A Review of the Impact of Sun Safety Interventions in Children.

INTRODUCTION: In the United States, melanoma and non-melanoma skin cancers comprise the largest proportion of new cancer diagnoses every year. The prevalence of skin cancer can be largely reduced if proper preventative behaviors are adopted at an early age. OBJECTIVES: We assessed the impact of various informational, economic, and environmental interventions on sun-protective behaviors, knowledge, attitudes, and sun exposure in the pediatric population reported in previous studies. METHODS: A systematic search for relevant articles was conducted using three databases. Studies were included if they met the following three criteria: study subjects less than 18 years old, clear, measurable interventions and outcomes, and publication in the English language. RESULTS: A total of 66 studies were included, of which 48 resulted in positive behavioral changes (i.e. increases in sunscreen application, use of hats and sun-protective clothing, shade-seeking, and avoidance of outdoor activities during peak UV radiation), 28 resulted in increased knowledge, 2 resulted in changes in attitudes towards tanning, and 10 resulted in decreased sun exposure effects (i.e. new sunburns, number of new nevi, and change in pigmentation of the skin). CONCLUSIONS: It is crucial that children be educated on the importance and benefits of sun protection. Although a variety of interventions showed promise in achieving this goal, the challenges associated with adopting change were evident. This review provides direction for future interventions aimed at improving sun safety in children and illustrates the potential impact that early intervention can have on the incidence of skin cancer in future generations.

Phytophotodermatitis due to a Citrus-Based Hand Sanitizer: A Case Report.

Phytophotodermatitis, a cutaneous reaction caused by direct contact with photosensitive substances in plants and subsequent exposure to ultraviolet light, is commonly caused by psoralens in plants, including citrus fruits. We describe a case of phytophotodermatitis caused by a hand sanitizer containing a blood orange (Citrus sinensis) extract. To our knowledge, this is the first reported case of phytophotodermatitis caused by a hand sanitizer. A 41-year-old woman presented with a 2-week history of pruritic cutaneous eruptions on her right thigh. Approximately 24 hours prior to the onset of her symptoms, she applied a new citrus-based hand sanitizer. Immediately after applying the hand sanitizer, her right thigh was exposed to sunlight for approximately 5 hours. Extracts from oranges are used in many cosmetics, including perfumes and fragrances. With the increased use of hand sanitizers during the coronavirus disease 2019 pandemic, physicians should note that phytophotodermatitis due to scented hand sanitizers may occur more frequently.

Cutaneous adverse events in 155 patients with metastatic melanoma consecutively treated with anti-CTLA4 and anti-PD1 combination immunotherapy: Incidence, management, and clinical benefit.

BACKGROUND: In response to the increased use of combination checkpoint inhibitors (CPIs) and the resulting increased cutaneous adverse events (CAEs), this study reviewed patients with melanoma treated with combination CPIs to characterize CAE features and their clinical impact, correlation to adverse events in other organs, and correlation to tumor response. METHODS: Patients from the authors' institutional database who received at least 1 dose of ipilimumab in combination with either nivolumab or pembrolizumab between January 1, 2012, and December 31, 2017, for stage IV or unresectable stage III melanoma were identified. The time to next treatment (TTNT) was calculated from the start of CPI therapy to the start of the next treatment or death, and the development of CAEs was tested in a time-dependent Cox regression to identify associations with TTNT. RESULTS: Eighty-one patients (52.3%) experienced a total of 92 CAEs, including eczematous dermatitis (25.0%), morbilliform eruption (22.8%), vitiligo (12.0%), and pruritus without rash (8.7%). The median times to the onset and resolution of CAEs were 21 days (range, 0-341 days) and 50 days (range, 1-352 days), respectively. Most CAEs resolved after patients entered the CPI maintenance phase and treatment with oral antihistamines with or without topical steroids. CPI discontinuation occurred in 4 patients (2.6%) because of CAEs, in 49 (31.6%) because of other immune-related adverse events, and in 20 (12.9%) because of melanoma progression or death. For patients definitively treated with CPIs (n = 134; 86.5%), TTNT was significantly longer with CAEs than without CAEs (hazard ratio, 0.567; 95% CI, 0.331-0.972; P = .039). CONCLUSIONS: CAEs were mostly reversible and rarely required therapy discontinuation. The development of CAEs was associated with a longer TTNT, and this suggested a possible clinical benefit.

Cutaneous Toxicities in the Setting of Immune Checkpoint Blockade:: The Era of Oncodermatopathology.

