Immune checkpoint inhibitor-induced neurotoxicity is not associated with seroprevalence of neurotropic infections.

BACKGROUND: Immune checkpoint inhibitors (ICI) substantially improve outcome for patients with cancer. However, the majority of patients develops immune-related adverse events (irAEs), which can be persistent and significantly reduce quality of life. Neurological irAEs occur in 1-5% of patients and can induce severe, permanent sequelae or even be fatal. In order to improve the diagnosis and treatment of neurological irAEs and to better understand their pathogenesis, we assessed whether previous neurotropic infections are associated with neurological irAEs. METHODS: Neurotropic infections that might predispose to ICI-induced neurological irAEs were analyzed in 61 melanoma patients from 3 countries, the Netherlands, Australia and Germany, including 24 patients with neurotoxicity and 37 control patients. In total, 14 viral, 6 bacterial, and 1 protozoal infections previously reported to trigger neurological pathologies were assessed using routine serology testing. The Dutch and Australian cohorts (NL) included pre-treatment plasma samples of patients treated with neoadjuvant ICI therapy (OpACIN-neo and PRADO trials; NCT02977052). In the Dutch/Australian cohort a total of 11 patients with neurological irAEs were compared to 27 control patients (patients without neurological irAEs). The German cohort (LMU) consisted of serum samples of 13 patients with neurological irAE and 10 control patients without any documented irAE under ICI therapy. RESULTS: The association of neurological irAEs with 21 possible preceding infections was assessed by measuring specific antibodies against investigated agents. The seroprevalence of all the tested viral (cytomegalovirus, Epstein-Barr-Virus, varicella-zoster virus, measles, rubella, influenza A and B, human herpes virus 6 and 7, herpes simplex virus 1 and 2, parvovirus B19, hepatitis A and E and human T-lymphotropic virus type 1 and 2), bacterial (Borrelia burgdorferi sensu lato, Campylobacter jejuni, Mycoplasma pneumoniae, Coxiella burnetti, Helicobacter pylori, Yersinia enterocolitica and Y. pseudotuberculosis) and protozoal (Toxoplasma gondii) infections was similar for patients who developed neurological irAEs as compared to control patients. Thus, the analysis provided no evidence for an association of described agents tested for seroprevalence with ICI induced neurotoxicity. CONCLUSION: Previous viral, bacterial and protozoal neurotropic infections appear not to be associated with the development of neurological irAEs in melanoma patients who underwent therapy with ICI across 3 countries. Further efforts are needed to unravel the factors underlying neurological irAEs in order to identify risk factors for these toxicities, especially with the increasing use of ICI in earlier stage disease.

The effectiveness of an extra-curricular lecture for STI prevention and sexual education.

While the incidence of infections with the human immunodeficiency virus largely remained unchanged in Germany, an increase of other sexually transmitted infections (STIs) was observed. The aim was to analyse the effectiveness of our sexual education lecture for students in improving the awareness, knowledge and prevention of STIs. We conducted a cross-sectional survey after students had attended our extra-curricular lecture at the Department of Dermatology of the Ludwig-Maximilians-University of Munich, Germany (LMU). We compared the data with a previously performed study in which the same survey was carried out before the lecture had started. A total of 5866 questionnaires were included in the analysis. After attending the lecture significantly more students were aware of STIs (syphilis: 36.8% (before) vs. 63.5% (after); chlamydia: 30.5% vs. 49.3%; gonorrhoea: 22.4% vs. 38.2%; human papillomaviruses (HPV): 17.7% vs. 30.2%), the transmission pathways of STIs (oral: 36.6% vs. 82.6%; vaginal: 81.8% vs. 97.3%; anal: 42.8% vs. 94.0%; penile: 68.7% vs. 92.1%), knew that the HPV vaccination is directed against a virus (36.8% vs. 56.9%) and were interested in receiving a vaccination (57.7% vs. 78.8%). This study demonstrates the positive educative effects of our lecture for awareness and improved knowledge of STIs. To satisfy the need for a comprehensive sexual education, a combination of school and health facility-based programmes should be implemented as one single lecture cannot convey the entire information about STIs.

Risks and benefits of dermatological machine learning health care applications-an overview and ethical analysis.

