Case report: Regression of in-transit metastases of cutaneous squamous cell carcinoma with combination pembrolizumab and topical diphencyprone.

While typically low-risk, cutaneous squamous cell carcinoma (cSCC) can infrequently progress to metastatic disease with in-transit lesions, localized to the dermis or subcutaneous tissue between the primary tumor and draining regional lymph nodes. These lesions are associated with poor prognostic values, including decreased survival rates and increased risk of recurrence. We present the case of a 75-year-old male with cSCC and in-transit metastases on his scalp treated with the immune checkpoint inhibitor (ICI) pembrolizumab in conjunction with diphencyprone (DPCP), a topical hapten that induces a delayed-type hypersensitivity reaction in the skin. The patient was enrolled in a clinical trial (NCT05481658) that involved the twice-weekly application of DPCP 0.04% ointment to four of the in-transit metastases on his frontal scalp, concurrent with pembrolizumab 300 mg administered every three weeks. Following effective sensitization and a twelve-week treatment course, complete clearance of all lesions, DPCP-treated and non-DPCP treated, was achieved, with no adverse events. The immunologic profiles of the post-treatment biopsies were analyzed by TaqMan Low Density Array quantitative real-time polymerase chain reaction to measure immune marker gene expression. Relative to the non-DPCP-treated lesion, the DPCP-treated lesion demonstrated increased pro-inflammatory genetic markers and T-cell activation. This case represents the first reported instance of in-transit metastases of cSCC successfully treated with DPCP and an ICI. It highlights the potential safety and efficacy of DPCP with systemic immunotherapy for the management of in-transit metastases of cSCC in patients for whom surgery and radiation may be contraindicated.

Trends in Accuracy and Appropriateness of Alopecia Areata Information Obtained from a Popular Online Large Language Model, ChatGPT.

BACKGROUND: Patients with alopecia areata (AA) may access a wide range of sources for information about AA, including the recently developed ChatGPT. Assessing the quality of health information provided by these sources is crucial, as patients are utilizing them in increasing numbers. OBJECTIVES: The aim of the study was to evaluate appropriateness and accuracy of responses to common patient questions about AA generated by ChatGPT. METHODS: Responses generated by ChatGPT 3.5 and ChatGPT 4.0 to 25 questions addressing common patient concerns were assessed by multiple attending dermatologists in an academic center for appropriateness and accuracy. Appropriateness of responses by both models for use in two hypothetical contexts as follows: (1) for patient-facing general information websites, and (2) for electronic health record (EHR) message drafts. RESULTS: The accuracy across all responses was 4.41 out of 5. Accuracy scores of responses ChatGPT 3.5 responses had a mean of 4.29, whereas those generated by ChatGPT 4.0 had mean accuracy score of 4.53. Assessments ranged from 100% of responses rated as appropriate for the general question category to 79% questions about management for an EHR message draft. Raters largely preferred responses generated by ChatGPT 4.0 versus ChatGPT 3.5. Reviewer agreement was found to be moderate across all questions, with a 53.7% agreement and Fleiss' κ co-efficient of 0.522 (p value <0.001). CONCLUSIONS: The large language model ChatGPT outputted mostly appropriate information for common patient concerns. While not all responses were accurate, the trend toward improvement with newer iterations suggests potential future utility for patients and dermatologists.

Pruritic Rash in a Woman With Endometrial Cancer.

A woman in her 60s presents with a pruritic rash that initially developed on the legs and progressed to her feet, arms, hands, and trunk, with associated symptoms of a burning sensation and occasional pain. What is your diagnosis?

Diagnostic work-up and treatment in patients with pyoderma gangrenosum: retrospective analysis of US insurance claims-based data.

Pyoderma gangrenosum (PG) is a rare, and often challenging to diagnose, inflammatory disorder with relatively high rates of morbidity and mortality. Central to the diagnosis of PG is histologic evaluation and exclusion of other entities. Large-scale studies investigating the proportion of patients receiving a thorough diagnostic work-up, as well as prevalence studies regarding comorbidities and systemic treatment in PG using claims-based data, are sparse. Our objective was to identify patients diagnosed with PG and describe the diagnostic work-up and prevalence of common comorbidities and therapies in this population using claims-based data in a retrospective cohort study. In order to better understand practices of diagnostic work-up, we captured rates of skin biopsy, tissue culture, and/or surgical debridement prior to initial diagnosis. We also identified the prevalence of PG-associated comorbidities and initial immunosuppressive therapy given for PG. Of the 565 patients diagnosed with PG, 9.4% underwent skin biopsy, 8% tissue culture, and 1.4% both skin biopsy AND tissue culture prior to diagnosis. Inflammatory bowel disease was the most prevalent comorbidity (16.3%). The most common treatment administered was systemic corticosteroids (17%). Although practice guidelines explicitly delineate histology and exclusion of infection as important diagnostic criteria, only a minority of patients in this study underwent skin biopsy and/or tissue culture prior to receiving a diagnosis of PG, suggesting that patients may receive a diagnosis of PG without having tissue evaluation. Such discordance between practice guidelines and "real-world" practice inevitably increases the risk for misdiagnosis of PG and misdirected treatment with immunosuppressants for presumptive PG in cases of PG mimickers. Moreover, comorbidities associated with PG may occur, or be identified in, a lower proportion of patients as compared with what is reported in the existing literature. Study limitations include a population restricted to < 65 years with commercial insurance and the reliance upon ICD diagnostic coding to capture the population.

