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.

Efficacy and safety of bexarotene combined with photo(chemo)therapy for cutaneous T-cell lymphoma.

Cutaneous T-cell lymphoma (CTCL) is a chronic condition with low malignancy. International treatment guidelines for CTCL are widely followed in Europe and the USA. Combination therapy with therapeutic agents for CTCL and phototherapy is effective on the basis of European data. The efficacy and safety of combination therapy for Japanese CTCL patients are not established. We investigated the efficacy and safety of combination therapy with photo(chemo)therapy and bexarotene in Japanese CTCL patients. Twenty-five patients received daily oral bexarotene (300 mg/m2 body surface), followed by bath-psoralen plus ultraviolet (UV)-A (PUVA) or narrowband UV-B. Treatment results were evaluated using the modified Severity-Weighted Assessment Tool (mSWAT) and the Physician Global Assessment of Clinical Condition (PGA) up to week 24. Safety was also assessed. Twenty-four weeks after initiating treatment, the total response rate was 80.0% (mSWAT) and 84.0% (PGA). Response rates did not differ when stratified by disease stage. Number of days (mean ± standard deviation) for time to response, duration of response and time to progression determined by the mSWAT were 20.7 ± 9.62, 117.0 ± 43.0 and 163.6 ± 28.8, respectively. T-helper 2 chemokine levels in patients at stage IIA or more decreased significantly at weeks 12 and 24. All patients experienced adverse events and adverse drug reactions. Serious adverse drug reactions included sepsis, anemia and congestive cardiac insufficiency (n = 1 each). Other adverse drug reactions were of mild to moderate severity. Combination therapy with bexarotene and PUVA was safe and effective in Japanese CTCL patients.

Assessment of medication adherence and treatment satisfaction in Japanese patients with psoriasis of various severities.

Psoriasis is a chronic, relapsing, inflammatory keratotic skin disease. To elucidate the medication adherence and treatment satisfaction, we performed a questionnaire survey using the eight-item Morisky Medication Adherence Scale (MMAS-8) and nine-item Treatment Satisfaction Questionnaire for Medication (TSQM-9) of 163 psoriatic patients who regularly visited hospitals or clinics. To assess the relationship between the MMAS-8/TSQM-9 outcomes and severity of psoriasis, two different clinical severity indices were used: the Psoriasis Area and the Severity Index (PASI) for disease severity and the Psoriasis Disability Index (PDI) for quality of life (QOL) impairment. The MMAS-8 score for oral medication was significantly higher than that for topical medication. The oral and topical MMAS-8 scores were significantly correlated with the PDI score, but not with the PASI score, indicating that QOL impairment lowered treatment motivation. All of the TSQM-9 domain scores (effectiveness, convenience and global satisfaction) were significantly correlated with both the PASI and PDI scores, suggesting that patients whose skin and QOL conditions were under good control had high satisfaction with treatment. Patients treated with biologics had higher satisfaction than those treated with non-biologics.

Low incidence of hypercalcemia following combined calcipotriol hydrate/betamethasone dipropionate ointment treatment in Japanese patients with severe psoriasis vulgaris.

PURPOSE: Topical active vitamin D3 application alone or in combination with topical steroid application is widely used to treat psoriasis. In Japan, combined calcipotriol hydrate/betamethasone dipropionate ointment has been used for patients with psoriasis vulgaris since September 2014. Current evidence regarding the incidence of hypercalcemia due to the use of this combination product, however, is insufficient. We evaluated the incidence of hypercalcemia following combined calcipotriol hydrate/betamethasone dipropionate ointment in patients with severe psoriasis vulgaris. METHODS: Japanese patients (n = 22) with extensive plaque psoriasis (body surface area: 20-30%) applied the combined calcipotriol hydrate/betamethasone dipropionate ointment once daily for 8 weeks, and their serum Ca concentrations were measured periodically. RESULTS: The mean serum Ca concentration changed only marginally, from 9.04 ± 0.34 mg/dL before treatment to 9.08 ± 0.39 mg/dL after 8 weeks of treatment. None of the patients had an elevated serum Ca concentration throughout the study. No cases of hypercalcemia were reported as an adverse event. No correlation was detected between the amount of the combined calcipotriol hydrate/betamethasone dipropionate ointment applied and changes in the serum Ca concentration. CONCLUSION: The incidence of hypercalcemia due to topical application of a combined calcipotriol hydrate/betamethasone dipropionate ointment is low in Japanese patients with severe psoriasis vulgaris.

Bath-PUVA therapy improves impaired resting regulatory T cells and increases activated regulatory T cells in psoriasis.

BACKGROUND: Bath-psoralen plus ultraviolet light A (PUVA) therapy is an effective, safe, and inexpensive treatment for psoriasis. Psoriasis might be due to an unbalanced ratio of Th17 cells and regulatory T cells (Treg). The Treg functional ratio is significantly lower in patients with psoriasis compared with controls and is inversely correlated with the Psoriasis Area and Severity Index score. We previously reported that bath-PUVA therapy significantly increases the number of Treg and restores Treg function to almost normal in most patients with psoriasis. OBJECTIVES: We examined the effects of bath-PUVA therapy on three distinct Foxp3+ subsets: activated Treg (aTreg), resting Treg (rTreg), and cytokine-secreting non-suppressive T cells. METHODS: We enrolled 15 patients with psoriasis and 11 healthy controls. We examined aTreg, rTreg, and cytokine-secreting non-suppressive T cells in peripheral blood obtained from the psoriasis patients before and after every fifth bath-PUVA therapy session. RESULTS: Levels of aTreg, which are considered to have the strongest suppressive activity in patients with psoriasis, were significantly increased in the early bath-PUVA therapy sessions, and then diminished. Levels of rTreg were lower in psoriasis patients than in healthy controls, and increased during bath-PUVA therapy. CONCLUSIONS: Bath-PUVA therapy induced aTreg and rTreg concomitantly with an improvement in the psoriatic lesions, suggesting a mechanism for the effectiveness of bath-PUVA therapy for psoriasis patients.

Serum interleukin-6 levels in response to biologic treatment in patients with psoriasis.

OBJECTIVES: Psoriasis is a chronic autoimmune disease involving a complex network of cytokines such as interleukin (IL)-6. We tested the hypothesis that serum IL-6 level is a useful indicator of disease activity and predicts the treatment response to biologics in patients with psoriasis. METHODS: We analyzed 113 psoriasis patients treated with biologics (73 with infliximab [IFX], 24 with adalimumab [ADA], and 16 with ustekinumab [UST]) in our hospital. Disease severity was assessed using the Psoriasis Area and Severity Index (PASI) score, and Disease Activity Score 28 based on C-reactive protein (DAS28-CRP). RESULTS: Before treatment, serum IL-6 levels significantly correlated with PASI scores in patients with psoriasis vulgaris (r = 0.432, p = 0.001) and with DAS28-CRP in patients with psoriatic arthritis (r = 0.469, p = 0.010). Serum IL-6 levels were significantly decreased by IFX (from 4.8 to 1.5) and ADA (from 2.5 to 1.4) therapy. In psoriatic arthritis, serum IL-6 levels at the endpoint tended to be lower in patients who achieved DAS28-CRP <2.3 (European League Against Rheumatism remission criteria) than in patients who did not. CONCLUSION: Serum IL-6 level may be a useful biomarker for assessing disease activity in patients with psoriasis and for predicting responsiveness of joint symptoms to biologic treatment.