BACKGROUND: Visual data are particularly amenable for machine learning techniques. With clinical photography established for skin surveillance and documentation purposes as well as progress checks, dermatology is an ideal field for the development and application of emerging machine learning health care applications (ML-HCAs). To date, several ML-HCAs have detected malignant skin lesions on par with experts or found overlooked visual patterns that correlate with certain dermatological diseases. However, it is well established that ML-HCAs come with ethical and social implications. OBJECTIVES: Currently, there is a lack of research that establishes model design, training, usage and regulation of such technologies sufficient to ensure ethically and socially responsible development and clinical translation, specifically within the field of dermatology. With this paper, we aim to give an overview of currently discussed ethical issues relating to dermatological ML-HCAs. METHODS: On the basis of a thematic, keyword-based literature search, we performed an ethical analysis against established frameworks of biomedical ethics. We combined our results with current, relevant normative machine learning ethics literature to identify the status quo of the ethics of ML-HCAs in dermatology. We describe the benefits and risks of dermatological ML-HCAs that are currently being developed for clinical purposes. RESULTS: The potential benefits range from better patient outcomes to better knowledge accessibility to decreasing health care disparities, that is, standards of care between different population groups. The risks associated with ML-HCAs range from confidentiality issues to individual patient outcomes as well as the exacerbation of prevalent health care disparities. We discuss the practical implications for all stages of dermatological ML-HCA development. CONCLUSION: We found that ML-HCAs present stakeholder-specific risks for patients, health care professionals and society, which need to be considered separately. The discipline lacks sufficient biomedical ethics research that could standardize the approach to ML-HCA model design, training, use and regulation of such technologies.

Deep learning-based classification of dermatological lesions given a limited amount of labelled data.

BACKGROUND: Artificial intelligence (AI) techniques are promising in early diagnosis of skin diseases. However, a precondition for their success is the access to large-scaled annotated data. Until now, obtaining this data has only been feasible with very high personnel and financial resources. OBJECTIVES: The aim of this study was to overcome the obstacle caused by the scarcity of labelled data. METHODS: To simulate the scenario of label shortage, we discarded a proportion of labels of the training set. The training set consisted of both labelled and unlabelled images. We then leveraged a self-supervised learning technique to pretrain the AI model on the unlabelled images. Next, we fine-tuned the pretrained model on the labelled images. RESULTS: When the images in the training dataset were fully labelled, the self-supervised pretrained model achieved 95.7% of accuracy, 91.7% of precision and 90.7% of sensitivity. When only 10% of the data were labelled, the model could still yield 87.7% of accuracy, 81.7% of precision and 68.6% of sensitivity. In addition, we also empirically verified that the AI model and dermatologists are consistent in visually inspecting the skin images. CONCLUSIONS: The experimental results demonstrate the great potential of the self-supervised learning in alleviating the scarcity of annotated data.

Association of sex and systemic therapy treatment outcomes in psoriasis: a two-country, multicentre, prospective, noninterventional registry study.

BACKGROUND: Few systematic data on sex-related treatment responses exist for psoriasis. OBJECTIVES: To evaluate sex differences with respect to systemic antipsoriatic treatment. METHODS: Data from patients with moderate-to-severe psoriasis in the PsoBest or Swiss Dermatology Network of Targeted Therapies (SDNTT) registries were analysed. Treatment response was defined as achieving a ≥ 75% reduction in Psoriasis Area and Severity Index (PASI 75) or PASI ≤ 3 at treatment months 3, 6 and 12, supplemented by patient-reported outcomes [i.e. Dermatology Life Quality Index (DLQI) ≤ 1 and delta DLQI ≥ 4]. RESULTS: In total, 5346 patients registered between 2007 and 2016 were included (PsoBest, n = 4896; SDNTT, n = 450). The majority received nonbiological treatment (67·3% male, 69·8% female). Women showed slightly higher PASI response rates after 3 (54·8% vs. 47·2%; P ≤ 0·001), 6 (70·8% vs. 63·8%; P ≤ 0·001) and 12 months (72·3% vs. 66·1%; P ≤ 0·004). A significantly higher proportion of women achieved a reduction in DLQI ≥ 4 [month 3: 61·4% vs 54·8% (P ≤ 0·001); month 6: 69·6% vs. 62·4% (P ≤ 0·001); month 12: 70·7% vs. 64·4% (P ≤ 0·002)]. Regarding PASI ≤ 3, women on biologics showed a significantly superior treatment response compared with men at 3 (57·8% vs. 48·5%; P ≤ 0·004) and 6 months (69·2% vs. 60·9%; P ≤ 0·018). Women in the nonbiological treatment group had a significantly better treatment response (PASI response, PASI 75 and PASI ≤ 3) over 12 months compared with men. CONCLUSIONS: We provide evidence that women experience better treatment outcomes with systemic antipsoriatic therapy than men.

