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Table 2. Summary of Dermoscopic Features of New and Changing Suspicious Lesions No. (%) Benign (n = 35)

Melanoma (n = 7)

Benign vs Melanoma

Negative network

3 (9)

4 (57)

0.002a

Atypical network

Dermoscopic Feature

14 (40)

4 (57)

0.403

Atypical dots/globules

8 (23)

3 (43)

0.272

Off-center blotches

9 (26)

2 (29)

0.875

Blue-white veil over raised areas

5 (14)

2 (29)

0.355

Blue-white veil over flat areas

3 (9)

1 (14)

0.638

Streaks/pseudopods

0

0

Polymorphous vessels/vascular blush

5 (14)

3 (43)

0.079

Peripheral structureless

4 (11)

2 (29)

0.237

Chrystaline structures

0

1 (14)

0.024

inconspicuous new primary melanomas. The rate of new primary melanomas is approximately 17 times higher than has been reported in a high-risk atypical-mole syndrome population with a history of melanoma.5 BRAF inhibitor therapy can theoretically cure patients of their BRAFV600E mutated melanoma, but BRAF wild-type melanomas remain a challenge. As yet, the underlying driver mutation in these changing MLs remains to be elucidated, although NRAS (OMIM *164790) mutations have occasionally been found.1 Dermoscopy helps identify melanoma, and all melanomas in our series demonstrated at least 1 melanomaspecific feature. A limitation of our study was patient selection bias, as only patients undergoing BRAF inhibitor therapy and seen by the dermatology department were assessed. Many of these patients had a high-risk phenotype with many nevi and dysplastic nevi. Further studies are needed to determine the extent of changes in all patients taking BRAF inhibitors. In addition, it remains to be seen if melanocytic changes are less dynamic in the setting of combined therapy with a MEK inhibitor, as was the case with squamous cell carcinomas.6 We support total-body photography and short-term mole monitoring with dermoscopy as a method for monitoring atypical-pigmented lesions in the setting of highly volatile melanocytic changes in patients taking a BRAF inhibitor. Sarah Yagerman, MD Eileen Flores, MPH Klaus Busam, MD Mario Lacouture, MD Ashfaq A. Marghoob, MD

Abbreviation: NA, not applicable. a

P < .05 using a proportion test.

Acquisition, analysis, or interpretation of data: All authors. Drafting of the manuscript: Yagerman, Flores, Marghoob, Lacouture. Critical revision of the manuscript for important intellectual content: All authors. Statistical analysis: Yagerman, Flores. Administrative, technical, or material support: Yagerman, Flores, Lacouture, Marghoob. Study supervision: Yagerman, Flores, Lacouture, Marghoob. Conflict of Interest Disclosures: None reported. Previous Presentation: A portion of this study was presented at the American Society of Clinical Oncology 49th Annual Meeting of Science and Society; June 3, 2013; Chicago, Illinois. 1. Zimmer L, Hillen U, Livingstone E, et al. Atypical melanocytic proliferations and new primary melanomas in patients with advanced melanoma undergoing selective BRAF inhibition. J Clin Oncol. 2012;30(19):2375-2383. 2. Su F, Viros A, Milagre C, et al. RAS mutations in cutaneous squamous-cell carcinomas in patients treated with BRAF inhibitors. N Engl J Med. 2012;366(3): 207-215. 3. Haenssle HA, Kraus SL, Brehmer F, et al. Dynamic changes in nevi of a patient with melanoma treated with vemurafenib: importance of sequential dermoscopy. Arch Dermatol. 2012;148(10):1183-1185. 4. Marghoob AA, Malvehy J, Braun RP, eds. Atlas of Dermoscopy. 2nd ed. New York, NY: Springer-Verlag; 2012. 5. Marghoob AA, Slade J, Kopf AW, et al. Risk of developing multiple primary cutaneous melanomas in patients with the classic atypical-mole syndrome: a case-control study. Br J Dermatol. 1996;135(5):704-711. 6. Cebon K, Weber J, Kim K, et al. Comparison of BRAF inhibitor (BRAFi)–induced cutaneous squamous cell carcinoma (cuSCC) and secondary malignancies in BRAF mutation-positive metastatic melanoma (MM) patients (pts) treated with dabrafenib (D) as monotherapy or in combination with MEK1/2 inhibitor (MEKi) trametinib (T). J Clin Oncol. 2013 (suppl).

