Involvement of T cells in early evolving segmental vitiligo.

Recent studies have suggested an overlapping autoimmune mechanism between segmental vitiligo (SV) and nonsegmental vitiligo (NSV). Although T-cell infiltration is observed in the margins of active lesions in NSV, the histopathological characteristics of the active margin of SV are not well known. To determine if T-cell inflammatory responses are present in the active margin of SV lesions, biopsies were taken from the active margin of a lesion in 12 patients with early or actively spreading SV and compared with a normal control sample (on the symmetrical, opposite site of the same dermatome). The samples were stained for CD4, CD8, CD25 and interferon-γ. Lymphocytic infiltration was seen in 70% of patients. CD4+ T cells infiltrated the dermis, while CD8+ T cells were present in the epidermis or attached to the basal layer. The increase in the number of CD8+ T cells was significant (P < 0.04), while CD4+ or CD25+ T cells also appeared to be increased in number, but this was not significant. These results suggest that SV also has an autoimmune mechanism in the early evolving stage.

Three cases of pruritic urticarial papules and plaques of pregnancy (PUPPP) treated with intramuscular injection of autologous whole blood.

BACKGROUND: Pruritic urticarial papules and plaques of pregnancy (PUPPP), also known as polymorphic eruption of pregnancy, is a common and benign but exceedingly uncomfortable dermatosis of pregnancy. Investigation of new treatment options has been limited by patient concerns about the negative fetal effects of medication. OBJECTIVE: To assess the efficacy of intramuscular injection of autologous whole blood (AWB) for treatment of PUPPP. METHODS: This is a retrospective descriptive case series of three patients with PUPPP, all of whom were treated with intramuscular injection of AWB. RESULTS: All patients showed good responses to intramuscular injection of AWB, tolerated the treatment, and there were no adverse effects to the patients or their babies. CONCLUSION: AWB may be an alternative treatment option for patients with PUPPP who are worried about the risk of medication use during pregnancy or breastfeeding. Whole blood collected from the patient's own body may be preferable to foreign medications. Future investigation into the exact mechanism with controlled clinical studies using a large number of patients will be necessary to provide supporting evidence for this potential treatment.

Hypopigmented keratosis: is it a hyperkeratotic variant of idiopathic guttate hypomelanosis?

We have occasionally seen patients with acquired well-demarcated, scattered hypopigmented papules. In this study, we investigated the clinical and histopathological characteristics of such lesions. Biopsies were taken from the lesional and perilesional normal skin from 10 of 13 patients, which were compared with 10 idiopathic guttate hypomelanosis (IGH) samples. The lesions were scattered, well-circumscribed, flat-topped, hypopigmented papules. There was no age or gender predilection. Marked hyperkeratosis was present, with clear-cut margins distinguishable from the adjacent normal epidermis. The melanin content was decreased in the lesional epidermis, which was associated with a decrease in expression of melanogenesis-associated markers such as tyrosinase and NKI/beteb (marker of gp100) and reduction in the number of melanocytes. These histological findings were similar to those of IGH except for the additional finding of a thicker stratum corneum in this case seem to represent a 'hyperkeratotic' variant of IGH.

Revised classification/nomenclature of vitiligo and related issues: the Vitiligo Global Issues Consensus Conference.

During the 2011 International Pigment Cell Conference (IPCC), the Vitiligo European Taskforce (VETF) convened a consensus conference on issues of global importance for vitiligo clinical research. As suggested by an international panel of experts, the conference focused on four topics: classification and nomenclature; definition of stable disease; definition of Koebner's phenomenon (KP); and 'autoimmune vitiligo'. These topics were discussed in seven working groups representing different geographical regions. A consensus emerged that segmental vitiligo be classified separately from all other forms of vitiligo and that the term 'vitiligo' be used as an umbrella term for all non-segmental forms of vitiligo, including 'mixed vitiligo' in which segmental and non-segmental vitiligo are combined and which is considered a subgroup of vitiligo. Further, the conference recommends that disease stability be best assessed based on the stability of individual lesions rather than the overall stability of the disease as the latter is difficult to define precisely and reliably. The conference also endorsed the classification of KP for vitiligo as proposed by the VETF (history based, clinical observation based, or experimentally induced). Lastly, the conference agreed that 'autoimmune vitiligo' should not be used as a separate classification as published evidence indicates that the pathophysiology of all forms of vitiligo likely involves autoimmune or inflammatory mechanisms.

