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Background and objectives Q-switched Nd:YAG (QS-Nd:YAG) toning (low fluence, large spot size, and high frequency) has been used successfully for the treatment of melasma, especially in dark skin phototypes. Punctate leukoderma was found to be a frequent complication that reduced the safety of this procedure. Combining low power fractional CO2 laser, which is another effective melasma laser therapy, might improve the efficacy and safety of this procedure. The aim of this study was to evaluate the effect of combining low power fractional CO2 laser with QS-Nd:YAG toning in the treatment of melasma. Study design/materials and methods A randomized comparative split-face study included a total of 30 patients with bilateral, symmetrical melasma. All patients received QS-Nd:YAG toning on one randomly selected side of the face, while the other side randomly received either low power fractional CO2 alone (group A) or combined QS-Nd:YAG toning with low power fractional CO2 (group B). QS-Nd:YAG toning sessions were scheduled every two weeks for nine consecutive sessions, and low power fractional CO2 sessions were received every 4 weeks for three consecutive sessions. The assessment was done using the modified melasma area and severity index (mMASI) score, spectrophotometry (melanin index [MI] and erythema index [EI]), photography, blinded physician assessment, and patient satisfaction (at baseline, 1 week and 8-12 weeks after the last treatment sessions). Results A significant reduction in the mMASI score and MI was obtained with all treatment regimens. On comparing different modalities, group A reduction in mMASI and MI was significantly greater on the side receiving QS-ND:YAG toning (64.03% and 8.27%, respectively), than the side receiving low power fractional CO2 laser alone (36.02%. 2.64%, respectively). On the other hand, reduction of mMASI score and MI showed no statistical significance between the side receiving QS-Nd:YAG toning alone and the combined modality. Punctate leukoderma occurred in four cases (13%) on the side receiving QS-Nd:YAG toning. Conclusion QS-Nd:YAG toning is significantly more effective than low power fractional CO2 in the treatment of melasma when used separately. Although combining low power fractional CO2 with QS-Nd:YAG toning does not increase its efficacy, it minimizes the incidence of the undesirable punctate leukoderma complication and achieves lower recurrence. This combination can thus be recommended as a safe and effective measure for the treatment of melasma. © 2021 Wiley Periodicals LLC.

Individuals who used skin‐whitening cosmetics (quasi‐drugs) containing 2% rhododendrol‐containing agents, developed leukoderma at a higher frequency than those who have used other skin‐whitening cosmetics. The Rhododenol Research Team (RD‐Team) was formed and commissioned by Kanebo Cosmetics Inc. to conduct research in treatments of rhododendrol‐induced leukoderma (RDL), to evaluate effective treatment options from a medical standpoint, and provide information to a wide range of people. In this study, we evaluated the efficacy of various treatments for RDL from a medical perspective, based on the information published in the literature as original or review articles. We searched the PubMed (international) and the Igaku Chuo Zasshi (ICHUSHI) (Japanese) databases using the keywords “Rhododenol” and “rhododendrol”, for articles published between July 2013 and November 2020. We discuss the main clinical findings and treatments (topical, oral, phototherapy, and surgical) of this condition based on the literature review. We found that ultraviolet light therapy is the most effective treatment for RDL. We have also summarized reports of the efficacy of oral vitamin D3 in RDL. A topical prostaglandin derivative has been reported in a new study to be effective. We have provided guidance for patients using self‐tanning and skin‐whitening agents to improve their quality of life. Finally, we have highlighted the importance of providing patients with information on contact dermatitis and instructing them to discontinue product use immediately if they develop any symptoms of contact dermatitis while using skin‐whitening agents.

Background Rhododendrol (RD) is cytotoxic to melanocytes and can cause leukoderma at the application site. Patients with RD-induced leukoderma usually recover after discontinuation of application (improved cases). However, occasionally lesions may expand or new lesions may develop in unapplied sites (aggravated cases). Objective To understand the pathomechanism of RD-induced leukoderma in aggravatedcases. Methods We performed immunohistochemical study to compare the expression of the catalytic subunit of glutamate cysteine ligase (GCLC), E-cadherin, and mast cell tryptase in 22 improved cases, 16 aggravated cases, and 39 normal controls. Results GCLC expression in melanocytes surrounding leukoderma was higher in improved cases than in normal controls and aggravated cases. E-cadherin expression in melanocytes was upregulated both in improved and aggravated cases and increased levels of degranulated mast cells were observed in aggravated cases. Conclusion Our results indicate that downregulation of GCLC expression due to low levels of glutathione along with reduced melanocyte migration and increased E-cadherin expression can aggravate RD-induced leukoderma. Additionally, increased degranulation of mast cells may prolong the persistence of RD-induced leukoderma.

