Clinical, onychoscopic, nail clipping, and histopathological findings of malignant onychopapilloma.

This report describes the clinical, onychoscopic, nail clipping, and histopathologic features of a malignant onychopapilloma. A 71-year-old male presented to our outpatient clinic for a stable, asymptomatic lesion on his left middle finger that had been present for 2 years. Prior nail clipping histopathology showed nail plate thinning with subungual abnormal onychocytes. Clinical examination revealed a 2-mm-wide streak of longitudinal xanthonychia extending to the proximal nail fold, with distal hyperkeratosis and onycholysis. Onychoscopy showed irregular longitudinal nail plate ridging with scattered punctate hemorrhagic foci. An excisional nail unit biopsy demonstrated cellular atypia of the nail bed epithelium, matrix metaplasia, longitudinal abnormal onychocytes, increased Ki-67 staining, and negative HPV immunoperoxidase staining, confirming the diagnosis of malignant onychopapilloma.

Autosomal recessive congenital ichthyosis due to novel CYP4F22 mutation presenting with a collodion membrane and ocular manifestations.

Autosomal recessive congenital ichthyoses (ARCI) are a range of genetic disorders of keratinization. The rare CYP4F22 gene mutation can present with or without collodion membrane at birth and leads to the development of mild ichthyosis phenotype. We report a case of a novel pathogenic CYP4F22 genetic mutation presenting with collodion membrane and ocular manifestations. Ocular manifestations have recently been reported in a patient with ARCI with known CYP4F22 mutation, which further supports a possible correlation between the CYP4F22 mutation and this distinct phenotype.

Avelumab for Advanced Merkel Cell Carcinoma: Global Real-World Data on Patient Response and Survival.

Introduction: Avelumab is a programmed cell death-ligand 1 (PD-L1) inhibitor approved by the Food and Drug Administration for advanced Merkel cell carcinoma (MCC). Studies conducted in real-world settings have shed light on its effectiveness and safety in clinical settings. Areas Covered: Real-world studies on avelumab for MCC from North and South America, Europe, and Asia have been presented in this review. Most studies are on patients over age 70 and have a male-predominant sex ratio. Overall response rates range from 29.1% to 72.1%, (disease control rate: 60.0-72.7%; complete response rate: 15.8%-37.2%; partial rate: 18.2-42.1%; stable disease: 7.1-30.9%; progressive disease: 7.1-40.0%) and median progression free survival ranges from 8.1 to 24.1 months depending on the population studied. Immunosuppressed patients appear to benefit from avelumab as well, with response rates equivalent to the general population. Patients receiving avelumab as a first-line agent tend to have better outcomes than those using it as a second-line therapy. Fatigue, infusion-related reactions, and dyspnea were some of the most common adverse events identified in real-world studies. Autoimmune hepatitis and thyroiditis were also observed. Conclusion: The use of avelumab as a safe and effective treatment option for advanced MCC is supported by real-world data, although additional study is required to assess long-term efficacy and safety outcomes.

Cutaneous adverse reactions resulting from targeted cancer therapies: histopathologic and clinical findings.

Targeted cancer treatments-designed to interfere with specific molecular signals responsible for tumor survival and progression-have shown benefit over conventional chemotherapies but may lead to diverse cutaneous adverse effects. This review highlights clinically significant dermatologic toxicities and their associated histopathologic findings, resulting from various targeted cancer drugs. Case reports and series, clinical trials, reviews, and meta-analyses are included for analysis and summarized herein. Cutaneous side effects resulting from targeted cancer therapies were reported with incidences as high as 90% for certain medications, and reactions are often predictable based on mechanism(s) of action of a given drug. Common and important reaction patterns included: acneiform eruptions, neutrophilic dermatoses, hand-foot skin reaction, secondary cutaneous malignancies, and alopecia. Clinical and histopathologic recognition of these toxicities remains impactful for patient care.

Low-dose methotrexate in dermatology: the utility of serological monitoring in a real-world cohort.

