Tuberculosis remains a leading contributor to morbidity due to serious infections in Indian patients of SLE.

INTRODUCTION: Infections are a major cause of morbidity and mortality in systemic lupus erythematosus (SLE). We assessed the incidence and risk factors for major infections in SLE in India. METHODS: A retrospective review of a cohort of 1354 patients of adult SLE (ACR 1997 criteria) seen between 2000 and 2021 at a single center was conducted. Serious infections (need for hospitalisation, prolonged intravenous antibiotics, disability, or death) were recorded. Cox regression was used to determine factors associated with serious infection and the effects of serious infection on survival and damage. RESULTS: Among the 1354 patients (1258 females, mean age of 30.3 years, follow-up of 7127.89 person-years), there were 439 serious infections in 339 patients (61.6 per 1000 person-years follow-up). Bacterial infections (N = 226) were the most common infection followed by mycobacterial infections (n = 81), viral (n = 35), and then invasive fungal infections (N = 13). Mycobacterium tuberculosis was the single most common microbiologically confirmed organism with incidence of 1136.4/100,000 person-years with 72.8% of them being extrapulmonary. Infection free survival at 1 year and 5 years was 82.9% and 73.8%. There were 119 deaths with infection attributable mortality in 65 (54.6%). On multivariable Cox regression analysis, higher baseline activity (HR 1.02, 1.01-1.05), gastrointestinal involvement (HR 2.75, 1.65-4.69), current steroid dose (HR 1.65, 1.55-1.76), and average cumulative steroid dose per year (HR 1.007, 1.005-1.009) were associated with serious infection and higher albumin (HR 0.65, 0.56-0.76) was protective. Serious infections led to greater damage accrual (median SLICC damage index of 1 vs. 0) and mortality (HR was 18.2, 32.7 and 81.6 for the first, second, and third infections). CONCLUSION: Serious infections remain a major cause of mortality and damage accrual in SLE and higher disease activity, gastrointestinal involvement, hypoalbuminemia, current steroid dose, and cumulative steroid dose are the risk factors for it.

Charcot arthropathy of elbow due to syringomyelia: a case series and systematic review of literature.

Syringomyelia is an important etiology of Charcot arthropathy of the elbow. We present five interesting patients, along with a systematic literature review summarizing the clinical profile and management of syringomyelia-induced Charcot arthropathy of the elbow. PUBMED, SCOPUS, EMBASE, and Science Direct databases were screened for English articles published between 1980 and 2022 using the search query: "Syringomyelia" AND "elbow" AND ("arthropathy" OR "neuropathic" OR "Charcot"). Articles without full text and/or lack of conclusive evidence of elbow arthropathy due to syringomyelia were excluded. The reference lists of the selected articles were reviewed to identify additional articles describing syringomyelia-induced Charcot arthropathy of the elbow. All five patients in the current series had elbow arthritis with variable motor weakness and dissociated sensory loss. The literature review included 31 reports (45 patients) and five patients from our center (n = 50). The median age at presentation was 45 (13-77) years. The median duration of arthropathy was 24 (0.5-180) months. Thirty-three patients had isolated elbow arthropathies. The other joints affected included the shoulder (n = 13), wrist (n = 7), metacarpophalangeal joints (n = 3), and interphalangeal joints (n = 1). Chiari malformations were present in 33 (66%) patients. Sensory deficits, motor deficits, and ulnar neuropathies were described in 36 (72%), 31 (62%), and 14 (28%) patients, respectively. Surgical decompression for syringomyelia was performed in 13 (26%) patients. The presence of dissociated sensory loss, with or without motor weakness, is key to the suspicion of syringomyelia-induced Charcot arthropathy of elbow. Chiari malformation and ulnar neuropathy are frequently associated with this condition. Key Points • Charcot arthropathy of elbow is not so uncommon as believed • Syringomyelia is an important etiology of Charcot arthropathy of elbow • Therefore, all patients with elbow arthropathy of unknown etiology must be evaluated for dissociative sensory loss • Chiari malformation and ulnar neuropathy are commonly associated with syringomyelia-induced Charcot arthropathy of elbow joint.

The comparison of cardiovascular disease risk prediction scores and evaluation of subclinical atherosclerosis in rheumatoid arthritis: a cross-sectional study.