Halo nevi, known as leukoderma acquisitum centrifugum, Sutton nevus, leukopigmentary nevus, perinevoid vitiligo, or perinevoid leukoderma, together with vitiligo and melanoma-associated hypopigmentation, belong to the group of dermatoses designated as immunological leukodermas. The etiology and pathogenesis of halo nevi has not been fully elucidated. There are several mechanisms through which a lymphocytic infiltrate can induce tumoral regression. In this review, we aimed to update the knowledge about Sutton nevi starting with the clinical appearance and dermoscopic features, continuing with information regarding conventional microscopy, immunohistochemistry, and the immunological mechanisms responsible for the occurrence of halo nevi. We also included in the article original unpublished results when discussing dermoscopic, pathologic and immunohistochemical results in halo nevi. Sutton nevi are valuable models for studying antitumor reactions that the human body can generate. The slow and effective mechanism against a melanocytic skin tumor can teach us important lessons about both autoimmune diseases and anticancer defenses.

Noncicatricial patchy alopecia of the scalp and focal areas of skin hypopigmentation imply a diagnosis of alopecia areata and vitiligo. We present a case of a 22-year-old patient in whom these symptoms were associated with positive spirochete reactions, which allowed making a diagnosis of syphilitic alopecia coexisting with leukoderma syphiliticum. Skin lesions and hair loss resolved after the treatment with benzathine benzylpenicillin. Trichoscopy in syphilitic alopecia is nonspecific, but the absence of features typical for alopecia areata such as exclamation mark hairs may be important on an early stage of the clinical workup.

Cutaneous malignant melanoma is a rapidly progressing skin tumor accounting for most deaths from skin malignancies. Four morphological variants (nodular, superficial spreading, lentigo maligna, and acral lentiginous) are described in the literature. Here we are reporting malignant melanoma in a 35-year-old male who presented with depigmented plaques with few hyperpigmented areas and extensive overlying scaling. The patient progressed to the nodular stage within 2 weeks and succumbed to death during chemotherapy. We are reporting such rare presentation of malignant melanoma to create awareness among dermatologists to avoid misdiagnosis and delayed treatment which can lead to rapid progression and fatal outcome.

Complex odontogenic infections can occur at any age, regardless of gender or social class. This type of complication has two origins: the first due to pulp necrosis with bacterial invasion to the periapical tissue and the second, due to a deep periodontal pocket. A complex odontogenic infection is characterized by its greater potential for dissemination among facial spaces, generating risk to the patient's life. In these cases, complementary exams, such as laboratory and imaging tests, are indispensable for a correct diagnosis and treatment conduct. In addition to an aggressive and intense clinical and surgical treatment, aiming at the patient's well-being. The objective of this work is to report a clinical case of complex odontogenic infection, in a leukoderma patient, male, 28 years old and without systemic involvement. The treatment performed was under general anesthesia, where the professional opted for tooth extraction, surgical drainage of the region with the installation of drains and the use of antibiotics. There were no complications during the surgical procedure and it did not show any changes during the 14 - day postoperative control. Key word: Odontogenic Infection; Dentistry; Oral surgery.

Autoimmune dermatoses targeting melanocytes have gained attention in human medicine due to their progressive nature and the social impact suffered by affected individuals. In veterinary medicine, vitiligo and the uveodermatological syndrome are the two autoimmune diseases that are known to affect skin melanocytes. In the first part of this article, we will review the signalment, clinical signs, histopathology and the treatment outcome of vitiligo in dogs, cats and horses; where pertinent, we compare the animal diseases to their human homologue. In a similar fashion, the information on the uveodermatological syndrome in dogs is reviewed and, where relevant, it is compared to the Vogt-Koyanagi-Harada (VKH) syndrome in humans. Canine, feline and equine vitiligo have many features that mirror their human counterparts. The most effective treatment and outcome of vitiligo in animals remain unclear. The canine uveodermatological syndrome resembles the incomplete VKH variant in humans; for affected individuals, an immediate diagnosis and aggressive treatment are crucial to prevent the development of blindness. Electronic supplementary material The online version of this article (10.1186/s12917-019-2003-9) contains supplementary material, which is available to authorized users.

Face vascularized composite allografts (FVCAs) have helped patients with severe facial disfigurement, with acute rejection now largely controlled through iatrogenic immunosuppression. However, little is known regarding the incidence and mechanism(s) of more long-term pathologic alterations in FVCAs that may affect function and graft durability. Protocol surveillance biopsy specimens for up to an 8-year interval in 7 patients who received FVCAs at our institution revealed histopathologic evidence of chronic rejection. Clinical manifestations included features of premature aging, mottled leukoderma accentuating suture lines, telangiectasia, and dryness of nasal mucosa. Pathologic changes consisted of epidermal thinning accompanied by discrete foci of lymphocyte-mediated cytotoxicity, hyperkeratosis, follicular plugging, vascular ectasia, and sclerosis beneath the epidermal layer associated with collagen type I deposition. Genomic interrogation and immunohistochemistry of sclerotic zones revealed upregulation of the AP-1 pathway components, JunB and c-Fos, previously implicated in overproduction of type I dermal collagen in the setting of systemic sclerosis. We conclude that some patients develop chronic rejection in FVCAs with striking similarities to alterations seen in certain autoimmune cutaneous disorders (lupus erythematosus and scleroderma/chronic sclerodermoid graft-versus-host disease). Identification of relevant pathways and genes, such as JunB and c-Fos, may provide new targets for preventative therapies for chronic immune-mediated changes in vascularized composite allografts.

