Search

Background/objective: Proteus syndrome, caused by a mosaic activating AKT1 variant, typically presents in toddlers with progressive, asymmetric overgrowth of the skin and bones. We aimed to define the spectrum of dermatologic disease in individuals with genetically confirmed Proteus syndrome., Methods: We conducted a retrospective review of records from dermatologic examinations of individuals evaluated at the NIH with a molecular diagnosis of Proteus syndrome. The types, prevalence, and localization of dermatologic findings were assessed., Results: Fifty-one individuals (29 males, 22 females, mean age: 9 years) with clinical features of Proteus syndrome had the mosaic c.49G>A, p.Glu17Lys AKT1 variant. Fifty (98%) had at least one cutaneous feature constituting current clinical diagnostic criteria, including vascular malformations in 42 (82%), epidermal nevus in 41 (80%), volar cerebriform connective tissue nevi in 34 (67%), and adipose dysregulation in 30 (59%). Forty-nine (96%) had at least one dermatologic finding not included within the diagnostic criteria, including confluent volar skin-colored to hypopigmented papules or nodules (n = 33, 65%), papules or nodules on the digits or face (n = 27, 53%), and nonlinear epidermal nevi (n = 15, 29%). Other frequently observed features include nail changes (n = 28, 55%), hyperpigmented macules (n = 27, 53%), patchy dermal hypoplasia (n = 18, 35%), gingival/oral mucosal overgrowth (n = 17, 33%), hypopigmented macules (n = 16, 31%), dental enamel changes (n = 9, 18%), acrochordons (n = 6, 12%), and lingual overgrowth (n = 4, 8%)., Conclusions: The range of mucocutaneous features occurring in Proteus syndrome is broader than previously considered. These observations may assist in earlier diagnosis and management and provide novel insights regarding the pathogenesis of the condition., (© Published 2021. This article is a U.S. Government work and is in the public domain in the USA.)

Background: PReferentially expressed Antigen in MElanoma (PRAME) immunohistochemical (IHC) staining is used to aid melanoma diagnosis. PRAME expression in nevus-associated melanoma (NAM) has not been evaluated., Methods: PRAME IHC was applied to cases of NAM; staining for each population of melanocytes (benign and malignant) was graded based on the percentage of labeled cells. No labeling was graded 0, 1% to 25% labeling was 1+, 26% to 50% was 2+, 51% to 75% was 3+, and >76% was 4+., Results: Thirty-six cases were reviewed. Sixty-seven percent (24/36) of melanomas were PRAME positive (4+) while no (0/36) nevi showed 4+ positivity. Eighty-one percent (29/36) of nevi were completely PRAME negative compared to 17% (6/36) of melanomas. In 67% of cases (24/36) PRAME differentiated between benign and malignant melanocyte populations., Conclusions: We identified a high rate (67%) of differential PRAME staining in adjacent benign and malignant melanocyte populations in NAM. In PRAME positive (4+) melanomas, PRAME differentiates 100% (24/24) of benign and malignant melanocyte populations. When 4+ staining is used as the threshold for positivity, PRAME staining has a sensitivity of 67% (24/36) and a specificity of 100% (36/36). These results support PRAME IHC can assist in distinguishing melanocyte populations in melanoma arising within nevi., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background/objective: Papular epidermal nevus with skyline basal cell layer (PENS) is a recently described type of epidermal nevus with characteristic histopathologic findings, mainly regular, rectangular acanthosis and a well-demarcated basal cell layer with clear palisading and separation between basal cell nuclei and the first row of Malpighian cell nuclei. Although the first reports described randomly distributed lesions appearing sporadically in otherwise healthy patients, cases of Blaschkoid distribution, lesions associated with extracutaneous manifestations, and familial cases have been reported., Methods: We performed a review of the clinical charts of all patients with histologic diagnosis of PENS in our hospital. We evaluated epidemiologic, clinical, and histologic features. We then reviewed the literature with a particular emphasis on the presence or absence of extra-cutaneous associations., Results: Three patients with PENS are described. One had a single lesion, one had three lesions, and one, a patient with mild developmental delay, a curved penis, and hypospadias, had multiple lesions., Conclusion: The probability of having extracutaneous manifestations is 6.3 times as great in individuals with more than four lesions. Therefore these patients may need closer follow-up., (© 2016 Wiley Periodicals, Inc.)

