Clinical, dermoscopic, and histopathologic findings of hidroacanthoma simplex: a case report and literature review.

Hidroacanthoma simplex (HS) is a rare benign intraepidermal tumor that originates in the acrosyringial portion of the eccrine duct. Clinically, they are well-defined lesions, flat or verrucous brownish plaque, and can be misdiagnosed with other types of benign or malignant tumors. Dermoscopy reveals small black globules and fine scales. The histopathology of HS is characterized by typical intraepidermal nests, well-circumscribed, composed of uniform basaloid and poroid cells within the acanthotic epidermis with cystic or ductal structures in the nests. We report a case of HS that changes its clinical appearance, dermoscopy, and histopathologic findings over time. Differential diagnoses included seborrheic keratosis, Bowen disease, melanoma, and malignant HS.

Flushing episodes in the context of frontal fibrosing alopecia with facial papules.

Frontal fibrosing alopecia (FFA) is a progressive frontotemporal hairline recession with eyebrow loss. Facial papules are present in up to 14% of FFA cases and can start with facial flushes. Nevertheless, these flushes are commonly associated with rosacea, a much more prevalent disease. In this case, a woman with FFA had, at first, clinical and histopathological findings of rosacea and was treated with ivermectin 1% cream with no improvement. She returned reporting new papules in the frontal region, reaching the frontotemporal hairline. Trichoscopy of the scalp showed mild perifollicular erythema and follicular scale. The new skin biopsy was compatible with FFA, and oral finasteride (5 mg/day) and hydroxychloroquine were introduced to stabilise the disease.

Comparison of clinical and histologic findings in daylight photodynamic therapy for skin field cancerization: A randomized controlled four-arm study on physical methods-assisted delivery of methyl aminolevulinate.

BACKGROUND: Daylight photodynamic therapy (DL-PDT) has similar efficacy to conventional photodynamic therapy in treating actinic keratosis (AKs). Good clinical outcomes have been reported when associated with physical methods such as microneedles, but a comparison of different methods and histologic studies is lacking. OBJECTIVES: To evaluate clinical and histologic modifications induced by standard DL-PDT and compare with DL-PDT associated with physical methods in treating skin field cancerization of the face. METHODS: Forty patients with photodamaged skin and at least one AK lesion on the face were randomly distributed into four groups, ten patients in each (I: Standard DL-PDT; II: DL-PDT + microneedles; III: DL-PDT + CO2 laser; IV: DL-PDT + microdermabrasion) and underwent two DL-PDT sessions with methyl aminolevulinate cream and 2-hour daylight exposure. Skin biopsies were performed on all patients before and 3 months after. All fragments were stained using the hematoxylin-eosin, orcein, and picrosirius. RESULTS: All 40 patients completed the study. Group III had a higher AK-clearance after 1 (p = 0,002) and 3 (p = 0,034) months, but it was similar in every group at 6 months (p = 0,441). Group III and IV had better clinical global improvement on texture, pigmentation and fine lines. In the groups associated with physical methods, the improvement of the keratinocytes' atypia and solar elastosis were remarkable. Only group III showed a significant reduction in solar elastosis (p = 0.034) and increased collagen type I (p = 0.028) after treatment. CONCLUSION: DL-PDT-associated with physical methods had better clinical and histologic results. AK-clearance were significantly higher after 1 and 3 months with pretreatment-CO2 laser. Photorejuvenation were more evident with pretreatment-CO2 laser and microdermabrasion. Pretreatment-CO2 laser showed a significant reduction in solar elastosis and increase of collagen type 1. These results pointed to the pretreatment with laser as a potentially better option for skin field cancerization of the face.

Nevus lipomatosus cutaneous superficialis.

Nevus lipomatosus cutaneous superficialis is a rare benign hamartomatous skin tumor characterized by dermal deposition of mature adipose tissue. Two clinical forms have been described (classical and solitary types). We describe a case of nevus lipomatosus cutaneous superficialis with a 13-year history of growth in a young woman who had a solitary skin-colored tumoral mass on the right buttock. Histopathological findings were typical and confirmed the diagnosis. In this case, the lesion was a skin-colored isolated mass, as described in the solitary type, but its localization and age of appearance were compatible with the classical type. The combination of simultaneous clinical findings of both types had not been published before.

Merkel cell carcinoma in an immunosuppressed patient.

