A 12-month follow-up of hypopigmentation after laser hair removal

Introduction: Laser hair removal is becoming an increasingly popular alternative to traditional methods such as shaving, waxing, among other methods. Semiconductor diode lasers are considered the most efficient light sources available and are especially well suited for clinical applications including hair reduction. The effectiveness of laser hair reduction depends on many variables, including the skin type of the patient. Material and Methods: A patient with Fitzpatrick Skin Type IV was submitted to laser hair removal of the arms with a high-power diode laser system with long pulses with a wavelength of 800 nm, a fluence of 40 J/cm2 and a pulse width of 20 ms. A 12-month follow-up assessment was performed and included photography and questionnaire. Results: Hypopigmentation was observed after a single laser hair removal section. After 6 months with the area totally covered, a gradual suntan with a sun screen lotion with an SPF of 15 was prescribed by the dermatologist. After 12 months of the initial treatment, a complete recovery of the hypopigmentation was achieved. Conclusion: Although a safe procedure, lasers for hair removal may be associated with adverse side effects including undesired pigment alterations. Before starting a laser hair removal treatment, patients seeking the eradication of hair should be informed that temporary, and possibly permanent, pigmentary changes may occur. © 2013 Informa UK, Ltd.

A 12-month follow-up of hypopigmentation after laser hair removal

Introduction: Laser hair removal is becoming an increasingly popular alternative to traditional methods such as shaving, waxing, among other methods. Semiconductor diode lasers are considered the most efficient light sources available and are especially well suited for clinical applications including hair reduction. The effectiveness of laser hair reduction depends on many variables, including the skin type of the patient. Material and Methods: A patient with Fitzpatrick Skin Type IV was submitted to laser hair removal of the arms with a high-power diode laser system with long pulses with a wavelength of 800 nm, a fluence of 40 J/cm2 and a pulse width of 20 ms. A 12-month follow-up assessment was performed and included photography and questionnaire. Results: Hypopigmentation was observed after a single laser hair removal section. After 6 months with the area totally covered, a gradual suntan with a sun screen lotion with an SPF of 15 was prescribed by the dermatologist. After 12 months of the initial treatment, a complete recovery of the hypopigmentation was achieved. Conclusion: Although a safe procedure, lasers for hair removal may be associated with adverse side effects including undesired pigment alterations. Before starting a laser hair removal treatment, patients seeking the eradication of hair should be informed that temporary, and possibly permanent, pigmentary changes may occur.

Mosaic Trisomy 18 in a Five-Month-Old Infant - Case Report

Individuals with mosaic trisomy 18, only approximately 5% of all trisomy 18 cases, carry both a trisomy 18 and an euploid cell line. Their clinical findings are highly variable, from the absence of dysmorphic features to the complete trisomy 18 syndrome. A five month old daughter of a 38-year-old mother, with vomiting and feeding problems, was referred to our department. She was undernourished and had axial hypotony and developmental delay, an irregular pattern of hypopigmentation on the right side of the abdomen, and moderate sagittal body asymmetry with left-side muscular hemihypotrophy.Mild craniofacial dysmorphy included dolichocephaly, frontal bossing, prominent occiput, long downslanting palpebral fissures, hypertelorism, and retrognathia. A complex heart defect with atrial and ventricular septal defects, pulmonary artery stenosis, and bicuspid aortic valve was identified. Cytogenetic analysis revealedmosaic trisomy 18with trisomy in 90%of peripheral lymphocytes and 17%of skin fibroblasts.This case adds to our knowledge of the phenotypic spectrum and the natural history of mosaic trisomy 18 by adding a dysmorphic feature and a cardiac abnormality that, to the best of our knowledge, had not been previously described.

Superior pedicle breast reduction for hypertrophy with massive ptosis.

