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Florian Anzengruber,1,2 Adhideb Ghosh,1–3 Julia-Tatjana Maul,1,2 Mathias Drach,1,2 Alexander A Navarini1–3 1Department of Dermatology, University Hospital Zurich, Zurich, Switzerland; 2Faculty of Medicine, University of Zurich, Zurich, Switzerland; 3Competence Center Personalized Medicine University of Zurich/Swiss Federal Institute of Technology (ETH) Zurich, Switzerland Purpose: Several studies have suggested that an HLA-Cw6+ allele can predict an improved outcome of treatment in psoriasis patients. The aim of the study was to assess whether the published association between HLA-Cw6 allele carriers and response to ustekinumab has the potential to impact treatment decisions. Patients and methods: Differences in Psoriasis Activity and Severity Index 50, 75, and 90; Nail Psoriasis Severity Index; and Dermatology Life Quality Index at 16 weeks were evaluated between HLA-Cw6 allele carriers vs. non-carriers. Thirty patients with moderate-to-severe psoriasis under treatment with ustekinumab were included in our study. Results: There was no difference between the two groups with respect to Psoriasis Activity and Severity Index 50, 75, and 90 or in terms of change in Nail Psoriasis Severity Index or Dermatology Life Quality Index. Conclusion: In our retrospectively analyzed cohort, we could not detect the previously reported better response in HLA-Cw6+ vs. HLA-Cw6− patients. Keywords: human leukocyte antigen, Cw6, genetic variations, HLA-Cw6, ustekinumab

The striking rise in the Internet utilization worldwide has led to major changes in the methods of data collection and processing. Online surveying has been used to assess different health services, explore patients' perceptions and measure interventions. The discipline of dermatology is one of the fields that gained benefits from surveying patients and dermatologists online; however, some disadvantages such as the low response rate and participation bias were suggested. This review summarizes the applications of online surveying in dermatology and discusses the methods of enhancing response to online surveys. It also offers a guide for dermatologists to formulate their online surveys and avoid the possibility of bias. The role of social network in data collection and the concerns about anonymity and data security have been discussed. [ABSTRACT FROM AUTHOR]

Background Narrowband ( TL-01) UVB phototherapy ( UVB nb) is effective in treating inflammatory skin disease. The addition of UVA is traditionally advocated to reduce pruritus, but lacks evidence for this recommendation. Objectives The aim of this study was to assess the effect of UVB nb and UVA phototherapy in combination compared against UVB nb monotherapy on pruritus, disease activity and quality of life. Methods In this double-blind randomized clinical trial, 53 patients suffering from inflammatory skin diseases with pronounced itching (Visual Analogue Scale ( VAS) for pruritus ≥5) were randomized into two treatment groups. One group received UVB nb (311 nm) phototherapy alone and another group received a combination of UVB nb and UVA (320-400 nm) phototherapy. UV therapy was performed three times per week over 16 weeks. Pruritus ( VAS and 5-D itch score), disease activity and quality of life (Dermatology Life Quality Index, DLQI) were assessed at baseline and weeks 4, 8, 12 and 16. Results In both treatment groups, there was a reduction in pruritus scores, disease activity and DLQI. No difference in pruritus score, disease activity and quality of life could be detected between the group receiving UVB nb alone and those receiving UVB nb combined with UVA. Conclusions Phototherapy with UVB nb alone, and UVB nb combined with UVA are equally effective in treating inflammatory skin disease and indifferent in reducing disease-associated pruritus. Given this non-inferiority for UVB nb monotherapy, the recommendation of adding UVA to UVB nb phototherapy for pruritic inflammatory skin disease should be abandoned. [ABSTRACT FROM AUTHOR]