Merkel cell carcinoma is an uncommon neuroendocrine carcinoma with a rising incidence and an aggressive behavior. It predominantly occurs in older patients, with onset occurring at a mean age of 75-80 years. Recognized risk factors are ultraviolet sunlight exposure, immunosuppression, and, more recently, Merkel cell polyomavirus. We report a case of Merkel cell carcinoma in a young HIV positive patient with Merkel Cell polyomavirus detected in the tumor.

Nevus lipomatosus cutaneous superficialis

Abstract: Nevus lipomatosus cutaneous superficialis is a rare benign hamartomatous skin tumor characterized by dermal deposition of mature adipose tissue. Two clinical forms have been described (classical and solitary types). We describe a case of nevus lipomatosus cutaneous superficialis with a 13-year history of growth in a young woman who had a solitary skin-colored tumoral mass on the right buttock. Histopathological findings were typical and confirmed the diagnosis. In this case, the lesion was a skin-colored isolated mass, as described in the solitary type, but its localization and age of appearance were compatible with the classical type. The combination of simultaneous clinical findings of both types had not been published before.

Herpes-zóster oftálmico apos injeção de onabotulinotoxina para tratamento cosmético - Relato de caso / Herpes zoster ophthalmicus after onabotulinumtoxin for cosmetic treatment: a case report

Episódios de herpes-zóster após procedimentos têm sido documentados recentemente na literatura. Uma vez que o uso da toxina botulínica atualmente se faz presente em diversas especialidades médicas, é crucial o estudo de seus efeitos colaterais e complicações. Uma revisão da literatura mostrou 65 casos de reativação de zóster após procedimentos, sendo três relacionados a injeções de toxina botulínica tipo A (dois para tratamento de rítides faciais e um para migrânea crônica). Em nosso caso, uma mulher de 43 anos previamente hígida apresentou herpe-zóster na face e couro cabeludo após injeções de toxina botulínica tipo A com fins estéticos, tendo recuperação completa após tratamento antiviral.

Herpes zoster outbreaks following minor procedures have been documented recently in literature. Since the use of botulinum toxin is nowadays spread in several medical areas for different purposes, it is crucial to study its side effects and complications. Literature review revealed 65 cases of zoster reactivation following minor procedures, and three cases related to BTA injections (two for facial lines treatment and one for chronic migraine). In our case, a 43 year old healthy woman had herpes zoster on the face and scalp after receiving BTA injections for cosmetic purpose, with complete recovery after anti-viral treatment.

Merkel cell carcinoma in an immunosuppressed patient

Abstract Merkel cell carcinoma is an uncommon neuroendocrine carcinoma with a rising incidence and an aggressive behavior. It predominantly occurs in older patients, with onset occurring at a mean age of 75-80 years. Recognized risk factors are ultraviolet sunlight exposure, immunosuppression, and, more recently, Merkel cell polyomavirus. We report a case of Merkel cell carcinoma in a young HIV positive patient with Merkel Cell polyomavirus detected in the tumor.

Necrose de parafinoma peniano após injeção de óleo mineral por profissional não médico / Penile paraffinoma necrosis after mineral oil injection applied by a non-medical professional

Parafinoma decorre da implantação de óleo mineral na pele, sendo caracterizado por reação inflamatória do tipo corpo estranho com período de latência variável. As lesões iniciais são nódulos endurecidos, que podem ulcerar, fistulizar ou necrosar. Esta técnica foi muito utilizada para fins estéticos no século XX, não sendo mais realizada por médicos. Contudo, ainda é empregada por profissionais não médicos ou pelos próprios pacientes, principalmente na região genital, para melhoria da prática sexual. Relata-se caso de implante de óleo mineral no pênis, realizado por profissional não médico para fins estéticos, que evoluiu com necrose após três anos.

Paraffinoma results from the implantation of mineral oil in the skin, being characterized by inflammatory reaction of foreign body type, with variable latency period. Initial lesions consist of hardened nodules, which can ulcerate, fistulate or necrose. This technique was widely used for aesthetic purposes in the 20th century, and is no longer performed by physicians. However, it is still used by non-medical professionals or by the patients themselves, mainly in the genital region, aimed at improving sexual activity. This paper reports a case of implantation of mineral oil in the penis, performed by a non-medical professional, for aesthetic purposes that evolved with necrosis after three years.

