A masquerade: An uncommon presentation of a dual infection of leprosy and human immunodeficiency virus.

Leprosy and human immunodeficiency virus (HIV) often mimic clinical features of connective tissue disease (CTD). They can present such as lupus, rheumatoid arthritis, scleroderma, or overlap syndromes and it sometimes creates confusion about the diagnosis. Serology may not be enough to differentiate the two and effective tissue biopsies are often the answer. We report the case of a 38-year-old female, who presented clinically with features of multisystem involvement suspected to be CTD, but was found to have dual infection: HIV and borderline tuberculoid leprosy.

A study of clinical, radiological features and HLA-B27 serology of axial spondyloarthropathy with comparison of radiographic and non-radiographic disease.

Background: Axial spondyloarthropathy is a type of disease which affects the axial skeleton affecting productive years. Methods: This was a cross-sectional, observational study in which 28 consecutive patients more than 16 years of age, fulfilling the Assessment of SpondyloArthritis International Society (ASAS) criteria for axial spondyloarthropathy were included. They were further sub-grouped into radiographic and non-radiographic axial spondyloarthropathy. Clinical features, joint involvement, measurements, HLA-B27 serology, and disease activity were evaluated. Data was entered into Microsoft Excel, and SPSS (Statistical Package for Social Sciences) software 2.0 was used for analyzing the data. Results: Mean age was 28.5 ± 6.3 years. 85.7% were males. Inflammatory low back pain was the most common clinical feature at presentation (89.2%). Enthesitis was the most common extra-articular feature seen in 35.7% of patients. 42.8% were non-radiographic axial spondyloarthritis. 85.7% of patients were HLA-B27 positive. 50% of patients had bone marrow edema on MRI, and only one patient had ankylosis indicating predominantly early disease. 50%-70% of our patients had high disease activity and 89.3% were responding well to non-steroidal anti-inflammatory drugs (NSAIDs). There was no significant difference between the radiographic axial spondyloarthritis group and the non-radiographic group except for elevated C-reactive protein (CRP). Conclusion: Ankylosing spondylitis in western India occurs mostly in the age group of 20-30 years, suggesting affection of productive age group. There was a delay of diagnosis for approximately three years from the onset of symptoms. There was a positive association with HLA-B27 in majority of the patients. Most of our patients had early disease based on radiological findings, suggesting that there was room for therapeutic intervention before irreversible ankylosis had set in.

High Prevalence of Active Tuberculosis in Adults and Children with Idiopathic Inflammatory Myositis as Compared with Systemic Lupus Erythematosus in a Tuberculosis Endemic Country: Retrospective Data Review from a Tertiary Care Centre in India.

AIM: Infections are the leading cause of morbidity and mortality in idiopathic inflammatory myositis (IIM) with India being endemic for Tuberculosis (TB). We compared and contrasted the prevalence, clinical profile and outcomes of active TB in IIM with systemic lupus erythematosus (SLE). METHODS: Medical records were reviewed for adults and children with IIM (Bohan and Peter criteria) and SLE (ACR criteria) at a tertiary care hospital in India from January 2015 to October 2017. Follow-up was recorded until February 2020 for all those who had developed active TB. RESULTS: Of 167 (132 adults and 35 juvenile) IIM and 280 (131 adults and 149 juvenile) SLE, active TB occurred in 24 (14.4%) IIM (22 (16.7% of 132) adults; 2 (5.71% of 35) juvenile) and 18 (6.4%) SLE [(8 (6.1% of 131) adults; 10 (6.7% of 149) juvenile, p-value < 0.01]. Patients with IIM had higher odds of developing TB as compared with SLE [OR 2.24 (CI 1.5-5.5), p=0.007]. The risk of developing active TB was 68-fold and 30.4-fold higher in patients with IIM and SLE, respectively, as compared with the general population. Extrapulmonary forms were more common (14/24). Nearly half developed TB during active IIM, at a glucocorticoid dose of 0.25 (0-1.5) mg/kg/day. Over a follow-up duration of 27 months (8-184), all were cured of TB, though prolonged course of anti-tuberculous treatment was required in 25%, and five IIM relapsed during treatment. CONCLUSION: Patients with IIM have increased risk of active TB, with common extrapulmonary forms, slow response, and relapses during treatment.

