wuhan strain. TRIAL REGISTRATION: CTRI/2021/12/038928.