Palmoplantar depigmentation in Macaca fascicularis following Blaschko linear pattern.

Hypomelanosis of Ito is a rare neurocutaneous syndrome, characterized by streaks and swirls of hypopigmentation arranged in a Blaschkoid pattern. Other associated anomalies are observed. We report a case of a male cynomolgus monkey (Macaca fascicularis) who presented the characteristic of hypomelanosis of Ito with palmoplantar involvement and polythelia.

Terminal osseous dysplasia with pigmentary defects (TODPD) in a Turkish girl with new skin findings.

Terminal osseous dysplasia with pigmentary defects (TODPD; MIM #300244) is an extremely rare, X-linked dominant, in utero male-lethal disease, characterized by skeletal dysplasia of the limbs, pigmentary defects of the skin, and recurrent digital fibromatosis of childhood. Delayed/abnormal ossification of bones of the hands and feet, joint contractures, and dysmorphic facial features may accompany. A single recurrent mutation (c.5217 G>A) of the FLNA gene which causes cryptic splicing was identified as the cause of the disease. We here present the first TODPD case from Turkey with full-blown phenotype who exhibit unique additional findings, hypopigmented patch on the lower extremity following Blaschko's lines and smooth muscle hamartoma of the scalp in review of all the previously reported TODPD cases.

Striking contiguous depigmentation across the lower limbs in piebaldism and its implications for understanding melanocytic migration and development.

Piebaldism is a rare autosomal dominant disorder of pigmentation that is characterized by variable patches of depigmentation on the face, chest, abdomen, and extremities. We describe two cases of piebaldism, in whom the remarkable asymmetric distribution of the depigmented patches in a connected, contiguous pattern across the legs provides embryologic insights. This finding is not explained by the traditional theory that melanocytic migration only originates in the neural crest and progresses unilaterally down each leg. We propose that our cases, and other similar cases, can be explained by a recent theory of mesodermal melanocyte migration.

Autopsy findings in EPG5-related Vici syndrome with antenatal onset.

Vici syndrome is one of the most extensive inherited human multisystem disorders and due to recessive mutations in EPG5 encoding a key autophagy regulator with a crucial role in autophagosome-lysosome fusion. The condition presents usually early in life, with features of severe global developmental delay, profound failure to thrive, (acquired) microcephaly, callosal agenesis, cataracts, cardiomyopathy, hypopigmentation, and combined immunodeficiency. Clinical course is variable but usually progressive and associated with high mortality. Here, we present a fetus, offspring of consanguineous parents, in whom callosal agenesis and other developmental brain abnormalities were detected on fetal ultrasound scan (US) and subsequent MRI scan in the second trimester. Postmortem examination performed after medically indicated termination of pregnancy confirmed CNS abnormalities and provided additional evidence for skin hypopigmentation, nascent cataracts, and hypertrophic cardiomyopathy. Genetic testing prompted by a suggestive combination of features revealed a homozygous EPG5 mutation (c.5870-1G>A) predicted to cause aberrant splicing of the EPG5 transcript. Our findings expand the phenotypical spectrum of EPG5-related Vici syndrome and suggest that this severe condition may already present in utero. While callosal agenesis is not an uncommon finding in fetal medicine, additional presence of hypopigmentation, cataracts and cardiomyopathy is rare and should prompt EPG5 testing.

Multimodal imaging and functional correlations identify unusual cases of macular retinal pigment epithelium hypopigmentation occurring without functional loss.

PURPOSE: Patients with unusual macular retinal pigment epithelium (RPE) hypopigmentation are described and analyzed using retinal multimodal imaging. METHODS: We report three cases of patients with unilateral (2) or bilateral (1) macular lesions discovered incidentally on fundoscopy. A comprehensive ophthalmic examination including visual acuity, fundoscopy, spectral-domain optical coherence tomography (SD-OCT), short-wavelength light and near-infrared autofluorescence, fluorescein angiography, microperimetry, multifocal electroretinogram, adaptive optics (AO), and OCT-angiography (OCT-A) has been performed. RESULTS: Visual acuity was 20/20 in both eyes of all patients. The lesion appeared hyperautofluorescent on short-wavelength light and hypoautofluorescent on near-infrared light. Fluorescein angiography revealed a sharply demarcated macular hyperfluorescence without any leakage, suggesting a window defect. Interestingly, SD-OCT revealed only a choroidal hyperreflectivity in relation to the lesions without any abnormality of the outer retinal layers. Microperimetry was normal except for 1 patient with bilateral lesion and subtle decrease in macular sensitivity. Mf ERG was normal in all three patients. AO showed a well-preserved cone mosaic, suggesting that the abnormality was localized under the photoreceptor layers. OCT-A revealed hyperreflectivity just below the RPE layer, corresponding to the macular lesion observed on fundoscopy and the choroidal hyperreflectivity seen on SD-OCT. CONCLUSIONS: Macular RPE hypopigmentation should be considered in case of an isolated macular lesion without functional visual impairment or anatomical defect on SD-OCT.

