Explore the vast range of titles available.

In a randomized trial involving patients with the rare but disabling disorder generalized pustular psoriasis, the anti–interleukin-36 monoclonal antibody spesolimab greatly curtailed disease activity as compared with placebo over a period of 1 week. Systemic drug reactions and infections occurred with spesolimab.

Although anti-tumor necrosis factor (TNF) agents are highly effective in the treatment of psoriasis, 2–5% of treated patients develop psoriasis-like skin lesions called paradoxical psoriasis. The pathogenesis of this side effect and its distinction from classical psoriasis remain unknown. Here we show that skin lesions from patients with paradoxical psoriasis are characterized by a selective overexpression of type I interferons, dermal accumulation of plasmacytoid dendritic cells (pDC), and reduced T-cell numbers, when compared to classical psoriasis. Anti-TNF treatment prolongs type I interferon production by pDCs through inhibition of their maturation. The resulting type I interferon overexpression is responsible for the skin phenotype of paradoxical psoriasis, which, unlike classical psoriasis, is independent of T cells. These findings indicate that paradoxical psoriasis represents an ongoing overactive innate inflammatory process, driven by pDC-derived type I interferon that does not lead to T-cell autoimmunity. The pathogenesis of paradoxical psoriasis in patients receiving anti-TNF treatments for classical psoriasis is unclear. Here, the authors show that anti-TNF drugs enhance the production of type I interferon by plasmacytoid dendritic cells, causing skin lesions that, unlike classical psoriasis, lack T- cell autoimmunity.

Acute generalized exanthematous pustulosis (AGEP) is a rare, acute, severe cutaneous adverse reaction mainly attributed to drugs, although other triggers, including infections, vaccinations, ingestion of various substances, and spider bites, have also been described. AGEP is characterized by the development of edema and erythema followed by the eruption of multiple punctate, non-follicular, sterile pustules and subsequent desquamation. AGEP typically has a rapid onset and prompt resolution within a few weeks. The differential diagnoses for AGEP are broad and include infectious, inflammatory, and drug-induced etiologies. Diagnosis of AGEP depends on both clinical and histologic criteria, as cases of overlap with other disease processes have been reported. Management includes removal of the offending drug or treatment of the underlying cause, if necessary, and supportive care, as AGEP is a self-limited disease. This review aims to provide an overview and update on the epidemiology, pathogenesis, reported precipitating factors, differentials, diagnosis, and management of AGEP.

Purpose The association between smoking and the risk of skin cancers has been studied without reaching consistent findings. This study aims to assess this association through an updated meta-analysis of cohort studies. Methods We retrieved cohort studies that investigated the temporal association between smoking and the risk of basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and malignant melanoma (MM). Pooled relative risks (RRs) and confidence intervals (CIs) of the included articles were calculated for current, former, and heavy smoking compared with never smoking. Publication bias was detected using the Egger’s regression. Results A total of 15 studies, published between 1990 and 2018, were included. Current smoking was associated with a higher risk of SCC (pooled RR = 1.32, 95% CI 1.15, 1.52) but with a lower risk of BCC (pooled RR = 0.85, 95% CI 0.75, 0.96) and MM (pooled RR = 0.72, 95% CI 0.64, 0.82). No publication bias was detected, and no single study had a substantial impact on the pooled results. Similar results were detected for heavy smoking, while former smoking was not associated with the risk of skin cancer. Conclusion Current smoking and heavy smoking were associated with a higher risk of SCC but a decreased risk of BCC and MM, while former smoking was not associated with skin cancer risk.

Data evaluating the chronological order of appearance of extraintestinal manifestations (EIMs) relative to the time of inflammatory bowel disease (IBD) diagnosis is currently lacking. We aimed to assess the type, frequency, and chronological order of appearance of EIMs in patients with IBD.MethodsData from the Swiss Inflammatory Bowel Disease Cohort Study were analyzed.ResultsThe data on 1249 patients were analyzed (49.8% female, median age: 40 [interquartile range, 30–51 yr], 735 [58.8%] with Crohn's disease, 483 [38.7%] with ulcerative colitis, and 31 [2.5%] with indeterminate colitis). A total of 366 patients presented with EIMs (29.3%). Of those, 63.4% presented with 1, 26.5% with 2, 4.9% with 3, 2.5% with 4, and 2.7% with 5 EIMs during their lifetime. Patients presented with the following diseases as first EIMs: peripheral arthritis 70.0%, aphthous stomatitis 21.6%, axial arthropathy/ankylosing spondylitis 16.4%, uveitis 13.7%, erythema nodosum 12.6%, primary sclerosing cholangitis 6.6%, pyoderma gangrenosum 4.9%, and psoriasis 2.7%. In 25.8% of cases, patients presented with their first EIM before IBD was diagnosed (median time 5 mo before IBD diagnosis: range, 0–25 mo), and in 74.2% of cases, the first EIM manifested itself after IBD diagnosis (median: 92 mo; range, 29–183 mo).ConclusionsIn one quarter of patients with IBD, EIMs appeared before the time of IBD diagnosis. Occurrence of EIMs should prompt physicians to look for potential underlying IBD.

