Trajectories of Nevus Development From Age 3 to 16 Years in the Colorado Kids Sun Care Program Cohort.

Importance: Nevi are a risk factor for melanoma and other forms of skin cancer, and many of the same factors confer risk for both. Understanding childhood nevus development may provide clues to possible causes and prevention of melanoma. Objectives: To describe nevus acquisition from the ages of 3 to 16 years among white youths and evaluate variation by sex, Hispanic ethnicity, and body sites that are chronically vs intermittently exposed to the sun. Design, Setting, and Participants: This annual longitudinal observational cohort study of nevus development was conducted between June 1, 2001, and October 31, 2014, among 1085 Colorado youths. Data analysis was conducted between February 1, 2015, and August 31, 2017. Main Outcomes and Measures: Total nevus counts on all body sites and on sites chronically and intermittently exposed to the sun separately. Results: A total of 557 girls and 528 boys (150 [13.8%] Hispanic participants) born in 1998 were included in this study. Median total body nevus counts increased linearly among non-Hispanic white boys and girls between the age of 3 years (boys, 6.31; 95% CI, 5.66-7.03; and girls, 6.61; 95% CI, 5.96-7.33) and the age of 16 years (boys, 81.30; 95% CI, 75.95-87.03; and girls, 77.58; 95% CI, 72.68-82.81). Median total body nevus counts were lower among Hispanic white children (boys aged 16 years, 51.45; 95% CI, 44.01-60.15; and girls aged 16 years, 53.75; 95% CI, 45.40-63.62) compared with non-Hispanic white children, but they followed a largely linear trend that varied by sex. Nevus counts on body sites chronically exposed to the sun increased over time but leveled off by the age of 16 years. Nevus counts on sites intermittently exposed to the sun followed a strong linear pattern through the age of 16 years. Hispanic white boys and girls had similar nevus counts on sites intermittently exposed to the sun through the age of 10 years, but increases thereafter were steeper for girls, with nevus counts surpassing those of boys aged 11 to 16 years. Conclusions and Relevance: Youths are at risk for nevus development beginning in early childhood and continuing through midadolescence. Patterns of nevus acquisition differ between boys and girls, Hispanic and non-Hispanic white youths, and body sites that are chronically exposed to the sun and body sites that are intermittently exposed to the sun. Exposure to UV light during this period should be reduced, particularly on body sites intermittently exposed to the sun, where nevi accumulate through midadolescence in all children. Increased attention to sun protection appears to be merited for boys, in general, because they accumulated more nevi overall, and for girls, specifically, during the adolescent years.

Vemurafenib-induced neutrophilic panniculitis in a child with a brainstem glioma.

Neutrophilic panniculitis is a rare adverse effect of therapy with selective BRAF inhibitors. We report a case of neutrophilic panniculitis in a 15-year-old girl receiving treatment with vemurafenib for a brainstem glioma. Clinicians should be aware of this rare but important side effect of vemurafenib. This is the first report of neutrophilic panniculitis in a child treated with vemurafenib.

Interactions between ultraviolet light and MC1R and OCA2 variants are determinants of childhood nevus and freckle phenotypes.

BACKGROUND: Melanocytic nevi (moles) and freckles are well known biomarkers of melanoma risk, and they are influenced by similar UV light exposures and genetic susceptibilities to those that increase melanoma risk. Nevertheless, the selective interactions between UV exposures and nevus and freckling genes remain largely undescribed. METHODS: We conducted a longitudinal study from ages 6 through 10 years in 477 Colorado children who had annual information collected for sun exposure, sun protection behaviors, and full body skin exams. MC1R and HERC2/OCA2 rs12913832 were genotyped and linear mixed models were used to identify main and interaction effects. RESULTS: All measures of sun exposure (chronic, sunburns, and waterside vacations) contributed to total nevus counts, and cumulative chronic exposure acted as the major driver of nevus development. Waterside vacations strongly increased total nevus counts in children with rs12913832 blue eye color alleles and facial freckling scores in those with MC1R red hair color variants. Sunburns increased the numbers of larger nevi (≥2 mm) in subjects with certain MC1R and rs12913832 genotypes. CONCLUSIONS: Complex interactions between different UV exposure profiles and genotype combinations determine nevus numbers and size, and the degree of facial freckling. IMPACT: Our findings emphasize the importance of implementing sun-protective behavior in childhood regardless of genetic make-up, although children with particular genetic variants may benefit from specifically targeted preventive measures to counteract their inherent risk of melanoma. Moreover, we demonstrate, for the first time, that longitudinal studies are a highly powered tool to uncover new gene-environment interactions that increase cancer risk.

