Topical diacerein for epidermolysis bullosa: a randomized controlled pilot study
© Wally et al.; licensee BioMed Central Ltd. 2013
Received: 4 March 2013
Accepted: 2 May 2013
Published: 7 May 2013
Blistering in epidermolysis bullosa simplex type Dowling-Meara (EBS-DM) is associated with an inflammatory phenotype, which can be disrupted by diacerein in vitro. In this pilot study we hypothesized, that a topical formulation of diacerein 1% reduces blistering. Five patients initially applied diacerein underneath both armpits. Then, each participant received 1% diacerein-cream for one armpit, and placebo for the other (randomized withdrawal). The number of blisters was reduced significantly (left: -78%; right: -66% of baseline) within two weeks and remained significantly below the initial level even during withdrawal in four patients. These findings point to a relevant effect of diacerein and provide important information for a confirmative study.
KeywordsEpidermolysis bullosa Small molecule therapies Pilot study Keratin 14 Diacerein Interleukin-1ß
EBS-DM is the consequence of dominantly inherited mutations in either the keratin 5 (K5) or keratin 14 (K14) gene, which encode proteins constituting the intermediate filament (IF) network of basal keratinocytes. Mutations lead to an increased mechanical susceptibility of keratinocytes, manifesting in a collapse of the IF network . Clinically, patients suffer from blistering of the skin upon minor trauma, resulting in an impaired quality of life due to pain and pruritus . In vitro studies on EBS-DM keratinocytes showed a significant upregulation of interleukin-1beta (IL-1ß), resulting in the activation of the c-jun N-terminal-kinase (JNK) stress pathway and subsequently in the overexpression of K14 and IL-1ß in a positive feedback loop. When impairing IL-1ß signaling, using anti-IL-1ß antibody or the small molecule diacerein, levels of IL-1ß, JNK and K14 decreased and the IF network was stabilized . Based on this information, we launched a double-blinded, randomized, placebo-controlled pilot study using a 1% diacerein in the commonly used care cream ultraphil® as intervening agent, and ultraphil® alone as placebo.
Diacerein, a prodrug of the IL-1 converting enzyme inhibitor rhein, is approved for the systemic treatment of osteoarthritis (Verboril®) [4, 5]. It is metabolized in the liver and cleared by the kidneys. Up to now there are no data available on topical application.
The chosen dose and treatment regimen can lead to substantial reduction of blisters within 2 weeks.
This effect seems to be rather stable and can persist for several weeks after cessation.
Thus, it seems reasonable to include only patients with a substantial blistering at study entry and study the reduction of blisters in a randomized controlled manner.
Furthermore, assessment of blistering should be done by study staff, because the validity of self-evaluation showed to be critical, although patients received a training in blister counting and foto-documentation.
Written informed consent was obtained from the patients or the patient's parents for publication of this report and any accompanying images.
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