Infections Are Leading Cause of In-Hospital Mortality in Indian Patients With Inflammatory Myopathy.

OBJECTIVES: We explored causes of in-hospital mortality in patients with inflammatory myositis at a tertiary care center in Northern India. METHODS: Records of adults and children diagnosed with dermatomyositis (DM), polymyositis, or anti-synthetase syndrome (ASSD) who died between 2000 and 2018 were reviewed, and causes of death were determined. RESULTS: Of the 38 patients, 20 had DM (including 2 clinically amyopathic DM), 4 juvenile DM, 12 polymyositis, whereas 2 had ASSD. Median age at death was 42.0 (interquartile range, 32.8-52.5) years. Median disease duration at death was 18.5 (interquartile range, 2.0-23.5) months. Twenty-four (63.2%) had infection as the primary cause of death. Other causes of death included pharyngeal muscle weakness and aspiration (n = 6), myocarditis (n = 2), respiratory failure (n = 2), cerebral bleed (n = 2), and pulmonary embolism (n = 1). One patient succumbed to rapidly progressive interstitial lung disease, whereas another patient with ASSD died following respiratory distress after rituximab infusion. In post hoc analysis, although thrombocytopenia appeared to be a risk factor for early mortality (odds ratio, 13.3; 95% confidence interval, 1.4-123.8; p = 0.01), this was not supported in the multivariate analysis. CONCLUSIONS: Infections are the most common cause of in-hospital mortality in myositis patients.

Juvenile Reactive Arthritis and other Spondyloarthritides of Childhood: A 28-year Experience from India.

OBJECTIVES: Understanding of Juvenile reactive arthritis (jReA) and other spondyloarthritides of childhood (jSpA) is limited to small case series. Since most of them have speculated pathogenic origins in the gut, we compared and contrasted jReA with other jSpA -Enthesitis-related arthritis (ERA) and undifferentiated SpA (jUSpA). METHODS: A record-based medical data review of jReA, and jUSpA was compared with cohort data of ERA collected for other studies. Data are presented as median (interquartile range) and non-parametric tests used for analysis. RESULTS: Of 179 juvenile SpA (61 jReA; 101 ERA; and 17 jUSpA), 61 had jReA [M:F-52:9; 15.5 (12-18) years] with a disease duration of 2.75(1-36) months. Inflammatory backache IBP (32%), dactylitis (21%) and enthesitis (29%) were common. A significant proportion (14 of 17, 82.3% at >6 months follow-up) had a chronic course. 101 ERA [M:F-93:7; age-16(14-20) years] had a longer disease duration (45 vs 2.75 months, p<0.001), as compared with jReA. Enthesitis and IBP was more common in ERA (OR-2.3 and 3.4 respectively). jUSpA (n=17) had a similar clinico-laboratory profile and exhibited significant (7 of 17, 58.3%) chronicity over 9.5(4.8-37) months follow-up. CONCLUSION: jReA and jSpA exhibit similar features apart from varying disease duration, suggesting that jspA may form a continuum with similar clinico-laboratory profiles plausibly due to shared pathogenesis.

Outcomes of Pregnancy in Women With Inflammatory Myositis: A Cohort Study From India.