When prescribing low-dose methotrexate, frequent serological testing is recommended in the dermatologic literature, although much of the supporting data is extrapolated from non-dermatologic conditions. We performed a retrospective cohort study to determine the cumulative incidence and timing of low-dose methotrexate-associated serological abnormalities over the first year of therapy, in a pragmatic cohort of patients with dermatologic compared to non-dermatologic diagnoses. Laboratory values recorded included white blood cell count, hemoglobin, platelet count, estimated glomerular filtration rate, alanine aminotransferase, and aspartate aminotransferase. Among 1376 patients, there were no cases of methotrexate-associated grade 4/very severe lab abnormality or fatality. Baseline risk factors associated with moderate-to-severe lab abnormalities included non-dermatologic diagnoses, low hemoglobin, low estimated glomerular filtration rate, and elevated transaminases. The incidence of moderate-to-severe lab abnormalities was 4.4% among all patients, 3.1% among patients with dermatologic diagnoses, and 2.3% among patients with normal baseline lab values. Lab abnormalities led to discontinuation of therapy in 0.8% of patients. Serious changes did not occur in the first two weeks of therapy. We conclude that the cumulative incidence of low-dose methotrexate-associated lab abnormality was lower in patients with dermatologic diagnoses or normal baseline testing and these factors may be used to adjust monitoring practices.

Patient Experience Surveys Reveal Gender-Biased Descriptions of Their Care Providers.

Patient experience surveys (PES) are collected by healthcare systems as a surrogate marker of quality and published unedited online for the purpose of transparency, but these surveys may reflect gender biases directed toward healthcare providers. This retrospective study evaluated PES at a single university hospital between July 2016 and June 2018. Surveys were stratified by overall provider rating and self-identified provider gender. Adjectives from free-text survey comments were extracted using natural language processing techniques and applied to a statistical machine learning model to identify descriptors predictive of provider gender. 109,994 surveys were collected, 17,395 contained free-text comments describing 687 unique providers. The mean overall rating between male (8.84, n = 8558) and female (8.80, n = 8837) providers did not differ (p = 0.149). However, highly-rated male providers were more often described for their agentic qualities using adjectives such as "informative," "forthright," "superior," and "utmost" (OR 1.48, p < 0.01)-whereas highly-rated female providers were more often described by their communal qualities through adjectives such as "empathetic," "sweet," "warm," "attentive," and "approachable" (OR 2.11, p < 0.0001). PES may contain gender stereotypes, raising questions about their impact on physicians and their validity as a quality metric which must be balanced with the need for unedited transparency. Future prospective studies are needed to further characterize this trend across geographically and racially diverse healthcare providers.

Validation of a novel patient-operated device for measuring skin barrier function in atopic dermatitis.

BACKGROUND: Transepidermal water loss (TEWL) and capacitance are used in atopic dermatitis (AD) trials to provide objective data on clinical change and response to therapy. Many barrier devices are costly, limiting their utility. GPSkin is a novel low-cost, patient-operable device that measures both TEWL and capacitance via smartphone application. OBJECTIVE: This validation study investigated the correlation of GPSkin with the AquaFlux and Corneometer, and the reliability of these devices, in patients with AD. METHODS: Fifty AD patients with varying disease severity performed self-measurements with GPSkin, while investigators collected data with all 3 devices, on both nonlesional and lesional skin. CONCLUSION: GPSkin and AquaFlux demonstrated strong correlation for TEWL on nonlesional and lesional skin by Spearman's correlation (rs ), independent of device user. For capacitance, GPSkin and the Corneometer showed moderate correlation when obtained by patients, yet a strong correlation when obtained by a clinician. Despite good correlation, GPSkin showed poor agreement with both the AquaFlux and Corneometer in Bland-Altman plots. GPSkin underestimated both TEWL and capacitance. Overall, the devices had good test-retest reliability. None of the devices could discriminate between AD severity states. While GPSkin marks an exciting advancement in barrier technology, further study is needed for validation on AD skin.

Initial validation of the product of the signs global assessment and body surface area in atopic dermatitis.

BACKGROUND: Current valid instruments that measure the signs of atopic dermatitis in clinical trials may not be suitable for clinical practice because of their complexity. The product of a clinician-derived 5-point signs global assessment and body surface area (SGA × BSA) may represent a simple approach to quickly assess the severity of signs in patients with atopic dermatitis in clinical practice. OBJECTIVES: Evaluate the basic measurement properties of the SGA × BSA. METHODS: Retrospective chart review of patients with atopic dermatitis treated in an outpatient dermatology clinic at Oregon Health & Science University from 2015 to 2018 who had a recorded BSA and SGA. RESULTS: We identified 138 patients completing 325 clinic visits. SGA × BSA demonstrated strong and statistically significant (P < .001) correlations with the Eczema Area and Severity Index (r = 0.91, n = 19), average daily pruritus (r = 0.71, n = 177), patient global assessment (r = 0.74, n = 170), and a derived global scale composed of the average of 4 signs rated between 0 and 3 (r = 0.77, n = 282). Acceptability, responsiveness, and floor or ceiling effects of the measure were deemed adequate. Severity banding was maximized at 1, 21, and 87 (κ = 0.4902). LIMITATIONS: The patient cohort was gathered exclusively from a tertiary care clinic setting in the Pacific Northwest and lacked ethnic diversity. CONCLUSIONS: The results from this study suggest that SGA × BSA is a valid and feasible instrument for atopic dermatitis signs in clinical practice.