Onychomycosis in the Denver pediatrics population, a retrospective study.

Onychomycosis (OM) is a common nail disorder in adults but has been rare in children. Recent international studies have demonstrated a rise in the prevalence of OM in children and adolescents, with Trichophyton rubrum being the most common pathogen. This 5-year retrospective chart review of children (aged <18) found that 66 of 141 patients (46.8%) presenting to Children's Hospital Colorado or Denver Health Medical Center Dermatology clinics with nail complaints had OM, with the highest prevalence in those aged 6 to 10 and a slight male predominance. Toenails were more commonly affected, and Trichophyton rubrum was the most common pathogen.

Parents' perceptions of skin cancer threat and children's physical activity.

INTRODUCTION: Sun exposure is a major risk factor for skin cancer, but without physical activity, children are at risk of childhood obesity. The objective of this study was to explore relationships between parental perceptions of skin cancer threat, sun protection behaviors, physical activity, and body mass index (BMI) in children. METHODS: This is a cross-sectional analysis nested within the Colorado Kids Sun Care Program sun safety intervention trial. In summer 2007, parent telephone interviews provided data on demographics, perceptions of skin cancer threat, sun protection behaviors, and physical activity. Physical examinations provided data on phenotype, freckling, and BMI. Data from 999 Colorado children born in 1998 were included in analysis. We used analysis of variance, Spearman's rho (ρ) correlation, and multivariable linear regression analysis to evaluate relationships with total amount of outdoor physical activity. RESULTS: After controlling for sex, race/ethnicity, skin color, and sun protection, regression analysis showed that each unit increase in perceived severity of nonmelanoma skin cancer was associated with a 30% increase in hours of outdoor physical activity (P = .005). Hours of outdoor physical activity were not related to perceived severity of melanoma or perceived susceptibility to skin cancer. BMI-for-age was not significantly correlated with perceptions of skin cancer threat, use of sun protection, or level of physical activity. CONCLUSION: The promotion of sun safety is not likely to inhibit physical activity. Skin cancer prevention programs should continue to promote midday sun avoidance and sun protection during outdoor activities.

Mailed intervention to promote sun protection of children: a randomized controlled trial.

BACKGROUND: Sun exposure, especially during childhood, is the most important preventable risk factor for skin cancer, yet few effective interventions to reduce exposure exist. PURPOSE: To test the effectiveness of a partially tailored mailed intervention based on the Precaution Adoption Process Model, delivered in the spring over 3 years to parents and children. DESIGN: RCT, with data collection through telephone interviews of parents and skin exams of children at baseline (Summer 2004) and annually (Summer 2005-2007). The control group received no intervention. SETTING/PARTICIPANTS: Families recruited in the Denver CO area, through private pediatric clinics, a large MCO, and community settings. Children born in 1998 were approximately 6 years of age at baseline; 867 children met inclusion criteria; analysis is reported for 677 white, non-Hispanic participants at highest risk for skin cancer. MAIN OUTCOME MEASURES: Primary outcomes were parent-reported child sun protection behaviors. Secondary outcomes included parents' risk perception, perceived effectiveness of and barriers to prevention behaviors, stage of change, reported sunburns, and observed tanning and nevus development. The longitudinal mixed-model analysis was conducted between 2008 and 2011. RESULTS: The intervention group reported more use of sunscreen, protective clothing, hats, shade-seeking, and midday sun avoidance; fewer sunburns; more awareness of the risk of skin cancer; higher perceived effectiveness of sun protection; higher stage of change; and lower perception of barriers to sun protection (all p<0.05). The intervention group had fewer nevi ≥2 mm in 1 year of the study, 2006 (p=0.03). No differences were found in tanning or nevi <2 mm. CONCLUSIONS: The level of behavior change associated with this single-modality intervention is not likely sufficient to reduce skin cancer risk. However, the intervention shows promise for inclusion in longer-term, multicomponent interventions that have sufficient intensity to affect skin cancer incidence.

