I. Overview
A. Types of inflammatory arthritides of the spine
1. Rheumatoid arthritis (RA)
2. Seronegative spondyloarthropathies (negative rheumatoid factor)
a. Ankylosing spondylitis
b. Psoriatic spondylitis
c. Enteropathic arthritis
d. Reiter syndrome
B. Pathoanatomy
1. All types of inflammatory arthritides of the spine are characterized by inflammatory changes in the bone, connective tissue, and synovium of the spine.
2. The seronegative spondyloarthropathies (inflammatory arthropathies) are associated with human leukocyte antigen (HLA)-B27 and enthesitis. They share the following characteristics:
a. Negative rheumatoid factor
b. Sacroiliitis with or without spondylitis
c. Peripheral inflammatory arthritis
d. Genetic predisposition
II. Rheumatoid Arthritis
A. Epidemiology/overview
1. RA is a chronic, systemic autoimmune disorder.
2. RA affects 1% to 2% of the population.
3. Symptoms typically first occur between 20 and 45 years of age.
4. Approximately 70% of affected individuals are female.
5. A positive rheumatoid factor is present in about 85% of patients, but it is not specific for RA and may be present in unaffected individuals.
6. RA primarily affects the smaller joints of the appendicular skeleton in a symmetric fashion.
7. Progressive joint swelling, pain, and stiffness develop secondary to synovitis.
8. Spine involvement is usually restricted to the cervical spine.
B. Pathoanatomy
1. Disease manifestations are seen in the synovial-lined joints secondary to erosive synovitis. This destructive synovitis is believed to be the result of an autoimmune response to an antigen expressed by the synovial cells.
a. Rheumatoid factor is an immunoglobulin that is directed against antigens of targeted synovial cells.
b. This antigen-antibody interaction leads to the release of proteolytic enzymes that destroy the joint.
2. Spinal disease eventually occurs in about 60% of patients with RA.
a. Patients with more severe disease and longer duration of disease are at higher risk for cervical spine involvement.
b. Once instability begins, the disease tends to progress to more complex instability patterns.
c. In particular, atlantoaxial subluxation tends to progress to superior migration of the odontoid.
3. Atlantoaxial instability
a. Rheumatoid synovitis may affect the synovial joints around the dens.
b. This leads to erosion of the dens and progressive damage of the transverse, alar, and apical ligaments, leading to atlantoaxial subluxation.
c. Pannus formation posterior to the dens may further contribute to cord compression.
4. Superior migration of the odontoid occurs from bony erosion between the occipitoatlantal and atlantoaxial joints or bilateral erosion of the lateral masses. These changes can result in brain stem compression and vascular compromise to the basivertebral and anterior spinal arteries.
5. Subaxial cervical spine subluxation can occur as a result of erosion of the facet joints and degeneration of the interspinous ligaments and facet joints. Multiple-level subluxation can lead to a "stepladder" appearance or a kyphotic deformity.
6. A positive rheumatoid factor, greater peripheral joint involvement, male gender, and corticosteroid use have been linked to greater cervical involvement.
C. Evaluation
1. Clinical presentation
a. The clinical presentation of RA is variable and ranges from asymptomatic patients to those with severe deformity and neurologic compromise.
[
Figure 1. Flexion-extension radiographs of the cervical spine of a patient with RA. A, Flexion view. Note the anterior ADI of 5 mm. B, Extension view. Note that the anterior ADI corrects to normal.]
b. Neck pain is the most common initial symptom. The pain is often localized to the upper cervical spine and associated with occipital headaches.
c. Greater occipital nerve root irritation (C2) can lead to referred pain in the face, ear, and mastoid regions.
d. Vertebrobasilar insufficiency can cause vertigo, nausea, vomiting, dysphagia, and dysarthria.
e. Patients with cord compression will show symptoms of myelopathy.