OBJECTIVES: Idiopathic inflammatory myositis (IIM) commonly affects women in the childbearing age group. Both disease activity and immunosuppressants used may have adverse effects on fertility and outcomes of pregnancy. We explored these outcomes in a cohort of women with IIM. METHODS: Women 18 years or older with IIM (Bohan and Peter criteria) were interviewed for demography, menstrual status, history of conception, outcomes, and disease features. Comparisons were drawn between pregnancies occurring before and after onset of disease. RESULTS: Eighty-one IIM patients with median age of 32 years (interquartile range, 26-50 years) and disease duration of 4 years (interquartile range, 2-9 years) were interviewed. Forty-five patients had dermatomyositis, 20 had polymyositis, and 16 had overlap myositis. Sixty-three patients had conceived before disease onset, resulting in 205 pregnancies and 155 live births over 315.2 patient-years of follow-up.After disease onset, there were 24 pregnancies (6 live births, 16 spontaneous abortions, and 2 induced abortions) in 7 women over 77.5 patient-years. Of the live births, 1 had cleft palate, 1 had low birth weight, and 1 was preterm. None of the patients who conceived had antiphospholipid antibodies.Obstetric complications (relative risk [RR] = 7.6; p < 0.0001) and fetal complications (RR = 2.7; p = 0.002) occurred more frequently in pregnancies after the onset of myositis, although there was no difference in maternal complications. Conception after the onset of myositis had higher risk of abortion (RR = 3.6; p < 0.0001). CONCLUSIONS: Women with IIM suffer from poor fetal outcomes as well as high rates of spontaneous abortion rates in the absence of clinical or serologic anti-phospholipid syndrome.

Poor obstetric outcomes in Indian women with Takayasu arteritis.

INTRODUCTION: Takayasu's arteritis (TA) affects young women in the childbearing age group. We studied obstetric outcomes in these patients before and after disease onset. METHODS: Women aged more than 18 years with Takayasu's arteritis (ACR 1990 criteria) were included. Demographic data, clinical features, disease activity using Indian Takayasu Arteritis clinical score (ITAS), Disease Extent Index for TA (DEI.TaK) and damage assessment using TA Damage score (TA), history of conception and maternal and fetal outcomes were recorded from hospital records and telephonic interview. Results are in median and IQR. RESULTS: Of the 64 women interviewed, aged 29 (24-38) years and disease duration 5 (4-10) years, 74 and 38 pregnancies had occurred before and after disease diagnosis in 29 and 20 women respectively. In eight, the diagnosis was made during pregnancy. Age at disease onset was 22 (18-30) years. Type 5 disease was the most common (n = 32, 59.3%), and an equal number of patients had Ishikawa's class I and II disease (n = 26, 40.6%). Median ITAS (n = 44) was 13 (7-16), DEI.Tak 12.5 (9-16.75) and TADS 8 (6.5-10). Twenty-five patients wanted to get pregnant, of which 8 (32%) did not do so because of their disease. Fifteen were unmarried of whom 6 did not marry due to disease. Obstetric outcomes were poorer in pregnancies that occurred after the onset of disease as compared with those before it (RR = 1.5, p = 0.01). Pregnancies after the onset of TA carried a very high risk of maternal [RR3.9 (1.8-8.5), P < 0.001] as well as fetal complications [RR = 2.0 (1.2-3.4), p = 0.001]. Hypertension was the most common maternal complication and occurred most often in the last trimester. The baby weight at birth was lower in pregnancies after disease (2.3 vs. 3.0, p = 0.01). Wong's score greater than or equal to 4 predicted lower birth weight (p = 0.04). ITAS, ITAS-A, DEI. Tak and TADS could not predict obstetric outcomes, and ITAS score exhibited moderate correlation with DEI. Tak (r = 0.78) and TADS (r = 0.58). CONCLUSION: Women with TA suffer from extremely high risk of poor maternal and foetal outcomes. Wong's scoring can be useful to predict birth weight.