Sun damage in ultraviolet photographs correlates with phenotypic melanoma risk factors in 12-year-old children.

BACKGROUND: Ultraviolet (UV) photography has been used to motivate sun safety in behavioral interventions. The relationship between sun damage shown in UV photographs and melanoma risk has not been systematically investigated. OBJECTIVE: To examine the relationship between severity of sun damage in UV photographs and phenotypic melanoma risk factors in children. METHODS: UV, standard visible and cross-polarized photographs were recorded for 585 children. Computer software quantified sun damage. Full-body nevus counts, skin color by colorimetry, facial freckling, hair and eye color were collected in skin examinations. Demographic data were collected in telephone interviews of parents. RESULTS: Among 12-year-old children, sun damage shown in UV photographs correlated with phenotypic melanoma risk factors. Sun damage was greatest for children who were non-Hispanic white and those who had red hair, blue eyes, increased facial freckling, light skin and greater number of nevi (all P values < .001). Results were similar for standard visible and cross-polarized photographs. Freckling was the strongest predictor of sun damage in visible and UV photographs. All other phenotypic melanoma risk factors were also predictors for the UV photographs. LIMITATIONS: Differences in software algorithms used to score the photographs could produce different results. CONCLUSION: UV photographs portray more sun damage in children with higher risk for melanoma based on phenotype. Therefore sun protection interventions targeting those with greater sun damage on UV photographs will target those at higher melanoma risk. This study establishes reference ranges dermatologists can use to assess sun damage in their pediatric patients.

Effect of hair color and sun sensitivity on nevus counts in white children in Colorado.

BACKGROUND: It has been widely reported that individuals with a light phenotype (ie, light hair color, light base skin color, and propensity to burn) have more nevi and are at greater risk for developing skin cancer. No studies have systematically investigated how phenotypic traits may interact in relation to nevus development. OBJECTIVE: We sought to systematically examine whether any combinations of phenotype are associated with a greater or lesser risk for nevus development in white children. METHODS: In the summer of 2007, 654 children were examined to determine full body nevus counts, skin color by colorimetry, and hair and eye color by comparison with charts. Interviews of parents were conducted to capture sun sensitivity, sun exposure, and sun protection practices. RESULTS: Among 9-year-old children with sun sensitivity rating type II (painful burn/light tan), those with light hair had lower nevus counts than did those with dark hair (P value for interaction = .03). This relationship was independent of eye color, presence of freckling, sex, usual daily sun exposure, sunburn in 2004 to 2007, sun protection index, and waterside vacation sun exposure. The difference in nevus counts was further determined to be specific to small nevi (<2 mm) and nevi in intermittently exposed body sites. LIMITATIONS: Geographic and genetic differences in other study populations may produce different results. CONCLUSION: The standard acceptance that dark phenotype is a marker for low melanoma risk and light phenotype a marker for high risk may need to be reevaluated. In non-Hispanic white children, dark-haired individuals who burn readily and then tan slightly are more prone to nevus development, and may therefore be a previously underrecognized high-risk group for melanoma.

Vitiligo treatment in childhood: a state of the art review.

