Critical peripheral ischemia: Higher prevalence in Indian systemic lupus erythematosus inception cohort for research (INSPIRE).

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.

SARS-CoV-2 seroprevalence in patients with autoimmune rheumatic diseases versus family controls: a multi-city cross-sectional survey.

There is uncertainty regarding the effect of the SARS-CoV-2 infection on patients with autoimmune rheumatic diseases (AIRD) who are on immunosuppressive drugs. We did a multicity cross-sectional seroprevalence study conducted in five different cities in India before COVID-19 immunization. Patients with a diagnosis of AIRD and DMARDs were included. Relatives of the patients, preferably staying in the same household with no known rheumatic diseases served as controls. Serum IgG antibodies to SARS-CoV-2 Receptor Binding Domain (RBD) of the spike protein and nucleoprotein (NP) were assayed in eight hundred and eighty nine sera (subjects with disease = 379 and in subjects without disease = 510). IgG antibodies to either RBD and/or NP were positive in 135 (36%) subjects with AIRD as compared to 196 (38%) controls. The seroprevalence of anti-RBD and anti-NP varied between different cities but was not significantly different between subjects with and without disease in Mumbai, Ahmedabad, Bengaluru and Bhubaneswar. However, the occurrence of IgG antibodies to RBD was significantly (p < 0.05) lower in subjects with disease (28/65;43%) as compared to subjects without disease (42/65;65%) in Kolkata, where the positivity rate was lower in connective tissue disease group than in inflammatory arthritis group. Overall, patients with rheumatic diseases on DMARDs have IgG antibodies to RBD and NP of SARSCoV-2 at a comparable level with that of subjects without disease, but the level of antibodies to RBD is lower in patients with connective tissue disease on immunosuppressive drugs in one centre.

Pattern of disease expression in SLE patients with antiphospholipid antibodies: data from Indian Systemic Lupus Erythematosus Inception cohort (INSPIRE).

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-ß2-glycoprotein I(ß2GPI)] 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 ß2-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.

Low-dose rituximab is efficacious in refractory idiopathic inflammatory myopathies.

OBJECTIVES: Rituximab (RTX) use early in the course of refractory idiopathic inflammatory myopathy (IIM) is not well studied. This study sought to determine the short-term efficacy of RTX in a registry-based cohort of refractory IIM. METHODS: Registry-based observational data about IIM patients receiving RTX between 2018 and 2021 were included. Total improvement score was calculated from the core set measures as per International Myositis Assessment and Clinical Studies group (IMACS) at baseline, 6 months and 12 months of follow-up. RESULTS: Forty-two patients (F:M, 29:13), with a mean (s.d.) age of 39.5 (11.5) years were studied. Majority of patients received RTX for refractory myositis, after a median (interquartile range) duration of 8 (4,18) months. Twenty-eight received RTX at a dosage of 1 g × two doses, while 14 received 500 mg × two doses with an interval of 15 days. At 6 months and 12 months post-RTX, the improvement was recorded in manual muscle testing (MMT-8) scores, physician global assessment (PGA), patient global assessment (PtGA) and median steroid dosage as compared with the baseline (P < 0.01 for all). A mean (s.d.) improvement of 44.5 (16) and 48.7 (19.2) in total improvement score was recorded at 6 and 12 months, respectively. The change in MMT-8, PGA and PtGA scores from baseline between the two dosage regimens of RTX were comparable at 6 and 12 months. Severe lower respiratory tract infections requiring hospitalization occurred in three patients of the cohort. CONCLUSION: RTX improved IMACS core set measures and had steroid sparing efficacy at 6 and 12 months in patients with IIM in this registry-based study. Rituximab as an induction regimen of two doses of 500 mg can be as efficacious as 1 g at 6 months and 12 months of follow-up.

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.

Clusters based on demography, disease phenotype, and autoantibody status predicts mortality in lupus: data from Indian lupus cohort (INSPIRE).

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.

Risk factors associated with COVID-19 in systemic lupus erythematosus: Results from a longitudinal prospective cohort.