Adults with psoriasis have a greater risk of developing metabolic syndrome (MetS) and cardiovascular disease (CVD), but few studies have investigated the prevalence of MetS and other risk factors for CVD in children with psoriasis. In an assessor-blinded study, 20 children ages 9-17 years with a current or previously documented history of psoriasis involving 5% or more of their body surface area or psoriatic arthritis were compared with a cohort of age- and sex-matched controls with benign nevi, warts, or acne. MetS, our primary endpoint, was defined by the presence of abnormal values in at least three of the following measures: triglycerides, high-density lipoprotein cholesterol (HDL-C), fasting blood glucose (FBG), waist circumference, and blood pressure. Secondary endpoints included high-sensitivity C-reactive protein (hs-CRP), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C). Thirty percent (6/20) of children with psoriasis met the criteria for MetS, compared with 5% (1/20) of the control group (p < 0.05). Subjects with psoriasis had higher mean FBG (91.1 mg/dL) than the control group (82.9 mg/dL) (p = 0.01). There were no statistically significant differences in the other four components of MetS, BMI, BMI percentile, hs-CRP, TC, or LDL-C. The results of this trial demonstrate that children with psoriasis have higher rates of MetS than age- and sex-matched controls. It may therefore be important to evaluate children with psoriasis for components of MetS to prevent future CVD morbidity and mortality., (© 2013 Wiley Periodicals, Inc.)

We performed a retrospective study covering a 10-year period (January 1997-January 2007) on children referred to our unit or followed up for Becker's nevus (BN). The aim of this study was to better define the characteristics of BN in childhood, when this hypermelanosis is more frequent than the limited number of studies might suggest. Our data show that BN in children has predilection sites similar to those in adults, but hypertrichosis is rarer. Sun exposure does not appear to play an etiopathogenetic role. The higher incidence in men reported in adult case studies was not found in children. During and after puberty, androgenic stimulation is known to play a pathogenetic role in BN, especially in men, but our cases were mostly younger than 6 years old., (© 2012 Wiley Periodicals, Inc.)

Nevus sebaceous (NS) is a common congenital hamartoma of the skin, usually found on the head and neck. It may undergo malignant transformation to basal cell carcinoma (BCC). However the incidence and lifetime risk of malignant transformation is unknown. We performed an 18-year review of all NS excisions at our institution, to report the number of cases of BCC and other neoplasms within excised NS. The aim is to inform physicians who must weigh the risks in recommending excision of a NS in a pediatric patient population with the risk of malignancy. After a database query for years 1990-2008, charts were reviewed and data were extracted on demographics and surgical history relating to NS. Thirty-one NS with abnormal findings were reviewed microscopically by a dermatopathologist. There were 651 NS distinct lesions among 631 patients and 690 excisions. Twenty-one intralesional diagnoses were found in 18 patients. Five patients (0.8%) had BCC (mean age 12.5 yrs, range 9.7-17.4 yrs). Seven (1.1%) had syringocystadenoma papilliferum (SP) (mean age 8.8 yrs, range 1.7-16.9 yrs), a lesion that may undergo malignant transformation. Malignant transformation of NS can occur in childhood or adolescence. We believe all NS should be excised, however timing of excision can be flexible. Our data do not support age cutoffs or morphologic changes to determine optimal excision time. In conjunction with the treating physician, the parent and patient may weigh the small risk of malignant transformation of NS against the morbidity associated with excision and anesthesia.

Background: We describe the planning, recruitment, key challenges, and lessons learned in the development of a study of the evolution of nevi (moles) among children in a school setting., Methods: This population-based study of digital photography and dermoscopy of the child's back (overview, close-up, and dermoscopic images) and genetic specimens took place among fifth graders in the Framingham, Massachusetts School System. Schoolchildren and their parents completed baseline surveys on sun protection practices, sunburns, and past ultraviolet exposures, including summer and vacation experiences., Results: Prestudy outreach was conducted with children, parents, nurses, administrators, and pediatricians. Of the 691 Framingham families with a fifth grader (aged 10-11), 443 consented to complete surveys and undergo digital photography and dermoscopy during the school's routine scoliosis testing. Of the 443 families providing consent, 369 agreed to genetic testing. We identified key factors to consider when implementing school-based studies: (a) pilot studies to demonstrate feasibility, (b) inclusion of school administration and parents, (c) grassroots approach with multiple contacts, and (d) embedding research studies within preexisting school health services., Conclusions: Launching an observational study within the school environment required an academic/school collaboration across numerous disciplines including dermatology, epidemiology, genetics, medical photography, school health, community health education, and most notably, the need for the presence of a full-time study nurse in the school. A large school system proved to be an excellent resource to conduct this first prospective study on the evolution of moles in US schoolchildren. The key challenges and lessons learned may be applicable to other investigators launching school-based initiatives.

