Reduced-Intensity Conditioning Regimens, Prior Chronic Lymphocytic Leukemia, and Graft-Versus-Host Disease Are Associated with Higher Rates of Skin Cancer after Allogeneic Hematopoietic Stem Cell Transplantation.

To assess incidence and risk factors for skin cancer associated with allogeneic hematopoietic stem cell transplantation, we evaluated 1,974 adult allogeneic hematopoietic stem cell transplantation patients from Beth Israel Deaconess Medical Center and Dana-Farber Cancer Institute who received transplants between January 1995 and July 2013 for hematologic malignancy and survived at least 100 days. Median age was 51.1 years, and median follow-up time was 3 years. Overall, 119 patients had 221 skin cancers. The incidences of squamous cell carcinomas (incidence rate ratio = 9.8; 95% confidence interval = 7.7-12.3), basal cell carcinomas (incidence rate ratio = 2.5; 95% confidence interval = 1.9-3.2), and melanoma (standardized incidence ratio = 3.3; 95% confidence interval = 1.7-5.9) were elevated in our cohort. In multivariable models, risk factors for squamous cell carcinomas were increased age (P < 0.0001), chronic lymphocytic leukemia (P = 0.02), and chronic graft-versus-host disease (P = 0.0002). Risk factors for basal cell carcinomas were chronic lymphocytic leukemia (P = 0.003), reduced-intensity conditioning (P = 0.02), acute graft-versus-host disease (P = 0.03), and chronic graft-versus-host disease (P = 0.003). To our knowledge, previously unreported risk factors in this contemporary cohort include prior CLL for squamous cell carcinoma and basal cell carcinoma and reduced-intensity conditioning for basal cell carcinoma. This study also supports chronic graft-versus-host disease as a risk factor for nonmelanoma skin cancer, particularly squamous cell carcinoma.

Local radiation and phototherapy are the most cost-effective treatments for stage IA mycosis fungoides: A comparative decision analysis model in the United States.

BACKGROUND: Treatments for early-stage mycosis fungoides (MF) include topical steroids, topical nitrogen mustard, topical bexarotene, narrowband ultraviolet B (NBUVB), psoralen plus ultraviolet A (PUVA), and local radiation. The relative cost-effectiveness of each treatment given the differences in treatment failure, disease progression, and therapy escalation is not established. OBJECTIVE: To compare the cost-effectiveness (CE) of treatment options for stage IA MF. METHODS: A state-transition model was constructed with health states of stage IA to stage IV disease, no MF, and death. Treatment-specific remission and relapse rates were obtained from the literature. Lifetime costs were calculated by accounting for medications, office visits, laboratory monitoring, related procedures, work absences, and travel. RESULTS: The order of CE of the study treatments was determined to be as follows: local radiation, $225,399 for 15.40 life-years (LYs); NBUVB, $344,728 for 15.17 LYs; PUVA, $371,741 for 15.07 LYs; topical corticosteroids, $469,354 for 14.65 LYs; topical nitrogen mustard, $951,662 for 14.29 LYs; and topical bexarotene, 11,892,496 for 13.55 LYs. Sensitivity analyses confirmed the CE rankings. LIMITATIONS: We assumed a constant probability of response, relapse rates, and 3-month treatment intervals. CONCLUSIONS: Local radiation is the most cost-effective treatment for limited local disease, whereas phototherapy (NBUVB or PUVA) is cost-effective for generalized disease. Our findings can serve to inform future studies and recommendations regarding selection of therapy for stage IA MF.

Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: Associations, Outcomes, and Pathobiology-Thirty Years of Progress but Still Much to Be Done.

Although rare, Stevens-Johnson syndrome and toxic epidermal necrolysis remain among the most devastating of acute conditions involving the skin. In the past 30 years, tremendous progress has been made in understanding the causes and pathobiology of this often life-threatening condition. Su et al demonstrate associations between IL 15 serum levels and the outcome of patients with Stevens-Johnson syndrome and toxic epidermal necrolysis. Their findings provide ideas for further investigations that may help us better understand the role of cytokines in this T-cell mediate disease and provides clues to possible new therapies.

Risk of serious infections, cutaneous bacterial infections, and granulomatous infections in patients with psoriasis treated with anti-tumor necrosis factor agents versus classic therapies: Prospective meta-analysis of Psonet registries.

