Summary To gain further insight into the genetic architecture of psoriasis, we conducted a meta-analysis of three genome-wide association studies (GWAS) and two independent datasets genotyped on the Immunochip, involving 10,588 cases and 22,806 controls in total. We identified 15 new disease susceptibility regions, increasing the number of psoriasis-associated loci to 36 for Caucasians. Conditional analyses identified five independent signals within previously known loci. The newly identified shared disease regions encompassed a number of genes whose products regulate T-cell function (e.g. RUNX3, TAGAP and STAT3). The new psoriasis-specific regions were notable for candidate genes whose products are involved in innate host defense, encoding proteins with roles in interferon-mediated antiviral responses (DDX58), macrophage activation (ZC3H12C), and NF-κB signaling (CARD14 and CARM1). These results portend a better understanding of shared and distinctive genetic determinants of immune-mediated inflammatory disorders and emphasize the importance of the skin in innate and acquired host defense.

To identify new susceptibility loci for psoriasis, we undertook a genome-wide association study of 594,224 SNPs in 2,622 individuals with psoriasis and 5,667 controls. We identified associations at eight previously unreported genomic loci. Seven loci harbored genes with recognized immune functions (IL28RA, REL, IFIH1, ERAP1, TRAF3IP2, NFKBIA and TYK2). These associations were replicated in 9,079 European samples (six loci with a combined P < 5 × 10⁻⁸ and two loci with a combined P < 5 × 10⁻⁷). We also report compelling evidence for an interaction between the HLA-C and ERAP1 loci (combined P = 6.95 × 10⁻⁶). ERAP1 plays an important role in MHC class I peptide processing. ERAP1 variants only influenced psoriasis susceptibility in individuals carrying the HLA-C risk allele. Our findings implicate pathways that integrate epidermal barrier dysfunction with innate and adaptive immune dysregulation in psoriasis pathogenesis

We report the clinical, histopathologic, immunohistologic, and prognostic findings in 19 patients with cutaneous leiomyosarcoma, eight males and 11 females (mean age, 66 years; age range, 41-93 years). The tumors presented mainly as solitary lesions and were located on the head and neck (eight lesions), trunk (four lesions), upper extremities (three lesions), and lower extremities (four lesions). Histopathologically, two predominant growth patterns were observed: nodular (12 cases) and diffuse (seven cases). Neoplasms with a nodular growth pattern were characterized by high cellularity and prominent nuclear atypia, and they showed conspicuous mitoses, several necrotic cells, and sometimes extensive necrotic areas. By contrast, most cutaneous leiomyosarcomas with a diffuse growth pattern revealed low cellularity, well-differentiated smooth muscle cells, inconspicuous mitotic figures, and few or no necrotic cells. Immunohistologic investigations revealed all cutaneous leiomyosarcomas to express vimentin and smooth muscle actin. Pan-muscle actin (HHF-35) was also expressed in most cases (15 lesions). However, only 12 lesions showed positive staining for desmin. Remarkable was the expression of cytokeratins in five lesions. Clinical follow-up revealed local recurrences in five patients (three cases with nodular pattern and two lesions with a diffuse pattern) after a period ranging from 8 months to 3 years after surgical excision. No distant metastases have been observed in our series. We conclude that cutaneous leiomyosarcoma with a diffuse growth pattern may constitute a pitfall in histopathologic diagnosis because of the presence of only subtle criteria for malignancy. Cutaneous leiomyosarcoma may show different immunophenotypes, thus emphasizing the importance of using a large panel of antibodies (smooth muscle actin, HHF-35, desmin, vimentin, cytokeratins, and S-100 protein) in immunohistologic diagnosis. Cutaneous leiomyosarcoma sometimes reveals local recurrences, but it has negligible potential for distant metastases.

Our study shows that the most useful histopathologic criteria for distinguishing LEP from SPTCL are the presence of involvement of the epidermis, lymphoid follicles with reactive germinal centers, mixed cell infiltrate with prominent plasma cells, clusters of B lymphocytes, and polyclonal TCR-gamma gene rearrangement.

MPAP and resistance in the upper normal range at rest and moderate exercise are associated with decreased exercise capacity and may indicate early pulmonary vasculopathy in patients with systemic sclerosis. Investigations on the prognostic and therapeutic implications of such borderline findings are warranted. Clinical trial registered with http://www.clinicaltrials.gov (NCT00609349).

Mobile teledermatology is a valuable tool for the home monitoring of patients with psoriasis that makes a meaningful difference in their lives. It is well accepted by both patients and the physicians involved.

Summary Background Drug survival rates reflect efficacy and safety and may be influenced by the availability of alternative treatment options. Little is known about time‐dependent drug survival in psoriasis and the effect of increasing numbers of biologic treatment options. Objectives To determine whether drug survival is influenced by the availability of treatment options and by factors such as gender, psoriatic arthritis or previous biologic treatment. Methods This observational, retrospective, multicentre cohort study analysed data from patients registered in the Austrian Psoriasis Registry (PsoRA) who were treated with biologics between 1 January 2015 and 30 November 2019. Results A total of 1572 patients who received 1848 treatment cycles were included in this analysis. The highest long‐term Psoriasis Area and Severity Index improvement was observed after treatment with ixekizumab, followed by ustekinumab and secukinumab, adalimumab and etanercept. Overall, ustekinumab surpassed all other biologics in drug survival up to 48 months. However, when adjusted for biologic naïvety, its superiority vanished and drug survival rates were similar for ixekizumab (91·6%), secukinumab (90·2%) and ustekinumab (92·8%), all of them superior to adalimumab (76·5%) and etanercept (71·9%) at 12 months and beyond. Besides biologic non‐naïvety (2·10, P < 0·001), the introduction of a new drug such as secukinumab or ixekizumab (relative hazard ratio 1·6, P = 0·001) and female gender (1·50, P = 0·019) increased the risk of treatment discontinuation overall, whereas psoriatic arthritis did not (1·12, P = 0·21). Conclusions The time‐dependent availability of drugs should be considered when analysing and comparing drug survival. Previous biologic exposure significantly influences drug survival. Women are more likely to stop treatment.

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