Combination treatment by 10 600 nm ablative fractional carbon dioxide laser and narrowband ultraviolet B in refractory nonsegmental vitiligo: a prospective, randomized half-body comparative study.

BACKGROUND: Vitiligo is a common acquired depigmentation disorder caused by the loss of melanocytes. Despite the numerous treatment modalities available for vitiligo, responses to treatment are still unsatisfactory. For this reason, new treatment modalities and approaches are needed. OBJECTIVES: To investigate the effects of fractional carbon dioxide (CO(2) ) laser therapy followed by systemic narrowband ultraviolet B (NB-UVB) phototherapy on nonsegmental vitiligo (NSV) as a prospective and randomized left-right comparative study. METHODS: Ten patients with NSV who presented symmetrical vitiligo lesions with no further improvement despite more than 1 year of conventional treatment were enrolled. Two sessions of half-body fractional CO(2) laser therapy were performed at a 2-month interval. NB-UVB phototherapy was then administered to the entire body 5 days after each fractional laser treatment twice a week, increasing the dose incrementally by 15% at each session. Objective clinical assessments were made by two blinded dermatologists using a quartile grading scale, and the patients' overall satisfaction was evaluated using a 10-point visual analogue scale. RESULTS: Two months after the last treatment, mean improvement scores, assessed by physicians, were significantly higher for those treated with half-body fractional CO(2) laser therapy followed by NB-UVB phototherapy, compared with those treated with NB-UVB alone (P=0·034). In addition, according to subjective assessment, the half-body laser treatment followed by NB-UVB showed significantly higher improvements compared with NB-UVB treatment alone (P=0·023). Noticeable adverse events, such as infection, scarring and Koebner phenomenon, were not found in any patient. CONCLUSIONS: This study suggests that fractional CO(2) laser therapy followed by NB-UVB phototherapy could be used effectively and safely as an alternative modality for the treatment of refractory vitiligo.

Classification of segmental vitiligo on the face: clues for prognosis.

BACKGROUND: The origin of the distribution of segmental vitiligo (SV) has not yet been clearly elucidated. Segmental configurations of cutaneous disorders have been explained using two main interpretations, i.e. following either dermatomal or blaschkolinear distributions. However, facial SV does not always correspond to either of these distributions. OBJECTIVES: We classified facial SV into several distinctive subtypes according to specific distributions based on long-term observations. METHODS: In total, 257 patients with facial SV were included, all of whom were closely observed for more than 1 year. The distribution patterns of facial SV were classified according to morphological similarities based on clinical observations. RESULTS: The lesions of facial SV were categorized into six subtypes: types I-a and I-b, and types II-V. Type I-a and type IV broadly involved the mid-level face from the forehead to the lower cheek, but type IV lesions selectively appeared on the right side of the face and did not cross the midline. Type I-b lesions chiefly involved the forehead and scalp hair. Types II and III involved the lower face and, frequently, the neck area, and type V lesions were distributed mostly around the right orbital area. The most frequent type of lesion in this study was type I-a (28·8%), followed by types II (16·0%), III (14·4%), IV (10·9%), I-b (10·5%) and V (8·6%). CONCLUSIONS: Newly established patterns of facial SV may be valuable for certain aspects of prognosis, such as the likely degree and path of lesion spreading.

Quality of life and psychological adaptation of Korean adolescents with vitiligo.

AIM: The aim of the study was to evaluate the impact of vitiligo on the quality of life and psychological adaptation in a Korean adolescent population. METHODS: Fifty-seven adolescents aged 12 to 18 years with vitiligo were evaluated using self-report scales, namely the Skindex-29, Piers-Harris self-concept, Center for Epidemiologic Studies Depression Scale (CES-D), and Revised Children's Manifest Anxiety Scale (RCMAS). RESULTS: Mean Skindex-29 subscales were as follow; 21.8 (global), 16.3 (symptom), 18.6 (function) and 29.5 (emotion). Several clinical variables, such as duration of vitiligo, facial involvement, history of previous treatment, and patient-assessed severity, affected the Skindex-29 subscales in various ways. However, differences in Skindex-29 scores according to the type of vitiligo, extent of involvement, and family history were not observed. The Piers-Harris self-concept scores showed a negative correlation with Skindex-29 scores, while other psychological measures (CES-D and RCMAS) were positively correlated. CONCLUSION: The quality of life of adolescents with vitiligo is closely related to the patients' apprehensions about their disease, psychosocial adjustment, and psychiatric morbidity, rather than the clinical severity of the condition itself. Clinicians should recognize and deal with psychological adaptation along with medical intervention when treating adolescent patients with vitiligo.

