Efficacy of bath-psoralen and ultraviolet A therapy for mycosis fungoides - retrospective analysis of 62 cases.

Photochemotherapy with psoralen and ultraviolet A (PUVA) is widely used for refractory skin diseases. Bathwater delivery of 8-methoxypsoralen (8-MOPS) with subsequent UVA irradiation (bath-PUVA) or oral administration of 8-MOPS with UVA is used to treat mycosis fungoides. We retrospectively analyzed 62 patients with mycosis fungoides (8 stage IA, 30 stage IB, 5 stage IIB, 18 stage IIIA, and 1 stage IVA2) treated with bath-PUVA at the Dermatology Clinic of Nagoya City University Hospital from November 2004 to December 2013. A complete response was achieved in 37 (59.7%) patients, a partial response was achieved in 16 (25.8%), and stable disease was achieved in 6 (9.7%). Progressive disease was observed in 3 (4.8%) patients. Almost all patients in stage IA/IB achieved a complete response. Of the 5 stage IIB patients, 2 achieved a partial response, 1 achieved stable disease, and 2 had progressive disease. The serum concentrations of soluble interleukin-2 receptor and lactate dehydrogenase decreased significantly following treatment with bath-PUVA (p < 0.001). We examined the risk factors of patients whose stage progressed despite PUVA treatment. A multivariate Cox regression analysis of risk factors associated with stage progression yielded a hazard ratio of 28.5 for stage IIb. Treatment with bath-PUVA is highly effective in the early stages of mycosis fungoides, and partially effective in advanced stages.

Ultraviolet A1 phototherapy for the treatment of localized scleroderma.

Ultraviolet (UV)A1 phototherapy is effective for T-cell-mediated skin diseases such as atopic dermatitis and mast cell-mediated skin diseases such as mastocytoma. UVA1 phototherapy is also effective against the sclerotic lesions of systemic sclerosis and morphea. Currently, in Japan, access to UVA1 phototherapy is limited because the UVA1 phototherapy device has not yet been approved. On the basis of our experience, we report three patients with localized scleroderma who responded successfully to UVA1 phototherapy. Efficacy was assessed by histological analysis and elastography. UVA1 successfully ameliorated sclerotic lesions, including morphea, linear scleroderma and morphea lesions in a patient with limited cutaneous systemic sclerosis. No side-effects were observed during UVA1 phototherapy.

Bath-PUVA therapy decreases infiltrating CCR4-expressing tumor cells and regulatory T cells in patients with mycosis Fungoides.

BACKGROUND: Mycosis fungoides (MF) is a malignant lymphoma characterized by expansion of CD4(+) memory T-cell clones. Infiltrating cells express CCR4, which is attracted to CC chemokine ligands 17 and 22 (thymus and activation-regulated chemokine [TARC]/CCL17 and TARC/CCL22). Bath-psoralen plus ultraviolet A (PUVA) is effective against MF. In patients with psoriasis, bath-PUVA induces circulating regulatory T cells (Tregs), which suppress effector T cells. To understand the mechanisms in MF, we analyzed lesion-infiltrating cells before and after bath-PUVA therapy. PATIENTS AND METHODS: Thirteen patients with MF (12 stage IB, 1 stage III; mean age 69.2 years, range 35-87 years; 6 men, 7 women) were recruited. RESULTS: Immunohistochemical analysis revealed that lesion CCR4-positive (CCR4(+)) cells and Tregs significantly decreased from 105.1 ± 164.8 cells/10(-2) mm(2) to 31.4 ± 39.0 cells/10(-2) mm(2) and from 78.1 ± 67.8 cells/10(-2) mm(2) to 24.7 ± 25.0 cells/10(-2) mm(2), respectively. Serum TARC levels significantly correlated with infiltrating CD3(+) (r = 0.997), CCR4(+) (r = 0.991), and forkhead box P3-positive (Foxp3(+)) cells (r = 0.843). Circulating Tregs before bath-PUVA therapy were not significantly different from those in healthy volunteers. Bath-PUVA did not significantly change the percentage of circulating Tregs. CONCLUSIONS: Bath-PUVA decreased CCR4(+) cells and Tregs in MF lesions but did not induce circulating Tregs, which might suppress effector T cells. Direct effects through skin lesions might eliminate both pathogenetically relevant cells and Tregs. Systemic immunosuppression was not induced.

Successful treatment of psoriasis vulgaris with targeted narrow-band ultraviolet B therapy using a new flat-type fluorescent lamp.

