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.

Dasatinib-Associated Acneiform Eruption Successfully Treated With Sarecycline in a Patient With Chronic Myeloid Leukemia.

Dasatinib is a second-generation tyrosine inhibitor that is used for the treatment of patients with chronic myeloid leukemia (CML). It can cause a myriad of skin toxicities, including pruritis, pigmentary abnormalities of hair and skin, and maculopapular rashes. Rarely, it can be associated with acneiform eruptions, which are typically treated with doxycycline. However, doxycycline may not be an ideal therapy, especially for long-term use, due to the risk of gut flora disruption, antimicrobial resistance, and side effects. We present a case of a CML patient who developed an acneiform eruption associated with dasatinib and was successfully treated with sarecycline, a narrow-spectrum tetracycline. Given its targeted spectrum of activity, sarecycline has a lower risk of antimicrobial resistance and an improved safety profile compared to first- and second-generation tetracyclines such as doxycycline. As acneiform drug eruptions can have a significant impact on a patient's quality of life, effective management by dermatologists is paramount. Sarecycline may be a suitable treatment with a favorable safety profile, making it an appropriate choice for patients, especially those who require long-term therapy.

Outcomes and Follow-Up Data From Two Skin Cancer Screening Events.

This study investigated the outcomes and follow-up behaviors of participants from two free skin cancer screening events in the United States. This survey, with 296 participants and a 31% response rate, gathered information on participant demographics, personal history of skin cancer, knowledge of skin screening practices, and follow-up behaviors. There was a high follow-up rate of 92.3% among individuals recommended for further dermatological consultation, but a low (22%) concordance rate between the preliminary diagnoses from the screening and patient-recalled diagnoses. Additionally, about one-sixth of participants identified limited access to care as a motivation for participating in the screening. The study emphasizes the need to improve awareness about the limitations of free screenings, enhance participant education, and ensure equitable access to skin cancer screening. Future research should focus on factors influencing follow-up behaviors and the development of targeted interventions to increase awareness and access to skin cancer screening.

Dermatologic Manifestations of Neurofibromatosis Type 1 and Emerging Treatments.

Neurofibromatosis type 1 (NF1) is an autosomal dominant tumor predisposition syndrome that increases one's risk for both benign and malignant tumors. NF1 affects every organ in the body, but the most distinctive symptoms that are often the most bothersome to patients are the cutaneous manifestations, which can be unsightly, cause pain or pruritus, and have limited therapeutic options. In an effort to increase awareness of lesser-known dermatologic associations and to promote multidisciplinary care, we conducted a narrative review to shed light on dermatologic associations of NF1 as well as emerging treatment options. Topics covered include cutaneous neurofibromas, plexiform neurofibromas, diffuse neurofibromas, distinct nodular lesions, malignant peripheral nerve sheath tumors, glomus tumors, juvenile xanthogranulomas, skin cancer, and cutaneous T-cell lymphoma.

Sources of exposure and risk among employees infected with severe acute respiratory coronavirus virus 2 (SARS-CoV-2) in a large, urban, tertiary-care hospital in the United States.

Objective: Hospital employees are at risk of SARS-CoV-2 infection through transmission in 3 settings: (1) the community, (2) within the hospital from patient care, and (3) within the hospital from other employees. We evaluated probable sources of infection among hospital employees based on reported exposures before infection. Design: A structured survey was distributed to participants to evaluate presumed COVID-19 exposures (ie, close contacts with people with known or probable COVID-19) and mask usage. Participants were stratified into high, medium, low, and unknown risk categories based on exposure characteristics and personal protective equipment. Setting: Tertiary-care hospital in Boston, Massachusetts. Participants: Hospital employees with a positive SARS-CoV-2 PCR test result between March 2020 and January 2021. During this period, 573 employees tested positive, of whom 187 (31.5%) participated. Results: We did not detect a statistically significant difference in the proportion of employees who reported any exposure (ie, close contacts at any risk level) in the community compared with any exposure in the hospital, from either patients or employees. In total, 131 participants (70.0%) reported no known high-risk exposure (ie, unmasked close contacts) in any setting. Among those who could identify a high-risk exposure, employees were more likely to have had a high-risk exposure in the community than in both hospital settings combined (odds ratio, 1.89; P = .03). Conclusions: Hospital employees experienced exposure risks in both community and hospital settings. Most employees were unable to identify high-risk exposures prior to infection. When respondents identified high-risk exposures, they were more likely to have occurred in the community.

