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Supplemental digital content is available in the text., Background Itch, the most bothersome symptom in atopic dermatitis, is largely mediated by pruritogenic cytokines via Janus kinase 1 signaling in cutaneous sensory neurons. Objectives The aims of the study were to assess the magnitude and rapidity of itch relief with the Janus kinase 1 selective inhibitor abrocitinib and to evaluate the extent to which the effect of abrocitinib on itch relief is independent of overall disease improvement. Methods Pooled data from 1 phase 2b (NCT02780167) and 2 phase 3 (NCT03349060, NCT03575871) double-blind, randomized, placebo-controlled monotherapy trials in moderate to severe atopic dermatitis (N = 942) were analyzed. Results Abrocitinib produced significant and clinically meaningful itch relief versus placebo from week 2 through week 12 (end of treatment) that was associated with marked sleep and quality-of-life improvements. Mean percentage reductions in itch scores 24 hours after the first dose were greater for both abrocitinib doses (200 and 100 mg) versus placebo. Itch improvement occurred regardless of baseline itch severity, sex, race, body mass index, or Investigator Global Assessment response, suggesting that abrocitinib-associated itch relief is at least partially independent of overall disease improvement. Conclusions Abrocitinib showed a rapid and profound antipruritic effect, partially independent of improvement in overall disease.

Given the lack of head‐to‐head studies of systemic therapies in moderate‐to‐severe atopic dermatitis (AD), network meta‐analyses (NMAs) can provide comparative efficacy and safety data to inform clinical decision‐making. In this NMA, eligible randomized controlled trials (RCTs) published before 24 October 2019 were identified by a systematic literature review. Short‐term (12–16 weeks) efficacy (Investigator’s Global Assessment [IGA] and Eczema Area and Severity Index [EASI] responses), patient‐reported outcomes (PROs) and safety data from each trial were abstracted and analysed separately for monotherapy and combination therapy (systemic plus topical anti‐inflammatory therapy). RCTs were analysed in fixed‐effects and random‐effects Bayesian NMA models. Overall, 19 phase 2 and phase 3 RCTs of abrocitinib, baricitinib, dupilumab, lebrikizumab, nemolizumab, tralokinumab and upadacitinib were included. In monotherapy RCTs, upadacitinib 30 mg once daily (QD) had the numerically highest efficacy (83.6% achieved ≥50% improvement in EASI [EASI‐50 response]), followed by abrocitinib 200 mg QD (74.6%), upadacitinib 15 mg QD (70.5%), dupilumab 300 mg every 2 weeks (Q2W) (63.4%) and abrocitinib 100 mg QD (56.7%). Similar trends in EASI‐75 and EASI‐90 response were observed. In combination therapy RCTs, abrocitinib 200 mg QD had the highest EASI‐50 (86.6%), followed by dupilumab 300 mg Q2W (82.4%) and abrocitinib 100 mg QD (79.7%). Similar findings were observed for IGA response and PROs. In monotherapy and combination therapy RCTs, the probability of treatment‐emergent adverse events (TEAEs) was higher among all active treatments than with placebo (except for dupilumab 300 mg Q2W [odds ratio (OR), 0.96; 95% credible interval (CrI), 0.45–2.18] and abrocitinib 100 mg QD [OR, 0.95; 95% CrI, 0.35–2.66] in combination therapy RCTs), although active treatments did not significantly differ from one another. Abrocitinib, dupilumab and upadacitinib were consistently the most effective systemic therapies in adult and adolescent patients with AD, with no significant TEAE differences in short‐term RCTs.

As the most common human cancer worldwide and continuing to increase in incidence, basal cell carcinoma is associated with significant morbidity and cost. Continued advances in research have refined both our insight and approach to this seemingly ubiquitous disease. This 2-part continuing medical education article will provide a comprehensive and contemporary review of basal cell carcinoma. The first article in this series describes our current understanding of this disease regarding epidemiology, cost, clinical and histopathologic presentations, carcinogenesis, natural history, and disease associations.

As the most common human cancer worldwide and continuing to increase in incidence, basal cell carcinoma is associated with significant morbidity and cost. Continued advances in research have refined both our insight and approach to this seemingly ubiquitous disease. This 2-part continuing medical education series provides a comprehensive and contemporary review of basal cell carcinoma. The second article in this series will present both the current standard of care and newly developed approaches to diagnosis, treatment, and prevention of this disease.

Efforts to increase patient comfort by minimizing pain and anxiety have been shown to improve clinical outcomes, reduce pain thresholds, decrease analgesic requirements and complication risk, strengthen the physician-patient relationship, and increase overall patient satisfaction. Patients also have a strong preference for patient-centered communication and educational discussion with physicians. In recent years, the increasing emphasis on patient experience scores as a metric for quality care has had significant implications for physician practice and has reinforced attempts to provide more patient-centered care. Though different pharmacologic agents and techniques have been extensively reviewed in the dermatologic literature, there have been few studies of non-pharmacologic strategies for improving patient-centered care. This evidence-based review describes alternative techniques that have been suggested for use in dermatologic surgery. Mechanoanesthesia, cold therapy, verbal and audiovisual distraction, music, optimal needle insertion methods, hypnosis and guided-imagery, perioperative communication, and educational strategies have been reported to improve the patient experience in dermatologic surgery. These interventions are often cost-effective and easy to implement, avoid medication side effects, and serve as adjunct approaches to enhance patient comfort. This review examines the corresponding evidence for these nonpharmacologic strategies to provide a clinical resource for the dermatologic surgeon seeking to optimize the patient experience.

