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Background: Improving health-related quality of life (HRQoL), disease severity, and treatment adherence through patient education is an increasingly important, yet relatively new area in dermatology. This randomized controlled trial aims to contribute to this growing area of research by exploring the effects of a 9-week educational program for patients with chronic skin diseases. Objective: The aim of the study was to evaluate the effect of a multidisciplinary educational program on HRQoL and disease severity in patients with psoriasis or atopic dermatitis (AD). Methods: Sixty-four patients with diagnosed psoriasis or AD were recruited from University Hospital Zurich and randomized (1:1) to the intervention or control group. To assess HRQoL, the following self-reported questionnaires were used: Dermatology Life Quality Index (DLQI), Skindex-29, EuroQol-5D (EQ-5D), RAND 36-Item Short Form Survey (SF-36), and Beck Depression Inventory (BDI) to measure depression symptoms. Psoriasis Area and Severity Index (PASI) and the Eczema Area and Severity Index (EASI) were used to capture disease extent. These scores were assessed at four study visits, which were performed at baseline and 3, 6, and 9 months after the start of the program. Results: At month 6, an improvement of at least 25% in BDI was recorded in 15 (68.2%) of 22 patients in the intervention group and 6 (27.3%) of 22 patients in the control group (difference 40.9%, p = 0.016). 53.3% (16 of 30) of patients achieved an improvement in one subdomain of the SF-36 score (role limitations due to emotional problems) at 6-month follow-up, compared with 23.1% (6 of 26) of those not attending the educational program (difference 30.2%; p = 0.042). No significant differences in DLQI, Skindex-29, EQ-5D, PASI, and EASI between both groups at the three time points were found. Conclusion: An educational program may improve HRQoL and depression status of patients with psoriasis or AD.

Cutaneous melanoma represents a major cause of cancer death in Europe. Without adequate therapy, the 5-year survival rate is 15-20% in distant metastatic disease. Evaluating the status quo of treatment standards in advanced melanoma and rationale for therapy decisions in Switzerland between January 2016 and September 2018. In this retrospective, anonymized registry, data of male and female patients with unresectable advanced/metastatic BRAF-positive cutaneous melanoma treated in first-, second- and third-line with registered substances were analyzed using descriptive statistics. Forty-one patients (56.1% male) were included providing a total of 70 treatment lines (first-line: n = 41; second-line: n = 18; and third-line: n = 11). Within the patients presenting with stage III or IV melanoma, immunotherapy with checkpoint inhibitors was more frequently administered as first-line treatment than targeted therapy (TT) (70.7% vs. 29.3%). Across all lines, patients received TT in 47.1% (predominantly combined BRAF-MEK-inhibition) and immunotherapy in 52.9% of the cases (anti-PD-1 monotherapy in 62.2% and anti-PD-1/anti-CTLA-4 combinations in 37.8%). Most commonly, the treatment type was switched from TT to immunotherapy or vice versa upon disease progression. The most frequent rationales for prescribing either TT or immunotherapy were physician's preference (40.0%) or remission pressure (28.6%), respectively. Disease progression led to treatment discontinuation more frequently than undesired events. Patients in Switzerland with unresectable advanced or metastatic BRAF-mutant melanoma predominantly receive guideline-recommended treatments. IO was used as predominant front-line therapy, with TT/immunotherapy switch being the predominant treatment principle. Sequencing studies are underway to identify the optimal treatment regimen for those patients. 32: 366-372 Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.

Junctional epidermolysis bullosa (JEB) is an incurable blistering skin disorder with high infant mortality often caused by nonsense variants in the genes that encode laminin 332.To evaluate the safety and outcomes following intravenous gentamicin readthrough therapy and subsequent laminin 332 expression in patients with JEB.This open-label, pilot nonrandomized clinical trial assessed 1 course of low- or high-dose intravenous gentamicin, including follow-up at 30 and 90 days after treatment. Five pediatric patients with JEB (2 with intermediate JEB and 3 with severe JEB) and confirmed nonsense variants in LAMA3 or LAMB3 in 1 or 2 alleles and decreased expression of laminin 332 at the dermal-epidermal junction of their skin participated in the study, which was performed at a single institution in collaboration with physicians and home infusion services near the patients from April 1, 2019, to February 28, 2021, with follow-up until May 31, 2021.Three patients received gentamicin at 7.5 mg/kg daily for 14 days, and 2 patients received gentamicin at 10 mg/kg daily for 24 days.Primary outcomes were change in expression of laminin 332 in patients' skin and assessments for safety (ototoxic effects, nephrotoxic effects, and autoimmune response). Secondary outcomes included wound healing in monitored wounds and Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI) score.After gentamicin treatment, all 5 patients (age range, 3 months to 10 years, 4 [80%] female) exhibited increased laminin 332 in the dermal-epidermal junction. By 1 month, 7 of 9 wounds in patients receiving low-dose intravenous gentamicin and all wounds in patients receiving high-dose intravenous gentamicin exhibited at least 50% wound closure. By 3 months, 8 of 9 wounds in patients receiving low-dose gentamicin and all wounds in patients receiving high-dose intravenous gentamicin exhibited greater than 85% closure. All 3 patients who were evaluated with EBDASI showed a decrease in total activity scores that met minimal clinically important differences 1 month after treatment. All 5 patients completed the study, and no ototoxic effects, nephrotoxic effects, or anti-laminin 332 antibodies were detected.In this nonrandomized clinical trial, intravenous gentamicin therapy was associated with induced readthrough of nonsense variants in patients with JEB, restored functional laminin 332 in their skin, and wound closure during the 3-month study period. Although long-term safety and efficacy requires further evaluation, a single cycle of intravenous gentamicin may be a safe and readily available therapy in the short term for this population of patients with JEB.ClinicalTrials.gov Identifiers: NCT03526159 and NCT04140786.