Toxic epidermal necrolysis (TEN) is a fatal drug-induced skin reaction triggered by common medications and is an emerging public health issue 1-3 . Patients with TEN undergo severe and sudden epidermal detachment caused by keratinocyte cell death. Although molecular mechanisms that drive keratinocyte cell death have been proposed, the main drivers remain unknown, and there is no effective therapy for TEN 4-6 . Here, to systematically map molecular changes that are associated with TEN and identify potential druggable targets, we utilized deep visual proteomics, which provides single-cell-based, cell-type-resolution proteomics 7,8 . We analysed formalin-fixed, paraffin-embedded archived skin tissue biopsies of three types of cutaneous drug reactions with varying severity and quantified more than 5,000 proteins in keratinocytes and skin-infiltrating immune cells. This revealed a marked enrichment of type I and type II interferon signatures in the immune cell and keratinocyte compartment of patients with TEN, as well as phosphorylated STAT1 activation. Targeted inhibition with the pan-JAK inhibitor tofacitinib in vitro reduced keratinocyte-directed cytotoxicity. In vivo oral administration of tofacitinib, baricitinib or the JAK1-specific inhibitors abrocitinib or upadacitinib ameliorated clinical and histological disease severity in two distinct mouse models of TEN. Crucially, treatment with JAK inhibitors (JAKi) was safe and associated with rapid cutaneous re-epithelialization and recovery in seven patients with TEN. This study uncovers the JAK/STAT and interferon signalling pathways as key pathogenic drivers of TEN and demonstrates the potential of targeted JAKi as a curative therapy., Competing Interests: Competing interests: A patent for treatment of TEN, SJS–TEN and SJS with JAKi has been filed (US patent: provisional application no. 63/531,677; European patent: provisional application no. 23 190 686.8, with T.M.N., L.E.F. and M.M. as inventors). The patent application belongs to the Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. M.M. is an indirect investor in Evosep Biosystems. The authors declare no other competing interests., (© 2024. The Author(s).)

Background: The risk of developing deep vein thrombosis (DVT) after endovenous ablation of varicose veins varies in the literature. Little is known about the characteristics of this complication and associated factors. This study aimed: 1) to study the occurrence of DVT after ultrasound-guided foam sclerotherapy (UGFS) alone or combined with endovenous laser ablation (EVLA) for lower-limb varicose veins; 2) to identify factors associated with DVT. Patients and methods: The study included all outpatients aged 18 years or older who underwent UGFS and EVLA or UGFS alone at the University Hospital of Zurich between 2011 and 2015. Data were extracted from the hospital electronic medical record. Patients were surveyed about their level of pain after the procedure and their level of satisfaction with the procedure. Duplex ultrasound was used to assess the deep venous system 7-10 days and 6-8 months after the procedure. Regression analysis was used to examine the association of patient and procedure characteristics with the development of DVT. Results: A total of 334 patients (561 procedures performed in 393 different sessions) were included: 73% of the patients underwent combined UGFS and EVLA and 27% underwent UGFS alone. DVT occurred in 24 (7.2%) patients, of whom 88% underwent combined procedures and 17% underwent interventions involving both the great and small saphenous veins on the same session. DVT occurred in 8.2% of patients receiving thromboprophylaxis and in 9.5% of patients not receiving thromboprophylaxis. DVT occurred in 5.2% of women and 11.9% of men. No factors associated with a diagnosis of DVT after intervention were identified. Pain and satisfaction levels did not differ between patients with and without DVT. Conclusions: This study adds to the knowledge of the risk of DVT following UGFS alone or combined with EVLA. Further studies are needed to revise thromboprophylaxis.

Introduction: Erythema nodosum (EN) is the most common form of panniculitis that predominantly affects the shins. While EN in atypical sites has been described by many authors, there are currently only case studies published on this topic. This study aimed to evaluate clinical differences between patients suffering from EN on the shins, compared to patients with EN in atypical locations., Methods: We analyzed 105 patients in a retrospective, single-center study at a university hospital in Switzerland. Typical EN was defined as lesions, found only on the lower legs, while atypical EN as lesions on the upper legs, trunk, arms, or face, only or in addition to lesions on the lower legs. The patients were assessed for age, gender, dermatologic history, time until first medical consultation, time to diagnosis, and time until remission. Further, etiology, symptoms, and applied therapies were investigated. Findings were then compared between the typical and atypical EN cohorts., Results: Overall, we included 70 patients (37.99 ± 15.67 [3-81] years) with EN solely on the shins and 35 patients (41.27 ± 16.85 [9-76] years) with EN on other locations. Interestingly, time until diagnosis was significantly shorter in atypical EN (p = 0.034, 1.14 ± 4.68 vs. 0.46 ± 1.14 months). Time to remission was similar in both groups (3.61 ± 2.73 vs. 3.05 ± 2.86 months, respectively). Sarcoidosis was the only etiologic factor significantly more frequent in atypical EN compared to typical EN (23% vs. 9%, p = 0.042). Besides that, solely subtle differences were seen regarding etiology, gender, age at onset, course of the disease, and symptoms., Conclusions: Our study suggests that only minor alterations between both study populations exist. Significant differences were found in time to diagnosis (shorter for atypical EN), as well as in sarcoidosis as an etiologic factor (more frequent in atypical EN). While adalimumab was only prescribed in atypical EN cases, prognosis seems to be similar for typical and atypical EN (similar time to remission, similar amount of reoccurring cases). Due to the limited sample size, however, our study population may have been too small to detect the relevant differences, and bigger studies may be needed., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Background: The Venous Clinical Severity Score (VCSS) and the Venous Disability Score (VDS) represent assessment tools for chronic venous disease (CVD) combining physician and patient reported outcomes. To date, German versions are not available. The present study aimed at translating the VCSS and VDS into German and validating the questionnaires., Methods: Translations of VCSS and VDS were compiled based on published guidelines considering potential differences in the use of German language in different countries. For validation, 33 patients with chronic venous disease and 5 healthy individuals were included in the pre-testing phase. Patients were examined twice by independent investigators to validate test-retest-validity culminating in 142 limb examinations. Internal consistency, inter-rater dependence and external reliability were subsequently evaluated., Results: All assessed metrics showed good internal consistency. Intra-class correlation coefficients were .75 for the VDS, .98 for the VCSS of the right leg and .90 for the VCSS of the left leg, indicating inter-rater independence. Furthermore, VCSS scores showed a modest positive correlation with CEAP C class and both VCSS and VDS showed a negative correlation with the physical component of the SF-12, indicating adequate external reliability., Conclusion: A pan-cultural German version of both the VCSS and VDS was established and validated as reliable tools to evaluate the severity of CVD in German speaking countries., (© 2023. The Author(s).)

Hidradenitis suppurativa is a chronic disease that disrupts patients' physical and psychological well-being. A disease-specific measure was developed and validated for assessing health-related quality of life in hidradenitis suppurativa. After qualitative item development, the quality of life in hidradenitis suppurativa instrument was tested in 101 patients, applying convergent measures and a usability questionnaire. Descriptive and validation-specific analyses were conducted. There was no ceiling, but moderate floor effects (scores between 0 and 3.13 on a scale of 0-4). Few missing values were observed (21 of 23 items < 5%). Internal consistency was satisfying: 2 subscales with 6 and 16 items were identified (Cronbach's alpha=0.95 and 0.88). The quality of life in hidradenitis suppurativa instrument correlated significantly with all convergent criteria (including change in convergent patient-reported outcomes; p < 0.05) except for Hurley stage (p = 0.490). In conclusion, the quality of life in hidradenitis suppurativa questionnaire is an internally consistent, valid, responsive, and usable instrument to assess quality of life in patients with hidradenitis suppurativa.

Psoriasis is a chronic inflammatory skin disease characterized by epidermal hyperplasia and hyperkeratosis, immune cell infiltration and vascular remodeling. Despite the emerging recognition of vascular normalization as a potential strategy for managing psoriasis, an in-depth delineation of the remodeled dermal vasculature has been missing. In this study, we exploited 5' single-cell RNA sequencing to investigate the transcriptomic alterations in different subpopulations of blood vascular and lymphatic endothelial cells directly isolated from psoriatic and healthy human skin. Individual subtypes of endothelial cells underwent specific molecular repatterning associated with cell adhesion and extracellular matrix organization. Blood capillaries, in particular, showed upregulation of the melanoma cell adhesion molecule as well as its binding partners and adopted postcapillary venule‒like characteristics during chronic inflammation that are more permissive to leukocyte transmigration. We also identified psoriasis-specific interactions between cis-regulatory enhancers and promoters for each endothelial cell subtype, revealing the dysregulated gene regulatory networks in psoriasis. Together, our results provide more insights into the specific transcriptional responses and epigenetic signatures of endothelial cells lining different vessel compartments in chronic skin inflammation., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL, LT) is an aggressive lymphoma variant. Anthracycline-based chemotherapy with rituximab is recommended as first-line treatment. Radiotherapy (RT) has been considered as a therapeutic option for local disease control in patients with solitary or localized lesions., Methods: We report the results of a retrospective analysis of PCDLBC, LT patients treated either with RT alone or with physician's decision as first-line treatment, aiming to assess disease progression and/or first recurrence in these treatment groups., Results: We retrospectively analyzed 20 patients treated either with RT alone (n = 8) or with investigator's choice treatment (n = 12), which included chemotherapy alone or combined with local therapy (RT and wide local excision). Complete response (CR) was achieved in 8 patients from the first group and 9 patients from the second group, with 1 treatment failure. Six patients treated with RT alone progressed with a median time to progression (TTP) of 12.5 months. In the second group, 5 patients progressed with a median TTP of 5.2 months. RT showed good local disease control in both groups without any skin relapses during the follow-up period., Conclusion: RT as first-line monotherapy followed by watchful waiting did not significantly improve the overall risk of disease progression but resulted in good local disease control. After progression, RT could still easily be combined with systemic treatment. The strength of this analysis needs to be evaluated in a larger patient cohort., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Physicians' and patients' perspectives can vary significantly. For a long time, physicians considered psoriasis a non-pruritic dermatosis until a survey found pruritus to be the most bothersome symptom among psoriasis patients. In our study, we wanted to get an insight into the factors that affect patients and evaluate whether gender differences exist. A link of an anonymous online survey ( www.fightpsoriasis.ch ) with 24 questions was placed on the website of the Swiss Psoriasis and Vitiligo Patient Association ( www.spvg.ch ) from May 2016 until June 2017. 3164 persons participated in this online survey, of which 1979 were diagnosed with psoriasis. Significantly more females than males were affected by psoriatic pruritus [713 (36%) vs. 500 (25.3%), p ≤ 0.001] and 756 (39.7%) of all patients identified pruritus as the most life quality-limiting factor. Fewer women reported high satisfaction with their therapy compared to men [96 (4.9%) vs. 110 (5.6%), p ≤ 0.015]. Pruritus remains the most bothersome symptom and women were more often affected by it, leading to a lower treatment satisfaction among female patients.

Introduction: Colchicine is an ancient, but rarely used drug. Little data exist on its efficacy and safety in patients suffering from skin diseases. The objective of our study was to determine whether colchicine showed favorable efficacy and safety in our patients during the last 20 years. Methods: The hospital database was searched for patients treated with colchicine in the last 20 years (January 1, 1998 to December 31, 2017). Overall, total of 41 patients were included in our study. Results: In 63.4% of all patients, either a complete response or an improvement of disease was observed. Adverse events occurred rarely. Discussion: Colchicine is an effective and safe treatment.

Background: The use of digital health resources is growing quickly as they are easily accessible and permit self-evaluation. Yet, research on consumer health informatics platforms is insufficient. Chatbots, interactive conversational platforms based on artificial intelligence, can facilitate access to specific information. Hidradenitis suppurativa (HS) is burdensome and has a high threshold for consultation., Objectives: We aimed to identify the most important principles for the assembly of medical chatbots through the analysis of usage data., Methods: The HS Chatbot1 is a question-and-answer platform in the style of a chatbot. Usage data were collected over the course of a year. 254 responses were statistically analysed., Results: 239 users were alleged patients. 82.9% were looking for a tentative diagnosis. The users were on average 32.49 (±11.33) years old and predominantly female (70.2%). The average number of clicks per visit on the website was 14.69 (±8.83)., Conclusions: A medical chatbot has to be customised to the specific subject whilst general principles have to be considered. High-quality information has to be available in just a few clicks. People concerned about HS are looking for a diagnosis online and often have not seen a doctor previously. Guidance towards appropriate care should be provided., (© 2021 The Author(s) Published by S. Karger AG, Basel.)

Topical treatment is crucial for the successful management of plaque psoriasis. Topicals are used either as a stand-alone therapy for mild psoriasis or else in combination with UV or systemic treatment for moderate-to-severe disease. For the choice of a suitable topical treatment, the formulation matters and not just the active substances. This expert opinion paper was developed via a non-structured consensus process by Swiss dermatologists in hospitals and private practices to illustrate the current treatment options to general practitioners and dermatologists in Switzerland. Defining treatment goals together with the patient is crucial and increases treatment adherence. Patients' personal preferences and pre-existing experiences should be considered and their satisfaction with treatment and outcome regularly assessed. During the induction phase of "classical" mild-to-moderate psoriasis, the fixed combination of topical calcipotriol (Cal) 50 μg/g and betamethasone dipropionate (BD) 0.5 mg/g once daily is frequently used for 4-8 weeks. During the maintenance phase, a twice weekly (proactive) management has proved to reduce the risk of relapse. Of the fixed combinations, Cal/BD aerosol foam is the most effective formulation. However, the individual choice of formulation should be based on a patient's preference and the location of the psoriatic plaques. Tailored recommendations are given for the topical management of specific areas (scalp, facial, intertriginous/genital, or palmoplantar lesions), certain symptoms (hyperkeratotic or hyperinflammatory forms) as well as during pregnancy or a period of breastfeeding. As concomitant basic therapy, several emollients are recommended. If topical treatment alone does not appear to be sufficient, the regimen should be escalated according to the Swiss S1-guideline for the systemic treatment of psoriasis., (© 2021 The Author(s) Published by S. Karger AG, Basel.)

Objective: The aim of this study was to test whether an investigational two layer stocking exerting 27-29 mmHg pressure at the medial supramalleolar level, but without compression in the foot and heel, is easier to put on and take off than a standard stocking of the same compression class (23-32 mmHg), and also to assess the prevention of diurnal oedema with both types of stocking., Methods: This was an open label randomised controlled trial, which included 47 patients. All participants were at least 65 years of age and suffered from chronic venous disease class C3 - C6 in one leg. The primary end point was donning success; secondary endpoints were doffing success, prevention of diurnal oedema over one day, and the comfort of wearing the stocking. Patients were randomly allocated to one of two groups. Both types of compression stocking were compared in each group for ease of donning and doffing in the manner of a crossover study. Subsequently, patients wore the stocking type assigned to their group for a whole day to evaluate comfort and the effect on diurnal leg volume., Results: All participants were able to don the investigational stocking unaided, compared with 75% for the standard stocking (p < .001). Unaided removal success was 100% with the investigational stocking vs. 66% for the standard stocking (p < .001). There was no significant difference in leg volume reduction between the study groups after a day of wear. The investigational stocking was also rated as being more comfortable than the standard stocking (p < .001)., Conclusion: The investigational stocking, which has no compression in the foot or heel area, is significantly easier to don and doff, with no inferiority in oedema prevention, compared with a standard stocking of the same compression class., (Copyright © 2020 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)

Introduction: Facial moisturizers are commonly used by healthy women and increasingly men of all age groups. This study aimed to investigate the effects of moisturizer discontinuation and the subsequent evolution of symptoms., Methods: Two prospective observational split-face comparison pilot studies were performed in Switzerland and enrolled (I) 20 healthy women aged 17-25 years in winter and (II) 36 female subjects 15-20 and 40-55 years of age in summer. Moisturizers were stopped on the investigational half of the face. On the control side, the usual skin care regimen was continued. Daily subjective (I/II) and objective (I) skin assessments for the occurrence of typical symptoms of dry skin (dryness, itching, scales, redness, wrinkles) were collected., Results: In the winter study (cohort I) in both the subjective and objective assessment, all skin changes increased significantly within 1 day after discontinuation. On day 7, dryness (p < 0.001), itching (p < 0.025), redness (p < 0.001) and scales (p < 0.049) were significantly different in the subjective assessment and redness (p < 0.004) and scales (p < 0.001) in the objective assessment. Skin dryness reverted to baseline levels after 6 days in the objective assessment and 10 days in the subjective assessment. The control side's condition was reached after 6 days. In the summer study (II), only among the 15-20-year-olds was dryness significantly higher on the intervention side from day 1 (p < 0.028) to day 14 (p < 0.009). Their recovery time was 11 days until dryness intensity scores comparable to baseline were reached, and 21 days until the control side's values were matched. Over a 7-day period, the overall mean dryness score was significantly different between the interventional and control sides for both young and old participants., Conclusions: Both healthy young and aging female subjects react with typical symptoms of temporary dryness to a sudden stop of a previous long-term moisturizer treatment but regain normal levels quickly without continuation of moisturizers. The skin recovery time for skin dehydration is 1-3 weeks in young female subjects with varying intensities depending on the season.

Sézary syndrome (SS) is an aggressive leukemic variant of cutaneous T-cell lymphoma (L-CTCL) that arises from malignant clonally derived skin-homing CD4 + T cells. Based on advancements in our understanding of the mechanisms underlying L-CTCL, boosting the suppressed immune response emerges as a promising strategy in SS management. Immune checkpoint inhibitory molecules have already demonstrated efficacy in a wide spectrum of malignancies. Currently, agents targeting the programmed death-1 (PD-1) axis are under evaluation in L-CTCL. Here we investigated the expression of PD-1 and its ligands, PD-L1 and PD-L2 in blood and skin from patients with L-CTCL. We demonstrate that PD-1 expression is markedly increased on tumor T cells compared to non-tumor CD4 + T cells from SS patients and to CD4 + cells from healthy individuals. In contrast, PD-L1 shows decreased expression on tumor T cells, while PD-L2 expression is low without significant differences between these groups. Functional PD-1 blockade in vitro resulted in reduced Th2 phenotype of non-tumor T lymphocytes, but enhanced the proliferation of tumor T cells from SS patients. Our study sheds some light on the PD-1 axis in both peripheral blood and skin compartments in SS patients, which may be relevant for the treatment of L-CTCL with immune checkpoint inhibitor., (© 2020 The Author(s). Published with license by Taylor & Francis Group, LLC.)

Background: Early and precise diagnosis of cutaneous T-cell lymphomas (CTCL) is challenging. Currently, polymerase chain reaction (PCR)-based clonality assessment of the T-cell receptor (TCR) is a helpful tool for this diagnosis., Objectives: In this retrospective study, we aimed to assess the sensitivity and specificity of this method for the diagnosis of CTCL., Materials and Methods: Monoclonal rearrangement of the TCR was investigated retrospectively by PCR-based clonality assessment based on 292 DNA samples from skin biopsies of patients with a suspicion of CTCL. Algorithms were based on different ratios (three or five-fold difference) between the dominant PCR peak and the third highest PCR peak., Results: A PCR peak five-fold higher than the third highest PCR peak demonstrated significantly greater specificity (83.7% versus 76.4%) but lower sensitivity (59.8% versus 68.6%) compared to a cut-off of three-fold higher., Conclusion: Our results confirm the diagnostic value of TCR clonality analysis which may be used to define the ideal cut-off in order to optimize sensitivity and specificity.

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., (© 2019 S. Karger AG, Basel.)

