Abhishek Zanwar

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

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.

The pathogenesis of scleroderma

Systemic sclerosis (SSc) results from the complex interplay between the immune system, vasculature and tissue-repair mechanisms. Endothelial injury is the prime event; environmental triggers in the susceptible individual trigger the pathologic process, which translates into fibrosis. The outcome of SSc is not as bleak as it looked a couple of decades ago. With a greater understanding of older pathways, as well as elucidation of newer ones, the potential targets to block and even reverse fibrosis bring around a revolution in the way we look at this once dreaded disease.

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.

NMR-based Serum Metabolomics of patients with Takayasu arteritis (TA) - 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.

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.

Dacrocystitis and orbital pseudotumor in a patient with Granulomatosis with polyangitis

A 38-year-old male presented with decreased vision and diplopia in his right eye over the past month. On performing an examination, he had proptosis, periorbital puffiness, dilated episcleral vessels, sluggish pupillary reflex, external ophthalmoplegia, and diminished vision. He also had left dacryocystitis (Figure 1a). He had presented six years ago with bilateral hearing loss, recurrent sinusitis, and hemoptysis and was diagnosed with GPA (anti-PR3 titer >100 units/mL and a necrotizing granuloma in the nasal biopsy). He was initially treated with steroids and intravenous cyclophosphamide that were discontinued after the second dose as he developed pneumonia twice; he was subsequently treated with mycophenolate mofetil, followed by azathioprine and steroids. His current anti-PR3 titer was <3 units/ ml. An MRI orbit showed an ill-defined T1/T2 isointense-to-hypointense lesion (pseudotumor) replacing the orbital fat that diffusely involved intraand extraconal compartments (Figure 1b, arrows). The extraocular muscles were encased by the lesion and appeared bulky, with mild flattening of the posterior globe (Figure 1c, arrows). The lesion encased the optic nerve and mildly compressed the optic nerve in the orbital apex. The patient was administered three doses of methylprednisolone pulses and two doses of rituximab (500 mg) two weeks apart. He responded well to treatment; he showed resolution of dacryocystitis, periorbital puffiness (Figure 1d), and diplopia and improvement in his vision. GPA has a wide spectrum of orbital manifestations, which can occur in up to 52% of patients. Patients with GPA Sajal Ajmani, Abhishek Zanwar, Pradeepta Patro, Able Lawrence Images in Rheumatology

Leprosy in the rheumatology clinic: an update on this great mimic

Leprosy is a chronic granulomatous infection caused by Mycobacterium leprae. The first description of the disease dates back to the 6th century BC by Indian surgeon Sushruta. The invasion of Asia by the armies of Alexander the Great saw the spread of the disease across Europe. Leprosy now remains endemic predominantly in the developing world, with pockets of high prevalence identified in Brazil, Indonesia and India (South-east Asia [SEA]). Together, these three countries account for 80% of all newly registered cases. Although the number of new cases detected globally has been on the declining trend, it remains a major problem in some of developing countries. Improved connectivity across the continents has led to increasing global travel, and case reports of this disease amongst the migrants have surfaced in developed nations as well. These are likely to be missed by unaware physicians. The use of newer immunosuppressants, anti-tumor necrosis factor in particular, have also been associated with reports of leprosy. Early diagnosis and full course of treatment are critical for prevention of lifelong neuropathy and disability in these cases. Although a vast majority of cases manifest with dermatologic and neurologic features, musculoskeletal manifestation are also quite common. The prevalence of rheumatic manifestations in leprosy varies across case series, ranging from 1–2% described in large dermatology series to 60–80% from rheumatology clinics. This wide variability in the reported prevalence suggests that documentation of rheumatologic signs and symptoms depends on the specialty in which the patient is being treated, and rheumatic manifestations of leprosy as a whole is often under-reported by non-rheumatology services. Therefore, it is a felt need for awareness of the condition among rheumatologists, as joint involvement can be the only manifestation in some cases.