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.

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.

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.

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.

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.

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.

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.

Haemophagocytic lymphohistiocytosis associated with liver injury in systemic sarcoidosis.

Hepatic involvement in sarcoidosis, though common, is usually asymptomatic. Hepatomegaly and deranged liver function tests are the usual manifestations. However, unexplained hepatomegaly in sarcoidosis not responding to immunosuppressive therapy could indicate an alternative pathology. Haemophagocytic lymphohistiocytosis (HLH), although seldom reported in sarcoidosis, can cause hepatosplenomegaly and cytopenias. HLH occurring concomitantly with hepatic sarcoidosis is extremely rare. We report a patient of systemic sarcoidosis who presented with fever, hepatosplenomegaly and jaundice despite being on steroid therapy. He was subsequently diagnosed with HLH. The clinical response to treatment with pulse steroid and oral cyclosporine was dramatic.

Use of Animal and Animal Products for Rheumatoid Arthritis Treatment: An Explorative Study in Odisha, India.

Severe fatigue, pain, deformity, and disability, are the major concerns for rheumatoid arthritis (RA). The extreme pain experienced by the patients often force them to experiment with various indigenous substances including animals and animal products. However, there is little evidence on the use of animals or animal products as traditional medicine in RA. Hence, this study was aimed to explore the experience and perception of patients toward the use of animals and animal products for the treatment of RA. A qualitative, explorative study was conducted at the out-patient-department of Rheumatology of a tertiary care medical college and hospital at Cuttack, Odisha, India. Out of 113 patients with RA, 18 patients gave history of use of animal and/or animal products and were selected for in-depth interviews. The content analysis methods were used for data analysis. Four major categories emerged: (1) prevailing patterns of traditional treatment of RA using animals, (2) beliefs and values behind the traditional treatment of RA, (3) sources and traditional learning pathway of indigenous practices on RA, and (4) ethical aspects of the indigenous practice of using animals and/or animal products in the treatment of RA. This study revealed the practice of eating dead animals to get relief from RA. However, there was hardly any perceived positive outcome of the practice; which indicates the lack of awareness of rational, scientific, treatment, and prevalence of irrational and unethical practices for the treatment of RA. Hence, community awareness, social mobilization, and newer screening tools are necessary to improve the timely detection and prevention of irrational treatment practices among RA patients.