Search

Background: The differential diagnosis of psoriasis and seborrheic dermatitis can be difficult when both conditions are localized to the scalp without the involvement of other skin sites. Objective: We aimed to evaluate the histopathological differences between psoriasis and seborrheic dermatitis on the scalp and identify favorable criteria for their differential diagnosis. Methods: We evaluated 15 cases of psoriasis and 20 cases of seborrheic dermatitis of the scalp that had been clinicopathologically diagnosed. Skin biopsy sections stained with H&E were examined. Additional immunohistochemistry was performed, including Ki-67, keratin 10, caspase- 5, and GLUT-1. Results: On histopathological examination, mounds of parakeratosis with neutrophils, spongiform micropustules of Kogoj, and clubbed and evenly elongated rete ridges were significantly more frequently observed in psoriasis. Follicular plugging, shoulder parakeratosis and prominent lymphocytic exocytosis were significantly more common in seborrheic dermatitis. Moreover, significantly higher mitotic figures were observed in psoriatic lesions than in seborrheic dermatitis. Immunohistochemistry did not show any difference between psoriasis and seborrheic dermatitis. Conclusion: Histopathological features favoring psoriasis include mounds of parakeratosis with neutrophils, spongiform micropustules of Kogoj, clubbed and evenly elongated rete ridges, and increased mitotic figures (≥ 6/high-powered field). Features indicating seborrheic dermatitis are follicular plugging, shoulder parakeratosis and prominent lymphocytic exocytosis. Immunohistochemistry was not helpful in differentiating psoriasis from seborrheic dermatitis. (Ann Dermatol 28(4) 427∼432, 2016)

Dear Editor: Lymphedema is a common sequelae after cancer surgery with lymph node dissection1. A lymphedematous limb, which is prone to the development of infections or tumors, suggests an alteration in regional immune competence2. Neutrophilic dermatosis on postmastectomy lymphedema (NDPL) is a newly suggested disease by Demitsu and Tadaki3 It is also referred to as localized Sweet's syndrome (SS) because of the histological similarities between the two conditions4. Herein, we report additional cases of neutrophilic dermatosis confined within a lymphedematous site and a review of the disease entity. All three cases involved female patients, two of whom were breast cancer patients who underwent modified radical mastectomy with axillary lymph node dissections (Table 1). The third patient had undergone radical hysterectomy with pelvic lymph node dissection for cervical cancer. Lymphedema was confined to the lymphnode-dissected limb developed in all three patients after the surgery. All of them rapidly developed erythematous rashes on their lymphedematous limb (Fig. 1A, B). Skin biopsy revealed marked papillary dermal edema and dense dermal neutrophil infiltrates, consistent with the histopathologic features of SS (Fig. 1C, D). The laboratory findings, including white blood cell count, percentage of neutrophils, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP), were within the normal ranges, except in case 3 (ESR: 35 mm/h; CRP: 4.09 mg/dl). Each case was treated with topical or oral corticosteroid, or oral antibiotics. In case 3, the lesion recurred rapidly after initially being treated with oral antibiotics. After the administration of oral corticosteroid, the lesion rapidly resolved within 1 week. On the basis of the characteristic distribution of the lesion and the histopathologic features, a diagnosis of 'neutrophilic dermatosis on the lymphedematous area' was made. Fig. 1 (A) Case 1. Multiple variable-sized erythematous papules, vesicles, and plaques localized on the right lymphedematous arm. (B) Case 3. Multiple erythematous papules and patches confined on the left lymphedematous leg. (C, D) Histopathological findings. ... Table 1 Clinical characteristics of the three cases Neutrophilic dermatosis or SS localized on the area of lymphedema is rare, and only 11 cases have been reported1,3,4. The clinical presentations of previously reported cases were erythematous papules, plaques, and vesicles on the lymphedematous arm after a mastectomy, which are consistent with our cases1,3,4. The pathomechanism cannot be fully demonstrated; however, the vulnerability of the lymphedematous area seems to be the main factor1,2,5. The stasis of protein-rich lymphatic fluid contains numerous cytokines that might attract neutrophils and also result in the impairment of immune surveillance2,5. Because this dermatosis shows typical clinicohistopathological findings of SS, they are considered a localized variant of SS4. However, other systemic presentations, such as leukocytosis, neutrophilia, or fever, were less frequent than in typical SS. Therefore, several other reports suggested the use of the new term NDPL1,3. Other clinical differential diagnosis included cellulitis or erysipelas. Contrary to cellulitis or erysipelas, the lesion was confined only to the lymphedematous area and was well treated with oral or topical corticosteroid1,4. Although the 11 reports to date were cases of a lesion on a lymphedematous arm after a mastectomy, our report includes one case of a lesion that had developed on the lymphedematous leg after a hysterectomy for cervical cancer. Consequently, our cases suggest a novel point that a lesion could develop on any lymphedematous limb after lymph node dissection. Therefore, we suggest the term 'neutrophilic dermatosis on the lymphedematous area' rather than NDPL.

