Clinical Characteristics

DISH is a seronegative osteoarthritis characterized by widespread ligamentous ossification and calcification. When initially described, it was thought to affect only the axial skeleton; however, it may diffusely involve the entire musculoskeletal system.

DISH causes ossification of the anterior longitudinal ligament and adjacent paraspinal soft tissues. This leads to formation of the characteristic “flowing” syndesmophytes that bridge multiple vertebral bodies, but leave the intervertebral spaces relatively intact. Original radiographic criteria required involvement of at least four contiguous vertebrae ; however, more recent criteria require only three contiguous vertebrae in the presence of peripheral enthesophytes. DISH most commonly affects the thoracic spine and favors the right side. It may also involve the cervical and lumbar spine. Involvement at these levels more commonly involves the lower cervical and upper lumbar regions and has been known to cause cervical myelopathy, lumbar stenosis, and oropharyngeal dysphagia due to esophageal compression by osteophytes.

DISH is commonly asymptomatic or minimally symptomatic. Presenting symptoms may include decreased range of motion and stiffness of the spine. In advanced cases, immobility of the spine may be severe and lead to kyphotic postural abnormalities reminiscent of AS. Syndesmophytes may lead to a variety of compressive syndromes including dysphagia, respiratory failure, and lumbar radiculopathy.

The diagnosis is based on radiographic findings: (1) flowing calcification and ossification along the anterolateral aspects of at least four contiguous vertebral bodies with or without associated localized point excrescences at the intervening vertebral body-disc junctions; (2) a relative preservation of intervertebral disc height in the involved vertebral segments and the absence of extensive radiographic changes of “degenerative” disc disease, including vacuum phenomena and vertebral body marginal sclerosis; (3) absence of apophyseal joint bony ankylosis and sacroiliac joint erosion, sclerosis, or bony fusion ( Table 36-1 ).

The syndesmophytes are horizontally oriented and hyperostosis is heaviest just anterior to the disc space and lightest just below and above the site of vertebral body attachment. Within the cervical spine, there may be hyperostosis around the atlantoaxial joint and occiput, as well as ossification within the posterior longitudinal ligament and ligamentum nuchae. Ossification within the lumbar spine involves mainly the anterior longitudinal ligament, however, unlike in thoracic spine, ossification here equally affects the right and left sides.

The effect of DISH on bone mineral density (BMD) has been heavily investigated. Initial studies with dual-energy x-ray absorptiometry (DXA) scan showed a significantly higher body BMD in patients with DISH compared to controls. One study concluded that this finding may even decrease the fracture risks in patients with DISH. However, more recent studies have found that DXA significantly overestimates the BMD in patients with DISH. This is thought to be due to the contribution of ossification of the anterior longitudinal ligament as measurements on the right side of the spine were significantly higher than those taken on the left. More recent studies using quantitative computed tomography (CT) have shown no significant differences in body BMD between patients with DISH and control subjects.

Epidemiology

As opposed to AS, DISH is a disease of the aging population. An autopsy study found an incidence of 28% with an average age of 65 years old. Other studies based on radiographic criteria have found an increasing incidence of the disease after the age of 50 years, with the highest prevalence being in patients older than the age of 70 years. It affects males more commonly than females and may have some genetic predisposition as whites have been found to be more commonly affected in the U.S. population and prevalence in Koreans and African blacks is quite low. As DISH is associated with age, diabetes, and obesity, its prevalence can be expected to increase as societies Westernize and life expectancies increase. An increasing prevalence of DISH along with advancements in radiographic imaging may also lead to a higher incidence of fractures in this patient population.

Etiology and Pathophysiology

The pathogenesis of aberrant bone formation seen in DISH is still largely unknown. As opposed to AS, the incidence of human leukocyte antigen B27 (HLA-B27) positivity is low in DISH. Several metabolic derangements have been associated with DISH. These include dyslipidemia, hyperuricemia, oral vitamin A therapy, diabetes mellitus, hypertension, hyperinsulinemia, obesity, elevated growth hormone, and insulinlike growth factor 1 (IGF-1) levels. Patients with DISH have also been found to be at higher risk for the development of metabolic syndrome, cardiovascular disease, and stroke.