2. Imaging
a. Lateral radiographs are the most helpful for initial evaluation of the cervical spine. The following factors should be assessed: the posterior atlanto-dens interval (ADI), the anterior ADI, subaxial subluxation, and superior migration of the odontoid.
b. Flexion-extension lateral cervical radiographs are useful for evaluation of dynamic instability (Figure 1). An anterior ADI >3.5 mm is considered abnormal; however, the posterior ADI has more prognostic value. An anterior ADI >9 to 10 mm or posterior ADI <14 mm is associated with an increased risk of neurologic injury and usually requires surgery.
c. MRI or CT imaging is recommended because diagnosing superior migration of the odontoid can be difficult to determine. Several methods can be used to evaluate basilar invagination.
d. Redlund-Johnell criterion (
Figure 2, A)
i. The distance between the McGregor line and the midpoint of the inferior border of C2 is measured.
ii. A measurement <34 mm in males and <29 mm in females indicates basilar invagination.
[Figure 2. Methods of evaluating basilar invagination. A, Redlund-Johnell criterion. B, The Clark stations. C, The Ranawat criterion.]
e. Clark stations method (Figure 2, B)
i. In this method, the odontoid is divided into three equal parts: top, middle, and bottom.
ii. If the anterior ring of the atlas is level with the middle third, basilar invagination is diagnosed.
f. Ranawat criterion (Figure 2, C)
i. The distance between the pedicle of C2 and the ring of C1 is measured.
ii. A distance <15 mm in males and <13 mm in females indicates basilar invagination.
D. Classification
1. The Ranawat classification (
Table 1) is often used for myelopathy.
2. Classification is helpful in guiding surgery. Surgery is less successful in patients with advanced disease (class IIIB).
E. Treatment—The goals of treatment of RA are to alleviate pain and prevent neurologic injury.
1. Nonsurgical treatment
a. Early diagnosis and treatment with disease-modifying antirheumatic drugs (DMARDs) such as methotrexate, hydroxychloroquine sulfate, and sulfasalazine gold can have a significant impact.
b. Oral steroids are also often used.
c. Agents that target tumor necrosis factor (TNF)-α (infliximab, etanercept, and adalimumab) and interleukin-1 (IL-1) (anakinra) can be added for patients that do not respond well to the DMARDs.
2. Surgical treatment
a. Surgery is considered for patients with intractable pain or neurologic deficits. Surgical intervention should be attempted before the onset of Ranawat class IIIB myelopathy, because neurologic improvement is limited once the condition reaches this degree of severity.
b. C1-C2 fusion is recommended for patients with a posterior ADI <14 mm or if there is >3.5 mm of segmental mobility. Fusion may be performed with wires; transarticular C1-C2 screws; or C1 lateral mass screws with C2 isthmic, pedicle, or laminar screws.
c. If basilar invagination has occurred, an occiput-to-C2 fusion is recommended. Decompression may be accomplished with a C1 arch removal or transoral odontoid resection.
d. In patients with subaxial subluxation requiring surgery, a posterior fusion with either wires or lateral mass screws is sufficient.
[Table 1. Ranawat Classification for Myelopathy]
III. Ankylosing Spondylitis
A. Epidemiology/overview
1. Ankylosing spondylitis is a chronic seronegative inflammatory disease of unknown origin that primarily affects the axial spine.
2. Ankylosing spondylitis begins in the third decade of life.
3. The male-to-female ratio is 3:1.
4. Ankylosing spondylitis occurs in about 0.2% to 0.3% of the US population.
5. 95% of patients with ankylosing spondylitis are HLA-B27 positive; 6% to 8% of Caucasians are HLA-B27 positive.
6. There is a definite genetic predisposition, but the mode of inheritance remains unknown.
B. Pathoanatomy
1. There are several theories regarding the link between HLA-B27 and ankylosing spondylitis.
a. One involves the binding of HLA-B27 to a peptide in the joint and the resultant stimulation of the pathologic cascade.
b. Another is that HLA-B27-positive individuals are more susceptible to certain microorganisms, such as Klebsiella pneumoniae, leading to a disease-producing synovitis.
c. Some believe that autoimmunity against HLA-B27 itself by cytotoxic T-cells also may play a role.