Vitiligo: Not Simply a Skin Disease.

Melanocytes, the cells responsible for skin pigmentation, are present in other parts of the body, such as the ocular, auditory, nervous, and cardiac systems. Within these systems, their roles serve a different purpose than their classical counterparts in skin as pigment cells. Such roles include cell turnover in retinal pigment epithelium, maintenance of balance and prevention of environmental damage in the auditory neuroepithelium, role-playing as dendritic cells within the leptomeninges, and prevention of oxidative damage in adipose tissue. Vitiligo, commonly known as a skin pigmentation disorder, has also been associated with several systemic disorders, such as Vogt-Koyanagi-Harada disease and Alezzandrini, Kabuki, and MELAS syndromes. Therefore, since these conditions involve compromise of systems in which melanocytes reside, it is not surprising that vitiligo has other systemic associations. The authors present a detailed review of systemic associations of vitiligo and melanocytes' roles in other organ systems with a focus on systemic disease.

Pigmentation in African American skin decreases with skin aging.

BACKGROUND: Tristimulus colorimetry, which uses the Commission Internationale de l'Eclairage L*a*b* model to quantify color, has previously been used to analyze pigmentation and erythema in human skin; however, colorimetry of African American skin is not well characterized. OBJECTIVE: We sought to analyze skin color patterns in African Americans and compare them with those of Caucasians. METHODS: Colorimetry readings of the sun-protected buttock and sun-exposed back of forearm were taken from 40 Caucasian and 43 African American participants from March 2011 through August 2015. African American participants also completed a lifestyle questionnaire. Correlation coefficients, paired t tests, and multivariable linear regression analyses were used for statistical comparisons. RESULTS: Forearm skin was lighter in African Americans ages 65 years and older versus 18 to 30 years (P = .02) but darker in Caucasians ages 65 years or older versus 18 to 30 years (P = .03). In African Americans ages 18 to 30 years, the buttock was darker than the forearm (P < .001), whereas in Caucasians the buttock was lighter than the forearm (P < .001). A lighter forearm than buttock was correlated with supplement use, smoking (ages 18-30 years), and less recreational sun exposure (ages ≥65 years) in African Americans. LIMITATIONS: Our study was limited by the sample size and focal geographic source. CONCLUSIONS: Pigmentation patterns regarding sun-protected and sun-exposed areas in African Americans may differ from that of Caucasians, suggesting that other factors may contribute to skin pigmentation in African Americans.

Pigment Loss in Patients with Large Congenital Melanocytic Nevi: Various Clinical Presentations Documented in a Large Series.

BACKGROUND/OBJECTIVES: The association between vitiligo and congenital melanocytic nevi remains incompletely understood. The objective of this study was to investigate the frequency of depigmentation, including vitiligo, in patients with a large congenital melanocytic nevus (LCMN), which is a rare melanocytic tumor variant. METHODS: We retrospectively reviewed the files of 92 patients with an LCMN, including photographic documentation regarding the presence of pigment loss on the nevus mass, around the nevus, around the satellites, and elsewhere on the body. RESULTS: Depigmentation was observed in 8 (8.7%) of 92 patients with an LCMN. Depigmented areas within the main nevus mass were observed in six patients, and adjacent or remote vitiligo was observed in four patients. One patient also demonstrated halo depigmentation around some satellite nevi. CONCLUSION: The coexistence of an LCMN with vitiligo does not appear to be rare and may occur with a spectrum of clinical presentations.

Ventral midline blanching in the setting of segmental infantile hemangiomas: clinical observations and pathogenetic implications.

Areas of blanched skin in children may be seen as an independent finding or in association with vascular birthmarks. We performed a retrospective chart review to identify and describe infants with areas of ventral midline blanching in the presence of segmental infantile hemangiomas. We identified nine full-term infants with partial or full segmental hemangiomas and areas of midline ventral blanching. Additional ventral wall defects were seen in five patients. Six had cardiac anomalies and six had intracranial anomalies. Five were diagnosed with definite PHACE (posterior fossa, hemangioma, arterial, cardiac, and eye abnormalities) syndrome and three had possible PHACE syndrome. Eight were complicated by ulceration. Treatment varied according to the case. Ventral blanching, even in the absence of overt midline defects, can be seen in infants with segmental hemangiomas at risk for PHACE syndrome. We hypothesize that midline blanching may represent a minor manifestation of a developmental ventral defect.