Expansion of vitiligo lesions is associated with reduced epidermal CDw60 expression and increased expression of HLA-DR in perilesional skin.

BACKGROUND: Detection of CDw60 in skin is representative of ganglioside D3 expression. This ganglioside is expressed primarily by melanocytes, and is of interest as a membrane antigen targeted by immunotherapy for melanoma patients. Expression of CDw60 by keratinocytes is defined by the presence of T-helper cell (Th)1 vs. Th2 cytokines, and can serve as a sentinel molecule to characterize an ongoing skin immune response. OBJECTIVES: These immunobiological characteristics have provided the incentive to study the expression of CDw60 in the context of progressive vitiligo. METHODS: Frozen sections were obtained from control skin and from vitiligo lesions and immunostained to show CDw60. Cells were cultured, their CDw60 expression studied and ribonuclease protection assays run to detect cytokine mRNA. RESULTS: Resistance to cytokine-mediated regulation of CDw60 expression was demonstrated in vitro by melanocytes, which appeared capable of generating autocrine and paracrine regulatory molecules supporting CDw60 expression. Induction of CDw60 expression was inhibited by antibodies to interleukin (IL)-4, suggesting that this cytokine was responsible, at least in part, for melanocyte-induced CDw60 expression. Marginal skin from patients with progressive generalized vitiligo consistently showed a reduction in epidermal CDw60 expression alongside elevated human leucocyte associated antigen (HLA)-DR expression at the margin. It thus appears that inflammatory infiltrates present in marginal skin generate type 1 rather than type 2 cytokines, supportive of a cell-mediated autoimmune response. CONCLUSIONS: These results support an active role of melanocytes within the skin immune system, and associate their loss in generalized vitiligo with a cell-mediated immune response mediated by type 1 cytokines.

Livedoid vasculitis responding to PUVA therapy.

BACKGROUND: Livedoid vasculitis is a chronic disorder manifested as recurrent, painful, reticulated, and ulcerative lesions of the legs, which result in ivory atrophic scars with peripheral telangiectasia and hyperpigmentation. Its etiology remains obscure and therapy is difficult. In this study, we evaluated the clinical efficacy of psoralen plus UVA (PUVA) therapy and its side-effects in the treatment of livedoid vasculitis. METHODS: Eight South Korean patients with livedoid vasculitis were treated with UVA and 8-methoxypsoralen (8-MOP). Systemic PUVA was started with 4 J/cm2 of UVA two or three times a week, and then the dose was increased by 0.5 or 1 J/cm2 increments at each subsequent treatment as tolerated. The effects of treatment were evaluated using photographs of before, during, and after the study. RESULTS: All patients experienced rapid cessation of new lesion formation, significant symptom relief, and complete healing of primary lesions. The mean times for each of the above were 3.6, 5.9, and 10 weeks, and the mean cumulative doses of UVA for each of the above were 55.9, 96.8, and 197.9 J/cm2, respectively. The patients tolerated PUVA therapy well without unacceptable side-effects. CONCLUSIONS: We propose that systemic PUVA using 8-MOP should be investigated further as an alternative treatment for patients with livedoid vasculitis.

A clinical analysis of 11 patients with chronic actinic dermatitis in Korea.

Chronic actinic dermatitis is a rare disease worldwide and also in Korea. However there has been no clinicohistologic and photobiological analysis of chronic actinic dermatitis in Korea. We examined 11 patients who were diagnosed as chronic actinic dermatitis and the results of this study were compared with previous reports. Most patients were elderly men who had erythematous papules or lichenified plaques on sun-exposed areas such as the face, neck, and dorsum of the hands with severe itching sensation. All patients had severe sensitivity to UVB and biopsied specimens showed findings of chronic eczema. Five patients had positive photopatch test materials. The patients were treated with systemic and topical steroid, cyclosporine and antihistamine.

The classification of segmental vitiligo on the face.

Segmental vitiligo usually has an onset early in life and spreads rapidly within the affected area. Among 1,300 patients with vitiligo, 191 patients with segmental vitiligo involving the face were evaluated. In this study, the distribution of segmental vitiligo on the face could be classified into 5 patterns which have distinctive features. This classification of facial segmental vitiligo can provide some indication of the future distribution of early lesions if they have begun to spread.

