Ultraviolet-induced pigmentary changes: benefits and hazards.
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Cell Division↗
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Topical prostaglandin analog (PGE2) in vitiligo--a preliminary study.
BACKGROUND: Several therapeutic options are available for the treatment of vitiligo, but none is uniformly effective. Prostaglandin has been shown to play a role in melanocyte proliferation and melanogenesis. Topical application of prostaglandin E2 (PGE2) over mice skin has been shown to increase melanocyte density. AIM: To evaluate the role of topical PGE2 in the treatment of vitiligo. METHODS: We enrolled 27 patients with limited vitiligo lesions in this study. Patients were instructed to apply a translucent gel containing 0.5 mg/3 g (166.6 micro g/g) PGE2 to depigmented skin. RESULTS: Twenty-four patients were evaluated at the end of 6 months, as three patients withdrew for reasons unrelated to the study. At the end of treatment, 15 patients showed marked to complete repigmentation and three patients showed moderate repigmentation. The remaining six patients showed none to minimal repigmentation. CONCLUSIONS: Marginal repigmentation with hyperpigmented borders was seen in the majority of lesions. Our results are encouraging and offer a new and potentially efficacious treatment for this pigmentation disorder.
Administration, Topical↗
[Deposition of colored lipids in the skin, following phenacetin abuse].
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Adult↗
Successful treatment of dark-colored epidermal nevus with ruby laser.
The pulsed ruby laser has a selective thermolytic effect. Recently, it has been available for the treatment of superficial pigmented disorders. We studied 5 cases of epidermal nevus treated with the pulsed ruby laser. In comparison with the usual methods including electrocautery, cryotherapy and skin abrasion, ruby laser therapy is an excellent tool due to technological ease and rapid improvement. Depigmentation after treatment in 2 cases was the only side effect of this therapy. Bose cases had a dark pigmentation of the skin. Despite of the risk of discoloration, the ruby laser is one of the most effective tools for therapy of pigmented epidermal nevus.
Adolescent↗
Alterations in the epidermal-dermal melanin axis and factor XIIIa melanophages in senile lentigo and ageing skin.
BACKGROUND: Senile lentigo (SL) is a pigmentation disorder that occurs predominantly on the dorsa of the hands, the forearms and the face; its incidence increases with age. Histological hallmarks of SL lesions are hyperpigmentation of the epidermis and elongation of the epidermal rete ridges. Various factors such as alpha-melanocyte-stimulating hormone, endothelin-1 or stem cell factor are involved in the onset and maintenance of the increased pigmentation. Alterations of the dermal compartment have not yet been analysed in detail in SL. OBJECTIVES: To study the occurrence and distribution of melanin in the dermis from SL and aged skin, biopsies from 12 subjects were morphologically analysed by light and electron microscopy in comparison with unaffected skin. METHODS: Punch biopsies of SL and adjacent skin from 12 male or female volunteers aged 52-81 years were prepared for light and electron microscopy and samples were analysed by morphological, morphometric, histochemical and immunohistochemical methods. RESULTS: The epidermis from SL revealed morphological features such as hyperpigmentation of basal keratinocytes and the formation of elongated rete ridges. S100+ melanocytes in the stratum basale were not markedly increased, indicating that the hyperpigmentation is predominantly due to changes in melanin synthesis, distribution or turnover. Quantification of epidermal cells expressing the proliferation marker Ki67 did not show an increase of this parameter in SL, indicating that at least in the established lesion cell proliferation is not enhanced. We further focused on the dermal compartment and observed granulated cells which were more abundant in SL. Electron microscopic and histochemical analysis revealed that the granulation of these cells is based on melanosomes, mostly present in large melanosomal complexes. Immunohistochemistry using antibodies to CD68 and factor XIIIa (FXIIIa) showed these melanophages to be predominantly FXIIIa+ dermal dendrocytes, which were about six times more abundant than CD68+ macrophages. CONCLUSIONS: In SL an increased number of melanophages was found compared with unaffected skin from the same subject. These melanophages were identified as FXIIIa+ dermal dendrocytes. Possible functional consequences of the massive melanin uptake by dermal dendrocytes are discussed.
