Primary Sjogren's syndrome : rarity in India

Objective : Primary Sjogren's syndrome (SS) is rarely reported from India. We have studied the clinical spectrum and immunological profile of patients with primary SS. Methods : A prospective analysis of patients with primary Sjogren's syndrome fulfilling San Francisco criteria, seen at our clinic in the last 10 years was carried out. Results : The study included 26 patients, 21 being women. The presenting symptoms included dry eyes, dry mouth, and arthritis/ arthralgia. Extra-glandular manifestations were glomerulonephritis, vasculitis, renal tubular acidosis and peripheral neuropathy. The important laboratory abnormalities were hypergammaglobulinaemia (16/20), antinuclear antibodies (18/26), anti-La (11/19) and anti-Ro (10/19). Minor salivary gland provided a definitive diagnosis in 16/26 (60%). Conclusion : The prevalence of primary Sjogren's syndrome is rare even in tertiary care rheumatology clinics. The clinical and immunological profile as seen here is similar to that reported in Western countries

COVID-19: Can we treat the mother without harming her baby?

First published online: 25 January 2021Medical care is predicated on ‘do no harm’, yet the urgency to find drugs and vaccines to treat or prevent COVID-19 has led to an extraordinary effort to develop and test new therapies. Whilst this is an essential cornerstone of a united global response to the COVID-19 pandemic, the absolute requirements for meticulous efficacy and safety data remain. This is especially pertinent to the needs of pregnant women; a group traditionally poorly represented in drug trials, yet a group at heightened risk of unintended adverse materno-fetal consequences due to the unique physiology of pregnancy and the life course implications of fetal or neonatal drug exposure. However, due to the complexities of drug trial participation when pregnant (be they vaccines or therapeutics for acute disease), many clinical drug trials will exclude them. Clinicians must determine the best course of drug treatment with a dearth of evidence from either clinical or preclinical studies, where at least in the short term they may be more focused on the outcome of the mother than of her offspring.Michael D. Wiese, Mary J. Berry, Pravin Hissaria, Jack R.T. Darby, and Janna L. Morriso

Aberrant expression of high mobility group box protein 1 in the idiopathic inflammatory myopathies

Introduction: High Mobility Group Box Protein 1 (HMGB1) is a DNA-binding protein that exerts inflammatory or pro-repair effects upon translocation from the nucleus. We postulate aberrant HMGB1 expression in immune-mediated necrotising myopathy (IMNM). Methods: Herein, we compare HMGB1 expression (serological and sarcoplasmic) in patients with IMNM with that of other myositis subtypes using immunohistochemistry and ELISA. Results: IMNM (n = 62) and inclusion body myositis (IBM, n = 14) patients had increased sarcoplasmic HMGB1 compared with other myositis patients (n = 46). Sarcoplasmic HMGB1 expression correlated with muscle weakness and histological myonecrosis, inflammation, regeneration and autophagy. Serum HMGB1 levels were elevated in patients with IMNM, dermatomyositis and polymositis, and those myositis patients with extramuscular inflammatory features. Discussion: Aberrant HMGB1 expression occurs in myositis patients and correlates with weakness. A unique expression profile of elevated sarcoplasmic and serum HMGB1 was detected in IMNM.Jessica Day ... Pravin Hissaria, Susanna Proudman, Vidya Limaye and John D. Hayball ... et al

Pragmatics of Yes/No Indirect-responses (YNIRs)

AbstractHow do people transmit information with “question-answer” structures? What happens when a speaker utters a meaningful question and the hearer understands it? The present paper focuses on YNIRs in terms of (a) a radical lack of consensus about their potential in production of messages in interpersonal communication; (b) the ways in which they are used to establish and maintain coherent conversation, and (c) to what extent commentary, and supplementary indirect responses can invoke goal (in) compatibility, and how this kind of conflict can prevent stagnation, stimulate interest, and finally contribute to “escalation” of mutual understanding. Although the functional horizons of general questions and the answers to them vary from context to context, the addressee can “control” his judgements and attitudes (apology, ignorance, consent, or refusal) by his deeper exposure to the situation, what, in the end, enables his affiliation with others. The other major concern of the paper is to specify the cases when the pragmatic interpretation of questionless responses is defined as unification of the semantic representation and the internal utterance context

Defective protein prenylation in a spectrum of patients with mevalonate kinase deficiency

