Epithelial-immune cell interplay in primary Sjogren syndrome salivary gland pathogenesis

In primary Sjogren syndrome (pSS), the function of the salivary glands is often considerably reduced. Multiple innate immune pathways are likely dysregulated in the salivary gland epithelium in pSS, including the nuclear factor-kappa B pathway, the inflammasome and interferon signalling. The ductal cells of the salivary gland in pSS are characteristically surrounded by a CD4(+) T cell-rich and B cell-rich infiltrate, implying a degree of communication between epithelial cells and immune cells. B cell infiltrates within the ducts can initiate the development of lymphoepithelial lesions, including basal ductal cell hyperplasia. Vice versa, the epithelium provides chronic activation signals to the glandular B cell fraction. This continuous stimulation might ultimately drive the development of mucosa-associated lymphoid tissue lymphoma. This Review discusses changes in the cells of the salivary gland epithelium in pSS (including acinar, ductal and progenitor cells), and the proposed interplay of these cells with environmental stimuli and the immune system. Current therapeutic options are insufficient to address both lymphocytic infiltration and salivary gland dysfunction. Successful rescue of salivary gland function in pSS will probably demand a multimodal therapeutic approach and an appreciation of the complicity of the salivary gland epithelium in the development of pSS. Salivary gland dysfunction is an important characteristic of primary Sjogren syndrome (pSS). In this Review, the authors discuss various epithelial abnormalities in pSS and the mechanisms by which epithelial cell-immune cell interactions contribute to disease development and progression

Topical diclofenac and its role in pain and inflammation: an evidence-based review

OBJECTIVE: Topical diclofenac is widely used in the treatment of pain and inflammation. This comprehensive review assesses the safety and efficacy of topical diclofenac in a range of painful and inflammatory disorders. METHODS: Double-blind, randomized, placebo- or active-controlled trials (RCT) evaluating topical diclofenac in soft-tissue injuries, soft-tissue rheumatic disorders and osteoarthritis were identified through detailed literature searches. In addition, non-RCT evidence from publications evaluating the pharmacologic characteristics of topical diclofenac were also included in this review to obtain a more complete picture of the drug's profile, its efficacy and safety. RESULTS: Studies demonstrate that the drug preferentially distributes to the target tissues in sufficient concentrations to produce a therapeutic effect. A total of 19 double-blind RCTs in more than 3000 patients, supported by single-blind or open trials, consistently show that topical diclofenac significantly reduces pain and inflammation in acute and chronic conditions compared with placebo and is comparable to other topical non-steroidal anti-inflammatory drugs (NSAIDs) and some oral NSAIDs (diclofenac, ibuprofen, naproxen). Improvements have also been observed in patients' functional capacity and mobility. Topical diclofenac is well tolerated, resulting mostly in mild, easily resolved local skin irritation, and is associated with fewer side-effects than other topical NSAIDs and a lower rate of gastrointestinal complications than oral NSAIDs (diclofenac, ibuprofen, naproxen). CONCLUSION: This evidence-based review shows topical diclofenac to be an effective and well tolerated treatment in painful and inflammatory conditions, at least in the short-term. However, only published RCT studies have been included in this analysis, which may exclude some interesting data from non-RCT studies. Future trials of topical diclofenac need to be of longer duration, be better reported and consider a broader spectrum of acute and chronic pain indications