Kaplan G, Haettich B
Baillieres Clin Rheumatol. 1991 Apr;5(1):77-97. doi: 10.1016/s0950-3579(05)80297-3.
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.
异维A酸和阿维A酯是维生素A的合成衍生物,广泛用于治疗皮肤病,主要是那些影响角质化的疾病。它们有许多副作用,其中风湿症状并非最常见或最严重的。维甲酸类药物主要的骨骼不良反应是骨质增生。它主要发生在长期治疗和高剂量使用时,用药几年后其发生率可能超过80%。骨质增生发生在中轴骨,位于颈椎和胸椎,可能导致活动受限;在四肢骨,附着点病发生在足部、骨盆、髋部,较少见于肩部和肘部。它们通常较轻且无症状。影像学表现与弥漫性特发性骨肥厚非常相似。异维A酸往往导致中轴骨受累,阿维A酯则导致外周部位受累。其他骨骼副作用不常见,包括骨膜增生、前臂骨间膜钙化和弥漫性骨透亮增加。在儿童中,骨骺过早闭合非常罕见。约20%的患者主诉肌肉骨骼疼痛和关节痛。有少数真正关节炎的病例报告。维甲酸类药物可能导致肌肉损伤和类似于僵人综合征的肌张力异常。在用维甲酸类药物治疗的患者中观察到一些坏死性血管炎病例和三例韦格纳肉芽肿病例。除了这些有争议的病例外,维甲酸类药物引起的类风湿综合征相当良性,不应成为其治疗应用未来发展的障碍。