کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3207095 1587568 2012 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Morphea-like skin reactions in patients treated with the cathepsin K inhibitor balicatib
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی امراض پوستی
پیش نمایش صفحه اول مقاله
Morphea-like skin reactions in patients treated with the cathepsin K inhibitor balicatib
چکیده انگلیسی

BackgroundIn a multicenter clinical trial in North America and Europe that tested the cathepsin K (catK) inhibitor balicatib for the treatment of osteoporosis, several patients developed hardening of the skin.ObjectiveWe sought to characterize these observed adverse events.MethodsPatients with skin hardening were examined by a local dermatologist. All of those patients except one had at least one biopsy specimen taken from affected skin, which was read by local and two central dermatopathologists. Workup was directed for consideration of systemic scleroderma.ResultsNine patients of 709 treated with balicatib developed skin hardening and were given a diagnosis of morphea-like skin changes. No such events were observed in patients taking placebo or the lowest balicatib dose. After discontinuation of balicatib, skin changes resolved completely in 8 and partially in one patient.LimitationsEach patient was seen by a different dermatologist in 6 different countries.ConclusionsThese observations are likely dose-related adverse effects of balicatib. Although catK was originally thought to be expressed only in osteoclasts, it has more recently also been found in lung and dermal fibroblasts and been implicated in the degradation of the extracellular matrix in the lung and the skin. It is therefore plausible that the observed dermal fibrosis in balicatib-treated patients is a result of impaired degradation of extracellular matrix proteins and may represent a class effect of catK inhibitors. We recommend that further exploration of catK inhibition for the treatment of osteoporosis or cancer should include monitoring for similar adverse effects.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of the American Academy of Dermatology - Volume 66, Issue 3, March 2012, Pages e89–e96
نویسندگان
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