The rare autoinflammatory disease mevalonate kinase deficiency (MKD, which includes HIDS and mevalonic aciduria) is caused by recessive, pathogenic variants in the MVK gene encoding mevalonate kinase. Deficiency of this enzyme decreases the synthesis of isoprenoid lipids and thus prevents the normal post-translational prenylation of small GTPase proteins, which then accumulate in their unprenylated form. We recently optimized a sensitive assay capable of detecting unprenylated Rab GTPase proteins in peripheral blood mononuclear cells (PBMCs) and showed that this assay distinguished MKD from other autoinflammatory diseases. We have now analyzed PBMCs from an additional six patients with genetically-confirmed MKD (with different compound heterozygous MVK genotypes), and compared these with PBMCs from three healthy volunteers and four unaffected control individuals heterozygous for the commonest pathogenic variant, MVK V377I . We detected a clear accumulation of unprenylated Rab proteins, as well as unprenylated Rap1A by western blotting, in all six genetically-confirmed MKD patients compared to heterozygous controls and healthy volunteers. Furthermore, in the three subjects for whom measurements of residual mevalonate kinase activity was available, enzymatic activity inversely correlated with the extent of the defect in protein prenylation. Finally, a heterozygous MVK V377I patient presenting with autoinflammatory symptoms did not have defective prenylation, indicating a different cause of disease. These findings support the notion that the extent of loss of enzyme function caused by biallelic MVK variants determines the severity of defective protein prenylation, and the accumulation of unprenylated proteins in PBMCs may be a sensitive and consistent biomarker that could be used to aid, or help rule out, diagnosis of MKD.Marcia A. Munoz, Julie Jurczyluk, Anna Simon, Pravin Hissaria, Rob J. W. Arts, David Coman, Christina Boros, Sam Mehr, and Michael J. Roger

S.4.1 N-terminal pro-brain natriuretic peptide levels predict incident pulmonary arterial hypertension in SSc

Introduction. Pulmonary arterial hypertension (PAH) is a major cause of mortality in SSc. NT-proBNP may be a useful biomarker of prevalent PAH but its role in screening for incident PAH has not been evaluated. Methods. Patients recruited into the Australian Scleroderma Cohort Study undergo annual echocardiography, pulmonary function tests (PFTs), 6-min walk test (6MWT) and have serum NT-proBNP measured (ElecsysproBNP II). The diagnosis of PAH is based on Dana point criteria at right heart catheterization (RHC). Patients with LV dysfunction or eGFR 36 mmHg, (ii) FVC/DLCO% >1.6 and no significant ILD, (iii) DLCO 189.2 pg/ml had a likelihood ratio of 26.4 for presence of PAH (c-statistic = 0.9; sensitivity 85%; specificity 97%). An NT-proBNP level 189.2 pg/ml and <82.9 pg/ml defining patients with a high and low likelihood of PAH, respectively. Further prospective studies are required in unselected patients in order to confirm these finding

N-terminal pro-brain natriuretic peptide in a novel screening algorithm for pulmonary arterial hypertension in systemic sclerosis: a case-control study

INTRODUCTION: Pulmonary arterial hypertension is a major cause of mortality in systemic sclerosis. N-terminal probrain natriuretic peptide (NT-proBNP) has emerged as a candidate biomarker that may enable the early detection of systemic sclerosis-related pulmonary arterial hypertension (SSc-PAH). The objective of our study was to incorporate NT-proBNP into a screening algorithm for SSc-PAH that could potentially replace transthoracic echocardiography (TTE) as a more convenient and less costly “first tier” test. METHODS: NT-proBNP levels were measured in patients from four clinical groups: a group with right heart catheter (RHC)-diagnosed SSc-PAH before commencement of therapy for PAH; a group at high risk of SSc-PAH based on TTE; a group with interstitial lung disease; and systemic sclerosis (SSc) controls with no cardiopulmonary complications. NT-proBNP levels were compared by using ANOVA and correlated with other clinical variables by using simple and multiple linear regression. ROC curve analyses were performed to determine the optimal cut point for NT-proBNP and other clinical variables in prediction of PAH. RESULTS: NT-proBNP was highest in the PAH group compared with other groups (P < 0.0001), and higher in the risk group compared with controls (P < 0.0001). NT-proBNP was positively correlated with systolic pulmonary artery pressure (PAP) on TTE (P < 0.0001), and mean PAP (P = 0.013), pulmonary vascular resistance (P = 0.005), and mean right atrial pressure (P = 0.006) on RHC. A composite model wherein patients screened positive if NT-proBNP was ≥ 209.8 pg/ml, and/or DLCOcorr was < 70.3% with FVC/DLCOcorr ≥ 1.82, had a sensitivity of 100% and specificity of 77.8% for SSc-PAH. CONCLUSION: We have proposed a screening algorithm for SSc-PAH, incorporating NT-proBNP level and PFTs. This model has high sensitivity and specificity for SSc-PAH and, if positive, should lead to TTE and confirmatory testing for PAH. This screening algorithm must be validated prospectively.Vivek Thakkar, Wendy M. Stevens, David Prior, Owen A. Moore, Jillian Byron, Danny Liew, Karen Patterson, Pravin Hissaria, Janet Roddy, Jane Zochling, Joanne Sahhar, Peter Nash, Kathleen Tymms, David Celermajer, Eli Gabbay, Peter Youssef, Susanna M. Proudman and Mandana Nikpou

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

Parasitic infection and immunomodulation: a possible explanation for the hygiene hypothesis in autoimmune and allergic disease

Abstract not availableJovanka King, Pravin Hissari

Efficacy of rituximab in refractory antisynthetase syndrome

We report the successful use of repeated administration of rituximab in a patient with antisynthetase syndrome refractory to conventional immunosuppressive medications. A literature review revealed that previous experience with rituximab in this condition has been sparse. The rationale for the use of B-cell depleting therapies in antisynthetase syndrome has been explored in light of the current understanding of the pathogenesis of this condition.V. Limaye, P. Hissaria, C.-L. Liew and B. Koszyk