Atopic dermatitis (AD) is a multifactorial inflammatory skin disease and an altered skin microbiota with an increase of Staphylococcus aureus has been reported. However, the role of fungi remains poorly investigated.We aimed to improve the understanding of the fungal skin microbiota, the mycobiota, in AD in relation to the bacterial colonization.Skin swabs of 16 AD patients and 16 healthy controls (HC) from four different skin sites, that is antecubital crease, dorsal neck, glabella and vertex from multiple time points were analysed by DNA sequencing of the internal transcribed spacer region 1 (ITS1) and 16S rRNA gene for fungi and bacteria, respectively.Malassezia spp. were the predominant fungi in all subjects but with a decreased dominance in severe AD patients in favour of non-Malassezia fungi, for example Candida spp. For bacteria, a decrease of Cutibacterium spp. in AD patients in favour of Staphylococcus spp., particularly S. aureus, was observed. Further, both bacterial and fungal community compositions of severe AD patients significantly differed from mild-to-moderate AD patients and HC with the latter two having overall similar microbiota showing some distinctions in bacterial communities.We conclude that severe AD is associated with a pronounced dysbiosis of the microbiota with increased fungal diversity. Potentially infectious agents, for example Staphylococcus and Candida, were increased in severe AD.

Introduction: In image interpretation education, many educators have shifted away from traditional methods that involve passive instruction and fragmented learning to interactive ones that promote active engagement and integrated knowledge. By training pattern recognition skills in an effective manner, these interactive approaches provide a promising direction for dermoscopy education. Objectives: A narrative review of the literature was performed to probe emerging directions in medical image interpretation education that may support dermoscopy education. This article represents the second of a two-part review series. Methods: To promote innovation in dermoscopy education, the International Skin Imaging Collaboration (ISIC) assembled an Education Working Group that comprises international dermoscopy experts and educational scientists. Based on a preliminary literature review and their experiences as educators, the group developed and refined a list of innovative approaches through multiple rounds of discussion and feedback. For each approach, literature searches were performed for relevant articles. Results: Through a consensus-based approach, the group identified a number of theory-based approaches, as discussed in the first part of this series. The group also acknowledged the role of motivation, metacognition, and early failures in optimizing the learning process. Other promising teaching tools included gamification, social media, and perceptual and adaptive learning modules (PALMs). Conclusions: Over the years, many dermoscopy educators may have intuitively adopted these instructional strategies in response to learner feedback, personal observations, and changes in the learning environment. For dermoscopy training, PALMs may be especially valuable in that they provide immediate feedback and adapt the training schedule to the individual’s performance.

BACKGROUND AND OBJECTIVES Molluscum contagiosum (MC) is a common viral infection. Hypersensitivity reactions reminiscent of Gianotti-Crosti syndrome, termed Gianotti-Crosti syndrome-like reaction (GCLR), have been reported in a subset of patients. We report a series of patients with GCLR, better delineating its clinical presentation and course. PATIENTS AND METHODS Retrospective chart review of all children presenting with GCLR at our Pediatric Skin Center between 2015 and 2020. RESULTS 26 children (14 boys) with a median age of 6.5 (3-11.3) years were included. GCLR involved the extensor surfaces of the extremities in all patients. More widespread eruptions also affected the trunk and face in 7 (27��%) and 6 (23��%) children respectively. Involvement of the skin overlying the Achilles tendons was a new finding in 4 (15��%) children. Itch was the predominant symptom in 20 (77��%) patients. The rash responded to topical and/or systemic corticosteroids and resolved within four weeks. GCLR was followed by clearance of MC in all patients within 9 (4-24) weeks. CONCLUSIONS GCLR is a characteristic acute, wide-spread, pruritic papular eruption, which often leads to emergency consultations and anxiety in affected patients. GCLR responds well to corticosteroid treatment, has a benign course, and heralds the healing of MC.

