Clinics in dermatology
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Clinics in dermatology · May 2013
ReviewAdjuvant immunotherapy of melanoma and development of new approaches using the neoadjuvant approach.
Melanoma is the third most common skin cancer but the leading cause of death from cutaneous malignancies. Although early-stage disease is frequently cured by surgical resection with excellent long-term survival, patients with deeper primary lesions (AJCC stage IIB-C) and those with microscopic (IIIA) or clinically evident regional lymph node or in-transit metastases (IIIB-C) have an increased risk of relapse and death, the latter approaching 70% or more at 5 years. In patients at high risk of recurrence/metastases, adjuvant therapy with high-dose interferon alpha-2b (HDI) following definitive surgical resection has been shown to improve relapse-free and overall survival. ⋯ Several neoadjuvant trials have been conducted in the phase II setting, which have illuminated the mechanism of IFN-α, as well as providing insight to the effects of anti-CTLA4 blocking antibodies. These agents (anti-CTLA4 blocking antibody ipilimumab, and BRAF inhibitor vemurafenib) are likely to be followed by other immunotherapies that may overcome the PD-1 checkpoint (anti-PD1 and anti-PDL-1) as well as other molecularly targeted agents such as the BRAF inhibitor dabrafenib and the MEK inhibitors trametinib, selumetinib, and MEK162 in the near future. Evaluation of the clinical role of these agents as adjuvant therapy will take years to accomplish to ascertain the relapse-free survival benefits and overall survival benefits of these agents, but neoadjuvant exploration may provide early critical evidence of the therapeutic benefits, as well as clarifying the mechanisms of these agents alone and in combination.
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Melanoma cells frequently metastasize to the brain, and approximately 50% of patients with metastatic melanoma develop intracranial disease. Historically, central nervous system dissemination has portended a very poor prognosis. Recent advances in systemic therapies for melanoma, supported by improved local therapy control of brain lesions, have resulted in better median survival for these patients. We review current local and systemic approaches for patients with melanoma brain metastases.
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Pruritus and psyche are intricately and reciprocally related, with psychophysiological evidence and psychopathological explanations helping us to understand their complex association. Their interaction may be conceptualized and classified into 3 groups: pruritic diseases with psychiatric sequelae, pruritic diseases aggravated by psychosocial factors, and psychiatric disorders causing pruritus. ⋯ Pharmcotherapeutic agents that are useful for chronic pruritus with comorbid depression and/or anxiety comprise selective serotonin reuptake inhibitors, mirtazapine, tricyclic antidepressants (amitriptyline and doxepin), and anticonvulsants (gabapentin, pregabalin); the role of neurokinin receptor-1 antagonists awaits verification. Antipsychotics are required for treating itch and formication associated with schizophrenia and delusion of parasitosis (including Morgellons disease).
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Psychiatric medications are among the most widely prescribed medications in the United States. Adverse cutaneous drug reactions are associated with psychiatric medications in approximately 2% to 5% of the individuals for whom they are prescribed. Although most adverse cutaneous drug reactions associated with psychotropic medications are benign and easily treated, some can be disfiguring or life-threatening, particularly those associated with the mood stabilizers. Adverse cutaneous drug reactions associated with antidepressants, antipsychotics, and mood stabilizers are reviewed, and important issues that are of concern for the dermatologist who must consider when and how to safely discontinue a psychotropic medication in their patients are presented.