Skin Remodeling Using Hyaluronic Acid Filler Injections in Photo-Aged Faces.

BACKGROUND: Hyaluronic acid (HA) filler is an important dermatological procedure. Although many studies have reported clinical improvement with this procedure, histology with morphometric evidence is not well documented. OBJECTIVE: To evaluate the clinical and histological results of a HA filler injection and to quantify dermis remodeling at 3 and 9 months after HA injections into aged faces. MATERIALS AND METHODS: Twenty patients were enrolled in this study. Hyaluronic acid filler was injected into the nasolabial folds and preauricular regions of the patients. Skin biopsies of the preauricular regions were performed before the procedure and at 3 and 9 months after the procedure. RESULTS: Sixteen women (aged 40-50 years) completed the clinical study and demonstrated improvement for 12 months. Twenty patients completed the histologic studies. Morphologic evaluation showed increases in the epidermal layers. The morphometric study showed a statistically significant increase in collagen fibers at 3 and 9 months after the procedure (34.2% ± 31.5% and 39.5% ± 39.7%, respectively, p < .05). CONCLUSION: Sustained clinical results for HA filler can be explained not only by the presence of HA gel on the dermis but also by the dermal remodeling induced by HA filler injected into the face.

[Not Available]. / Pitiríase rotunda: uma apresentação incomum.

Pityriasis rotunda disorder of keratinization clinically described as persistent, large, sharply defined circular patches of ichthyosiform scaling with no inflammatory changes. Patients with pityriasis rotunda may be classified into one of two groups, which are based on ethnicity, number of lesions, family history, and association with systemic diseases. A 45-year-old woman presented with asymptomatic, sharply-demarcated, round, scaly, hyperpigmented lesions on her leg that had been present for several years. Our patient did not have systemic disease or malignancy and so does not fit into groups already described.

A double-blind randomized study comparing the association of Retinol and LR2412 with tretinoin 0.025% in photoaged skin.

INTRODUCTION: Topical tretinoin is considered the gold standard to treat photoaged skin, but it is associated with side effects and only available upon prescription. AIM OF THE STUDY: To compare the efficacy, tolerance, and perception of a fixed proprietary combination (Retinol 0.2%/LR2412 2%) vs. tretinoin 0.025% cream in women with photoaged skin. MATERIAL/METHODS: In this randomized, parallel, double-blind, controlled clinical study, women applied to the entire face for 3 months in the morning a SPF 50 sunscreen and in the evening either the association of Retinol 0.2%/LR2412 2% or tretinoin 0.025%. Clinical and instrumental parameters were assessed at days 0, 28, 56, and 84. Subject perception of the efficacy, tolerance and cosmeticity of the tested products were assessed at days 28, 56, and 84. RESULTS: A total of 120 women (60 to Retinol 0.2%/LR2412 2% cream and 60 to tretinoin 0.025% cream) were included in the study. Both products improved considerably wrinkles, mottled pigmentation, pores, and global photodamage. No statistically significant differences were noted between Retinol 0.2%/LR2412 2% cream and tretinoin 0.025% cream. Adverse effects were mostly graded mild. Overall, Retinol 0.2%/LR2412 2% cream was better tolerated than tretinoin 0.025% cream. At all visits, subject perception of the association of Retinol 0.2%/LR2412 2% was either comparable to or better than tretinoin 0.025% cream. CONCLUSION: The treatment outcome of Retinol 0.2%/LR2412 2% cream does not differ from the one of tretinoin 0.025% cream. Clinical results were not statistically different. Furthermore, Retinol 0.2%/LR2412 2% cream is better tolerated and better perceived by women used to rejuvenation procedures.

Transepidermal drug delivery: a new treatment option for areata alopecia?

BACKGROUND: Transepidermal drug delivery (TED) is a new potential method in dermatology. Permeability alterations induced by ablative fractional resurfacing have been described with the aim to increasing the delivery of different substances into the skin. OBJECTIVE: To evaluate clinical response and side effects of TED in areata alopecia (AA) treatment using ablative fractional methods associated with acoustic pressure ultrasound (US) to deliver triamcinolone solution into the skin. METHODS AND MATERIALS: Five cases of AA underwent treatment which comprised of 3 steps: 1) Ablative fractioned RF or CO2 laser 2) topical application of triamcinolone 3) acoustic pressure wave US. The number of sessions varied according to the clinical response, ranging from one to six sessions. RESULTS: All patients had complete recovery of the area treated. Two of them treated with ablative fractional RF + triamcinolone + US had complete response after three and six sessions. The other two treated with ablative fractional CO2 + triamcinolone + US had complete response after one session. CONCLUSION: Fractioned ablative resurfacing associated with acoustic pressure wave US is a new option to areata alopecia treatment with good clinical result and low incidence of side effects.

