Histopathological risk factors for malignancy in dermatomyositis.

AIMS: To identify possible histopathological risk factors for malignancy in skin biopsies of dermatomyositis patients. METHODS AND RESULTS: We analysed clinical metadata and studied 30 skin biopsies of 11 patients with and 12 patients without associated malignancy, who were treated in one secondary and one tertiary German medical centre between 2009 and 2022 and fulfilling the EULAR/ACR classification criteria for dermatomyositis. Specimens were categorized by malignancy status and evaluated based on haematoxylin and eosin (H&E), periodic acid Schiff (PAS), Alcian Blue, and anti-CD123 immunohistochemistry stains. After correcting for multiple testing, biopsies of patients with cancer exhibited more severe basement membrane thickening (P < 0.05) and pigment incontinence (P < 0.05) compared to patients without tumour burden. Patients with numerous subepidermal melanophages had a more than 5-times increased odds ratio to suffer from an internal malignancy (odds ratio [OR] 5.3, 95% confidence interval [CI] 1.3-54.2, P < 0.05). Furthermore, specimens of the malignancy group presented a distinct superficial distribution pattern of CD123+ plasmacytoid dendritic cells (PDCs, P < 0.01). Extravascular eosinophils were absent in all cases. CONCLUSION: Severity of basement membrane thickening, extent of pigment incontinence, and superficial distribution pattern of CD123+ PDCs could serve as useful histopathological indicators of risk for malignancy in dermatomyositis.

Atopic dermatitis displays stable and dynamic skin transcriptome signatures.

BACKGROUND: Skin transcriptome studies in atopic dermatitis (AD) showed broad dysregulation as well as "improvement" under therapy. These observations were mainly made in trials and based on microarray data. OBJECTIVES: Our aim was to explore the skin transcriptome and the impact of systemic treatment in patients of the TREATgermany registry. METHODS: Biopsy specimens from 59 patients with moderate-to-severe AD before and 30 patients 12 weeks after start of systemic treatment (dupilumab [n = 22] or cyclosporine [n = 8]) and from 31 healthy controls were subjected to mRNA sequencing. Differential expression, pathway enrichment, correlation, and coexpression network analysis were conducted. RESULTS: Both lesional and nonlesional skin showed a stable "core" signature characterized by disturbed epidermal differentiation and activation of IL-31/IL-1 signaling. A second dynamic signature showed progressive enrichment for type 2 inflammation, TH17 signaling, and natural killer cell function. Markers correlated with disease activity have functions in epidermal barrier properties and immune modulation. IL4RA was among the top 3 central dysregulated genes. Cyclosporine led to a more pronounced global transcriptome reversion and normalized TH17 cell/IL23 signaling, whereas dupilumab led to a stronger increase in level of epidermal differentiation markers. Both treatments strongly decreased levels of type 2 markers, but overall the residual profile was still profoundly different from that of healthy skin. Lower levels of IL4RA and IL13 and high IL36A expression were related to a stronger clinical response to dupilumab. CONCLUSION: The AD core signature is characterized by dysregulation of genes related to keratinocyte differentiation and itch signaling. A dynamic signature reflects progressive immune responses dominated by type 2 cytokines with an additional role of TH17 and natural killer cell signaling.

S3-Guideline on allergy prevention: 2014 update: Guideline of the German Society for Allergology and Clinical Immunology (DGAKI) and the German Society for Pediatric and Adolescent Medicine (DGKJ).

The continued high prevalence of allergic diseases in Western industrialized nations combined with the limited options for causal therapy make evidence-based primary prevention necessary. The recommendations last published in the S3-guideline on allergy prevention in 2009 have been revised and a consensus reached on the basis of an up-to-date systematic literature search. Evidence was sought for the period between May 2008 and May 2013 in the Cochrane and MEDLINE electronic databases, as well as in the reference lists of recent review articles. In addition, experts were surveyed for their opinions. The relevance of retrieved literature was checked by means of two filter processes: firstly according to title and abstract, and secondly based on the full text of the articles. Included studies were given an evidence grade, and a bias potential (low/high) was specified for study quality. A formal consensus on the revised recommendations was reached by representatives of the relevant specialist societies and (self-help) organizations (nominal group process). Of 3,284 hits, 165 studies (one meta-analysis, 15 systematic reviews, 31 randomized controlled trials, 65 cohort studies, 12 case-control studies and 41 cross-sectional studies) were included and evaluated. Recommendations on the following remain largely unaltered: full breastfeeding for 4 months as a means of allergy prevention (hypoallergenic infant formula in the case of infants at risk); avoidance of overweight; fish consumption (during pregnancy/lactation and in the introduction of solid foods for infants); vaccination according to the recommendations of the German Standing Committee on Vaccination (Ständige Impfkommission, STIKO); avoidance of air pollutants and tobacco exposure and avoidance of indoor conditions conducive to the development of mold. The assertion that a reduction in house-dust mite allergen content as a primary preventive measure is not recommended also remains unchanged. The introduction of solid foods into infant diet should not be delayed. In the case of children at risk cats should not be acquired as domestic pets. Keeping dogs is not associated with an increased risk of allergy. The updated guideline includes a new recommendation to consider the increased risk of asthma following delivery by cesarean section. Additional statements have been formulated on pre- and probiotic agents, psychosocial factors, medications, and various nutritional components. Revising the guideline by using an extensive evidence base has resulted not only in an endorsement of the existing recommendations, but also in modifications and in the addition of new recommendations. The updated guideline enables evidence-based and up-to-date recommendations to be made on allergy prevention. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available for this article at 10.1007/s40629-014-0022-4 and is accessible for authorized users.