Tolerability of Narrow-band Ultraviolet-B Phototherapy for Different Dermatological Diseases in Relation to Co-medications.

Phototherapy is an efficient therapy for a variety of skin diseases. Various drugs can cause photosensitivity and impact tolerability of phototherapy. The tolerability was investigated of narrowband ultraviolet-B 311 nm therapy in dependence on the underlying disease and long-term co-medication. A total of 534 narrowband ultraviolet-B therapy courses were examined. Compared with psoriasis, adverse events were observed more frequently in eczematous diseases and, in some cases, other indications. About two-thirds of all courses were carried out in patients taking at least one photosensitising drug, according to the summaries of product characteristics. Phototherapy was more frequently associated with adverse events when medication was taken concomitantly. When considering the tolerability of phototherapy in dependence on individual substances or drug classes, no statistically significant result was shown after adjustment.

Effects of psoriasis and psoralen exposure on the somatic mutation landscape of the skin.

Somatic mutations are hypothesized to play a role in many non-neoplastic diseases. We performed whole-exome sequencing of 1,182 microbiopsies dissected from lesional and nonlesional epidermis from 111 patients with psoriasis to search for evidence that somatic mutations in keratinocytes may influence the disease process. Lesional skin remained highly polyclonal, showing no evidence of large-scale spread of clones carrying potentially pathogenic mutations. The mutation rate of keratinocytes was similarly only modestly affected by the disease. We found evidence of positive selection in previously reported driver genes NOTCH1, NOTCH2, TP53, FAT1 and PPM1D and also identified mutations in four genes (GXYLT1, CHEK2, ZFP36L2 and EEF1A1) that we hypothesize are selected for in squamous epithelium irrespective of disease status. Finally, we describe a mutational signature of psoralens-a class of chemicals previously found in some sunscreens and which are used as part of PUVA (psoralens and ultraviolet-A) photochemotherapy treatment for psoriasis.

Atopic dermatitis.

Atopic dermatitis is a common inflammatory skin disorder characterised by recurrent eczematous lesions and intense itch. The disorder affects people of all ages and ethnicities, has a substantial psychosocial impact on patients and relatives, and is the leading cause of the global burden from skin disease. Atopic dermatitis is associated with increased risk of multiple comorbidities, including food allergy, asthma, allergic rhinitis, and mental health disorders. The pathophysiology is complex and involves a strong genetic predisposition, epidermal dysfunction, and T-cell driven inflammation. Although type-2 mechanisms are dominant, there is increasing evidence that the disorder involves multiple immune pathways. Currently, there is no cure, but increasing numbers of innovative and targeted therapies hold promise for achieving disease control, including in patients with recalcitrant disease. We summarise and discuss advances in our understanding of the disease and their implications for prevention, management, and future research.

Atopic dermatitis.

Atopic dermatitis (AD) is the most common chronic inflammatory skin disease, with a lifetime prevalence of up to 20% and substantial effects on quality of life. AD is characterized by intense itch, recurrent eczematous lesions and a fluctuating course. AD has a strong heritability component and is closely related to and commonly co-occurs with other atopic diseases (such as asthma and allergic rhinitis). Several pathophysiological mechanisms contribute to AD aetiology and clinical manifestations. Impairment of epidermal barrier function, for example, owing to deficiency in the structural protein filaggrin, can promote inflammation and T cell infiltration. The immune response in AD is skewed towards T helper 2 cell-mediated pathways and can in turn favour epidermal barrier disruption. Other contributing factors to AD onset include dysbiosis of the skin microbiota (in particular overgrowth of Staphylococcus aureus), systemic immune responses (including immunoglobulin E (IgE)-mediated sensitization) and neuroinflammation, which is involved in itch. Current treatments for AD include topical moisturizers and anti-inflammatory agents (such as corticosteroids, calcineurin inhibitors and cAMP-specific 3',5'-cyclic phosphodiesterase 4 (PDE4) inhibitors), phototherapy and systemic immunosuppressants. Translational research has fostered the development of targeted small molecules and biologic therapies, especially for moderate-to-severe disease.

Influence of external, intrinsic and individual behaviour variables on serum 25(OH)D in a German survey.

The objective of the present study was to identify external, intrinsic or behavioural factors that significantly influenced serum 25-hydroxyvitamin D (25(OH)D) concentrations in a German survey. Data from 3061 participants in the Cooperative Health Research in the Region of Augsburg, Germany (KORA) F4 survey were used to relate potential determinants to measured mean serum 25(OH)D concentrations using multivariable regression models. The factors significantly associated with hypovitaminosis D (defined as 25(OH)D<25 nmolL(-1)) were season (winter, spring and autumn), urban environment and high body mass index. In contrast, times spent in sunny regions, hours per day spent outdoors in the summer as well as additional oral intake were associated with higher 25(OH)D concentrations. These results suggest that mainly ambient UV exposure but also individual behaviour are the most important determinants for personal 25(OH)D concentrations. The analyses further showed that in winter 43% of subjects were vitamin D deficient and 42% insufficient. Even in summer over half the population has insufficient vitamin D status with 8% deficient and 47% insufficient. Therefore measures to mitigate widespread vitamin D insufficiency such as regular short-term sun exposure and/or improved dietary intake/supplementation recommendations by public health bodies need to be considered.

Seasonality in symptom severity influenced by temperature or grass pollen: results of a panel study in children with eczema.

Although seasonal variations are well known in many patients with eczema, no systematic population-based panel study evaluating seasonality and quantifying the influence of factors like climate and pollen on symptom variations has been conducted so far. Thirty-nine children with eczema, who had been identified in 1996 in a cross-sectional study on 1673 6-y-olds in Augsburg (Germany), participated in the study. Between March and September 1999, they daily recorded itch, extent, and possibly triggering factors on quantitative scales. Daily temperature, humidity, radiation, and pollen concentration were measured. Mixed linear models, taking the time series structure and confounding into account, were used for analysis. Seasonal patterns were significantly different between children: twenty-one had symptoms mainly in winter. They were affected by changes in outdoor temperature: itch was reduced by 22% (95% confidence interval (CI): 16%-27%) and extent by 65% (CI: 54%-72%) per 15 degrees C temperature increase. Eighteen children exhibited more symptoms in summer and especially during days with high grass-pollen exposure when itch was 16% higher (CI: 8%-24%) and extent 19% (CI: 2%-39%). This effect was stronger for children sensitized against pollen. Consideration of the individual type of eczema may help to arrange appropriate preventive and therapeutic measures.