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Drug-induced lupus erythematosus (DILE) is an important differential to consider in a clinical setting of mild lupus. Numerous drugs ranging from the classically described procainamide and hydralazine to novel biological agents such as anti-tumor necrosis factors and immune checkpoint inhibitors are implicated in causing DILE. Various pathophysiologic mechanisms such as decreased central tolerance, molecular cross-reactivity, and epigenetic modifications of immune cells are known to play a role in the precipitation of drug-induced autoimmunity. Early recognition and prompt withdrawal of the offending agent is often sufficient to treat these autoimmune manifestations. A thorough knowledge of DILE is essential to ensure better patient care and better understand the role of xenobiotics in precipitating autoimmunity.

Background: The ACR in 2021 and the EULAR in 2022 published recommendations for management of ANCA-associated vasculitis. Given the differences in the demographic, clinical profiles, and the socio-economic realities between various countries, there is a need for development of guidelines for the management of AAV for less economically developed regions of the world., Methods: These guidelines were made following the GRADE methodology. After the systematic literature review, recommendations were formulated and opinion was sought from the 18-member expert panel consisting of 17 clinicians and one patient representative., Results: Twenty recommendations were formulated. We recommend ANCA testing by ELISA over IIF. For remission induction in active GPA or MPA, we recommend use of intravenous cyclophosphamide or rituximab in combination with glucocorticoids. We conditionally recommend the use of reduced dose glucocorticoids over standard dose glucocorticoids for remission induction in active GPA or MPA. For remission maintenance in patients with GPA or MPA, we recommend the use of rituximab over azathioprine for at least 48 months from diagnosis. We conditionally recommend the use of plasma exchange in patients with severe renal vasculitis. For remission induction in EGPA, we recommend use of cyclophosphamide or rituximab in severe disease and mepolizumab or azathioprine or methotrexate or mycophenolate mofetil in non-severe disease., Conclusions: These are the first ever Indian recommendations for the management of AAV. Despite our effort to formulate these recommendations based on high quality evidence, some recommendations were still based on low quality evidence but with high rate of agreement among expert panel members., Competing Interests: Declaration of competing interest Nil., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: To assess the longitudinal effect of cyclophosphamide (CYC) treatment on type-I interferon (IFN) signature in proliferative lupus nephritis (LN) and its role in predicting treatment response., Methods: Fifty-four biopsy proven proliferative LN patients scheduled to receive high-dose (HD) or low-dose (LD) CYC were recruited and followed up for six months. At six months, patients were classified as clinical responders (CR) or non-responders (NR) to treatment, using the EULAR/EDTA criteria. An IFN-gene based score (IGS) was developed from the mean log-transformed gene expression of MX1, OAS1, IFIT1, OASL, IFIT4, LY6E, IRF7 at baseline, three and six months. Longitudinal changes of IGS within and between groups were assessed and ΔIGS, which is the difference in IGS between baseline and three months was calculated. Independent predictors of non-response were identified and an ROC analysis was performed to evaluate their utility to predict NR., Results: There was a dynamic change in IGS within the HD, LD, CR, and NR groups. Compared to baseline, there was a significant decrease in IGS at three months in HD and LD groups (HD group: 2.01 to 1.14, p = .001; LD group = 2.01 to 0.81, p < .001), followed by a significant increase from three to six months in LD group (LD: 0.81 to 1.51, p = .03; HD: 1.14 to 1.54, p = .300). A decrease in IGS from baseline to three months was seen in both CR (2.13 to 0.79, p < .001) and NR groups (1.83 to 1.27, p = .046), and a significant increase from three to six months was observed only in the CR group (CR: 0.79 to 1.57, p = .006; NR: 1.27 to 1.46, p = 1). ΔIGS (baseline to three months) was higher in CR compared to NR group (-1.339 vs -0.563, p = .017). ROC analysis showed that the model comprising of 0.81 fold decrease in IGS from baseline to three months, endocapillary hypercellularity and interstitial inflammation on renal histopathology predicted non-response with a sensitivity of 83.3% and specificity of 71.4%., Conclusion: In proliferative LN, treated with HD or LD-CYC, combined model comprising of decrease in IGS score by 0.81 fold from baseline to three months, along with important histopathological features such as endocapillary