Checkpoint inhibitor-induced lichen planus differs from spontaneous lichen planus on the clinical, histological, and gene expression level.

Background: Although highly efficacious, immune checkpoint inhibitors induce a multitude of immune-related adverse events including lichenoid skin reactions (irLP) that are often therapy-resistant. Objectives: To compare the clinical, histological, and transcriptional features of irLP with spontaneous lichen planus (LP). Methods: Clinical and histological presentations of irLP and LP, as well as the gene expression profiles of irLP and LP lesional and healthy skin were assessed. Results: irLP differed considerably from LP with regard to the distribution pattern of skin lesions with irLP appearing mostly in an exanthematous form, whereas lesions were more localized in the LP group. Histologically, dermal lymphocyte infiltration was significantly lower in irLP compared with LP, whereas lymphocyte exocytosis and apoptotic keratinocytes were significantly higher in irLP. Gene expression analysis revealed irLP to have a more inflammatory profile with elevated IFNG levels and a possible role of phagosome signaling compared with LP. Limitations: The study is descriptive and necessitates further investigation with larger cohorts and broader analyses. Conclusion: irLP differs from spontaneous LP on the clinical, histopathological, and gene expression level. The inflammatory gene signature in irLP suggests that topical JAK inhibitors could be an effective treatment, targeting local skin inflammation without systemic immunosuppression.

Line-field confocal optical coherence tomography, a novel non-invasive tool for the diagnosis of onychomycosis.

BACKGROUND AND OBJECTIVES: Onychomycosis is common and important to distinguish from other nail diseases. Rapid and accurate diagnosis is necessary for optimal patient treatment and outcome. Non-invasive diagnostic tools have increasing potential for nail diseases including onychomycosis. This study evaluated line-field confocal optical coherence tomography (LC-OCT) as a rapid non-invasive tool for diagnosing onychomycosis as compared to confocal laser scanning microscopy (CLSM), optical coherence tomography (OCT), and conventional methods. PATIENTS AND METHODS: In this prospective study 86 patients with clinically suspected onychomycosis and 14 controls were examined using LC-OCT, OCT, and CLSM. KOH-preparation, fungal culture, PCR, and histopathology were used as comparative conventional methods. RESULTS: LC-OCT had the highest sensitivity and negative predictive value of all methods used, closely followed by PCR and OCT. Specificity and positive predictive value of LC-OCT were as high as with CLSM, while OCT scored much lower. The gold standard technique, fungal culture, showed the lowest sensitivity and negative predictive value. Only PCR and culture allowed species differentiation. CONCLUSIONS: LC-OCT enables quick and non-invasive detection of onychomycosis, with advantages over CLSM and OCT, and similar diagnostic accuracy to PCR but lacking species differentiation. For accurate nail examination, LC-OCT requires well-trained and experienced operators.

Tumor lysis syndrome induced by tebentafusp.

Tebentafusp, a bispecific T-cell receptor fusion protein directed against gp100 and CD3, can improve survival in patients with metastatic uveal melanoma and was recently approved for the treatment of HLA-A*02:01-positive uveal melanoma patients. Since tebentafusp often induces cytokine-release syndrome, doses must be escalated and patients monitored as inpatients after the first infusions. The occurrence of tumor lysis syndrome, a potentially life-threatening condition, after administration of a single dose of tebentafusp, is reported here. With adequate therapy, including the application of rasburicase, the patient made a full recovery. It is important to raise awareness of the adverse event profile of this new therapeutic approach among healthcare professionals to promptly recognize and treat side effects.

Tebentafusp is a new treatment for a type of eye cancer called uveal melanoma. It helps the body's defense system fight against cancer cells and has shown promise in helping patients live longer. However, not all patients with uveal melanoma can use this treatment. Only those who have a specific gene marker called HLA-A*02:01-positive can benefit from it. Like any new treatment, tebentafusp may have some side effects. One of them is called cytokine-release syndrome, which can cause symptoms like rash, fever and flu-like feelings. Usually, this side effect is not serious and can be treated well. There was a rare but serious case where one patient had a bad reaction after getting only one dose of tebentafusp. This reaction is called tumor lysis syndrome, which happens when cancer cells break down quickly and release harmful substances into the blood. This can be life-threatening. Thankfully, the patient received the right treatment and got better. This information is shared here with doctors and patients, so they know about possible side effects and can use tebentafusp safely.

