BJD GUIDELINES British Journal of Dermatology British Association of Dermatologists guidelines on the efficacy and use of acitretin in dermatology A.D. Ormerod, E. Campalani* and M.J.D. Goodfield Department of Dermatology, University of Aberdeen, Foresterhill, Aberdeen AB9 2ZB, U.K. *Department of Dermatology, Royal London Hospital, Whitechapel Road, London E1 1BB, U.K. Department of Dermatology, Leeds General Infirmary, Great George Street, Leeds LS1 3EX, U.K.
Correspondence Acitretin, a synthetic retinoid, is the pharmacologically active Anthony Ormerod. metabolite of etretinate. It replaced etretinate in the late 1980s E-mail: [email protected] because of its more favourable pharmacokinetic profile, and it is an established systemic second-line therapy for severe psori- Accepted for publication asis resistant to topical therapy. Bioavailability is enhanced by 9 February 2010 food, especially fatty food.1 Acitretin is 50 times less lipophilic Key words than etretinate and has a shorter elimination half-life. How- acitretin, ichthyosis, psoriasis, safety, systematic ever, there is evidence that small amounts of acitretin are review, treatment guidelines re-esterified to etretinate, which has a very long half-life, especially in the presence of alcohol.2,3 Intracellularly, it inter- Conflicts of interest acts with cytosolic proteins and nuclear receptors, which are None declared. part of the steroid-thyroid hormone superfamily. We know that these nuclear receptors act as transcriptional factors for This is a new set of guidelines prepared for the BAD specific DNA sequences; however, their role in the retinoid Clinical Standards Unit, made up of the Therapy & pathway is largely unknown. In psoriasis and other disorders Guidelines Subcommittee (T&G) and the Audit & of keratinization, acitretin normalizes epidermal cell prolifera- Clinical Standards Subcommittee (A&CS). Members tion, differentiation and cornification.4,5 It is thought to exert of the Clinical Standards Unit are: H.K. Bell these effects by interfering with the expression of epidermal (Chairman T&G), L.C. Fuller (Chairman A&CS), N.J. Levell, M.J. Tidman, P.D. Yesudian, J. Lear, growth factor genes. There is also evidence that acitretin has J. Hughes, A.J. McDonagh, S. Punjabi, N. Morar, immunomodulatory properties by inhibiting dermal micro- 6 7,8 S. Wagle (British National Formulary), S.E. vascular endothelial cells and neutrophil migration. Acit- Hulley (British Dermatological Nursing Group), retin is licensed for use in severe extensive psoriasis which K.J. Lyons (BAD Scientific Administrator) and M.F. is resistant to other forms of therapy, including topical, Mohd Mustapa (BAD Clinical Standards Manager). light and systemic; palmoplantar pustular psoriasis; severe Darier disease (keratosis follicularis) and severe congenital Guidelines produced in 2010 by the British ichthyosis. Association of Dermatologists; proposed revision in It is highly teratogenic and must not be used by women 2015. who are pregnant or are planning a pregnancy. Acitretin is Disclaimer highly bound to plasma protein and metabolized in the These guidelines have been prepared on behalf of the liver. It is excreted to an equal extent by renal and hepatic British Association of Dermatologists (BAD) and routes. reflect the best data available at the time the report Although available for 20 years there have not been any was prepared. Caution should be exercised in published guidelines on the use of acitretin. Its clinical use is interpreting the data; the results of future studies almost completely restricted to dermatology and it has impor- may require alteration of the conclusions or tant metabolic, skeletal and teratogenic side-effects. We felt it recommendations in this report. It may be necessary important to produce evidence-based guidelines on its use in or even desirable to depart from the guidelines in the dermatology. interests of specific patients and special circumstances. Just as adherence to guidelines may not constitute defence against a claim of negligence, Materials and methods so deviation from them should not necessarily be deemed negligent. A scoping meeting decided that the guideline would include only evidence pertaining to acitretin and would not make DOI 10.1111/j.1365-2133.2010.09755.x direct inferences from studies of the parent drug etretinate. The target audience for the guideline is dermatologists.