Clinical effectiveness of efinaconazole 10% solution for treatment of onychomycosis with longitudinal spikes.

Onychomycosis with longitudinal spikes in the nail plate has been reported to be refractory to oral drugs as with dermatophytoma. We evaluated the efficacy of 10% efinaconazole solution in the treatment of onychomycosis with longitudinal spikes. Of the 223 subjects who were enrolled in a previous study, a post-hoc analysis of 82 subjects with longitudinal spikes was performed in this study. The opacity ratio of longitudinal spikes was decreased over time from 8.1 to 0.9 at the final assessment. In addition, the longitudinal spike disappearance rate increased early after the application to 81.7% at the final assessment. Therefore, 10% efinaconazole solution can be a first-line drug for longitudinal spikes, which have been regarded as refractory to oral drugs.

Efficacy of long-term treatment with efinaconazole 10% solution in patients with onychomycosis, including severe cases: A multicenter, single-arm study.

We evaluated the efficacy of efinaconazole 10% topical solution in long-term use, for up to 72 weeks, for onychomycosis, including severe cases. Among 605 participants, 219 patients diagnosed as having onychomycosis were evaluated for the efficacy of efinaconazole. The treatment success rate (<10% clinical involvement of the target toenail) at the final assessment time point was 56.6%, the complete cure rate was 31.1% and the mycological cure rate was 61.6%, all of which increased over time, demonstrating that continuous application contributed to the improvement of cure rate. Even in severe cases, reduction of the affected nail area was observed, showing the potential efficacy of the treatment. Responses to a quality of life questionnaire among patients with onychomycosis, OnyCOE-t, suggested that efinaconazole treatment improved the patients' quality of life. The incidence of adverse drug reaction in the patients eligible for the assessment was 6.3%, and this developed only in the administration site in all cases. No systemic adverse event was observed. In addition, no increase in the incidence of adverse drug reaction due to long-term use was found. Efinaconazole therapy was proved to exhibit excellent balance between efficacy and safety, and thus may serve as a useful treatment option for onychomycosis.

Symptoms of and Palliative Treatment for Unresectable Skin Cancer.

OPINION STATEMENT: The symptom prevalence in patients with advanced cancer depends on the type of primary cancer, and the palliative treatment varies according to the nature of the primary cancer. Palliative treatment for unresectable skin cancer has not been fully discussed. Patients with unresectable skin cancer sometimes show the primary lesion in the skin and metastases to the lung, skin, liver, and bone. Pain, anorexia, and dyspnea commonly occur in such patients, and bleeding, exudate, and offensive odor are characteristically observed. For the last three symptoms, surgery and radiation are effective therapeutic options, and cryotherapy, Mohs' chemosurgery, electrochemotherapy, and some topical ointments and dressing materials are also additional options. For pain due to bone metastasis, pharmacotherapy with opioid and/or non-opioid agents is the most basic treatment, and radiation and bisphosphonate therapies are other options. For dyspnea, which is an intractable and uncomfortable symptom, morphine and oxygen play a leading role in treatment. Red blood cell transfusions may be effective for some patients with dyspnea induced by anemia. Nutritional supports and pharmacotherapy are therapeutic options for anorexia. As nutritional supports, enteral nutrition is better than parenteral nutrition. There is some evidence of progestins and corticosteroids having supportive effects for anorexia. Dermatologic oncologists should be skilled with symptom managements to maintain the quality of life in patients with unresectable skin cancer and their families.

Skin metastasis of hypopharyngeal carcinoma to the nasal tip.

Head and neck squamous cell carcinoma (SCC) rarely metastasizes to the skin. Metastases to the nasal tip from hypopharyngeal malignancies are extremely rare. We present a patient with nasal tip metastasis from hypopharyngeal SCC. A 74-year-old man with hypopharyngeal and esophageal carcinomas had a red nodule on his nasal tip (so-called "clown nose"). Histopathologically, atypical squamoid cell nests had proliferated in a lobular fashion from the dermis to subcutaneous tissue. Those atypical cells were identical to primary tumor cells in the hypopharynx. Based on these findings, a diagnosis of skin metastasis from hypopharyngeal SCC was made. In patients with malignant disease, biopsy should be performed for any suspicious skin lesion. In a patient like ours, "clown nose" might be a symptom of cutaneous metastasis. When clinicians note a "clown nose", they should consider malignancies in the neck and chest areas.

