Effect of Topical Fluorouracil Cream on Photodamage: Secondary Analysis of a Randomized Clinical Trial.

Importance: Photoaging, which is premature skin aging caused by long-term UV exposure, is of aesthetic concern to many patients. Objective: To investigate the effect of topical fluorouracil, 5%, cream on photoaging using validated photonumeric scales. Design, Setting, and Participants: The Veterans Affairs Keratinocyte Carcinoma Chemoprevention Trial was a randomized clinical trial of 932 US veterans with a recent history of 2 or more keratinocyte carcinomas performed from September 30, 2011, through June 30, 2014, to assess the chemopreventive effects of a standard course of topical fluorouracil. Photographs were taken at baseline and at numerous time points for up to 4 years. In our secondary analysis, 2 independent dermatologists graded these photographs using 4 validated photonumeric scales. A total of 3042 photographs from 281 participants randomized to apply topical fluorouracil or placebo were evaluated at baseline, 6 months, 12 months, and 18 months using 4 photonumeric scales (Griffiths scale, Allergan forehead lines scale, melomental folds scale, and crow's feet scale). Data analysis was performed from November 1, 2016, to January 1, 2017. Interventions: Participants were randomized to apply topical fluorouracil, 5%, cream or a vehicle control cream to the face and ears twice daily for 2 to 4 weeks for a total of 28 to 56 doses. Main Outcomes and Measures: Effect of a standard course of fluorouracil on the extent of photodamage as measured using 4 photonumeric scales. Results: The study population was predominantly male (274 [97.5%]) and white (281 [100%]), with a mean (SD) age of 71.5 (0.57) years. No statistically significant changes were found in photodamage between baseline and 6 months (Griffiths scale: χ2 = 0.01, P = .93; Allergan forehead lines scale: χ2 = 0.18, P = .67; melomental fold scale: χ2 = 0.03, P = .87; crow's feet scale: χ2 = 2.41, P = .12), 12 months (Griffiths scale: χ2 = 1.39, P = .24; Allergan forehead lines scale: χ2 = 0.64, P = .43; melomental fold scale: χ2 = 0.12, P = .73; crow's feet scale: χ2 = 1.07, P = .30), and 18 months (Griffiths scale: χ2 = 3.11, P = .08; Allergan forehead lines scale: χ2 = 0.89, P = .34; melomental fold scale: χ2 = 1.64, P = .20; crow's feet scale: χ2 = 0.46, P = .50). Conclusions and Relevance: This study did not demonstrate improvement in photoaging with a standard course of topical fluorouracil, 5%, cream, a finding that may be attributable to a true lack of effect in photodamage or limitations of the photonumeric scales in capturing the effect. The development of photonumeric scales that include manifestations of photoaging other than rhytids, such as lentigines, hyperpigmentation, and telangiectasias, should be considered. Trial Registration: clinicaltrials.gov Identifier: NCT00847912.

Validation of Photograph-Based Toxicity Score for Topical 5-Fluorouracil Cream Application.

BACKGROUND: An objective tool quantifying the toxicity of 5-fluorouracil (5-FU) from photographs was recently reported, and its reliability was confirmed. OBJECTIVE: The aim of this study was to validate the photograph-based toxicity score. METHODS: Photograph-based toxicity scores of participants assigned to the 5-FU arm of a randomized placebo-controlled trial were tested for correlations with their patient-reported symptom scores and baseline characteristics. RESULTS: Each pair of individual and overall scores of patient-reported symptoms and photograph-based toxicity was correlated at 2 and 4 weeks (correlation coefficient range, 0.34-0.95; P < .001 for all). Older age, more actinic keratoses, previous topical 5-FU use, and more keratinocyte carcinomas on the face and ears in the previous 5 years were correlated with increased 5-FU toxicity at 2 weeks (P < .05). An increase in the total number of 5-FU applications during the trial was correlated with less severe toxicity at 2 weeks (P < .001), but with increased toxicity at 4 weeks (P < .001). CONCLUSION: This study provides evidence for construct validity of the photograph-based 5-FU toxicity score. The tool can be used to objectively measure 5-FU toxicity in clinical or research setting, and it can be a prototype for toxicity measurements of other topical medications.

Vision Loss After Central Retinal Artery Occlusion Secondary to Orbital Sarcoid Mass.