The "epithelial barrier hypothesis" proposes that the exposure to various epithelial barrier damaging agents linked to industrialization and urbanization underlies the increase in allergic diseases. The epithelial barrier constitutes the first line of physical, chemical and immunological defense against environmental factors. Recent reports have shown that industrial products disrupt the epithelial barriers. Innate and adaptive immune responses play an important role in the epithelial barrier damage. In addition, recent studies suggest that epithelial barrier dysfunction plays an essential role in the pathogenesis of the atopic march by allergen sensitization through the transcutaneous route. It is evident that external factors interact with the immune system triggering a cascade of complex reactions that damage the epithelial barrier. Epigenetic and microbiome changes modulate the integrity of the epithelial barrier. Robust and simple measurements of the skin barrier dysfunction at the point-of-care are of significant value as a biomarker, as recently reported using electrical impedance spectroscopy to directly measure barrier defects. Understanding epithelial barrier dysfunction and its mechanism is key to developing novel strategies for the prevention and treatment of allergic diseases. The aim of this review is to summarize recent studies on the pathophysiological mechanisms triggered by environmental factors that contribute to the dysregulation of the epithelial barrier function. This article is protected by copyright. All rights reserved.

Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer worldwide. Cancer-associated stroma (CAS) is central to tumor development and strongly influences therapy response. Perineural infiltration (PNI) represents a major risk factor for cSCC and likely influences CAS reprogramming. However, stromal reprogramming in cSCC remains poorly characterized, and it is unknown whether and how PNI influences CAS. To address these questions, we analyzed CAS and matched normal stroma from 20 cSCC cases (11 without PNI and 9 with PNI) by laser-capture microdissection using RNA sequencing. Our analysis reveals extensive stromal reprogramming strongly driven by changes in immune cells, as validated using immunohistochemistry. Furthermore, CAS of cSCC displays markers of immune exhaustion, and multiplex spatial analysis suggests that PD-L1 expression on NK T cells contributes to T-cell exhaustion and immunosuppression. Finally, PNI is characterized by increased IL-17A. In PNI-negative cases, IL-17A derives predominantly from CD3+ cells. However, with PNI, we observe an increased contribution of fibroblasts to high IL-17A, which coincides with a significant increase in FAP+ cells. Our analysis elucidates the molecular landscape of CAS in cSCC and identifies the presence of immunosuppressive mechanisms, supporting further research into immunotherapy and anti‒IL-17A in cSCC, especially for cases with PNI.

Over-the-counter antiaging formulations aim to prevent or minimize the signs of aging skin, and to maintain the benefits obtained from different cosmetic procedures. Even though a huge selection of such products is available on the market, evidence and good clinical practice of the data supporting their use are oftentimes lacking. In this systematic review, the authors reviewed scientific data available in the published literature on the most common ingredients used in antiaging cosmetics, with a particular focus on in vivo studies.

We recently described mucocutaneous findings in pediatric patients with community-acquired pneumonia caused by Mycoplasma pneumoniae,1 of whom 3 (6.8%) were diagnosed with M pneumoniae–induced rash and mucositis (MIRM).2 ,3 We wish to describe another MIRM patient, who recently presented with a unique clinical picture following the resolution of MIRM, which is, to our knowledge, the first case of M pneumoniae–associated flagellate erythema.

Negative pressure wound treatment (NPWT) is very useful for the treatment of chronic or deep wounds and in the setting of skin grafting. Due to the need for adhesive dressings, this treatment is rarely attempted in patients with skin fragility secondary to hereditary epidermolysis bullosa (EB). We present a neonate with EB simplex, severe generalized in a critical clinical state where NPWT was successfully applied and describe the measures taken to avoid any further skin damage. This case is of clinical importance to physicians and health care staff treating patients with this rare disease where additional therapeutic measures for the treatment of chronic wounds are scarce.

Purpose of Review Treatment of equine insect bite hypersensitivity (IBH) needs to be improved. Allergen-specific immunotherapy (ASIT), the only curative treatment of allergy, currently has only a limited efficacy for treatment of IBH. This review highlights the latest findings in prophylactic and therapeutic strategies. Recent Findings Prophylactic vaccination against IBH using recombinant Culicoides allergen has been developed in unexposed Icelandic horses and is ready to be tested. Therapeutic virus-like particle (VLP)–based vaccines targeting equine interleukin- (IL-) 5 or IL-31 improved clinical signs of IBH by induction of anti-cytokine antibodies thus reducing eosinophil counts or allergic pruritus, respectively. Summary First studies for development of ASIT using pure r-Culicoides allergens have yielded promising results and need now to be tested in clinical studies for both prevention and treatment of IBH. Therapeutic vaccines inducing neutralizing antibodies against IL-5 or IL-31 will be valuable future treatments for reduction of clinical signs of IBH.