BACKGROUND: Anti-tumor necrosis factor (TNF) therapy in psoriasis has been associated with an increased risk of serious infections compared with nonbiologic systemic therapies. OBJECTIVE: We sought to quantify the risk of: (1) serious infections (leading to hospitalization, sequelae, or death); and (2) "any infection," bacterial cutaneous infections, and granulomatous infections among patients receiving anti-TNF therapy compared with nonbiologics (acitretin, methotrexate, cyclosporine). METHODS: We used prospective meta-analysis to combine data from the Psocare registry (Italy), Biobadaderm registry (Spain), and Clalit Health Services database (Israel), including 17,739 patients and 23,357.5 person-years of follow-up. RESULTS: For serious infections, age, gender, and Charlson morbidity index adjusted hazard ratio of exposure to anti-TNFs compared with nonbiologics was 0.98 (95% confidence interval 0.80-1.19), for bacterial cutaneous infections it was 1.00 (95% confidence interval 0.62-1.61), and for granulomatous infections it was 1.23 (95% confidence interval 0.82-1.84). Using methotrexate as comparator and comparing first year of exposure with later exposure did not modify the results. For any infectious episode, risks and relative risks were heterogeneous among registries, probably because of different definitions of outcome. LIMITATIONS: There was lack of power to describe risk of single drugs. CONCLUSION: In current clinical practice, treatment with anti-TNF drugs was not associated with a higher risk of serious infections than treatment with nonbiologic systemic therapy.

Suicidal ideation, mental health problems, and social function in adolescents with eczema: a population-based study.

There are few studies on psychosocial problems in adolescents with eczema. We performed a cross-sectional, questionnaire-based study to explore the relationship of suicidal ideation, mental health problems, and social functioning with eczema. A total of 4,744 adolescents (18-19 years) were invited for the study, of whom 3,775 (80%) participated. The overall prevalence of current eczema was 9.7%. Among those with current eczema, 15.5% reported suicidal ideation compared with 9.1% among those without eczema, significantly associated in a multivariate model (odds ratio 1.87, 95% confidence interval 1.31-2.68). In a subgroup analyses, the prevalence of suicidal ideation in those with both eczema and itch was 23.8%, and was significantly associated, compared with those without eczema (3.57, 2.46-5.67). Eczema was associated with mental health problems assessed by the Strength and Difficulties Questionnaire (1.72, 1.21-2.45) and the Hopkins Symptom Checklist 10 (1.63, 1.23-2.16). Five questions assessed social function: feeling attached to family and friends; thriving at school; experiencing bullying; and romantic relationships. Boys with current eczema were less likely to have had romantic relationships (1.93, 1.21-3.08). Eczema in late adolescence is associated with suicidal ideation and mental health problems but rarely with social problems. Our findings point to the importance of addressing mental health issues in adolescents with eczema.

Telaprevir-related dermatitis.

OBJECTIVE: To evaluate the incidence, type, and severity of telaprevir-associated skin reactions. DESIGN: Three dermatologists assessed available information including photographs, biopsy results, and clinical summaries of all cases with skin eruptions reported as moderate or severe during the telaprevir clinical development program. For cases from placebo-controlled trials, they were masked to exposure. SETTINGS: Phase 1 to 3 studies of telaprevir combination therapy for hepatitis C. PATIENTS: All patients with skin eruptions enrolled in telaprevir clinical trials prior to 2011 MAIN OUTCOME MEASURES: Incidence, diagnosis, morphologic features, extent, and severity of skin eruption. RESULTS: Skin eruptions were more frequent in patients who received telaprevir as part of hepatitis C treatment compared with pegylated interferon (peginterferon) and ribavirin alone (56% vs 34% overall; 3.7% vs 0.4% severe). Occurring at any time during the 12 weeks of telaprevir combination regimen, in more than 90% of cases, this eruption is pruritic eczematous dermatitis. None of the clinical or genetic factors examined were substantial risk factors for dermatitis. Three cases of Stevens-Johnson Syndrome (SJS), and 11 cases of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) were suspected, with 2 SJS and 3 DRESS cases considered likely. CONCLUSIONS: Telaprevir-related dermatitis occurs in a majority of telaprevir-treated patients. It is an eczematous dermatitis that differs in timing and appearance from the eruptions usually associated with drug reactions. The strong signal for an increased risk of DRESS or SJS requires particular vigilance in telaprevir-treated patients.

Cost effectiveness of Mohs micrographic surgery.

Chren's study provides further evidence that for primary facial nonmelanoma skin cancers (NMSCs), recurrence rates with Mohs micrographic surgery (MMS) are modestly better than those for excision surgery. In 20 years, use of MMS has grown ∼10-fold and its cost now exceeds two billion dollars annually. Clinical experience and available data suggest that the skill of the treating physician is at least as important a determinant of outcome as the choice of MMS or excision. As patients and referring physicians increasingly share in the cost of more expensive procedures, evidence-based guidelines that establish the clinical circumstances in which the additional benefits of MMS outweigh its higher cost are needed, still lacking, and unlikely to become available.

Topical tretinoin, another failure in the pursuit of practical chemoprevention for non-melanoma skin cancer.

