Pruritus is a common symptom in patients with chronic plaque psoriasis.
Systemic lupus erythematosus (SLE) patients have increased levels of interferon-alfa (IFN-alpha) in the circulation but a reduced number of functionally intact natural IFN-alpha producing cells (IPC) in peripheral blood. In search for tissue localisation of activated IPC, we investigated skin biopsies from SLE patients for the occurrence of such cells. Eleven SLE patients with inflammatory skin lesions and six healthy controls were biopsied. An immunohistochemical technique (IH) and in situ hybridisation (ISH) were used to detect intracellular IFN-alpha protein and IFN-alpha mRNA, respectively. In all 11 biopsies from SLE lesions, a high number of IPC were detected by IH. In the nonlesional SLE biopsies we could also demonstrate IPC in 10/11 patients. In 6/11 SLE patients, IFN-alpha mRNA containing cells could be detected in the specimens. A low number of IPC were detected in 1/6 healthy controls by IH, but no ISH positive cells were seen. Our results demonstrate that SLE patients have active IPC in both dermal lesions and in noninflammatory skin. A recruitment of IPC from blood to peripheral tissues may explain the low number of circulating natural IPC in SLE patients. Because the type I IFN system is involved in the SLE disease process, these results are of interest for the understanding of the pathogenesis in SLE.
Pirfenidone is currently the only approved therapy for idiopathic pulmonary fibrosis, following studies demonstrating that treatment reduces the decline in lung function and improves progression-free survival. Although generally well tolerated, a minority of patients discontinue therapy due to gastrointestinal and skin-related adverse events (AEs). This review summarizes recommendations based on existing guidelines, research evidence, and consensus opinions of expert authors, with the aim of providing practicing physicians with the specific clinical information needed to educate the patient and better manage pirfenidone-related AEs with continued pirfenidone treatment. The main recommendations to help prevent and/or mitigate gastrointestinal and skin-related AEs include taking pirfenidone during (or after) a meal, avoiding sun exposure, wearing protective clothing, and applying a broad-spectrum sunscreen with high ultraviolet (UV) A and UVB protection. These measures can help optimize AE management, which is key to maintaining patients on an optimal treatment dose.Electronic supplementary materialThe online version of this article (doi:10.1007/s12325-014-0112-1) contains supplementary material, which is available to authorized users.
Serotonin (5-hydroxytryptamine; 5-HT) is an important mediator of bidirectional interactions between the neuroendocrine system and the skin. The rate of synthesis of 5-HT from l-tryptophan can be enhanced by brain-derived neuronal growth factor, cytokines, exposure to ultraviolet light and steroids. The major source of 5-HT in the skin are platelets, which, upon aggregation, release this biogenic amine. Moreover, the epidermal and dermal skin express the enzymes required for the transformation of tryptophan to 5-HT, and certain skin cells, such as melanocytes, have been demonstrated to produce 5-HT. In addition, rodent mast cells produce 5-HT, but human mast cells have not yet been fully examined in this respect. Skin cells express functionally active, membrane-bound receptors for 5-HT, as well as proteins that transport 5-HT. The interactions of 5-HT with these various proteins determines the nature, magnitude and duration of serotonergic responses.The immune and vasculature systems in the skin are traditional targets for bioregulation by 5-HT. Moreover, recent findings indicate that keratinocytes, melanocytes and dermal fibroblasts also respond to this amine in various ways. Thus, mammalian skin is both a site for the production of and a target for bioregulation by 5-HT. This indicates that agonists and antagonists directed towards specific 5-HT receptors could be useful in connection with treatment of skin diseases. Based on our increasing knowledge concerning these receptors and their plasticity, future research will focus on the development of serotonergic drugs that exert metabotrophic effects on the cells of the skin without affecting the central nervous system.
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