2. The seronegative spondyloarthropathies share fundamental differences from RA besides being rheumatoid factor negative.
a. This class of disease affects the entheses (the bony insertions of ligaments and tendons), whereas RA affects the synovial lining.
b. Inflammation of the entheses leads to bony erosions followed by new or reactive bone formation and eventual ankylosing.
[
Figure 3. Radiographs of the spine of a patient with ankylosing spondylitis. A, AP view. Note the marginal syndesmophytes that create the characteristic "bamboo spine" appearance. B, Lateral view. C, andD, AP and lateral views of the same patient after L2 pedicle subtraction osteotomy.]
c. Inflammation of the anulus fibrosis leads to formation of bridging syndesmophytes.
d. The seronegative spondyloarthropathies tend to affect the entire axial spine, whereas RA is limited primarily to the cervical spine.
3. The spondyloarthropathies are characterized by sacroiliitis and a distinctive pattern of involvement of the appendicular skeleton.
a. In the peripheral skeleton, ankylosing spondylitis involves the entheses.
b. Patients with psoriatic arthritis have interphalangeal destruction.
c. Reiter syndrome affects the synovial joints of the lower extremity.
4. Nonspinal manifestations of ankylosing spondylitis
a. Large peripheral joint (hip and shoulder) arthritis
b. Acute anterior uveitis
c. Renal amyloidosis
d. Ascending aortic abnormalities (stenosis, aortitis, and regurgitation)
e. Cardiac conduction abnormalities
C. Evaluation
1. Clinical presentation
a. Most patients present with chronic low back pain in early adulthood.
b. Pain is often localized to the gluteal and sacroiliac regions initially.
c. With further inflammatory changes, back stiffness develops that is exacerbated by periods of inactivity.
d. Patients have decreased chest expansion relative to other people.
e. Any patient with ankylosing spondylitis who presents with a sudden onset of back or neck pain must be worked up for a fracture.
i. These fractures are considered unstable because they extend across all three columns and create two rigid segments that move independently of each other.
ii. Rapid neurologic deterioration can occur as a result of spinal instability or hematoma formation.
iii. Most fractures are located in the midcervical to cervicothoracic junction and at the thoracolumbar junction.
f. Patients may present with a flexion deformity of the spine that is due to multiple microfractures that occur over time.
2. Radiographs
a. The earliest sign of ankylosing spondylitis is erosion on the iliac side of the sacroiliac joint.
b. Ankylosing spondylitis has a predilection for bilateral sacroiliitis and marginal thin-flowing syndesmophytes, leading to the characteristic "bamboo spine" appearance (Figure 3, A and B).
c. The chin-brow to vertical angle—the angle between a line connecting the chin and brow and a vertical line—can be measured to determine the degree of deformity. This angle is helpful in determining the amount of correction needed when doing an osteotomy.
3. Scintigraphy is sensitive to the inflammation in sacroiliac joints, but it lacks specificity.
4. CT detects early bony changes but does not show active inflammation. If a fracture is suspected, fine-cut CT scans with sagittal reconstructions should be ordered in addition to plain radiographs.
5. MRI can detect active inflammation, making it the best imaging modality for early detection. MRI should also be considered when evaluating for hematomas. Fractures can be missed in up to 50% of cases on plain radiographs.
D. Treatment
1. Nonsurgical treatment
a. NSAIDs have been the mainstay of treatment, but they provide minimal relief.
b. Recent studies have shown promising results with TNF-α-blocking agents.
c. Physical therapy that includes a program to improve flexibility and strength is recommended.
d. Bracing can be considered for pain control.
e. Patients with stable fractures may be treated in a brace or halo traction.