INTRODUCTION: Patients with SLE (systemic lupus erythematosus) have a higher risk of infection due to dysregulated immune system as well as long-term use of immunosuppressants (IS). This could influence the risk of COVID-19 and its outcome. METHODS: We conducted a longitudinal prospective study across 15 rheumatology centres during the first wave of the pandemic to understand the risk factors contributing to COVID-19 in SLE patients. During the 6 months follow-up, those who tested positive for COVID-19, their clinical course and outcome information were recorded. RESULTS: Through the study period (April-December 2020), 36/1379 lupus patients (2.9%) developed COVID-19. On analysing the COVID-19 positive versus negative cohort during the study period, male gender (adjusted RR 3.72, 95% C.I. 1.85,7.51) and diabetes (adjusted RR 2.94, 95% C.I. 1.28, 6.79) emerged as the strongest risk factors for COVID-19, in the adjusted analysis. There was no significant influence of organ involvement, hydroxychloroquine, glucocorticoid dosage (prednisolone< 7.5 mg or ≥ 7.5 mg/day) or IS on the risk of COVID-19. There was only one death (1/36) among the lupus patients due to COVID-19. CONCLUSION: Traditional risk factors rather than lupus disease process or IS influenced the risk of COVID-19 in our cohort.

Neuropsychiatric manifestations are associated with increased mortality in Indian patients with lupus: A single centre retrospective observational study.

OBJECTIVE: To study the prevalence of different NPSLE manifestations in our cohort and to compare clinical and immunological features and outcomes including mortality of patients with NPSLE and SLE controls without NP involvement. METHODS: This was a retrospective study in a tertiary care referral centre. All patients of SLE seen in the last 10 years and fulfilling the SLICC criteria with neuropsychiatric manifestations as per the ACR definitions were included. Patients of SLE without NP involvement were sequentially assigned as controls in a ratio of 1:2. RESULTS: Of the 769 patients diagnosed with SLE from Jan 2011 to December 2020, 128 (16.6%) had NPSLE manifestations as per the ACR definitions. The commonest NPSLE manifestation was seizures (6.5%) followed by cerebrovascular accident (3.9%). NPSLE manifestation occurred at the first presentation of SLE in 99/128 (77.3%) patients and 58 (45.3%) patients had more than one NPSLE manifestation. Lupus anticoagulant and anticardiolipin antibody were tested in 120 patients and were positive in 16 (13.3%) and 12 (10%), respectively. No difference was found in anti-ribosomal p, lupus anticoagulant and anticardiolipin antibodies between the cases and controls. Twenty-one (16.4%) deaths occurred in patients with NPSLE (median follow-up of 40 months) as compared to 13 (5%) in controls (median follow-up of 32 months) (p = <0.001). The cumulative survival of patients with NPSLE was lower as compared to controls (p < 0.001). Relapse of NPSLE was seen in 11(8.6%) patients and was associated with mortality (p = 0.017). CONCLUSIONS: Seizures and cerebrovascular accidents are the commonest NPSLE syndromes in our patients. The presence of NPSLE was associated with high mortality in Indian patients with lupus.

Clinical features, severity and outcome of acute pancreatitis in systemic lupus erythematosus.

Acute pancreatitis (AP) is a rare but life threatening manifestation of Systemic Lupus Erythematosus (SLE). The current study aims to study the clinical characteristics, severity, mortality, and outcome of SLE-related AP in Indian population. We retrospectively reviewed medical records of patients with SLE who had AP in the past. Data from 13 rheumatology centers across India were compiled. All patients satisfied SLICC criteria for SLE and ATLANTA criteria for AP. AP was classified in to mild, moderate and severe using revised Atlanta classification. Patients with known risk factors like gall stone and alcohol were excluded.Sixty-six patients (six, children) were studied. Majority of patients were females (82%). The median age of presentation was 24 (11-63) years and most patients (57.5%) presented within first year of diagnosis of lupus. AP occurred mostly in the setting of active lupus (89%). Active nephritis was seen in 39% while a fourth had CNS disease. Patients with severe AP had lower C3. Ascites and sepsis were most common local and systemic complications, respectively. Mortality was 17%. Hypocalcemia, presence of sepsis and shock predicted mortality. In the multivariate analysis, only presence of shock remained as independent predictor of death (OR 63.0, 95% CI: 5.2-760.3). Pancreatitis is an early manifestation of SLE and is associated with active disease. Significant mortality is seen particularly with severe pancreatitis.

Identification and stratification of systemic lupus erythematosus patients into two transcriptionally distinct clusters based on IFN-I signature.