Breast hypertrophy, combined with massive ptosis with a suprasternal notch-to-nipple distance of more than 40 cm, remains an endeavour. Different refinements of the initial technique with free nipple grafts have been described to circumvent the problems of nipple underprojection, areolar hypopigmentation and loss of sensibility secondary to nipple grafting, as well as lacking breast projection due to scarce glandular tissue. Techniques relying on nipple areola complex transposition, rather than grafting, have been described with inferior, superomedial and medial pedicles. The aim of this study is to present the results obtained in a series of 10 patients suffering from bilateral breast hypertrophy with massive ptosis, which was defined as a distance >40 cm from the suprasternal notch-to the nipple. All breasts were managed with a superior pedicle and inverted T technique. The mean preoperative suprasternal notch-to-nipple distance was 44 ± 2 cm, and the resection weight ranged from 800 to 2490 g per breast with an average of about 1450 g in this patient population presenting with overweight or obesity. With a mean nipple areola complex (NAC) lift of 20 ± 3 cm, neither nipple nor areola necrosis was observed. One partial epidermolysis of the areola and two cases of delayed wound healing at the trifurcation point of the inverted T were conservatively managed. Only one re-operation was necessary for an important wound dehiscence of the lateral part of the horizontal scar. These results underscore the safety of the superior pedicle technique in cases of massive ptosis with transposition of the NAC of approximately 20 cm, that is, a pedicle length of about 25 cm.

Grado de aclaramiento de tatuajes y eventos adversos, posterior a una sesión con láser q-switch

Introducción: Los resultados de la remoción de tatuajes con láser de sesión a sesión según los parámetros utilizados son limitados en la literatura. Objetivo: Evaluar los cambios en el aclaramiento de tatuajes y factores asociados posterior a una sesión con láser y los efectos adversos. Materiales y Métodos: Estudio longitudinal retrospectivo de antes y después de 1 sesión de con láser para remoción de tatuajes, donde se determinaron parámetros del tratamiento, aclaramiento y efectos adversos. Resultados: Se evaluaron 35 pacientes para un total de 98 sesiones, fototipo de piel II y IV. Equipos utilizados laser Q-Switch Nd Yag 1064 (83.3%), láser Q-Switch Nd YAG 532(11.3%) y laser Q-Switch Rubí (4.1%). El aclaramiento posterior a la sesión de láser fue evaluado por dos evaluadores independientes, mostrando concordancia significativa (Kappa de 0.615, p<0.001), con aclaración en un 96% de los tatuajes después de la sesión de láser. (p< 0.001). Se encontraron cambios significativos entre la densidad de energía aplicada y las categorías de aclaramiento de la escala de 0 a 3, siendo a mayor densidad mayor el nivel de aclaramiento (p= 0.05). No se encontró asociación significativa entre el número de pases y el aclaramiento del tatuaje. Los efectos adversos fueron del 5.4%. Cicatriz 2%, hiperpigmentación 2% y hipopigmentación 1%. Conclusión: Posterior a una sesión de remoción de tatuajes con láser Q-Switch hay un aclaramiento significativo en un 96% asociado con la densidad de energía, a mayor densidad de energía mayor el nivel de aclaramiento y no al número de pases realizados.

The metallochaperone Atox1 plays a critical role in perinatal copper homeostasis

Copper plays a fundamental role in the biochemistry of all aerobic organisms. The delivery of this metal to specific intracellular targets is mediated by metallochaperones. To elucidate the role of the metallochaperone Atox1, we analyzed mice with a disruption of the Atox1 locus. Atox1−/− mice failed to thrive immediately after birth, with 45% of pups dying before weaning. Surviving animals exhibited growth failure, skin laxity, hypopigmentation, and seizures because of perinatal copper deficiency. Maternal Atox1 deficiency markedly increased the severity of Atox1−/− phenotype, resulting in increased perinatal mortality as well as severe growth retardation and congenital malformations among surviving Atox1−/− progeny. Furthermore, Atox1-deficient cells accumulated high levels of intracellular copper, and metabolic studies indicated that this defect was because of impaired cellular copper efflux. Taken together, these data reveal a direct role for Atox1 in trafficking of intracellular copper to the secretory pathway of mammalian cells and demonstrate that this metallochaperone plays a critical role in perinatal copper homeostasis.