The authors describe the first report in the literature of central retinal artery occlusion as the presenting manifestation of sarcoidosis. A 33-year-old man with asthma, headache, and 6 days of intermittent, transient vision loss in the OS presented with persistent vision loss in the OS. Ophthalmic examination was consistent with diagnosis of central retinal artery occlusion in the OS. Vascular imaging with CT angiography revealed an incidental finding of an intraconal mass surrounding the left optic nerve and hilar lymphadenopathy. Broncho scopic lymph node biopsy demonstrated noncaseating granulomas consistent with sarcoidosis. This case proffers a unique mechanism of vision loss in sarcoidosis and highlights that atypical causes of central retinal artery occlusion must be considered in patients without typical risk factors.

Measuring the severity of topical 5-fluorouracil toxicity.

BACKGROUND: Topical 5% 5-fluorouracil (5-FU) is known to cause toxicity, such as erythema, pain, and crusting/erosions. OBJECTIVES: We sought to develop a scale to measure this toxicity and test the scale for reliability. METHODS: A scale was developed involving four parameters: erythema severity, percentage of face involved in erythema, crusting/erosions severity, and percentage of face involved in crusting/erosions. Thirteen raters graded 99 sets of photographs from the Veterans Affairs Keratinocyte Carcinoma Chemoprevention (VAKCC) Trial using these parameters. RESULTS: Intraclass correlation overall for 13 raters was 0.82 (95% CI 0.77-0.86). There was no statistically significant trend in reliability by level of training in dermatology. CONCLUSIONS: This scale is a reliable method of evaluating the severity of toxicity from topical 5-fluorouracil and can be used by dermatologists and nondermatologists alike.

Review: higher vitamin D status and supplementation may be associated with risks.

The prevalence of low vitamin D levels and associated risks has led to an increase in supplementation. However, a "U-shaped" relationship has been suggested between vitamin D status and adverse effects, with risks observed both in low and high levels. While risks associated with low levels of vitamin D have been extensively studied, the risks of higher levels of vitamin D have not been as widely circulated. We sought to describe key observed adverse risks with vitamin D supplementation and higher serum 25(OH)-D levels in healthy adult populations.

Higher melanoma incidence in coastal versus inland counties in California.

The incidence of melanoma is increasing and there is significant variation by geographical location between and within countries. We sought to determine the incidence of melanoma in coastal versus inland counties in California. Data on melanoma incidence were obtained for 2000-2009 from the Surveillance, Epidemiology, and End Results program of the National Cancer Institute. Incidences for melanoma in situ and invasive melanoma for major racial and ethnic groups for coastal and inland counties were analyzed using multivariable Poisson regression, with adjustment for socioeconomic factors (income, education), ultraviolet index, and latitude. Further analyses were carried out for the non-Hispanic white population through stratification of in-situ versus invasive melanoma, age, thickness, and anatomic distribution. The incidence of melanoma in situ is greater in coastal counties of California than inland counties (incidence rate ratio 1.23, 95% confidence interval 1.04-1.47) after adjusting for socioeconomic factors, ultraviolet index, and latitude. In non-Hispanic whites, this difference is significant for in-situ and thin (≤ 1.00 mm) melanomas, but not for melanomas of greater thickness. In melanoma in situ and thin melanomas in non-Hispanic whites, the incidence is greater in coastal versus inland counties. Causes may include differences in exposures, differences in detection, or artifacts such as residual confounding. Our study highlights the need for further research in identifying and addressing these differences.

Safety of cosmetic dermatologic procedures during pregnancy.

BACKGROUND: Safety of cosmetic procedures in pregnant women has not been extensively studied. Maternal and fetal health risks are important to consider in any procedure performed. With the increasing popularity of cosmetic procedures, dermatologic surgeons will be faced with scenarios necessitating knowledge regarding the safety of such procedures during pregnancy. Furthermore, dermatologic surgeons may inadvertently perform cosmetic procedures during the first trimester, before the patient is aware of the pregnancy. OBJECTIVE: To investigate the safety of cosmetic procedures during pregnancy and the postpartum period. METHODS AND MATERIALS: A literature search of PubMed and Google Scholar was conducted of all English-language articles published from 1960 through 2012. RESULTS: Definitive recommendations on the safety of procedures such as chemical peels, injectables, fillers, and most laser therapies during pregnancy cannot be made. The safety of onabotulinum toxin usage is well documented in the neurology literature, although isolated events of miscarriage have been reported with high doses of toxin in women with a previous history of miscarriage. Carbon dioxide laser therapy for genital condylomas has considerable evidence supporting its safety during pregnancy. CONCLUSION: There is a lack of controlled trials addressing the safety of cosmetic procedures during pregnancy and postpartum periods. It is advisable to delay elective cosmetic procedures until after the baby is born.