Depigmented lesions may occur as postinflammatory sequelae of subacute cutaneous lupus erythematosus (SCLE), leading to great psychosocial impact. A 53-year-old male patient presented with post-SCLE depigmented facial lesions after five years of disease stability. We proposed surgical treatment with melanocyte-keratinocyte transplantation procedure (MKTP), and after five months the patient achieved 90% repigmentation, without Koebner phenomenon (KP). In theory, KP is a possible complication of MKTP procedure since the preparation of the receptor area involves the use of dermabrasion. In an attempt to avoid it, we suggest to maintain the treatment of the underlying disease and wait for a minimum period of disease stability before the procedure.

We report the case of a 73-year-old woman with leukoderma induced by cosmetics containing ascorbic acid. She had noticed the sudden appearance of a hypopigmented macule on the cheek within 1 month after use of the cosmetics with the brand name Obaji C Serum. No history of use of rhododenol-containing cosmetics was declared. Histopathological analysis revealed that the number of matured melanocytes was apparently decreased, and T lymphocytes abundantly infiltrated mainly the perifollicular region. In addition to the discontinuation of using Obaji C Serum, phototherapy by excimer light was noticeably effective for repigmentation. To our knowledge, there has been no other report so far showing hypopigmented lesions induced by this cosmetic.

Background: Although vitiligo shows a similar clinical picture to other disorders in which patients exhibit depigmented spots, there are few reports on the differentiation of these conditions from each other. Purpose: We aimed to investigate the differences and similarities between vitiligo and nevus depigmentosus in children based on the clinical course and characteristics. Materials and Methods: We conducted an examination of the disease type, treatment, progress, and differentiation of 85 cases of vitiligo and nevus depigmentosus that developed before 15 years of age among patients who visited the Osaka University Department of Dermatology with a chief complaint of white patches from January 2010 to March 2017. Results: The median age at the onset of symptoms of 79 patients with vitiligo was 4.5 years and while that of 6 patients with nevus depigmentosus was 0.8 years, indicating that the onset of nevus depigmentosus occurred earlier. While vitiligo often developed in the head and neck regions, with a tendency for depigmented spots in multiple regions, nevus depigmentosus did not show this tendency in these regions. Upon performing Wood’s lamp observation in 38 cases of vitiligo, 35 cases were found to be fluorescent chalky white and in 3 cases histologically diagnosed as vitiligo, no clear fluorescent color was observed. All 6 patients diagnosed with nevus depigmentosus exhibited a non-fluorescent off-white color under a Wood’s lamp. Conclusions: This study indicates that non-invasive observation using a Wood’s lamp is useful in the differential diagnosis of pediatric leukoderma, in addition to the subsequent clinical course, such as the presence or absence of lesional repigmentation and/or enlargement.

The aim of this study was to report a clinical case of osteonecrosis caused by bisphosphonates and its treatment with the aid of laser therapy. Low-level laser therapy (LLLT) is a resource used that is characterized by photobiostimulation and photobiomodulation, promoting analgesia and anti-inflammatory effects and can also be a tool for treating osteonecrosis induced by bisphosphonates (BFs), when associated also to drug therapy. The present case is a 63-year-old patient, leukoderma, with thyroid disorder and osteoporosis, making continuous use of medicaments classified as BF’s. He had a dental fracture and sensitivity to cold and treatment started with prophylaxis. After radiography of the dental elements, restorations were performed and tooth extraction (element 46). In the postoperative period, the patient reports pain and a bone exposure were observed clinically in the region of the extracted area, with osteonecrosis being diagnosed. Drug therapy was promptly applied and the use of LLLT was chosen as an adjunctive and supportive therapy. It is plausible to infer the need for attention to patients undergoing drug treatment with bisphosphonates, fully evaluating the best treatment for the possible occurrence of osteonecrosis in view of LLT as an effective complementary therapeutic approach. El objetivo de este estudio fue reportar un caso clínico de osteonecrosis por bifosfonatos y su tratamiento con la ayuda de la terapia a láser. La terapia con láser de baja intensidad (LLLT) es un recurso utilizado que se caracteriza por la fotobioestimulación y fotobiomodulación, promoviendo efectos analgésicos y antiinflamatorios y puede ser también una herramienta para el tratamiento de la osteonecrosis inducida por el uso de bisfosfonatos (BFs), cuando se asocia también a terapia de medicamentos. El presente caso trata de un paciente de 63 años, leucodermia, con trastorno tiroideo y osteoporosis, que hace uso continuo de fármacos clasificados como LM. Tenía una fractura dentaria y sensibilidad al frío y el tratamiento se inició con profilaxis. Luego de la radiografía de los elementos dentarios, se realizaron restauraciones y extracción del elemento 46. En el postoperatorio el paciente refiere dolor y se observó clínicamente una exposición ósea en la región del área extraída, con diagnóstico de osteonecrosis. La terapia con medicamentos se aplicó rápidamente y se eligió el uso de LLLT como terapia complementaria y de apoyo. Es plausible inferir la necesidad de atención a los pacientes en tratamiento farmacológico con bifosfonatos, evaluando a fondo el mejor tratamiento para la posible aparición de osteonecrosis de los maxilares en vista del LLT como un eficaz abordaje terapéutico complementario. O objetivo deste estudo foi relatar um caso clínico de osteonecrose causada por bisfosfonatos e seu tratamento com o auxílio de laserterapia. A terapia com laser de baixa intensidade (LLLT) é um recurso utilizado que se caracteriza pela fotobioestimulação e fotobiomodulação, promovendo analgesia e efeitos anti-inflamatórios podendo também ser uma ferramenta de manejo da osteonecrose induzida pelo uso de Bisfosfonatos (BFs), quando associada também à terapia medicamentosa. O presente caso trata-se de uma paciente de 63 anos, leucoderma, com distúrbio da tireoide e osteoporose, fazendo uso contínuo de medicamentos classificados como BF’s. Apresentava fratura dentária e sensibilidade ao frio e o tratamento iniciou com uma profilaxia. Após a radiografia dos elementos dentários, foram realizadas restaurações e uma exodontia do dente 46. No pós-operatório paciente relata dor e foi observado clinicamente uma exposição óssea na região do dentre extraído, sendo diagnosticada a osteonecrose. Prontamente aplicou-se terapia medicamentosa e se optou pelo uso de LLLT como terapia coadjuvante e auxiliadora no tratamento. É plausível inferir a necessidade de atenção a pacientes que fazem tratamento medicamentoso com bisfosfonatos, avaliando de forma completa o melhor tratamento para a possível ocorrência de osteonecrose dos maxilares tendo em vista a LLT como uma conduta terapêutica complementar eficaz.