The ocular albinism type 1 gene product is a membrane glycoprotein localized to melanosomes.

Ocular albinism type 1 (OA1) is an inherited disorder characterized by severe reduction of visual acuity, photophobia, and retinal hypopigmentation. Ultrastructural examination of skin melanocytes and of the retinal pigment epithelium reveals the presence of macromelanosomes, suggesting a defect in melanosome biogenesis. The gene responsible for OA1 is exclusively expressed in pigment cells and encodes a predicted protein of 404 aa displaying several putative transmembrane domains and sharing no similarities with previously identified molecules. Using polyclonal antibodies we have identified the endogenous OA1 protein in retinal pigment epithelial cells, in normal human melanocytes and in various melanoma cell lines. Two forms of the OA1 protein were identified by Western analysis, a 60-kDa glycoprotein and a doublet of 48 and 45 kDa probably corresponding to unglycosylated precursor polypeptides. Upon subcellular fractionation and phase separation with the nonionic detergent Triton X-114, the OA1 protein segregated into the melanosome-rich fraction and behaved as an authentic integral membrane protein. Immunofluorescence and immunogold analyses on normal human melanocytes confirmed the melanosomal membrane localization of the endogenous OA1 protein, consistent with its possible involvement in melanosome biogenesis. The identification of a novel melanosomal membrane protein involved in a human disease will provide insights into the mechanisms that control the cell-specific pathways of subcellular morphogenesis.

Endothelin receptor B and neural crest derived melanocyte development

Neural Crest cells (NCC) constitute a unique embryonic cell population that arises between the prospective epidermis and the dorsal aspect of the neural tube of vertebrates. NCC migrate ventromedially and dorsolaterally throughout the developing embryo giving rise to the peripheral nervous system constituents and melanocytes that ultimately reside in the skin and hair follicles respectively. Mice and humans with mutations in the Endothelin receptor b (Ednrb) gene manifest strikingly similar phenotypes characterized by hypopigmentation, hearing loss and megacolon these are due to absence of melanocytes in the skin and inner ear and lack of enteric ganglia in the distal part of the gut, respectively. Piebald lethal mice and humans with Hirschsprung's disease or Waardenburg syndrome carry different mutations in the Ednrb gene. The major goals of this project were to determine whether the action of Ednrb in NCC is required prior to commitment of these cells to the melanocytic lineage and to investigate its potential participation in the actual process of commitment. In order to achieve these goals transgenic mice that express Ednrb under two different regulatory elements were created. The first, Dct-Ednrb, expresses Ednrb under the control of the DOPAchrome tautomerase (Dct) promoter to direct expression to already committed melanocyte precursors. The second, Nes-Ednrb, expresses Ednrb under the regulation of the human nestin gene second enhancer to direct expression to pre-migratory NCC. Crosses of the Dct-Ednrb mouse with piebald lethal showed that the transgene was capable of rescuing the hypopigmentation phenotype of the later. This result indicates that the action of Ednrb after NCC commit to the melanocytic lineage is sufficient for normal melanocyte development. The Dct-Ednrb was further crossed with two other hypopigmentation mutants that carry mutations in the transcription factors Sox10 and Pax3. The transgene rescued the phenotype of the Sox10 mutant only. This suggests that Ednrb interacts with Sox10 but not with Pax3 during melanocyte development. The Nes-Ednrb mice developed a hypopigmentation phenotype that was augmented when crossed with piebald lethal or lethal spotting (mutation in Edn3, the ligand for Ednrb) mice but was rescued by over expression of Edn3. These results suggest that alterations in Ednrb expression early in development affect melanocyte development. This study provides novel information necessary to better understand the early embryonic development of NCC, clarifies specific interactions between different melanogenic genes and, could eventually help in the implementation of therapies for human pigmentary genetic disorders. ^

