Serpentine supravenous hyperpigmentation induced by chemotherapy: a systematic review.

Serpentine supravenous hyperpigmentation (SSH) describes increased skin pigmentation that develops in the area immediately overlying the vessels through which chemotherapeutic drugs are administered. While SSH can be cosmetically distressing and there are no definitive management options, the literature is severely limited and the variations in clinical presentation, risk factors, and histopathology of SSH across patients are not well understood. We aimed to systematically summarize characteristics from current available data, and thus improve SSH awareness and management. A literature search was conducted in PubMed using specific eligibility criteria through the end of December 2022. Included articles focused on patients who experienced SSH after chemotherapy infusion. Study quality was assessed using a modified Oxford Centre for Evidence-Based Medicine quality rating scheme. Of the 41 articles identified by literature search, 24 met eligibility criteria. Two additional articles were identified through the reference sections of retrieved articles, for 26 articles total. All articles were case reports, representing 28 patients total. Locations of SSH were mostly in the forearm near the site of injection (85%), and the most common associated symptom was erythema. Histopathologic analysis was available for half of cases, the majority of which were inflammatory in nature. The most common inflammatory pattern observed was a vacuolar/lichenoid interface dermatitis. Duration of SSH ranged from days to > 1 year after the chemotherapy was stopped. Six (21%) patients were managed with topical steroids and oral vasodilators, six (21%) patients switched to central venous infusion rather than peripheral infusion, five (18%) patients received only supportive care, three (11%) patients received venous washing with chemotherapy, three (11%) patients stopped chemotherapy, and one (4%) patient reduced the chemotherapy dosage. Ten (36%) patients attained complete resolution, seven (25%) had SSH that was near resolution/fading, and three (11%) had persistent hyperpigmentation. Although SSH often spontaneously resolves once the chemotherapeutic agent is stopped, it can persist in some patients and cause significant distress. As the literature is severely limited and there are no definitive treatments, additional research using more standardized definitions and methods of assessments is necessary to improve characterization of SSH and evaluate potential interventions.

Histopathologic Evolution of Melanocytes Associated With Rapid Clinical Progression of Melanoma: Clinicopathologic Presentation of Hyperprogressive Disease in a Patient Treated With Immunotherapy.

ABSTRACT: This report describes the case of a 71-year-old woman with nodular melanoma who experienced rapid clinical deterioration 3 weeks after receiving immunotherapy treatment. Given this presentation, there was high suspicion for tumor hyperprogression, which has been observed as a paradoxical response to the use of immunotherapy in the treatment of melanoma. Histopathologic and genomic changes of primary tumor are documented at several different timepoints relative to immunotherapy treatment that may depict important alterations associated with hyperprogressive disease. To our knowledge, this case is the first to document the evolution of histopathologic features of melanoma associated with hyperprogressive disease.

Systemic Medications Associated With Hair Texture Changes.

BACKGROUND: In addition to hair loss, alterations in hair texture can be a worrisome side effect of certain medications yet are seldom reported and poorly characterized. OBJECTIVE: To systematically analyze the scientific literature to characterize medication-associated hair texture changes. METHODS: Relevant primary literature within PubMed and Cochrane was reviewed from 1985-2021 including 31 articles (1 randomized controlled trial with texture changes incidentally noted, 6 cohort, 1 cross-sectional, 23 case studies), comprising 2594 patients. RESULTS: Texture changes were associated primarily with antineoplastic agents (n = 97), antiepileptics (n = 56), retinoids (n = 15), immunomodulators (n = 3), and antiretroviral therapy (n = 1). Average age was 48.4 years old (41.2% female). De novo or exaggerated curling patterns were most commonly reported. Average time to texture change varied from 4.5 months (immunomodulators) to 17 months (antiretrovirals). Prognosis was seldom discussed with reversibility noted across all medication classes (n = 17/21; 3 weeks to 5 years post therapy). Irreversible changes were linked with antiretrovirals, retinoids, and antineoplastics. LIMITATIONS: Inability to define true incidence rates, ethnicity, and severity of texture changes due to the nature of available literature. CONCLUSIONS: Hair texture changes are potential side effects of antineoplastics, antiepileptics, retinoids, immunomodulators, and antiretroviral therapy. As these can have associated psychosocial impact, awareness among prescribing physicians is important.J Drugs Dermatol. 2022;21(9):989-996 doi:10.36849/JDD.6852.

Topical therapy for regression and melanoma prevention of congenital giant nevi.