A small proportion of individuals utilizing cosmetics containing rhododendrol developed leukoderma with various pathological conditions, in some cases indistinguishable from vitiligo. In this review, we investigate and evaluate the major considerations for developing rhododendrol‐induced leukoderma based on data from original or review articles published in the literature to provide a wide range of information regarding the pathophysiology, mechanisms, risk evaluation, and possible mechanism‐based treatments. We compile and discuss the latest information, including data related to the cytotoxicity of rhododendrol, cytoprotective functions, and involvement of the immune system, and consider the possibility of novel treatments based on the differences between individual patients and on the mechanism underlying the onset of the condition. Understanding the pathophysiology of rhododendrol‐induced leukoderma helps not only elucidate the mechanisms of non‐segmental vitiligo onset and progression, but also suggests prevention and treatment.

We present two patients with stage IV melanoma, the first with BRAF wild-type melanoma with multiple visceral metastases treated with immunotherapy (pembrolizumab) and the second with BRAFV600E melanoma with subcutaneous and lymph nodes metastasis treated with BRAF and MEK-inhibitors (dabrafenib/trametinib). Already after the second cycle of immunotherapy, the first patient developed a diffuse regression of nevi, perceptible only with the use of dermoscopy and 3 months later a clinically evident poliosis of the eyebrows. The second patient, treated with dabrafenib/trametinib, developed small areas of leukoderma on his chest and white halos around nevi with a dermoscopic globular or structureless pattern. Both observations are suggestive for an immune reaction against melanocytic cells, which is further supported by the complete response to systemic therapy in both patients. It has been demonstrated that the development of vitiligo-like depigmentation during immunotherapy is associated with a better prognosis; in our patient, the phenomenon of poliosis appeared much later than the dermoscopic presence of regression among his nevi, suggesting that the latter may be an early sign (along with vitiligo-like phenomena) of good response to immunotherapy. On the other hand, the development of halo nevi and leukoderma during treatment with BRAF/MEK-inhibitors, suggests that not only immunotherapy but also targeted therapy may induce an immunologic response against melanoma and nevi, again indicative of a favorable prognosis. More data are needed to confirm these findings; however, they indicate that dermatologists should be involved in the follow-up of patients with melanoma, both in studies and clinical practice.

In the past few years, the glucose sensor FreeStyle Libre® has been associated with several cases of allergic contact dermatitis. The allergen responsible for most of these cases is isobornyl acrylate, a substance present within the sensor that migrates through the adhesive, thereby reaching the skin. Acquired leukoderma, which may occur in an area previously affected by allergic contact dermatitis, has been described in several medical devices with adhesives. However, until the present, only one case of leukoderma induced by allergic contact dermatitis to FreeStyle Libre® has been described. We report the case of a 41-year-old woman with diabetes mellitus type 1, who developed leukoderma in association with allergic contact dermatitis to this glucose sensor.