Interactions between endothelin receptor B and transcription factors Sox10 and Pax3 in the melanocyte lineage

Genetic interactions that underlie developmental processes such as cell differentiation and pattern formation are complex and difficult to elucidate. Neural Crest (NC) cells and their derivatives offer an optimal system in which to probe for these complex interactions as they acquire different cell fates and constitute a variety of structures. The transcription factors Sox10 and Pax3 as well as the transmembrane receptor Endothelin receptor b (Ednrb) are temporally and spatially co-expressed early in NC cells and mutations in these genes lead to similar hypopigmentation phenotypes due to a reduced number of NC-derived melanocyte precursors, the melanoblasts. The goal of this study was to establish whether Sox10 and Ednrb or Pax3 and Ednrb interact to promote normal murine melanocyte development. Crosses of Sox10 or Pax3 with Ednrb heterozygous mutants showed that the double heterozygous hypopigmentation phenotype was significantly more pronounced than phenotypes of single heterozygotes, implying that a synergistic interaction exists between Sox10 and Ednrb and Pax3 and Ednrb. This interaction was further explored by the attempt to rescue the Sox10 and Pax3 hypopigmentation phenotypes by the transgenic addition of Ednrb to melanoblasts. Pigmentation was completely restored in the Sox10 and partially restored in the Pax3 mutant mice. The comparison of the number of melanoblasts in transgenic and non-transgenic Sox10 mutant embryos showed that the transgenic rescue occurred as early as E11.5, a critical time for melanoblast population expansion. Cell survival assays indicated that the rescue was not due to an effect of the transgene on melanoblast survival. A novel phenotype arose when studying the interaction between Ednrb and Pax3. Newborns appeared normal but by 3.5 weeks of age, the affected pups were smaller than normal littermates and developed a dome-shaped head; some also developed thoracic kyphosis. Affected pups were dead by 4 weeks of age: 80% were Pax3Sp/+ and 75% were female. When compared to normal littermates, affected mice had brains with enlarged 4th ventricles and more glia while skeletal staining showed kyphosis, wider rib cages and pelvic differences. An epistatic interaction resulting from the mixing of genetic backgrounds that is exacerbated in the presence of Pax3 heterozygosity is suspected.

Inducible Overexpression of Endothelin-3 in a Transgenic Mouse Leads to Hyperpigmentation That Decreases Over Time

Endothelin-3 (Edn3) has been shown to be an essential environmental cue in melanocyte development. Edn3 and its receptor, EdnrB, are allelic to mouse mutations occurring at the lethal spotting and piebald loci, respectively; these mutations result in hypopigmentation phenotypes. Mutations in the genes for both Edn3 and EdnrB are implicated in human pigmentation disorders such as Waardenburg-Shah syndrome, which is characterized by pigmentation defects, deafness, and megacolon. In this study, a tetracycline-inducible transgenic mouse model that overexpresses Edn3 under the control of the Keratin 5 promoter was shown to produce a hyperpigmentation phenotype that decreases over time. The expression pattern of transgenic Edn3 and its effects on the melanocyte population were examined in transgenic embryos, postnatal skin, and the skin of adult mice that exhibit faded hyperpigmentation. These studies suggest that overexpression of Edn3 in this model is restricted primarily to the roof plate of the neural tube and surface ectoderm in the developing embryo and to keratinocytes in the epidermis of postnatal mice. A decline in transgenic expression and a reduction in the dermal melanocytes and free melanin that characterize the phenotype in juvenile mice were shown to correlate with the fading of the hyperpigmentation phenotype. Transgenic mice in which transgenic expression was repressed (resulting in the disappearance of the hyperpigmentation phenotype) also exhibited a decrease in the dermal melanocyte population. The Edn3-overexpressing mice used in this study might be helpful m understanding human skin conditions characterized by dermal melanocytosis.