OBJECTIVE: Despite the significant advancement in the understanding of the pathophysiology of systemic lupus erythematosus (SLE) variable clinical response to newer therapies remain a major concern, especially for patients with lupus nephritis and neuropsychiatric systemic lupus erythematosus (NPSLE). We performed this study with an objective to comprehensively characterize Indian SLE patients with renal and neuropsychiatric manifestation with respect to their gene signature, cytokine profile and immune cell phenotypes. METHODS: We characterized 68 Indian SLE subjects with diverse clinical profiles and disease activity and tried to identify differentially expressed genes and enriched pathways. To understand the temporal profile, same patients were followed at 6 and 12-months intervals. Additionally, auto-antibody profile, levels of various chemokines, cytokines and the proportion of different immune cells and their activation status were captured in these subjects. RESULTS: Multiple IFN-related pathways were enriched with significant increase in IFN-I gene signature in SLE patients as compared to normal healthy volunteers (NHV). We identified two transcriptionally distinct clusters within the same cohort of SLE patients with differential immune cell activation status, auto-antibody as well as plasma chemokines and cytokines profile. CONCLUSIONS: Identification of two distinct clusters of patients based on IFN-I signature provided new insights into the heterogeneity of underlying disease pathogenesis of Indian SLE cohort. Importantly, patient within those clusters retain their distinct expression dynamics of IFN-I signature over the time course of one year despite change in disease activity. This study will guide clinicians and researchers while designing future clinical trials on Indian SLE cohort.

Impact of the COVID-19 pandemic on patients with systemic lupus erythematosus: Observations from an Indian inception cohort.

INTRODUCTION: The ongoing pandemic of COVID-19 has led to severe disruption of healthcare services worldwide. We conducted this study to assess the impact of COVID-19 pandemic on the management of Systemic Lupus Erythematosus (SLE) patients who were enrolled in the nation-wide inception cohort. METHODS: A questionnaire was administered to the SLE patients enrolled in the inception cohort. Questions related to the effect on disease activity, preventive measures adopted against COVID-19, the incidence of COVID-19, hardships faced in getting access to health care professionals and availability of medicines, adherence, fear of COVID-19 and the potential benefits of being part of the registry. RESULTS: A total of 1040 (90% females) patients completed the questionnaire. The mean age was 27.5 ± 19.1 years and the mean disease duration was 1.25 years. Twenty-Four (2.3%) patients had developed fever (>1 day) during this period, including one patient with additional symptoms of diarrhoea and anosmia, however, none of the patients developed COVID-19 infection. 262 patients (25.2%) reported financial difficulty during this period and patients reported an average excess expenditure of at least 2255.45 INR ($30) per month. 378 patients (36%) reported problems in getting their prescribed medicines due to lockdown. Of these, 167 (40%) patients needed to change their medication schedule due to this non-availability. Almost 54% of patients missed their scheduled follow up visits during the lockdown period and 37% of patients were unable to get their investigations done due to closure of laboratories and hospitals. 266 patients (25.5%) reported worsening of various symptoms of SLE during this period. Almost 61% patients felt confident that being associated with the inception cohort had helped them in managing their disease better during this period of lockdown as they received help in the form of timely and frequent telephonic consults, assistance in making the medicines available, and regular counselling resulting in abetment of their fears and anxieties. CONCLUSION: The current COVID-19 pandemic has made a huge impact on our SLE patients. Patients faced difficulty in the availability of medicines, missed the doses of medicines, had financial constraints, and spent more money on health during the pandemic.

Indian SLE Inception cohort for Research (INSPIRE): the design of a multi-institutional cohort.

Systemic lupus erythematosus (SLE) cohorts across the world have allowed better understanding of SLE, including its bimodal mortality, and the impact of social factors and ethnicity on outcomes. The representation of patients from South Asia has been poor in the existing SLE cohorts across the world. Hence, we planned to initiate an inception cohort to understand the diversity of lupus in India. Indian SLE Inception cohort for REsearch (INSPIRE), planned over 5 years is a multi-centric cohort of adult and childhood lupus patients of Indian origin, fulfilling the SLICC-2012 classification criteria, with an aim to provide cross-sectional information on demography, ethnicity, socio-economic status, standard disease variables, quality of life, and prospective information on new events like hospitalization, infections, pregnancies, changes in disease activity, and damage. One of the other deliverables of this project is the establishment of a biorepository. The instruments to be used for each variable and outcome were finalized, and a web-enabled case report form was prepared to encompass SLEDAI, BILAG, SLICC damage scores, and Lupus quality-of-life index.Ten centers located in different geographic areas of India would enroll patients who are seen for the first time after the start of the study. In the first 8 months, 476 patients (63 children, 36 males) have been enrolled with a median disease duration of 10 (IQR 4-17) months and mucocutaneous features being the most prevalent clinical manifestations. INSPIRE is the first prospective Indian SLE cohort to study the diversity of Indian patients.

