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.

Prophage-encoded methyltransferase drives adaptation of community-acquired methicillin-resistant Staphylococcus aureus.

We recently described the evolution of a community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) USA300 variant responsible for an outbreak of skin and soft tissue infections. Acquisition of a mosaic version of the Φ11 prophage (mΦ11) that increases skin abscess size was an early step in CA-MRSA adaptation that primed the successful spread of the clone. The present report shows how prophage mΦ11 exerts its effect on virulence for skin infection without encoding a known toxin or fitness genes. Abscess size and skin inflammation were associated with DNA methylase activity of an mΦ11-encoded adenine methyltransferase (designated pamA). pamA increased expression of fibronectin-binding protein A (fnbA; FnBPA), and inactivation of fnbA eliminated the effect of pamA on abscess virulence without affecting strains lacking pamA. Thus, fnbA is a pamA-specific virulence factor. Mechanistically, pamA was shown to promote biofilm formation in vivo in skin abscesses, a phenotype linked to FnBPA's role in biofilm formation. Collectively, these data reveal a novel mechanism-epigenetic regulation of staphylococcal gene expression-by which phage can regulate virulence to drive adaptive leaps by S. aureus.

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.

Minimizing Bias in Alopecia Diagnosis in Skin of Color Patients.

Alopecia is one of the most common dermatologic conditions affecting black patients, with a significantly negative impact on quality of life.1,2 Timely and accurate diagnosis is therefore critical in order to reverse or halt progression of disease.3 Unfortunately, lack of representation of skin of color (SOC) patients in the current literature may contribute to misdiagnosis as providers may be unfamiliar with the clinical spectrum of alopecia presenting in darker scalps.4 Some scarring alopecia subtypes such as Central Centrifugal Cicatricial Alopecia (CCCA) are more prevalent in certain racial groups. However, focusing solely on patient demographics and gross clinical findings may obscure accurate diagnoses. To distinguish alopecia findings in Black patients, a dedicated approach using a combination of clinical exam findings and patient history, along with trichoscopy and biopsy, is essential to prevent misdiagnosis and improve clinical and diagnostic outcomes. We present three cases of alopecia in patients of color which the initial suspected clinical diagnosis did not correspond with trichoscopic and biopsy results. We challenge clinicians to reexamine their biases and fully evaluate patients of color with alopecia. An examination should include a thorough history, clinical examination, trichoscopy, and potentially a biopsy, particularly when findings do not correlate. Our cases highlight the challenges and disparities that exist in diagnosis of alopecia in Black patients. We emphasize the need for continued research regarding alopecia in skin of color and the importance of a complete workup for alopecia to improve diagnostic outcomes.Balazic E, Axler E, Nwankwo C, et al. Minimizing bias in alopecia diagnosis in skin of color patients. J Drugs Dermatol. 2023;22(7):703-705. doi:10.36849/JDD.7117.  .

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.

Dermatomal Granulomatous Dermatitis and Vasculitis Following Herpes Zoster Ophthalmicus.

Cutaneous granulomatous dermatoses are uncommon sequelae of herpes zoster (HZ) infection that have been documented in the literature, with granulomatous vasculitis described in rare cases. Here, we report a patient with HZ ophthalmicus who developed edematous plaques with central scarring in a V1 dermatomal distribution with histopathological changes of a granulomatous dermatitis including features of granulomatous vasculitis. J Drugs Dermatol. 2022;21(10):1127-1128. oi:10.36849/JDD.6749.

Reversible Hair Loss in Lichen Planopilaris: Regrowth With Low-Dose Naltrexone and Platelet-Rich Plasma.

Lichen planopilaris (LPP) is a cicatricial alopecia that presents with patchy or diffuse hair loss at the vertex or parietal scalp. The literature has limited evidence on treatments for this challenging disease, with most reports involving small groups of patients with varied or suboptimal clinical responses. Amongst individuals who do respond to therapy and eventually achieve disease remission, hair regrowth within scarred alopecic patches is rare.1 Herein, we report a patient with biopsy confirmed LPP who demonstrated remarkable hair regrowth at a previously scarred alopecic patch after initiating low-dose naltrexone (LDN) and platelet-rich plasma (PRP), despite minimal response to 4 months of prior therapy with intralesional corticosteroids, topical clobetasol, topical minoxidil, finasteride, doxycycline, and ketoconazole shampoo. This case highlights the importance of remaining flexible and diligent in therapeutic approaches to LPP and the need for more robust literature on prognosis and treatment options for LPP patients. J Drugs Dermatol. 2022;21(6):671-673. doi:10.36849/JDD.6810.

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.

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.