Purpose of Review: This review aims to evaluate new insights into allergen immunotherapy (AIT) and review the mechanism, different protocols used, and response rate of this treatment option for canine atopic dermatitis. Recent Findings AIT is the only etiological treatment available for canine atopic dermatitis. Selection of allergens is based on clinical history in conjunction with positive reactions on intradermal and serum testing. During decades AIT was applied subcutaneously (SCIT) using aqueous or aluminum-precipitated solution of allergens, but in the last few years, new routes like sublingual (SLIT), intralymphatic (ILIT), and epicutaneous administration are on the rise. AIT combines a satisfactory success rate (around 70%) with a good safety profile. Adverse effects include mainly increased pruritus and anaphylactic reactions are rarely seen in animals. Pilot studies with different adjuvants to further increase safety and efficacy have been published. Summary: AIT is a safe and effective therapy for canine atopic dermatitis. However, as most of the published studies are case series with often rather small numbers of animals included, more and larger randomized studies of immunotherapy are needed in a clinical setting to provide guidance on the optimal selection of allergens, adjuvants, dosing, success rate, and adverse effects of the various protocols of immunotherapy in dogs.

In recent years, our knowledge of congenital melanocytic nevi (CMN) has greatly expanded. This has led to a paradigm shift. The present article represents a commentary by an interdisciplinary group of physicians from German-speaking countries with extensive experience in long-term care and surgical treatment of children and adults with CMN (CMN surgery network, "Netzwerk Nävuschirurgie", NNC). The authors address aspects such as the indication for treatment as well as treatment planning and implementation under these new premises. Adequate counseling of parents on conservative and/or surgical management requires an interdisciplinary exchange among physicians and individualized planning of the intervention, which frequently involves a multi-stage procedure. Today, the long-term aesthetic outcome is at the center of any therapeutic endeavor, whereas melanoma prevention plays only a minor role. The premise of "removal at any cost" no longer holds. Potential treatment-related adverse effects (hospitalization, wound healing disorders, and others) must be carefully weighed against the prospects of a beneficial outcome. In this context, the use of dermabrasion in particular must be critically evaluated. At a meeting of the NNC in September 2018, its members agreed on a consensus-based position on dermabrasion, stating that the procedure frequently leads to impaired wound healing and cosmetically unfavorable or hypertrophic scarring. Moreover, dermabrasion is considered to be commonly associated with considerable repigmentation that usually occurs a number of years after the procedure. In addition, the NNC members saw no benefit in terms of melanoma prevention. In the future, physicians should therefore thoroughly caution about the potential risks and often limited cosmetic benefits of dermabrasion.

Background: The ancient drug dapsone has antimicrobial and anti-inflammatory features. In dermatology, dapsone is primarily used for neutrophil-dominant skin diseases. However, real-life data assessing the long-term efficacy of dapsone across multiple dermatological diseases is missing. ­Objectives: To determine the efficacy and safety of dapsone in patients with inflammatory skin diseases treated at the Department of Dermatology of the University Hospital Zurich. Methods: The hospital database was searched for patients treated with dapsone in the last 20 years (from January 1, 1998, to December 31, 2017). Overall, 175 patients were included in our study. Results: Thirty-four patients received dapsone for eosinophilic dermatoses, 82 for neutrophilic dermatoses and 59 for other dermatoses. After 3 months, 8% of all patients reached complete remission, 40.6% showed improvement, 30.3% had stable disease, and only 9.1% had disease progression. Final treatment evaluation revealed complete response in 13.2%, disease improvement in 47.4%, stable disease in 25.7% and disease progression in only 12.0%. Patients who showed remission or improvement after 3 months were significantly older than patients with stable or progressive disease. In addition, remission after 3 months was associated with a significantly lower dose of dapsone compared to improvement only. Hemolysis was the most common adverse event (21.7%). Conclusions: Our data show that dapsone is a valid treatment option in various dermatological diseases, leading to a favorable response in the vast majority of patients. In addition, it is well tolerated, safe and inexpensive. Randomized, controlled trials are needed to further elucidate the role of this high-potential drug.