Vitiligo is a common depigmenting disorder affecting about 1-2% of the world population. Approximately half of the affected individuals develop the disease before adulthood. Etiologic hypotheses for vitiligo include biochemical, neural and autoimmune mechanisms. The most compelling of these suggests a combination of genetic and immunologic factors that result in an autoimmune melanocyte destruction. We reviewed studies carried out on various treatment modalities used in childhood vitiligo. Topical corticosteroids were found to have excellent repigmentation rates, whereas calcineurin inhibitors have comparable efficacy and a better safety profile compared with topical corticosteroids. These two groups of topical medications are good first-line treatment modalities for localized vitiligo. For the treatment of generalized vitiligo, phototherapy has excellent efficacy. Narrow-band ultraviolet B (UVB) has better overall repigmentation rates and safety profile than either topical or oral psoralens and ultraviolet A (PUVA). Other treatment modalities may be considered depending on a patient's specific condition, such as surgical options and depigmentation. With adequate sun protection, the option of no treatment with or without corrective camouflage, is an innocuous alternative to any of these treatment modalities.

Tanning and increased nevus development in very-light-skinned children without red hair.

OBJECTIVE: To examine the relationship between tanning and nevus development in very-light-skinned children. DESIGN: Prospective cohort nested within a randomized controlled trial. Skin examinations in 3 consecutive years (2004, 2005, and 2006) included full-body counts of nevi, skin color and tanning measurement using colorimetry, and hair and eye color evaluation by comparison with charts. Telephone interviews of parents provided sun exposure, sun protection, and sunburn history. SETTING: Large managed-care organization and private pediatric offices in the Denver, Colorado, metropolitan area. PARTICIPANTS: A total of 131 very-light-skinned white children without red hair and 444 darker-skinned white children without red hair born in Colorado in 1998. MAIN OUTCOME MEASURES: Full-body nevus counts at ages 6 to 8 years. RESULTS: Among very-light-skinned white children, geometric mean numbers of nevi for minimally tanned children were 14.8 at age 6 years; 18.8 at age 7 years; and 22.3 at age 8 years. Mean numbers of nevi for tanned children were 21.2 at age 6 years; 27.9 at age 7 years; and 31.9 at age 8 years. Differences in nevus counts between untanned and tanned children were statistically significant at all ages (P < .05 for all comparisons). The relationship between tanning and number of nevi was independent of the child's hair and eye color, parent-reported sun exposure, and skin phototype. Among darker-skinned white children, there was no relationship between tanning and nevi. CONCLUSIONS: Very-light-skinned children who tan (based on objective measurement) develop more nevi than children who do not tan. These results suggest that light-skinned children who develop tans may be increasing their risk for developing melanoma later in life.

The anatomic distribution of melanoma and relationships with childhood nevus distribution in Colorado.

The nature of the relationship between nevus development in childhood and later development of melanoma is unclear. Data on melanoma diagnoses by histologic type and anatomic site were obtained for 2351 white, non-Hispanics in Colorado from the Colorado Central Cancer Registry between 2000 and 2004. Nevus size and body site were ascertained during skin exams conducted in the summer of 2007 on 717 white, non-Hispanic children aged 8-9 years. Chi-square goodness-of-fit analysis was used to assess the association between the anatomic site distributions of nevi versus melanoma. Superficial spreading melanoma was the most frequent histology, followed by lentigo maligna melanoma. Nodular melanoma was the least common histology. For males, there was no significant difference between the distribution of medium-sized (> or =2 mm) nevi and the distribution of both superficial spreading and nodular melanomas. For females, there was no significant difference between the anatomic distribution of small-sized (<2 mm) nevi and the distribution of nodular melanoma, and there was marginal evidence for a difference between the distribution of medium-sized (> or =2 mm) nevi and the distribution of nodular melanoma. There was evidence for a difference between all of the nevus distributions and the distributions of superficial spreading and lentigo maligna melanoma in females. The similarities between the nevus and melanoma distributions are interesting findings, but it is difficult to interpret the significance of these findings based on the current state of knowledge of melanoma etiology.