5 . Positive reaction to p-tertbutylphenol formaldehyde resin is related to contact with waterproof glue, bonded leather, and con- struction materials, whereas that to p-phenylenediamine is related to contact with permanent or semipermanent hair dyes, dyed textiles, and cosmetics; however, these are less relevant compared with our case. In conclusion, this report suggests that patients with HHE should be comprehensively evaluated through history taking and correctly treated by avoiding the suspicious material.

Dear Editor: Imatinib mesylate, a tyrosine kinase inhibitor targeting c-kit and platelet-derived growth factor, has been used for the treatment of hematologic malignancies. Its cutaneous adverse effects are diverse, including maculopapular exanthema, vasculitis, and Stevens-Johnson syndrome1. A well-established pigmentary change is hypopigmentation, which is characterized by generalized skin lightening, vitiligo-like lesions, and hair graying2. However, paradoxical hyperpigmentary changes were rarely observed3,4. We present a case of hyperpigmentation of the nose and hard palate associated with imatinib mesylate. A 58-year-old man was referred for discoloration of the nose. He was diagnosed with chronic myelogenous leukemia and was treated with imatinib mesylate (Gleevec; Novartis, Basel, Switzerland). Not long after imatinib treatment, he noticed insidious pigmentary changes on his nose. He had no history of skin eruptions or use of other medication. Physical examination revealed an ill-defined, slate-gray patch on the nose and on the hard palate, which suggested a diagnosis of dermal pigmentary disorders including acquired bilateral nevus of Ota-like macules (Fig. 1). Biopsy of the lesional skin and perilesional normal skin of the nose was performed. Fontana-Masson staining showed increased basal pigmentation and dermal melanophages in the lesional skin compared with the perilesional normal skin (Fig. 2A). Imunohistochemical staining with the NKI/beteb antibody confirmed the absence of melanocytes in the dermis (Fig. 2B). Therefore, the pigmentation was speculated to be imatinib-associated hyperpigmentation. Although hypopigmentation is a well-known pigmentary change due to imatinib treatment, paradoxical hyperpigmentation has been rarely reported. In hyperpigmentation, the changes are not generalized like hypopigmentary changes. The disorder pigmentation is localized in the oral cavity, including the hard palate and gum, nose, ear lobe, or nails3,4. The present case was consistent with these features, and the patient showed localized pigmentation on the nose and hard palate. There has been no report about the prognosis of this pigmentary change. In case of hypopigmentation, it could be reversible when the doses are tapered or the treatment is stopped2. Our patient is continuing imatinib treatment, and there has been no change in the pigmentation. It has been suggested that imatinib-induced hypopigmentation is mediated by c-kit inhibition, resulting in reduced tyrosinase activity in melanocytes5. The mechanism of this paradoxical hyperpigmentation is unclear. However, an in vitro study has shown the stimulating effect of imatinib on the tyrosinase activity of cultured melanocytes, which suggests the target-dependent stimulating effects of imatinib mesylate on pigmentation. Further studies are required to elucidate these pigmentary changes related to imatinib mesylate medication. Herein, we report a case of paradoxical hyperpigmentation of the nose and hard palate after imatinib mesylate treatment, warranting further evaluation of this mechanism. Fig. 1 Ill-defined slate grey-colored pigmentation on nose (A) and palate (B). Fig. 2 (A) Increased epidermal pigmentation and dermal melanophages in the lesional skin (L) compared with perilesional normal skin (N) (Fontana-Masson stainining, ×200). (B) There were no melanocytes in the dermis (gp100, ×200).