Giant congenital melanocytic nevi are NRAS-driven proliferations that may cover up to 80% of the body surface. Their most dangerous consequence is progression to melanoma. This risk often triggers preemptive extensive surgical excisions in childhood, producing severe lifelong challenges. We have presented preclinical models, including multiple genetically engineered mice and xenografted human lesions, which enabled testing locally applied pharmacologic agents to avoid surgery. The murine models permitted the identification of proliferative versus senescent nevus phases and treatments targeting both. These nevi recapitulated the histologic and molecular features of human giant congenital nevi, including the risk of melanoma transformation. Cutaneously delivered MEK, PI3K, and c-KIT inhibitors or proinflammatory squaric acid dibutylester (SADBE) achieved major regressions. SADBE triggered innate immunity that ablated detectable nevocytes, fully prevented melanoma, and regressed human giant nevus xenografts. These findings reveal nevus mechanistic vulnerabilities and suggest opportunities for topical interventions that may alter the therapeutic options for children with congenital giant nevi.

Implementation and Impact of a Store-and-Forward Teledermatology Platform in an Urban Academic Safety-Net Health Care System.

Background:Minority and low-income patients disproportionately experience dermatologic access challenges. Store-and-forward (SAF) teledermatology has emerged as a model of care delivery that may improve access. We sought to evaluate patterns of utilization and overall impact after SAF teledermatology implementation in a safety-net health care system. Methods:We performed a retrospective review of 3,285 teledermatology consultations from 2014 to 2017 in an urban academic safety-net health care system. Results:A total of 1,680 (51.2%) patients were referred for inflammatory/rash conditions and 967 (29.5%) for skin lesions. The teledermatologist recommended in-person evaluation in 1,199 encounters (36.5%). Median wait time for a subsequent appointment was 36 days (range 0-244 days). Of subsequent in-clinic visits, 237 patients (26.4%) underwent skin biopsy. No-show rate after referral was 11.8%. In comparison, median wait time for dermatology appointment through standard referral was 64 days, with a no-show rate of 18.6%. Biopsy rate of patients referred via teledermatology was 26.4%, in comparison to a rate of 10.9% of patients referred directly from primary care provider. Discussion:Implementation of SAF teledermatology in a safety-net health system resulted in avoidance of 63.5% potential dermatology visits. Consultation typically resulted in a change in suspected diagnosis or management plan. Rates of concordance between teledermatology consults and in-person evaluations were high. Median wait time was reduced by almost half, no-show rate was reduced ∼37%, and biopsy rate was more than double for teledermatology patients compared with standard referral. Conclusion:These findings suggest that SAF teledermatology may improve access to high-quality dermatologic care and increase clinic efficiencies for patients in safety-net health care systems.

Laser Plume From Human Papillomavirus-Infected Tissue: A Systematic Review.

BACKGROUND: Laser procedures are becoming more prevalent across multiple medical specialties for a variety of indications. The plumes created by these lasers have raised concern for the dissemination of an infectious material. OBJECTIVE: To review and summarize the information on viral dissemination in laser plumes available in the literature. MATERIALS AND METHODS: Data Sources A systematic review was performed on English and non-English articles using the PubMed and the Cochrane databases. A manual search of bibliographies from relevant articles was also performed to collect additional studies. STUDY SELECTION: Only articles in the English language with full texts available that pertained to viral particles in laser plumes were included. Data Extraction Two authors performed independent article selections using predefined inclusion and exclusion criteria. RESULTS: There have been case reports of possible transmission of human papillomavirus (HPV) by inhalation of laser-produced aerosols. Multiple investigators have attempted to recreate this scenario in the laboratory to qualify this risk. Others have conducted clinical experiments to determine the presence of HPV in laser plumes. CONCLUSION: The current body of the literature suggests that laser surgeons are at a risk for HPV exposure by inhalation of laser-derived aerosols. We offer best practice recommendations for laser operators.

Hyperpigmentation Due to Cyclosporine Therapy.

For a myriad of immune disorders, cyclosporine has demonstrated marked efficacy in relieving clinical symptoms and reversing pathological developments. We present a case of hyperpigmentation induced by cyclosporine therapy used to treat prurigo nodularis, an extremely rare adverse effect of cyclosporine that has been reported only once, to our knowledge, in the dermatologic literature. After four months of cyclosporine therapy, our patient developed noticeable hyperpigmentation on the dorsal hands and feet and to a lesser degree on her arms and legs. Prior research has discovered a dose-dependent decrease in tyrosinase activity and pigment formation in cultured melanocytes due to cyclosporine - an effect opposite to what was observed in our case. Thus, further study into this relationship is necessary. In essence, physicians should be aware of unwanted cutaneous changes after the initiation of cyclosporine therapy and may want to counsel patients about the importance of ultraviolet (UV) radiation protection.