Line-field optical coherence tomography: in vivo diagnosis of basal cell carcinoma subtypes compared with histopathology.

BACKGROUND: Basal cell carcinoma (BCC) is the most common skin cancer in the general population. Treatments vary from Mohs surgery to topical therapy, depending on the subtype. Dermoscopy, reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) have gained a foothold in daily clinical practice to optimize diagnosis and subtype-oriented treatment. The new technique of line-field confocal OCT (LC-OCT) allows imaging at high resolution and depth, but its use has not yet been investigated in larger studies. AIM: To evaluate the main LC-OCT criteria for the diagnosis and subtyping of BCC compared with histopathology, OCT and RCM. METHODS: In total, 52 histopathologically confirmed BCCs were evaluated for imaging criteria. Their frequency, predictive values and ROC curves were calculated. A multinominal regression with stepwise variables selection to distinguish BCC subtypes was performed. RESULTS: Nodular BCCs were mainly characterized by atypical keratinocytes, altered dermoepidermal junction (DEJ), tumour nests in the dermis, dark clefting, prominent vascularization and white hyper-reflective stroma. Superficial BCCs showed a thickening of the epidermis due to a series of tumour lobules with clear connection to the DEJ (string of pearls pattern). Infiltrative BCCs were characterized by elongated hyporeflective tumour strands, surrounded by bright collagen (shoal of fish pattern). The overall BCC subtype agreement between LC-OCT and conventional histology was 90.4% (95% CI 79.0-96.8). CONCLUSION: LC-OCT allows noninvasive, real-time identification of BCCs and their subtypes in vertical, horizontal and three-dimension mode compared with histology, RCM and OCT. Further larger studies are needed to better explore the clinical applications of this promising device.

Line-field confocal optical coherence tomography for the in vivo real-time diagnosis of different stages of keratinocyte skin cancer: a preliminary study.

BACKGROUND: The treatment of keratinocyte cancers (KC) strictly depends on their differentiation and invasiveness. Non-invasive diagnostic techniques can support the diagnosis in real time, avoiding unnecessary biopsies. This study aimed to preliminarily define main imaging criteria and histological correlations of actinic keratosis (AK), Bowen's disease (BD) and squamous cell carcinoma (SCC) using the novel device line-field confocal optical coherence tomography (LC-OCT). METHODS: Dermoscopy and LC-OCT images of 73 histopathologically confirmed lesions (46 AKs, 11 BD and 16 SCCs) were included in the study. Exemplary lesions (10 AKs, 5 BD and 5 SCCs) were additionally investigated with optical coherence tomography and reflectance confocal microscopy. RESULTS: Most common LC-OCT findings of KC in the descriptive statistics were hyperkeratosis/parakeratosis, disruption of stratum corneum, broadened epidermis, basal and suprabasal keratinocyte atypia, dilated vessels/neoangiogenesis and elastosis/collagen alterations. In the univariate multinomial logistic regression, a preserved DEJ was less common in SCC compared with AK and BD, BD displayed marked keratinocyte atypia involving all epidermal layers (bowenoid pattern), while SCC showed ulceration, increased epidermal thickness, keratin plugs, acantholysis, not visible/interrupted DEJ and epidermal bright particles. LC-OCT increased the diagnostic confidence by 24.7% compared with dermoscopy alone. CONCLUSIONS: Our study describes for the first time specific LC-OCT features of different stages of KC and their histopathological correlates, focusing on keratinocyte morphology and architecture of the epidermis and DEJ. LC-OCT may open new scenarios in the bedside diagnosis, treatment planning and follow-up of KC.

Improved protection of outdoor workers from solar ultraviolet radiation: position statement.

The vast majority of non-melanoma skin cancer (NMSC) is attributable to excessive exposure to ultraviolet radiation (UVR). Outdoor workers are exposed to an UVR dose at least 2 to 3 times higher than indoor workers and often to daily UVR doses 5 times above internationally recommended limits. The risk of UVR workplace exposure is vastly neglected, and the evident future challenges presented in this statement are contrasted with the current situation regarding legal recognition, patient care and compensation. While prevention is crucial to reduce cancer risks for outdoor workers, it is as much of relevance to better protect them through legally binding rules and regulations. Specific actions are outlined in five recommendations based on a Call to Action (table 1). The role of health professionals, including dermatologists, in this context is crucial.