BACKGROUND Children with congenital melanocytic nevi (CMN) were historically managed with surgical removal to lower the risk of malignant transformation. The evolving literature over the last decade has indicated a significantly lower risk than previously estimated. Indications for excision currently revolve around aesthetic and psychosocial concerns. This study describes and evaluates the perspectives and expectations of patients and families referred to a pediatric plastic surgery clinic on CMN management. METHOD A two-part questionnaire was administered before and after an initial clinic appointment to evaluate patient and family concerns of lesion growth, risk of malignancy, treatment expectations, and stigmatization. RESULTS Thirty questionnaires were completed for 11 male and 19 female patients, mean age 9.2 years (1-25). Referring doctors (majority dermatologists) were rarely concerned about malignancy (8%), but parents listed it as a top reason for wanting the CMN removed (37%) and the most common expectation for the visit followed by information about surgical options and outcome. Before the clinic, 93% were at least "slightly" worried about CMN growth and 96% about malignancy, whereas 63% and 72%, respectively, after the clinic. CONCLUSIONS Families want information about surgical excision and are concerned about malignancy, indicating lingering misinformation or misconception about melanoma risk. For the majority, CMN removal remains at least slightly important, presumably for aesthetic reasons and remaining concern about malignancy. Involved health care professionals should assure reliable and coherent patient information about MM risk, indications for surgery and expected outcome to best support families' decision-making.

BACKGROUND Conventional laboratory diagnosis of dermatophyte infection is cumbersome and time-consuming. OBJECTIVES We aimed to establish a simple, robust and rapid molecular diagnostic assay for the detection of dermatophytes and optionally nondermatophytes in clinical specimens. MATERIALS AND METHODS We developed a two-tube pan-dermatophyte polymerase chain reaction (PCR) assay using six sloppy molecular beacon (SMB) probes. The first PCR uses dermatophyte-specific primers and enables detection and identification of most dermatophyte species. The second PCR with pan-fungal primers allows further differentiation of Trichophyton interdigitale and T. mentagrophytes/T. quinckeanum, T. violaceum and T. soudanense, and T. tonsurans and T. equinum, and detection of nondermatophytes. The test was evaluated with 306 clinical specimens by comparing it with the results of microscopy and culture. RESULTS In melting-curve analyses, species-specific melting temperature signatures of the SMBs were defined, and thus, our new PCR enabled detection and species-level identification of at least 19 dermatophyte species. Sensitivity and specificity of PCR for detection of dermatophytes in clinical samples were estimated to be 96·9% and 90·4%, for culture 46·7% and 98·7%, and for microscopy 91·4% and 84·0%, respectively. The detection of nondermatophytes by PCR and culture did not correlate. CONCLUSIONS The new assay showed excellent performance characteristics for the detection of dermatophytes and is significantly faster than culturing techniques, which makes it very promising for routine diagnostics of dermatophytosis. We noted that the detection of nondermatophytes in our assay currently has no benefit.

Terra firma-forme dermatosis (TFFD) is a little-known disease of unknown etiology that clinically presents with asymptomatic brown to black plaques and resembles dirty skin. Here, we report the case of a 38-year-old woman with skin changes on her areolae that were mistakenly diagnosed as “dermatitis neglecta” by several physicians. Cleansing with water and soap had no impact on the skin appearance. But a swab of 70% isopropyl alcohol removed the plaques immediately, which confirmed the diagnosis of TFFD. Only a few cases of TFFD have been published, and this skin condition is not mentioned in many textbooks. Given the unfamiliarity of this disease, TFFD is speculated to be immensely underdiagnosed, even though a simple diagnostic sign exists.

Acute generalized exanthematous pustulosis (AGEP) is a severe adverse cutaneous drug reaction. Although an involvement of drug-specific T cells has been reported, the physiopathology of AGEP and mechanism of neutrophilic skin inflammation remains incompletely understood. Recently, mutations in IL-36RN, the gene encoding the IL-36 receptor antagonist, have been reported to be more frequent in AGEP patients and pustular psoriasis. Here, we show that IL-36 cytokines, in particular IL-36γ, is highly expressed in lesional skin of AGEP patients, keratinocytes and macrophages being a major source of IL-36γ. Such an IL-36γ overexpression could not be observed in patients with drug-induced maculo-papular rash (MPR). In vitro, the causative drug specifically induced IL-36γ release either directly by peripheral blood monocytes from AGEP patients, or indirectly by keratinocytes in presence of autologous peripheral blood mononuclear cells. Such culprit drug induction of IL-36γ secretion in vitro was specific for AGEP and involved the sensing of drug/albumin complex as danger signal by Toll-like receptor 4. Our results suggest that IL-36γ secretion by monocytes/macrophages and keratinocytes in response to culprit drug exposure likely plays a key role in the pathogenesis of AGEP.