Dear Editor: Nevus depigmentosus (ND) is characterized by a congenital hypopigmented macule or patch. The pathophysiology of ND is poorly understood, but likely associated with a functional defect in melanosome transfer from melanocytes to keratinocytes1. ND is known to remain generally stable in size and distribution throughout life1. Herein, we describe a case of a 6-year-old boy whose ND disappeared, suggesting the possibility of spontaneous resolution of ND. A 10-month-old male was brought to our clinic because of whitish patches on his right leg that had been present since his birth. Physical examination revealed hypopigmented patches on the medial side of right thigh (Fig. 1a). A diffuse bluish patch that was suspected to be an aberrant Mongolian spot surrounded the hypopigmented areas. A 2-mm punch biopsy of the hypopigmented patches and adjacent perilesional normal skin at 1 cm from margin was performed. There were no remarkable findings on H&E staining (Fig. 2a). Fontana-Masson staining showed decreased epidermal pigmentation in the lesional skin compared to the perilesional normal skin (Fig. 2b). There was no difference in the number of NKI/beteb positive melanocytes between the lesional and perilesional normal skin (Fig. 2c). These findings were consistent with ND. The patient did not receive any treatment and was lost to follow-up until his recent revisit 6 years later. At that time, he returned with a facial mobiliform eruption, accompanied by fever and conjunctival injection, and was diagnosed with erythema infectiosum. Interestingly, during physical examination, it was noted that the previous ND and the surrounding aberrant Mongolian spot had completely disappeared (Fig. 1b). The patient's parents did not recall the time of the ND disappearance. Fig. 1 Spontaneous disappearance of hypopigmented macules and patches. (a) A 10-month-old male presented with hypopigmented macules and patches on his right thigh in linear configuration since birth. A diffuse bluish patch that was suspected to be an aberrant ... Fig. 2 Histological findings. (a) There were no remarkable findings on H&E staining. (b) Fontana-Masson staining showed decreased epidermal pigmentation in the lesional skin compared to the perilesional normal skin. (c) There was no difference in the ... Spontaneous resolution of ND has never been reported. However, it should be noted that there has been no epidemiological study regarding the fate of ND. Moreover, there have been several reports suggesting the possibility that the functional defect of the melanocytes in ND is reversible2,3. Bardazzi et al.2 described the development of lentigines within ND after narrow band ultraviolet B exposure. They suggested the possibility of partial activation of melanosome transfer, resulting in overproduction of melanin within ND. Oiso et al.3 reported a case of acquired junctional melanocytic nevus development in ND. These cases suggest that melanocytes in ND could transform from a functionally defective stage to an active stage or shift to other forms such as nevus cells. Interestingly, in our case, the ND and Mongolian spots were coexistent at the initial visit and both had disappeared at the next visit. The possible relationship between Mongolian spots and spontaneous regression of ND could be suspected. There was no confirmative diagnosis of ND. It is important to consider the other hypopigmenting conditions, such as postinflammatory hypopigmentation or hypomelanosis of Ito4. Because the lesion was present from birth and he did not have any history of inflammation on the hypopigmented lesion, postinflammatory hypopigmentation could be differed from our case. Hypomelanosis of Ito consists of hypopigmented zones or spots with irregular borders, whorls, patches, or linear streaks with various patterns of distribution5. It follows the lines of Blaschko that represent a peculiar pattern of distribution. In addition, hypomelanosis of Ito usually encounter the extracutaneous manifestation. Reviewed in aspect of distribution of lesions and extracutaneous symptoms, we thought that hypomelanosis of Ito was less likely in our case. Therefore, considering the congenital hypopigmented macules, distribution, and other clinical manifestations, the hypopigmented macules and patches were most likely ND. In conclusion, our case suggests the possibility that ND could disappear. An epidemiological study of ND with long term follow up is further needed to know if ND could disappear, as in our case, or is persistent throughout life.

Dear Editor: The treatment of localized vitiligo usually involves a stepwise strategy; the first-line treatment is topical corticosteroids or calcineurin inhibitors, and a combination strategy has been proposed for patients with refractory lesions1. However, these schemes require many months to years of treatment and can result in disappointing outcomes. Moreover, previous studies have demonstrated that the longer the duration of the disease, the worse the prognosis were for the treatment, including surgical treatment2. Therefore, delay in treatment initiation may make treatment more difficult, and thus there is a strong need for early intervention for a successful treatment. Multiple combination modalities have been suggested, including topical agents and phototherapy, or systemic corticosteroid and surgery3. In this open pilot study, we investigated the efficacy of a triple combination treatment, consisting of systemic corticosteroids, excimer laser, and topical tacrolimus, in patients with recently developed localized vitiligo. Fourteen patients (eight men, six women; mean age, 28.9 years) were enrolled in this study. Five patients had segmental vitiligo, whereas nine had focal vitiligo. All patients had recent-onset vitiligo lesions that had been evident for at least 6 months. The average duration of the vitiligo was 6.6 weeks. The mean body surface area of the vitiligo was 25%~50% repigmentation; good effect, >50%~75% repigmentation; excellent effect, >75%~99% repigmentation; and complete effect, 100% repigmentation. Repigmentation was confirmed by the examination of treated lesions under a Wood's lamp; three dermatologists performed the photographic assessments. The treatment was ceased early in patients who showed complete repigmentation before 12 weeks. All patients were followed for 7 months to assess the stability of the pigmentation. Safety profiles were assessed simultaneously throughout the study. All patients completed the 12-week treatment period. The lesions were located on the head and neck (n=12) and on the trunk (n=3). Among the 14 patients, repigmentation was scored as complete in five (35.7%) (Fig. 1), excellent in four (28.6%), good in one (7.1%), moderate in two (14.3%), and weak in two (14.3%) patients. There was no difference in treatment efficacy between the focal type and the segmental type. Complete repigmentation was achieved in 3 of 10 lesions in the focal type and in 2 of 5 lesions in the segmental type. Fig. 1 Complete repigmentation. (A) Before treatment and (B) after 3 months of triple combination treatmentin patients 1, 8, 10, and 11. (C) At the end of the 7-week follow up, patient 6 with Hashimoto's thyroiditis had developed some areas of depigmentation ... Initial repigmentation was noted within 2 weeks in most of the patients. Among the five patients with complete repigmentation, two showed complete repigmentation within 1 month (patients 10 and 11). The response to treatment was generally poor in lesions accompanied by poliosis (good in one, moderate in two, and weak in two). At the 7-month follow-up, patient 6 (with Hashimoto's thyroiditis) had developed some areas of depigmentation over the repigmented sites, whereas the pigmentation remained stable in the other patients. Three patients complained of adverse effects, including slight pain and bulla due to laser therapy, and abnormal menstruation, which may be due to the systemic steroid. However, the adverse effects were not serious and were reversible, and therefore did not affect the treatment schedule. The demographics of the patients and a summary of the treatment results are presented in Table 1. Table 1 Demographics and treatment results in 14 patients with recent onset vitiligo Previous studies have consistently reported that combination interventions of topical therapy and phototherapy were superior to monotherapies1. Phototherapy induces a predominantly perifollicular pattern of repigmentation, whereas topical agents exhibit a diffuse type, acting synergistically when combined4. A significant finding of this study is that complete repigmentation occurred in 35.7% of the patients, which was much higher than that reported for other modalities of current vitiligo therapy. One previous study revealed that the combination of excimer laser and topical 0.1% tacrolimus ointment achieved >75% repigmentation in 70% of patients. However, complete repigmentation occurred in only 2 of 23 lesions within 2 months5. When excimer laser was combined with topical hydrocortisone for the treatment of vitiligo of the face and neck, >75% repigmentation was observed in 42.8% of the patients and complete repigmentation occurred in 21.4% of the patients6. Therefore, the higher rate of complete repigmentation in this study is meaningful, as most patients do not favor inhomogeneous repigmentation. In addition, complete repigmentation was more rapid and was achieved within 1 month in two patients. The rapid onset of repigmentation improved the patients' motivation and their compliance to therapy. We added a systemic corticosteroid that had been suggested to suppress disease activity or progression without any noticeable adverse effects7,8. It was suggested that early dynamic events in vitiligo, including for the segmental type, are characterized by the infiltration of inflammatory cells on histological examination, which is implicated in the development of vitiligo9. The combination of a systemic corticosteroid and topical tacrolimus was also reported in two cases of recent-onset vitiligo10. These cases were treated successfully and suggest the necessity of early intervention. The limitation of this study was the small population size. In conclusion, we propose that the triple combination treatment with systemic corticosteroids, excimer laser, and topical tacrolimus is effective for recent-onset vitiligo as a first-line therapy. It is likely that early intervention with this combination treatment can prevent disease progression, and achieve a more rapid and complete repigmentation.

