Biological Therapy in Primary Sjogren's Syndrome: Effect on Salivary Gland Function and Inflammation

Primary Sjögren's syndrome (pSS) is a chronic, systemic autoimmune disease. It is the second most common rheumatic autoimmune disorder, affecting 0.7% of European Americans and up to 1% of people globally. pSS is characterized by the impaired secretory function of exocrine glands, including salivary and lachrymal glands. A lymphocytic infiltration of these organs leads to the common and debilitating symptoms of oral and ocular dryness, majorly affecting the quality of life of these patients. Currently, no disease-modifying drug has been approved for the treatment of pSS, with therapies largely aimed at relieving symptoms of dry mouth and dry eyes. In particular, management of oral dryness still represents a major unmet clinical need in pSS and a significant burden for patients with this condition. Recently, several randomized clinical trials in pSS with biological therapies targeting specific mechanistic pathways implicated in the disease pathogenesis, including B-cell hyperactivity, T-cell co-stimulation and the aberrant role of cytokines, have been completed with mixed results. In this review, we summarize evidence from recent clinical trials investigating biological therapy in pSS, specifically highlighting efficacy, or lack thereof, in modulating local inflammation and improving salivary gland function

British Society for Rheumatology guideline on management of adult and juvenile onset Sjögren disease

Sjögren disease (SD) is a chronic, autoimmune disease of unknown aetiology with significant impact on quality of life. Although dryness (sicca) of the eyes and mouth are the classically described features, dryness of other mucosal surfaces and systemic manifestations are common. The key management aim should be to empower the individual to manage their condition-conserving, replacing and stimulating secretions; and preventing damage and suppressing systemic disease activity. This guideline builds on and widens the recommendations developed for the first guideline published in 2017. We have included advice on the management of children and adolescents where appropriate to provide a comprehensive guideline for UK-based rheumatology teams.</p

Constructing public health policies in post crisis countries: lessons to learn from the associations between free-sugars consumption and diabetes, obesity and dental caries before, during and after sanctions in Iraq.

BACKGROUND: This article aims to provide evidence for an informed public health policy on free-sugar consumption in post-crisis countries. METHODS: Iraq was selected as a case study. A systematic search for published data on the prevalence/incidence of type-2 diabetes, overweight/obesity, dental caries and free-sugar consumption levels in Iraq was conducted using MEDLINE, the Iraqi Academic Scientific journals and relevant international organisations' websites. Comparable data before (1980-1990), during (1991-2002) and after (2003-2015) the United Nations sanctions (UNS) were included. RESULTS: Ten studies were included. Quality scores ranged between 3 and 7/8. Free-sugar consumption decreased dramatically during the UNS (from 50 to 16.3 kg/person/year) and started increasing afterwards (24.1 kg/person/year). Changes in type-2 diabetes, overweight/obesity and caries levels mirrored those of free-sugar consumption. Caries declined markedly during UNS and started increasing afterwards. Comparable data on diabetes and overweight/obesity were only available for the periods during and after the UNS. Both of these conditions started increasing with increased free-sugar consumption after lifting the UNS. CONCLUSIONS: There is a need to develop a public health policy in post-crisis countries to maintain the reduction in free-sugar consumption, and hence promote both general and dental health, by integrating the common risk factor approach into the social determinant framework

Effect of rituximab on a salivary gland ultrasound score in primary Sjögren’s syndrome: results of the TRACTISS randomised double-blind multicentre substudy

Objectives To compare the effects of rituximab versus placebo on salivary gland ultrasound (SGUS) in primary Sjögren’s syndrome (PSS) in a multicentre, multiobserver phase III trial substudy. Methods Subjects consenting to SGUS were randomised to rituximab or placebo given at weeks 0, 2, 24 and 26, and scanned at baseline and weeks 16 and 48. Sonographers completed a 0–11 total ultrasound score (TUS) comprising domains of echogenicity, homogeneity, glandular definition, glands involved and hypoechoic foci size. Baseline-adjusted TUS values were analysed over time, modelling change from baseline at each time point. For each TUS domain, we fitted a repeated-measures logistic regression model to model the odds of a response in the rituximab arm (≥1-point improvement) as a function of the baseline score, age category, disease duration and time point. Results 52 patients (n=26 rituximab and n=26 placebo) from nine centres completed baseline and one or more follow-up visits. Estimated between-group differences (rituximab-placebo) in baseline-adjusted TUS were −1.2 (95% CI −2.1 to −0.3; P=0.0099) and −1.2 (95% CI −2.0 to −0.5; P=0.0023) at weeks 16 and 48. Glandular definition improved in the rituximab arm with an OR of 6.8 (95% CI 1.1 to 43.0; P=0.043) at week 16 and 10.3 (95% CI 1.0 to 105.9; P=0.050) at week 48. Conclusions We demonstrated statistically significant improvement in TUS after rituximab compared with placebo. This encourages further research into both B cell depletion therapies in PSS and SGUS as an imaging biomarker

Current concepts in the pathogenesis and management of oral mucositis as a complication of cancer therapy

