Azathioprine has been used by dermatologists as a corticosteroid-sparing agent for 30 years, but its mechanism and pharmacokinetics remain unclear. Azathioprine is metabolized by the liver to 6-mercaptopurine, which in turn is converted to either active 6-thioguanine nucleotides (6-TGN) or the inactive 6-methylmercaptopurine. The current standard of care involves measurement of thiopurine methyltransferase activity prior to treatment to determine the level of this important enzyme that is involved in the hematopoietic toxic effects of azathioprine. In this prospective longitudinal study, el-Azhary et al determined optimal levels of 6-TGN for disease remission in patients with immunobullous disease, offering dermatologists a guide for monitoring patients receiving azathioprine.
Fluorouracil is an antimetabolite chemotherapeutic agent that inhibits the synthesis of thymine, a critical building block of DNA. Topical fluorouracil has taken a place among the top tier of therapies for the treatment of actinic keratoses. A softening and smoothing of the skin's texture has been noted incidentally following such treatment. In this nonrandomized, open-label, 2-week study of treatment with fluorouracil cream, 5% Sachs et al demonstrate improvement in both actinic keratoses and photoaging that was associated with the molecular correlates of epidermal injury and the subsequent wound-healing response.
Cutaneous T-cell lymphoma (CTCL) is classified according to the World Health Organization and the European Organization for Research and Treatment of Cancer classification system for cutaneous lymphomas. This scheme recognizes 2 broad categories of CTCL: mycosis fungoides (MF)/Sézary syndrome and non-MF CTCLs. The latter group is much less common and is classified by histopathologic features and clinical behavior. In this case series, Poligone et al describe 3 patients with a CTCL variant localized to the legs, predominantly below the knee. The aggressive nature of these cases suggests that the lower leg site may be associated with either a compromised antitumor response or promotion of tumor progression.
Large congenital nevi carry a slightly elevated risk of melanoma. Pregnancy poses additional challenges for monitoring these lesions because the role of pregnancy in melanoma remains unclear. In this case report, Nading et al describe a young woman with a giant congenital nevus who developed lightening of her nevus and various satellite nevi during pregnancy followed by nevus darkening post partum. Immunohistochemical studies demonstrated decreased estrogen receptor β (ERβ) staining during pregnancy and increased staining following delivery. Because acquired melanocytic nevi demonstrate increased ERβ staining during pregnancy, the authors suggest that congenital nevi may be unique in their response to altered estrogen levels.
Psoriasis is a common skin disorder with systemic inflammatory manifestations. Not only are cardiovascular disease risk factors more prevalent among patients with psoriasis, but psoriasis itself confers an independent risk for myocardial infarction. Because atherosclerosis is a systemic disease, it is reasonable to assume that other manifestations of atherosclerosis might also be increased among patients with psoriasis. In this observational study of patients with psoriasis, Prodanovich et al demonstrate a higher prevalence of not only ischemic heart disease but also cerebrovascular and peripheral vascular disease. Psoriasis was found to be an independent risk factor for mortality, suggesting that clinicians caring for patients with psoriasis may consider a lower threshold for atherosclerotic disease screening.
This Month in Archives of Dermatology. Arch Dermatol. 2009;145(6):631. doi:10.1001/archdermatol.2009.113