Spinal Fractures in Diffuse Idiopathic Skeletal Hyperostosis

Patients with DISH are at risk for vertebral column fractures as discoligamentous supporting structures become ossified and the spine becomes rigid. Increased disease burden leads to increased fracture risk, as the spine loses its soft structural supports and takes on the characteristics of a long bone with long lever arms. As segments become rigid and fuse, the length of the lever arm grows, putting more stress on adjacent nonfused levels and predisposing them to fracture. The creation of lever arms also increases the drive for fracture displacement and, thus, the risk of neurologic injury after fracture.

The cervical spine is the most common site of fracture, with most injuries occurring between the C5 and C7 levels. The frequency of fractures decreases down through the thoracic and into the lumbar spine. Hyperextension is the most common fracture mechanism, accounting for injury in up to 89% of patients compared with 2.4% in the general population. Other mechanisms causing fracture include compression and rotation with flexion rarely representing a traumatic fracture mechanism. Fractures are generally unstable as they typically involve both the anterior and posterior elements of the spinal column. The majority of fractures in DISH occur through the vertebral body, as opposed to through the disc space, which is more typical in AS. The discrepancy between these two fracture patterns is likely due to the lack of apophyseal joint ankylosis and relative preservation of intervertebral disc anatomy seen in DISH. Although BMD is relatively well preserved in DISH, the pattern of ossification likely also contributes to the unique fracture pattern seen. Verlaan and colleagues quantified the volume of the anterolateral ossification mass (ALOM) seen in DISH. They found that the ALOM volume was lowest at the mid-vertebral level and highest at the mid-intervertebral disc space. This relative lack of bone density at the mid-third of the vertebral body may represent a biomechanically weak point at higher risk for fracture.

The mechanism of injury leading to fracture in patients with DISH is often subtle. The majority of patients will have low-energy impacts leading to unstable fractures. The most common mechanism in several case series is a fall from standing. Oftentimes, patients are unable to recall any causative traumatic event. Unfortunately, this leads to a much higher rate of delayed diagnosis than the general population. Caron and coworkers found that nearly 20% of patients with ankylosing spinal disease, including DISH, experienced a delay in diagnosis, and this delay was associated with an 81% likelihood of decline of neurologic function. In a series of 8 cases of patients with DISH and fracture, Paley and colleagues found that diagnosis was delayed in 3 of 8 patients. The cause for this delay is multifactorial. First, the patient may only have minimal symptoms at the time of trauma and may not present for medical evaluation. Second, the index of suspicion for the assessing physician may be low as these patients often present with unimpressive mechanisms and symptoms. Third, radiographic evaluation of fractures in an ankylosed spine is difficult, resulting in subtle, but unstable, fractures going unnoticed on plain radiographic evaluation. Both CT scanning and magnetic resonance imaging (MRI) are essential in the evaluation of patients with DISH as they have a much higher sensitivity for the detection of fractures than plain radiographs. Specifically, T2-weighted MRIs can often detect marrow edema, indicating an occult fracture that was otherwise not seen. As mentioned before, fractures are most commonly transvertebral, but may involve the intervertebral disc space and often span all three columns of the spine. Transdiscal fractures can be identified by widening of the intervertebral space, which may be accompanied by a tear within the anterior longitudinal ligament. Transvertebral fractures most often present as a lucency across the vertebral body on CT with associated marrow edema near the fracture site on MRI, although this edema may be lacking in certain cases. These fractures are almost always accompanied by disruption of the posterior osteoligamentous structures. Patients with DISH present with nonhealing fractures that display evidence of pseudarthrosis. This is evident as osteolysis with occasional sclerosis and vacuum phenomenon involving the intervertebral space, endplates, and vertebral bodies adjacent to the fracture site. This process can mimic infectious spondylodiscitis. Patients have also been known to present with a fluid collection within the fracture site on T2-weighted MRI after hyperextension injury, which may be misleading for an infectious or neoplastic etiology.