Waardenburg syndrome (WS) is an interesting inherited audio-pigmentary disorder. The syndrome shows no gender, racial, or ethnic predilection. This unique disorder is characterized by pigmentary abnormalities, deafness, and neural crest-derived tissue defect. WS can be recognized by some specific clinical features that appear after birth; not all affected individuals possess all the clinical features. It has four clinical sub types based on the mutant gene and characteristic morphology. These morphological features are broad nasal root, white forelock, the difference in the colour of eyes, congenital leukoderma, and sensorineural deafness. We report an interesting case of WS in twin boys who fulfill the criteria of WS-II. Our cases have four major criteria (white forelock, heterochromia, sensorineural hearing loss, first degree relative with WS), and 1 minor criterion to establish the diagnosis of WS-II. Most clinical features of WS-II except sensorineural deafness are benign and do not need any intervention but severe deafness can be a serious problem. The current report is unique and is a rare case of WS in twin infants. We present this case for its rarity, relative paucity of literature, and also to emphasize the clinical presentation of this extremely rare disease in twins.

The lips are considered of great importance for the perception of beauty and there is still a lacuna in the attempt to successfully re-pigment resistant areas of vitiligo especially the lips. No technique evolved so far ensures 100% pigmentation with a good cosmetic appearance. To study the efficacy and cosmetic outcome following primary excision and closure in the management of lip vitiligo and assessing postoperative morbidity using the created surgical site morbidity score (SSMS). Twenty-five patients with vitiligo involving the inner margin of lower lips were posted for primary excision and closure of the vitiliginous area. Patients were followed up at 7 days and every 6 months. A SSMS including pain (P), healing time (H), and presence of complications (C) as parameters for assessment of postoperative morbidity were recorded at every follow-up visit. All patients showed healthy lip mucosa within 7 days of the procedure and no recurrence was noted at 24 months of follow up. The postoperative morbidity based on the SSMS was minimal, with a mean score of P2H8C0. Primary excision and closure technique is a safe and inexpensive modality in the management of lip vitiligo with immediate results and excellent cosmetic outcomes.

Introduction: Chemical leukoderma (CL) is an acquired depigmenting disorder caused by repeated exposure to chemical compounds. Thymol is a phenol derivative used as a preservative or antiseptic in many commercially available products. Here, we present the second reported case of CL caused by a thymol-containing compound. Case Presentation: A 48-year-old woman presented with a 4-month history of depigmentation of the nail folds of all ten fingers. This occurred after 1 month of twice-daily application of a thymol-containing compound intended for the removal of gel nails. No improvement was noted after the product was discontinued. There was no family history of vitiligo or other autoimmune disorders. On physical exam, depigmentation of all ten proximal and lateral nail folds was seen, with accentuation on Wood’s lamp exam. Partial re-pigmentation was achieved after 32 treatments with 308-nm excimer laser. Discussion: A thorough history and physical exam are instrumental in differentiating CL from other causes of depigmentation. Avoidance of the offending agent is an essential part of management. It is important to note that many cosmetic products are not tightly regulated by the FDA. Excimer laser is an effective treatment for CL with a favorable side-effect profile.

Skin cancers are rather uncommon malignancies comprising less than 1% of all the cancers in India. Drawstring dermatitis is a type of frictional dermatitis that can result from traditional tightly worn garments like "sari" and "salwaar-kameez". The resulting chronic friction at the waist can lead to lichenified grooves, post inflammatory depigmentation/leukoderma and aggravating pre-existing dermatoses like vitiligo and lichen planus. Chronic friction combined with sweating and humid environment of the tropics predisposes to candida, dermatophytes and bacterial infections. Rarely, squamous cell carcinoma has been reported. Prevention of the condition lies in weight reduction and tying the drawstrings loosely, especially in those inclined to develop koebnerizing conditions. Saree cancer is a rare type of squamous cell carcinoma (SCC). Saree and dhoti are traditional male and female costumes, respectively, which is unique to the Indian subcontinent. Constant wear of this clothing tightly around the waist results in changes in pigmentation and scaling of the skin, acanthosis, scar and ulceration and subsequent, gradual malignant changes. The process of repeated trauma over a long time and consequent interference with the healing process may be the reason for malignant transformation. We are presenting a rare case of saree cancer in a 68-year-old woman, with distant ulceroproliferative growth in left loin, along the waistline, which showed well-differentiated SCC on biopsy. Wide excision with primary closure was done.

Postburn leukoderma is challenging to treat with different surgical and nonsurgical treatments resulting in variable outcomes. We report a case of a 56-year-old female with postburn leukoderma treated successfully with topical daylight psoralen UVA therapy for 6 months. The treatment was well tolerated and showed excellent improvement. In conclusion, we report the successful use of topical daylight PUVA for postburn leukoderma with almost complete repigmentation. This is a simple, convenient, and cheap nonsurgical treatment option.