Prevalence and Clinical Correlates of Myositis Specific Autoantibodies in Idiopathic Immune-Mediated Inflammatory Myositis - Results from a Multicentric Cohort (MyoIN) from India.

There is a need to understand the clinical and antibody associations in patients with IIM in various ethnicities and geographical areas. Patients who fulfilled Bohan's and Peter criteria of IIM and seen between October 2017 through Jan 2020 were enrolled in this study at 3 centres. Clinical and relevant laboratory parameters were recorded in a pre designed case record form. MSA and MAA to 16 antigens were performed by line blot assay using Euroimmun (Luebec, Germany) as per manufacturer's instruction. Of the 150 patients, 13 were juvenile onset. Ninety sera had either one MSA or MAA. Sixty sera had neither MSA/MAA. anti-Ro 52 were the commonest antibody and anti-Mi-2α and b the commonest MSA. Novel associations identified were severe myositis with anti-Ro 52, cutaneous ulcerations with anti-MDA5 and anti-PM-Scl and calcinosis with anti-PM-Scl. One-third sera had no MSA or MAA. Larger sample size and use of antibody assays together with muscle biopsy will improve subtyping and phenotype associations in IIM.

Urinary C3d is elevated in patients with active Lupus nephritis and a fall in its level after 3 months predicts response at 6 months on follow up.

INTRODUCTION: Complement activation is central to the pathogenesis of lupus nephritis (LN). Low serum complement C3 and C4, are traditionally used as markers of lupus disease activity in general and LN in particular. In this study we prospectively measured plasma and urine C3d and C4d, degradation products of C3 and C4 corrected to creatinine in a cohort of biopsy proven LN in a longitudinal fashion for its correlation with disease activity. METHODS: Twenty eight biopsy proven active lupus nephritis (AN) were recruited along with four inactive nephritis (IN) and 10 healthy controls (HC). Plasma and urine were collected at baseline, prior to induction treatment and 3 months later. Clinical measures of disease activity, Systemic lupus erythematosus disease activity index 2000 (SLEDAI 2K), renal SLEDAI, serum C3, C4 and antibodies to ds DNA, urine protein and creatinine excretion (UP/UC) were collected. Plasma and urine C3d and C4d were measured using ELISA and normalized to spot urine creatinine value. RESULTS: Twenty eight AN of median age of 26.5 (20-31.50) years and disease duration of 3 (0.7-5) years were enrolled. The median urinary C3d/creatinine before treatment was 388.20 (48.98-1296) ng/mg which fell significantly to 62.69 (28.04-502.4) ng/mg at 3 months followup (p-0.01). The baseline values for the active renal disease was significantly different from IN group (9.9 (4.5-46.53 ng/mg) p-0.00). Treatment responders (partial and complete) at 6 months showed a significant fall in urinary C3d at 3 months whereas non responders had a non significant change in value. There was a significant correlation of urine C3d/creatinine with SLEDAI2K (r-0.433, p-0.00), renal SLEDAI (r-0.356, p-0.00), UP/UC ratio (r-0.489, p-<0.0001) but no significant correlation with C3 or C4. There was a significant fall in the median values of plasma C3d from 791.1 (516.0.00-1550.43) µg/ml to 338.52 (211.35-525.82) (p-0.00) µg/ml at the end of 3 months. The values showed a significant correlation with SLEDAI 2K, renal SLEDAI, UP/UC along with a significant negative correlation with C3 and C4. CONCLUSION: Urinary C3d/creatinine levels and plasma C3d levels can be used as biomarker of disease activity and treatment response.

Maternal and fetal outcomes of lupus pregnancies: A collective effort by Karnataka Rheumatologists.