Aged↗
A comparison of Q-switched alexandrite laser and intense pulsed light for the treatment of freckles and lentigines in Asian persons: a randomized, physician-blinded, split-face comparative trial.
BACKGROUND: Q-switched (QS) pigmented lasers and intense pulsed light (IPL) successfully treat pigment disorders. OBJECTIVE: We sought to compare efficacy and side effects of QS alexandrite laser (QSAL) and IPL for freckle and lentigo treatment in Asians. METHODS: In all, 15 patients with freckles and 17 patients with lentigines were treated randomly with one session QSAL in one cheek and two sessions IPL in the other cheek at 4-week intervals. Efficacy was determined using a new pigmentation area and severity index score. RESULTS: All patients experienced improvement (P < .0001). Postinflammatory hyperpigmentation developed in one patient with freckles and 8 patients with lentigines after QSAL. No postinflammatory hyperpigmentation occurred after IPL. Freckles achieved greater improvement after QSAL than IPL (P = .04). In lentigines, the results after IPL were better than QSAL among those with postinflammatory hyperpigmentation after QSAL. LIMITATIONS: Limitations include a small case number and short follow-up period. CONCLUSION: QSAL was superior to IPL for freckle treatment. IPL should be used for lentigines in Asian persons.
Adult↗
Comparative linkage mapping of the Grey coat colour gene in horses.
Grey horses are born coloured, turn progressively grey and often develop melanomas late in life. Grey shows an autosomal dominant inheritance and the locus has previously been mapped to horse chromosome 25 (ECA25), around the TXN gene. We have now developed eight new single nucleotide polymorphisms (SNPs) associated with genes on ECA25 using information on the linear order of genes on human chromosome 9q, as well as the human and mouse coding sequences. These SNPs were mapped in relation to the Grey locus using more than 300 progeny from matings between two Swedish Warmblood grey stallions and non-grey mares. Grey was firmly assigned to an interval with flanking markers NANS and ABCA1. This corresponds to a region of approximately 6.9 Mb on human chromosome 9q. Furthermore, no recombination was observed between Grey, TGFBR1 and TMEFF1, the last two being 1.4 Mb apart in human. There are no obvious candidate genes in this region and none of the genes has been associated with pigmentation disorders or melanoma development, suggesting that the grey phenotype is caused by a mutation in a novel gene.
Animals↗
Effects of acidum vitamin A on tyrosinase activity.
OBJECTIVE: To investigate the effect of acidum vitamin A on tyrosinase activity and provide experimental evidence for therapy of pigment disorder of skin. METHODS: Tyrosinase activity was estimated by measuring the rate of oxidation of DL-dopa. RESULTS: The levels of tyrosinase activity in the acidum vitamin A group were significantly greater than those of the control group (P < 0.01). CONCLUSION: Tyrosinase activity can be increasingly induced by acidum vitamin A.
Humans↗
Treponema pallidum in leukoderma syphiliticum demonstrated by electron microscopy.
Punch biopsies from syphilitic leukoderma lesions and from unaffected skin in 3 patients with secondary syphilis were studies in the transmission electron microscope. In one of the patients the pigment disorder was not preceded by any visible syphilids, and in the biopsy from the leukodermal skin in this patient Treponemata pallidium were demonstrated around vessels and inside nerve fibres in which the myelin sheaths of the axons showed evidence of degeneration. In the other 2 patients the depigmented areas appeared while macular and papular syphilitic lesions were healing. In the biopsies from the leukodermal lesions of these 2 patients and from unaffected skin of all 3 patients, no treponemes were demonstrated. The study indicates that syphilitic leukoderma is not invariably a post-inflammatory phenomenon, but the pigmented skin lesions may themselves represent stigmata of an active syphilitic infection.
Adult↗
Identification of a novel transcript produced by the gene responsible for the Hermansky-Pudlak syndrome in Puerto Rico.