Acute Generalized Exanthematous Pustulosis: Clinical Characteristics, Pathogenesis, and Management.

BACKGROUND: Acute generalized exanthematous pustulosis (AGEP) is a potentially severe adverse cutaneous drug reaction, which typically occurs within 24-48 h after the intake of the culprit drug. SUMMARY: AGEP is characterized by numerous sterile subcorneal pustules on erythematous skin and in less than a third of cases it can be associated with organ manifestations possibly leading to life-threatening symptoms (e.g., cholestasis, nephritis, and lung and bone marrow involvement). In contrast to generalized pustular psoriasis, it can involve mucosal regions and typically resolves rapidly if the culprit drug is removed, and adequate therapy with topical or systemic steroids administered. Diagnosis based on patient history, clinical signs, and characteristic cutaneous histology is rarely challenging. Identification of the culprit drug may be aided by patch testing or lymphocyte transformation tests that are of limited value. KEY MESSAGES: Recent experimental data reviewed herein are supportive of an early role of drug-induced innate immune activation and innate cytokines such as interleukin (IL)-1, IL-36, and IL-17 in the pathogenesis of AGEP. This explains the rapid onset and neutrophilic character of the cutaneous inflammation, but also provides new avenues for in vitro tests aimed at better identifying the culprit drug.

Comparison of Different Anti-Demodex Strategies: A Systematic Review and Meta-Analysis.

BACKGROUND: Demodex mites are related to some inflammatory diseases such as rosacea and blepharitis and could be harmful in patients with immunodeficiency or immunosuppression, especially notable in patients using biologic like dupilumab. In order to have an objective observation of different anti-Demodex strategies, we conducted this study, based on interventional clinical evidence with quantified Demodex mite data. METHODS: We used the PubMed, Embase, ClinicalTrials.gov, Medline, and International Clinical Trials Registry Platform (ICTRP) as databases. To assess the risk of bias, the RoB2 and ROBINS-I tools were used. The certainty of evidence was assessed following the GRADE guideline. Furthermore, the effect sizes (ESs) of different strategies were compared in different time periods (0-1, 1-2, 2-3, >3 months), as well as Demodex decrease rates. RESULTS: 1,618 studies were identified in the databases, with 21 of which included in the final quantitative synthesis. Interventions in these studies included ivermectin, tea tree oil (TTO), permethrin, crotamiton, metronidazole, light therapies, combined therapies, and other therapies. During 0-1 month, the ES varied from 0.07 (cleanser) to 1.95 (systemic ivermectin-metronidazole). During 1-2 months, the ES varied from 0.88 (topical permethrin) to 4.40 (topical ivermectin). During 2-3 months, the ES varied from 0.79 (topical permethrin) to 8.37 (topical ivermectin). During the time of 3 months, the ES varied from 0.59 (topical permethrin) to 2.25 (intense pulsed light [IPL]). In terms of Demodex decrease rates, topical ivermectin, TTO, permethrin, IPL, and baby shampoo had achieved a nearly 100% decrease. The reported adverse events were mostly mild, without severe adverse events reported in any of the studies. CONCLUSIONS: We found ivermectin (topical and systemic), ivermectin-metronidazole (topical), and TTO (topical) are promising anti-Demodex interventions. In addition to traditional pharmacotherapy, light therapies, especially IPL and skin cleansing, could also be considered as effective methods to control Demodex mite infestation.

Cannabinoids in hyperhidrosis.

Hyperhidrosis can significantly curtail patient quality of life, from debilitating physical symptoms to social stigmatization and reduced life opportunities. Current treatments often prove unsatisfactory, especially in sufferers of generalized hyperhidrosis. In this open trial, we present the case of a refractory generalized hyperhidrosis treated with cannabinoids. We found a remarkable reduction in the volume of sweat and an improvement to the patient's quality of life using this novel low-cost and low-impact approach.

Cutaneous T-cell Lymphomas: A Single-center Retrospective Analysis.