Dear Editor: Acute pigmentation due to tanning is commonly understood as increased melanization of the epidermis observed in the skin after ultraviolet (UV) exposure, and the mechanisms underlying this condition are well understood now. Keratinocyte-derived gene products are upregulated by UV irradiation and act as paracrine factors in the skin to stimulate melanogenesis and melanin transfer by melanocytes1. Although acute pigmentation disappears over time, some types of hyperpigmentary disorders such as freckles, solar lentigines, and melasma, tend to persist if patients do not receive any treatments such as topical cosmetic products, medication, or laser. Solar lentigines are dark brown spots that occur on sun-exposed areas2, typically on the face, upper back, and shoulders. Multiple solar lentigines are considered a hallmark of aged skin. It is thought that cumulative UV exposure causes these spots. Therefore, pigmented spots of solar lentigines can be considered as indications of photoaging. Melasma is a common acquired symmetrical hypermelanosis on sun-exposed areas of the skin and is very common among Oriental women3. The major etiological factors include genetic influences, exposure to UV radiation, and sex hormones. However, the mechanisms underlying the persistence of hyperpigmentation in solar lentigines and melasma are not yet fully understood. Keratinocyte growth factor (KGF) or fibroblast growth factor-7 (FGF-7) is a member of the FGF family4. KGF is secreted from cultured stromal fibroblasts derived from the skin and gastrointestinal tract, and is expressed in vivo in dermal cells, but not in epidermal cells5. In addition, this paracrine growth factor also plays a role in the stimulation of melanogenesis5,6, proliferation of human melanoblasts, and differentiation of melanocytes7. A previous study reported higher levels of KGF in five patients with solar lentigines, suggesting the permeation of KGF from the dermis to the epidermis, which may result in the persistence of solar lentigines6. In this study, we quantitatively investigated the accumulation of KGF in the epidermis of patients with two major types of hyperpigmentary disorders, facial solar lentigines, and melasma to identify novel effective topical measures for their treatment. We examined 24 Korean women with newly diagnosed facial solar lentigines and 13 others with newly diagnosed melasma, which were determined on physical examination and histological examination. This study was approved by the ethics committee of Ajou University Hospital (No. MED-KSP-12-171). Punch biopsies from lesions and perilesional normal skin were obtained from each patient. The perilesional normal skin was taken from the area within 1 cm away from the lesional border. Twenty-four pairs of facial solar lentigines and 13 pairs of melasma tissue were prepared for immunohistopathological examination. We examined KGF protein accumulation in the epidermis of both facial solar lentigines and melasma. Paraffin-embedded sections of both lesional and perilesional normal skin were processed with monoclonal antibodies against KGF (dilution, 1:100; Abcam, Boston, MA, USA) for 20 min at 48℃. The stained area per epidermal area (SA/EA) and SA per single rate ridge length (SA/1R) of lesional and perilesional skin were measured. In both facial solar lentigines and melasma lesions, distinctly positive immunoreactivity against KGF was noticed in the epidermis, whereas perilesional normal skin only showed weak immunoreactivity (Fig. 1). The SA/EA of perilesional normal skin samples was 0.184±0.139 for facial solar lentigines and 0.134±0.071 for melasma, and that of lesional skin samples was 0.237±0.107 for facial solar lentigines and 0.210±0.084 for melasma (Fig. 2A). The differences were statistically significant (p=0.014 for facial solar lentigines and p=0.016 for melasma). The SA/1R of perilesional normal skin samples was 10.216±7.194 for facial solar lentigines and 8.699±4.923 for melasma, and that of lesional skin samples was 19.350±8.744 for facial solar lentigines and 13.172±4.709 for melasma (Fig. 2B). The differences were statistically significant (p=0.000035 for facial solar lentigines and p=0.014 for melasma). Fig. 1 Immunostaining with an antibody against keratinocyte growth factor (KGF). Significant amount of KGF protein was accumulated in the epidermis of lesional skin compared to that in perilesional normal skin of (A) solar lentigines and (B) melasma (A, B: ×400). ... Fig. 2 Quantitative analysis of immunostaining. Immunohistochemical analysis for keratinocyte growth factor (KGF) was quantified in two ways: the stained area per epidermal area (SA/EA) (A) and the stained area per single rate ridge length (SA/1R) (B). Each ... In the present study, we demonstrated that KGF protein accumulation in the epidermis of facial solar lentigines and melasma was significantly increased. We performed the following two analytical techniques: first, the SA for KGF was normalized to the EA; second, the SA for KGF was normalized with 1R, which is independent from epidermal thickness. In both analyses, we found a statistical difference between perilesional normal and lesional skin of both facial solar lentigines and melasma. In this study, we did not take the duration and stage of solar lentigines and melasma into consideration because of the small number of patients, although they could have affected the results. We expect that a study with a larger number of patients in varied stages and duration of solar lentigines and melasma will demonstrate the correlation between KGF protein accumulation level and the duration or stage of solar lentigines and melasma. Iriyama et al.8 revealed that the degradation of heparan sulfate at the dermal-epidermal junction in photoaged skin impaired the function of the basement membrane, which regulates the transfer of several growth factors between the epidermis and dermis. Moreover, they demonstrated that heparan sulfate at the dermal-epidermal junction was specifically reduced in solar lentigines on the human back, and that the degradation of heparan sulfate enhanced melanogenesis in a skin equivalent model. In addition, recent histological studies on melasma described changes in the basement membrane in the lesional skin of melasma9,10. The basement membrane structure in lesional skin was not intact and appeared disrupted. Thus, the loss of heparan sulfate at the dermal-epidermal junction of facial solar lentigines and the loosening of the basement membrane in melasma may enhance the transfer of dermis-derived factors such as KGF. Our present study strongly supports the hypothesis that in hyperpigmentary disorders, such as facial solar lentigines and melasma, the fibroblast-derived KGF is transferred into the epidermis in which it accumulates, thereby leading to the persistence of hyperpigmentation. Thus, targeting the dermal-derived KGF itself and the degradation of heparan sulfate at the dermal-epidermal junction, which allow an excess amount of KGF to transfer into the epidermis, could be effective topical measures like cosmetic or medication use for treating hyperpigmentary disorders.

