Faculty Bibliography

Necrobiosis lipoidica diabeticorum (NLD) is an idiopathic granulomatous skin disorder. We review previously described therapies from the recent literature and report the first case of successful treatment of NLD with oral chloroquine

BACKGROUND: The purine nucleoside phosphorylase inhibitor peldesine is a new agent being evaluated as a T-cell inhibitor. OBJECTIVE: We attempted to determine the efficacy of peldesine (BCX-34) in a 1% dermal cream formulation as a treatment for cutaneous T-cell lymphoma (CTCL). METHODS: Ninety patients with patch and plaque phase CTCL, histologically confirmed by a referee dermatopathologist, were enrolled in a randomized, double-blind, placebo-controlled study. BCX-34 dermal cream 1% or the vehicle cream (as a placebo control) was applied twice daily to the entire skin surface for up to 24 weeks. Efficacy of the topical therapy was assessed in terms of complete or partial (> or = 50%) clearing of patches and plaques. RESULTS: Of the 89 patients able to be examined, 43 received BCX-34 and 46 received the placebo vehicle cream. One patient withdrew early and was not analyzed. The two groups were well balanced for potential prognostic factors. A total of 28% (12/43) of the patients treated with BCX-34 showed a response, but 24% (11/46) of patients who received vehicle also responded (P =.677). CONCLUSION: Although BCX-34 dermal cream 1% was not significantly better than the control as therapy for patch and plaque-phase CTCL, this appears to be the first published placebo-controlled trial evaluating treatment for CTCL. Whether the vehicle cream has more than a placebo therapeutic effect is unclear. The relatively high (24%) placebo response rate should be kept in mind in assessing other treatments for early-stage CTCL

Atopic dermatitis is a chronic, relapsing skin condition that affects over 2% of the population. The pathophysiology of this disease is not completely understood, but immunologic abnormalities and the subsequent release of inflammatory mediators play a central role. Treatment with glucocorticoids has long been the standard of care, but their use is limited by their adverse effect profile. Leukotrienes (LTB4, LTC4, LTD4, and LTE4) are metabolites of arachidonic acid produced through the 5-lipoxygenase pathway. They play an important role in inflammatory and atopic conditions. LT modulating agents have been used with success in asthma. Recently, there has been increased interest in the potential utility of LT antagonists in atopic dermatitis. In vitro and in vivo data have demonstrated that LTs may play a key role in atopic dermatitis. The 2 different types of LT-modulating agents are 5-lipoxygenase inhibitors and LT receptor antagonists. Since the 5-lipoxygenase inhibitor acts at an earlier step in the LT synthetic pathway, it has the ability to alter the production of all the LTs, including LTB4, while the receptor antagonists target only the cysteinyl LTs, LTC4, LTD4, and LTE4. This reduction of LTB4 activity may point to a therapeutic advantage in using LT synthesis inhibitors as opposed to LT receptor antagonists for atopic dermatitis. Clinical evidence of the use of LT agents in atopic dermatitis is limited, but initial results have been promising and these agents may one day serve as corticosteroid-sparing treatments for atopic dermatitis

The definitions of psoriasis severity and clinically significant improvement in psoriasis are used to classify treatments, obtain Food and Drug Administration approval, and determine product labeling and reimbursement. The Medical Advisory Board of the National Psoriasis Foundation has addressed these issues because of their importance in the clinical trials that are conducted to gain FDA approval of indications. Narrow indications, which are without a sound rational basis, will-in this era of constant oversight by third party payers-affect physicians' ability to manage patients with psoriasis. Body surface area (BSA) is usually used to define severity for clinical trials. It is not optimal for defining psoriasis severity because there are some patients with low BSA involvement who have very severe psoriasis and some patients with high BSA involvement who have mild psoriasis. We conclude that a quality of life (QOL) standard is better than BSA measurement for identifying patients with severe psoriasis. The second issue is what defines clinically significant improvement for patients with psoriasis. Setting an arbitrarily high criterion of clinical efficacy for new psoriasis treatments will likely limit the development and approval of useful treatments. To maximize the availability of useful psoriasis treatments, it is our thesis that psoriasis treatments should be approved when they have been shown to produce a statistically significant level of improvement in well-designed clinical trials