Genomic profiling of late-onset basal cell carcinomas from two brothers with nevoid basal cell carcinoma syndrome.

BACKGROUND: Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant genetic disorder. It is commonly caused by mutations in PTCH1 and chiefly characterized by multiple basal cell carcinomas (BCCs) developing prior to the age of 30 years. In rare cases, NBCCS presents with a late onset of BCC development. OBJECTIVE: To investigate BCC tumorigenesis in two brothers, who showed characteristic features of NBCCS but developed their first BCCs only after the age of 40 years. Two other siblings did not show signs of NBCCS. RESULTS: We obtained blood samples from four siblings and nine BCCs from the two brothers with NBCCS. Whole exome sequencing and RNA sequencing revealed loss of heterozygosity (LOH) of PTCH1 in eight out of nine tumours that consistently involved the same haplotype on chromosome 9. This haplotype contained a germinal splice site mutation in PTCH1 (NM_001083605:exon9:c.763-6C>A). Analysis of germline DNA confirmed segregation of this mutation with the disease. All BCCs harboured additional somatic loss-of-function (LoF) mutations in the remaining PTCH1 allele which are not typically seen in other cases of NBCCS. This suggests a hypomorphic nature of the germinal PTCH1 mutation in this family. Furthermore, all BCCs had a similar tumour mutational burden compared to BCCs of unrelated NBCCS patients while harbouring a higher number of damaging PTCH1 mutations. CONCLUSIONS: Our data suggest that a sequence of three genetic hits leads to the late development of BCCs in two brothers with NBCCS: a hypomorphic germline mutation, followed by somatic LOH and additional mutations that complete PTCH1 inactivation. These genetic events are in line with the late occurrence of the first BCC and with the higher number of damaging PTCH1 mutations compared to usual cases of NBCCS.

European dermatology forum: Updated guidelines on the use of extracorporeal photopheresis 2020 - Part 2.

BACKGROUND: Following the first investigational study on the use of extracorporeal photopheresis for the treatment of cutaneous T-cell lymphoma published in 1983, this technology has received continued use and further recognition for additional earlier as well as refractory forms. After the publication of the first guidelines for this technology in the JEADV in 2014, this technology has maintained additional promise in the treatment of other severe and refractory conditions in a multidisciplinary setting. It has confirmed recognition in well-known documented conditions such as graft-vs.-host disease after allogeneic bone marrow transplantation, systemic sclerosis, solid organ transplant rejection including lung, heart and liver and to a lesser extent inflammatory bowel disease. MATERIALS AND METHODS: In order to further provide recognized expert practical guidelines for the use of this technology for all indications, the European Dermatology Forum (EDF) again proceeded to address these questions in the hands of the recognized experts within and outside the field of dermatology. This was done using the recognized and approved guidelines of EDF for this task. All authors had the opportunity to review each contribution as it was added. RESULTS AND CONCLUSION: These updated 2020 guidelines provide at present the most comprehensive available expert recommendations for the use of extracorporeal photopheresis based on the available published literature and expert consensus opinion. The guidelines were divided into two parts: PART I covers Cutaneous T-cell lymphoma, chronic graft-vs.-host disease and acute graft-vs.-host disease, while PART II will cover scleroderma, solid organ transplantation, Crohn's disease, use of ECP in paediatric patients, atopic dermatitis, type 1 diabetes, pemphigus, epidermolysis bullosa acquisita and erosive oral lichen planus.

[Cancer-associated genodermatoses]. / Tumorassoziierte Genodermatosen.

Hereditary tumor syndromes are characterized by a familial occurrence of tumors/cancer. A hereditary tumor syndrome should be suspected if a familial occurrence of cancer is seen and/or persons at younger age are affected. Some of the currently known tumor syndromes are associated with specific skin symptoms that can aid the physician in establishing the correct diagnosis. Examples are fibrofolliculoma in Birt-Hogg-Dubé syndrome, epidermal cysts, sebaceous cysts, neurofibroma in Gardner syndrome and sebaceous neoplasms or keratoacanthoma in Muir-Torre syndrome. If a genetic tumor syndrome is suspected, genetic testing and counselling should be performed in the index patient and is also recommended for family members. Affected patients should be offered regular clinical surveillance by the appropriate medical disciplines. Since curative therapy does not exist so far, preventive screening is of great importance.