Dear Editor: Melasma is a common acquired hyperpigmentary disorder of the face, but its treatment remains challenging. A procedure called "laser toning" that uses a low-energy 1064-nm Q-switched Nd:YAG laser was recently introduced for the treatment of melasma, demonstrating good results1,2,3. However, the possibility of mottled hypopigmentation is a major concern with this treatment, because it rarely recovers spontaneously4. The underlying mechanisms of mottled hypopigmentation are not completely understood. Whether the hypopigmentation is caused by reduced pigmentation with intact melanocytes or a decrease or absence of melanocytes remains to be elucidated. Therefore, this study investigated the changes in melanin and melanocytes in hypopigmented lesions that develop after low-fluence 1,064-nm Q-switched Nd:YAG laser treatment for melasma. This study was approved by the institutional review board of Ajou University Hospital (AJIRB-MED-KSP-12-374). Patient 1, a 41-year-old woman with Fitzpatrick skin type IV, presented with typical mottled hypopigmentation after treatment with 1,064-nm Q-switched Nd:YAG laser for melasma (Fig. 1A). The duration of hypopigmentation was 7 years. Skin biopsies were obtained from the hypopigmented, hyperpigmented (i.e., melasma), and adjacent perilesional normal skin areas. Hematoxylin and eosin and Fontana-Masson staining as well as immunohistochemical staining using melanocyte-specific markers including monoclonal antibodies against human gp100 (NKI/ beteb; Monosan, Uden, the Netherlands), tyrosinase (Thermo Scientific, Fremont, CA, USA), and microphthalmia-associated transcription factor (MITF; Leica Biosystems, Newcastle, UK) were performed. The numbers of MITF+ melanocytes per 1-mm length of rete ridge were counted. The expression levels of gp100 and tyrosinase were measured as the ratio of stained area to measured epidermal area. Fig. 1 (A) Mottled hypopigmentation developing after laser toning for melasma treatment in a 41-year-old woman with Fitzpatrick skin type IV. Hypopigmented, hyperpigmented (i.e., melasma), and adjacent perilesional normal skin were evaluated. Circles indicate ... The general histological findings of the hypopigmented skin were unremarkable. There was no collagen remodeling or scarring. Fontana-Masson staining demonstrated the almost complete absence of melanin pigment in hypopigmented skin (Fig. 1B). The number of melanocytes, as determined by MITF expression, was not substantially different in lesional skin (n=4) compared to perilesional normal skin (n=5) or melasma skin (n=3). Consistently, tyrosinase level was not lower in lesional skin than perilesional normal skin but was higher than that in melasma skin as expected. Interestingly, gp100 expression was higher in the hypopigmented lesion than perilesional normal skin and even melasma skin. Similar findings were observed in patient 2, a 49-year-old woman with Fitzpatrick skin type III who presented with typical mottled hypopigmentation after laser toning for 1 year (Fig. 2A). Lesional skin biopsy showed the complete absence of melanin pigment in hypopigmented skin. However, there was no reduction in the number of melanocytes, and gp100 expression was elevated (Fig. 2B). Fig. 2 (A) A 49-year-old woman with Fitzpatrick skin type III presented with typical mottled hypopigmentation after laser toning for 1 year. Circle indicates biopsy sites of the hypopigmented lesion. (B) Lesional skin biopsy showed the complete absence of melanin ... The results of the present study clearly demonstrate that the histologic features of laser toning-induced hypopigmentation are characterized by almost destroyed melanosome pigments and a preserved the number of melanocytes. However, it is unclear whether the number of melanocytes is reduced in the hypopigmented skin. One study indicates hypopigmentation might be due to melanocytopenia5. However, in that study, lesional skin was not compared with adjacent perilesional normal skin. The other studies suggest the number of melanocytes in hypopigmented skin is normal6,7. In the present study, there was no difference in the mean numbers of MITF-stained melanocytes between lesional skin and perilesional normal skin. Interestingly, we noticed that the levels of the structural protein gp100 were preserved and rather elevated in lesional skin compared to perilesional normal skin. Moreover, in patient 1, gp100 levels of hypopigmented skin were clearly elevated compared to that in hyperpigmented skin. Although the reason for this result is unclear, these findings nonetheless suggest the melanogenic activity in the melanocytes was impaired and the cells failed to produce fully matured melanosomes. Considering that the proposed action mechanism of laser toning is subcellular selective photothermolysis of melanosomes and not melanocytes, it is speculated that melanocytes survived but were functionally downregulated such that they did not produce fully matured melanosomes. The cumulative dose of repetitive laser treatment may affect melanocyte function, resulting in the development of hypopigmentation. Therefore, treatment activating or stimulating melanogenesis in the melanocytes would be required. To this end, treatment with focused narrowband ultraviolet B therapy has been used with some success8. In conclusion, laser toning-induced hypopigmentation is characterized by almost destroyed melanosome pigments and a preserved number of melanocytes, which seem to be functionally downregulated not to produce fully matured melanosomes. Thus, early intervention aiming to restore melanocyte function would be required.