INTRODUCTION: Identifying factors predicting adverse pregnancy outcomes involving systemic lupus erythematosus (SLE) is a research priority. The aims of this study were to investigate (a) the maternal and fetal outcomes of pregnant lupus patients and the factors associated with adverse pregnancy outcomes, and (b) the effect of pregnancy on lupus disease activity of these patients. METHODS: This was an ambi-directional study collecting information from five multi-specialist referral centres across the state of Karnataka, India over 5 years (2013-2018). Clinical details of pregnancies and outcomes that were temporally associated with lupus disease were recorded using a structured pro forma. The Safety of Estrogen in SLE National Assessment-SLE Disease Activity Index (SELENA-SLEDAI) was used to assess lupus activity during the 6 months prior to pregnancy and the intra- and post-partum periods. Modifications suggested in the SLE Pregnancy Disease Activity Index were considered while scoring. RESULTS: A total of 121 pregnancies in 80 SLE patients with a mean age of 27.1 (±4.5) years and with a mean disease duration of 4.6 (±4.1) years were reviewed. Largely patients were in clinical remission (109/121; 90.1%). Antiphospholipid antibody positivity was seen in 45/121 (37.2%) patients. A history of lupus nephritis was noted in 29/121 (24%) patients. Maternal complications (32%) were mainly due to hypertensive disorders of pregnancy (HDP; 19/121; 15.7%). Adverse fetal outcomes (58%) were mainly in the form of spontaneous first-trimester abortions (21/121; 16%), stillbirth (14/121; 11.6%) and prematurity (24/121; 20%). HDP is strongly associated with stillbirth and prematurity and is independent of active lupus. Disease activity was associated with a three-fold increased risk of adverse fetal outcome in univariate analysis. The risk of major flare during pregnancy is low (4.1%) when conception occurs during stable disease. Hydroxychloroquine (HCQ) use was associated with reduced risk of flare (p = 0.001) in patients in remission at the time of conception. CONCLUSIONS: The risk of major flare during pregnancy is low when conception happens during stable disease. HCQ use was associated with reduced risk of flare in patients in remission at the time of conception. HDP was strongly associated with stillbirth and prematurity and are independent of active lupus in our cohort.

Eltrombopag: Efficacy and Safety in Steroid Refractory Lupus-Associated Immune Thrombocytopenia.

BACKGROUND: Eltrombopag, a thrombopoietin receptor agonist, is effective in chronic immune thrombocytopenia (ITP). The data in lupus ITP are sparse. This study aimed to assess the efficacy and safety of eltrombopag in lupus ITP. METHODS: This is a single-center study conducted between 2012 and 2017 of 12 subjects with systemic lupus erythematosus-associated ITP. Patients with inadequate or suboptimal response to steroids and other immunosuppressants treated with eltrombopag were included in the study. Time taken for response to therapy (defined as platelets >1 lakh), dose, duration of treatment, and adverse effects of the drug were noted. RESULTS: A total of 12 subjects were included in the study. The median platelet count at initiation of eltrombopag was 19,000 per µL. The time taken for response to therapy was 8 days. The median platelet count at 1-month follow-up was 241,000 per µL. All patients were concurrently treated with steroids and other immunosuppressants. Sustained benefit after stopping eltrombopag was noted in all patients. No adverse events including thrombotic complication were noted. CONCLUSIONS: Eltrombopag is a new drug in our arsenal for treatment of ITP in lupus. It is a rapidly effective, safe, and orally administered medication. It indirectly contributes to reduction in the dose of steroids and immunosuppressants, thereby minimizing their cumulative adverse effects. It is a promising and safe option for the treatment of lupus-associated thrombocytopenia, but this needs further confirmation from multicenter, multiethnic, randomized controlled trials.

Incidence of infection other than tuberculosis in patients with autoimmune rheumatic diseases treated with bDMARDs: a real-time clinical experience from India.

Biologic disease-modifying anti-rheumatic drugs (bDMARD) have transformed the treatment paradigm of chronic autoimmune rheumatic diseases (ARDs), but they are often associated with adverse drug reactions. The present study evaluated the frequency, characteristics and type of infections, other than tuberculosis (TB), in ARD patients receiving bDMARDs. The multicentre, cross-sectional, retrospective, observational study was conducted across 12 centers in Karnataka, India, between January to August 2016. The study included patients receiving bDMARD therapy for various ARDs. Outcome variables considered were any infection, minor infections and major infections, other than TB. Clinical variables were compared between infection and no infection group, and the increase in the likelihood of infection with respect to various clinical variables was assessed. The study involved 209 subjects with a median (range) age of 41 (16-84) years and male to female ratio of 0.97:1. A total of 29 (13.88%) subjects developed infection following bDMARD therapy, out of whom a majority had minor infection (n = 26). The likelihood of developing any infection was noted to be more in subjects receiving anti-TNF (golimumab, P = 0.03) and those on three or more conventional synthetic (cs) DMARDs (P < 0.01). Infection risk was higher in patients with systemic lupus erythematosus (P = 0.04), other connective tissue disease (P < 0.01) and in patients with comorbidities (P = 0.13). The risk of infection was associated with the use of anti-TNF therapy and more than three csDMARDs, co morbidities and Adds such as systemic lupus erythematosus and connective tissue disease.

