Clinical use of TNFα (tumor necrosis factor α) inhibitors, adalimumab and infliximab, for psoriasis began in January 2010 when an additional indication for this disease was approved. In January 2011, an interleukin-12/23 p40 (IL-12/23 p40) inhibitor, ustekinumab, was newly approved as the third biologic agent with an indication for psoriasis. All of these biologic agents are expected to exhibit excellent efficacy against not only psoriasis but also psoriatic arthritis, and to contribute to the improvement of quality of life (QOL) of psoriatic patients. At the same time, however, they require safety measures to prevent adverse drug reactions such as serious infections. We therefore decided to prepare this Guideline/Safety Manual for the Use of Biologic Agents in Psoriasis (The 2011 Version) by revising that for the use of TNFα Inhibitors prepared by the Biologics Review Committee of the Japanese Dermatological Association in February 2010. In this new unified version for all three biologic agents including ustekinumab, requirements for clinical facilities for the use of biologic agents, contents of safety measures against reactivation of tuberculosis and hepatitis B, and recommendable combination therapies with biologic agents, have been renewed and added. This guideline/safety manual has been prepared to assist dermatology specialists experienced in clinical practice of psoriasis to use biologic agents safely and properly.
A 79-year-old man had had a black macule on his left heel for several years. The macule enlarged and formed a tumor, so he came to our hospital in October of 2005. Physical examination showed an eroded tumor with irregularly-shaped, black to brown macule on his left heel. A clinical diagnosis of malignant melanoma was made, and wide local excision and inguinal lymph node dissection were done. The post-operative pathological tumor stage was pT4bN1aM0. After surgery, he was followed up with local injection of interferon-β. Seven months after the operation, multiple in-transit metastases, multiple lung metastases, and one focus of liver metastasis were detected, so chemotherapy with DTIC/ACNU/VCR was started. Because this regimen produced no beneficial response, the therapy menu was changed to chemoimmunotherapy using monochemotherapy with dacarbazine and topical application of a potent contact sensitizer, SADBE. After successful SADBE sensitization, weekly or biweekly topical SADBE immunotherapy was started from a concentration of 0.01%. Local inflammation was minimal, and the application concentration was raised gradually up to 2%. Edematous erythema was observed only after application of 2% SADBE with an occulusive dressing technique; after that, the in-transit metastases became smaller and finally flat.
Statistical analyses of the therapeutic effects of amitriptyline and paroxetine on herpes zoster patients treated with an antiviral agent and non-steroid anti-inflammatory drug were performed. Two hundred and thirty-four patients admitted to the hospital within 14 days after the onset of herpes zoster were included in the analysis. Amitriptyline (25 mg) and paroxetine (10 mg) were administered daily to 113 and 121 patients, respectively. To determine the VAS score of pain after final administration of each drug, the VAS score before administration was set as 100. The VAS score of pain after final administration was significantly lower with paroxetine (37.7±1.8) than with amitriptyline (43.4±1.4) (P<0.01). There was no statistically significant difference of incidence of postherpetic neuralgia between amitriptyline and paroxetine. Side effects of paroxetine were observed in four cases (3.3%), including two cases of anorexia, one case of vomiting, and one case of nocturnal polyuria, whereas those of amitriptyline were observed in nine cases (8.0%), including seven cases of dizziness, one case of drowsiness, and one case of stiffness. Thus, it was confirmed that paroxetine may be an effective medicine for reducing pain in herpes zoster patients with few side effects.
We examined the causes of the different effects of bFGF solution (dissolved in ultrapure water) and Fiblast® Spray solution (dissolved in attached lysate) at high concentrations (100–1,000 ng/ml) on the cell growth of normal human keratinocytes and fibroblasts cultured on type I collagen. We compared the effects of three kinds of bFGF solutions—a bFGF solution dissolved in ultrapure water at 0–1,000 ng/ml concentrations of bFGF and two solutions of Fiblast® Spray, one dissolved in attached lysate and the other in ultrapure water—on the cell growth of normal human keratinocytes and fibroblasts. We utilized a five-day cell growth assay to evaluate toxicity. We also tested the effects of the attached lysate only and benzalkonium chloride only by the same assay. The results showed that all three kinds of bFGF solutions accelerated the cell growth of both cell types in a concentration-dependent manner. For both cell types, the effects of bFGF solution and the Fiblast® Spray solution dissolved in ultrapure water were the same. However, the effect of Fiblast® Spray solution dissolved in attached lysate was somewhat different. When compared with the other two kinds of bFGF solution, there was an inhibition of cell growth, and there were also changes in cell morphology in both cell types at high concentrations (1,000 ng/ml with both cell types and also at 100 ng/ml with the keratinocytes) of bFGF. The same findings were observed with the addition of the medium that contained the same amount of attached lysate only, in which high concentrations of Fiblast® Spray solution were prepared, and also with the medium that contained benzalkonium chloride only. From these data, we concluded that Fiblast® Spray solution dissolved in attached lysate inhibited cell growth of both cell types at high concentrations (100–1,000 ng/ml), unlike the other two kinds of bFGF solutions dissolved in ultrapure water. The cause was the cytotoxicity of benzalkonium chloride in the attached lysate. This study demonstrated that benzalkonium chloride in the attached lysate should be avoided to get maximal acceleration of cell growth of the both cell types by Fiblast® Spray.