Dear Editor: Becker's nevus is a unilateral, hyperpigmented hairy cutaneous hamartoma. Becker's nevi are commonly associated with several structural anomalies and cutaneous diseases1-5. They may be related to the presence of increased androgen receptors and/or mosaicism or be associated with the isotopic response phenomenon. Eczematous dermatitis associated with Becker's nevus is quite rare and described in only one case report. Herein, we describe a second case of eczema confined to Becker's nevus on the face. In addition, the melanocytes in Becker's nevus had the morphologic appearance of activated cells, a phenomenon which may have been due to inflammation. A 47-year-old man visited our clinic due to a pruritic, lichenified plaque overlying a hyperpigmented, hypertrichotic area on his left cheek. The hyperpigmented, hypertrichotic lesion had been present since around puberty and remained asymptomatic until 1 year prior to his arrival; at that time the pruritic lesion appeared. Physical examination revealed a lichenified plaque confined to the hyperpigmented, hypertrichotic patch on the left side of the patient's face (Fig. 1). A 3-mm punch biopsy was performed, and the histological findings were consistent with chronic eczema (Fig. 2A) coexisting with Becker's nevus (Fig. 2B). Interestingly, NKI/beteb staining showed hyperactivated dendritic melanocytes in the epidermis (Fig. 2C), which is not common in an ordinary Becker's nevus. The Becker's nevus is currently being treated with 5 sessions of fractional CO2 via laser therapy and is improving. Fig. 1 Eczematous lesion coexisting with Becker's nevus. Fig. 2 (A) H&E staining showed epidermal acanthosis with parakeratosis and superficial perivascular lymphohistiocytic infiltration in the upper dermis, consistent with chronic eczema (Original magnification ×50). (B) Hyperpigmentation of the ... Becker's nevi have been associated with several skin and structural anomalies. Cases of acneiform eruption, breast hypoplasia, smooth muscle hyperplasia, and hypertrophy of the sebaceous glands are reported to have been localized in Becker's nevi; this phenomenon is thought to be related to an increased level of androgen receptors in Becker's nevi1,2. Genetic mutation or mosaicism may contribute to the development of skin disorders, such as hypohidrosis colocalized with Becker's nevus3. Skin diseases, such as lichen planus and prurigo nodularis, have also been reported to be associated with Becker's nevi4,5. These occurrences may explain Wolf's isotopic response, which is the appearance of a new skin disorder at the exact site of another, unrelated skin disease that has long since healed. Our case, lichen simplex chronicus associated with Becker's nevus, may represent this isotopic response. The mechanism behind isotopic response is poorly understood6. Occurrence of a localized halo eczematous eruption surrounding acquired melanocytic nevi was first described by Meyerson in 1971 and was termed the Meyerson phenomenon or Meyerson's nevi7. This phenomenon is characterized by hypopigmentation around the involved nevi which clears after a few months. Our patient showed an eczematous eruption localized on Becker's nevus, but no surrounding halo like that seen in Meyerson's nevi was present. Therefore, our case is not considered to be Meyerson's nevi but an isotopic response. Melanocytes may respond to cutaneous inflammation. Inflammation-related factors, such as prostaglandins, histamine, and alpha-MSH may be responsible for the activation of melanocytes8. Our case clearly showed in vivo evidence of melanocytic activation during inflammation. The cells were large and dendritic, suggesting that the eczematous skin inflammation activated epidermal melanocytes. In conclusion, eczematous dermatitis localized in Becker's nevus represents an isotopic response, and cutaneous inflammation may activate melanocytes.