Unique protein signatures evolve during the course of a delayed-type hypersensitivity reaction in human skin.

Diphencyprone (DPCP) is a hapten that causes a delayed-type hypersensitivity reaction when applied topically. It has clinical uses in the treatment of various conditions such as melanoma metastases, warts, and alopecia areata, but the mechanisms are currently not well understood in humans. To further characterize the immunologic effects of DPCP, the authors performed a proteomic analysis of normal skin of eight healthy volunteers following a single application of DPCP and compared them with placebo-treated skin from the same volunteers. A total of 96 proteins were examined using the Olink immuno-oncology panel at 3 days (peak response), 14 days (partially resolved response), and 120 days (completely resolved response). Our analysis revealed significant upregulation of markers of immune cell activation (interleukin [IL] 8), vascular and tissue remodeling (matrix metallopeptidase 12 [MMP12], nitric oxide synthase 3 [NOS3]), antineoplastic markers (granzyme B [GZMB]), and the Th1 axis (interferon gamma [IFNG], chemokine (C-X-C motif) ligand [CXCL] 9, CXCL10, CXCL11) at days 3 and 14 compared with placebo (p < 0.05). In addition, several negative regulators of immune function such as programmed cell death 1 (PD1), programmed cell death ligand 1 (PDL1) (p < 0.001), and lymphocyte activation gene 3 (LAG3) (p < 0.05) were significantly upregulated at days 3 and 14. This induction of negative regulators may explain the seemingly paradoxical therapeutic benefits of DPCP in autoimmune conditions such as alopecia areata. The current analysis also indicated IL-4 upregulation only at day 3, followed by IL-12 upregulation only at day 14, suggesting a transient Th2 response followed by Th1 polarization. Overall, these data suggest a complex and evolving immunological delayed-type hypersensitivity response to a single application of DPCP over time. Future proteomic studies of samples from patients with melanoma metastases, warts, and alopecia areata treated long term with DPCP are needed to further evaluate its pharmacologic mechanisms.

Proteomic profiling of a patient with cutaneous melanoma metastasis regression following topical contact sensitizer diphencyprone and immune checkpoint inhibitor treatment.

Immune checkpoint inhibitors (ICIs) such as pembrolizumab have revolutionized the treatment of advanced melanoma, but many patients do not respond to ICIs alone, and thus there is need for additional treatment options. Topical immunomodulators such as diphencyprone (DPCP) also have clinical use in advanced melanoma, particularly in the treatment of cutaneous metastases. In a previous report, we characterized the enhanced clinical response to dual agent immunotherapy with pembrolizumab and DPCP in a patient with cutaneous melanoma metastases. To improve mechanistic understanding of this response, we analyzed proteomic data using the Olink immuno-oncology panel of 96 biomarkers from tissue and serum samples of this patient throughout his treatment course. Particular attention was paid to programmed death-1 (PD-1), programmed death-ligand 1 (PD-L1), and lymphocyte-activation gene 3 (LAG-3) given they are all targeted by ICIs in clinical practice. These proteins were upregulated during the period of DPCP monotherapy, then downregulated during pembrolizumab monotherapy, and then robustly upregulated again during dual therapy. Although not exclusively, the induction of checkpoint inhibitor proteins in the presence of DPCP suggests potential synergy between this agent and ICIs in the treatment of cutaneous melanoma metastases. Large-scale investigation is warranted to further evaluate this potential novel combination therapeutic approach.