Hermansky-Pudlak Syndrome (HPS) is a rare, autosomal recessive disorder that is characterized by oculocutaneous albinism, a predisposition to mild bleeding caused by storage-pool deficient platelets, and a ceroid storage disorder. A gene responsible for HPS in Puerto Rico maps to chromosome 10q2 and isolation of the gene has been reported. We have now identified a variant HPS cDNA that contains the same 5' sequence as the published HPS gene and a unique 3' sequence. Analysis of genomic DNA suggests that the two cDNA are derived from alternative transcripts of a single gene; two polyadenylated transcripts were found in normal human melanocytes, human bone marrow cells, human melanoma cells, lymphoblastoid cell lines, and megakaryocytic leukemia cells by reverse transcriptase polymerase chain reaction and northern analysis. The splicing exhibited by this gene is identical to the splicing found to produce two alternative transcripts of the Chediak-Higashi Syndrome gene, another pigment disorder exhibiting platelet storage pool deficiency. These studies show that the HPS gene on chromosome 10 is complex and may have more than one biologically active transcript.
Albinism, Oculocutaneous↗
Hair depigmentation is a biological readout for pharmacological inhibition of KIT in mice and humans.
Deregulated activation of the KIT receptor tyrosine kinase has been implicated in several human cancers and in inflammation, making it an attractive target for therapeutic intervention. Conversely, deficiencies in KIT signaling have been implicated in human and animal hair pigmentation disorders, reflecting a role for KIT in the development and function of melanocytes. The goal of this study was to explore the potential utility of hair depigmentation as a biological readout for systemic inhibition of KIT by SU11248 5-[5-fluoro-2-oxo-1,2-dihydroindol-(3Z)-ylidenemethyl]-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (2-diethylaminoethyl)amide), an oral multitargeted tyrosine kinase inhibitor with antitumor and antiangiogenic activity through targeting platelet-derived growth factor receptors, vascular endothelial growth factor receptors, KIT, and FLT3. Oral SU11248 treatment induced dose-dependent depigmentation of newly regrown hair in depilated C57BL/6 mice. Similar effects were seen after administration of a KIT-neutralizing antibody. SU11248-induced hair depigmentation was reversible with cessation of treatment. Histological and immunohistochemical evaluation of mouse skin samples supported these observations and revealed that SU11248 has no effect on levels of KIT-positive melanocytes associated with hair follicles, indicating that the inhibitory effect is at the level of melanocyte function rather than their development/survival. Similar hair depigmentation has been noted in several cancer patients receiving SU11248 in phase I trials. Strikingly, patient scalp hair exhibits bands of depigmentation and pigmentation that correspond, respectively, to periods of treatment and dosing rest periods. These data demonstrate that hair pigmentation can serve as a dose-dependent, dynamic, biological readout for KIT inhibition in mice, and, apparently, in humans.
Animals↗
Validation of a melasma quality of life questionnaire for Brazilian Portuguese language: the MelasQoL-BP study and improvement of QoL of melasma patients after triple combination therapy.
BACKGROUND: Pigmentation disorders, such as melasma, greatly influence the quality of life (QoL) of affected individuals who usually consider the disorder to be more severe than the objective clinical scores. Several instruments have been successfully developed to evaluate QoL. However, they must be adapted to the target population in terms of language and cultural diversity. The first, specific QoL questionnaire for melasma (MelasQoL) was developed for English speaking patients. OBJECTIVES: To validate the Brazilian Portuguese version of the MelasQoL evaluation questionnaire for patients with melasma (MelasQoL-BP) and to assess the impact of treatment with a triple combination cream (hydroquinone, fluocinolone acetonide and tretinoin) on the QoL of patients with moderate-to-severe melasma. METHODS AND RESULTS: Three hundred individuals from the five Brazilian geographic regions took part in this multicentre study. Their mean age was 42 years and skin phototype distribution was: type II 7.0% of patients, III 23.7%, IV 42.7% and V 22.7%. Melasma Area and Severity Index (MASI), MelasQoL-BP and the short version of the QoL assessment instrument from the World Health Organization (WHOQOL-BREF) were used to assess melasma severity and QoL at baseline. MelasQoL-BP was previously translated and culturally adapted from the English version, with participation of the