Fig. 53.1
Hyperostosis in a patient with long-term retinoid therapy. Lateral radiograph of the cervical spine shows multilevel flowing ossification in the distribution of the anterior longitudinal ligament (arrows)
ATRA has been implicated as a cause of differentiation syndrome (previously known as retinoic acid syndrome) in patients with acute promyelocytic leukemia, which consists of differentiation of leukemic blasts and promyelocytes that leads to cellular migration, endothelial activation, and release of interleukins and vascular factors responsible for tissue damage. This syndrome may consist of unexplained fever, weight gain, dyspnea with pulmonary infiltrates, pleuropericardial effusion, hypotension, and renal failure, and may present shortly after starting ATRA. There can also be pseudotumor cerebri and intracranial, subhyoid, or retinal hemorrhage. Administration of steroids can alleviate the differential syndrome.
Retinoic acid is also a teratogen that results in a constellation of congenital anomalies, most commonly the central nervous system and cardiovascular system. The central nervous system anomalies include microcephaly and hydrocephalus. Microtia or anotia is another frequent complication.
53.4 Differential Diagnosis
Early cervical hyperostotic changes consist of pointing of the anteroinferior margins of the vertebral bodies (unlike the hyperostoses found in diffuse idiopathic skeletal hyperostosis (DISH)), while later changes resemble the typical hyperostoses of DISH, and both conditions can be associated with ossification of the posterior longitudinal ligament (Fig. 53.2). Furthermore, patients with DISH often have relatively high levels of vitamin A. Other differential considerations for multilevel hyperostosis of the spine may include degenerative spondylosis and ankylosing spondylitis. Degenerative spondylosis is associated with increased age and includes the constellation of disc space narrowing, vacuum phenomenon, disc desiccation, vertebral osteophyte formation, disc herniation, and facet arthrosis (Fig. 53.3). Ankylosing spondylitis is an inflammatory process related to HLA-B27 positivity. The hallmark features include erosions and fusion of the sacroiliac joints and enthesitis at the edges of the discovertebral joints resulting in syndesmophyte development. Syndesmophytes start as thin vertically oriented projections of the bone that develop due to ossification within the outer fibers of the annulus fibrosus of the intervertebral disc. The cervical spine is less commonly involved than the lumbosacral spine, but can also have the characteristic bamboo spine appearance when multiple vertebral bodies are fused (Fig. 53.4). Patients with ankylosing spondylitis are also particularly susceptible to vertebral fractures.