Eosinophil-rich linear IgA bullous dermatosis induced by mRNA COVID-19 booster vaccine.

We present a case of eosinophil-rich linear IgA bullous disease (LABD) following the administration of a messenger RNA COVID-19 booster vaccine. A 66-year-old man presented to the emergency department with a 3-week history of a pruritic blistering rash characterized by fluid-filled bullae and multiple annular and polycyclic plaques. He was initially diagnosed with bullous pemphigoid based on a biopsy showing a subepidermal blister with numerous eosinophils. However, direct immunofluorescence studies showed linear IgA and IgM deposition along the basement membrane zone with no immunoreactivity for C3 or IgG. Additionally, indirect immunofluorescence was positive for IgA basement membrane zone antibody. The patient was subsequently diagnosed with LABD and initiated on dapsone therapy with resolution of his lesions at 3-month follow-up. This case illustrates the growing number of autoimmune blistering adverse cutaneous reactions from vaccination. Dermatopathologists should be aware that features of autoimmune blistering diseases can overlap and may not be distinguishable based on these histopathological findings alone. Confirmation with direct immunofluorescence and/or serological studies may be necessary for accurate diagnosis.

Clinical and histopathological spectrum of delayed adverse cutaneous reactions following COVID-19 vaccination.

BACKGROUND: As more people become vaccinated against the SARS-CoV-2 virus, reports of delayed cutaneous hypersensitivity reactions are beginning to emerge. METHODS: In this IRB-approved retrospective case series, biopsy specimens of potential cutaneous adverse reactions from the Pfizer-BioNTech or Moderna mRNA vaccine were identified and reviewed. Clinical information was obtained through the requisition form, referring clinician, or medical chart review. RESULTS: Twelve cases were included. Histopathological features from two injection-site reactions showed a mixed-cell infiltrate with eosinophils and a spongiotic dermatitis with eosinophils. Three biopsy specimens came from generalized eruptions that showed interface changes consistent with an exanthematous drug reaction. Three biopsy specimens revealed a predominantly spongiotic pattern, consistent with eczematous dermatitis. Small-vessel vascular injury was seen in two specimens, which were diagnosed as urticarial vasculitis and leukocytoclastic vasculitis, respectively. There were two cases of new-onset bullous pemphigoid supported by histopathological examination and direct immunofluorescence studies. Eosinophils were seen in 10 cases. CONCLUSIONS: Dermatopathologists should be aware of potential cutaneous adverse reactions to mRNA-based COVID-19 vaccines. Histopathological patterns include mixed-cell infiltrates, epidermal spongiosis, and interface changes. Eosinophils are a common finding but are not always present. Direct immunofluorescence studies may be helpful for immune-mediated cutaneous presentations such as vasculitis or bullous pemphigoid.

Assessing Patient Satisfaction with Live-Interactive Teledermatology Visits During the COVID-19 Pandemic: A Survey Study.

Introduction: Coronavirus disease 2019 (COVID-19) has brought teledermatology to the forefront. Understanding patients' experiences will clarify its benefits and limitations. Materials and Methods: Patients evaluated through live-interactive teledermatology at New York University Langone Health March-June 2020 were surveyed. Patient demographics, satisfaction with, and preferences between teledermatology and in-person visits across four domains (visit preparation, provider communication, physical examination, and treatment plan/follow-up) were collected. Results/Discussion: Of 602 respondents, >70% indicated at least equal satisfaction compared with in-person visits across all domains. More than a quarter of patients were dissatisfied with the virtual examination and more than half preferred in-person examinations. Male gender was associated with treatment plan/follow-up satisfaction (p = 0.03). Patients ≥66 years preferred in-person visit preparation, communication, and treatment plan/follow-up (all p < 0.01). New patients were less satisfied with teledermatology communication (p = 0.02) and treatment plan/follow-up (p < 0.01) but preferred teledermatology visit preparation (p = 0.01). Conclusions: Patients were satisfied with live-interactive teledermatology during the COVID-19 pandemic, although preferred in-person physical examinations. Satisfaction and preferences varied between patient populations.