Transgenic Expression of Endothelin Receptor-B Rescues the Aganglionosis Phenotype of Piebald Lethal Mice

Neural crest cells (NCC) are a unique population of cells in vertebrates that arise between the presumptive epidermis and the dorsal most region of the neural tube. During neurulation, NCC migrate to many regions of the body to give rise to a wide variety of cell types. NCC that originate from the neural tube at the levels of somite 1-7 colonize the gut and give rise to the enteric ganglia. The endothelin signaling pathway has been shown to be crucial for proper development of some neural crest derivatives. Mice and humans with mutations in the Endothelin receptor b (Ednrb) gene exhibit similar phenotypes characterized by hypopigmentation, hearing loss, and megacolon. Thesephenotypes are due to lack of melanocytes in the skin, inner ear and enteric ganglia in the distal portion of the colon, respectively. It is well established that Ednrb is required early during the embryonic development for normal innervation of the gut. However, it is not clear if Ednrb acts on enteric neuron precursor cells or in pre-committed NC precursors. Additionally, it is controversial whether the action of Ednrb is cell autonomous or non- autonomous. We generated transgenic mice that express Ednrb under the control of the Nestin second intron enhancer (Nes) which drives expression to pre-migrating NCC. These mice were crosses to the spontaneous mouse mutant piebald lethal, which carriers a null mutation in Ednrb and exhibits enteric aganglionosis. The Nes-Ednrb was capable of rescuing the aganglianosis phenotype of piebald lethal mutants demonstrating that expression of Ednrb in pre-committed precursors is sufficient for normal enteric ganglia development. This study provides insight in early embryonic development of NCC and could eventually have potential use in cellular therapies for Hirschsprung's disease.

The role of the transcription factor Ets1 in melanocyte development

Melanocytes, pigment-producing cells, derive from the neural crest (NC), a population of pluripotent cells that arise from the dorsal aspect of the neural tube during embryogenesis. Many genes required for melanocyte development were identified using mouse pigmentation mutants. The deletion of the transcription factor Ets1 in mice results in hypopigmentation; nevertheless, the function of Ets1 in melanocyte development is unknown. The goal of the present study was to establish the temporal requirement and role of Ets1 in murine melanocyte development. In the mouse, Ets1 is widely expressed in developing organs and tissues, including the NC. In the chick cranial NC, Ets1 is required for the expression of Sox10, a transcription factor critical for the development of melanocytes, enteric ganglia, and other NC derivatives. ^ Using a combination of immunofluorescence and cell survival assays Ets1 was found to be required between embryonic days 10 and 11, when it regulates NC cell and melanocyte precursor (melanoblast) survival. Given the requirement of Ets1 for Sox10 expression in the chick cranial NC, a potential interaction between these genes was investigated. Using genetic crosses, a synergistic genetic interaction between Ets1 and Sox10 in melanocyte development was found. Since Sox10 is essential for enteric ganglia formation, the importance of Ets1 on gut innervation was also examined. In mice, Ets1 deletion led to decreased gut innervation, which was exacerbated by Sox10 heterozygosity. ^ At the molecular level, Ets1 was found to activate a Sox10 enhancer critical for Sox10 expression in melanoblasts. Furthermore, mutating Ets1 at a site I characterized in the spontaneous variable spotting mouse pigmentation mutant, led to a 2-fold decrease in enhancer activation. Overexpression and knockdown of Ets1 did not affect Sox10 expression; nonetheless, Ets1 knockdown led to a 6-fold upregulation of the transcription factor Sox9, a gene required for melanocyte and chondrocyte development, but which impairs melanocyte development when its expression is prolonged. Together, these results suggest that Ets1 is required early during melanocyte development for NC cell and melanoblast survival, possibly acting upstream of Sox10. The transcription factor Ets1 may also act indirectly in melanocyte fate specification by repressing Sox9 expression, and consequently cartilage fate.^