Background: A 6-week personalized integrative multidisciplinary treatment programme (PIM) was developed for children with difficult to treat AD who appeared unresponsive to treatment according to current guidelines. Objective: The aim of the present study was to identify clinical and psychosocial characteristics that predict long-term treatment success after PIM. Methods: Treatment was considered successful when there was a 75% reduction on the Self-Administered Eczema Area and Severity Index and/or little impact of AD on daily life, measured with the Children's Dermatology Life Quality Index (score ≤ 6), 6 months after the end of PIM. PIM is a personalized, integrative, multidisciplinary treatment programme with clearly defined goals and strategies, addressing atopic, paediatric, mental health comorbidities and general well-being, for children and adolescents aged 8- to 18 years. Multivariate logistic regression models were constructed using a backward selection procedure. Questionnaires were used to assess psychosocial characteristics; clinical data was extracted from medical records. Results: In total, 79 children/adolescents with difficult to treat AD completed PIM and long-term treatment results were available for 74 children/adolescents. The majority (77%) of children/adolescents demonstrated long-term treatment success with PIM. Predictors of long-term treatment success (adjusted ORs) included maternal disease acceptance OR (95% CI) 1.84 (1.15–2.94). A group (23%) of mostly females OR (95% CI) 0.10 (0.02–0.54) with multiple somatic complaints OR (95% CI) 0.88(0.80–0.97), from families where the mother has anxiety for the use of topical corticosteroids OR (95% CI) 0.62(0.40–0.94), is less likely to obtain long-term treatment success. Conclusion: Most children and adolescents with difficult to treat AD, seemingly unresponsive to conventional treatment according to current guidelines, are able to improve with PIM. Psychosocial and family but not clinical variables, predicted long-term treatment success after participating in PIM.

Summary Background Adalimumab (ADA) (Humira®, AbbVie Inc., U.S.A.) is approved by the European Medicines Agency for children aged ≥ 4 years with severe plaque psoriasis. Objectives To evaluate the long‐term efficacy and safety of ADA in children with severe plaque psoriasis. Methods Results are presented from the 52‐week long‐term extension (LTE) of the randomized, double‐blind, double‐dummy, phase III trial, in children with severe plaque psoriasis (results from prior periods have been published). Patients aged ≥ 4 and < 18 years were randomized 1 : 1 : 1 to ADA 0·8 mg kg−1 (40 mg maximum) or 0·4 mg kg−1 (20 mg maximum) every other week or to methotrexate (MTX) 0·1–0·4 mg kg−1 (25 mg maximum) weekly. The 16‐week initial treatment (IT) period was followed by a 36‐week withdrawal period and a 16‐week retreatment period. Patients could enter the LTE at prespecified time points to receive ADA 0·8 mg kg−1 (blinded or open label) or ADA 0·4 mg kg−1 (blinded), or to remain off treatment. Efficacy is reported for patient groups according to doses received in the IT and LTE periods. Results Of the 114 patients randomized in the IT period, 108 entered the LTE (n = 36 in each group); 93 received ADA 0·8 mg kg−1. Efficacy (≥ 75% improvement from baseline in Psoriasis Area and Severity Index) was maintained or improved from entry to the end of the LTE: MTX(IT)/ADA 0·8(LTE) 31–86% of patients; ADA 0·4(IT)/0·4 or 0·8(LTE) 28–47%; ADA 0·8(IT)/0·8(LTE) 50–72%. No serious infections occurred in the LTE. Conclusions After 52 weeks of long‐term ADA treatment in children aged 4–18 years with severe plaque psoriasis, disease severity was reduced and maintained or further improved, as demonstrated by efficacy outcomes. No new safety risks were identified. What's already known about this topic? The results from the first three periods of this phase III trial in children aged 4–18 years with severe plaque psoriasis suggest that adalimumab is a safe and efficacious treatment option in this population. What does this study add? This is the first study to evaluate long‐term treatment of adalimumab in children with severe psoriasis, and the first to evaluate switching from methotrexate to adalimumab in this population., Linked Comment: https://doi.org/10.1111/bjd.18362. https://www.bjdonline.com/article/sustained-long-term-efficacy-and-safety-of-adalimumab-in-paediatric-patients-with-severe-chronic-plaque-psoriasis-from-a-randomized-double-blind-phase-iii-study/

A 57-year-old woman with angioimmunoblastic lymphoma received allogenic hematopoietic stem cell transplantation (aHCT) after complete remission under 4th -line chemotherapy. One month after aHCT, PET-scan showed progress of the lymphoma. Therefore, immunosuppressants (including mycophenolate mofetil and cyclosporine A) were reduced to enhance "graft versus tumor reaction". An anti-infective prophylaxis with cotrimoxazol (trimethoprim-sulfamethoxazole) was established.