Narrow-band ultraviolet B (NB-UVB) therapy is widely used for refractory skin diseases. Targeted phototherapy is now being used to reduce the number of sessions and to avoid exposing normal skin. We developed a targeted NB-UVB therapy using a flat-type lamp emitting a wavelength similar to that of the TL-01 fluorescent lamp. Six Japanese patients with psoriasis were recruited and treated with the flat-type NB-UVB device with an initial dose of 70% of the minimal erythema dose, with a 20% increase at each subsequent session. The plaque severity score was determined. All lesions of the tested patients were responsive to NB-UVB therapy using the flat-type lamp. The mean percent reduction of the lesion was 58.3 ± 17.7%. The mean cumulative dose was 20.8 ± 10.8 J/cm². No side effects were observed during treatment. The flat-type targeted NB-UVB device is compact and convenient, and highly effective for the treatment of limited psoriasis lesions.

Efficacy of 1-mm minigrafts in treating vitiligo depends on patient age, disease site and vitiligo subtype.

Vitiligo vulgaris is a refractory skin disease. Treatment modalities include topical steroids, phototherapy, suction blister roof grafts and cellular grafting techniques. Adverse effects may occur, however, and some cases remain unresponsive to treatment. To evaluate the efficacy of small (1-mm) punch minigraft therapy in relation to patient age, disease site, disease duration and vitiligo subtype. We used a recently developed disposable 1.0-mm punch apparatus to perform minigraft therapy in 20 patients with either generalized (n = 4), segmental (n = 9) or limited (n = 7) vitiligo, and evaluated the area and rate of repigmentation in relation to patient age, disease site, disease duration and vitiligo subtype. The area of repigmentation was significantly greater in patients with segmental vitiligo (n = 9) than in those with generalized vitiligo (n = 4). Repigmentation covered a broader area and occurred more quickly in patients under 15 years of age than in those over 20 years of age (n = 9). Disease duration did not affect the repigmentation rate. The results of the present study suggest that 1-mm minigrafts are effective for treating patients with vitiligo. Better results occurred in patients under 15 years of age, patients with facial grafts, and patients with segmental and limited subtypes.

Efficacy of excimer light therapy (308 nm) for palmoplantar pustulosis with the induction of circulating regulatory T cells.

In this open-label study, we investigated the efficacy of excimer light (308 nm) with a filter to cut off wavelengths below 297 nm for the treatment of palmoplantar pustulosis (PPP). Twenty patients with PPP were recruited and treated once a week for a total of 30 sessions. Patient response was assessed every 10 sessions based on the Palmoplantar Pustulosis Area and Severity Index (PPPASI) score. Levels of Th17 cells and regulatory T cells (Treg) in the peripheral blood in patients with PPP were also evaluated. Mean PPPASI score was 19.5 at baseline, 13.2 at 10 treatments, 10.9 at 20 treatments and 9.5 at 30 treatments. Th17 levels after excimer therapy were not significantly different from those at baseline. In contrast, Treg levels after excimer therapy were significantly higher than those at baseline.

Phototherapy reduces serum resistin levels in psoriasis patients.

This study investigated phototherapy-induced changes in certain adipokine levels in patients with psoriasis. Patients with psoriasis (n=36) were recruited and body mass index (BMI) and disease severity (Psoriasis Area and Severity Index) were recorded. Serum resistin and leptin levels before and after bath-psoralen and ultraviolet (UV) A or narrow-band UVB therapy were examined by enzyme-linked immunosorbent assay. Serum leptin levels correlated positively with BMI. Phototherapy induced no remarkable change in the leptin levels, but significantly decreased serum resistin levels from 9.02±8.83 to 4.86±3.30ng/ml. Serum resistin levels might be involved in insulin resistance and inflammation, and correlate with disease severity in patients with psoriasis. The reduction in serum resistin induced by phototherapy might be related to the clinical efficacy of this treatment for psoriasis.

Effects of a novel gaseous antioxidative system containing a rosemary extract on the oxidation induced by nitrogen dioxide and ultraviolet radiation.

Rosemary is commonly used as a spice and a flavoring agent in food processing. Although the antioxidative properties of its extracts have been investigated, there have been few reports on the volatile components of rosemary. We designed a novel antioxidative system which can generate the volatile constituents in the gaseous phase from a rosemary extract and evaluated the gaseous antioxidative activities against both lipid peroxidation and cell death induced by nitrogen dioxide and ultraviolet radiation. The antioxidative effects of the major volatile components on the oxidation of linoleic acid induced by azo compounds were also investigated in a solution. The volatile components in the novel antioxidative system suppressed the Jurkat cell death induced by nitrogen dioxide and the intracellular formation of reactive oxygen species in fibroblast cells induced by ultraviolet radiation. 1,8-Cineole among the volatile components exerted an antioxidative effect against the oxidation of linoleic acid in a solution induced by azo compounds and ultraviolet radiation. These data suggest that the volatile constituents of a rosemary extract had antioxidative properties and that gaseous exposure antioxidant is a promising method for promoting health.