Topical tacrolimus 0.1% ointment for treatment of cutaneous Crohn's Disease.

BACKGROUND: Cutaneous Crohn's Disease is a notoriously difficult condition to treat and causes significant morbidity, impacting heavily on quality of life. This is the first study in adults examining the effect of topical tacrolimus on the different cutaneous manifestations of Crohn's Disease. METHODS: This open label observational study of 20 patients with heterogeneous forms of cutaneous Crohn's disease used topical tacrolimus 0.1% ointment once daily to affected areas for 12 weeks with a maximal total dose of 90g. Therapy was stopped at 12 weeks to assess whether the condition relapsed. Thereafter relapsing patients optionally continued an open label extension of topical tacrolimus therapy and were observed for a total of 12 months. RESULTS: Of seventeen patients completing the twelve-week study, fifteen improved using a specifically designed physicians' global severity scale. One patient cleared, four showed a pronounced improvement (51-75%) and ten demonstrated a mild (1-25%) or moderate improvement (25-50%) in twelve weeks. Over twelve months eleven patients remained in the study, nine of which improved, one cleared and one showed no change. Perineal disease responded better with two out of twelve clearing, four showing pronounced benefit and four mild to moderate improvement. Long-term application of 0.1% tacrolimus applied to broken skin and mucosa was safe and serum levels of tacrolimus were undetectable in all subjects throughout the study. CONCLUSION: 0.1% tacrolimus ointment was safe and effective in treating cutaneous manifestations of Crohn's disease, particularly perineal disease and pyoderma gangrenosum, yet it seldom cleared the condition. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Protocol Registration System ID: 33000332.

Influence of isotretinoin on hippocampal-based learning in human subjects.

RATIONALE: The acne drug isotretinoin has 13-cis retinoic acid as its active agent. Adverse effects that have been described include severe depression. Animal studies indicate that the hippocampus is particularly sensitive to retinoic acid. Changes induced by isotretinoin to hippocampal function could contribute to depression but may be more evident in altered visuospatial learning and memory, the primary function of the hippocampus. OBJECTIVES: We aimed to test the hypothesis that a course of oral isotretinoin therapy would result in declining visuospatial learning and memory. METHODS: CANTAB tasks designed to assess visuospatial memory were performed repeatedly on 14 males and 3 females in an open prospective observational study of patients with severe acne undergoing isotretinoin therapy. Beck's Depression Inventory and Global Acne Grade were also administered. RESULTS: Performance stayed unchanged for DMS, SRM and PRM tasks, while surprisingly participants improved their speed on the PRM task. Performance improved across sessions on the PAL task, and moreover the dose of isotretinoin correlated with improvement in the total trial score, reduction in total error rate and stage completed at the first trial. CONCLUSION: Isotretinoin does not reduce learning and memory and our study suggests that it may instead lead to a dose-related improvement in specific aspects of hippocampal learning and memory. Retinoic acid functions in the hippocampus as the active metabolite of vitamin A, suggesting that this may be a limiting factor in the human hippocampus and addition of exogenous retinoic acid brings levels closer to an optimal state.