Advancements in cancer therapy with monoclonal immune checkpoint antibody blockade have impacted the practice of all medical specialties. Cutaneous immune-related adverse events (irAEs) are a frequent, unintended, off-target consequence of immune checkpoint inhibitor (ICI) therapy that have ushered in the era of oncodermatopathology. Knowledge of the diverse morphologic types of cutaneous irAEs from ICI therapy allows further classification of cutaneous irAEs according to major histopathologic reaction patterns. Early studies suggest that immune mechanisms of lichenoid dermatitis irAE, psoriasiform dermatitis irAE, and bullous pemphigoid irAE show some similarities and differences from their histopathologic counterparts not associated with ICI therapy.

Cutaneous Effects of Notch Inhibitor Therapy: A Report of Two Cases.

As aberrant Notch signaling has been linked to cancerous growth, Notch inhibitors represent a novel category of targeted oncological therapy. Notch pathways in tumor cells may contribute to proliferation or limit apoptosis and differentiation. Healthy skin differentiation and homeostasis are reliant on normal Notch expression, and disruption of this signaling has been implicated in dermatological conditions such as hidradenitis suppurativa, psoriasis, atopic dermatitis, and lichen planus. Here, we describe two cases of patients with cutaneous side effects from Notch inhibitor treatment for adenoid cyst carcinoma (ACC) and review the role of Notch signaling in skin disease. By illuminating connections between medication side effects and disease pathogenesis, our goal is to increase awareness of the cutaneous side effects of Notch inhibitor treatment.

Vancomycin-induced linear IgA bullous dermatosis.

Adverse medication side effects are not uncommon in the inpatient setting, where polypharmacy is the norm. Linear IgA bullous dermatosis (LABD) can be a cutaneous side effect of commonly used inpatient medications, such as vancomycin. Symptoms of LABD can be severe, and proper recognition of this drug-induced disease is important to ensuring proper treatment, including the removal of the inciting agent. This report describes a case of vancomycin-associated LABD in a 66-year-old man and the proper management of drug-induced LABD.

Dermatomyositis, pembrolizumab, and squamous cell carcinoma of the lung.

Cancer immunotherapy has impacted the treatment of numerous tumor types, including skin, lung, and colon cancers. Immune checkpoint inhibitors (ICI) activate the immune system to attack cancer cells, but this mechanism can also impact healthy cells. Dermatomyositis, an autoimmune syndrome affecting multiple organ systems, is often associated with cancer as a paraneoplastic syndrome, but this syndrome can also be induced by ICI. Here, we describe a case of dermatomyositis in a patient receiving pembrolizumab for treatment of squamous cell carcinoma of the lung and discuss the importance of recognizing complications of ICI.

Anti-CTLA-4 therapy-associated granuloma annulare in chronic myelomonocytic leukemia.

Immune checkpoint inhibitor (ICI) therapies activate the immune system to unmask cancer cells that the body might otherwise not detect. These cancer therapies alter the immune system at different "checkpoint" proteins such as PD-1, PD-L1, or CTLA-4 to better target tumor cells, but also have the potential to affect normal tissues. In patients receiving ICI therapy, cutaneous reactions have been frequently documented, ranging from mild urticarial rashes to widespread cutaneous necrosis. Proper identification and management of ICI therapy side effects is essential to the care of these patients. Here, we present an unusual granulomatous cutaneous reaction in a patient receiving anti-CTLA-4 therapy for chronic myelomonocytic leukemia.

Pyoderma gangrenosum-like ulceration of the lower extremity secondary to sunitinib therapy: a case report.

Sunitinib is a multi-targeted receptor tyrosine kinase inhibitor used for the treatment of multiple different types of malignancies. Serious grade 3-4 adverse events occur in <10% of the patient population and usually improve with dose reduction. One of the more rarely reported side effects of sunitinib therapy is the development of pyoderma gangrenosum-like ulcerations in the lower extremities. These pyoderma gangrenosum-like ulcerations are difficult to treat and distinguish from similar-appearing dermatological diagnoses. We present a patient with refractory lung carcinoma and a past medical history of squamous cell carcinoma of the lower extremity, who developed a non-healing ulceration at the previous site of her skin cancer while undergoing therapy with sunitinib. At the time of the initial evaluation, the ulceration mimicked recurrent squamous cell carcinoma, posing a diagnostic challenge. Histopathological findings showed epidermal hyperplasia, ulceration, and dense acute inflammation. Despite meticulous wound care and treatment of infection, the ulcer only improved with cessation of sunitinib.

Leukocytoclastic vasculitis with late-onset Henoch-Schönlein purpura after trifluridine/tipiracil treatment.

