Clinics in dermatology
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Nail abnormalities can arise in conjunction with or as a result of systematic pathologies. These pathologies include single-organ diseases, multisystemic diseases, and drug-induced insults. ⋯ The associated systemic pathologies may affect any part of the nail apparatus, including the nail matrix, the nail plate, the nail bed, the underlying vasculature, and the periungual tissues. The anatomical location and extent of damage determine the clinically manifested anomaly.
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Clinics in dermatology · Jul 2013
ReviewScleroderma: nomenclature, etiology, pathogenesis, prognosis, and treatments: facts and controversies.
Scleroderma refers to a heterogeneous group of autoimmune fibrosing disorders. The nomenclature of scleroderma has changed dramatically in recent years, with morphea (localized scleroderma), limited cutaneous systemic sclerosis, diffuse cutaneous systemic sclerosis, and systemic sclerosis sine scleroderma encompassing the currently accepted disease subtypes. Major advances have been made in the molecular studies of morphea and systemic sclerosis; however, their etiologies and pathogenesis remain incompletely understood. ⋯ Morphea can cause significant morbidity but does not affect mortality, whereas systemic sclerosis has the highest disease-specific mortality of all autoimmune connective tissue diseases. Treatment recommendations for morphea and systemic sclerosis are based on limited data and largely expert opinions. Current collaborative efforts in morphea and systemic sclerosis research will hopefully lead to better understanding of the etiology and pathogenesis of these rare and varied diseases and improved treatment options.
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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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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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Paracoccidioidomycosis is an endemic systemic mycosis that predominates in southern Mexico, parts of Central America, and South America. It is caused by a dimorphic fungus and is generally acquired through the lungs, from where it disseminates. ⋯ Treatment includes sulfamethoxazole-trimethoprim for mild forms and itraconazole for moderate cases. Fluconazole and voriconazole can be used for meningeal involvement, and amphotericin B is indicated for severe disease.