Transepidermal retinoic acid delivery using ablative fractional radiofrequency associated with acoustic pressure ultrasound for stretch marks treatment.

BACKGROUND: Striae distensae (SD) treatment still remains a therapeutic challenge to dermatologists. Ablative fractional laser and radiofrequency (RF) enhance skin-drug permeability for SD treatment. OBJECTIVE: To clinically evaluate the efficacy and safety as well as patient's satisfaction in relation to a method using ablative fractional RF associated with retinoic acid 0.05% cream and an acoustic pressure wave ultrasound (US) in patients with alba-type SD on the breast. METHODS AND MATERIALS: Eight patients with alba-type SD on the breast were treated with three step procedure: (1) fractional ablative RF for skin perforation; (2) topical application of retinoic acid 0.05% on the perforated skin; and (3) US was applied to enhance the retinoic acid penetration into the skin. Other eight patients with alba-type SD on the abdominal area were submitted to RF treatment isolated without retinoic acid or US. Three of them were submitted to skin biopsies. RESULTS: Three patients with SD on the breast area improved from "severe" to "moderate;" two patients improved from "severe" to "mild;" two patients from "moderate" to "mild;" one patient from "marked" to "mild." Clinical assessment demonstrated significant improvement in the appearance of SD in all patients treated with RF associated with retinoic acid 0.05% cream and US (P = 0.008), with low incidence of side effects and high level of patient's satisfaction. Among the patients treated only with RF, two patients improved from "severe" to "marked;" one patient from "marked" to "moderate;" and one patient improved from "marked" to "mild." Four patients did not show any sort of improvement. Clinical assessment demonstrated no significant improvement in the appearance of SD treated with RF isolated with low incidence of side effects, but low-level of patient's satisfaction. CONCLUSION: Ablative fractional RF and acoustic pressure US associated with retinoic acid 0.05% cream is safe and effective for alba-type SD treatment.

Tratamento da lipodistrofia ginoide com radiofrequência unipolar: avaliação clínica, laboratorial e ultrassonográfica / Treatment of gynoid lipodystrophy with unipolar radiofrequency: clinical, laboratory, and ultrasonographic evaluation

Introdução: A lipodistrofia ginoide pode acometer até 95% das mulheres pós-púberes. Os tratamentos visam melhorar o aspecto da pele. Procedimentos invasivos têm tempo de recuperação longo e podem causar complicações. Métodos não invasivos, como a radiofrequência, têm obtido popularidade. Objetivo: Avaliar a segurança e eficácia da radiofrequência unipolar no tratamento da lipodistrofia ginoide.Métodos: Oito mulheres com lipodistrofia ginoide grau II e III, na região glútea e coxas, foram submetidas ao tratamento com quatro sessões de radiofrequência unipolar com intervalos quinzenais. Foi realizada avaliação clinicofotográfica, laboratorial e ultrassonográfica das pacientes antes, durante e 30 dias após termo da última sessão. Resultados: Clinicamente, a melhora na flacidez da pele foi observada em todas as oito pacientes tratadas, e a melhora na morfologia em quatro delas. A avaliação ultrassonográfica mostrou aumento estatisticamente significativo (p < 0,05%) na espessura da derme após tratamento em sete das oito pacientes. Não foram observadas alterações laboratoriais. Conclusões: A radiofrequência unipolar é método eficaz e seguro no tratamento da lipodistrofia ginoide da região glútea e coxas.