A distinct Darier phenotype presenting with confetti-like hypopigmented macules was first described in 1965. Designated as "guttate leukoderma," this skin finding is a rarely-reported presentation of Darier disease. It has been theorized that the mutation in ATP2A2 causes defective E-cadherin, which in turn disrupts the adhesion of melanocytes to keratinocytes, thus leading to impaired dendrite formation, hindered melanin transfer, and ultimately to melanocyte apoptosis. Herein, we contribute a case of a 56-year old woman who presented with the rarely-described guttate leukoderma of Darier disease and acrokeratosis verruciformis of Hopf.

Introdução: A hipomelanose gutata idiopática (IGH) é uma manifestação comum de fotoenvelhecimento, ainda sem tratamento padrão, apresentando resultados variados às intervenções. Atualmente, no Brasil, o uso de microagulhamento associado ao 5-fluorouracil (5-FU) tem sido proposto para o tratamento da IGH. Objetivo: Comparar três tratamentos, quais sejam: o uso do MMP® (microinfusão de medicamentos na pele) com 5-FU, MMP® apenas para microagulhamento, e com o 5-FU intralesional injetado com seringa de insulina no tratamento da IGH. Métodos: Em um ensaio clínico randomizado e cego, comparamos o MMP® ao 5-FU com: microagulhamento isolado e com 5-FU intralesional por punção para o tratamento de 180 lesões de IGH no antebraço de nove pacientes. Resultados: Após duas sessões de tratamento, o 5-FU intralesional foi o tratamento mais efetivo, com significância estatística quando comparado ao uso de microagulhamento. A eficácia da MMP + 5-FU foi inferior a 5-FU injetável e superior ao microagulhamento isoladamente, embora sem significância estatística. Conclusões: A aplicação intralesional do 5-FU foi mais eficaz no tratamento da leucodermia solar. O uso de menor quantidade de medicamentos é a grande vantagem da técnica MMP + 5-FU. São necessários mais estudos para padronizar estas técnicas.

There are numerous disorders of hypopigmentation in black skin. This chapter discusses the various lesions and how they present differently in order to help clinicians differentiate among them.

Background/Objective: Idiopathic guttate hypomelanosis (IGH) is a common disease that appears mainly in trunk, arms, and legs. IGH is a benign leukoderma characterized by multiple, hypo- or depigmented discrete macules. Although melanocytes have been reported to decrease in number in the IGH macules, changes in melanoblast number are not known. Moreover, satisfactory therapies for this disease have not been established. In this study, we investigated the presence of melanoblasts in the IGH macules, and tried to treat the IGH macules by mini-punch grafting using a machine (mMG) in combination with narrow-band ultraviolet B (NB-UVB) therapy. Methods: Mini-punch biopsies of the lesional skin of five patients (11–72-year-old men and woman) were fixed and processed to dopa and combined dopa-premelanin reactions to detect melanocytes and melanoblasts. Results: Although similar melanocyte density was observed in the lesional epidermis compared with the normal epidermis, melanoblast density was dramatically decreased. Moreover, epidermal melanin accumulation was greatly reduced in the lesional skin. For the treatment of the IGH macules, numerous mini-punch biopsies were removed from both recipient lesional skin and donor normal scalp skin, and then the donor biopsies were placed into the holes of the lesional skin. After 1 week, we started to expose NB-UVB to the lesional skin and continued the exposures. Excellent color-matched repigmentation was soon obtained. Conclusion: These results suggest that melanoblast proliferation and/or differentiation in addition to the melanosome transfer are defected in IGH, and the mMG and NB-UVB can support the excellent color-matched repigmentation. Keywords: Idiopathic guttate hypomelanosis, Melanoblast, Melanocyte, Skin, Transplantation

Rhododendrol (RD), 4‐(4‐hydroxyphenyl)‐2‐butanol, inhibits melanin synthesis and had been used in skin‐whitening cosmetic products until 2013. However, some individuals developed leukoderma on the skin where RD had been applied and have suffered from refractory depigmentation even after discontinuing RD application. Bimatoprost is a prostaglandin F2α analog and is often used for eyelash growth for cosmetic reasons as well as in the treatment of glaucoma. It was reported that bimatoprost induced skin pigmentation in addition to iris pigmentation as adverse effects. Therefore, we conducted an open‐label single‐center pilot study to evaluate the effectiveness of bimatoprost on refractory RD‐induced leukoderma. Eleven Japanese female patients with skin type III who developed leukoderma on the exact or slightly extended area of skin where RD had been applied and gained a halt of enlargement of leukoderma or repigmentation on a part of the affected skin after discontinuation of RD were enrolled. Bimatoprost 0.03% solution was applied on the leukoderma once daily for 3 months, and then the frequency of application was increased to twice daily for the subsequent 3 months. Ten patients completed the 6‐month course of bimatoprost application. In four patients, bimatoprost application brought slight improvement in RD‐induced refractory leukoderma by dermatologists’ evaluation. Because the number of enrolled patients was limited, further larger studies are necessary to better assess the effectiveness of bimatoprost in inducing repigmentation in patients with RD‐induced refractory leukoderma.