Adverse Skin Reactions due to Ribavirin in Hepatitis C Combination Therapy with Pegylated Interferon-α2a.

The introduction of ribavirin to hepatitis C combination therapy with pegylated interferon (PEG-IFN)-α2a has improved sustained responses, but it has been accompanied by an increased incidence of cutaneous side effects. Most cases of drug eruption caused by ribavirin and PEG-IFN-α2 or IFN-α combination therapy were not severe and we progressed without discontinuation of the antiviral treatment. We describe a 59-year-old Japanese woman with a chronic hepatitis C infection who developed erythema during PEG-IFN-α2a and ribavirin combination therapy. The eruption at the injection site of IFN occurred after each injection, and then, eruption on her exposed skin was observed. Twenty milligrams of prednisolone was administered. The eruption recurred after each administration of prednisolone and ribavirin. She finally had infiltrative erythema without any mucosal symptoms on her body. It seemed to be an erythema multiforme type drug eruption of PEG-IFN-α2a, ribavirin and/or fluvastatin sodium from the clinical course. The lymphocyte transformation test (LTT) of ribavirin was positive. This is the first case of a positive result of an LTT for ribavirin. A photosensitive type drug eruption with ribavirin treatment has been reported. We should not only consider IFN, but also ribavirin in case of a generalized eruption, especially on an exposed area with combination therapy for HCV.

Syringocystadenoma papilliferum on the male nipple.

Syringocystadenoma papilliferum is a rare benign adnexal tumor that most frequently arises from an organoid nevus on the head and neck. Occurrence of this tumor on the male breast is extremely rare. A 74-year-old Japanese man presented with a nodule on his left nipple. Histopathological findings were typical for syringocystadenoma papilliferum. Ultrastructurally, constituent epithelial cells of the tumor were divided into three types. We focused on one cell type, undifferentiated clear cells, which have been suggested to be pluripotent cells bearing stem cell nature in syringocystadenoma papilliferum. Immunohistochemically, the tumor cells were negative for cytokeratin 15, which is known as a relatively specific marker for multipotent stem cells in the follicular bulge. We speculated that the clear cells are slightly differentiated toward apocrine rather than stem cells. We also ruled out the possibility of a relationship between the clear cells and Toker cells, which have a clear cytoplasm and are present in the areola region. Dermoscopic examination revealed amorphous milky white areas that corresponded to the pathological findings of luminal deposition of the tumor.

Olopatadine hydrochloride inhibits capsaicin-induced flare response in humans.

Capsaicin, a vanilloid, has the potential for releasing substance P (SP) from sensory nerves. Topical application of capsaicin induces a flare response in the skin. However, it has not been clarified whether the release of SP is involved in the process of flare response or not. A potent antihistamine drug, olopatadine hydrochloride, is known to have inhibitory action against the release of SP. We examined the effects of olopatadine (at a dose of 5 mg) on skin reaction induced by topical application of capsaicin in 10 healthy subjects. The scores of capsaicin-induced flare responses after olopatadine administration were significantly lower at 30 min than at baseline. Our findings suggest that olopatadine hydrochloride could inhibit capsaicin-induced flare responses.

Regulatory T cells and skin tumors.

Regulatory T cells (Tregs) are essential for maintaining self-tolerance and also play a pivotal role in diminishing anti-tumor immunoresponse. The frequency and activity of CD4(+)CD25(+)FoxP3(+) Tregs in the circulation and tumor microenvironment is increased in patients with various cancers. Although, the exact role of Tregs in cutaneous tumors remains unclear, Tregs contribute to tumor progression of skin cancers, explaining, in part, why immunotherapy with dendritic cell-based vaccination for melanoma patients has not been satisfactory. Therefore, there has been considerable interest in determining their function in order to treat skin cancers such as malignant melanoma. However, clinical trials with specific antibodies designed to overcome Treg-associated immunosuppression resulted in limited clinical efficacy with some adverse effects. A better understanding of the role of Tregs in the tumor environment might contribute to the development of novel approaches for treating various cutaneous tumors. In this review, we focus on clinical and basic research on Tregs in relation to skin tumors and describe some important patents for the treatment of skin cancers.