Poor obstetric outcomes in Indian women with Takayasu arteritis

Abstract Introduction: Takayasu's arteritis (TA) affects young women in the childbearing age group. We studied obstetric outcomes in these patients before and after disease onset. Methods: Women aged more than 18 years with Takayasu's arteritis (ACR 1990 criteria) were included. Demographic data, clinical features, disease activity using Indian Takayasu Arteritis clinical score (ITAS), Disease Extent Index for TA (DEI. TaK) and damage assessment using TA Damage score (TA), history of conception and maternal and fetal outcomes were recorded from hospital records and telephonic interview. Results are in median and IQR. Results: Of the 64 women interviewed, aged 29 (24-38) years and disease duration 5 (4-10) years, 74 and 38 pregnancies had occurred before and after disease diagnosis in 29 and 20 women respectively. In eight, the diagnosis was made during pregnancy. Age at disease onset was 22 (18-30) years. Type 5 disease was the most common ( n = 32, 59.3%), and an equal number of patients had Ishikawa's class I and II disease ( n = 26, 40.6%). Median ITAS ( n = 44) was 13 (7-16), DEI. Tak 12.5 (9-16.75) and TADS 8 (6.5-10). Twenty-five patients wanted to get pregnant, of which 8 (32%) did not do so because of their disease. Fifteen were unmarried of whom 6 did not marry due to disease. Obstetric outcomes were poorer in pregnancies that occurred after the onset of disease as compared with those before it (RR = 1.5, p = 0.01). Pregnancies after the onset of TA carried a very high risk of maternal [RR3.9 (1.8-8.5), P < 0.001] as well as fetal complications [RR = 2.0 (1.2-3.4), p = 0.001]. Hypertension was the most common maternal complication and occurred most often in the last trimester. The baby weight at birth was lower in pregnancies after disease (2.3 vs. 3.0, p = 0.01). Wong's score greater than or equal to 4 predicted lower birth weight ( p = 0.04). ITAS, ITAS-A, DEI. Tak and TADS could not predict obstetric outcomes, and ITAS score exhibited moderate correlation with DEI. Tak ( r = 0.78) and TADS ( r = 0.58). Conclusion: Women with TA suffer from extremely high risk of poor maternal and foetal outcomes. Wong's scoring can be useful to predict birth weight.(AU)

Approach to non-compressive back pain.

Back pain is the most common manifestation among rheumatologic conditions, with an 80% lifetime risk of development in each individual. Most patients have no specific identifiable etiology. Low back pain has always been an important public health problem, having a significant impact on the working class of the population. Hence, it is pertinent for the physician to be aware of the various causes of back pain and identify promptly the various red flags and poor prognostic markers. Lamentably, widespread access to technology and fear of litigation in this era of evidence based medicine has made us slaves of medical imagery in the context of back pain. It is crucial to recognize the teachings of ancient medicine, where keen observation, a detailed history-taking and a meticulous examination were the mainstay of good decision-making. Its precise management can help in obviating debility, preventing the work absenteeism, and consequently, decreasing health-care expenses.

NMR-Based Serum Metabolomics of Patients with Takayasu Arteritis: Relationship with Disease Activity.

Takayasu arteritis (TA) is a large vessel vasculitis of unknown pathogenesis. Assessment of disease activity is a challenge, and there is an unmet need for relevant biomarker(s). In our previous study, NMR based serum metabolomics had revealed distinctive metabolic signatures in TA patients compared with age/sex matched healthy controls and systemic lupus erythematosus (SLE). In this study we investigate whether the metabolites correlate with disease activity. Patients with TA fulfilling American College of Rheumatology (ACR) criteria were enrolled, and disease activity was assessed using Indian Takayasu Clinical Activity Score using acute phase reactant-erythrocyte sedimentation rate [ITAS-A (ESR)]. Sera were analyzed using 800 MHz NMR spectrometer to identify metabolites [based on partial least squares discriminant analysis (PLS-DA) VIP (variable importance in projection) score > 1.0 and permutation test, p-value <0.01]. 45 active and 53 inactive TA patients with median age 27 [(IQR) 22-35 years] and 27 [(IQR) 23-37 years], female to male ratio 3.5:1 and 4.9:1, and median duration of illness 5 [(IQR) 2-9 years] and 3 [(IQR) 1-6 years], respectively, were enrolled. The key metabolites with highest discriminatory potential in active TA (ITAS-A ≥ 4) were glutamate and N-acetyl glycoprotein (NAG), both elevated, with area under the curve 0.775 and 0.769 ( p-value <0.001). On follow up assessment, metabolic spectra started to differ with change in disease activity. This large cohort of patients revealed metabolic profiles discriminating between clinically active and inactive TA patients. It suggests glutamate and NAG have strong potential as biomarkers for disease activity in TA and may serve as a guide to therapy. We are now working to further validate these results in longitudinal studies.

Prospective validation of the Juvenile Spondyloarthritis Disease Activity Index in children with enthesitis-related arthritis.