The role of cutaneous human papillomavirus (HPV) infection in the development of subsequent cutaneous squamous cell carcinoma (SCC) is unknown. Pathologically confirmed cases of SCC (n=150) enrolled in a previously conducted case-control study were included in a retrospective cohort study to examine the association of cutaneous HPV at the time of SCC diagnosis with the risk of subsequent SCC development. Data on HPV seropositivity, HPV DNA in eyebrow hairs (EB) and SCC tumors were available from the parent study. Incidence of subsequent SCC was estimated using person-years of follow up. Cox Proportional Hazards ratios were estimated to evaluate the associations of both, HPV seropositivity and HPV DNA positivity with subsequent SCC. The five year cumulative incidence of subsequent SCC was 72%. Seropositivity to cutaneous HPV was not associated with the risk of subsequent SCC (HR = 0.83, 95% CI = 0.41–1.67). Any beta HPV infection in EB was associated with reduced risk (HR = 0.30, 95% CI = 0.11–0.78) of subsequent SCC among cases who were positive for beta HPV DNA in tumor tissue. Infection with beta HPV type 2 (HR = 0.32, 95% CI = 0.12–0.86) in EB was associated with reduced risk of subsequent SCC among HPV DNA positive SCCs. In conclusion, beta HPV infection was inversely associated with the risk of subsequent SCC.

Background 5-fluorouracil (5-FU) has proven to be an effective therapy in the treatment of a variety of dermatologic conditions. Approved by the United States Food and Drug Administration for the treatment of actinic keratoses and superficial basal cell carcinoma, topical 5-FU has also demonstrated efficacy in the treatment of a variety of other dermatologic diseases. Methods A search of the MEDLINE standard computer database, MEDLINE advanced database, and EMBASE database was conducted. Results Thirty-four articles met criteria for inclusion in this review. These articles represented 16 randomized controlled trials and 18 case series. Each article was reviewed and summarized. Conclusions Topical 5-FU is used in a variety of dermatologic disease processes with a wide range of efficacy and levels of evidence. Based on extent and level of evidence, our disease-specific systematic review found that the evidence is strongest for topical 5-FU use in the treatment of actinic keratosis, squamous cell carcinoma, and basal cell carcinoma. This review serves as a comprehensive summary of topical 5-FU use in dermatology.

PurposeDermatologic adverse events (dAEs) in cancer treatment are frequent with the use of targeted therapies. These dAEs have been shown to have significant impact on health-related quality of life (HRQoL). While standardized assessment tools have been developed for physicians to assess severity of dAEs, there is a discord between objective and subjective measures. The identification of patient-reported outcome (PRO) instruments useful in the context of targeted cancer therapies is therefore important in both the clinical and research settings for the overall evaluation of dAEs and their impact on HRQoL.MethodsA comprehensive, systematic literature search of published articles was conducted by two independent reviewers in order to identify PRO instruments previously utilized in patient populations with dAEs from targeted cancer therapies. The identified PRO instruments were studied to determine which HRQoL issues relevant to dAEs were addressed, as well as the process of development and validation of these instruments.ResultsThirteen articles identifying six PRO instruments met the inclusion criteria. Four instruments were general dermatology (Skindex-16©, Skindex-29©, Dermatology Life Quality Index (DLQI), and DIELH-24) and two were symptom-specific (functional assessment of cancer therapy-epidermal growth factor receptor inhibitor-18 (FACT-EGFRI-18) and hand-foot syndrome 14 (HFS-14)).ConclusionsWhile there are several PRO instruments that have been tested in the context of targeted cancer therapy, additional work is needed to develop new instruments and to further validate the instruments identified in this study in patients receiving targeted therapies.

We present a multimodality mapping approach to guide staged excision for challenging lentigo maligna (LM) and lentigo maligna melanoma (LMM) lesions. LM/LMM often present with ill-defined clinical borders and subclinical tumor extension on the head and neck, where preservation of functionality and cosmesis can be critical. In our approach, pre-surgical evaluation of clinical margins is defined with the use of Wood’s Lamp, dermoscopy, confocal microscopy, and scouting punch biopsies. Once pre-operative margin mapping has been completed, a staged excision with complete pathologic assessment prior to final excision and subsequent closure is performed. Our approach ensures complete resection of these difficult-to-manage LM/LMM cases while preserving healthy tissue in order to minimize the impact on cosmesis and functionality.

The majority of toxic epidermal necrolysis (TEN) cases are provoked by “high risk” medications (e.g. allopurinol, aromatic anticonvulsants, nevirapine, oxicam non-steroidal anti-inflammatory agents, and sulfonamides). TEN usually occurs 1 to 8 weeks after initial administration of the offending agent, but re-administration can evoke TEN within hours to days [1]. Hydroxychloroquine has rarely been associated with TEN, with one case proving fatal [2-4]. Herein, we report a case of hydroxychloroquine-induced fatal TEN complicated by angioinvasive Rhizopus. To our knowledge, this is the first case report of angioinvasive Rhizopus in a TEN patient. Initial misidentification of the offending agent causing TEN also serves as an important teaching point worth highlighting.