Fentanyl transdermal patches induced chemical leucoderma.

Chemical leucoderma is defined as hypopigmentation or vitiligo-like hypomelanosis caused by repeated chemical exposure, and the diagnosis can be made clinically. Chemical leucoderma induced by fentanyl transdermal patches is rare. This case report involves a 53-year-old man with chronic back pain caused by herniated nucleus pulposus at the L4-L5 level. The patient had used fentanyl transdermal patches for about 2 years. Depigmented lesions were observed in the areas where fentanyl transdermal patches had been applied. Chemical leucoderma was the most likely diagnosis. There remains a debate regarding whether there is a fentanyl dose-response relationship and whether the duration of exposure is relevant. Spontaneous repigmentation may occur after discontinuing the chemical exposure, and follow-ups are recommended to monitor whether spontaneous repigmentation occurs. Additionally, several treatment options have been proposed as specific treatments for chemical leucoderma, including psoralens, corticosteroids, calcineurin inhibitors, immunosuppressive agents and phototherapy.

Herb Sanqi-Derived Compound K Alleviates Oxidative Stress in Cultured Human Melanocytes and Improves Oxidative-Stress-Related Leukoderma in Guinea Pigs.

Sanqi, a traditional Chinese herb, is widely used for cardiovascular diseases, and its neuroprotective effects against oxidative stress were recently discovered. The purpose of this study was to investigate whether Sanqi-derived compound K (Sanqi-CK), an active metabolite of Sanqi, could protect melanocytes from oxidative stress. Cultured human primary skin epidermal melanocytes (HEMn-MPs) were treated with hydrogen peroxide (H2O2) in the presence or absence of Sanqi-CK. Sanqi-CK exhibited protective effects against H2O2-induced cell death by reducing oxidative stress. In addition, treatment with Sanqi-CK reversed the decreased glutathione reductase activity and decreased ratio of reduced glutathione (GSH)/oxidized glutathione (GSSG) seen in H2O2-treated melanocytes. Furthermore, topical application of Sanqi-CK alleviated leukoderma in guinea pigs, a disorder characterized by melanocyte cell death resulting from rhododendrol-induced oxidative stress. Taken together, these data suggest that Sanqi-CK protects melanocytes against oxidative stress, and its protective effects are associated with modulating the redox balance between GSH and GSSG and activating glutathione reductase. Thus, Sanqi-CK may be a good candidate for preventing melanocyte loss in oxidative-stress-associated pigmentary disorders.

Attenuation of melanogenesis by Nymphaea nouchali (Burm. f) flower extract through the regulation of cAMP/CREB/MAPKs/MITF and proteasomal degradation of tyrosinase.

Medicinal plants have been used to treat diseases from time immemorial. We aimed to examine the efficacy of the ethyl acetate fraction of Nymphaea nouchali flower extract (NNFE) against melanogenesis process, and the underlying mechanisms in vitro and in vivo. Paper spray ionisation mass spectroscopy and (+) mode electrospray ionisation revealed the presence of seven flavonoids, two spermidine alkaloids, 3,4,8,9,10-pentahydroxy-dibenzo[b,d]pyran-6-one, and shoyuflavone C in NNFE. NNFE (100 µg/mL) significantly inhibited the monophenolase and diphenolase activities of mushroom tyrosinase at 94.90 ± 0.003% and 93.034 ± 0.003%, respectively. NNFE significantly suppressed cellular tyrosinase activity and melanin synthesis in vitro in melan-a cells and in vivo in HRM2 hairless mice. Furthermore, NNFE inhibited tyrosinase (TYR), tyrosinase-related protein (TYRP)-1, TYRP-2, and microphthalmia-associated transcription factor (MITF) expression, thereby blocking melanin synthesis. In particular, NNFE suppressed cAMP production with subsequent downregulation of CREB phosphorylation. Additionally, it stimulated MAP kinase phosphorylation (p38, JNK, and ERK1/2) and the proteasomal debasement pathway, leading to degradation of tyrosinase and MITF and the suppression of melanin production. Moreover, selective inhibitors of ERK1/2, JNK, and p38 attenuated NNFE inhibitory effects on melanogenesis, and MG-132 (a proteasome inhibitor) prevented the NNFE-induced decline in tyrosinase protein levels. In conclusion, these findings indicate that NNFE is a potential therapy for hyperpigmentation.

Chemical leukoderma.

Chemical leukoderma is defined as an acquired, hypopigmented dermatosis that results from repeated cutaneous application of an agent that destroys epidermal melanocytes in genetically susceptible patients. Chemical leukoderma may develop both at the site of contact with the chemical as well as remotely from the exposure. Avoidance of the causative agent may lead to spontaneous repigmentation, but treatments commonly used in vitiligo, such as narrow-band ultraviolet B phototherapy, PUVA photchemotherapy, or topical immunosuppressants, often are necessary. We present a case of chemical leukoderma secondary to pyrethroid insecticides that has progressed despite avoidance of the agent for over ten years.

Insights into the mechanism of Piper betle leaf-induced contact leukomelanosis using C57BL/6 mice as the animal model and tyrosinase assays.