Given the high incidence of non-melanoma skin cancer (NMSC), a preventative intervention would be desirable. Except for regular sunscreen use, the quest for chemoprevention of NMSC in the general population has been unsuccessful. Weinstock et al. assessed the effects of 0.1% topical tretinoin on NMSC. Like earlier efforts at chemoprevention, this study failed to show therapeutic benefit. Future successful preventative strategies will likely rely on short-term, intermittent therapy or treatments used for other common indications.

The risk of squamous cell and basal cell cancer associated with psoralen and ultraviolet A therapy: a 30-year prospective study.

BACKGROUND: By 1977, psoralen and ultraviolet A (PUVA) was established as a highly effective therapy for psoriasis. Because of concerns about potential long-term adverse effects, particularly cancer, the PUVA Follow-Up Study was established to assess long-term risk and benefits of PUVA. OBJECTIVE: We sought to determine the association of certain squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) risk with exposure to PUVA. METHODS: For nearly 30 years, this prospective cohort study of 1380 patients with psoriasis first treated with PUVA in 1975 to 1976 documented exposures and incident events including biopsy-proven skin cancers. RESULTS: From 1975 to 2005, 351 of 1380 (25%) cohort patients developed 2973 biopsy-proven SCC and 330 (24%) developed 1729 BCCs. After adjusting for age, gender, and significant confounders, the risk of developing one or more SCC in a year was strongly associated with total number of PUVA treatments (350-450 vs <50 treatments, incidence rate ratio [IRR] = 6.01, 95% confidence interval [CI] = 4.41-8.20). When all tumors are included this risk is significantly higher (IRR = 20.92, 95% CI = 14.08-31.08). Corresponding risks for BCC were much lower (person counts IRR = 3.09, 95% CI = 2.36-4.06; tumor counts IRR = 2.12, 95% CI = 1.47-3.05). LIMITATIONS: This was an observational prospective study of a cohort with severe psoriasis. An unknown factor associated with higher dose exposure to PUVA in our cohort that was not included in our analysis could account for the observed associations. CONCLUSION: Exposure to more than 350 PUVA treatments greatly increases the risk of SCC. Exposure to fewer than 150 PUVA treatments has, at most, modest effects on SCC risk. Even high-dose exposure to PUVA does not greatly increase BCC risk. The risks of SCC in long-term PUVA-treated patients should be considered in determining the risk of this therapy relative to other treatments for severe psoriasis.

How epidemiology has contributed to a better understanding of skin disease.

Epidemiology literally means "the study of what is upon the people." It puts the individual's condition in a population context and is the path to disease prevention. In the first part of this review, important aspects of epidemiology are discussed. Fundamentals of epidemiologic research include the measurement of occurrence of an event (prevalence and incidence) and the identification of factors that are associated with this event. The main study designs in observational studies are cohort, case-control, and cross-sectional studies, all of which have intrinsic strengths and limitations. These limitations include a variety of biases, which can be regrouped into selection bias, information bias, and confounding. The STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) checklist is an important tool to further improve the reporting and quality of epidemiologic studies, and it is introduced. In the second part of this review, practical examples are presented, illustrating how dermatoepidemiology has contributed to an improved understanding of skin diseases and patient care, specifically in the case of melanoma therapy, serious cutaneous adverse reactions, Lyme disease, long-term safety of psoralin plus UVA (PUVA), teratogenicity of isotretinoin, and comorbidities in psoriasis.

Long-term use of nonsteroidal anti-inflammatory drugs decreases the risk of cutaneous melanoma: results of a United States case-control study.

Experimental and observational studies continue to demonstrate conflicting results regarding the role of several commonly used drugs as melanoma chemopreventive agents. This case-control study was designed to assess the associations between cutaneous melanoma (CM) and exposure to nonsteroidal anti-inflammatory drugs (NSAIDs) and statins in current users. A total of 400 CM and 600 eligible age- and gender-matched community-based controls were prospectively recruited and interviewed. We assessed participants' demographic characteristics, CM risk factors, and current and previous use of medications. Multivariable conditional logistic regression models were used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for associations between NSAIDs and/or aspirin (ASA), statin exposure, and CM risk. Half of the subjects were men (mean age 60 years). After adjusting for confounders, use of any type of NSAIDs for more than 5 years significantly reduced the risk of melanoma development compared with the low-exposure group (adjusted OR=0.57; 95% CI=0.43-0.77). Subgroup analyses showed that the observed risk reduction was primarily driven by continuous ASA use (>5 years adjusted OR=0.51, 95% CI=0.35-0.75). No significant protective effect was observed with statin exposure (OR=0.97, 95% CI=0.73-1.29). Long-term use of NSAIDs, especially ASA, is associated with a significantly decreased risk of CM development. Clinical intervention studies are warranted to further investigate the potential role of ASA and other NSAIDs as chemopreventive agents for CM.