Vitamin D3 derivatives, alone or in combination with glucocorticoids, suppress streptococcal pyrogenic enterotoxin A-stimulated proliferation of peripheral blood mononuclear cells in patients with psoriasis.

Bacterial colonization on skin or tonsil may influence the clinical response of patients with psoriasis to immunosuppressive drugs. However, few studies have investigated the effects of bacterial superantigens on therapy in these patients. Recently, combination therapy with topical glucocorticoids (GC) and vitamin D3 (VD3) appears to be more effective than GC or VD3 monotherapy for psoriasis. We evaluated the suppressive effects of betamethasone butyrate propionate (BBP), three VD3 derivatives (calcipotriol, maxacalcitol and tacalcitol), cyclosporin and BBP plus VD3, on concanavalin A (ConA)- or streptococcal pyrogenic enterotoxin A (SPEA)-stimulated proliferation of peripheral blood mononuclear cells (PBMC) obtained from 35 psoriasis patients. Drug concentrations effecting 50% inhibition concentration of ConA- or SPEA-stimulated PBMC proliferation were estimated. Cytokine levels of tumor necrosis factor-α, γ-interferon, interleukin-1b, -2, -4, -5, -6, -8 -10 and -12p70 in PBMC culture supernatants were measured with bead-array procedures. Suppression of PBMC proliferation by BBP was significantly lower when PBMC were stimulated by SPEA than when stimulated by ConA. In contrast, the suppressive effects of calcipotriol and tacalcitol increased significantly when PBMC were stimulated by SPEA than when stimulated by ConA. The suppressive effect of BBP on SPEA-stimulated PBMC proliferation was improved significantly by adding 1-1000 ng/mL calcipotriol, compared with BBP alone. Cytokine levels in PBMC culture supernatants were not significantly different between ConA- and SPEA-stimulated PBMC. Calcipotriol and BBP in combination markedly suppressed SPEA-stimulated PBMC proliferation. SPEA produced by colonization of hemolytic streptococci may reduce the efficacy of BBP but not VD3 derivatives in the treatment of psoriasis.

Combination therapy using maxacalcitol and corticosteroid lotions preliminary to monotherapy with maxacalcitol lotion for scalp psoriasis.

Topical treatment with betamethasone butyrate propionate lotion on 37 patients with scalp psoriasis was replaced with a combination therapy using maxacalcitol lotion (on weekdays) and BBP (on the weekends). This combination therapy was later switched to MXA monotherapy. To identify the optimum duration of the combination therapy, the patients were divided into two groups: a 4-week group and an 8-week group, which were given combination therapy and monotherapy. In both groups, the total mean scores for the skin symptoms had significantly improved in comparison with that obtained at the outset of the study (p < 0.01). In terms of overall improvement, 20.0% of the 4-week group and 72.7% of the 8-week group yielded scores reflecting moderate or greater improvement. The treatment administered to the 8-week group was significantly more effective than that given to the 4-week group at the end of the trial (p < 0.01). This study also suggests that a 4-week combination therapy is an option before switching to monotherapy, but that an 8-week therapy is preferable in severe cases.

A case of malignant peripheral nerve sheath tumor with rhabdomyoblastic differentiation: malignant triton tumor.

Malignant peripheral nerve sheath tumors (MPNST) constitute a rare variety of soft tissue sarcomas thought to originate from Schwann cells or pluripotent cells of the neural crest. Malignant triton tumor (MTT), a very rare, highly aggressive soft tissue tumor, is a subgroup of MPNST and is comprised of malignant Schwann cells coexisting with malignant rhabdomyoblasts. We herein report the case of a 24-year-old man who presented a subcutaneous mass in his right thigh. The mass was removed surgically in its entirety and radiation therapy was applied locally to prevent tumor regrowth. Nonetheless, the patient died 10 months after surgery from metastases to the lung and brain. He presented neither cafe-au-lait spots nor cutaneous neurofibromas. The histopathology showed a transition from a neurofibroma to an MTT, making this the second report of an MTT arising from a neurofibroma without neurofibromatosis type 1, an autosomal dominant disorder with which 50-70% of tumors reported in previous studies were associated. A histopathological examination using immunostaining with desmin confirmed this diagnosis. MTT has a poorer prognosis than MPNST and should therefore be regarded as a distinct clinical entity.

Low-dose, short-term ciclosporin (Neoral®) therapy is effective in improving patients' quality of life as assessed by Skindex-16 and GHQ-28 in mild to severe psoriasis patients.

Therapies for psoriasis have focused not only on ameliorating the severity of the skin lesions, but also on the quality of life (QOL). Here, the efficacy of low-dose, short-term administration of ciclosporin (Neoral®, as CyA) was investigated. Forty-one psoriasis patients were given CyA orally (3 mg/kg per day) twice daily before breakfast and dinner until the psoriatic area and severity index (PASI) scores decreased by at least 75%. Surveys were conducted before and after the therapy to ascertain QOL, itch, nail condition, joint pain, stress associated with topical application and therapy satisfaction. QOL was assessed by using the Japanese version of Skindex-16 specific to skin diseases, and the Japanese version of the GHQ-28, which assesses mental health. Data collected from 35 patients were analyzed. Remission was achieved in 26 patients (74%), and the average length required to achieve remission was 101.5 days. The average PASI score significantly decreased from 17.8 to 3.3 after the therapy. Remission lasted 6 months or longer in 40% of the patients. The average length of time before restarting systemic therapy was 182.0 days. This duration for patients with PASI scores of <13 was 287.5 days while for patients with PASI scores of ≥13, it was significantly shorter at 120.1 days. Five adverse events were recorded in three patients, but were not serious. The total Skindex-16 score significantly decreased especially in the "emotions' and "functioning" categories. GHQ scores also significantly decreased in "somatic symptoms,""anxiety and insomnia," and "depression". With regard to patients' satisfaction with their therapy, 88.5% of the patients reported "satisfied" or "slightly satisfied". These results demonstrate that low-dose, short-term administration of CyA (3 mg/kg per day) is one of the best therapies for psoriasis patients with PASI scores of <13, while QOL assessment is a very useful tool for evaluating the value of therapy.