Background It was previously thought that persons with genetic predispositions to vitiligo develop the condition after exposure to various precipitating environmental factors. However, in many cases, the aggravating factors of vitiligo have not been clearly identified. Objective To identify the aggravating factors of vitiligo in the working environment and daily life. Methods A total of 489 vitiligo patients were recruited from 10 institutions in South Korea; patients were provided with a questionnaire about environmental factors and behavior patterns in the workplace and in daily life, and their association with vitiligo. Results Ninety-five of the 470 enrolled patients (20.2%) answered that environmental risk factors in daily life and in the workplace affected the development of vitiligo. The most frequently attributed causes were trauma and burn (13.6%), followed by sunlight (12.8%), stress (12.8%), cleaning products/disinfectant/chemicals (4.9%), and hair dye (2.1%). Conclusion Vitiligo of the hand and foot was associated with frequent exposure to aggravating materials and overexposure to sunlight, along with frequent trauma of these areas, all of which could be considered important risk factors of vitiligo. The development of vitiligo could potentially be controlled through the early detection of aggravating factors.

Background: Recently, photodynamic therapy (PDT) has been shown to be an effective first-line treatment for actinic keratosis (AK). However, a major limitation of PDT is the long incubation time required to allow penetration of the photosensitizer. Objective: The aim of this study was to assess if pretreatment with an ablative carbon dioxide (CO2) fractional laser can reduce the incubation time of the photosensitizer. Methods: Initially, 29 patients with a total of 34 AK lesions were treated with an ablative CO2 fractional laser at Ajou University Hospital between January and December 2010. Immediately after the laser treatment, topical 20% 5-aminolevulinic acid or methyl-aminolevulinate was applied to the AK lesions and incubated for 70 to 90 minutes. Then, the treated areas were illuminated with a red light source. Improvement was clinically or histologically assessed eight weeks after the treatment. Results: In spite of the short incubation time, 24 lesions (70.6%) showed a complete response (CR) within three sessions of PDT (10 lesions a clinical CR and 14 lesions a clinical/histological CR). There were no significant side effects associated with the combination of ablative CO2 fractional laser and PDT. Conclusion: Ablative CO2 fractional laser may be considered an additional treatment option for reducing the incubation time of the photosensitizer in PDT. (Ann Dermatol 25(4) 417∼422, 2013)

Background Xanthium stramarium (XAS) and Psoralea corylifolia (PSC), phototoxic oriental medicinal plants, has been used in traditional medicines in Asian countries. Objective The effects of highly purified XAS or PSC extract combined with ultraviolet A1 (UVA1) irradiation on cell proliferation and transforming growth factor-beta1 (TGF-β1) expression of the keloid fibroblast were being investigated to define potential therapeutic uses for keloid treatments. Methods The keloid fibroblasts were treated with XAS or PSC alone or in the combination with UVA1 irradiation. The cell viability, apoptosis, and expression of TGF-β1 and collagen I were investigated. Results XAS and PSC in combination with UVA1 irradiation suppressed cell proliferation and induced apoptosis of keloid fibroblasts. Furthermore, the XAS and PSC in combination with UVA1 irradiation inhibited TGF-β1 expression and collagen synthesis in keloid fibroblasts. Conclusion These findings may open up the possibility of clinically used XAS or PSC in combination with UVA1 irradiation for keloid treatments.