Corynebacterium kroppenstedtii subsp. demodicis is the endobacterium of Demodex folliculorum.

BACKGROUND: Demodex spp. mites are the most complex member of the human skin microbiome. Mostly they are commensals, although their pathophysiological role in inflammatory dermatoses is recognized. Demodex mites cannot be cultivated in vitro, so only little is known about their life cycle, biology and physiology. Different bacterial species have been suggested to be the endobacterium of Demodex mites, including Bacillus oleronius, B. simplex, B. cereus and B. pumilus. OBJECTIVES: Our aim was to find the true endobacterium of human Demodex mites. METHODS: The distinct genetic and phenotypic differences and similarities between the type strain and native isolates are described by DNA sequencing, PCR, MALDI-TOF, DNA-DNA hybridization, fatty and mycolic acid analyses, and antibiotic resistance testing. RESULTS: We report the true endobacterium of Demodex folliculorum, independent of the sampling source of mites or life stage: Corynebacterium kroppenstedtii subsp. demodicis. CONCLUSIONS: We anticipate our finding to be a starting point for more in-depth understanding of the tripartite microbe-host interaction between Demodex mites, its bacterial endosymbiont and the human host.

Clinical and pathogenic aspects of the severe cutaneous adverse reaction epidermal necrolysis (EN).

The severe cutaneous adverse reaction epidermal necrolysis (EN) which includes toxic epidermal necrolysis and the milder Stevens-Johnson syndrome is characterized by epidermal loss due to massive keratinocyte apoptosis and/or necroptosis. EN is often caused by a drug mediating a specific TCR-HLA interaction via the (pro)hapten, pharmacological interaction or altered peptide loading mechanism involving a self-peptide presented by keratinocytes. (Memory) CD8 + T cells are activated and exhibit cytotoxicity against keratinocytes via the perforin/granzyme B and granulysin pathway and Fas/FasL interaction. Alternatively drug-induced annexin release by CD14 + monocytes can induce formyl peptide receptor 1 death of keratinocytes by necroptosis. Subsequent keratinocyte death stimulates local inflammation, activating other immune cells producing pro-inflammatory molecules and downregulating regulatory T cells. Widespread epidermal necrolysis and inflammation can induce life-threatening systemic effects, leading to high mortality rates. Research into genetic susceptibility aims to identify risk factors for eventual prevention of EN. Specific HLA class I alleles show the strongest association with EN, but risk variants have also been identified in genes involved in drug metabolism, cellular drug uptake, peptide presentation and function of CD8 + T cells and other immune cells involved in cytotoxic responses. After the acute phase of EN, long-term symptoms can remain or arise mainly affecting the skin and eyes. Mucosal sequelae are characterized by occlusions and strictures due to adherence of denuded surfaces and fibrosis following mucosal inflammation. In addition, systemic pathology can cause acute and chronic hepatic and renal symptoms. EN has a large psychological impact and strongly affects health-related quality of life among EN survivors.

The more the better? An appraisal of combination therapies for actinic keratosis.

Actinic keratoses (AK) are common precancerous lesions of the skin. Numerous interventions exist for the treatment of AK, including lesion- and field-directed approaches. In daily practice, different treatment modalities are often combined to maximize clearance rates. However, whether a combination therapy is preferable to monotherapy in terms of efficacy and safety has been subject of intense debate. In this review, we summarize the current knowledge on the efficacy and safety of local combination therapies for the treatment of patients with AK. Combination approaches of cryosurgery followed by photodynamic therapy (PDT), laser-assisted PDT, PDT in combination with topical interventions and microneedling-assisted PDT have shown slightly better efficacy results with similar tolerability compared to the respective monotherapy. However, the individual usage of combination therapies should be checked on a case-by-case basis and take into account individual patient- and lesion-specific aspects as more resources are needed and because the individual monotherapies are already highly effective.

Retrospective analysis of alpha-human papillomavirus (HPV) types in tissue samples from anogenital dysplasias - introduction of the RICH (Risk of HPV-related Carcinoma in HIV+/- patients) score.