hypercellularity and interstitial inflammation had better predictive capability for non-response., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Low copy numbers (CNs) of C4 genes are associated with systemic autoimmune disorders and affects autoantibody diversity and disease subgroups. The primary objective of this study was to characterize diversity of complement (C4) and C4-Human Endogenous Retrovirus (HERV) gene copy numbers in SLE. We also sought to assess the association of C4 and C4-HERV CNs with serum complement levels, autoantibodies, disease phenotypes and activity. Finally, we checked the association of C4 and HERV CNs with specific HLA alleles. Genomic DNA from 70 SLE and 90 healthy controls of south Indian Tamil origin were included. Demographic, clinical and serological data was collected in a predetermined proforma. CNs of C4A and C4B genes and the frequency of insertion of 6.4kb HERV within C4 gene (C4AL, C4BL) was determined using droplet digital polymerase chain reaction (ddPCR). A four digit high resolution HLA genotyping was done using next generation sequencing. In our cohort, the total C4 gene copies ranged from 2 to 6. Compared to controls, presence of two or less copies of C4A gene was associated with SLE risk (p = 0.005; OR = 2.79; 95% CI = 1.29-6.22). Higher frequency of HERV insertion in C4A than in C4B increases such risk (p = 0.000; OR = 12.67; 95% CI = 2.80-115.3). AL-AL-AL-BS genotype was significantly higher in controls than SLE (9%vs1%, p = 0.04; OR = 0.15, 95% CI = 0.00-0.16). Distribution of HLA alleles was not different in SLE compared to controls as well as in SLE subjects with ≤ 2 copies and > 2 copies of C4A, but HLA allele distribution was diverse in subjects with C4B ≤ 2 copies and > 2 copies. Finally, there was no correlation between the C4 and the C4-HERV diversity and complement levels, autoantibodies, disease phenotypes and activity. In conclusion, our data show that, low C4A copy number and higher insertion of HERV-K in C4A increases the risk for SLE. C4 and C4-HERV CNs did not correlate with serum complements, autoantibodies, disease phenotypes and activity in SLE. Further validation in a larger homogenous SLE cohort is needed., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: There is limited literature on digital ischemia in systemic Lupus erythematosus (SLE). We report the prevalence, associations and outcome of digital infarcts and gangrene from the Indian SLE inception cohort (INSPIRE)., Methods: From the web-based database of INSPIRE, we extracted information for patients with 'Digital Infarct' and 'Digital gangrene' at enrolment into cohort, together considered as critical peripheral ischemia (CPI); all others were controls. We describe the associations of CPI with SLE clinical phenotype, autoantibodies, and disease activity at enrolment. We also report short term outcomes viz. Digital tissue loss and early mortality up to 6 months and recurrence of digital ischemic events in cases till date., Results: Of 2503 SLE patients enrolled into the INSPIRE cohort, we identified 75 (2.9%) patients with CPI, 72 (96%) women and 6 (8%) children. Of them, 55 (73.3%) had digital gangrene and 21 (28%) patients had digital infarcts. Majority of digital gangrene resulted in amputation distal to terminal phalanx (63.6%). Multivariable analysis showed that pulmonary hypertension AOR [6.34 (1.99, 20.2)], coexistent thrombosis AOR [27.8 (15.7, 48.7)], triple antiphospholipid antibody positivity AOR [5.36 (1.67, 16.9)] and the presence of anti-Scl-70-antibody AOR [5.59 (1.86, 16.7)] were more likely while patients with class 3 or 4 lupus nephritis AOR [0.37 (0.15, 0.95)] and anti-nucleosome antibodies AOR [0.47 (0.23, 0.99)] were less likely to be associated with CPI. SLEDAI and short-term mortality were similar between cases and controls., Conclusions: CPI occurred in a higher proportion (2.9%) of SLE patients in the INSPIRE cohort as compared to earlier reports. Both prothrombotic state and vasculopathy contribute to its occurrence., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The synovial fluid (SF) microenvironment in rheumatoid arthritis (RA) may alter the stability and function of Tregs. In the present study, we assessed cytokine levels and percentage of Tregs, Tregs expressing CXCR3 (Th1-like Treg), CCR6 (Th17-like Treg) in RA peripheral blood (PB) and RA-SF using fluorescence cytometry. Effect of autologous SF on plasticity and function of RA-PB Tregs (pTregs; CD4 + CD25 hi CD127 Lo/- ) and induced vimentin-pulsed Tregs (iTregs VIM ) was assessed in vitro. Cytokines and percentage of Th1-like and Th17-like Tregs were higher in RA-PB than OA-PB; higher in RA-SF than osteoarthritis (OA)-SF. Compared to OA-SF exposed OA-pTregs, RA-SF exposed RA-pTregs showed higher percentage of Th1-like (11% vs 20%) and Th17-like (16% vs 36%) Tregs; higher T-bet (p = 0.0001), RORγ (p = 0.0001) and lower FOXP3 (p = 0.0001) gene expression; and diminished percentage suppression of autologous T effector cells (36% vs 74%). RA-SF exposed iTregs VIM showed increased percentage of Th1-like and Th17-like Tregs compared to iTregs VIM exposed to AB serum (8% vs 0.1%; 21% vs 0.1%). IL-2, Tocilizumab and 5-azacytidine reduced the conversion of iTregs VIM (8% vs 2.4%; 21% vs 6.9%), when used in combination. To conclude, microenvironment in the RA synovial fluid is possibly responsible for conversion of pTregs into Th-like Tregs and their functional loss. A blockade of cytokine receptors and methyl transferases could inhibit Tregs conversion, providing clinical relevance for future Tregs targeting therapies., Competing Interests: Declaration of competing interest All the authors declare that they have no conflict of interests., (Copyright © 2024 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.)

Antiphospholipid antibodies (APLA) are present in one-third of systemic lupus erythematosus (SLE) patients, and they are associated with both criteria and non-criteria manifestations. We studied the prevalence, clinical associations, and impact on mortality of APLA in SLE patients from India. Among the Indian SLE inception cohort (INSPIRE), patients who had data on all five routinely performed APLAs [lupus anticoagulant (LA), IgG and IgM anticardiolipin antibody (aCL) and anti-β2-glycoprotein I(β2GPI)] at enrolment were selected. Patients were divided into four categories based on the presence/absence of APLA associated manifestations and presence/absence of the APLA viz SLE-APS, SLE-APLA, SLE: events but no APLA, and SLE: no events, no APLA (reference group). 1035 SLE patients at least 1 APLA antibody was detected in 372 (35.9%). LA was present in 206 (19.9%), aCL in 126 (12.2%) and β2-GPI in 178 (17.2%). There were 88 thrombotic events in 83 patients (8.0%); 73 (82.9%) being arterial; APLA positivity was present in 37 (44.6%) [AOR 1.70 (1.054, 2.76)]. SLE-APS patients were younger and had higher mortality [AOR 4.11 (1.51, 11.3)], neuropsychiatric and hematologic disease. SLE-APLA also had a higher mortality rate [AOR 2.94 (1.06, 8.22)] than the reference group. The mortality was highest in the subset of patients with thrombotic events in the presence of APLA [AOR 7.67 (1.25, 46.9)]. The mere presence of APLA also conferred higher mortality even in the absence of thrombotic events [AOR 3.51 (1.43, 8.63)]. Hematologic manifestations (36.1%) were the most common non-criteria-manifestation. One-third of SLE patients have APLA and its presence is associated with non-criteria hematologic manifestations, arterial thrombosis and higher mortality rate., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To conduct an exploratory cluster analysis of systemic sclerosis patients from the baseline data of the Indian systemic sclerosis registry., Methods: Patients satisfying American College of Rheumatology-European League Against Rheumatism classification criteria for systemic sclerosis were included. The clusters formed using clinical and immunological parameters were compared., Results: Of the 564 systemic sclerosis registry participants, 404 patients were included. We derived four clusters of which three were anti-topoisomerase I predominant and one was anti-centromere antibody 2 dominant. Cluster 1 ( n -82 (20.3%)) had diffuse cutaneous systemic sclerosis patients with the most severe skin disease, anti-topoisomerase I positivity, males, younger age of onset and high prevalence of musculoskeletal, vasculopathic and gastrointestinal features. Cluster 2 ( n -141 (34.9%)) was also diffuse cutaneous systemic sclerosis and anti-topoisomerase I predominant but with less severe skin phenotype than cluster 1 and a lesser prevalence of musculoskeletal, vasculopathic and gastrointestinal features. Cluster 3 ( n -119 (29.5%)) had limited cutaneous systemic sclerosis patients with anti-topoisomerase I positivity along with other antibodies. The proximal muscle weakness was higher and digital pitting scars were lower, while other organ involvement was similar between clusters 2 and 3. Cluster 4 ( n -62 (15.30%)) was the least severe group with limited cutaneous systemic sclerosis and anti-centromere antibody predominance. Age of onset was higher with low musculoskeletal disease and a higher presence of upper gastrointestinal features. The prevalence of interstitial lung disease was similar in the three anti-topoisomerase I predominant clusters., Conclusion: With exploratory cluster analysis, we confirmed the possibility of subclassification of systemic sclerosis along a spectrum based on clinical and immunological characteristics. We also corroborated the presence of anti-topoisomerase I in limited cutaneous systemic sclerosis and the association of interstitial lung disease with anti-topoisomerase I., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article., (© The Author(s) 2023.)