authors and according to the standards of the World Health Organization (WHO). From the original sample, we randomized150 volunteers to treat melasma and repeated the evaluation after 8 weeks. The analysis of the MelasQoL-BP baseline answers demonstrated an important impact of the disease on skin appearance (65% of patients were bothered all the time or most of the time), frustration (55%), embarrassment (57%) and influence of the disease on interpersonal relationships (42%). Forty-three per cent of patients felt not attractive or even dirty due to their skin condition. MelasQoL-BP results showed significant internal consistency (Cronbach's alpha coefficient 0.919; P < 0.001) and good correlation with MASI scores. After treatment, the global assessment showed good or excellent results in 91.4% of the patients. The clinical outcome was not associated with the initial MASI score (P = 0.814; chi-square), skin colour (P = 0.449; probability ratio) or skin pigmentation (P = 0.814; chi-square). There was also a significant reduction on MelasQoL-BP scores (Wilcoxon test; P < 0.001) after treatment, with the mean +/- SD results shifting from 44.4 +/- 14.9 at baseline to 24.3 +/- 15.5 after treatment. The analysis of the MelasQoL-BP before and after treatment showed an important effect of the impact of treatment on a number of QoL measures. Of note, skin appearance (69.8 vs. 10.1% of patients were bothered all the time or most of the time, respectively), frustration (59.7% vs. 12.2%, respectively), embarrassment (56% vs. 9.3%, respectively) and influence of the disease on interpersonal relationships (35.3% vs. 5.8%, respectively) were greatly improved. CONCLUSIONS: This study demonstrates that MelasQoL-BP is a valid instrument and can be used to evaluate the quality of life and response to melasma treatment in Brazilian patients. The triple combination treatment produced significant results, regarding both clinical severity and quality of life.
Adult↗
Clinical study of 40 cases of incontinentia pigmenti.
OBJECTIVE: To analyze the distribution of manifestations in a pediatric cohort and define guidelines for follow-up of incontinentia pigmenti (IP). DESIGN: Retrospective study of 47 children referred to the Department of Pediatric Dermatology with a diagnosis of IP between 1986 and 1999. SETTING: The private or institutional practice of participating dermatologists and pediatricians. MAIN OUTCOME MEASURES: Evaluation of IP clinical diagnosis using the Landy and Donnai criteria. RESULTS: Because hyperpigmentation following the Blaschko lines may be observed in several pigmented disorders, 7 patients were found misdiagnosed. During the neonatal period, erythema, vesicles, and hyperkeratotic le sions were rarely absent in the patients with IP. Ocular and neurological abnormalities were frequent (20% and 30%, respectively) but rarely severe (8% and 7.5%, respectively). CONCLUSIONS: Clinical diagnosis is the first main step for a correct phenotype/genotype correlation, which remains indispensable to better understand the pathological mechanisms of IP and develop new therapies. In doubtful cases, molecular analysis is helpful but characteristic histological features must be added as major criteria for IP diagnosis. Multidisciplinary follow-up is needed, particularly during the first year of life, to detect possible ophthalmologic and neurological complications. Neuroimaging ought to be performed in the case of abnormal neurological examination results or when vascular retinopathy is detected.
Child↗
Localized carotenoid pigmentation (aurantiasis).
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Carotenoids↗
Laser iridectomy therapy of glaucoma.
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Absorption↗
The outflow tract in pigmentary glaucoma: a light and electron microscopic study.
Buttons obtained by trephination from both eyes of a 44-year-old myopic man with pigmentary glaucoma were studied by light and electron microscopy. Although clinically both eyes exhibited heavy pigmentation of the trabecular meshwork in the whole circumference, microscopically the trabecular meshwork of the left eye contained more pigment granules than that of the right eye, which appeared relatively acellular with collapse of the trabecular sheets. In both eyes endothelial cells covering the trabecular sheets were filled with pigment and showed various stages of degeneration. The intertrabecular spaces contained free pigment granules as well as cell debris. These observations suggest that plugging of the trabecular spaces by pigment and cell debris together with fragmentation and collapse of trabecular sheets contribute to the decrease in the facility of outflow that occurs in pigmentary glaucoma.
Endothelium↗