Interactions between Endothelin Receptor B and Transcription Factors Sox10 and Pax3 in the Melanocyte Lineage

Genetic interactions that underlie developmental processes such as cell differentiation and pattern formation are complex and difficult to elucidate. Neural Crest (NC) cells and their derivatives offer an optimal system in which to probe for these complex interactions as they acquire different cell fates and constitute a variety of structures. The transcription factors Sox10 and Pax3 as well as the transmembrane receptor Endothelin receptor b (Ednrb) are temporally and spatially co-expressed early in NC cells and mutations in these genes lead to similar hypopigmentation phenotypes due to a reduced number of NC-derived melanocyte precursors, the melanoblasts. The goal of this study was to establish whether Sox10 and Ednrb or Pax3 and Ednrb interact to promote normal murine melanocyte development. Crosses of Sox10 or Pax3 with Ednrb heterozygous mutants showed that the double heterozygous hypopigmentation phenotype was significantly more pronounced than phenotypes of single heterozygotes, implying that a synergistic interaction exists between Sox10 and Ednrb and Pax3 and Ednrb. This interaction was further explored by the attempt to rescue the Sox10 and Pax3 hypopigmentation phenotypes by the transgenic addition of Ednrb to melanoblasts. Pigmentation was completely restored in the Sox10 and partially restored in the Pax3 mutant mice. The comparison of the number of melanoblasts in transgenic and non-transgenic Sox10 mutant embryos showed that the transgenic rescue occurred as early as E11.5, a critical time for melanoblast population expansion. Cell survival assays indicated that the rescue was not due to an effect of the transgene on melanoblast survival. A novel phenotype arose when studying the interaction between Ednrb and Pax3. Newborns appeared normal but by 3.5 weeks of age, the affected pups were smaller than normal littermates and developed a dome-shaped head; some also developed thoracic kyphosis. Affected pups were dead by 4 weeks of age: 80% were Pax3Sp/+ and 75% were female. When compared to normal littermates, affected mice had brains with enlarged 4th ventricles and more glia while skeletal staining showed kyphosis, wider rib cages and pelvic differences. An epistatic interaction resulting from the mixing of genetic backgrounds that is exacerbated in the presence of Pax3 heterozygosity is suspected.

Ophthalmic findings in albinism

Purpose: Albinism is a rare genetic disorder of melanin production, which can affect only eyes or simultaneously eyes and skin/hair, resulting respectively in ocular (OA) or oculocutaneous albinism (OCA). Through of a case report of a child with OCA we pretend review ophthalmological manifestations of albinism. Case Report: A girl of West African descent was referenced to our appointment for ophthalmological evaluation of oculocutaneous albinism. Visual acuity was 20/310 OD e 20/630 OS by teller cards. In biomicroscopy, iris hypopigmentation and transillumination was visible, allowing to see spiral vessels and other iris details. Fundoscopy showed a denser and complex choroidal circulation due to lack of pigment in retinal pigment epithelium. Foveal hypoplasia was assumed because foveal pit is not apparent and vessels become less respectful of normal arcade and transverse the macula. Results: Melanin plays an important role in the development of the optic system and it’s absence leads to diverse ocular manifestations, such as: iris hypopigmentation and transillumination , reducted pigmentation of retinal pigment epithelium cells, photoreceptor rod cell deficits, foveal hypoplasia, optic nerve hypoplasia and misrouting of optic nerve at the chiasm, with temporal retina fibers inappropriately routed contralaterally instead of ipsilaterally. Photophobia, nystagmus, reduced visual acuity, color impairment and strabismus are other manifestations usually seen in albinism. Conclusion: Ophthalmologists must be familiar with the specific visual manifestations and needs of these patients. It is essential to correct refractive error to optimize visual acuity. Patients should also be advised to wear tinted glasses and sunblock. In more severely affected children they may benefit of low vision consultation and specialized low vision aids like telescopes.