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Dear Editor: Prostate cancer is a common malignancy in men, and its incidence is increasing rapidly. Because prostate cancer shows androgen dependency in the early stages1, androgen-deprivation therapy with gonadotropin-releasing hormone (GnRH) agonists is the most effective systemic treatment2. Leuproreline (Lucrin; Abbot, Amstelveen, The Netherlands) is a GnRH agonist that blocks pituitary GnRH receptors, leading to the downregulation of luteinizing hormone and follicle-stimulating hormone3. This chemical castration provides long-term maximal androgen deprivation1. A 79-male-old man, who had painful tender erythematous subcutaneous nodules on the abdomen, visited our dermatologic department in June 2012. He received androgen-deprivation therapy consisting of pretreatment with leuprorelin 11.25 mg at 3-month intervals to treat underlying prostate cancer. A lesion arose from a previous leuprorelin injection site 2 weeks after the last injection (Fig. 1A). He was initially treated with antibiotics and non-steroidal anti-inflammatory drugs, but no improvement was observed. Subsequent histological examination showed neutrophilic and eosinophilic infiltration in the reticular dermis (Fig. 2). Laboratory examination results, including bacterial culture and tuberculosis polymerase chain reaction, were negative. Therefore, he was diagnosed with a sterile abscess caused by GnRH agonist injection and treated with systemic methylprednisolone 16 mg/day. The lesion had almost cleared after 4 weeks and remains in remission as of writing (Fig. 1B). Fig. 1 Painful tender erythematous subcutaneous swelling on abdomen. (A) Before treatment. (B) After 4 weeks of systemic steroid therapy. Fig. 2 Histologic slide stained with hematoxylin and eosin reveals neutrophilic and eosinophilic infiltrates in the reticular dermis. Leuprorelin, a GnRH agonist, is the most effective therapeutic modality for prostate cancer. Although GnRH agonist therapy appears to have significant benefits for patients, it also has serious side effects including anemia, cognitive changes, obesity, lipid alterations, insulin resistance, coronary artery disease, and osteoporosis2,3. The efficacy and side effects of GnRH agonists have recently been reported. In particular, sterile abscess formation has been reported in 3% of patients who received a GnRH agonist4. In Korea, only two patients, who were injected with a GnRH agonist for the treatment of central precocious puberty, have been reported to have developed a sterile abscess at the injection site5. Thus, our case is the first case of a sterile abscess in a Korean patient with prostate cancer treated with leuprorelin. There are many theories about the cause of sterile abscess5. One possible cause is an additive polymer of leuprorelin similar to that used in resorbable sutures. However, there is a report about granulomatous reactions induced by leuprorelin alone3. Thus, this could be thought of as a positive allergic reaction to leuprorelin. Furthermore, these reactions occurred in patients who received daily subcutaneous leuprorelin injections without additive polymer5. Thus, these cases suggest leuprorelin itself could be the cause of sterile abscess and granulomatous reaction. Previous reports describe spontaneous healing of sterile abscesses over several months without treatment4,5. Our patient was treated with a systemic steroid and remained in remission for 1 month. Thus, systemic steroid therapy may be a potential therapeutic modality for GnRH agonist-induced sterile abscess. Dermatologic clinicians should be aware of the potential adverse effects of leuprorelin injection, including sterile abscess and granulomatous reactions.

Dear Editor: Although verruca vulgaris (a common wart) is highly prevalent, but its treatment method is still not accepted by both patients and doctors1. Current modalities depend on the ablation of warts (cryotherapy, laser vaporization, electrodesiccation, salicylic acid, silver nitrate and trichloroacetic acid) or the interruption of cell division (podofilox, intralesional or systemic interferon, intralesional bleomycin and 5-fluorouracil)2,3. All contemporary therapies are connected to significant pain, tissue destruction and common recurrence2,3. No accessible drug therapy is known to successfully eradicate viral infection or replication. Until now, imiquimod, 1-(2-methylpropyl)-1Himidazo[4,5-c]-quinolin-4-amine has been used as a topical immune response to effectively treat external anogenital warts4. Because cell mediated immunity is the primary mechanism accountable for the regression of warts5, we accessed imiquimod as a promising therapy for these frequent viral diseases. In addition, several reports6,7 have recommended that occlusion with adhesive tape could also be an efficacious therapy for the treatment of warts. Given that duct tape therapy is economical and painless, we decided to use this method. The aim of this study was to estimate the safety, tolerance and effectiveness of combination therapy with imiquimod and duct tape for the treatment of the common verruca that have been resistant to prior treatment options. This was a phase II, open-label, clinical study. Approval of the Institutional Review Board (Approved No. AS10101) was obtained prior to the initiation of the study, and written consent was obtained from all patients prior to enrollment. Inclusion criteria were the following: (1) ability to understand and provide informed consent; (2) age greater than 18 years; (3) having at least 1 common wart with a diameter of 2 to 15 mm; and (4) lesions recalcitrant to prior reiterated medical and/or destructive treatment and patient denial to go through painful treatment. Fifty patients were enrolled in the study. Ten patients, 5 from the petrolatum group and 5 from the imiquimod 5% cream group, were not available for follow-up and thus were not included in the analysis. Patients obtained either petrolatum or imiquimod 5% cream. Imiquimod 5% cream or petrolatum was instructed to be self-applied, and then the wart was occluded with duct tape (Silver Duct Tape; 3M, St. Paul, MN, USA) by the patient once daily for 5 days per week. Patients were requested to apply either petrolatum or imiquimod 5% cream to the lesions in an amount that could be rubbed into the skin. In addition, a supply