The ubiquitous nature of oral mucositis in patients undergoing chemotherapy, radiotherapy and bone marrow transplantation and its effect on patient quality of life, coupled with notable recent advances in better understanding of the pathobiology of mucositis, have brought about a shift from the symptomatic approach in management to a preventive one. This has been reflected in the literature over the past five years or so, and has culminated in the introduction of a variety of new medications, the majority of which are still being investigated. A universal management scheme for oral mucositis is far from being realised, but the current management guidelines as developed by the Multinational Association of Supportive Care in Cancer is invaluable for clinicians of all disciplines involved. The introduction of the recently-approved human recombinant keratinocyte growth factor (palifermin) is perhaps one of the most notable achievements in mucositis research; but the possibility of a topical preparation and its potential in other disease conditions have not been tapped into as ye

Smell Dysfunction in Patients with Primary Sjögren’s Syndrome: Impact on Quality of Life

Objectives: Patients with primary Sjögren’s syndrome (pSS) often report smell and taste disturbances. However, the correlation between smell impairment and mucosal dryness is not well understood. The objectives of this study were to investigate the following: (1) the prevalence of smell hypofunction in patients with SS; (2) the impact of smell hypofunction on their quality of life (QoL); (3) whether the patients’ smell is correlated with xerostomia; and (4) whether the patients’ smell is affected by taste hypofunction, disease duration, age, smoking or self-reported neuropathy. Methodology: An ethically approved cross-sectional study was conducted on 65 female patients with SS and 62 sex-matched healthy controls. Their smell was assessed using the University of Pennsylvania Smell Identification Test. Their taste acuity was assessed using the Taste Strips Test. A visual analogue scale was used for the self-assessment of smell and taste functions. Xerostomia was assessed by the salivary flow rate, clinical oral dryness score and the Xerostomia Inventory. The patients’ QoL and mental health well-being were assessed using validated questionnaires. Results: In the SS group, the patients’ smell function was impaired in 27/65 patients compared with the controls (15/62, p p = 0.6) or self-reported nasal dryness (r = −0.02, p = 0.7). In the patients’ group, smell hypofunction was not correlated with disease duration (β = 0.1, 95% CI = −0.07–0.1) or smoking (β = −0.02, 95% CI = −8–7). Age was not correlated with the smell function in the patients’ group (β = −0.1, p = 0.5) but was correlated significantly with smell in the healthy participants’ group (β = −0.3, p = 0.02). Neuropathy affected 81.2% of the patients’ group. Their QoL and mental health well-being were not affected by smell hypofunction. Conclusion: Smell hypofunction appears to be a clinical manifestation in patients with SS, but it does not seem to be associated with the severity of mucosal dryness or with taste disturbance

Topical betamethasone and systemic colchicine for treatment of recurrent aphthous stomatitis: a randomised clinical trial

Abstract Background Recurrent Aphthous Stomatitis (RAS) is painful oral ulceration frequently treated with topical steroids. There is limited published evidence for the efficacy of any treatment for RAS and there remains a need for longitudinal randomised clinical trials to evaluate and compare the effectiveness of different therapies in the management of RAS. The aim of the current project was to assess the efficacy of betamethasone mouthwash and colchicine tablets, individually and combined, for the treatment of RAS, and to establish the optimum treatment period necessary for a significant reduction in the disease severity. Methodology A randomised, prospective, parallel-group clinical trial was conducted over one year, to compare the efficacy of three therapies in RAS. One hundred and six patients were randomized into three groups; 35 received betamethasone mouthwash, 35 had colchicine tablets and 36 received both therapies. The response was evaluated quantitatively every 3 months for 1 year, using the Ulcer Severity Score (USS). Results For all three treatment regimes, the mean USS decreased by about 30% in the first 3 months (p < 0.001). Further improvement was noted for up to 9 months. At the end of the study, the mean USS had improved by 50% from 34.9 ± 7.2 before treatment to 17.5 ± 8.9 after treatment (p < 0.001). Of included participants, 86% showed significant clinical improvement by the end of the study. There were no significant differences in outcomes between the three regimes (p < 0.05). Conclusions This clinical trial has provided evidence for the efficacy of betamethasone mouthwash and for colchicine tablets in the treatment of RAS and has shown that at least six months of treatment may be required for optimum effect. Clinical trial registration number: ISRCTN3267716. Date of clinical trial registration: 15/04/201

B cell depletion with rituximab in the treatment of primary Sjögren's syndrome: what have we learnt?

Despite the well-established role of B cells in the pathogenesis of primary Sjögren's syndrome (pSS), the beneficial role of B-cell depletion therapy with rituximab remains elusive in this condition, contrary to other autoimmune diseases. Although early, small-scale studies showed promising results, two recent large randomised controlled trials did not meet their primary end-points. It is evident from most trials that rituximab has a positive impact on B-cell numbers and activity, both in the peripheral blood and in salivary glands, but clinical outcomes vary among studies. We review here the evidence to date of B-cell depletion in pSS, analysing the underlying causes for the discrepancies in different studies and their limitations. We also discuss the potential use of peripheral and salivary gland biomarkers for patient stratification and targeted patient selection. Overall, rituximab remains a plausible treatment for pSS provided future studies address the shortfalls that emerged from our current knowledge of the use of B-cell depletion in this condition