Introduction: Gynoid lipodystrophy may affect up to 95% of post-pubertal women. Treatments are aimed at improving the skin's appearance. Invasive procedures have long recovery times and may cause complications. Non-invasive methods, such as radiofrequency, are increasingly becoming popular. Objective: To evaluate unipolar radiofrequency's safety and efficacy in the treatment of gynoid lipodystrophy. Methods: Eight women with gynoid lipodystrophy grades II and III, in the gluteus region and thighs, underwent treatment with four sessions of unipolar radiofrequency at fortnightly intervals. Clinical-photographic, laboratory, and ultrasound evaluations of the patients were performed before, during, and 30 days after the end of the last session. Results: Improvement in the sagging of the skin was clinically observed in all treated patients. Four patients also had improvement in morphology. The ultrasound evaluation showed a statistically significant increase (p <0. 05%) in dermal thickness after the treatment in seven of eight patients. There were no laboratory abnormalities. Conclusions: Unipolar radiofrequency is an effective and safe method in the treatment of gynoid lipodystrophy in the gluteus region and thighs.

Aplicação transepidérmica de medicamento associado a terapia fotodinâmica no tratamento de ceratoses actínicas / Transepidermal application of medication combined with photodynamic the- rapy in the treatment of actinic keratosis

A terapia fotodinâmica (TFD) tópica é método consagrado no tratamento de alguns tipos de cânceres de pele não melanoma. Recentemente, vem sendo descritas modificações noprotocolo-padrão com o objetivo de aumentar sua eficácia terapêutica. Relatam-se casos de duas pacientes com ceratoses actinícas múltiplas tratadas simultaneamente com o protocolo padrão de metilaminolevulinato (MAL-TFD) e com um protocolo modificado, pelo uso de radiofrequência fracionada (RF) associada ao ultrassom (US), em duas áreas diferentes, simetricamente acometidas. O objetivo deste trabalho é avaliar a eficácia da aplicação transepidérmica de medicamento na TFD através da associação de métodos como nova proposta terapêutica.

Topical photodynamic therapy is an established method of treating some types of non-melanoma skin cancers. Modifications to the standard protocol have recently been adopted that increase its therapeutic efficacy. This case study describes two female patients with multiple actinic keratoses who were simultaneously treated with the standard and modified protocols for methyl aminolevulinate and fractional radiofrequency combined with ultrasound in two different, symmetrically located, affected areas. This study?s objective is to evaluate the effectiveness of the transepidermal application of drugs in photodynamic therapy combined with new methods such as the proposed treatment.

Photodynamic therapy: a review of the literature and image documentation.

Photodynamic therapy (PDT) consists of a chemical reaction activated by light energy that is used to selectively destroy tissue. The reaction requires a photosensitizer in the target tissue, a light source and oxygen. The most extensively studied photosensitizing agents for PDT are 5-aminolevulinic acid for the treatment of actinic keratosis and methyl-aminolevulinate, which has been approved for the treatment of actinic keratosis, basal cell carcinoma and Bowen's disease. The light sources used in photodynamic therapy should emit light at wavelengths within the absorption spectrum of the photosensitizer used in PDT treatment. Light emitting diode (LED) lamps are indicated for the photodynamic treatment of nonmelanoma skin cancer. PDT should be considered as a therapeutic option, particularly in the case of patients with superficial, multiple or disseminated lesions and for immunosuppressed patients. More recently, PDT has been indicated for a wide range of dermatological conditions such as photo-damaged skin, acne, hidradenitis, scleroderma, psoriasis, warts and leishmaniosis, among others. This article provides an extensive review of photodynamic therapy, its mechanisms, indications and results.

Terapia fotodinâmica: revisão da literatura e documentação iconográfica / Photodynamic therapy: a review of the literature and image documentation

A terapia fotodinâmica é uma reação química ativada por luz usada para destruição seletiva de um tecido e requer um agente fotossensibilizante no tecido-alvo, uma fonte de luz e oxigênio. Estão disponíveis, no momento, o ácido 5-aminolevulínico para tratamento de ceratoses actínicas e o metilaminolevulinato, aprovado para tratamento de ceratoses actínicas, carcinoma basocelular e doença de Bowen. As fontes de luz utilizadas para a terapia fotodinâmica devem emitir comprimentos de onda no espectro de absorção do fotossensibilizante escolhido. As lâmpadas LED (light emitting diode) são as indicadas para terapia fotodinâmica tópica no tratamento do câncer de pele não melanoma. A terapia fotodinâmica deve ser considerada, em particular, para pacientes que apresentam lesões superficiais, múltiplas, disseminadas e para pacientes imunossuprimidos. Mais recentemente, a terapia fotodinâmica tem sido indicada no tratamento do fotoenvelhecimento, acne, hidrosadenite, esclerodermia, psoríase, verrugas, leishmaniose, entre outras. Por este trabalho será possível ter acesso a uma extensa revisão da literatura sobre terapia fotodinâmica, seus mecanismos, indicações e resultados, seguida de comentários e críticas pertinentes ao assunto.