Dear Editor: Schamberg disease is a type of pigmented purpuric dermatosis that is characterized by red-brown purpuric macules that are known as 'cayenne pepper' spots. It usually develops insidiously on one or both lower legs and onset occurs on average in the fifth decade of life. Herein, we report a generalized form of Schamberg disease that occurred in a child. A 12-year-old boy presented with a 2-month history of an asymptomatic widespread rash. There was no specific history such as recent drug intake. He had been treated previously with topical steroids, but there had been no significant change in his condition. Physical examination revealed purpuric and telangiectatic macules and patches scattered all over his trunk and extremities (Fig. 1). Laboratory findings, including clotting profile, were within normal limits. Histological examination of a skin biopsy revealed extravasated red blood cells and enlarged vessels with perivascular lymphocytic infiltrates in the upper dermis (Fig. 2). Based on these clinical and histopathological findings, the patient was diagnosed with Schamberg disease. After treatment with oral prednisolone (10 mg) and pentoxifylline (400 mg) daily for 4 weeks, the skin lesions improved, leaving hyperpigmentation. Fig. 1 Physical examination revealed purpuric and telangiectatic macules and patches scattered all over his trunk (A; inset: a close-up new) and extremities (B). Fig. 2 Skin biopsy revealed extravasated red blood cells and enlarged vessels with perivascular lymphocytic infiltrates in the upper dermis (A: HE B: H&E, ×200). The onset age in the present case was interesting as most cases occur in adulthood. However, some authors have suggested that Schamberg disease is relatively common in children, sometimes occurring before puberty1. Torrelo et al1. reviewed 13 cases of Schamberg disease that occurred before 10 years of age and found that it predominantly occurred in girls, consistently involved the lower limbs, and was a chronic persistent disease. A case of a 1-year-old infant with Schamberg disease has also been reported2. An interesting feature of the present case was that the eruptions were generalized. The lesions in Schamberg disease usually develop on one or both lower legs, and they sometimes spread and involve the trunk or upper extremities. Three cases of generalized Schamberg disease have been reported, all of which occurred in children3,4. In these three cases, the generalized lesions responded well to psoralen plus ultraviolet A or narrow band ultraviolet B therapy and treatment resulted in clearing of the lesions after either the tenth, twelfth, or twentieth treatment session. The present case improved after treatment with an oral corticosteroid and pentoxifylline. These results indicate the benign nature of generalized Schamberg disease in childhood. Corticosteroids are well known anti-inflammatory agents that have shown positive outcomes in several cases of Schamberg disease. The administration of pentoxifylline can have several effects, including decreased fibrinogen concentration, and reduced platelet adhesiveness. In addition, it inhibits T-cell adherence to endothelial cells and keratinocytes. Childhood Schamberg disease needs to be distinguished from other dermatoses such as drug hypersensitivity reactions, Henoch-Schonlein purpura, and thrombocytopenia associated with viral infection. Dermoscopic examination can be used for the diagnosis of pigmented purpuric dermatosis5, as findings will show purpuric globules over a purpuric and orange-brown background. In conclusion, we reported a case of generalized Schamberg disease occurring in a child. Accurate diagnosis of pigmented purpuric eruptions in childhood is needed considering the benign nature of this condition.

Melasma is a common acquired hyperpigmentary skin disorder characterized by light to dark brown macules and patches occurring in the sun-exposed areas of the face. Melasma lesional skin is characterized by epidermal hyperpigmentation through increased melanogenesis in epidermal melanocytes. Some patients have dermal melanin but its amount is not significant and its distribution is very heterogeneous in the whole melasma lesional skin. Melasma is not homogeneous disease and there are personal characteristics of patients with melasma. The pathogenesis of melasma is not fully understood, but several hypotheses have been suggested. Increased vascularity in melasma lesions has suggested the role of increased number of enlarged vessels in the development of melasma. Endogeneous and exogeneous stimuli such as sex hormones and ultraviolet irradiation respectively may stimulate the microenvironment leading to the release of various mediators that cause activation of melanocytes and/or these stimuli may directly activate the melanocytes. Melasma patients may have specialized melanocytes with an intrinsic sensitivity to these stimuli.

Idiopathic eruptive macular pigmentation is a rare condition characterized by asymptomatic pigmented macules involving the neck, trunk, and proximal portions of the extremities. On histopathologic examination, there was increased pigmentation of the basal layer in otherwise normal epidermis and scattered melanophages in the papillary dermis. We report a case of a 26-year-old woman with idiopathic eruptive macular pigmentation involving only the flexural areas of the body. This condition should be considered in the differential diagnosis of flexural hyperpigmented skin lesions.