Endothelin-1 and its A and B receptors: are they possibly involved in vitiligo?

Endothelin-1 (ET-1), expressed by keratinocytes, has paracrine effects on melanocytes. The endothelin 1-axis [ET-1, endothelin A receptor (ETAR) and endothelin B receptor (ETBR)] is thought to play a role in the depigmentation process occurring in vitiligo, with no studies on the cutaneous protein expression of this axis in the disease. The aim of the present study was to compare the expression of ET-1 axis in lesional and perilesional normal epidermis of vitiligo patients with healthy controls. Ten patients with non-segmental stable vitiligo and ten healthy controls were included. Skin biopsies from all subjects were studied immunohistochemically for ET-1, ETAR and ETBR expression. No significant difference was detected in the rate of expression and the degree of staining of ET-1 axis in controls compared with each of lesional vitiligo and perilesional normal epidermis (P>0.05). There was no statistically significant difference between lesional vitiligo and perilesional normal epidermis regarding to the rates of ET-1, ETAR and ETBR expression (P=0.82, P=0.5 and P=0.99, respectively). Semi-quantitative analysis of ETAR revealed higher staining grades in lesional compared with perilesional normal epidermis, with a statistically significant difference (P=0.04). There was no statistically significant difference between the two groups regarding the staining grades of ET-1 and ETBR (P>0.05 for both markers). A highly significant positive correlation was found between ET-1 and ETAR (r =0.99, P<0.05) and between ET-1 and ETBR (r=0.87, P<0.05). The study demonstrated unaltered expression of ET-1 axis in keratinocytes in lesional vitiligo and perilesional normal epidermis. Additional studies on the differential expression of this axis in keratinocytes and melanocytes are therefore required.

Immunohistochemical assessment of angiogenesis and vascular endothelial growth factor expression in cutaneous lichen planus: relation to the degree of inflammation.

Neo-angiogenesis is reported to be essential in the pathogenesis of oral lichen planus (LP). We aimed to investigate angiogenesis through CD34 staining and vascular endothelial growth factor (VEGF) expression in cutaneous LP lesions and to evaluate the relation of these markers with the degree of inflammation. Thirty patients with cutaneous LP and 10 healthy controls were included. Skin biopsies from all subjects were studied immunohistochemically for microvessel density (MVD) by CD34 staining and for VEGF expression. Relation of these parameters with the grade of inflammation was evaluated. The mean MVD was significantly higher in patients than controls (32.60, 95% CI: 27.71-37.49 vs. 9.60, 95% CI: 6.86-12.34; t = 5.43; P < 0.001). Positive VEGF expression was detected at a significantly higher rate in LP patients compared with controls (76.7% vs. 30.0%, OR (95% CI) 7.67(1.56-37.80), P < 0.05). Patients with positive VEGF expression showed significantly higher mean MVD compared with those having negative VEGF expression (37.39, 95% CI 32.66-42.12 vs. 16.86, 95%CI 13.59-20.12 respectively, P < 0.001). Increasing mean MVD and VEGF positivity were significantly observed with higher grades of inflammation (P < 0.05). This work confirms a role for angiogenesis and increased VEGF expression in cutaneous LP and a relation of these events with the degree of inflammation in the disease.

Successful treatment of resistant alopecia areata with a phototoxic dose of ultraviolet A after topical 8-methoxypsoralen application.

BACKGROUND: The efficacy of a phototoxic dose of ultraviolet A (UVA) after topical application of 8-methoxypsoralen (8-MOP) in the treatment of alopecia areata (AA) was evaluated previously in only one study. However, the possibility of spontaneous regrowth of hair cannot be excluded as sessions were carried out every 3 months. OBJECTIVE: To determine the efficacy of a phototoxic dose of UVA after topical application of 8-MOP in the treatment of AA resistant to other lines of treatment. SUBJECTS/METHODS: Thirty-five patients with AA were treated by topical 8-MOP application to the lesions followed by UVA irradiation using a phototoxic dose every 3 months for a maximum of four sessions. Severity grading of AA was carried out using the Severity of Alopecia Tool (SALT) score before and after treatment. RESULTS: Fifty-seven percent of patients showed a positive treatment response (40% showed complete and 17% showed partial response) with significant improvement of SALT score. The mean cumulative UVA dose was 22±8.3 J/cm(2). Mild reversible side effects were observed in 63% of patients after the first session. CONCLUSION: Phototoxic psoralen and ultraviolet A therapy after topical application of 0.1% 8-MOP is an effective treatment option for resistant AA, with low total cumulative UVA dose, few treatment sessions, and minimal reversible side effects.

Bath psoralen+ultraviolet A photochemotherapy vs. narrow band-ultraviolet B in psoriasis: a comparison of clinical outcome and effect on circulating T-helper and T-suppressor/cytotoxic cells.

BACKGROUND: Comparative success rates of bath psoralen+ultraviolet A (PUVA) and narrow band-ultraviolet B (NB-UVB) in psoriasis treatment are variably reported with no previous studies on the possible effect of bath PUVA on circulating CD4+ and CD8+ T cells. OBJECTIVE: We aimed to compare the effect of bath PUVA and NB-UVB clinically and on circulating T-helper and T-suppressor/cytotoxic cells in psoriasis. PATIENTS AND METHODS: Thirty-four psoriatic patients divided into a bath PUVA-treated group (18 patients) and a NB-UVB-treated group (16 patients) were compared regarding the disease severity by psoriasis area and severity index (PASI) score and percentage of circulating CD4+ and CD8+ T cells by flow cytometry before and after treatment. RESULTS: After treatment, the bath PUVA group showed a significantly higher reduction of PASI score (85.44%) than the NB-UVB group (58.72%). Mean peripheral CD4+ T-cell percentage was significantly lower after [36.8; 95% confidence interval (CI) 33.80, 39.97] compared with before treatment (42.06; 95% CI 38.29, 45.83) (P<0.05) in the bath PUVA group while this difference was insignificant in the NB-UVB group (P>0.05). CONCLUSION: Bath PUVA therapy is superior to NB-UVB in the treatment of moderate and severe psoriasis with mild reversible side effects. Both modalities have a systemic effect decreasing peripheral CD4+ T cells, which is more with bath PUVA.

Comparative study of human papilloma virus in untreated and ultraviolet-treated psoriatic patients.

BACKGROUND: Psoriasis is a proliferative disease, and human papilloma virus (HPV) may be one of the causative factors underlying its pathogenesis. AIM OF THE STUDY: To study whether the presence of the virus in psoriatic patients is due to the proliferative nature of the disease or due to the immunosuppression induced in patients receiving phototherapy. PATIENTS AND METHODS: Using a nested polymerase chain reaction, a skin biopsy was taken and examined for HPV expression in 20 untreated psoriatic patients, 20 psoriasis patients under phototherapy [narrow band ultraviolet B (UVB)], 20 psoriasis patients under systemic photochemotherapy (psoralen and UVA), 10 healthy controls, and 10 non-psoriatic patients under UV treatment. RESULTS: The virus detection rate in psoriatic patients under photochemotherapy (60%) was significantly higher (P<0.05) compared with the other groups, while the frequency of the virus in the untreated psoriatic group (0%) was statistically insignificant compared with the normal control group (20%). CONCLUSION: UV treatment may be an underlying factor predisposing patients with psoriasis to infectivity by HPV together with other factors.