Despite the prevalence of low-energy injuries in patients with DISH, the incidence of significant neurologic injury is very high. In a series of 33 patients with DISH and cervical spine trauma, Bransford and colleagues found the incidence of spinal cord injury to be 76%, of which 28% of these were complete. Westerveld performed a literature review including 55 cases of DISH with fracture and found the rate of neurologic injury at time of admission was 40%, and 14% of patients went on to develop neurologic dysfunction at some later point in time. Numerous other case reports have been published showing catastrophic neurologic injury even after minor trauma. This high rate of neurologic injury is relatively proportional to the rate of unstable spinal column fractures seen in this population. This is complicated by the fact that many of these unstable fractures are not diagnosed at initial encounter and a potentially preventable neurologic injury occurs in a delayed fashion. Another contributing factor may be the frequency in which epidural hematomas are associated with fracture in this patient population. Caron and colleagues described an incidence of 7% of patients with DISH/AS having epidural hematomas associated with their fracture. Some have speculated that this might be secondary to an increased likelihood of bleeding from the cancellous bone in these patients, although this has been debated. The severity of instability has been correlated with the length of the ankylosed spinal segment, that is, patients with longer ankylosed segments are prone to more severe spinal cord injury.

Clinical Characteristics

Sacroiliitis is the hallmark of AS and the presenting manifestation in the majority of patients who typically complain of morning stiffness with lower back and sacral pain that classically improves with activity. In the early stages of the disease, patients may also complain of mild constitutional symptoms associated with a systemic inflammatory process including low-grade fever, malaise, and loss of appetite. In time, lower back pain progresses to involve the rib cage, the thoracic spine, and the cervical spine. Chronic inflammation leads to ossification of affected joints and ligaments, and with advanced disease the spine becomes ankylosed and is rendered completely rigid, and effectively functions as a long bone or “bamboo spine” housing the spinal cord. Normal spinal curvature is lost and replaced by a fixed hyperkyphosis which can, in severe cases, significantly impair the patient’s vertical gaze as the head is fixed in a downward position. This pattern of ascending involvement is characteristic, but atypical patterns, more commonly seen in women, are also observed. Peripheral joint involvement is a less common manifestation and is seen mostly in chronic progressive disease. The hips are the most commonly affected joint (50% of patients) and the joint most often requiring surgical intervention. The glenohumeral and knee joints are also frequently affected (30%), whereas the joints of the hands, wrists, and feet are only occasionally involved. In addition to joint disease, 25% to 40% of AS patients suffer from a number of extraarticular manifestations. These occur more commonly in patients with the HLA-B27 allele and include the cardiovascular (aortitis, cardiomyopathy, pericarditis, cardiac conduction defects), pulmonary (restrictive ventilation, apical pulmonary fibrosis, pulmonary cavitation), renal (amyloidosis with renal failure) and visual systems (uveitis). With the exception of uveitis, which affects up to 20% of patients, these extraarticular manifestations are rare. The natural history of the disease is benign in most cases with greater than 90% of patients remaining functionally active over a follow-up period of 35 years in one study. Approximately two-thirds of these patients, however, suffered from lifelong back problems. Prognosis can be predicted by the degree of progression in the first 10 years, with slower progression predictive of a more benign course.

Epidemiology

Symptomatic onset usually occurs between the ages of 15 and 35 years with an average age of 28 years. Only 10% of patients are younger than 15 years and only 5% are older than 50 years at disease onset. AS has a prevalence of approximately 1 to 1.5% in the white population, but its prevalence varies by region, ethnic group, and sex. Although early studies reported an overwhelming 10 : 1 male predominance, more recent studies indicate that there is less gender disparity with a ratio closer to 2 to 3 : 1. Although the overall pattern of disease expression is similar, females tend to be diagnosed later in life and have milder spinal disease.

Etiology and Pathophysiology

An association between the development of AS and the presence of the HLA-B27 antigen, an allele of the major histocompatibility complex, was first described in 1973 by two independent groups. Calin reported that 90% of U.S. whites with AS tested positive for the HLA-B27 antigen. However, because only 6% to 7% of those with the HLA-B27 antigen develop AS, with an approximately equal portion developing another spondyloarthropathy, the antigen is thought to only enhance genetic susceptibility, perhaps interacting with other genetic loci or an environmental trigger. The infectious agent, Klebsiella pneumoniae, has been suspected as a possible trigger. Additionally, while the presence of the HLA-B27 antigen is highly associated with disease development in whites, the same does not hold true for African Americans and Japanese. There additionally appears to be a familial association of the disease, with relatives of those affected being 11 to 29 times more likely than nonrelatives to develop the disease. HLA-B27 positive relatives of those affected are afflicted with the disease 20% of the time.