It is important but challenging for prospective health professionals to learn the visual distinction between potentially harmful and harmless skin lesions, such as malignant melanomas and benign nevi. Knowledge about factors related to diagnostic performance is sparse but a prerequisite for designing and evaluating evidence-based educational interventions. Hence, this study explored how the characteristics of 240 skin lesions, the number of classified lesions and the response times of 137 laypeople were related to performance in diagnosing pigmented skin cancer. Our results showed large differences between the lesions, as some were classified correctly by more than 90% and others by less than 10% of the participants. A t -test showed that for melanomas, the correct diagnosis was provided significantly more often than for nevi. Furthermore, we found a significant Pearson correlation between the number of solved tasks and performance in the first 50 diagnostic tasks. Finally, t -tests for investigating the response times revealed that compared to true decisions, participants spent longer on false-negative but not on false-positive decisions. These results provide novel knowledge about performance-related factors that can be useful when designing diagnostic tests and learning interventions for melanoma detection.

Extraintestinal cutaneous manifestations of IBD represent a severe disease complication and an early and accurate treatment might positively influence the disease course. Using the patient collective of the Swiss IBD Cohort Study (SIBDCS), we analysed epidemiological as well as clinical factors being associated with the onset of pyoderma gangrenosum, erythema nodosum and aphthous ulcers in IBD patients. We included 3266 SIBDCs patients, 1840 with Crohn's disease (CD) and 1426 with ulcerative colitis (UC) or IBD unclassified (IBDU) and analysed the association of cutaneous manifestations with age, age at diagnosis time, type of disease, gender, family history, HLA-allotype, smoking, intestinal disease activity, therapy and other extraintestinal manifestations (EIM). 354 CD patients and 136 UC/IBDU patients presented with skin manifestations at any time during their disease course. In both, CD and UC, female gender and younger age at IBD diagnosis were significantly associated with extraintestinal skin manifestations. For CD, we also detected a positive family history as associated factor. As an indicator of more intensive intestinal disease activity, patients with cutaneous manifestations of IBD needed more frequently therapy with antibiotics, steroids, immunomodulators and anti-TNF. Multivariate analysis revealed female gender, younger age at diagnosis and presence of other extraintestinal manifestations as factors being associated with skin EIM in IBD patients and anti-TNF as well as immunomodulatory treatment in CD patients. Our results suggest that young females with a positive family history of IBD might be at increased risk for the onset of skin manifestations and require a careful screening for such complications.

With rising melanoma incidence and mortality, early detection and surgical removal of primary lesions is essential. Multispectral imaging is a new, non-invasive technique that can facilitate skin cancer detection by measuring the reflectance spectra of biological tissues. Currently, incident illumination allows little light to be reflected from deeper skin layers due to high surface reflectance. A pilot study was conducted at the University Hospital Basel to evaluate, whether multispectral imaging with direct light coupling could extract more information from deeper skin layers for more accurate dignity classification of melanocytic lesions. 27 suspicious pigmented lesions from 23 patients were included (6 melanomas, 6 dysplastic nevi, 12 melanocytic nevi, 3 other). Lesions were imaged before excision using a prototype snapshot mosaic multispectral camera with incident and direct illumination with subsequent dignity classification by a pre-trained multispectral image analysis model. Using incident light, a sensitivity of 83.3% and a specificity of 58.8% were achieved compared to dignity as determined by histopathological examination. Direct light coupling resulted in a superior sensitivity of 100% and specificity of 82.4%. Convolutional neural network classification of corresponding red, green, and blue lesion images resulted in 16.7% lower sensitivity (83.3%, 5/6 malignant lesions detected) and 20.9% lower specificity (61.5%) compared to direct light coupling with multispectral image classification. Our results show that incorporating direct light multispectral imaging into the melanoma detection process could potentially increase the accuracy of dignity classification. This newly evaluated illumination method could improve multispectral applications in skin cancer detection. Further larger studies are needed to validate the camera prototype.

IntroductionGeneralized pustular psoriasis (GPP) is a rare, potentially life-threatening disease characterised by recurrent flares of widespread neutrophilic aseptic skin pustular eruption. Despite the availability of approved biologics for GPP in Japan, Taiwan and Thailand, associated evidence is largely based on uncontrolled studies in which acute flares were not directly assessed. Therefore, there is a high unmet need to investigate new rapid-acting effective treatments that resolve symptoms associated with acute GPP flares. A prior Phase I proof-of-concept study showed rapid improvements in skin and pustule clearance with a single intravenous dose of spesolimab, a novel anti-interleukin-36 receptor antibody, in patients presenting with an acute GPP flare. Here, we present the design and rationale of Effisayil 1, a global, Phase II, placebo-controlled study to evaluate the efficacy, safety and tolerability of spesolimab in patients presenting with an acute GPP flare.Methods and analysisAt least 51 patients with an acute GPP flare will be randomised 2:1 to receive a single 900 mg intravenous dose of spesolimab or placebo and followed for up to 28 weeks. The primary endpoint is a Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) pustulation subscore of 0 (pustule clearance) at Week 1. The key secondary endpoint is a GPPGA score of 0 or 1 (clear or almost clear) at Week 1. Safety will be assessed over the study duration by the occurrence of treatment-emergent adverse events. Blood and skin biopsies will be collected to assess biomarkers. Superiority of spesolimab over placebo in the proportion of patients achieving the primary and key secondary endpoints will be evaluated.Ethics and disseminationThe study complies with the ethical principles of the Declaration of Helsinki, the International Council for Harmonisation’s Good Clinical Practice and local regulations. Ethics committee approvals have been obtained for each centre from all participating countries and are listed in online supplementary file 1. Primary results will be published in a peer-reviewed journal.Trial registration detailsClinicalTrials.gov identifier: NCT03782792; Pre-results.