Vacations to waterside locations result in nevus development in Colorado children.

Nevi are a main risk factor for malignant melanoma, and most nevi develop in childhood. This study examined the relationship between vacations and nevi in 681 White children born in 1998 who were lifetime residents of Colorado. Vacation histories were assessed through telephone interviews of parents, whereas nevus and phenotypic characteristics were assessed through skin exams at age 7. Multiple linear and logistic regression were used to assess the influence of vacations on counts of nevi <2 mm in size and the presence of any nevi > or = 2 mm after controlling for other variables. Each waterside vacation > or = 1 year before the exam at age 7 was found to be associated with a 5% increase in nevi <2 mm. Waterside vacations <1 year before the skin exam were not related to nevus count (<2 mm); regardless of timeframe, waterside vacations were not related to the presence of nevi > or = 2 mm. UV dose received on waterside vacations, number of days spent on waterside vacations, and nonwaterside vacations were not significantly related to nevi <2 or > or = 2 mm. These results suggest that there is a lag of at least 1 year in the development of new nevi after vacation sun exposure. It appears that a threshold dose of UV exposure is received quickly on each waterside vacation. Parents of young children should exercise caution in selection of vacation locations to reduce melanoma risk.

Melanocytic nevus development in Colorado children born in 1998: a longitudinal study.

OBJECTIVE: To describe the development of nevi from 3 to 8 years of age in a birth cohort of children in Colorado. DESIGN: Longitudinal observational study. SETTING: Large managed care organization and university and private primary care practices. PARTICIPANTS: Annual convenience samples of children born in 1998 (range, n = 137 to n = 870) (participation rates, 18.8%-76.0%). We recruited children through the managed care organization, private primary care practices, and community settings. MAIN OUTCOME MEASURES: Total whole body nevus counts, counts by nevus diameter (< 2, 2 to < 5, or > or = 5 mm), and counts for chronically and intermittently exposed body sites. RESULTS: Non-Hispanic white children had significantly more nevi than did other racial/ethnic groups and developed an average of 4 to 6 new nevi per year from 3 to 8 years of age. Non-Hispanic white boys had significantly more nevi than did girls beginning at 6 years of age (median, 21 [interquartile range, 28] vs 17 [17]; P = .002). This difference was due to nevi of less than 2 mm and nevi in chronically exposed body sites. Development of new nevi leveled off in chronically exposed body sites at 7 years of age and at a higher level for boys than girls. CONCLUSIONS: Children in Colorado developed more small nevi and fewer large nevi compared with children in other regions of the world, highlighting the importance of studying nevus development in various locations where sun exposure patterns and behavioral norms vary. The sex difference in nevus development could be owing to variation in sun exposure and/or a biological predisposition of boys to develop more nevi. Studies of nevus development can aid in the understanding of the complicated relationship between nevus development and malignant melanoma.

Melanocytic nevi and sun exposure in a cohort of colorado children: anatomic distribution and site-specific sunburn.

Sun exposure and high prevalence of melanocytic nevi are major risk factors for melanoma, but the relationship between them is not well understood. This study examines the relationship between sun exposure (detailed by anatomic location and history of site-specific sunburns) and the presence of melanocytic nevi on 743 White children in Denver, Colorado. Parental reports of site-specific sunburns were collected annually for 2 years starting at ages 5 to 6 years. In the third year, nevi were counted and mapped by anatomic location. Nevus density was higher for boys (36.0 nevi/m2) than for girls (31.0 nevi/m2; P = 0.04). Nevus density was highest on the face, neck, and lateral forearms and was significantly higher in chronically versus intermittently sun-exposed areas (P < 0.0001). Compared with girls, boys had higher nevus density on the face, neck, and trunk, and lower nevus density on the upper arms and thighs (P < 0.01). In 2 years of reports, most subjects (69%) received at least one sunburn. The face, shoulders, and back were the most frequently sunburned areas of the body. When adjusted for host factors, total number of sunburns was significantly associated with higher total nevus prevalence (P = 0.01 for one burn). Site-specific sunburns were significantly associated with nevus prevalence on the back (P = 0.03 for three or more sunburns), but not on the face, arms, or legs. In this high-risk population, there is evidence for two pathways to nevus accumulation: by chronic sun exposure and by intermittent exposure related to sunburns.

