Adverse Effects of Retinoids

Michael David, Emmilia Hodak, Nicholas J. Lowe

Oral retinoids, synthetic derivatives of vitamin A, have been used in the treatment of various dermatoses over the last decade. The most useful drugs have been isotretinoin (13-cis-retinoic acid) for nodulocystic acne and etretinate for psoriasis vulgaris. Retinoids are also effective in the treatment of papulosquamous dermatoses other than psoriasis (i.e. inherited disorders of keratinisation), cutaneous T-cell lymphoma and in chemotherapy and chemoprevention of cancer. However, systemic administration of these compounds is frequently associated with mucocutaneous side effects, liver toxicity and abnormalities of serum lipid profiles, which might be related to an increased risk of coronary heart disease. Of particular concern is the teratogenic effect of all retinoids, which limits their use in women of child-bearing potential. Chronic toxicities from long term therapy with retinoids may result in skeletal abnormalities, usually mimicking diffuse idiopathic hyperostosis syndrome. Furthermore, the chronic use of retinoids in children may inhibit their growth due to premature epiphyseal closure. In contrast to other side effects of retinoids which are dose dependent and reversible upon withdrawal of the drug, it seems unlikely that bone abnormalities will resolve after discontinuation of the medication. In view of the wide spectrum of toxicities, treatment with retinoids requires appropriate selection of patients, careful consideration of the benefit to risk ratio for each individual, periodic monitoring of clinical response and laboratory tests. Clinicians should use special management techniques in order to prevent or minimize slide effects. Extensive investigations are currently being conducted in an attempt to develop new retinoids which will improve the therapeutic efficacy and reduce unwanted reactions.