INTRODUCTION: Cutaneous T-cell lymphomas (CTCLs) are rare diseases characterized by infiltration of malignant T-cells into the skin. We evaluated the prevalence, epidemiology, and therapy of CTCLs, focusing on its most well-known subtypes, namely mycosis fungoides (MF) and Sézary syndrome (SS). PATIENTS AND METHODS: We retrospectively analyzed the medical data of patients with a histologically confirmed diagnosis of CTCL presenting to our outpatient department during a 5-year period from January 2015 to December 2019. RESULTS: We evaluated the files of 102 patients, of whom 67% were men and 33% women. The overall mean age was 59.1±14.1 (24-86) years. Ninety-two patients (90%) were diagnosed with MF and ten patients (10%) with SS. According to ISCL/EORTC, the majority of patients initially classified as stage IA (34%) and IB (45%). Disease frequency decreased at advanced stages (II: 4%; III: 7%; IV: 10%). Forty-five patients (44.1%) received only skin-directed therapy (SDT). Twenty patients (19.6%) progressed from SDT to systemic therapy (ST). Thirty-seven patients (36.3%) received ST combined with SDT (TS) from the start of treatment. Overall, fifty different therapeutic approaches of TS were initiated due to lack of response to therapy or disease progression. CONCLUSION: Management of CTCLs aims to maintain patient quality of life while minimizing side-effects. As CTCLs are usually incurable diseases, the focus of treatment is on symptom control and prevention of disease progression. Due to the large patient group and the long observation period, our study allows for a valid evaluation of the frequency and therapy of MF and SS in a university outpatient clinic in Germany. We favor topical therapies in early stages with more invasive therapies in advanced stages.

Impact of the COVID-19 pandemic on patients with hidradenitis suppurativa.

The COVID-19 pandemic caused collateral damage to patients with acute and chronic conditions. In this mono-centre cross-sectional study, we sought to evaluate the impact of the COVID-19 pandemic on patients with hidradenitis suppurativa (HS). In June 2020, we sent an anonymous survey to 109 patients, who were diagnosed with HS in our outpatient clinic from May 2018 to April 2020. Fifty patients (45.9%) completed and returned the survey. Forty-five participants (90.0%) denied any cancellation of hospitalisation due to the COVID-19 pandemic. Hospitalisation was postponed in 8% of cases and cancelled in 2%. Compared to prior to the pandemic, fewer patients consulted their primary physician for changing wound dressings and more changed the dressings themselves or were assisted by their family members. 13% of patients avoided doctor visits due to fear of COVID-19 and 26.1% minimised doctor visits. The Dermatology Life Quality Index showed a moderate to very severe impact on patients' Quality of Life (mean score = 10.06). Only one patient used telemedicine. Due to limited access to primary care and fear of COVID-19, the pandemic had a detectable impact on the hospital management of patients with HS in our facility. Telemedicine still plays a negligible role in primary wound care.

Lichen Planus Pigmentosus Inversus: A Rare Subvariant of Lichen Planus Pigmentosus.

Lichen planus pigmentosus inversus (LPPI) is a rare subvariant of Lichen planus pigmentosus (LPP), presenting with sharply defined brown to gray macules, papules, and plaques limited to the intertriginous areas, with only a few cases reported in the medical literature so far. While LPP mostly affects patients with Fitzpatrick skin type III-IV in sun-exposed areas such as the neck, LPPI is seen in Caucasians and spares sun-exposed areas. Skin lesions tend to be very refractory to treatment attempts including potent topical steroids and oral corticosteroids. Given the increased penetration of potent topical steroids and the high risk of skin atrophy, especially when applied to intertriginous areas, this case shows that topical calcineurin inhibitors (tacrolimus 0.1%) might offer an effective and safe treatment option for LPPI.

Increased prevalence of irritant hand eczema in health care workers in a dermatological clinic due to increased hygiene measures during the SARS-CoV-2 pandemic.

BACKGROUND: Hand hygiene measures in the general population and in health care workers have increased considerably since the outbreak of the COVID-19 pandemic. OBJECTIVES: To investigate the prevalence and symptoms of hand eczema, as well as hygiene measures and concepts of care, in German health care workers. MATERIALS & METHODS: This was an observational questionnaire study to investigate hygiene and skin care habits, as well as the prevalence and symptoms of hand eczema in 66 nurses and doctors of our dermatology department before and during the SARS-CoV-2 pandemic. RESULTS: Hand washing and hand disinfection procedures increased significantly during the COVID-19 pandemic. Self-diagnosed hand eczema was reported by 33% of the participants, with a median duration of 14 days. The majority of staff currently affected by hand eczema were free of eczema a month previously (82%) and would treat their skin condition with emollients (77%). Erythema, scaling, burning and fissures were reported by 66.1% of the participants and were classified as predominant signs of toxic-irritant hand dermatitis rather than contact allergy. CONCLUSION: Overall, the SARS-CoV-2 pandemic has led to a significant increase in the incidence of signs of irritant hand eczema despite intensified emollient use as a preventive measure. Awareness of the prevalence of hand eczema in health care workers in Germany during the COVID-19 pandemic should be raised, and preventive measures should be intensified.

In-Vivo LC-OCT Evaluation of the Downward Proliferation Pattern of Keratinocytes in Actinic Keratosis in Comparison with Histology: First Impressions from a Pilot Study.

It is known that actinic keratoses (AKs) can progress to invasive squamous cell carcinoma (SCC). The histological PRO grading of AKs is based on the growth pattern of basal keratinocytes and relates to their progression risk. AKs can be non-invasively characterized by line-field confocal optical coherence tomography (LC-OCT). The aim of the study was to define criteria for an LC-OCT grading of AKs based on the PRO classification and to correlate it with its histological counterpart. To evaluate the interobserver agreement for the LC-OCT PRO classification, fifty AKs were imaged by LC-OCT and biopsied for histopathology. PRO histological grading was assessed by an expert consensus, while two evaluator groups separately performed LC-OCT grading on vertical sections. The agreement between LC-OCT and histological PRO grading was 75% for all lesions (weighted kappa 0.66, 95% CI 0.48-0.83, p ≤ 0.001) and 85.4% when comparing the subgroups PRO I vs. PRO II/III (weighted kappa 0.64, 95% CI 0.40-0.88, p ≤ 0.001). The interobserver agreement for LC-OCT was 90% (Cohen's kappa 0.84, 95% CI 0.71-0.91, p ≤ 0.001). In this pilot study, we demonstrated that LC-OCT is potentially able to classify AKs based on the basal growth pattern of keratinocytes, in-vivo reproducing the PRO classification, with strong interobserver agreement and a good correlation with histopathology.

Rat bite fever, a diagnostic challenge: case report and review of 29 cases.

Rats can transmit Streptobacillus moniliformis, which may cause rat-bite fever (RBF), a rare and potentially lethal zoonosis. Fastidious in vitro growth and unspecific symptoms, including fever, arthralgia, and polymorphous skin lesions, complicate the diagnosis. Rat-bite fever follows exposure to contaminated bodily fluids of infected rodents; however, reports on Streptobacillus moniliformis-related infections are few so far. A female patient presented with painful hemorrhagic pustules and purpuric lesions on hands and feet. She developed fever and migratory polyarthralgia. Blood culture yielded growth with Streptobacillus moniliformis. The patient owned rats and handled contaminated rat feces and urine, making this the most likely etiology of infection. We report a case of RBF due to Streptobacillus moniliformis in a rat handling-patient. Difficulties in clinical and microbiological diagnosis highlight the need for a thorough and complete history-taking and a greater understanding of this rare infectious disease.

Patient Perception of Mobile Phone Apps for the Care and Prevention of Sexually Transmitted Diseases: Cross-Sectional Study.