Changing incidence trends of cutaneous T-cell lymphoma.

IMPORTANCE: Cutaneous T-cell lymphoma (CTCL) incidence and survival have been increasing steadily for over 25 years. OBJECTIVE: We sought to measure changes in CTCL incidence trends and survival rates. DESIGN, SETTING, AND PARTICIPANTS: Population-based study. The CTCL incidence and survival data were obtained from the 9 original registries (1973-2009) and the 4 additional registries (1992-2009) of the Surveillance, Epidemiology and End Results (SEER) program of the National Cancer Institute (NCI). Trend analysis was performed using the Joinpoint Regression Program provided by the NCI. Survival analysis was performed using the SeerSTAT statistical software of the NCI. The total number of cases of CTCL from 1973 to 2009 was 6230. MAIN OUTCOMES AND MEASURES: Diagnoses of CTCL. RESULTS: Overall CTCL incidence has stabilized since 1998 (95% CI, 1994-2002), with an annual percent change (APC) of 5.7% from 1973 to 1998 (95% CI, 4.9%-6.5%) and an APC of 0.1% from 1998 to 2009 (95% CI, -1.4% to 1.5%). Similar incidence stabilization patterns were found in subgroup analyses of race, sex, age, diagnosis, and registry. Five-year CTCL survival rates increased until 2004. CONCLUSIONS AND RELEVANCE: The incidence of CTCL is no longer increasing. Causes for this trend change may include real incidence stabilization, stabilization of physician detection, or artifact.

Compact fluorescent lamps and risk of skin cancer.

BACKGROUND: Previously considered safe for typical use, concerns have recently been expressed regarding the potential effect of compact fluorescent lamps (CFLs) on human skin and, in particular, on skin cancer risk. OBJECTIVE: We sought to address this concern by reviewing the current literature on CFLs, ultraviolet (UV) radiation, and photocarcinogenic exposure. RESULTS: On average, the UV radiation from CFLs and subsequent carcinogenic exposure is lower than that from incandescent bulbs. However, defective bulbs can emit higher levels of UV radiation, which may cause significant damage. CONCLUSION: Our review calls for further investigation to determine how frequently these bulbs are sufficiently defective to lead to adverse effects.

Predictors of squamous cell carcinoma in high-risk patients in the VATTC trial.

Invasive squamous cell carcinoma (SCC) of the skin is one of the most common cancers in the United States, with no proven means for prevention other than systemic retinoids, which have significant toxicity, and sunscreen. We sought to determine the risk factors for invasive SCC on the face or ears in a high-risk population comprising 1,131 veterans in the Veterans Affairs Topical Tretinoin Chemoprevention (VATTC) Trial. Participants were required to have been diagnosed with at least two keratinocyte carcinomas (KCs) in the 5 years prior to enrollment. The median duration of follow-up was 3.7 years. Twenty-three percent of the participants developed a new invasive SCC, and the cumulative risk of invasive SCC was 30% at 5 years. The following factors independently predicted for new invasive SCCs: number of invasive SCCs and number of in situ SCCs in the 5 years prior to enrollment, actinic keratoses count at enrollment, a history of ever use of topical 5-fluorouracil, and total occupational time spent outdoors. In contrast, the use of angiotensin-convering enzyme inhibitors or angiotensin receptor blockers during the study and a history of warts anywhere on the body were found to protect against new invasive SCCs. These independent predictors remained the same for all SCCs (invasive and in situ combined). The number of basal cell carcinomas in the 5 years prior to enrollment, sunburns, sun sensitivity, and recreational sun exposure were not associated with new SCCs. These findings identify key risk factors for additional SCCs in patients with multiple prior KCs, and suggest that a history of warts may be associated with reduced SCC risk.