Objective: To measure disease activity in children with enthesitis-related arthritis the Juvenile Spondyloarthritis Disease Activity Index (JSpADA) was developed and retrospectively validated. We prospectively validated JSpADA and also assessed performance of adult SpA scores. Methods: Children with enthesitis-related arthritis (ILAR criteria) less than 18 years of age were enrolled. Baseline characteristics and different disease activity measures (JSpADA, BASDAI, Ankylosing Spondylitis Disease Activity Score-ESR, juvenile arthritis DAS-10 joints), and Childhood HAQ, physician global assessment and patient global assessment were recorded at baseline. In some children follow-up was also done. Results: The mean (s.d.) age of 127 children (116 boys) was 14.3 (2.4) years and disease duration was 36.9 (3) months. Ninety of 104 (86.5%) children were HLA-B27 positive. JSpADA showed high correlation with physician global assessment (r = 0.87; P < 0.0001), patient global assessment (r = 0.80, P < 0.0001), juvenile arthritis DAS-10 joints (r = 0.89; P < 0.0001) and Childhood HAQ (r = 0.83, P < 0.0001). The JSpADA scores showed good internal consistency, discriminative validity and sensitivity to change. In 15% of children back mobility could not be tested due to active arthritis in lower limbs. The 7-variable JSpADA excluding back mobility performed as well as the original JSpADA. Adult scores showed good construct validity, discriminative capacity and sensitivity to change, and had good correlation with JSpADA (BASDAI, r = 0.84; Ankylosing Spondylitis Disease Activity Score-ESR, r = 0.84). Conclusion: JSpADA is a valid score for measuring disease activity in enthesitis-related arthritis. Adult scores also performed well. Excluding back mobility needs to be assessed in future to improve JSpADA performance.

Serum BAFF and APRIL levels in Indian patients with Takayasu arteritis.

Despite many studies focused on involvement of T cell in pathogenesis of Takayasu arteritis (TaK), very few have explored the role of B cells. Hence, we sought evidence of B cell involvement in a large cohort of TaK by measuring serum levels of B cell survival factors activation factor (BAFF) and A proliferation inducing ligand (APRIL). Serum BAFF and APRIL levels were measured by ELISA in 50 patients and 48 healthy individuals, and further assessed for correlation with outcome measures, such as Indian Takayasu Clinical Activity Score-ESR (ITAS-ESR) and Takayasu arteritis Damage score (TADS). Forty women and ten men of median age 26 (11-52) and disease duration of 3 years (0.1-22) were studied. Type V disease was the most common subset (n = 31), while type I, II, III, and IV was seen in ten, four, three, and two patients respectively. Serum APRIL levels were raised in patients as compared to healthy controls [2087.5 pg/ml (1480.0-2279.0) vs. 1288.64 pg/ml, (844.2-1632.9) p = 0.01]. Median serum APRIL level was also raised in patients with active disease (n = 24) as compared to inactive disease (n = 26) 2098.79 pg/ml, (1930.75-2768.75) vs. 1802.5 pg/ml, (1066.75-2098); p = 0.03). Serum BAFF levels were not raised in patients with TaK when compared to healthy Individuals. Neither BAFF, nor APRIL levels correlated with disease activity (ITAS-ESR) or TADS. Elevated APRIL levels in active TaK suggest probable role of B cells in pathogenesis.

NMR-Based Serum Metabolomics Reveals Reprogramming of Lipid Dysregulation Following Cyclophosphamide-Based Induction Therapy in Lupus Nephritis.