Bier spots are an under-recognized cutaneous manifestation of lower extremity lymphedema: a case series and brief review of the literature.

Bier spots represent a benign vascular mottling characterized by multiple irregular white macules along the extensor surfaces of the arms and legs. They have been reported in a variety of diverse conditions with no consistent disease association. We have identified a novel association between these physiologic anemic macules and lower extremity lymphedema. Eleven patients between 23 and 70 years of age (5 male and 6 female) were diagnosed with Bier spots as evidenced by reversible white macules ranging from 3 to 8 mm in diameter on the extensor portions of the feet, ankles, and calves. The thighs were affected as well in 2 morbidly obese subjects. We suspect that these lesions are not uncommon in lymphedema but are simply under-recognized.

Topical tacrolimus significantly promotes repigmentation in idiopathic guttate hypomelanosis: a double-blind, randomized, placebo-controlled study.

BACKGROUND: Idiopathic guttate hypomelanosis (IGH) is an idiopathic disorder affecting a large number of people. Effective treatments are not yet available. Objectives To investigate the efficacy of topical 0.1% tacrolimus ointment compared with placebo in the treatment of IGH. MATERIALS AND METHODS: Twenty-six patients were included in the study. Lesions on one side of the body were selected to have a treatment with 0.1% tacrolimus ointment, whereas those on the other side served as a control with placebo ointment that had the same physical appearance. Colorimeter was used to assess skin colour at baseline and at 1, 2, 3, 4 and 6 months of treatment. RESULTS: Mean luminosity scale after adjusted for baseline from the treated side gradually decreased and reached statistical significance compared with the control group after 6 months of treatment (P = 0.019). Physicians' improvement grading score showed that 11% of the patients demonstrated improvement of their skin lesions on the treated side after 6 months' treatment. CONCLUSION: Topical 0.1% tacrolimus ointment appeared to be an effective and safe treatment for IGH. The improvements were best observed by colorimetry, yet, they were not statistically significant upon clinical assessments.

Bier spots in two children.

Bier spots are a distinct pattern of vascular mottling. Most reported cases are in young adults, with the youngest case in the literature at age 15 years. We report two children, ages 11 and 12 years, with Bier spots. Patient 1 was an 11-year-old boy who presented with white spots on the dorsal aspect of his hands. Patient 2 was a 12-year-old girl who presented with similar spots on the dorsal aspect of her left forearm and left hand. In both patients, the spots were visible when extremities were placed in a dependent position and disappeared with elevation of the extremity. Both patients were otherwise healthy.

A practical classification of childhood hypopigmentation disorders.

Hypopigmentation disorders in children can be due to a wide variety of congenital and acquired diseases. A clinical approach to hypopigmentation disorders based on the typical age of onset and the extent of lesions is proposed. The disorders are categorized into onset in early and later childhood, and in each category they are subdivided into localized and generalized pigmentary disorders. Clinical findings, comprising the sites of involvement, degree of pigment loss, and associated morphological findings, are used to distinguish the disorders further. This classification provides a systematic approach to a clinical condition in which the causes are heterogeneous and histological examination of the skin is rarely diagnostic.

Heterogeneous seizure manifestations in Hypomelanosis of Ito: report of four new cases and review of the literature.

Hypomelanosis of Ito (HI) is a rare neuroectodermal disorder often associated with mental retardation and epilepsy. We report on four new HI patients presenting with heterogeneous seizure manifestations and we review the literature concerning epileptic seizures in HI. At one extreme, there are patients with generalized seizures well controlled by drug treatment, whereas at the opposite there are patients with severe, often pharmacoresistant, focal seizures. The genetic substrate for HI syndrome is not homogenous and only partially understood. Further researches are required to shed light on the pathogenesis of HI phenotypes.

Hypomelanosis of Ito with hemimegalencephaly.

Hypomelanosis of Ito is a neurocutaneous syndrome characterized by hypopigmented lesions occurring in streaks and whorls located on the trunk, head or extremities. The associated neurological manifestations include mental retardation, seizures, language disabilities and motor system dysfunction. Hemihypertrophy has also been described in this syndrome. We present a 3-month-old male infant with Hypomelanosis of Ito, hemi-hypertrophy and hemi-megalencephaly.