BACKGROUND/OBJECTIVES: Steamed piper betle leaves (PBL) were once used by many Taiwanese women to treat pigment disorders on the face. Most women claimed a quick, favourable response at first, only to be overcome with facial leukomelanosis later. METHODS: C57BL/6 mice were randomly assigned to different groups to study if PBL could cause the following effects: contact dermatitis, leukomelanosis, or hair bleaching. Intracellular melanin content was measured by tyrosinase assays. RESULTS: Most steamed PBL-treated mice developed contact dermatitis and postinflammatory hyperpigmentation (PIH) on their shaved backs. About half developed bleached hair to varying extents. The steamed PBL did not only bleach the hairs, but also, unexpectedly, stimulated melanocyte replication, indicated by the fact that the number of functional melanocytes in the tail epidermis increased significantly after treatment (P = 0.007). Using tyrosinase assays PBL extract at the undiluted concentration showed limited inhibition of melanogenesis, probably via melanocytotoxicity. CONCLUSIONS: The leukomelanosis observed in patients might be the consequence of PIH combined with a mixed reaction (hyper- and hypopigmentation), probably due to the different volatile chemicals that surface after steaming the PBL. This conflicting mixed reaction suggests that counteractive ingredients might exist in PBL. PBL, if purified, might be a promising source of a novel bleaching agent.

Leucoderma after use of a skin-lightening cream containing kojic dipalmitate, liquorice root extract and Mitracarpus scaber extract.

A lighter or whiter complexion is socially desirable in many cultures. This has led to an unregulated and highly profitable market in skin-lightening creams that are readily available over the counter or on the internet. Plant extracts and newer tyrosinase inhibitors such as kojic acid or its derivative kojic dipalmitate are popular ingredients in these creams. We report a patient who developed depigmented patches after using such a cream.

Chemical leucoderma: a clinico-aetiological study of 864 cases in the perspective of a developing country.

BACKGROUND: Chemical leucoderma, often clinically mimicking idiopathic vitiligo and other congenital and acquired hypopigmentation, has been increasing rapidly in incidence in developing countries such as India. OBJECTIVES: This study attempts to detect clinical and epidemiological patterns of chemical leucoderma. METHODS: Detailed history-taking, especially of exposure to contributory chemicals, clinical examination, relevant investigations, data recording and analysis were done. RESULTS: In a total of 864 cases of chemical leucoderma, 65.6% cases started de novo and vitiligo patches were pre-existing in the remaining cases. Patches were limited to the contact area in 73.7% but had spread to remote areas in 26.3% cases. The face (41.1%) and scalp (5.9%) were the commonest and least involved sites. Confetti macules were seen in 89% and pruritus was complained of in 21.8%. Aetiological agents identified were hair dye 27.4% (21% self-use; 6.4% not self-use), deodorant and spray perfume 21.6%, detergent and cleansers 15.4%, adhesive bindi 12%, rubber chappal 9.4%, black socks and shoes 9.1%, eyeliner 8.2%, lipliner 4.8%, rubber condoms 3.5%, lipstick 3.3%, fur toys 3.1%, toothpaste 1.9%, insecticides 1.7%, 'alta' 1.2%, amulet string colour 0.9%. Therapeutic response was much better in 'pure' chemical leucoderma (73.4%) than in those with co-existing vitiligo (20.9%). CONCLUSIONS: Chemical leucoderma, a disease of mostly industrial origin in developed countries, may be induced by common domestic products in developing countries. Diagnosis and differentiation from other causes of hypopigmentation can be done confidently by following the clinical criteria as proposed. The therapeutic response of chemical leucoderma is better than that of vitiligo.

Oral zinc sulphate causes murine hair hypopigmentation and is a potent inhibitor of eumelanogenesis in vivo.

BACKGROUND: C57BL/6 a/a mice have been widely used to study melanogenesis, including in electron paramagnetic resonance (EPR) studies. Zinc cations modulate melanogenesis, but the net effect of Zn2+ in vivo is unclear, as the reported effects of Zn2+ on melanogenesis are ambiguous: zinc inhibits tyrosinase and glutathione reductase in vitro, but also enhances the activity of dopachrome tautomerase (tyrosinase-related protein-2) and has agonistic effects on melanocortin receptor signalling. OBJECTIVES: To determine in a C57BL/6 a/a murine pilot study whether excess zinc ions inhibit, enhance or in any other way alter hair follicle melanogenesis in vivo, and to test the usefulness of EPR for this study. METHODS: ZnSO(4).7H2O was continuously administered orally to C57BL/6 a/a mice during spontaneous and depilation-induced hair follicle cycling (20 mg mL-1; in drinking water; mean+/-SD daily dose 1.2+/-0.53 mL), and hair pigmentation was examined macroscopically, by routine histology and by EPR. RESULTS: Oral zinc cations induced a bright brown lightening of new hair shafts produced during anagen, but without inducing an EPR-detectable switch from eumelanogenesis to phaeomelanogenesis. The total content of melanin in the skin and hair shafts during the subsequent telogen phase, i.e. after completion of a full hair cycle, was significantly reduced in Zn-treated mice (P=0.0005). Compared with controls, melanin granules in precortical hair matrix keratinocytes, hair bulb melanocytes and hair shafts of zinc-treated animals were reduced and poorly pigmented. Over the course of several hair cycles, lasting hair shaft depigmentation was seen during long-term exposure to high-dose oral Zn2+. CONCLUSIONS: High-dose oral Zn2+ is a potent downregulator of eumelanin content in murine hair shafts in vivo. The C57BL/6 mouse model offers an excellent tool for further dissecting the as yet unclear underlying molecular basis of this phenomenon, while EPR technology is well suited for the rapid, qualitative and quantitative monitoring of hair pigmentation changes.