Lichen aureus is a variant of pigmented purpuric dermatoses. The usual histopathology of lichen aureus is characterized by a subepidermal dense, band-like lymphocytic infiltrate, extravasated erythrocytes, and hemosiderin deposits. We report three patients with lichen aureus on the extremities with similar clinical, dermoscopic, and histopathological findings characterized by a dense band-like relatively deep dermal infiltrate accompanied by extravasation of erythrocytes and hemosiderin deposits occasioning a resemblance to a lymphoproliferative disorder.

RC is a consultant for Kyowa Kirin and served on an advisory board for Helsinn. JJS is a consultant for Kyowa Kirin, Takeda, Recordat, 4SC, Innate Pharma and Helsinn. She received a 1-year educational grant from Kyowa Kirin for work on quality of life in CTCL. She also has membership on an entity’s Board of Directors or advisory committees for Kyowa Kirin, Takeda, 4SC, Innate Pharma, Miragen and Helsinn. PLZ has received honoraria from MSD, Celltrion, Gilead, Janssen-Cilag, BMS and TG Therapeutics. He is also a consultant for MSD, EUSA Pharma, Sanofi and Verastem. He also has membership on an entity’s Board of Directors or advisory committees for MSD, Eusa Pharma, Celltrion, Gilead, Janssen-Cilag, BMS, Servier, Sandoz, Immune Design, Celgene, Portola, Roche, Kyowa Kirin, TG Therapeutics, and Verastem. He has also been on a Speakers Bureau for MSD, EUSA Pharma, Celltrion, Gilead, Janssen-Cilag, BMS, Servier, Immune Design, Celgene, Portola, Roche, Kyowa Kirin and Verastem. JPN has received honoraria from Pharmaceutical Industries, TEVA, Novartis AG, Biogen GmbH, Almirall Hermal AG, Actelion Pharmaceuticals, UCB Pharma, LaRoche Posay, Takeda Pharmaceuticals and Kyowa Kirin. He is also a consultant for Novartis AG, Biogen GmbH, Almirall Hermal AG, Actelion Pharmaceuticals, Innate Pharma, Kyowa Kirin and Takeda Pharmaceuticals. He has also received grants and personal fees from Pharmaceutical Industries outside of the submitted work. LS is a consultant for Dren Bio and served on an advisory board for Kyowa Kirin, Kymera Therapeutics and EUSA Pharma. LP-B has been an advisory board for Epizyme, Morphosys, Helsinn, Verastem and Actelion. She is also a consultant for Acrotech. PQ has received honoraria from Actelion, Innate Pharma, Takeda, Kyowa Kirin, Helsinn and Therakos. He also been on an advisory board for Actelion, Innate Pharma, Takeda, Kyowa Kirin, Helsinn and Therakos. LI has served as a consultant and/or paid speaker for and/or participated in clinical trials sponsored by AbbVie, Almirall, Amgen, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Centocor, Eli Lilly, Janssen-Cilag, Kyowa Kirin, LEO Pharma, MSD, Novartis, Pfizer, Sun Pharma and UCB. RD is a consultant for Merck Sharp & Dohme, Novartis, Bristol-Myers Squibb, Roche, Amgen, Takeda, Pierre Fabre, Sun Pharma, Sanofi, Catalym and Second Genome. AM is an investigator for Menlo, Soligenix, Pfizer, Elorac and miRagen. She has also received honoraria from Kyowa Kirin. She also has a membership on an entity’s Board of Directors or advisory committees for Helsinn. FF has received honoraria from Seagen, Mallinckrodt and Kyowa Kirin. She is also a consultant for Miragen. She had also served on a Data Safety Monitoring Board for Celgene. She was also the President of the US Cutaneous Lymphoma Consortium. TI is an employee of Kyowa Kirin, Inc. J-PR is an employee of Kyowa Kirin, Inc. MCM is an employee of Kyowa Kirin, Inc.

Background: Dermatophytosis is one of the most common infections affecting 3%-17% of the population. Resistance to antifungals so far was not of concern in the therapeutic management. However, recent reports of terbinafine-resistant strains in several countries are worrisome making antifungal susceptibility testing inevitable. Objectives: We aimed to develop and evaluate an optimised broth microdilution assay for antifungal drug susceptibility testing of dermatophytes. Methods: We first studied the effect of different inocula, incubation temperatures and incubation times to establish an optimised assay. Subsequently, we tested 79 clinical strains of 11 dermatophyte species with 13 antifungals. Results: We found inoculating with 0.5-5 × 104 colony forming units (CFU) and incubating at 29°C ± 1°C for 4 days to be appropriate. Terbinafine was the most active antifungal agent with minimum inhibitory concentration (MIC) values ≤ 0.06 µg/mL, expect for one resistant T mentagrophytes strain, which was isolated from an Indian patient. Also, a majority of MICs of other antifungals that are commonly used to treat dermatophytosis were low, except those of fluconazole. Fluconazole MICs do not correlate with the good efficacy in the clinical management. Conclusions: Our assay enables fast and reliable susceptibility testing of dermatophytes with a large panel of different antifungals. This helps to improve the therapeutic management of dermatophytosis by detecting resistant strains. Keywords: antifungal susceptibility testing; broth microdilution; dermatophytes; dermatophytosis; susceptibility tests; terbinafine resistance.

