Oral Retinoids
The oral retinoid of choice in the treatment of psoriasis is acitretin. This is the carboxylic acid metabolite of etretinate, the first oral retinoid drug to be used for this disease. Acitretin is readily absorbed and widely distributed after oral administration.
Efficacy
Acitretin has been shown to be an effective agent when given alone for psoriasis, Goldfarb et al found a 66% clearance after 24 weeks, and Berbis et al found an 80% or greater clearance in a 12 week study. Acitretin is effective as a monotherapy, and can be expected to produce about 70% clearance in approximately 8 weeks.
Long term treatment with acitretin may be required as retinoids are only suppressive. Anecdotal evidence suggests that the therapeutic effect is maintained and treatment resistance does not occur.
Synergy with other treatments
Combination with PUVA treatment was found superior to PUVA combined with placebo, with regard to clearance time (47.8 versus 65.4 days), the number of exposures (13.7 compared to 19.9), and the number of patients remitting completely (94% compared to 65% at 10 weeks). The major advantage of combining acitretin with PUVA is the reduction in the dose of UVA, and some reduction in the daily dose of acitretin, to achieve clearance. On this basis, it may be expected that there will be a reduction in the long term side effects of both forms of treatment.
Safety, side-effects and patient acceptability
Acitretin therapy is associated with a large number of side effects and toxicity reactions.
Mucocutaneous and other minor adverse reactions: Acitretin causes mucocutaneous side effects in virtually all patients to whom it is administered in therapeutic doses. Drying and cracking of the lips, referred to incorrectly as cheilitis, may be expected in all after 2 - 4 weeks. For the majority of patients, this is a minor inconvenience that can be improved symptomatically by the use of a bland greasy application, such as white soft paraffin.
Dryness of the nasal, buccal and conjunctival mucosae occurs in a relatively small proportion. An increased rate of loss of scalp hair occurs in 20 - 30% patients, but is only severe enough to be noticeable and cause distress in a few women. Peeling of the skin of the palms and soles, and the development of areas of dermatitis, occurs in 5-50% of patients. Skin stickiness, skin and nail fragility, and itchiness are also seen in a minority of patients. Paronychia, and the development of curly hair, are other infrequent side effects. Musculoskeletal side effects, with arthralgia and myalgia, are uncommon.
As with all retinoid drugs, there is a high risk of teratogenicity if acitretin is administered during the first 3 months of pregnancy. As acitretin can be reverse metabolised to etretinate which has a long half life, pregnancy should be avoided for a period of 2 years after stopping acitretin. Numerous congenital malformations may occur, including Fallot's tetralogy, other cardiac defects, microcephaly, spina bifida and limb defects. Great care must be undertaken to ensure that all fertile women who are described acitretin understand the risk, that they are not pregnant from the start, and that they comply with secure contraceptive measures.
Elevation of liver enzymes is common, occurring in 20 - 30% patients. It is mostly of a minor degree, may be transient, and is generally of little significance. Hepatitis is rare, and maybe of the hypersensitivity, direct toxic, or cholestatic types. Modest elevation of plasma lipid levels occurs in up to 25% of patients, with increases in low density lipoproteins and decreases in high density lipoproteins. In individuals taking acitretin for psoriasis in the longer term, there is a risk of accelerated atherosclerosis if hyperlipidaemia persists. Those with elevated levels of lipids, should be given dietetic advice and, if necessary, lipid lowering agents prescribed.
Retinoid drugs possess the potential for bone toxicity, but it is uncertain to what degree that risk exists in those taking acitretin at the recommended dosage for periods of a few months to up to 2 years. Ossification of ligaments and tendons, bony spurs, and diffuse skeletal hyperostosis, has been reported in 86% of patients taking acitretin for 1 - 3 years at a dose of 10 - 75mgs per day, but adequate determination of the existence of these defects prior to therapy was not made. Premature epiphyseal fusion, and other bone abnormalities such as ossification of interosseous membranes, is rare.
References
Goldfarb MT, Ellis CN, Gupta AK, et al. Acitretin improves psoriasis in a dose dependent fashion. J Am Acad Dermatol.1988;18:655-62.
Berbis P, Geiger JM, Vaisse C, et al. Benefit of progressively increasing doses during the initial treatment with acitretin in psoriasis. Dermatologica.1989; 178: 88-92
Saurat JH, Geiger JM, Amblard P, et al. Randomised double-blind multicenter study comparing acitretin PUVA, etretinate PUVA and placebo PUVA in the treatment of severe psoriasis. Dermatologica. 1988;177:218-24.
Kilcoyne RF. Effects of retinoids in bone. J Am Acad Dermatol. 1988;19: 212-16.
This information forms part of the current BAD guidance document for the general management of psoriasis. Other sections in the document comprise:
