Melanoma: An update on systemic therapies.

Despite advances in early detection as described in part 1 of this continuing medical education series, melanoma continues to be a large contributor to cutaneous cancer-related mortality. In a subset of patients with unresectable or metastatic disease, surgical clearance is often not possible; therefore, systemic and local therapies are considered. The second article in this series provides dermatologists with an up-to-date working knowledge of the treatment options that may be prescribed by oncologists for patients with unresectable stage III, stage IV, and recurrent melanoma.

Melanoma: How and when to consider clinical diagnostic technologies.

In response to rising rates of melanoma worldwide, novel noninvasive melanoma detection techniques are emerging to facilitate the early detection of melanoma and decrease unnecessary biopsies of benign pigmented lesions. Because they often report similar study findings, it may be difficult to determine how best to incorporate these technologies into clinical practice based on their supporting studies alone. The first article in this continuing medical education series provides practical advice on how and when to use various noninvasive melanoma detection techniques in clinical practice.

Dupilumab Facial Redness/Dupilumab Facial Dermatitis: A Guide for Clinicians.

Dupilumab facial redness (DFR), or the development of an eczematous rash of the face and neck with dupilumab use, has been observed in recent case reports. It is estimated to impact between 4 and 43.8% of dupilumab users, including children and adults. Aside from reviewing the pathogenesis and clinical presentation, we present potential diagnostic steps (such as skin scraping, serologies, biopsy, and patch testing) and management options for DFR ranging from allergen avoidance to dupilumab interruption. It is hoped that this article will serve as a means for clinicians to familiarize themselves with DFR regarding the differential diagnosis, diagnostic tools, and treatment options associated with this phenomenon.

Statins are associated with increased risk of squamous cell carcinoma of the skin: a whole-population study from Iceland.

Statins have been associated with an increased risk of keratinocyte carcinoma but data are limited and conflicting. Statins are hypothesized to contribute to KC through immunomodulation. A whole-population case-control study of the Icelandic population was conducted using the Icelandic Cancer Registry and Icelandic Prescription Medicine Register. These are high-quality registers which include all cancer diagnoses, as well as every prescription in the country. Cases included all first-time histologically confirmed diagnoses of (BCC), in situ squamous cell carcinoma (SCCis) and invasive SCC between 2003 and 2017. Each case was paired with 10 age- and sex-matched controls. Multivariate conditional logistic regression analysis was performed. Four thousand seven hundred patients with BCC, 1167 patients with SCCis and 1013 patients with invasive SCC were identified and paired with 47,292, 11,961 and 10,367 controls, respectively. Overall statin use was associated with an increased risk of invasive SCC and SCCis but not BCC (adjusted OR [95% CI]: 1.29 [1.11-1.50]; 1.43 [1.24-1.64]; 1.03 [0.95-1.12], respectively). Subgroup analysis demonstrated that statins were significantly associated with invasive SCC and SCCis in patients over 60, but not in those under 60. Atorvastatin was only associated with an increased risk of SCCis; whereas, simvastatin was associated with an increased risk of both invasive SCC and SCCis. This whole-population study of Iceland demonstrates that statin exposure is associated with increased risk of SCC, but not BCC, in a low UV environment. The reasons are unclear, but our results may suggest that individuals receiving atorvastatin and simvastatin have differing levels of baseline keratinocyte cancer risk or that properties of a statin other than 'statin intensity' affect association with SCC.

Effects of tobacco and vaping on the skin.

Cigarette and electronic cigarette use are significant public health concerns across the United States. Tobacco use remains the single most preventable cause of morbidity and mortality in the world. Electronic cigarettes initially emerged as a better alternative to conventional cigarettes and for promoting smoking cessation; however, current evidence reveals similar deleterious health implications caused by both products on almost all organ systems, including the skin. Recognition of the cutaneous manifestations associated with cigarette and electronic cigarette use is essential for dermatologists in current clinical practice. Dermatologists play a vital role in educating and counseling patients on smoking cessation. We specifically highlight the cutaneous consequences of conventional cigarette smoking and electronic cigarettes on dermatologic disease.

Metformin is associated with decreased risk of basal cell carcinoma: A whole-population case-control study from Iceland.

BACKGROUND: Metformin has anticarcinogenic properties and is also known to inhibit the sonic hedgehog pathway, but population-based studies analyzing the potential protective effect for basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are needed. OBJECTIVES: To delineate the association between metformin use and invasive SCC, SCC in situ (SCCis), and BCC. METHODS: A population-based case-control study design was employed using all 6880 patients diagnosed in Iceland between 2003-2017 with first-time BCC, SCCis, or invasive SCC, and 69,620 population controls. Multivariate odds ratios (ORs) were calculated using conditional logistic regression. RESULTS: Metformin was associated with a lower risk of developing BCC (OR, 0.71; 95% confidence interval [CI], 0.61-0.83), even at low doses. No increased risk of developing SCC was observed. SCCis risk was mildly elevated in the 501-1500 daily dose unit category (OR, 1.40; 95% CI, 1.00-1.96). LIMITATIONS: This study was retrospective in nature with the inability to adjust for ultraviolet exposure, Fitzpatrick skin type, and comorbidities. CONCLUSION: Metformin is associated with decreased risk of BCC development, even at low doses. Metformin might have potential as a chemoprotective agent for patients at high risk of BCC, although this will need confirmation in future studies.

Association between hydrochlorothiazide and the risk of in situ and invasive squamous cell skin carcinoma and basal cell carcinoma: A population-based case-control study.

BACKGROUND: Population-based studies analyzing hydrochlorothiazide's (HCTZ's) effect on keratinocyte carcinoma, and particularly invasive squamous cell carcinoma (SCC), are lacking. OBJECTIVES: To characterize the association between HCTZ use and invasive SCC, SCC in situ (SCCis), and basal cell carcinoma (BCC). METHODS: This population-based case-control study included all 6880 patients diagnosed with first-time BCC, SCCis, and invasive SCC between 2003 and 2017 in Iceland and 69,620 population controls. Conditional logistic regression analyses were used to calculate multivariate odds ratios (ORs) for keratinocyte carcinoma associated with HCTZ use. RESULTS: A cumulative HCTZ dose above 37,500 mg was associated with increased risk of invasive SCC (OR, 1.69; 95% confidence interval [CI], 1.04-2.74). Users of HCTZ also had an increased risk of SCCis (OR, 1.24; 95% CI, 1.01-1.52) and BCC (OR, 1.14; 95% CI, 1.02-1.29). LIMITATIONS: Limitations include this study's retrospective nature with the resulting inability to adjust for ultraviolet exposure, Fitzpatrick skin type, and comorbidities. CONCLUSIONS: High cumulative exposure to HCTZ is associated with the development of keratinocyte carcinoma and, most importantly, invasive SCC. Sun protective behaviors alone may not eliminate the carcinogenic potential of HCTZ.

Art of prevention: Our approach to the measles-mumps-rubella vaccine in adult patients vaccinated against measles before 1968 on biologic therapy for the treatment of psoriasis.

BACKGROUND: In response to the evolving measles epidemic in the United States, the Centers for Disease Control and Prevention recommended that some adults be revaccinated against measles because they may have inadequate immunity against the virus. Patients receiving biologic medications for psoriasis face a clinical dilemma because they may be at an increased risk of developing severe measles; however, vaccination with the measles-mumps-rubella (MMR) vaccine is not recommended for those on biologic therapy according to the American Academy of Dermatology-National Psoriasis Foundation guidelines. OBJECTIVES: This study aimed to review available research on the safety and efficacy of live-attenuated vaccines in individuals receiving biologic therapy for psoriasis and to discuss our approach to vaccinating individuals on biologic agents for psoriasis with the MMR vaccine. METHODS: A review of the literature was performed via PubMed search. Our institution's anecdotal experiences are also discussed. RESULTS: Data, although limited, are available suggesting that live-attenuated vaccines may be safe for individuals on tumor necrosis factor-alpha inhibitors for psoriasis. Inadequate data are available for patients receiving other biologic medications. CONCLUSION: Providers should engage in shared decision-making to determine whether patients on tumor necrosis factor-alpha inhibitors for psoriasis should receive the MMR vaccine without an interruption in biologic therapy.

Dupilumab as a novel therapy for bullous pemphigoid: A multicenter case series.

BACKGROUND: Bullous pemphigoid (BP) is an autoimmune blistering disorder occurring mostly in the elderly that lacks adequate treatments. OBJECTIVE: To describe our experience using dupilumab in a series of patients with BP. METHODS: This is a case series of patients from 5 academic centers receiving dupilumab for BP. Patients were eligible if they had a clinical diagnosis of BP confirmed by lesional skin biopsy evaluated by one of more of the following: hematoxylin and eosin staining, direct immunofluorescence, or enzyme-linked immunosorbent assay for BP180 or BP230, or both. RESULTS: We identified 13 patients. Patients were an average age of 76.8 years, and the average duration of BP before dupilumab initiation was 28.8 months (range, 1-60 months). Disease clearance or satisfactory response was achieved in 92.3% (12 of 13) of the patients. Satisfactory response was defined as clinician documentation of disease improvement and patient desire to stay on the medication without documentation of disease clearance. Total clearance of the BP was achieved in 53.8% (7of 13) of patients No adverse events were reported. LIMITATIONS: Include small sample size, lack of a control group, lack of a standardized assessment tool, and lack of standardized safety monitoring. CONCLUSION: Dupilumab may be an additional treatment for BP, leading to disease clearance or satisfactory response in 92.3% of patients, including in those in whom previous conventional therapy had failed.

Dermatomyositis: Clinical features and pathogenesis.

Dermatomyositis (DM) is an idiopathic inflammatory myopathy that is clinically heterogeneous and that can be difficult to diagnose. Cutaneous manifestations sometimes vary and may or may not parallel myositis and systemic involvement in time course or severity. Recent developments in our understanding of myositis-specific antibodies have the potential to change the diagnostic landscape of DM for dermatologists. Although phenotypic overlap exists, anti-Mi2, -MDA5, -NXP2, -TIF1, and -SAE antibodies may be correlated with distinct DM subtypes in terms of cutaneous manifestations, systemic involvement, and malignancy risk. This review highlights new findings on the DM-specific myositis-specific antibodies and their clinical associations in both adults and children.

Dermatomyositis: Diagnosis and treatment.

The second article in this continuing medical education series reviews the initial evaluation of patients with suspected dermatomyositis (DM), the relevant work-up for malignancy and interstitial lung disease once a diagnosis of DM is made, and treatment recommendations for patients with DM based on disease severity, the presence of systemic symptoms, and myositis-specific antibody (MSA) profiles. This review emphasizes the emerging role of MSAs in the diagnosis of DM and highlights how MSAs can be used to guide the appropriate work-up for malignancy and interstitial lung disease. The treatment approach proposed by this continuing medical education series discusses both established and novel therapies for DM and highlights the importance of considering lesion type, degree of muscle involvement, presence of systemic symptoms, presence of MSAs, and patient age when determining the best treatment approach for a patient with DM.

Reflectance confocal microscopy to facilitate knifeless skin cancer management.

Management of nonmelanoma skin cancer (NMSC) in elderly patients carries a risk for morbidity; these patients frequently struggle to care for their biopsy sites and experience biopsy- and surgery-related complications. To minimize this treatment-related morbidity, we designed a knifeless treatment approach that employs reflectance confocal microscopy (RCM) in lieu of skin biopsy to establish the diagnosis of NMSC, then uses either intralesional or topical chemotherapy or immunotherapy (as appropriate, depending on depth of invasion) to cure the NMSC. By using this approach, the patient is spared surgery-related difficulties.