Topical Clofibrate Improves Symptoms in Patients With Atopic Dermatitis and Reduces Serum TARC Levels: A Randomized, Double-Blind, Placebo-Controlled Pilot Study
March 2014 | Volume 13 | Issue 3 | Original Article | 259 | Copyright © March 2014
Mototsugu Fukaya MDa and Hajime Kimata MD PHDb
aTsurumai Kouen Clinic, Nagoya, Japan
bDepartment of Allergy, Kyowakai Hospital, Osaka, Japan
BACKGROUND: Though topical corticosteroids (TC) are used for treating atopic dermatitis (AD) as a standard, there exist several problems including topical steroid addiction (TSA) or Red skin syndrome. Moreover, the number of patients, who refrain from using TC because of steroid-phobia, is increasing. Recently, topical PPAR alpha ligand application has been reported to improve experimental allergic dermatitis. The purpose of this study was to investigate the short-term efficacy and safety of topical clofibrate, one of PPAR alpha ligand, in such steroid-phobic patients with AD.
METHODS: This study was conducted as a double-blind design to investigate the effects of random administration of topical clofibrate and base (placebo) on skin manifestation and blood parameters of patients for 2 weeks. Severity was digitized using severity scoring systems for atopic dermatitis by the Japanese Dermatological Association (SSS-JDA) before and after two weeks. Subjective severity of patients was evaluated using visual analog scale (Pt-VAS). Serum thymus and activation-regulated chemokine (TARC) and immunoglobulin E (IgE) were also investigated.
RESULTS: Twenty patients were enrolled, and 19 of 20 patients completed the study. In 19 patients, the value of severity score using SSS-JDA was decreased significantly after administration of topical clofibrate (P=0.001). Subjective evaluation using Pt-VAS (P=0.008) and serum TARC levels (P=0.03) were also significantly decreased after two weeks of topical clofibrate. There was not a significant difference in serum IgE levels. No adverse effect was observed.
CONCLUSIONS: Topical clofibrate is useful for patients with AD especially who are reluctant to use topical steroids.
J Drugs Dermatol.
Topical corticosteroids (TC) are commonly regarded as a mainstay of AD therapy. However, there exist several problems including topical steroid addiction (TSA) or Red burning skin syndrome.1,2 There are a considerable number of patients with AD who are reluctant to use them because of steroid-phobia.3 Calcineurin inhibitors such as tacrolimus and pimecrolimus seemed to be good alternative medication for those patients. But still there are patients who don’t dare to accept the treatment because calcineurin inhibitors have potential risk of lymphomagenesis even though the result of long-term clinical observation is reported negative.4 On the other hand, recently it has been reported that Burkitt lymphoma was found in a child with AD and 7-year history of topical tacrolimus use.5 Such patients seem to require much more “gentle” and riskless medication.
Recently, topical PPAR alpha ligand application has been reported to improve experimental allergic dermatitis. Several interesting findings are reported about peroxisome proliferator-activated receptor (PPAR) and cutaneous inflammation. Especially PPAR alpha ligand topically applied not only suppresses mild to moderate dermatitis but also prevent the rebound phenomenon after TC use to experimental allergic dermatitis of mice.6
The rebound phenomenon after prolonged use of TC is initially reported by Kligman as “Steroid addiction” in 1970’s.1 The animal experimental model of rebound after TC use was established by by Grabbe in 1995.7 Several studies which prevent or suppress rebound flare after TC use are reported using Grabbe’s murine model since then.8,9 Severe rebound flare developed to the whole body was reported by Rapaport as “Red skin syndrome”.2 The serial phenomena from prolonged use of corticosteroids to rebound flare after discontinuance are called “Topical corticosteroid addiction” (TCA) by some patients and patients’ groups.10
Clofibrate is one of PPAR alpha ligand and formulated as an oral capsule medication for patients with hyperlipidemia. It is easy to prepare topical clofibrate from capsules for clinicians and seems to be useful if it could suppress AD without rebound flare after cessation of TC. As clofibrate is old and cheap medication and no adverse event has been reported about carcinogenicity or immune-suppression, patients with steroid-phobia might accept that “gentle” medication and their quality of life would be improved by using topical clofibrate. That is the background of the study and the purpose of the study is to assess the efficacy and safety of topical clofibrate 0.25% first of all.