Deep Learning and Pathomics Analyses Reveal Cell Nuclei as Important Features for Mutation Prediction of BRAF-Mutated Melanomas.

Image-based analysis as a method for mutation detection can be advantageous in settings when tumor tissue is limited or unavailable for direct testing. In this study, we utilize two distinct and complementary machine-learning methods of analyzing whole-slide images for predicting mutated BRAF. In the first method, whole-slide images of melanomas from 256 patients were used to train a deep convolutional neural network to develop a fully automated model that first selects for tumor-rich areas (area under the curve = 0.96) and then predicts for mutated BRAF (area under the curve = 0.71). Saliency mapping was performed and revealed that pixels corresponding to nuclei were the most relevant to network learning. In the second method, whole-slide images were analyzed using a pathomics pipeline that first annotates nuclei and then quantifies nuclear features, showing that mutated BRAF nuclei were significantly larger and rounder than BRAF‒wild-type nuclei. Finally, we developed a model that combines clinical information, deep learning, and pathomics that improves the predictive performance for mutated BRAF to an area under the curve of 0.89. Not only does this provide additional insights on how BRAF mutations affect tumor structural characteristics, but machine learning‒based analysis of whole-slide images also has the potential to be integrated into higher-order models for understanding tumor biology.

Revisiting Solitary Pedunculated Lipofibromas.

OBJECTIVES: Pedunculated lipofibromas are soft, compressible, skin-colored nodules that typically present as an acquired solitary lesion, predominantly located on the buttocks and thighs. We aimed to differentiate between pedunculated lipofibromas and nevus lipomatosus superficialis. Although benign, this may be important as treatment options vary. METHODS: We describe 3 cases of solitary pedunculated lipofibromas occurring in older, obese adults that required clinicopathologic correlation for the correct diagnosis. RESULTS: The histopathologic features of pedunculated lipofibromas include a broad-based lesion with aggregates of mature adipocytes extending upwards into the dermis without an associated inflammatory infiltrate. The primary histopathologic differential diagnoses include fibroepithelial polyps with adipocytes and nevus lipomatosus superficialis, which is more frequently found in children or young adults and is typically characterized clinically by multiple lesions with a cerebriform to verrucoid surface. CONCLUSIONS: While the precise relationship between pedunculated lipofibromas and nevus lipomatosus is still unknown, we propose using pedunculated lipofibroma as a more specific clinical term to refer to solitary pedunculated or broad-based fatty lesions with a smooth surface that occur in older patients and in a wide anatomic distribution.

Psychiatric disorders and suicidal behavior in patients with acne prescribed oral antibiotics versus isotretinoin: Analysis of a large commercial insurance claims database.

BACKGROUND: The association between isotretinoin and psychiatric disturbance, including depression and suicidal behavior, is controversial. OBJECTIVE: To investigate whether acne patients prescribed isotretinoin or antibiotics were more likely to have psychiatric disorders and/or engage in suicidal behavior. METHODS: Retrospective cohort study using the IBM MarketScan Research Databases, which contain commercial insurance claims in the United States, to identify acne patients who were prescribed isotretinoin or oral antibiotics between 2011 and 2017 and who were diagnosed with psychiatric disorders or suicidal behavior. RESULTS: A total of 72,555 patients were included in the study. Patients in the general population were 1.47 times more likely to be diagnosed with suicidal ideation or attempt compared to acne patients prescribed isotretinoin (adjusted odds ratio [OR] 1.47; confidence interval [95% CI], 1.27, 1.70; P < .0001). The general population (adjusted OR 0.87; 95% CI, 0.84, 0.89; P < .0001) and acne patients prescribed antibiotics (adjusted OR 0.88; 95% CI, 0.85, 0.91; P < .0001) were less likely to have a psychiatric diagnosis compared to acne patients prescribed isotretinoin. The prevalence of suicidal behavior during isotretinoin treatment was lower (0.10%; P = .082) than in the year prior to isotretinoin treatment (0.22%) and in the year following treatment (0.34%; P = .004). LIMITATIONS: The study excluded individuals with public insurance and those who were uninsured, and the data in the study relied on the accuracy of the medical coding. CONCLUSIONS: Compared to the general population, acne patients prescribed isotretinoin were less likely to engage in suicidal behavior. Further exploration into the slight increase in suicidal behavior seen in isotretinoin patients 1 year after therapy is warranted.