Photodynamic therapy (PDT) consists of a chemical reaction activated by light energy that is used to selectively destroy tissue. The reaction requires a photosensitizer in the target tissue, a light source and oxygen. The most extensively studied photosensitizing agents for PDT are 5-aminolevulinic acid for the treatment of actinic keratosis and methyl-aminolevulinate, which has been approved for the treatment of actinic keratosis, basal cell carcinoma and Bowen's disease. The light sources used in photodynamic therapy should emit light at wavelengths within the absorption spectrum of the photosensitizer used in PDT treatment. Light emitting diode (LED) lamps are indicated for the photodynamic treatment of nonmelanoma skin cancer. PDT should be considered as a therapeutic option, particularly in the case of patients with superficial, multiple or disseminated lesions and for immunosuppressed patients. More recently, PDT has been indicated for a wide range of dermatological conditions such as photo-damaged skin, acne, hidradenitis, scleroderma, psoriasis, warts and leishmaniosis, among others. This article provides an extensive review of photodynamic therapy, its mechanisms, indications and results.

Estudo duplo cego comparativo entre hidroquinona e extrato de uva-ursina no tratamento do melasma / Double-blind comparative study of hydroquinone and ursine grape extract in the treatment of melasma

Introdução: Melasma é hiperpigmentação adquirida e progressiva em áreas fotoexpostas. Seu tratamento continua sendo um desafio por ser dermatose recorrente e refratária. Objetivo: Avaliar a eficácia e segurança do Skin Whitening Complex no tratamento do melasma facial, e compará-lo à hidroquinona. Pacientes e Métodos: Estudo duplo-cego comparativo com 13 mulheres portadoras de melasma.Todas receberam duas formulações diferentes, identificadas como "lado direito da face" e "lado esquerdo da face", que foram aplicadas duas vezes ao dia durante 90 dias consecutivos. Apenas o farmacêutico responsável tinha conhecimento do conteúdo. Para análise estatística foram realizados os testes de Wilcoxon e χ2 de McNemar-Bowker. Resultados: Das 13 pacientes, 10 apresentaram melhora clínica global do melasma. Na hemiface tratada com hidroquinona a 4%, a melhora foi total em quatro pacientes, e parcial em seis (p = 0,004). Na hemiface tratada com Skin Whitening Complex 5%, a melhora foi total em duas pacientes, e parcial em seis (p = 0,007). Não houve diferença estatisticamente significativa entre os dois tratamentos (p = 0,223). Conclusões: Embora o tratamento com hidroquinona 4% apresente melhor resultado clínico, não houve diferença estatisticamente significativa entre os dois tratamentos. O SWC 5% mostrou-se eficiente e seguro no tratamento do melasma.

Introduction: Melasma is an acquired and progressive hyperpigmentation of photoexposed areas. For being a recurrent and refractory dermatosis, its treatment continues to be a challenge. Objective: To evaluate the efficacy and security of the Skin Whitening Complex in the treatment of the facial melasma, and to compare it to the hydroquinone. Materials and methods: Double-blind Comparative study of 13 women bearers of melasma. All received two different formulations, labelled as "right side of the face" and left "side of the face".The formulations were applied twice a day for 90 consecutive days. Only the pharmacist responsible for the formulations had knowledge of their content.The tests of Wilcoxon and χ2 of McNemar-Bowker were employed in the statistical analysis. Results: Ten of the 13 patients presented the global clinical improvement of the melasma. Four patients presented total improvement and six (p = 0004) presented partial improvement in the hemiface treated with hydroquinone 4%. In the hemiface treated with Skin Whitening Complex 5%, the improvement was total in two patients, and partial in six (p = 0007).There were no statistically significant differences between the two treatments (p = 0223). Conclusions: Although the treatment with hydroquinone 4% presents better clinical results, there were no statistically significant differences between the two treatments. Skin Whitening Complex 5% has shown efficient and safe in the treatment of the melasma.