of standard duct tape was provided. The tape was left off in the daytime and reapplied the following night. The therapy proceeded for a maximum of 16 weeks or until resolution of the wart. Patients were asked to revisit the hospital every 2 weeks, so the doctor could remeasure the wart and document the results on the data sheet. Statistical analysis of response to treatment was performed using Fisher's exact test, with p≤0.05 being considered significant. Of 40 patients who completed the study, 20 were in the petrolatum arm, and 20 were in the imiquimod 5% cream arm. There were no significant differences in the mean age or sex of the patients or in baseline size or location of the warts between the two groups. We found that imiquimod 5% cream and duct tape occlusion therapy was appreciably more effective than petrolatum and duct tape occlusion therapy. Eight (40%) of 20 patients in the imiquimod 5% cream and duct tape occlusion arm had complete resolution of their warts (Fig. 1) vs. 0 (0%) of 20 patients in the petrolatum and duct tape occlusion therapy arm (p=0.05). In addition, 6 patients (30%) enrolled in the imiquimod arm vs. 4 patients (20%) enrolled in the petrolatum arm had partial resolution (>50% size reduction) of their warts (Table 1). No recurrence of warts occurred during a follow-up period of 16 weeks. Although no major complications were noted in either group, the main adverse effects were erythema and itching sensation at the site. Fig. 1 Common warts before (A) and after (B) treatment with imiquimod 5% cream and duct tape occlusion therapy: complete response. Table 1 Treatment outcome of imiquimod 5% cream and duct tape occlusion therapy and petrolatum and duct tape occlusion therapy (p=0.05) In our study, we found that imiquimod 5% cream and duct tape occlusion therapy was more effective than petrolatum and duct tape occlusion therapy for the treatment of common warts. The mechanism of action of imiquimod in humans has not been exactly recognized, but several reports imply that it stimulates the cellular immune system, including the use of specific cytokines4,8. Through induction of interferon-alpha, imiquimod could improve antigen presentation by increasing the expression of major histocompatibility complex class I. Together with induced interleukin (IL)-12 p40, imiquimod augments the development of a Th1 type immune response. Other cytokines that are induced by imiquimod such as tumor necrosis factor-alpha, IL-1 and IL-6 may contribute to wart regression by increasing T-cell trafficking to the epidermis, enhancing natural killer cell cytotoxicity and stimulating B-cell proliferation. The therapeutic mechanism of duct tape for the treatment of verruca vulgaris has been mostly undetermined, but several theories have been proposed. The lay media often proposes the theory that occlusion results in a deprivation of oxygen to the virus, essentially leading to suffocation. A second theory is that duct tape debrides and debulks the wart. Allen and Dveirin9 suggested that duct tape may contribute to psychological aspects, thus, it may be more helpful in children than in adults. Additionally, duct tape occlusion creates a macerating and keratolytic environment10, which encourages penetration of imiquimod 5% cream. Thick stratum corneum may inhibit drug penetration, rendering the degree of keratinization, which is a possible explanation for the less impressive results on the common wart. Consequently, duct tape occlusion following the application of imiquimod may be helpful in overcoming this limitation. In conclusion, imiquimod 5% cream and duct tape occlusion combination therapy is an effective alternative treatment modality for the treatment of the common verruca. Additional studies with larger numbers of patients including randomized double blind trials are required to establish its effectiveness.

Hwa Jung Ryu,1,* Mu Yeb Seo,2,* Sung Kyu Jung,1 Eun Ho Maeng,2 Seung-Young Lee,2 Dong-Hyouk Jang,2 Taek-Jin Lee,2 Ki-Yeon Jo,2 Yu-Ri Kim,3 Kyu-Bong Cho,4 Meyoung-Kon Kim,3 Beom Jun Lee,5 Sang Wook Son1 1Department of Dermatology, Korea University College of Medicine, Seoul, 2Korea Testing and Research Institute, Gyunggido, 3Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul, 4Department of Clinical Laboratory Science, Shinheung College, Uijeongbu, 5College of Veterinary Medicine, Chungbuk National University, Cheongju, Republic of Korea *These authors contributed equally to this work and both should be considered first authors Abstract: Zinc oxide (ZnO) works as a long-lasting, broad-spectrum physical sunblock, and can prevent skin cancer, sunburn, and photoaging. Nanosized ZnO particles are used often in sunscreens due to consumer preference over larger sizes, which appear opaque when dermally applied. Although the US Food and Drug Administration approved the use of nanoparticles (NPs) in sunscreens in 1999, there are ongoing safety concerns. The aim of this study was to evaluate the subchronic toxicity of ZnO NPs after dermal application according to the Organization for Economic Cooperation and Development Test Guidelines 411using Good Laboratory Practice. Sprague Dawley rats were randomly divided into eight (one control, one vehicle control, three experimental, and three recovery) groups. Different concentrations of ZnO NPs were dermally applied to the rats in the experimental groups for 90days. Clinical observations as well as weight and food consumption were measured and recorded daily. Hematology and biochemistry parameters were determined. Gross pathologic and histopathologic examinations were performed on selected tissues from all animals. Analyses of tissue were undertaken to determine target organ tissue distribution. There was no increased mortality in the experimental group. Although there was dose-dependent irritation at the site of application, there were no abnormal findings related to ZnO NPs in other organs. Increased concentrations of ZnO in the liver, small intestine, large intestine, and feces were thought to result from oral ingestion of ZnO NPs via licking. Penetration of ZnO NPs through the skin seemed to be limited via the dermal route. This study demonstrates that there was no observed adverse effect of ZnO NPs up to 1,000 mg/kg body weight when they are applied dermally. Keywords: zinc oxide, nanoparticles, subchronic toxicity, dermal exposure