Management of metastatic melanoma: improved survival in a national cohort following the approvals of checkpoint blockade immunotherapies and targeted therapies.

BACKGROUND: Immune checkpoint blockade (ICB) and BRAFV600-targeted therapy have demonstrated substantial clinical efficacy for patients with stage 4 melanoma in clinical trials; however, their impact on survival and barriers to treatment in the "real-life" setting remains unknown. METHODS: Patients who presented with cutaneous melanoma during 2004-2015 using the National Cancer Database, which comprises > 70% of all newly diagnosed cancers in the U.S., were evaluated for predictors of presenting with stage 4 disease and receiving ICB, and for their associated unadjusted and risk-adjusted overall survival (OS). RESULTS: 17,975 patients presented with stage 4 metastatic cutaneous melanoma. Overall, patients who presented after the FDA's initial approvals (starting in 2011) for ICB and BRAFV600-targeted therapy demonstrated a 31% relative improvement in 4-year OS (p < 0.001), compared to pre-2011. Following the initial approvals in 2011, improved OS was associated in risk-adjusted analyses with ICB (HR 0.57, 95CI 0.52-0.63). ICB demonstrated improved median and 4-year OS of 16.9 months (95CI 15.6-19.3; vs. 7.7 months, 95CI 7.2-8.4) and 32.4% (95CI 29.5-35.3; vs. 21.0%, 95CI 19.6-22.2, all p < 0.001), respectively; improved OS was persistent in unadjusted and risk-adjusted landmark survival analyses. Uninsured patients and management in the community setting were less likely to receive ICB in multivariable analyses. CONCLUSIONS: In a national "real-life" treatment population, we show that the wide availability of the novel treatment modalities ICB and BRAFV600-targeted therapy has significantly improved the survival of patients with stage 4 melanoma. Our findings additionally suggest that there are opportunities for expanding coverage and access to these novel immunotherapies in community practice.

A UV-Independent Topical Small-Molecule Approach for Melanin Production in Human Skin.

The presence of dark melanin (eumelanin) within human epidermis represents one of the strongest predictors of low skin cancer risk. Topical rescue of eumelanin synthesis, previously achieved in "redhaired" Mc1r-deficient mice, demonstrated significant protection against UV damage. However, application of a topical strategy for human skin pigmentation has not been achieved, largely due to the greater barrier function of human epidermis. Salt-inducible kinase (SIK) has been demonstrated to regulate MITF, the master regulator of pigment gene expression, through its effects on CRTC and CREB activity. Here, we describe the development of small-molecule SIK inhibitors that were optimized for human skin penetration, resulting in MITF upregulation and induction of melanogenesis. When topically applied, pigment production was induced in Mc1r-deficient mice and normal human skin. These findings demonstrate a realistic pathway toward UV-independent topical modulation of human skin pigmentation, potentially impacting UV protection and skin cancer risk.

Craniofacial Measurements of Donors and Recipients Correlate with Aesthetic Outcome in Virtual Face Transplantation.

BACKGROUND: Face transplantation is an increasingly feasible option for patients with severe disfigurement. Donors and recipients are currently matched based on immune compatibility, skin characteristics, age, and gender. Aesthetic outcomes of the match are not always optimal and not possible to study in actual cases due to ethical and logistical challenges. We have used a reproducible and inexpensive three-dimensional virtual face transplantation (VFT) model to study this issue. METHODS: Sixty-one VFTs were performed using reconstructed high-resolution computed tomography angiographs of male and female subjects aged 20-69 years. Twenty independent reviewers evaluated the level of disfigurement of the posttransplant models. Absolute differences in 9 soft-tissue measurements and 16 bony cephalometric measurements from each of the VFT donor and recipient pretransplant model pairs were correlated to the reviewers' evaluation of disfigurement after VFT through a multivariate logistic regression model. RESULTS: Five soft-tissue measurements and 3 bony measurements were predictive of the rating of disfigurement after VFT (odds ratio; 95% confidence interval): trichion-to-nasion facial height (1.106; 1.066-1.148), endocanthal width (1.096; 1.051-1.142), exocanthal width (1.067; 1.036-1.099), mouth/chelion width (1.064; 1.019-1.110), subnasale-to-menton facial height (1.029; 1.003-1.056), inner orbit width (1.039; 1.009-1.069), palatal plane/occlusal plane angle (1.148; 1.047-1.258), and sella-nasion/mandibular plane angle (1.079; 1.013-1.150). CONCLUSIONS: This study provides early evidence for the importance of soft-tissue and bony measurements in planning of facial transplantation. With future improvements to immunosuppressive regimens and increased donor availability, these measurements may be used as an additional criterion to optimize posttransplant outcomes.