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., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: SLE is associated with significant mortality, and data from South Asia is limited. Thus, we analysed the causes and predictors of mortality and hierarchical cluster-based survival in the Indian SLE Inception cohort for Research (INSPIRE)., Methods: Data for patients with SLE was extracted from the INSPIRE database. Univariate analyses of associations between mortality and a number of disease variables were conducted. Agglomerative unsupervised hierarchical cluster analysis was undertaken using 25 variables defining the SLE phenotype. Survival rates across clusters were assessed using non-adjusted and adjusted Cox proportional-hazards models., Results: Among 2072 patients (with a median follow-up of 18 months), there were 170 deaths (49.2 deaths per 1000 patient-years) of which cause could be determined in 155 patients. 47.1% occurred in the first 6 months. Most of the mortality (n = 87) were due to SLE disease activity followed by coexisting disease activity and infection (n = 24), infections (n = 23), and 21 to other causes. Among the deaths in which infection played a role, 24 had pneumonia. Clustering identified four clusters, and the mean survival estimates were 39.26, 39.78, 37.69 and 35.86 months in clusters 1, 2, 3 and 4, respectively (P < 0.001). The adjusted hazard ratios (HRs) (95% CI) were significant for cluster 4 [2.19 (1.44, 3.31)], low socio-economic-status [1.69 (1.22, 2.35)], number of BILAG-A [1.5 (1.29, 1.73)] and BILAG-B [1.15 (1.01, 1.3)], and need for haemodialysis [4.63 (1.87,11.48)]., Conclusion: SLE in India has high early mortality, and the majority of deaths occur outside the health-care setting. Clustering using the clinically relevant variables at baseline may help identify individuals at high risk of mortality in SLE, even after adjusting for high disease activity., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Residual renal histopathological activity at clinical remission in Proliferative Lupus Nephritis (PLN) can predict renal flare upon immunosuppression withdrawal. Data on the role of histological renal remission in predicting extra-renal flares is lacking. We assessed renal histopathology prior to drug withdrawal and the occurrence of renal and extra-renal flares over 52 weeks after drug withdrawal in PLN patients in long-term clinical remission. This is a subgroup analysis of a non-inferiority, open-label randomized (1:1) controlled trial. Patients with biopsy-proven Class III/IV LN in the past (biopsy 1), on immunosuppressants (IS) ≥ 3 years, in clinical remission for ≥ 1 year, on stable prednisolone dose (≤ 7.5 mg/day) plus a maintenance IS and hydroxychloroquine (HCQ) were subjected to a repeat renal biopsy (biopsy 2). Individuals with biopsy 2 having activity index (AI) < 4/24 were randomised to either prednisolone or IS withdrawal. Primary end-point was the proportion experiencing a flare [SELENA-SLEDAI flare index (SFI)] at week 52. Twenty-eight eligible patients underwent biopsy 2 and randomized to prednisolone (n = 15) and IS (n = 13) withdrawal. At biopsy 1, 12 (43%) had class III, 15 (53.5%) had class IV, and 1 (3.5%) had class III + V. At biopsy 2, PLN persisted in 4 (14.2%) while 18 (64.2%) were in histological remission (AI = 0) with 6 (21.4%) in class II. Following drug withdrawal, 9/28 (32%) had flares especially musculoskeletal (55.5%), mucocutaneous (44.4%), and renal (33.3%). Among the four persistent PLN patients, one of the two (50%) with AI = 1 had extra-renal flare while both the two with AI = 2 (100%) had renal and extra-renal flares. In those with histological remission (biopsy 2), 6/18 (66.6%) experienced extra-renal flare of whom one also had renal flare. Upon drug withdrawal, renal histopathology findings with any activity index can predict renal flare while histological remission is not enough to predict extra-renal flare, thus making it an unsuitable marker for deep SLE remission., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: The primary objective of our study was to evaluate renal uptake of 68Ga-pentixafor in patients with lupus nephritis. Eighteen