The primary pathophysiology of AS involves infiltration of T cells and macrophages into the attachment sites of ligaments, tendons, and joint capsules where they release cytokines including interleukin-1B (IL-1B), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ). This inflammation causes cortical bone erosion and induces new bone formation. The initial erosive changes are well demonstrated on plain radiograph with the characteristic “Romanus lesion” caused by cortical erosions at the corners of the vertebral bodies with a reactive sclerosis. A similar process occurs in the peripheral joints, where a proliferative synovitis invades subchondral bone and cartilage, leading to ossification and bony ankylosis. It is unknown what triggers ossification of these joints as the exact molecular and cellular mechanisms of this process are poorly understood.

Spinal Fractures in Ankylosing Spondylitis

AS patients are predisposed to spinal fractures for several reasons. Osteoporosis is a frequent complication of AS, affecting 19% to 62% of patients. Its severity is largely correlated with other indices of disease severity such as patient age, male gender, peripheral joint involvement, degree of spinal fusion, and disease duration. The origins of osteoporosis can be attributable to several factors, including inflammatory mediators such as TNF-α and IL-6, immobility, and support provided by extraspinal bone. Decreased BMD in AS patients is largely confined to the axial skeleton and can be difficult to measure using traditional DXA techniques secondary to obscuration of the vertebral body by aberrant bony formations. More accurate assessment can be obtained using newer quantitative CT scanning or DXA scanning of the lateral portion of the L3 vertebral body. Nonetheless, decreased BMD in the peripheral and axial skeleton has been shown to be associated with vertebral body fractures in AS. Moreover, osteoporosis significantly increases the risk of vertebral compression fracture in these patients.

Other reasons that predispose AS patients to fracture is loss of flexibility and ability to absorb impact. Patients with total spinal involvement are at the greatest risk of fracture. Overall AS patients have a four- to sevenfold increase in the incidence of spinal fracture when compared with the general population. Furthermore, a recent epidemiologic study showed, for reasons thus far unclear, that the frequency of fracture in patients with AS is increasing. Even minimal trauma, including patient transfers, intubation, chiropractic manipulation, and ground-level falls can cause severe fractures in affected patients. Also, patients with AS have kyphotic deformities that affect their balance making them more likely to fall. Further, the head and face being forward of the trunk creates a point of contact creating an extension force.

Fractures in this population are classically transdiscal, but commonly involve the vertebral body as well. Axial hyperextension is the most common mechanism of injury followed by flexion, rotational, and compression type injuries. The cervical spine is most frequently fractured. Diagnosis is delayed in up to 85% of cases as the patients’ primary symptom is pain and many of these patients have a long history of chronic back pain. Similar to DISH, fractures in AS carry a significantly higher degree of morbidity than those in the nonankylosed patient. Of those fractures that are brought to clinical attention, approximately 60% are complicated by an associated neurologic injury, which is roughly three times the rate in patients without this disorder. The rate of neurologic injury appears to be similar for both thoracic and cervical spine fractures. Furthermore, vertebral fractures in this population are associated with a mortality of up to 30%. Noncontiguous fractures occur in up to 20% of cases, which can be easily overlooked unless careful scrutiny is given to the entire spinal column. Because of the high risk of overlooking fractures in this population, any new complaint of pain in a patient suffering AS must be treated as a fracture until proven otherwise.

Prognosis of Fractures in Ankylosed Spines

There are several reasons, which apply to both AS and DISH, for why these patients have such high levels of morbidity. Often there is a delay in diagnosis and there is a lack of effective nonoperative treatment. The fused spine creates enlarged lever arms, which concentrate force on the weakest area of the spine, often across the fused intervertebral disc space. When a fracture does occur, it is often a three-column injury affecting the complete diameter of the spinal column and is further rendered unstable by the ossification and loss of supporting ligamentous structures. Especially in AS, there is a high frequency of epidural hematoma associated with fractures. Fractures occurring in the middle of long fused segments have poor healing capacity and if treated incorrectly at onset will develop kyphosis and late neurologic deficits.