BACKGROUND: Chronic viral infections caused by highly contagious human papillomaviruses (HPVs) from the alpha genus are a substantial risk factor for tumour diseases. OBJECTIVES: The goal of this study was to compare the HPV infection pattern with histology in a patient group of immunocompromised HIV+ and non-immunocompromised patients with anal intraepithelial neoplasia. MATERIALS AND METHODS: Tissue samples (n = 210) from the anogenital area of 121 patients underwent retrospective histological and molecular examination for HPV DNA prevalence by chip analysis. The study was part of a cancer screening from the Dermatology Department of the LMU Munich, Germany. All data were collected and processed anonymously. RESULTS: HPV 6 or 11 are more abundant in tissue samples from histologically diagnosed condylomata acuminata (47.7%) compared to grade 1, 2, and 3 intraepithelial neoplasias (IN 1-3). Detection of high-risk (hr) alpha-HPV DNA was significantly higher in tissue samples from IN 3 (67.5%) compared to IN 1 and 2 (12.9%), and compared to condylomata acuminata (29.5%). No HPV types were detected in histologically unremarkable tissue samples. There was a significant association between the prevalence of HPV 16 and the classifications IN 1 to IN 3 (χ2 (2) = 13.62, P = 0.001). We identified a significant correlation between the prevalence of high-risk and low-risk (lr) HPV types and HIV, especially mixed infections of different HPV types correlated with high-grade IN. Based on the present data, we suggest the risk of carcinoma in HIV+/- patients (RICH) score and test it in the 121 patients. CONCLUSIONS: hr alpha-HPVs, mainly HPV 16, are associated with increased oncogenic potential of premalignant lesions (IN 1-3), especially in HIV+ patients. Based on the combination of HIV/HPV-testing and histological analysis, we identified correlations that could potentially forecast the risk of malignant transformation and summarized them in the form of RICH score.

Clinical diversity and treatment approaches to blastic plasmacytoid dendritic cell neoplasm: a retrospective multicentre study.

BACKGROUND: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, aggressive type of haematologic precursor malignancy primarily often manifesting in the skin. We sought to provide a thorough clinical characterization and report our experience on therapeutic approaches to BPDCN. METHODS: In the present multicentric retrospective study, we collected all BPDCN cases occurring between 05/1999 and 03/2018 in 10 secondary care centres of the German-Swiss-Austrian cutaneous lymphoma working group. RESULTS: A total of 37 BPDCN cases were identified and included. Almost 90% of the patients had systemic manifestations (bone marrow, lymph nodes, peripheral blood) in addition to skin involvement. The latter presented with various types of cutaneous lesions: nodular (in more than 2/3) and bruise-like (in 1/3) skin lesions, but also maculopapular exanthema (in circa 1/6). Therapeutically, 22 patients received diverse combinations of chemotherapeutic regimens and/or radiotherapy. Despite initial responses, all of them ultimately relapsed and died from progressive disease. Eleven patients underwent haematopoietic stem cell transplantation (HSCT; autologous HSCT n = 3, allo-HSCT n = 8). The mortality rate among HSCT patients was only 33.33% with a median survival time of 60.5 months. CONCLUSION: Our study demonstrates the clinical diversity of cutaneous BPDCN manifestations and the positive development observed after the introduction of HSCT.

European dermatology forum - updated guidelines on the use of extracorporeal photopheresis 2020 - part 1.

BACKGROUND: Following the first investigational study on the use of extracorporeal photopheresis for the treatment of cutaneous T-cell lymphoma published in 1983, this technology has received continued use and further recognition for additional earlier as well as refractory forms. After the publication of the first guidelines for this technology in the JEADV in 2014, this technology has maintained additional promise in the treatment of other severe and refractory conditions in a multi-disciplinary setting. It has confirmed recognition in well-known documented conditions such as graft-versus-host disease after allogeneic bone marrow transplantation, systemic sclerosis, solid organ transplant rejection including lung, heart and liver and to a lesser extent inflammatory bowel disease. MATERIALS AND METHODS: In order to further provide recognized expert practical guidelines for the use of this technology for all indications, the European Dermatology Forum (EDF) again proceeded to address these questions in the hands of the recognized experts within and outside the field of dermatology. This was done using the recognized and approved guidelines of EDF for this task. All authors had the opportunity to review each contribution as it was added. RESULTS AND CONCLUSION: These updated 2020 guidelines provide at present the most comprehensive available expert recommendations for the use of extracorporeal photopheresis based on the available published literature and expert consensus opinion. The guidelines are divided in two parts: PART I covers cutaneous T-cell lymphoma, chronic graft-versus-host disease and acute graft-versus-host disease while PART II will cover scleroderma, solid organ transplantation, Crohn's disease, use of ECP in paediatrics practice, atopic dermatitis, type 1 diabetes, pemphigus, epidermolysis bullosa acquisita and erosive oral lichen planus.