BACKGROUND: In the emerging era of digitalization and electronic health, various health-related apps have been launched, including apps for sexually transmitted diseases. Until now, little has been known about how patients perceive the value of such apps. OBJECTIVE: To investigate patient's attitudes and awareness toward sexually transmitted disease-related apps in an outpatient sexually transmitted disease clinic setting. METHODS: A cross-sectional study was conducted at a dermatovenereological outpatient unit between April and July 2019. Patients completed a self-administered questionnaire on their perceptions of the popularity and usefulness of sexually transmitted disease-related apps. Descriptive analysis was performed with expression of categorical variables as frequencies and percentages. For continuous variables, the median, range, and interquartile range were indicated. Contingency tables and chi-square tests were used to investigate associations between sociodemographic data and items of the questionnaire. RESULTS: A total of 226 patients were surveyed (heterosexual: 137/193, 71.0%; homosexual: 44/193, 22.8%; bisexual: 12/193, 6.2%); 11.9% (27/225) had previously used health-related apps. Nearly half of the patients (97/214, 45.3%) specifically considered sexually transmitted disease-related apps useful, 47.8% (100/209) voted that they could supplement or support the consultation of a physician. Interestingly, only 35.1% (74/211) preferred a printed patient brochure on sexually transmitted diseases over downloading and using an app, but 64.0% (134/209) would download a sexually transmitted disease-related app recommended by their physician. General information regarding sexually transmitted diseases (93/167, 55.7%), evaluation of skin diseases based on photos or videos (78/167, 53.3%), information on the prevention of sexually transmitted diseases (76/167, 45.5%), mediation of nearby contact points or test sites (74/167, 44.3%), anonymous medical advice (69/167, 41.3%), and calculation of the risk of having a sexually transmitted disease (63/167, 37.3%) were rated as the most important features. Men were more likely than women to find sexually transmitted disease-related apps useful in general (P=.04; χ2=6.28) and to pay for such apps (P=.01; χ2=9.19). Patients aged <40 years would rather download an app recommended by their physician (P=.03; χ2=7.23), whereas patients aged >40 years preferred reading a patient brochure on sexually transmitted diseases (P=.02; χ2=8.14). CONCLUSIONS: This study demonstrated high general interest in the use of sexually transmitted disease-related apps in this sample of dermatovenereological outpatients. In particular, young age and male sex were significantly associated with a positive perception, underlining the high potential of apps in the prevention and early recognition of sexually transmitted diseases in this group. Future studies are warranted to validate these findings in other populations.

Patient Attitudes and Their Awareness Towards Skin Cancer-Related Apps: Cross-Sectional Survey.

BACKGROUND: In the emerging era of digitalization and electronic health, skin cancer-related apps represent useful tools to support dermatologic consultation and examination. Yet, little is known about how patients perceive the value of such apps. OBJECTIVE: The aim of this study was to investigate patient attitudes and their awareness toward skin cancer-related apps. METHODS: A cross-sectional study including 200 patients from the oncological outpatient unit was conducted at the University Hospital (LMU Munich, Germany) between September and December 2018. Patients were asked to complete a self-administered questionnaire on the popularity and usefulness of health-related and skin cancer-related apps. A descriptive analysis was performed with the expression of categorical variables as frequencies and percentages. For continuous variables, the median and range were indicated. Contingency tables and chi-square tests were performed to investigate associations between sociodemographic data and selected items of the questionnaire. RESULTS: A total of 98.9% (195/197) of patients had never used skin cancer-related apps or could not remember. In 49.7% (93/187) of cases, patients were unsure about the usefulness of skin cancer apps, whereas 42.6% (78/183) thought that skin cancer apps could supplement or support the professional skin examination performed by a physician. However, 47.9% (90/188) were interested in acquiring more information by their dermatologists about skin cancer apps. Young age (P=.002), male gender (P=.02), a previous history of melanoma (P=.004), and higher educational level (P=.002) were significantly associated with a positive attitude. Nevertheless, 55.9% (105/188) preferred a printed patient brochure on skin cancer to downloading and using an app. CONCLUSIONS: The experience and knowledge of skin cancer-related apps was surprisingly low in this population, although there was a high general interest in more information about such apps. Printed patient brochures were the preferred information source.

Brentuximab as a treatment for CD30+ mycosis fungoides and Sézary syndrome.

IMPORTANCE: The prognosis of advanced cutaneous T-cell lymphoma (CTCL), including Sézary syndrome and mycosis fungoides (MF), is poor. So far, no curative option apart from allogeneic stem cell transplantation is available. Large cell transformation often hallmarks cases with a more aggressive clinical course, and large tumor cells may express CD30. Recently, brentuximab vedotin, a conjugate of an anti-CD30 antibody and monomethylauristatin E, which inhibits the polymerization of microtubuli, has produced promising results in phase 2 trials in CD30+ Hodgkin lymphoma and anaplastic large cell lymphoma. OBSERVATIONS: We describe 4 patients with advanced CTCL, 3 with MF and 1 with Sézary syndrome, who were treated with brentuximab. All patients had received multiple previous systemic therapies. In 2 cases of MF, a remission enabling subsequent allogeneic stem cell transplantation was achieved. CONCLUSIONS AND RELEVANCE: Brentuximab is a well-tolerated, promising new treatment option for advanced CTCL that can be integrated in an allogeneic stem cell transplantation plan by selectively depleting malignant CD30+ cutaneous lymphoma cells.