Isotretinoin and
etretinate are synthetic derivatives of
vitamin A widely used in the treatment of dermatological diseases, mainly those affecting keratinization. They have numerous side-effects, among which the rheumatic symptoms are not the most common or the most severe. The main skeletal adverse reaction of
retinoids is
hyperostosis. It mainly occurs with protracted treatments and high dosages, and its incidence may exceed 80% after a few years of administration.
Hyperostosis is axial, located in the cervical and thoracic spine, and may be responsible for limitation of movement; in the appendicular bone,
enthesopathies occur at the foot, pelvis, hip, and less commonly the shoulder and elbow. They are usually mild and asymptomatic. The radiological appearance is very similar to
diffuse idiopathic skeletal hyperostosis.
Isotretinoin tends to be responsible for axial involvement,
etretinate for peripheral locations. The other skeletal side-effects are uncommon and include periosteal proliferation, calcification of the interosseous membrane of the forearm and diffuse radiological bone hyperlucency. In children, premature epiphyseal closure is very rare. About 20% of patients complain of
musculoskeletal pain and
arthralgias. A few cases of true
arthritis have been reported.
Retinoids may be responsible for muscular damage and an abnormality of muscular tone resembling the
stiff-man syndrome. Some cases of necrotizing
vasculitis and three cases of
Wegener's granulomatosis have been observed in patients treated with
retinoids. Except for these latter arguable cases, rheumatoid syndromes due to
retinoids are rather benign, and should not be an obstacle to the future development of their therapeutic utilization.