Caregiver burden in families of children with juvenile idiopathic arthritis in India.

Juvenile Idiopathic Arthritis (JIA) causes caregiver burden on families with children affected with it. Our study aimed to explore this multifaceted burden in the Indian context. In this cross-sectional study, we administered the Hindi translated CAREGIVER questionnaire to adult caregivers in the families of JIA patients ≤ 18 years. The responses to the 28 items were used to calculate the burden scores in various dimensions. The relationship of the global burden scores with demographic and socioeconomic factors were analysed. Non parametric tests were used. Two hundred twenty-one caregivers participated with a median age of 39 years (IQR 32-45). This included 116 fathers, 50 mothers, 32 brothers, 18 uncles, three grandfathers, one sister, and one grandmother. The JIA patients had a median age of 15 (12-17) years, and the male-to-female ratio was 3.2:1. Enthesitis-related arthritis was the predominant subtype (72.4%). Most caregivers (70.6%) expressed sadness at diagnosis, and 29.9% continued to express sadness. Nearly two-thirds (65.6%) had to borrow money from others. More than half (59.3%) of the caregivers neglected their health, and 9.0% became sick. Male gender of the child, systemic JIA subtype, low socioeconomic status, high disease activity, extra-articular damage, high parent-reported disease activity and poor quality of life were associated with higher global caregiver burden. JIA has a significant emotional, social, economic, and labour impact on caregivers. Economic and psychosocial support needs to be given to family caregivers caring for children with JIA.

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.

Renal involvement in Sjogren's syndrome: predictors and impact on patient outcomes.

Renal disease in primary Sjogren's Syndrome(pSS) occurs as tubulointerstitial nephritis(TIN) or glomerulonephritis(GN). Data from India on pSS are sparse and even less on nephritis.We studied the prevalence and impact of renal disease on patient outcomes. We reviewed 179 (F:M 12.7:1, age 41.7 ± 12.9 years) patients of pSS from records at a single centre from 2000 to 2020. Data on nephritis, clinical and laboratory variables were collected from baseline visit. Outcomes studied were chronic kidney disease(CKD) and death. We identified predictors of nephritis and rising creatinine on follow-up.Fifty-four (30.17%) patients had nephritis. Their mean age was 40.19 ± 13.28 years with 157.3 person-years follow-up. Vasculitis (OR 2.33, 1.02-5.3), fatigue (OR 3.29, 1.63-6.65), ANA positivity (OR 7.79, 1-60.62), anti-Ro52 (OR 2.74, 1.18-6.39), anti-La (OR 2.13, 1.1-4.14), both Ro and La (OR 2.4, 1.23-4.69) and lymphopenia (OR 2.27, 1.16-4.41) predicted nephritis on univariate analysis. On multivariate analysis, only fatigue (OR 2.83, 1.22-6.57) and an interaction between polyarthritis and vasculitis (OR 9.17, 1.15-72.96) was associated with nephritis. Creatinine at one (1.6 ± 1.17 mg/dL vs. 0.8 ± 0.2 mg/dL) and 2 years (1.62 ± 1.19 mg/dL vs. 0.8 ± 0.2 mg/dL) follow-up was higher in the nephritis group. Baseline haematuria, leukocyturia, 24 h urinary protein and thrombocytopenia were independent predictors of rising creatinine. Six patients died and 10 developed CKD. Event-free (death or CKD) survival was 89.1% at 5 years. Patients with nephritis had worse event-free survival.Our cohort had a younger age of onset of Sjogren's syndrome and a higher prevalence of nephritis than previously reported. Fatigue, polyarthritis and vasculitis at baseline predicted the development of nephritis. Nephritis was associated with a higher probability of death or CKD.

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.

Genetics and Autoimmunity: Two Sides of the Same Coin or an Epiphenomenon?

Distinguishing hereditary forms of myopathy from certain forms of inflammatory myopathy can be challenging. We present 3 cases where a certain degree of overlap was observed between genetics and autoimmunity. A child with juvenile dermatomyositis where heterozygosity for a pathogenic mutation implicated in LGMD1C resulted in a delayed diagnosis. A young lady with anti-SRP positive insidious proximal polymyositis worsening post-partum, diagnosed eventually as LGMD2. An adolescent child referred for proximal myopathy in view of paternal history of LGMD2 but found to have signs of systemic sclerosis with overlap myositis with excellent recovery on therapy. While improvements in whole genome sequencing and detection of myositis specific antibodies have revolutionised the diagnosis and treatment of these diseases, they are still not robust enough and may cloud good clinical judgement in accurate diagnosis and management. Higher sensitivity of these assays is bringing to the fore the possibility that these diagnoses may not be mutually exclusive and might plausibly be concurrent, pending further investigation. These are three interesting cases depicting the difficulties frequently encountered by rheumatologists and neurologists in distinguishing inflammatory from genetic myopathies.