Leukoderma secondary to Q‐switched 1064‐nm neodymium‐doped yttrium aluminium garnet laser is usually refractory to treatment. The pathogenesis was cumulative phototoxic damage to melanocytes and eventually resulted in melanocytopenia. Wood's light or UV imaging can help observe early leukoderma before it becomes apparent clinically and determine the degree of melanocytopenia before conducting a biopsy. NB‐UVB phototherapy and 308‐nm excimer laser can potentially worsen the pre‐existing melasma lesions and may not be effective if the lesions have already become melanocytopenic. Epidermal grafting can replenish the hypopigmented area with melanocytes without worsening melasma.

Vitiligo is an acquired pigmentary skin of depigmentation occurring secondary to melanocyte destruction. Vitiligo and other leukodermas have a profound impact on quality of life. Current therapies include medical options, such as phototherapy, topical and systemic corticosteroids, topical calcineurin inhibitors, immunomodulators, and antioxidiants, and surgical options. Surgical options provide melanocytic cells to previously depigmented areas and use either tissue grafting or cellular grafting methods. Topical treatments are often insufficient, and many of the current surgical procedures have shown variable response rates. In this review, we discuss the process of the cellular grafting melanocyte-keratinocyte transplantation procedure (MKTP) and critically analyze its efficacy and safety in the treatment of vitiligo and other leukodermas. PubMed was searched for studies (2001-2017) describing the use of MKTP in patients with vitiligo or other leukodermas. Articles or trials discussing the use of MKTP for these patients were selected for in-depth review. Clinically relevant results regarding efficacy and safety of MKTP in vitiligo and leukoderma patients were analyzed. Numerous trials and case series/reports have demonstrated tolerability and efficacy of MKTP with repigmentation for patients with refractory, stable vitiligo. However, the response rates have been variable, likely influenced by vitiligo type and affected areas. Future research and clinical reporting will provide more insight on which phenotypes may benefit from MKTP.

We frequently encounter characteristic color variation including hypopigmentation, hyperpigmentation, and erythema in extramammary Paget’s disease (EMPD) lesions. Owing to unclear hypopigmentation, the lesional border of EMPD can be poorly defined and it is likely insufficient to perform its complete resection. Although the existence of Toker’s cells and lack of lesional bFGF production have been reported to cause hypopigmentation inside of EMPD lesions, exact mechanisms of hypopigmentation in EMPD are not fully explored. We experienced three EMPD patients with obviously hypopigmented EMPD macules and histopathologically confirmed a reduced number of melanocytes on the hypopigmented macules and their loss on the erythematous plaques or nodules. An ultrastructural analysis on the hypopigmented lesions revealed disturbance of melanosome maturation and melanosome transfer to the adherent Pagets’ cell on the basal layer. No Paget’s cells even adhered to remaining melanocytes with dendrites contained matured melanosome and a few number of matured melanosome complexes were observed in basal keratinocytes. In the present study, we hypothesize that severe disturbance of not only melanogenesis but also melanosome transfer to surrounding Paget’s cells and basal keratinocytes may cause characteristic hypopigmentation in EMPD. Future bioanalysis would reveal molecular mechanisms for hypopigmentation in EMPD.

Case series Patient: — Final Diagnosis: — Symptoms: Skin lesions Medication: — Clinical Procedure: — Specialty: Dermatology Objective: Unusual or unexpected effect of treatment Background: Vitiligo, also known as leukoderma, is an autoimmune skin condition that results in the loss of melanin pigment. Vitiligo is not a rare condition but is difficult to treat and is associated with psychological distress. Case Reports: A series of 14 cases of vitiligo are presented that were treated with individualized homeopathic remedies that were based on plant, animal, or mineral compounds. There were 13 women and one man in the case series, with a mean age 29.8 years, and a mean follow-up from treatment of 58 months. The mean time between the onset of the appearance of vitiligo and the first consultation at our clinic was 96 months. Homeopathic treatment for patients is holistic and was performed on an individualized basis as described in this case series. Photographic images of the skin are presented before and after treatment. Conclusions: In 14 patients with vitiligo treated with individualized homeopathy, the best results were achieved in the patients who were treated in the early stages of the disease. We believe that homeopathy may be effective in the early stages of vitiligo, but large controlled clinical studies are needed in this area.

Sixty patients with different clinical symptoms of secondary syphilis (ulcer chancres, pustular syphilis, hypertrophic papules, widespread leukoderma and alopecia) were examined in order to study the distribution pattern of histocompatibility antigens of the first class in patients with secondary syphilis of the skin and mucous membranes. As a result of the study, the presence of an associative relationship between the distribution pattern of histocompatibility antigens of the first class and various clinical manifestations in patients with secondary syphilis was established.