Dupilumab-Associated Ocular Surface Disease: Clinical Characteristics, Treatment, and Follow-Up.

PURPOSE: A consecutive case series of patients with dupilumab-associated ocular surface disease (DAOSD) that describes common ocular symptoms and signs, proposes a symptom disease severity grading system, and describes treatment strategies of DAOSD patients was evaluated. METHODS: A retrospective chart review of patients with concomitant dupilumab-treated atopic dermatitis and DAOSD with ophthalmic evaluation between January 2014 and May 2019 was conducted. RESULTS: Twenty-nine patients (mean age 46 years, M/F: 12/17) with 57 ophthalmic exams were identified. The most common ocular symptoms included irritation/pain (n = 28, 97%), redness (n = 24, 83%), pruritus (n = 18, 62%), discharge (n = 18, 62%), and light sensitivity (n = 6, 21%). The most frequent signs included conjunctival injection (n = 18, 62%), superficial punctate keratitis (n = 16, 55%), and papillary reaction (n = 8, 28%). Topical corticosteroids (TCS) (n = 23, 79%), tacrolimus (n = 6, 21%), and artificial tears (n = 7, 24%) were the most commonly used therapies. Of those with follow-up documentation (n = 21), 20 were noted to have partial or complete response with TCS based on symptoms and reduction of signs. Using our proposed symptom-based grading scale, scaled 1 to 5 based on the presence of common symptoms listed above, 66% (n = 19) requiring topical immunomodulating therapy were found in the 'severe' group (≥3 symptoms) and 17% (n = 5) were found in the 'mild' group (≤2 symptoms). CONCLUSIONS: This study provides insight into the commonly presenting ocular signs and symptoms associated with DAOSD and highlights the efficacy of TCS and other immunomodulators in improving symptoms associated with DAOSD. Based on our findings, we propose a symptom-based grading system that can guide nonophthalmic physicians regarding ophthalmology consult.

Adverse cutaneous reactions to chemotherapeutic drugs.

Drug reactions resulting from chemotherapy agents are common and frequently affect the skin. Although often benign, a select few of these cutaneous reactions may necessitate immediate changes to the antineoplastic regimens. Given the diversity of chemotherapeutic skin reactions and their complex implications on patient management, an organized conceptual schema is imperative for proper patient care. We evaluate a number of commonly seen chemotherapy-induced skin toxicities organized by pathogenic mechanism and drug class, providing a framework for the identification and categorization of adverse events to prevent unrecognition. Groupings of these reactions include direct cytotoxicity and/or drug accumulation, immunologic hypersensitivity, and aberrant molecular signaling.

Field Therapy in Solid Organ Transplant Recipients: Are We Initiating Early Enough?

Organ transplant recipients (OTRs) are at increased risk for more aggressive non-melanoma skin cancer (NMSC). Recent emphasis on field therapy has complimented the canonical surgical treatment paradigm. This retrospective analysis of survey responses by patients seen at Oregon Health and Science University from 2013-2018 offers insights into patient trends and practice gaps in caring for OTRs. All patients completed a 57-point questionnaire at their first clinic visit, which included questions regarding demographics, transplant history, dermatologic history, and use of field therapy. Of the 295 patients (mean age, 56 years; M/F: 193/102) who completed the questionnaire, field therapy was reported by 31 (11%) patients. Field therapy patients noted an overall higher AK and SCC burden, with a greater proportion of patients reporting >20 AKs and >10 SCCs. Field therapy use was sparse in the low AK/low SCC group (n=25) when compared to those reporting high AK/high SCC (n=11) burden (n=4 (16%) vs n=8 (73%), P<0.01). This data suggests that OTRs with several clinically evident AKs and/or a low number of SCCs are less likely to have been treated with field therapy modalities compared to OTRs who have developed >10 AKs or ≥6 SCCs. A delay in initiation of preventative measures or field therapy in this population, however, may be a missed opportunity for intervention. Early intervention with field therapy in particularly high-risk OTRs with a low skin cancer burden may mitigate future skin cancer development.J Drugs Dermatol. 2020;19(3): doi:10.36849/JDD.2020.4759.