Portable Shade Structure Use at a Youth Soccer Camp

Author Affiliations: Memorial Sloan-Kettering Skin Cancer Center, Hauppauge, New York. Accepted for Publication: December 15, 2013. Corresponding Author: Ashfaq A. Marghoob, MD, Memorial Sloan-Kettering Skin Cancer Center, 800 Veterans Memorial Hwy, Second Floor, Hauppauge, NY 11788 ([email protected]). Published Online: July 23, 2014. doi:10.1001/jamadermatol.2013.10413. Author Contributions: Drs Marghoob and Lacouture had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Yagerman, Flores, Lacouture, Marghoob. jamadermatology.com

NA

More than 3 million nonmelanoma skin cancers (NMSCs) are diagnosed annually in the United States.1,2 The incidence of malignant melanoma (MM) has increased annually by 2.4%.3 Open field activities in youth are a major source of sun exposure, which leads to skin cancer later in life.4-6 Few studies exist on the use of shade structures in open field sports, particularly soccer. In this pilot study, we assess the rate of use of portable shade structures among soccer-playing youths. Methods | The Virginia Commonwealth University (VCU) institutional review board approved this study, waiving participant written informed consent. A summer soccer camp for boys and girls in metropolitan Richmond, Virginia, consisted of JAMA Dermatology September 2014 Volume 150, Number 9

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Table. Players’ Use of Shade Structures During Youth Soccer Camp Rest Sessions Rest Sessions Observed, No.

Children Using Shade Structures, mean %

P Value

All rest sessions, crude (n = 78)

78

71.4

NA

All rest sessions, adjusted (n = 78)a

78

79.7

NA

Week 1 (sunnier)

12

98.0

Week 2 (cloudier)

66

66.0

46

76.6

Characteristic

Week .01

Time of day Morning (younger campers) Afternoon (older campers)

32

15 3-hour periods of play over 10 days, of which 8 periods were observed (rainfall forced cancellation of the other 7). Shade tents donated by Virginia Commonwealth University Medical Center and the Sun Safe Soccer program of the American Society for Dermatologic Surgery were erected within 10 yards of the field. Coaches neither encouraged nor discouraged use. Research assistants followed written protocols and recorded tallies of the number of players using the shade tents during the breaks. Two minutes after a rest period began, 2 data collectors independently counted the children beneath the shade structures and recorded the mean value. Rest periods ranged from 5 to 10 minutes. The UV index and temperature, accessed from the US Weather Service at Richmond International Airport, were recorded for the times at which the counts were made. The overall mean percentage of children using shade structures per rest session was calculated, with stratifications by age and week. Pearson correlation coefficients were calculated to assess the association between a session’s UV index and temperature and shade structure use. A generalized linear model was created to estimate overall shade structure use, controlling for the potential confounding variables of group, week, UV index, and temperature. Results | Seventy-eight rest sessions were observed on 7 different days (Table). The mean number of children observed during each session was 80.9. The mean (SD) percentage of children using shade structures was 71.4% (37.8%) across all rest sessions. The mean (SD) outside temperature was 84.3°F (2.7°F) (range, 79°F-93°F). Two recordings were below 80°F, at 79°F. There was no correlation between temperature and shade structure use (P = .19). However, there were differences in shade use by camper group: older campers (14-18 years) who attended the afternoon sessions (51.2%) were less likely to use shade structures than younger campers (8-18 years) in the morning sessions (76.6%) (P = .02). There were also differences in shade use between week 1 (98%) and week 2 (66%) (P = .01), which correspond with differences in cloud coverage as noted by data collectors. Controlling for camper group and week, the adjusted mean percentage of children using shade structures was 79.7% per rest session. Discussion | In this pilot study, we examine the rate of use of commercially available shade tents in soccer-playing youths. 1012

51.2

Abbreviation: NA, not applicable. .02

a

Adjusted for week and time of day the camp session occurred.