Of the patients with epidermal nevi, 10-18% may have disorders of the eye, nervous, and musculoskeletal systems. A predisposition to malignant neoplasms in ectodermal and mesodermal structures may also be found. There are six different epidermal nevus syndromes described so far: Proteus, congenital hemidysplasia with ichthyosiform nevus and limb defect syndrome, phakomatosis pigmentokeratotica, sebaceous nevus, Becker nevus, and nevus comedonicus. Thirty-five patients with epidermal nevus syndrome seen at the National Institute of Pediatrics in Mexico City during a 31-year period are described. This syndrome represented 7.9% of 443 patients with epidermal nevi; its relative frequency was 1 case per 11,928 pediatric patients and 1 case per 1080 dermatologic patients. Nine epidermal nevus syndrome patients (26%) had Proteus syndrome. Sebaceous nevus syndrome was found in six patients (17%), while the nevus comedonicus syndrome was found in three (8%). Two patients were diagnosed with phakomatosis pigmentokeratotica and one patient with congenital hemidysplasia with ichthyosiform nevus and limb defect syndrome. This is the first report of phakomatosis pigmentokeratotica and congenital hemidysplasia with ichthyosiform nevus and limb defect syndrome in Mexican patients. One patient had an inflammatory linear verrucous epidermal nevus with systemic involvement. Thirteen patients (37%) had keratinocytic nevi with systemic involvement. We propose the keratinocytic nevus syndrome to be defined as the association of a keratinocytic nevus with neuronal migration and/or musculoskeletal disorders in addition to a higher risk for mesodermal neoplasms.

Background: Melanocytic nevi have been identified as the most important risk factor for cutaneous melanoma. Sun exposure, sunburns, and light pigmentation have been found to be associated with their development in childhood. To the authors' knowledge, nevus proneness of parents and the exact type of ultraviolet (UV) exposure have not yet been investigated in this context. The authors' objective was to determine independent risk factors and their impact for nevus development in childhood., Methods: The current study was conducted by two university departments of dermatology in 49 public nursery schools in Stuttgart, Germany and in 38 public nursery schools in Bochum, Germany. The cross-sectional study included 1,812 children aged 2-7 years and their parents. Total body nevus counts in children, assessment of pigmentary features, and nevus counts on the arms of parents were performed. Parents underwent a standardized interview concerning national origin and lifestyle features, as well as habits and magnitude of sun exposure of children. Analysis was performed by multivariate linear regression analysis and by multiple logistic regression analysis., Results: The number of nevi was found to steadily increase with age from a median of 3 at age 2 years to 19 at age 7 years (P < 0.0001). High numbers of nevi in children were associated with the number of weeks on sunny holidays, outdoor activities at home, skin type, facial freckling, ethnicity of parents, and the number of nevi on the arms of parents. Previously experienced sunburns failed significance (P = 0.0620)., Conclusions: The authors found a strong association between nevus development in children and the number of parental moles, which most likely points to an inherited factor. Moderate sun exposure such as outdoor activities during a German summer without sunburns seemed to be sufficient for induction of melanocytic nevi. The authors believe that these findings will have direct impact on concepts for preventive strategies., (Copyright 2003 American Cancer Society.DOI 10.1002/cncr.11114)

Achromic nevus or nevus depigmentosus is a cutaneous abnormality consisting of a hypopigmented macular lesion which can present as circumscribed irregular, oval, or round or as a unilateral band or streak with a blocklike configuration or arranged along one or more Blaschko lines. When it is systematized, it is indistinguishable from hypomelanosis of Ito. Pigmentary anomalies along the lines of Blaschko can be associated with systemic features. For these reasons, 20 children, referred consecutively for evaluation of segmental, linear achromic nevus, were evaluated to define the incidence of associated abnormal systemic features. Extracutaneous abnormalities were present in 2 of 20 children (10%). The anomalies consisted of pes cavus ipsilateral to the hypopigmentation in one child and mental retardation, seizures, and hemihypertrophy in the second. This study confirms that achromic nevus, even when distributed along Blaschko lines, is commonly a benign lesion that is associated with systemic features in a small minority of cases.

An unselected cohort of 4,641 newborns was ascertained prospectively for the purpose of detecting any cutaneous lesion. These were catalogued into pigmented lesions, vascular lesions, and miscellaneous lesions. Several important findings were elucidated: congenital nevocellular nevi are speckled at their borders; no white newborn in the study had more than one café au lait mark; a hypopigmented tuft of hair was seen in one infant with tuberous sclerosis but is found more commonly in normal individuals; a previously undescribed lesion called zosteriform melanocytic nevus was seen as a normal pigmentary variant in blacks; and hypopigmented macules seen at birth are seen primarily in normal infants. It is hoped that these findings will allow the pediatrician and dermatologist to offer more meaningful prognostic information to their patients.

We observed 5387 infants over 10 years in weekly visits to a neonatal ward and obtained the following frequency data on these skin changes: erythema toxicum neonatorum, 40.8%; perianal dermatitis, 18.9%; scrotal pigmentation, 15.2%; miliaria, 8.5%; and adnexal polyp of neonatal skin, 4.1%. The frequencies of the types of birthmarks were: mongolian spots, 81.5%; salmon patches, 22.3%; nevocellular nevi, 2.7%; port-wine stains, 2.1%; strawberry marks, 1.7%; café au lait spots, 1.7% (including a case of von Recklinghausen's disease); epidermal and sebaceous nevi, 0.3%; accessory auricles, 0.3%; and smooth muscle hamartomas, 0.2%. A positive relationship was observed between infant maturity and the prevalence of erythema toxicum neonatorum. Apart from candidiasis, neonatal skin infections were extremely rare.