patients who satisfied the inclusion criteria were included in our study., Methods: The study participants were patients with histopathologically confirmed lupus nephritis who were referred to our department for 68Ga-pentixafor PET/CT scan. We studied the renal images in these patients for uptake patterns based on purely visual as well as semi-quantitative parameters. The visual parameters included uptake relative to the spleen and liver. Semi-quantitative analysis involved the uptake as given by SUVmax. These parameters were correlated with the patients' biochemical as well as histological parameters. Kendall's tau-b test was used to look for an association between renal uptake by visual assessment and histopathological findings. Mean SUVmax values were compared by using the Mann-Whitney U test and a p value < .05 was considered to be statistically significant., Results: No significant association between the mean renal SUVmax of the bilateral kidneys in pentixafor PET and histopathological class was observed. We did not observe any heterogeneity in uptake patterns that could be attributed to the disease process in our patients., Conclusion: 68Ga-pentixafor PET is not a suitable imaging modality for assessment of disease activity in lupus nephritis patients. There is a void in non-invasive testing for patients with this chronic and often disabling condition which calls for further research in this area., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: Systemic lupus erythematosus (SLE) has become the most prevalent autoimmune condition requiring admission in the intensive care units (ICU) in the last two decades. Here we analysed the clinical outcomes of SLE patients admitted to our ICU between 2011 and 2021, and studied the prognostic role of high-density lipoprotein (HDL) and procalcitonin in those enrolled after August 2019., Methods: Systemic lupus erythematosus (ACR/SLICC 2012) were enrolled, 72 retrospectively and 30 prospectively. Data on indications for ICU admission, complications, infections, and disease activity were recorded. Outcome was mortality at 90 days (prospective) whereas in the retrospective analysis outcome was hospital discharge or death in hospital. Serum HDL and procalcitonin (PCT) was estimated in the prospectively enrolled 30 patients and compared with 30 non ICU-SLE patients., Results: Indications for ICU admissions were respiratory causes in 78/102 (76.5%) patients; for haemodynamic monitoring and for invasive procedures in the remaining. Pneumonia was the primary reason for mechanical ventilation, followed by diffuse alveolar haemorrhage (DAH). Eighty-three (81.3%) patients died; infections ( n = 54) and SLE related causes ( n = 29). APACHE-II >16 ( p = .026), lymphopenia ( p = .021), infection ( p = .002), creatinine >1.3 mg/dL ( p = .023), and hypotension requiring vasopressor support ( p = .006) emerged as significant predictors of non-survival on multivariable analysis. HDL (mg/dL) day 1 was significantly lower in SLE-ICU patients compared to non ICU-SLE (31.8 ± 14.3 vs 38.8 ± 11.4 mg/dl); p = .045. On day 1, PCT (ng/mL) in SLE-ICU was significantly higher when compared to non-ICU SLE; median (IQR): 0.53 (0.26-5.27) versus 0.13 (0.05-0.47), p < .001), respectively. It was also significantly higher on day 5 in SLE-ICU than non-ICU SLE (median (IQR): 4.18 (0.20-14.67) versus 0.10 (0.08-0.46), p = .004., Conclusion: The mortality of SLE patients admitted to the ICU in this study is high, and infections were the principal reason for death. Baseline low HDL and higher procalcitonin are potential biomarkers to identify critically ill SLE patients., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Thrombocytopenia in patients with systemic lupus erythematosus (SLE) is associated with higher morbidity and mortality. We report frequency, associations and short-term outcome of moderate-severe thrombocytopenia in a prospective inception cohort from India (INSPIRE). We evaluated consecutive SLE patients classified per SLICC2012 for the occurrence of thrombocytopenia and its associations. The outcomes assessed included bleeding manifestations, kinetics of thrombocytopenia recovery, mortality and recurrence of