Musculoskeletal disorders in sickle cell anaemia--unusual associations.

Sickle cell anaemia coexisting with gout is a rare clinical association, as is gout and eosinophilia. This report records the second case of chronic tophaceous deposits in Sickle cell anaemia. The patient also had eosinophilia in association with gout. Skeletal fluorosis was an incidental finding in this patient. Treatment with packed cell transfusions, hydroxyurea and colchicine lead to the resolution of anaemia and symptoms of acute gout.

A study to determine the effect of hydroxychloroquine (HCQ) on central corneal thickness (CCT) in patients with rheumatoid arthritis (RA).

PURPOSE: Corneal thinning is common in rheumatoid arthritis (RA), thereby affecting the central corneal thickness (CCT). Effect of hydroxychloroquine (HCQ) in RA has abounding literature on retinal toxicity, but there is lack of data on its corneal effects. METHODS: A cross-sectional study was carried out to compare CCT in RA patients before treatment initiation (Group 1) with CCT in those on HCQ for ≥3 months (Group 2). RESULTS: Fifty patients were enrolled in each group. The mean age was 44.36 years with similar age, gender distribution and visual acuity in both groups. The mean CCT of patients in the cohort was 521.80 µm ± 32.57 µm and 523.94 µm ± 33.40 µm in the right eye (RE) and left eye (LE), respectively. Mean CCT in Group 1 was (RE) 522.80 µm/(LE) 524.26 µm and in Group 2 was (RE) 520.80 µm/(LE) 523.62 µm, and there was no significant difference in CCT between both the groups. Median duration of HCQ usage in Group 2 was 24 months, with the median cumulative dosage being 171 g and a majority having a dosage of 200 mg/day. There was no significant correlation between the duration/cumulative dosage of HCQ intake and CCT. No corneal deposits were identified in any patient. CONCLUSION: CCT of RA patients was similar to those reported in the Indian literature. However, there was no significant change in CCT or corneal deposits identified with an HCQ dosage of 200-400 mg/day. Longer follow-up would provide clarity on the impact of duration and cumulative dosage of HCQ on corneal changes and CCT.

Effectiveness of generic tofacitinib in idiopathic inflammatory myositis (IIM)-a retrospective analysis from Indian Myositis Registry (MyoIN).

OBJECTIVES: Determine domain-based-outcomes and steroid-sparing efficacy of generic tofacitinib in IIM. METHODS: This is a multicenter retrospective study wherein clinical phenotype, autoantibody profile, prior immunosuppressives, and outcomes at 3, 6, and 12 months were retrieved for IIM patients prescribed tofacitinib. Overall clinical response was assessed as complete or partial remission as per physician judgment. Changes in cutaneous and calcinosis domain were recorded as per physician global assessment (PGA), lung domain as per medical research council (MRC) dyspnea scale, and muscle strength by Manual Muscle Testing-8 (MMT-8). RESULTS: Forty-two patients of IIM with mean age 38.7 ± 16 years; (76.2% (N = 32) women), median duration of illness 48 (19;88) months were included. Commonest indication for initiating tofacitinib was either for refractory or as steroid sparing for cutaneous domain (N = 25/42, 59.5%) followed by calcinosis (N = 16/42, 38%). Overall complete and/or partial remission was achieved in 23/37 (64.8%), 30/35 (85.7%), and 29/30 (96.6%) patients at 3, 6, and 12 months, respectively. At 12-month follow-up, there was a reduction in prednisolone dose, with absolute decrease from a daily dose of 17.5 mg (IQR 5;50) to 2.5 mg (IQR 0;5) (p < 0.001). Individual domain assessments revealed improvement in cutaneous domain [16/25 (64%)] and calcinosis [6/15 (40%)]. Adverse effects included herpes zoster (N = 2/42, 4.8%) and dyslipidemia (N = 4/42, 9.5%). CONCLUSIONS: Treatment with generic tofacitinib significantly reduces the daily dose of corticosteroids and is effective in cutaneous domain including calcinosis in IIM. KEY POINTS: • This multicenter retrospective study is the first real-world data from India, elucidating steroid sparing efficacy of generic tofacitinib in patients with inflammatory myositis. • Domain-based outcome assessment suggests good clinical improvement especially in cutaneous domain, even those with refractory disease. • Modest benefits were evident in calcinosis, but its effect on the muscle and pulmonary domain appears limited.