We observed a mean adjusted use rate of 79.7%, which suggests that shade structures will be used if they are provided and sufficient time is allowed for use. Our study is limited by the small sample size, single club, and location in the southern United States. However, our findings suggest that inexpensive, portable shade structures at sporting events encourage sun protection, which could be augmented by providing sunscreen there as well. Larger, multicenter studies are needed to confirm the utility of shade structures to decrease UV exposure in a meaningful way and to inform policy makers, recreation facility managers, and architects of the public health value of shade structures for open field sports activities. Sheila Krishna, MD Eric Ambrecht, PhD Ian A. Maher, MD Author Affiliations: Department of Dermatology, Virginia Commonwealth University Health System, Medical College of Virginia, Richmond (Krishna, Maher); Department of Dermatology, St Louis University, St Louis, Missouri (Ambrecht, Maher); Center for Outcomes Research, St Louis University, St Louis, Missouri (Ambrecht). Corresponding Author: Ian A. Maher, MD, Department of Dermatology, St Louis University, 1755 S Grand Blvd, St Louis, MO 63104 ([email protected]). Accepted for Publication: December 17, 2013. Published Online: July 30, 2014. doi:10.1001/jamadermatol.2013.10502. Author Contributions: Drs Ambrecht and Maher had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Krishna, Maher. Acquisition, analysis, or interpretation of data: Krishna, Ambrecht, Maher. Drafting of the manuscript: Krishna, Ambrecht, Maher. Critical revision of the manuscript for important intellectual content: Krishna, Ambrecht, Maher. Statistical analysis: Ambrecht, Maher. Obtained funding: Maher. Administrative, technical, or material support: Ambrecht, Maher. Study supervision: Maher. Conflict of Interest Disclosures: None reported. Funding/Support: This study was supported in part by the Sun Safe Soccer program of the American Society of Dermatologic Surgery. Role of the Sponsor: The sponsor had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Additional Contributions: We are indebted to the Virginia Commonwealth University medical students who assisted with data collection.

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1. Rogers HW, Weinstock MA, Harris AR, et al. Incidence estimate of nonmelanoma skin cancer in the United States, 2006. Arch Dermatol. 2010;146 (3):283-287. 2. Stern RS, Weinstein MC, Baker SG. Risk reduction for nonmelanoma skin cancer with childhood sunscreen use. Arch Dermatol. 1986;122(5):537-545. 3. Whiteman DC, Whiteman CA, Green AC. Childhood sun exposure as a risk factor for melanoma: a systematic review of epidemiologic studies. Cancer Causes Control. 2001;12(1):69-82. 4. Balk SJ; Council on Environmental Health; Section on Dermatology. Ultraviolet radiation: a hazard to children and adolescents. Pediatrics. 2011;127 (3):e791-e817. 5. Mahé E, Beauchet A, de Paula Corrêa M, et al. Outdoor sports and risk of ultraviolet radiation-related skin lesions in children: evaluation of risks and prevention. Br J Dermatol. 2011;165(2):360-367. 6. Robinson JK, Rademaker AW, Sylvester JA, Cook B. Summer sun exposure: knowledge, attitudes, and behaviors of Midwest adolescents. Prev Med. 1997;26(3):364-372.