Lupus nephritis (LN) is a major cause of morbidity and mortality in lupus. Renal biopsy is the gold standard for classification of nephritis, but because of its impracticality, new approaches for improving patient prognostication and monitoring treatment efficacy are needed. We aimed to evaluate the potential of metabolic profiling in identifying biomarkers to distinguish disease and monitor treatment efficacy in patients with LN. Serum samples from patients with LN ( n = 18) were profiled on NMR-based metabolomics platforms at diagnosis and after 6 months of treatment. LN patients had a different metabolomic fingerprint as compared with healthy controls, with increased lipoproteins and lipids and reduced acetate and amino acids. Using multivariate statistical analysis, we found that the metabolic changes observed in naïve LN patients at diagnosis displayed a variation in the opposite direction upon responding to treatment. Increased levels of lipid metabolites including low- and very-low-density lipoproteins (LDL/VLDL) in LN patients significantly decreased after 6 months of treatment, whereas the serum levels of acetate increased. These levels correlated significantly with SLE Disease Activity Index (SLEDAI 2K), renal SLEDAI, and serum C3 and C4 levels. The result presented in this pilot longitudinal study revealed the reprogramming of metabolome in LN patients on immunosuppressive therapy using NMR-based metabolomics, and thus this approach may be used to monitor the response to treatment.

Effect of induction therapy on circulating T-helper 17 and T-regulatory cells in active proliferative lupus nephritis.

INTRODUCTION: T-helper 17 (Th17) cells and T-regulatory (Treg) cells have been suggested to play pathogenic roles in lupus nephritis. The in vivo effects of current therapies for lupus nephritis (LN) on these cells have not been adequately studied. METHODS: We conducted a prospective observational study among patients with active proliferative lupus nephritis (LN) who received Eurolupus induction therapy and assessed them as per the European League Against Rheumatism criteria for renal response. Peripheral circulatory Th17 and Treg cell numbers were enumerated at start of therapy, at 3 and 6 months follow-up periods using flow cytometry. Baseline values were compared with inactive lupus patients (iSLE) and healthy controls (HC). RESULTS: Thirty patients with LN, 20 iSLE and 22 HC were enrolled into the study. In LN, Th17 frequency was significantly higher compared to HC, and Treg frequency significantly lower compared to both iSLE and HC. Nineteen patients fulfilled criteria for response (partial or complete) at 6 months. Responder group showed a significant decline in Th17 frequency and an increasing trend in Treg frequency compared to baseline after 6 months of therapy. CONCLUSION: Circulating Th17 cells were significantly raised in patients with active proliferative LN and showed a significant reduction in responder patients following therapy.

Prominent midfoot involvement in children with enthesitis-related arthritis category of juvenile idiopathic arthritis.

Foot involvement is common in juvenile idiopathic arthritis (JIA) but is often unrecognized and difficult to treat. This study was done to assess clinical and radiological involvement of the feet and its impact on function in Indian children with enthesitis-related arthritis (ERA). We enrolled consecutive children with ERA with disease duration of less than 5 years. All patients underwent clinical examination of the feet and filled the juvenile arthritis foot index (JAFI) questionnaire. Ultrasound (US) of foot joints and entheses and extremity magnetic resonance imaging (MRI) scan of one foot were done. Fifty-five patients (53 boys), with median 14 years and disease duration 1.9 years, were included. Thirty-seven of 46 were HLA-B27-positive. Mean juvenile spondyloarthritis disease activity (JSpADA) index and juvenile idiopathic arthritis disease activity scrore-10 (JADAS10) scores were 4 and 14.25. Forty-six had history of foot pain, 36 had foot involvement on examination (15 ankle, 8 subtalar, 24 midfoot, 10 forefoot, and 21 tendoachilles), and 7 had plantar fascia involvement. On US (N = 55), 16 had ankle involvement and 8 had subtalar involvement, and 19 patients had midfoot arthritis, 24 had tendoachilles enthesitis, and 11 had plantar fasciitis. On MRI (N = 50), 27 had midfoot involvement. Thirty-three had bone edema. Fourteen had midfoot enthesitis and 17 had tenosynovitis. Clinical and US had 82% concordance at the midfoot and 90% at the ankle. MRI had 74% concordance with examination and 72% with US at the midfoot. The median JAFI scores were as follows: total JAFI = 4 (0-11), impairment = 1, activity limitation = 2, and participation restriction = 1. JAFI total and individual domains correlated with JADAS10, JSpADAS, and childhood health assessment questionnaire (CHAQ) but not duration of foot disease. JAFI was higher in children with midfoot arthritis on US. Foot joints and entheses are involved in a substantial proportion of patients with ERA patients and the midfoot is commonly involved. Foot disease produces significant functional limitation.