Klas Nordlind

The skin as a mirror of the soul: exploring the possible roles of serotonin

Abstract:  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.

Patients' perspective of pruritus in chronic plaque psoriasis : a questionnaire-based study

Background  Pruritus in psoriasis patients has not been regarded as a major symptom.

Pirfenidone in idiopathic pulmonary fibrosis: expert panel discussion on the management of drug-related adverse events.

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.

Study of substance P and its receptor neurokinin-1 in psoriasis and their relation to chronic stress and pruritus

Substance P and its receptor(R) neurokinin (NK)-1 may have a role in the pathogenesis of psoriasis. Stress has been reported to play a role in the onset and exacerbation of psoriasis, which might include the substance P-NK-1 receptor(R) pathway. A feature of psoriasis, that has been correlated to the severity of stress and secretion of substance P, is pruritus. The objective of this study was to investigate the expression of substance P and the NK-1R in involved and noninvolved psoriatic skin, using a biotinylated streptavidin technique. Moreover, a possible correlation between the patient´s level of chronic stress, measured by salivary cortisol samples, degree of lesional pruritus, measured by means of a visual analogue scale, and the expression of substance P- and the NK-1R, was investigated. There was a low number of substance P positive nerve fibres in noninvolved and involved skin, the major immunoreactivity for substance P being found in inflammatory cells. The number of substance P- and NK-1R positive inflammatory cells was increased in involved compared to noninvolved psoriatic skin. The substance P positive cells were mostly lymphocytes, while most of the NK-1R positive cells were mast cells. NK-1R immunoreactivity was also seen as a reticular pattern in the upper part of the epidermis of involved skin in the majority of the patients. Low cortisol ratios in the patients, being an indicator of chronic stress, were correlated to an increased number of substance P- and NK-1R positive inflammatory cells in noninvolved psoriatic skin, and higher cortisol ratios to the presence of keratinocyte NK-1R immunoreactivity in involved skin. The degree of pruritus could not be correlated to the number of substance P positive fibers nor cells. Nonneuronal substance P and its receptor NK-1 might have a role in psoriasis, also during chronic stress.

Expression of nicotinic receptors in the skin of patients with palmoplantar pustulosis.

Summary Background A suggested role for nicotine in the pathogenesis of palmoplantar pustulosis (PPP) has been discussed. The target for the inflammation in PPP is the acrosyringium. Nicotine acts as an agonist on nicotinic acetylcholine receptors (nAChRs) and can influence a variety of cellular functions.

Glutamate- and aspartate-like immunoreactivities in human normal and inflamed skin

SummaryThe presence of glutamate/aspartate-like immunoreactivity was studied in normal human skin and in skin with gold-induced inflammation. In normal skin all epithelial cells were glutamate and, apparently more weakly, aspartate immunoreactive. Both glutamate and aspartate immunoreactivities were also found in macrophage-like, HLA-DR positive cells in the dermis and in the epidermis. The intensity of glutamate and especially aspartate-like immunoreactivities seemed to be increased in the epidermis and dermis of the inflamed as compared to the normal skin, and this increase was particularly pronounced in the HLA-DR positive (dendritic) cells in the epidermis. Numerous cells, often of the mononuclear type, in the superficial dermis expressed glutamate- and aspartate-like immunoreactivities in the inflamed skin and many of these were HLA-DR positive. The functional role of glutamate and aspartate in normal skin, and the significance of the increase in the levels of these amino acids in several cell populations in the inflammatory skin is not known, but modulatory or protective roles may be considered. High concentrations of these amino acids could also induce cell damage. Moreover, the macrophage-like cells in the human skin may have a role in the processing of glutamate and aspartate on a recycling basis.

Influence of beta-endorphin, somatostatin, substance P and vasoactive intestinal peptide on the proliferative response of human peripheral blood T lymphocytes to mercuric chloride.

The influence of beta-endorphin, somatostatin, substance P (SP) and vasoactive intestinal peptide (VIP) was tested on the proliferative response to mercuric chloride of human peripheral blood T lymphocytes, cultured for 5 days. When beta-endorphin, 10(-8) M, was added 1 h after mercuric chloride, there was an enhancement of the response, while a slight suppression was obtained with a 10(-6) M concentration of SP and VIP. When beta-endorphin, 10(-7)-10(-9) M, somatostatin, 10(-6)-10(-9) M, and SP, 10(-11)-10(-12) M, were added 3 days after mercuric chloride, they enhanced the response. At 10(-6) M, SP gave a suppressive effect.

Palmoplantar Pustulosis: an Autoimmune Disease Precipitated by Smoking?

Ninety-five percent of patients with palmoplantar pustulosis are smokers at onset of the disease. The aim of this study was to determine whether these patients have serum antibodies to nicotinic acetylcholine receptors (nAChR ab) and if their sera induce a specific immunofluorescence in normal palmar skin. Sera from 45 patients with palmoplantar pustulosis and 23 patients with chronic hand eczema were analysed for muscle nAChR ab, and immunofluorescence was performed on healthy palmar skin. Forty-two percent of the patients with palmoplantar pustulosis but none of the eczema patients had raised levels of nAChR ab. Immunofluorescence showed staining on endothelial cells in the papillary dermis in 47% of all sera from patients with palmoplantar pustulosis and in those with nAChR ab in 68%. On palmar skin from smokers there was also a staining of the sweat duct. Sera from patients with chronic hand eczema were negative. Our findings indicate that palmoplantar pustulosis is an autoimmune disease, possibly induced by smoking.

Neuroimmune mechanisms in patients with atopic dermatitis during chronic stress.

Objective  To identify pathoaetiological neuroimmune mechanisms in patients with atopic dermatitis (AD) and chronic stress, focusing at nerve density, sensory neuropeptides, and the serotonergic system.

Immunohistochemical localization of interleukin-6-like immunoreactivity to peripheral nerve-like structures in normal and inflamed human skin.

Interleukin-6-like (IL-6-like) immunoreactivity was sought in inflamed and normal human skin using the same immunohistochemical technique as for detection of neuropeptides. Such immunoreactivity was found in dermal and in a few intraepidermal nerve-like fibres in biopsy specimens from inflamed skin from patients with positive epicutaneous patchtest reactions to nickel sulphate, and in skin specimens from patients with atopic dermatitis and prurigo nodularis. However, IL-6-like immunoreactivity was also found in nerve-like fibres in specimens from nonlesional skin. In skin from patients with positive epicutaneous patch-test reactions there was a statistically significantly (P<0.01) higher number of IL-6-positive nerve fibres in the epidermis than in normal skin, in contrast to the papillary dermis, in which no difference was found. Moreover, there were clusters of nerve-like fibres with IL-6-like immunoreactivity in the dermis of prurigo nodularis lesions. In these nerve-like fibres, the colocalization of the immunoreactivities for IL-6 and calcitonin gene-related peptide was indicated. Localization of immunoreactivity to nerve-like structures surrounding the eccrine sweat glands indicates that IL-6 is present in autonomic as well as in sensory nerve fibres.