An Oral Phosphodiesterase Inhibitor (Apremilast) for Inflammatory Rosacea in Adults: A Pilot Study Rosacea is a chronic skin disorder characterized by facial flushing, persistent erythema, telangiectasias, and inflammatory papules and pustules. In addition to the physical manifestations, rosacea may contribute to lower self-esteem, Supplemental content at thereby having significant jamadermatology.com psychosocial implications.1 Some patients do not respond to conventional treatments for rosacea or are unable to tolerate the adverse effects; therefore, effective new therapies are needed. We sought to investigate the safety and efficacy of apremilast, an oral phosphodiesterase 4 inhibitor, for the treatment of moderate to severe inflammatory rosacea. Apremilast modulates multiple proinflammatory and anti-inflammatory pathways through targeted phosphodiesterase type 4 inhibition, including augmenting interleukin 10 production, which in turn suppresses other proinflammatory cytokines.2,3 Inhibitors of phosphodiesterase type 4 have been tested for treatment of many inflammatory dermatologic diseases4 but never for rosacea. Methods | In this investigator-initiated, open-label pilot study, 10 patients with moderate to severe inflammatory rosacea were administered apremilast, 20 mg orally twice daily, for 12 weeks. The inclusion criteria for enrollment were age of 18 to 75 years and moderate to severe erythematotelangiectatic and papulopustular rosacea defined as a minimum of 10 papules and pustules, the presence of moderate to severe erythema, and the presence of telangiectasias. Patients avoided known triggers of rosacea or treatments that might affect rosacea severity. Extensive exclusion criteria were also used in screening. The study population included 3 men and 7 women (age range, 39 to 74 years). Patients were seen between May 5, 2010, and November 20, 2012. This study was approved by the institutional review board of Columbia University, and written informed consent was obtained from all patients. All patients received active drug. Visits occurred at baseline, every 2 weeks during treatment (weeks 2, 4, 6, 8, 10, and 12), and 1 month after discontinuation of treatment (week 16). Safety factors were assessed at each visit. Patients acclimatized for at least 15 minutes before being examined. jamadermatology.com

Statistical analyses were performed via paired t tests and powered to 80% to detect changes greater than 1 SD in all reported variables. The primary end point was also analyzed via Wilcoxon signed rank tests to compare median values. Results | The primary end point was the total number of papulopustular lesions at baseline compared with the end of treatment and with follow-up 1 month after treatment. Secondary outcomes assessed drug toxicity as well as efficacy as defined by changes in the telangiectasia counts, chromometer readings,5 and ratings on the Physician Global 7-Point Assessment, Patient Global Assessment, Physician Overall Erythema Severity, and physician-rated variable scales. When baseline scores were compared with those at the end of treatment, there was a statistically significant improvement in ratings on the Physician Global 7-Point Assessment (t statistic = −2.86, P = .02), Physician Overall Erythema Severity (t statistic = −4.85, P = .001), erythematotelangiectatic rating (t statistic = −3.67, P = .005), and nontransient erythema (t statistic = −2.45, P = .04) (Table and Figure). When baseline ratings were compared with those at follow-up 1 month after discontinuation of treatment, measures that reached statistical significance were Physician Overall Erythema Severity (t statistic = −3.0, P = .02) and nontransient erythema (t statistic = −2.45, P = .04) (Table and Figure). None of the remaining comparisons reached statistical significance, including the primary end point of papule and pustule count, which was additionally analyzed by the Wilcoxon signed rank test to compare median values (Figure and the eTable and eFigure in the Supplement). Comparisons of chromometer readings also were not significant (data not shown). Apremilast was well tolerated. Few patients experienced adverse effects; the most common event was minor infection, including urinary tract infections and upper respiratory tract infections (2 patients each). No adverse effects required treatment alteration or discontinuation. Discussion | These results support further investigation of treatment with apremilast in rosacea, in particular, to perhaps fill a gap for the treatment of the erythematous component of rosacea, which has historically been refractory to other therapies. Although brimonidine tartrate is used topically for this indication, adverse effects are common7 and alternative therapies are still needed. An overall trend toward improvement was observed, and 3 of 4 measures of erythema showed significant improvement, two of which were durable 1 month after Table. Physician’s Rating of Nontransient Erythema in 10 Patients Rating, No. (%) of Patientsa Visit

a

Mild

Moderate

Baseline

2 (20)

8 (80)

End of treatment

6 (60)

4 (40)

1 mo After discontinuation of treatment

6 (60)

4 (40)

The physician used a 4-point rating system to grade nontransient erythema: 0 indicates absent; 1, mild; 2, moderate; and 3, severe. No patient received a rating of 0 or 3 at any visit.

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Portable shade structure use at a youth soccer camp.

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