Trifluridine/tipiracil has been approved for the treatment of refractory metastatic colorectal cancer. Adverse effects of this drug combination include leukopenia, neutropenia, fatigue, diarrhea, and vomiting. We present a case of trifluridine/tipiracil-induced leukocytoclastic vasculitis (LCV) with late-onset Henoch-Schönlein purpura (HSP) in a 42-year-old man with metastatic appendiceal cancer. The patient's biopsy-proven LCV developed one month after he began trifluridine/tipiracil treatment and resolved after discontinuation of the drug. He presented to the emergency department two months after the appearance of his LCV with shortness of breath, elevated blood pressure, elevated creatinine, hematuria, and proteinuria. A kidney biopsy was performed and the presence of IgA deposits and cellular crescents indicated rapidly progressive glomerulonephritis secondary to Henoch-Schönlein purpura (HSP). Neither LCV nor HSP have been reported as adverse effects of trifluridine/tipiracil treatment. Malignancy as a cause of our patient's HSP is another possibility. The delay between our patient's skin findings and acute renal failure indicates that suspected HSP should be monitored by urinalysis for a period of time owing to the risk of life-threatening renal disease.

Lichenoid Dermatologic Toxicity From Immune Checkpoint Blockade Therapy: A Detailed Examination of the Clinicopathologic Features.

Immunotherapy targeting the programmed cell death 1 (PD-1) receptor has demonstrated tremendous promise in the treatment of advanced solid tumors. Dermatologic toxicities, however, are an emerging consequence of this therapy and have been clearly associated with immune checkpoint blockade antibodies. Distinctive clinical and histologic subtypes of dermatologic toxicity secondary to immunotherapy are emerging and include rare autoimmune bullous reactions (eg, bullous pemphigoid) and lichenoid eruptions. We report three patients who developed lichenoid dermatitis while receiving anti-PD-1 antibody therapy. The mean time to onset of lichenoid dermatologic toxicity was 42 days (range: 1-75 days) from initiation of anti-PD-1 antibody therapy. Lesions most frequently presented on the extremities and trunk as pustules, papules, and plaques. The face was not commonly involved. Of the five skin biopsies examined, all demonstrated dense band-like lymphocytic infiltrate, hyperkeratosis, hypergranulosis, saw-tooth rete ridge pattern, and dyskeratosis. Acanthosis was a feature in all of the skin biopsies, and in one, epidermal hyperplasia was prominent. In several skin biopsies, histologic features supporting a lichenoid drug eruption were present, including parakeratosis, spongiosis, periadnexal/perivascular inflammation, and eosinophils. Furthermore, the histologic features varied in skin biopsy specimens taken from the same patient at different sites, supporting a drug reaction. All patients' skin lesions improved with use of steroids: two were treated with topical steroids and one with systemic steroids. Recognition of the histopathologic patterns of dermatologic toxicities resulting from immune checkpoint blockade therapy will become increasingly important for ensuring appropriate management of dermatologic toxicities and optimal patient care.

Generalized eruptive histiocytosis associated with a novel fusion in LMNA-NTRK1.

Non-Langerhans cell histiocytosis (NLCH) is a histiocyte disorder comprised of dermal dendritic histiocytes with a characteristic staining pattern. Erdheim-Chester disease (ECD) is a subset of NLCH in which patients experience bone pain with corresponding changes on imaging. In addition, these patients show other evidence of systemic involvement, which can also be identified with imaging. This disease can occasionally present with cutaneous findings. We present a case of generalized eruptive histiocytosis (GEH), misdiagnosed as ECD, found to have an NTRK1 gene rearrangement. This is the first report of an NTRK1 kinase fusion with NLCH. The implication is unclear and further studies are warranted.

The antimicrobial peptide LL37 is a T-cell autoantigen in psoriasis.

Psoriasis is a common T-cell-mediated skin disease with 2-3% prevalence worldwide. Psoriasis is considered to be an autoimmune disease, but the precise nature of the autoantigens triggering T-cell activation remains poorly understood. Here we find that two-thirds of patients with moderate-to-severe plaque psoriasis harbour CD4(+) and/or CD8(+) T cells specific for LL37, an antimicrobial peptide (AMP) overexpressed in psoriatic skin and reported to trigger activation of innate immune cells. LL37-specific T cells produce IFN-γ, and CD4(+) T cells also produce Th17 cytokines. LL37-specific T cells can infiltrate lesional skin and may be tracked in patients blood by tetramers staining. Presence of circulating LL37-specific T cells correlates significantly with disease activity, suggesting a contribution to disease pathogenesis. Thus, we uncover a role of LL37 as a T-cell autoantigen in psoriasis and provide evidence for a role of AMPs in both innate and adaptive immune cell activation.