Article Text
Abstract
BACKGROUND Crohn's disease of the mouth or perineum is more common in young people, and notably resistant to treatment. However, there is increasing evidence that topical therapy with tacrolimus (FK506) may be effective in skin diseases resistant to cyclosporin because of its high uptake in inflamed skin and subsequent reduction in keratinocyte chemokine production.
PATIENTS AND METHODS Tacrolimus ointment was made up inhouse from the intravenous or oral formulation and suspended in appropriate vehicles for perioral or perianal administration at an initial concentration of 0.5 mg/g. This was administered open label to eight children (aged 5–18 years) with treatment resistant oral (three patients) and/or ulcerating perineal (six patients) Crohn's disease.
RESULTS Marked improvement was seen in 7/8 patients within six weeks and healing within 1–6 months. One child with gross perineal and colonic disease showed little response. Two of the responders showed rebound worsening when tacrolimus was stopped or the dosage reduced rapidly, and one of these eventually required proctectomy. Slower weaning of drug concentration has been successful in 6/8 patients, with four receiving intermittent treatment and two on regular reduced dosage (0.1–0.3 mg/g) with follow up times of six months to 3.5 years. Serum concentrations of tacrolimus were undetectable in all patients.
CONCLUSIONS Topical tacrolimus at low concentrations (0.5 mg/g) shows promise in the management of childhood perineal and oral Crohn's disease, with no evidence of significant systemic absorption. However, rapid weaning or abrupt cessation of therapy may cause rebound worsening of disease. Further controlled studies are required to assess the efficacy and safety of this treatment.
- Crohn's disease
- tacrolimus
- children
Abbreviations used in this paper
- TNF
- tumour necrosis factor
- HDPD
- highly destructive perianal disease
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Abbreviations used in this paper
- TNF
- tumour necrosis factor
- HDPD
- highly destructive perianal disease