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

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

Pulmonary mucormycosis in systemic lupus erythematosus: successful management of a case along with review of literature.

Pulmonary mucormycosis is rare in systemic lupus erythematosus. A 20-year-old lady with lupus nephritis and neuropsychiatric lupus was treated with injection methylprednisolone and cyclophosphamide. After few days, she developed fever, breathlessness, and hoarseness of voice. After neck and chest imaging, possibility of mucormycosis was considered which was later confirmed on microbiological test. Patient was treated with conventional amphotericin B. Literature review was done, and 8 patients with disseminated or pulmonary mucormycosis were identified with SLE. In patients with high index of suspicion, early imaging can help in diagnosis and early and aggressive management even with conventional amphotericin B can result in favorable outcome. Key Points • Pulmonary mucormycosis in systemic lupus erythematosus is rare. • Radiological investigation can guide towards diagnosis. • Early and aggressive treatment can lead to good outcome.

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.

Elevated urinary IL-36γ in patients with active lupus nephritis and response to treatment.

INTRODUCTION: IL-36 is a new member of the IL-1 family with pro-inflammatory properties. Serum levels of IL-36 are elevated in patients with Systemic Lupus Erythematosus (SLE). However, no data is available on urinary levels of IL-36 in Lupus Nephritis (LN). In psoriasis expression of IL-36 is site specific and expressed in skin. Hence, we studied urinary levels of IL-36 cytokines in SLE patients. METHODS: A total of 196 patients with SLE [97 active LN patients (ALN), 42 inactive LN (ILN) and 57 active lupus patients with no renal involvement (ANR)] and 25 healthy subjects were recruited for the study after obtaining informed consent. Urinary and plasma IL-36α, IL-36γ and IL-36Ra levels were measured by ELISA. RESULTS: Out of 196 patients 178 were females. Urinary IL-36γ levels in SLE patients [0(14.3) pg/ml] were significantly higher than healthy controls [0(0) pg/ml, (P < 0.01)]. Patients with ALN [0(40.6) pg/ml] had significantly higher IL-36γ when compared to ANR [0(0) pg/ml] as well as ILN [0(0) pg/ml]. Urinary IL-36γ levels in ALN patients had a fair correlation with renal SLEDAI (r = 0.26, P = 0.004).The levels reduced significantly post 3 months in patients with ALN. No inverse relationship was noted between IL-36Ra and IL-36α/IL36γ levels. CONCLUSION: Urinary IL-36γ is produced locally in kidney, correlates with renal disease activity and reduces upon treatment, suggesting that it may have a role in pathogenesis of LN.

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

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

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.

Comparison of Acute Physiology and Chronic Health Evaluation II, Modified Computed Tomography Severity Index, and Bedside Index for Severity in Acute Pancreatitis Score in Predicting the Severity of Acute Pancreatitis.

AIMS OF THIS STUDY: Severe acute pancreatitis has been defined recently based on the persistence of organ failure at 48 hours of admission. The bedside index for severity in acute pancreatitis (BISAP) score, a simplified scoring system to predict severity of acute pancreatitis, is proposed to be useful in early risk stratification of acute pancreatitis. Our aim was to prospectively compare BISAP score with the already established acute physiology and chronic health evaluation II (APACHE II) and modified computed tomography severity index (CTSI) scores in predicting the severity of acute pancreatitis. MATERIALS AND METHODS: A total of 87 consecutive cases presenting with the first attack of acute pancreatitis were included in the study. Acute physiology and chronic health evaluation II and BISAP scores were calculated from the worst parameters in the first 24 hours, and modified CTSI was reported at 48 hours of admission. Receiver-operating characteristic (ROC) curves were plotted, and predictive accuracy of each score was calculated from the area under the curve. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for each score. RESULTS: A total of 20 patients (23%) had severe acute pancreatitis with a total of 11 mortalities (12.64%), 10 of them in the severe acute pancreatitis group. Acute physiology and chronic health evaluation II, modified CTSI, and BISAP score all correlated well with each other. Modified CTSI and BISAP score also correlated with duration of hospital stay. Areas under the curve for APACHE II (≥8), modified CTSI (≥8), and BISAP score (≥2) were 0.826, 0.806, and 0.811, respectively, suggesting similar predictive accuracy. CONCLUSION: The BISAP score was similar to APACHE II and modified CTSI in terms of accuracy, sensitivity, specificity, and NPV. It is much easier to calculate and a useful risk stratification tool. It should be used for early triage and referral to a high dependency unit. HOW TO CITE THIS ARTICLE: Chatterjee R, Parab N, Sajjan B, Nagar VS. Comparison of Acute Physiology and Chronic Health Evaluation II, Modified Computed Tomography Severity Index, and Bedside Index for Severity in Acute Pancreatitis Score in Predicting the Severity of Acute Pancreatitis. Indian J Crit Care Med 2020;24(2):99-103.