[Computer-assisted skin cancer diagnosis : Is it time for artificial intelligence in clinical practice?] / Computerassistierte Hautkrebsdiagnose : Wann kommt künstliche Intelligenz in der Praxis an?

BACKGROUND: Artificial intelligence (AI) is increasingly being used in medical practice. Especially in the image-based diagnosis of skin cancer, AI shows great potential. However, there is a significant discrepancy between expectations and true relevance of AI in current dermatological practice. OBJECTIVES: This article summarizes promising study results of skin cancer diagnosis by computer-based diagnostic systems and discusses their significance for daily practice. We hereby focus on the analysis of dermoscopic images of pigmented and unpigmented skin lesions. MATERIALS AND METHODS: A selective literature search for recent relevant trials was conducted. The included studies used machine learning, and in particular "convolutional neural networks", which have been shown to be particularly effective for the classification of image data. RESULTS AND CONCLUSIONS: In numerous studies, computer algorithms were able to detect pigmented and nonpigmented neoplasms of the skin with high precision, comparable to that of dermatologists. The combination of the physician's assessment and AI showed the best results. Computer-based diagnostic systems are widely accepted among patients and physicians. However, they are still not applicable in daily practice, since computer-based diagnostic systems have only been tested in an experimental environment. In addition, many digital diagnostic criteria that help AI to classify skin lesions remain unclear. This lack of transparency still needs to be addressed. Moreover, clinical studies on the use of AI-based assistance systems are needed in order to prove its applicability in daily dermatologic practice.

[Psoriasis in dupilumab-treated atopic dermatitis]. / Psoriasis bei Dupilumab-behandeltem atopischem Ekzem.

Dupilumab is a monoclonal antibody that binds to the common alpha chain of the IL­4 and IL-13 receptor and blocks the Th2 signaling pathway, which plays a key role in the development of atopic dermatitis. We report on the case of a 40-year-old man, who developed histologically confirmed psoriasis after 6 weeks of dupilumab therapy. The arbitrary, abrupt stopping of the unusual, not guideline-based oral steroid therapy, together with the blockade of the Th2 signaling pathway by dupilumab were apparently the relevant trigger factors for the newly developed psoriasis in our patient.

Topical resiquimod dosing regimens in patients with multiple actinic keratoses: a multicentre, partly placebo-controlled, double-blind clinical trial.

BACKGROUND: Topical immune response modifiers are established for actinic keratosis (AK) treatment and efforts are underway to make further improvements to their efficacy and safety. OBJECTIVES: To investigate the optimal dosing regimens of the Toll-like receptor 7/8 agonist resiquimod in terms of efficacy, safety and tolerability. METHODS: In a multicentre, partly placebo-controlled, double-blind clinical trial, we randomized 217 patients with AK lesions to 0·03% resiquimod gel once-daily application three times per week for 4 weeks or seven times within 2 weeks or five times for 1 week (arms 1/2/3) followed by a treatment-free interval of 8 weeks and one repetition of the cycle. In two additional arms (arms 4/5), patients applied either resiquimod gel 0·01% or 0·03% three times per week up to a biological end point defined by skin erosion or for a maximum duration of 8 weeks. Clearance was assessed clinically and histologically. RESULTS: Complete clinical clearance ranged from 56% to 85% with the highest rate observed in arm 2. Resiquimod 0·03% gel was more effective than 0·01% gel. Clearance rates in arms 1/2/3 were comparable and higher than with placebo and were reached with 24, 14 and 10 gel applications, respectively. Overall, 128 patients (59%) experienced treatment-related adverse reactions. CONCLUSIONS: Resiquimod 0·03% gel is more effective than 0·01% gel. From the perspectives of safety and tolerability, the lower concentration and shorter duration are preferable. The clinical response in arms 2/3 was reached with fewer gel applications. The dosing regimens that used the biological end point (arms 4/5) proved equally efficacious as predefined treatment durations and may therefore be suitable for personalized AK treatment.