thrombocytopenia. Among a total of 2210 patients in the cohort, 230 (10.4%) had incident thrombocytopenia, of whom moderate (platelet count [PC] 20-50 × 10 9 /L) and severe thrombocytopenia (PC < 20 × 10 9 /L) were noted in 61 (26.5%) and 22 (9.5%), respectively. Bleeding manifestations were generally limited to the skin. Compared to controls, cases had a higher proportion of autoimmune haemolytic anaemia (p < 0.001), leukopenia (p < 0.001), lymphopenia (p < 0.001), low complement (p < 0.05), lupus anticoagulant (p < 0.001), higher median SLEDAI 2 K (p < 0.001) and lower proportion of anti-RNP antibody (p < 0.05). There was no significant difference in these variables between moderate and severe thrombocytopenia. There was a sharp rise in PC by 1 week that was sustained in the majority through the period of observation. There was three times higher mortality in the severe thrombocytopenia group as compared to moderate thrombocytopenia and controls. The thrombocytopenia relapse and lupus flare rates were similar across categories. We report a low occurrence of major bleeds and higher mortality in those with severe thrombocytopenia as compared to moderate thrombocytopenia and controls. Key Points • Severe thrombocytopenia occurs in 1% of patients with SLE; however, major bleeds are uncommon. • Thrombocytopenia has a strong association with other lineage cytopenias and lupus anticoagulants. • Response to initial glucocorticoids therapy is quick and is well sustained with additional immunosuppressants. • Severe thrombocytopenia increases mortality threefold in SLE., (© 2023. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Background and Objectives: Data on the association of vitamin D levels and clinical phenotype and disease activity in systemic lupus erythematosus (SLE) is controversial. Further, the optimal dose of oral vitamin D supplementation in SLE is not clear. Thus, the present study was designed to determine the association of plasma vitamin D levels with clinical phenotype, disease variables and serology in a large, cohort of SLE from South Asia and to evaluate the short-term effect of two different dosage regimens of oral vitamin D supplementation on disease flares and plasma vitamin D levels., Methods: This is a two-phase study. Phase I was a cross-sectional analytical study of patients from north (26.85° N) and south India (11.94° N). Plasma 25-hydroxyvitamin-D(25(OH)D) was measured, and its association with demography, serology, disease activity, Galectin-9 and CXCL-10 was analysed. In phase II, patients with SLEDAI-2KG < 10 and on stable immunosuppression were randomised to receive either high dose (weekly 60,000 U*5, followed by 60,000 U monthly) or routine dose (30,000 U monthly) oral vitamin D. Outcomes were assessed at 6 months RESULTS: Phase I included 702 patients with a mean age of 29.46 + 10.7 years. The median plasma vitamin D was 22.83 (13.8-31.8) ng/ml. Deficiency (< 20 ng/ml) was seen in 41.5% of patients. Patients from South India had higher vitamin D levels (27.06 ± 20.21 ng/dl) as compared to North India (17.15 ± 16.07 ng/ml) (p < 0.01). Univariate analyses demonstrated weak negative correlation of vitamin D with SLEDAI2K and positive correlation with age. Galactin-9 had modest correlation with SLEDAI2K but not with vitamin D levels. On multiple linear regression, centre of recruitment (β = 4.37) and age (β = 0.18) predicted (p < 0.05) plasma vitamin D levels. In the phase II, 91 randomised to 2 groups completed 6 months. Median change in plasma vitamin D levels was more in high dose (9.5 versus 2.6 ng/ml; p = 0.04). There were 14 SLE flares and six minor adverse events which were equal across both groups., Conclusion: Vitamin D deficiency is common in SLE. Geographical location of residence is the major determinant rather than the disease activity. The IFN regulated proteins reflect disease activity independent of vitamin D levels. High-dose oral vitamin D supplementation seems safe and more effective in improving vitamin D levels in SLE., Trial Registration: The second phase of this study was a registered randomised controlled trial CTRI/2019/06/019658 [registered on: 14/06/2019]., (© 2022. The Author(s).)