Idiopathic guttate hypomelanosis (IGH) is a commonly acquired benign leukoderma characterized by multiple discrete, hypo- or depigmented macules often on extremities that can be aesthetically undesirable for patients. This is the first study using excimer laser for treatment.To determine the effectiveness of excimer laser for repigmentation of idiopathic guttate hypomelanosis.In this longitudinal, split-body controlled, single-blinded pilot study, 6 patients were treated with excimer laser for 12 weeks using the vitiligo protocol. Effectiveness was graded by the blinded observer scale through photographic comparisons at the end of the study. Participants also graded their progress at intervals during the study. A descriptive trend analysis and an ANOVA model were used to determine outcomes.Lesions that received the excimer treatment had significantly higher repigmentation by the end of the study compared with baseline and untreated lesions.Excimer laser treatments are already considered to be a safe modality for a variety of skin conditions. This study suggests that excimer is an effective treatment option with acceptable cosmetic outcomes for IGH.

Objective To identify and characterize cases of chemical leukoderma, an underrecognized adverse event, associated with the methylphenidate transdermal system (MTS) reported to the US Food and Drug Administration Adverse Event Reporting System (FAERS). Study design We searched the Food and Drug Administration Adverse Event Reporting System for reports of chemical leukoderma associated with MTS, received by the Food and Drug Administration from April 6, 2006 to December 23, 2014. Results We identified 51 cases of chemical leukoderma reported with the use of MTS. The median age was 11 years; 43 cases reported leukoderma at or near the application site only, and 7 reported leukoderma at other parts of the body in addition to the application site; 1 case did not provide enough information to confirm the affected site. The time to onset ranged from 2 months to 4 years after the initiation of MTS. MTS was discontinued in 31 cases. Thirteen patients were prescribed treatment for repigmentation. Three cases reported continued spread of leukoderma after MTS was discontinued. Nineteen cases were diagnosed as vitiligo, including 5 cases reporting histologic features consistent with vitiligo. Leukoderma was persistent in all cases. The median follow-up interval after the discontinuation of MTS in 23 cases was 14 months. Conclusions As outlined in recent changes to the prescribing information for MTS, health care professionals need to be aware of the potential risk of chemical leukoderma caused by MTS, especially given that chemical leukoderma is often misdiagnosed as idiopathic vitiligo. MTS should be discontinued at the earliest sign of pigment loss and other treatment options considered.

patients with melanoma may develop vitiligo-like skin depigmentation referred to as melanoma-associated leukoderma (MAL), melanoma-associated hypopigmentation (MAH), melanoma-associated depigmentation (MAD) or melanoma-associated vitiligo (MAV) 1-3. Many dermatologists are not aware of the diagnosis MAL and may easily diagnose and treat these patients as having non-segmental vitiligo, thereby overlooking the underlying (metastatic) melanoma. At present, the prevalence of MAL and its clinical characteristics are not well established. This article is protected by copyright. All rights reserved.

A 60-year-old woman with leukoderma, retired, presented with a main complaint of “ball in the roof of the mouth,” evolution of 10 years, without change of size, and she had used a partial removable prosthesis for 20 years. However, in the last month she began to feel pain. She was a smoker for 10 years (1 pack/d). Clinical examination showed a nodule on the palate, normocorate, in the tooth region 24/25, 1 cm in diameter, hard to palpation, smooth surface, with defined and regular borders. An excisional biopsy was performed, which revealed gingival mucosa with hyperplastic parakeratinized squamous epithelium, and submucosa with fascicular arrangements of young fibroblast cells in dense bundles of collagen fibers. In the depth connective tissue, salivary glands with acinar atrophy and mononuclear inflammatory infiltrate and ductal dilation were noted. The diagnosis was fibroma, benign neoplasm uncommon in the oral mucosa. In the postoperative period, good healing was observed without recurrences.

Background Melanoma-associated leukoderma (MAL) is a depigmenting disorder that can occur spontaneously in patients with melanoma. The differences in clinical presentation between MAL and vitiligo are not well defined. This may lead to misdiagnosing MAL as vitiligo, resulting in delayed detection of melanoma. Objective The objective of this study was to assess whether experts in the field can distinguish between MAL and vitiligo, and to assess if discriminative features can be identified. Methods We designed an image comparison study in which 4 experts in the field blindly assessed photographs followed by medical history of 11 patients with MAL and 33 with vitiligo. Results The assessors misdiagnosed 72.7% of MAL cases and marked 80.0% of them as typical vitiligo. The median age at onset of the leukoderma was higher (55 years, P = .001) in MAL. No discriminative features were found. Limitations Sampling bias because of inclusion in tertiary referral center is a limitation. Conclusion The clinical presentation of leukoderma in patients with melanoma resembles that of vitiligo. We propose "melanoma-associated vitiligo" as the more appropriate term for leukoderma in patients with melanoma. Clinicians should be aware that depigmentation in vitiligo can also be caused by melanoma-associated vitiligo and a total body inspection should be performed.

Numerous cutaneous adverse effects have been associated with programmed death 1 (PD-1) inhibitors including maculopapular eruptions, pruritus, eczema, lichenoid reactions, leukoderma, psoriasis, sarcoidosis, immunobullous disorders, and Stevens-Johnson syndrome.1, 2 Here we report the first case, to our knowledge, of pityriasis rubra pilaris (PRP)-like erythroderma in the setting of anti–PD-1 therapy responsive to acitretin and topical steroids.