OBJECTIVES: Primary objectives estimated prevalence of traditional cardiovascular disease (CVD) risk factors and compared different CVD risk prediction algorithms in an Indian rheumatoid arthritis (RA) population. Secondary objectives evaluated associations between carotid intima-media thickness (CIMT) and subclinical atherosclerosis (SCA) with CVD risk factors and CVD risk scores. METHODS: The presence of CVD risk factors were recorded, and 10-year CVD risk was predicted using Framingham risk scoring (FRS) using lipids (FRS-Lipids), FRS using body mass index (FRS-BMI), QRISK-2, SCORE, and the algorithm recommended by ACC/AHA (ASCVD). CIMT was measured on the far-wall of the common carotid artery. Subclinical atherosclerosis was defined as CIMT > 0.9 mm or the presence of carotid plaque. RESULTS: A total of 332 patents were enrolled, 12% had diabetes mellitus, 21.4% hypertension, and 6.9% were current/past smokers. Proportions of RA with predicted 10-year CVD risk > 10% varied from 16.2 to 41.9% between scores. Highest magnitude of risk was predicted by FRS-BMI. Agreement between scores in predicting risk was moderate in general. Mean CIMT was 0.70 ± 0.15 mm. Age, male sex, and extra-articular manifestations associated with greater CIMT. All risk scores except SCORE moderately correlated with CIMT. About one-seventh had SCA defined as CIMT > 0.9 mm or the presence of carotid plaques, associated with increasing age, male gender, or higher ratio of total cholesterol to high-density lipoprotein cholesterol. ASCVD and QRISK-2 scores had maximum area under curve for distinguishing SCA. CONCLUSION: Individual CVD risk scores predict 10-year CVD risk differently in Indian patients with RA, and require validation for predicting hard end points (CVD events, mortality). Key Points • Diabetes mellitus and hypertension are the most prevalent cardiovascular disease risk factors in Indian patients with RA. • Individual cardiovascular risk prediction scores predict risk differently in Indian patients with RA, highest risk being predicted by the FRS-BMI. • Carotid intima-media thickness in RA associated with increasing age, male sex and extra-articular manifestations. • 14% RA had subclinical atherosclerosis, associated with increasing age, male sex, and higher total cholesterol to HDL-C ratio, best distinguished by ASCVD and QRISK-2 scores.

Role of interleukin-6 and interferon-α in systemic lupus erythematosus: A case-control study and meta-analysis.

BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disorder affecting various organ systems with unknown etiology. Interleukin-6 (IL-6) and interferon-alpha (IFN-α) have been shown to have a major role in disease pathogenesis, and they correlate with SLE disease activity, but reports in the literature are conflicting. The present study aims to investigate the significance of IL-6 and IFN-α levels in SLE pathogenesis in an eastern Indian cohort. MATERIAL AND METHODS: 70 SLE patients fulfilled SLICC 2012 criteria, and 40 age- and gender-matched healthy controls (HC) were enrolled. Baseline characteristics along with disease activity were recorded for all patients. Levels of IL-6 and IFN-α were measured by using ELISA. For the meta-analysis, published articles were searched through different databases. Two independent researchers extracted data, and the meta-analysis was performed with CMA v3.1. RESULTS: The plasma levels of IL-6 and IFN-α in SLE patients were significantly elevated compared to HC (IL-6: p < .0001, IFN-α: p = 0.01). SLEDAI score correlated positively with plasma IL-6 (p < .0001, r = 0.46) and IFN-α levels (p < .0001; r = 0.47). Meta-analysis of previous reports, including our case-control data, revealed higher IL-6 (p < .0001) and IFN-α (p = .005) in SLE patients compared to HC. Furthermore, IL-6 (p < .0001, r = 0.526) and IFN-α (p < .0001; r = 0.371) levels positively correlated with the disease activity. CONCLUSION: IL-6 and IFN-α levels are elevated in SLE and they correlate with disease activity. Further studies with a larger sample size in different populations are required to validate our findings.

Clinical spectrum of active tuberculosis in patients with systemic lupus erythematosus.