Clinical and histopathologic characteristics of trichrome vitiligo.

BACKGROUND: The term trichrome vitiligo describes lesions that have a tan zone of varying width between normal and totally depigmented skin, which exhibits an intermediate hue. However, the pathogenesis and the histopathologic characteristics of trichrome vitiligo are unknown. OBJECTIVE: Our purpose was to investigate the clinical and histopathologic characteristics and the pathogenesis of trichrome vitiligo. METHODS: Four punch biopsy specimens were taken from 21 patients with trichrome vitiligo; they were from vitiliginous skin, light brown skin, perilesional normal skin, and normal skin as far as 5 cm from the nearest vitiligo spot. The sections were stained with hematoxylin-eosin; in selected cases, we performed immunohistochemical staining with S-100 protein and CD1a. RESULTS: Trichrome vitiligo occurred most frequently on the trunk in active vitiligo vulgaris. Focal vacuolar degeneration of the basal cell layer and mild inflammatory cell infiltration of the epidermis and dermis were more prominent in light brown skin and perilesional normal skin than in vitiliginous skin and normal skin. The number of melanocytes was decreased in light brown skin compared with perilesional normal skin (P <.05) and in vitiliginous skin compared with light brown skin (P <.05); a few melanocytes were observed even in skin affected by trichrome vitiligo. The number of Langerhans cells was increased in the epidermis of light brown skin and perilesional normal skin compared with vitiliginous and normal skin (P <.05). PUVA therapy yielded excellent repigmentation. CONCLUSION: Trichrome vitiligo is a variant of active vitiligo. The changes of melanocytes, keratinocytes, and Langerhans cells may be involved in the pathogenesis of depigmentation in trichrome vitiligo.

A case of linear scleroderma and myasthenia gravis.

We report a case of a 28-year-old woman with myasthenia gravis who developed linear scleroderma seven years later. Myasthenia gravis and scleroderma are rarely found in direct association with each other; there are only five such reported cases, all of which were systemic scleroderma patients. Although localized and systemic scleroderma are distinct entities, autoimmunity is believed to be involved in the pathogenesis of both. Myasthenia gravis and scleroderma may occur coincidentally, but an autoimmune predisposition seems to be the more likely underlying cause, as evidenced by an increased incidence of autoantibodies and autoimmune diseases.

The efficacy of low-dose oral corticosteroids in the treatment of vitiligo patients.

BACKGROUND: One of the most probable pathogeneses of vitiligo is autoimmunity. Systemic corticosteroids suppress immunity and may arrest the progression of vitiligo and lead to repigmentation. The clinical efficacy of low-dose oral corticosteroids was assessed to minimize the side-effects in actively spreading vitiligo patients. METHODS: Eighty-one patients with vitiligo were evaluated. The patients took daily doses of oral prednisolone (0.3 mg/kg body weight) initially for 2 months; the dosage was then reduced to half of the initial dose for the third month and was halved again for the fourth and final month. The effects of treatment were evaluated using photographs of before and after the study. Side-effects were assessed at the first, second, third and fourth month of treatment. RESULTS: Arrested progression of vitiligo and repigmentation were noted in 87.7% and 70.4% of patients respectively. Male sex, a patient age of 15 years or under, and a duration of disease of 2 years or less showed increased repigmentation with statistical significance. The side-effects of treatment were minimal and did not affect the course of treatment. CONCLUSIONS: Low-dose oral corticosteroids are effective without serious side-effects in preventing the progression and inducing repigmentation of actively spreading vitiligo, which is difficult to treat with topical corticosteroids or photochemotherapy.

Serum levels of folic acid and vitamin B12 in Korean patients with vitiligo.

The association of vitiligo and pernicious anemia has been previously documented. The low levels of folic acid and vitamin B12 were thought to be related to vitiligo. To date, there have been very few reports about the serum levels of folic acid and vitamin B12 in patients with vitiligo. Using radioimmunoassay, we measured the serum levels of folic acid and vitamin B12 in 100 Korean patients with vitiligo. The mean serum levels of folic acid and vitamin B12 were 6.31 +/- 2.82 ng/ml and 630.25 +/- 230.94 pg/ml, respectively, in patients with vitiligo. These levels showed no significant difference compared to the normal control group, suggesting that folic acid and vitamin B12 do not appear to play a role in the pathogenesis of vitiligo.