Holocarboxylase synthetase deficiency presenting as ichthyosis.

Holocarboxylase synthetase deficiency is a rare autosomal recessive disorder of biotin metabolism. Clinical manifestations usually present within the first few days of life and include severe acidosis, feeding difficulties, breathing abnormalities, vomiting, seizures, progressive loss of consciousness, coma, and death. Skin findings, when present, usually develop within the first weeks of life and are described as an erythroderma-like dermatitis involving the eyebrows, eyelashes, and scalp. We were asked to consult on a newborn with a collodion membrane and severe metabolic acidosis who was eventually diagnosed with holocarboxylase synthetase deficiency and ichthyosis. The diagnosis of holocarboxylase synthetase deficiency might be considered in a newborn with collodion membrane, ichthyosis, and acidosis.

Dermatitis under soccer shin guards: allergy or contact irritant reaction?

We report a retrospective analysis of eight children aged 9 to 16 years who were evaluated for a persistent or recurrent dermatitis that appeared under soccer shin guards. To examine the possibility of contact allergy, all had 51 standard epicutaneous (patch) tests applied and three or four additional tests comprised of pieces of the shin guard components. Tests were read at 48 and 120 hours and all were negative in each subject. Irritant contact dermatitis, not allergy, was the cause of dermatitis in these subjects. It was postulated that sweating and friction contributed to the irritancy.

A randomized intervention study of sun protection promotion in well-child care.

BACKGROUND: This study evaluated the behavioral impact of a skin cancer prevention program in which health care providers delivered advice and materials to parents of infants over a 3-year period from 1998 to 2001. METHODS: Fourteen offices of a large managed care organization in Colorado were randomly assigned to the intervention or control groups. 728 infants and their parents were recruited within 6 months of birth. At intervention offices, health care providers attended orientation sessions, prompts for delivering sun protection advice were placed in medical records, and parents received sun protection packets at each well-child visit between 2 and 36 months of age. RESULTS: Based on provider self-report and exit interviews of parents, providers in the intervention group delivered approximately twice as much sun protection advice as providers in the control group. Annual telephone interviews of parents indicated small but statistically significant differences in parent sun protection practices favoring the intervention. Skin exams revealed no significant differences in tanning, freckling, or number of nevi. Behavioral differences between groups appeared to grow over the 3 years of follow-up. CONCLUSIONS: This intervention strategy was successful in increasing the delivery of sun protection advice by health care providers and resulted in changes in parents' behaviors. While the behavioral effect was probably not strong enough to reduce risk for skin cancer, the effect may increase as children age and have more opportunities for overexposure to the sun.

Atypical IgA/IgG pemphigus involving the skin, oral mucosa, and colon in a child: a novel variant of IgA pemphigus?

Immune-mediated blistering diseases are rare in childhood, with the subset of IgA pemphigus being extremely uncommon. A child with a bullous disorder of the oral mucosa, skin, and colon is reported because of the unusual nature of the clinical and laboratory findings. Immunofluorescence studies demonstrated both intercellular epidermal and basement membrane zone deposition of IgA and IgG antibodies, as well as intercellular colonic deposition of IgA antibodies. IgA and IgG ELISA tests were positive for desmoglein 3 as the intercellular epidermal antigen. The generation of multiple antibodies against several potential antigenic targets suggests epitope spreading may play a role in this disease. We believe this represents a novel variant of IgA pemphigus.