INTRODUCTION: There is paucity of data on tuberculosis in Indian patients with systemic lupus erythematosus (SLE). We retrospectively studied clinical features and outcome of tuberculosis in SLE. METHODS: Medical records of patients who developed tuberculosis simultaneous or after the diagnosis of SLE were retrospectively reviewed. All patients fulfilled 1997 ACR and/or SLICC 2012 classification criteria for SLE. A diagnosis of tuberculosis required bacteriological, histopathological or CT/MRI suggestive of tuberculosis and initiation of four drug antituberculous therapy. Baseline parameters were compared with the rest of cohort to identify predictors of tuberculosis. RESULTS: In our cohort of 1335 SLE patients, 48 (3.6%) developed tuberculosis. Incidence of tuberculosis was calculated to be 733 per 100,000 patient years and occurred after a mean disease duration of 3.0 ± 4.1 years. Extrapulmonary tuberculosis (n = 37) was commoner than pulmonary tuberculosis (n =11). Most common radiological pattern in pulmonary tuberculosis was miliary and musculoskeletal TB was most common extrapulmonary TB. A microbiological diagnosis was obtained in 52.1% patients. Male gender was associated with higher risk of tuberculosis [OR 3.30 (1.55-7.05)]. Mortality was 14.5% and all patients who died had either disseminated (n = 5) or central nervous system (CNS) tuberculosis (n = 2). CONCLUSION: Incidence of tuberculosis in SLE is higher than general population and is associated with different phenotype and higher mortality. Male gender was associated with increased risk of tuberculosis in SLE.

In-hospital mortality and its predictors in a cohort of SLE from Northern India.

BACKGROUND: Mortality in SLE has a bimodal peak with early deaths mainly related to disease activity and infection. Although mortality has reduced over years, it is still two to three folds compared to the general population. In India due to increased burden of infection and limited access to health care, the causes may be different. METHODS: Retrospective, review of records of all adult SLE patients fulfilling ACR 1997 criteria, who died in hospital between 2000-2019 at a teaching hospital in India was done. In addition, baseline clinical features were extracted for all adult SLE patients seen during this period.Infections were either bacteriologically proven or based on clinicradiological or serologic evidence. Active disease was defined as SLEDAI 2k ≥ 5. Logistic regression was performed to ascertain risk factors for mortality. RESULTS: A total of 1337 (92% females) patient records were reviewed .The mean age at presentation was 29.9 ± 9 years.60-75% of patients had fever, mucocutaneous disease and arthritis, while nephritis, hematologic, serositis and neurologic involvement was seen in 48.6%, 43.2%, 16% and 10.3% respectively as presenting mainfestations. There were 80 in hospital deaths .Infection was the most common cause of death, with 37 due to infection alone and in 24 disease activity also contributed. Only 18 deaths were due to active disease. Among bacterial infections lung was the most common site and gram negative organism were the most common pathogens. There were 10 deaths due to Tuberculosis(TB) and half of them had disseminated disease. Patients with disease activity had a SLEDAI of 14.8 ± 6.4, with neurological, renal and cardiovascular involvement being the major contributors to mortality in 11, 7 and 6 cases respectively. Higher age at onset, male gender, fever, myositis, neurological, cardiovascular, gastrointestinal involvement, vasculitis, elevated serum creatinine at baseline were independent predictors of death. CONCLUSION: Infections are the most common cause of in-hospital mortality in SLE and TB still accounts for 15% of deaths related to infection. Vasculitis, myositis, cardiovascular and gastrointestinal involvement emerged as novel predictors of mortality in our cohort.

Interstitial lung disease in Systemic sclerosis: insights into pathogenesis and evolving therapies.

Interstitial lung disease (ILD) is a leading cause of mortality in systemic sclerosis (SSc). However, mortality is improving as pathogenesis is being better understood and new therapies emerge. The roles of the inflammasome and NETosis in fibrosis are being elucidated. Epigenetic targets like DNA methylation and microRNA show promise as new targets for anti-fibrotic agents. The IL17-23 pathway has been shown to be active in SSc-ILD. Newer biomarkers are being described like CCL18 and the anti-eIF2B antibody. Hypothesis-free approaches are identifying newer genes like the ALOX5AP and XRCC4 genes. Computer-aided interpretations of CT scans, screening with ultrasonography and magnetic resonance imaging (MRI) are gradually emerging into practice. Imaging can also predict prognosis. A plethora of studies has shown the benefit of immunosuppression in halting ILD progression. Extent of lung involvement and PFT parameters are used to initiate therapy. The best evidence is for cyclophosphamide and mycophenolate. Besides these, corticosteroids and rituximab are being used in cases refractory to the first line drugs. Stem cell transplant is also backed by evidence in SSc. Longer studies on maintenance therapy are awaited. The inflammation in SSc is mostly subclinical and there is great interest in developing anti-fibrotic drugs for SSc-ILD. Perfinidone and nintedanib are under trial. The last resort is lung transplantation.