Background: Granuloma annulare is a chronic noninfectious granulomatous skin condition with variable clinical presentations. Generalized granuloma annulare, defined as widespread disease with >10 skin lesions, accounts for 15% of all cases. Numerous associated diseases have been controversially discussed, most importantly diabetes mellitus, dyslipidemia, thyroid disease, malignancy and systemic infections., Objectives: The objective of our study is to describe disease characteristics, treatment outcome and associated diseases in patients treated at the Department of Dermatology of the University Hospital Zurich during the last 20 years., Methods: The hospital database was searched for patients with generalized granuloma annulare in the last 20 years (January 1, 1998, to December 31, 2017). Overall, 61 patients, 14 males and 47 females, were included in our study. The mean age was 58 years at first consultation. The diagnosis was verified clinically and histologically., Results: Generalized granuloma annulare occurred at a mean age of 55 years, more commonly in females. Pruritus was absent in 51% of all patients. Metabolic diseases including diabetes mellitus, hypercholesterinemia and hypertriglyceridemia were present in 10.5, 8.2 and 4.9%, respectively. Thyroid disease was present in 9.8% and malignant disease in 23%, including colorectal cancer, lymphoproliferative disease, squamous cell carcinoma of the esophagus, basal cell carcinoma and gynecological malignancy. Therapy was initiated in 92%, while second- and third-line therapy was performed in 70 and 39%, respectively. Benefit during therapy (e.g., full and partial remission) was achieved in 39.3% during first-line, in 39.4% during second-line and in 33.8% during third-line treatment. Topical corticosteroids were the most commonly prescribed treatment, mostly leading to stable disease (46.6%). Combined full and partial remission occurred in a large proportion of patients receiving UVA1 (45%), PUVA (63.6%) and intralesional triamcinolone acetonide (100%)., Conclusions: Generalized granuloma annulare is a mostly asymptomatic and benign disease with a strong tendency for treatment resistance. We suggest to screen all patients for dyslipidemia, thyroid disease and malignant disease. While randomized trials are needed, we suggest topical corticosteroids as the first-line treatment, intralesional triamcinolone acetonide for persistent solitary lesions and, if further treatment is needed, UVA1 or PUVA., (© 2020 The Author(s) Published by S. Karger AG, Basel.)

Methotrexate (MTX) is a frequently used anti-psoriatic drug that is commonly recommended in international psoriasis guidelines. It is effective in treating skin lesions, nail changes and psoriatic arthritis. In 2017 a prospective, multicenter, randomized, double-blind, placebo-controlled, phase 3 trial, commonly known as the METOP trial, was published assessing the effectiveness and safety of subcutaneous administration of methotrexate. Because trial data do not always relate to real-life data with unselected patient populations, we wanted to determine whether the data obtained in the METOP-trial correspond to real-life registry data from our Swiss Dermatology Network for Targeted Therapies (SDNTT). Data of 449 patients with moderate to severe psoriasis who participated in the SDNTT registry between 2011 and 1st of July 2017 were analyzed. Only patients receiving methotrexate s.c. were included. 66 patients under MTX were included into this study. Baseline PASI was 6.3 ± 3.8 (SDNTT) compared to 15.9 ± 5.9 in the METOP trial. In our cohort, only 18% of all patients reached PASI 75 after 12 weeks, 6% showed a complete remission (PASI 100) compared to 41% and 4% in the METOP trial after 16 weeks. 22.7% of all patients showed increased liver enzymes in either study and nausea was seen in 15% (SDNTT) versus 22% (METOP) of patients. No severe adverse events were observed in our cohort. Compared to the METOP-trial, the response rates seen our real-world cohort were distinctly lower.

In Sézary syndrome (SS) impaired T-cell function and cytokine profile lead to immune evasion. Immune checkpoints non-redundantly regulate immune responses and targeting them is promising. We evaluated the expression of BTLA, CTLA-4, FCRL3, LAG-3, and TIGIT in tumor and non-tumor SS T-cells.Compared to CD4+ T helper cells from ten healthy individuals, tumor cells of eight SS patients had a significant upregulation of BTLA (1.5-fold; p  < .0001), FRCL3 (2.2-fold; p  < .0028) and TIGIT (2.2-fold; p  < .0003) expression. In contrast, we found a reduced expression of LAG-3+ cells in the blood of tumor patients (0.5-fold; p  < .0014). Only weak alternations between tumor, non-tumor cells, and healthy controls were observed regarding CTLA-4 (0.5-fold; p  < .2022). Our results show a diverse expression pattern of immune-regulatory molecules in SS patients. As these molecules are essential in the regulation of T-cell mediated tumor surveillance and defense, their specific targeting might be of clinical relevance.