Autoinflammatory syndromes are a steadily growing group of inflammatory diseases caused by abnormal regulations of the innate immune system. The clinical presentation is multifaceted, but recurrent fever, skin involvement, joint inflammation and other systemic symptoms of inflammation are characteristic. In contrast to classic autoimmune diseases, autoantibodies or specific T cells are not involved in the pathogenesis. In fact, innate immunity plays the most important role in autoinflammation. While activation of the innate immune system is usually self-limiting in healthy individuals, mutations and dysregulation can lead to chronic and excessive activation of innate immune responses and to the development of autoinflammatory diseases.

Primary cutaneous CD8+ aggressive epidermotropic T-cell lymphoma (CD8+ AECTCL) is a very rare subtype of cutaneous T-cell lymphoma. The frequency is less than 1% of all primary cutaneous lymphomas and prognosis is poor with a 5-year disease specific survival rate of 31% (1). Due to the rarity of this entity, there are no evidence-based treatment options. We report the case of a 70-year old female patient who presented with a red plaque with central ulceration on the left shin rapidly developing in two weeks.

BACKGROUND Studies suggest that patch testing with formaldehyde releasers (FRs) gives significant additional information to formaldehyde 1% aq. and should be considered for addition to the European baseline series (EBS). It is not known if this is also true for formaldehyde 2% aq. OBJECTIVES To determine the frequency of sensitization to formaldehyde 2% aq. and co-reactivity with FRs. To establish whether there is justification for including FRs in the EBS. MATERIALS AND METHODS A 4-year, multi-center retrospective analysis of patients with positive patch test reactions to formaldehyde 2% aq. and five FRs. RESULTS A maximum of 15 067 patients were tested to formaldehyde 2% aq. and at least one FR. The percentage of isolated reactions to FR, without co-reactivity to, formaldehyde 2% aq. for each FR were: 46.8% for quarternium-15 1% pet.; 67.4% imidazolidinyl urea 2% pet.; 64% diazolidinyl urea 2% pet.; 83.3% 1,3-dimethylol-5, 5-dimethyl hydantoin (DMDM) hydantoin 2% pet. and 96.3% 2-bromo-2-nitropropane-1,3-diol 0.5% pet. This demonstrates that co-reactivity varies between FRs and formaldehyde, from being virtually non-existent in 2-bromo-2-nitropropane-1,3-diol 0.5% pet. (Cohen's kappa: 0, 95% confidence interval [CI] -0.02 to 0.02)], to only weak concordance for quaternium-15 [Cohen's kappa: 0.22, 95%CI 0.16 to 0.28)], where Cohen's kappa value of 1 would indicate full concordance. CONCLUSIONS Formaldehyde 2% aq. is an inadequate screen for contact allergy to the formaldehyde releasers, which should be considered for inclusion in any series dependant on the frequency of reactions to and relevance of each individual allergen.

Background: Dermatophytosis is a world-wide distributed common infection. Antifungal drug resistance in dermatophytosis used to be rare, but unfortunately the current Indian epidemic of atypical widespread recalcitrant and terbinafine-resistant dermatophytosis is spreading and has sporadically been reported in Europe. Objectives: To explore the occurrence of clinical and mycological proven antifungal drug resistance in dermatophytes in Europe. Methods: A standardized questionnaire was distributed through the EADV Task Force of Mycology network to dermatologists in Europe. Results: Representatives from 20 countries completed the questionnaires of which 17 (85 %) had observed clinical and/or mycological confirmed antifungal resistance, two countries published cases of antifungal resistance and one country had no known cases. Conclusions: This pilot study confirms that both clinical and mycological antifungal resistance exist in Europe.

This guideline is an update from August 2020 the S2k-guideline "Atopic dermatitis" published in 2015. The reason for updating this chapter of the guideline were the current developments in the field of systemic therapy of atopic dermatitis. The agreed recommendations for systemic treatment in atopic dermatitis of the present guideline are based on current scientific data. Due to the approval of dupilumab for the treatment of moderate to severe atopic dermatitis, which cannot be treated sufficiently with topical drugs alone, this part of the guideline has now been adapted and newly consented. The indication for systemic therapy and the therapeutic response to topical and systemic treatment should be recorded and documented in a suitable form in clinic and practice. A standardized documentation of the indication for system therapy in atopic dermatitis can be recommended and is also part of the updated chapter of this guideline.