2. Surgical treatment
a. Unstable fractures require instrumentation and fusion.
i. Because of the risks of neurologic deterioration and the difficulty with bracing in the setting of thoracic kyphosis, surgery is often recommended for cervical spine fractures.
ii. Most fractures can be treated with posterior instrumentation, but anterior stabilization may be necessary when osteoporosis is present.
b. For patients with kyphotic deformities of the spine, surgery may be an option.
i. Goals of surgery are restoration of sagittal balance and horizontal gaze.
ii. Anterior-opening osteotomy or pedicle subtraction osteotomy (Figure 3, C and D) is the preferred surgical treatment. The osteotomy can be done at the cervical, thoracic, or lumbar spine, depending on the site of the deformity.
c. In patients with fixed flexion deformities, a cervical spine osteotomy may be performed; however, this is a high-risk procedure.
i. In the most severe cases, a "chin-on-chest" deformity is present.
ii. Cervical deformities impair the patient's ability to maintain a forward gaze, cause difficulties with personal hygiene, and lead to swallowing difficulties.
iii. The osteotomy typically is performed at C7-T1 because the vertebral artery normally enters the foramen transversarium at C6, and the spinal canal at C7-T1 is relatively more spacious. Furthermore, injury to C8 would cause less disability than to the other nerve roots.
IV. Psoriatic Spondylitis
A. Epidemiology/overview
1. Approximately 10% of patients with psoriatic arthritis develop a spondyloarthropathy.
2. Of these patients, 70% are HLA-B27 positive. In contrast, only 20% of patients without axial involvement are HLA-B27 positive.
3. Unlike ankylosing spondylitis, psoriatic spondyltis causes diskovertebral erosions and axial ankylosis in a noncontiguous asymmetric pattern with both marginal and nonmarginal syndesmophytes.
4. Patients with psoriatic spondylitis may also have a synovial proliferative process in the cervical spine similar to RA, with a similar clinical presentation.
B. Treatment
1. Medical treatment is similar to that for patients with RA, with early use of DMARDs and TNF-α-blocking agents.
2. Surgical indications are similar to those for patients with RA who have cervical disease or ankylosing spondylitis and a kyphotic deformity.
V. Reiter Syndrome
A. Epidemiology/overview
1. Reiter syndrome is thought to occur as a postinfectious reactive arthritis.
2. It typically affects people in the third and fourth decade of life.
3. Symptoms occur within 1 month of urethritis or enteritis.
4. Lumbar spine involvement occurs in approximately 50% of patients, but cervical spine involvement is rare.
5. In contrast to ankylosing spondylitis, asymmetric sacroiliitis and nonmarginal syndesmophytes are seen in patients with spine involvement.
B. Treatment
1. Treatment is symptomatic.
2. Surgery is rarely necessary.
VI. Enteropathic Arthritis
A. Epidemiology—80% of patients with enteropathic arthritis who have spinal involvement are HLA-B27 positive.
B. Presentation/treatment
1. The clinical presentation and treatment are identical to that of idiopathic ankylosing spondylitis.
2. Spondylitis sometimes occurs in association with ulcerative colitis or Crohn disease. The spine involvement is independent of the bowel disease course and may even occur before the onset of intestinal symptoms.
VII. Diffuse Idiopathic Skeletal Hyperostosis
A. Epidemiology/overview
1. Diffuse idiopathic skeletal hyperostosis (DISH; also known as Forestier disease) is an enthesopathy of the spine, shoulder, elbow, knee, and calcaneus.
2. DISH typically occurs in patients who are middle-aged or older.
3. DISH is more common in patients with diabetes or gout.
4. In contrast to ankylosing spondylitis, DISH is characterized by large, nonmarginal syndesmophytes with involvement of at least four contiguous vertebral bodies, and there is no involvement of the sacroiliac joints.
B. Clinical presentation
1. Thoracic and lumbar involvement leads to stiffness and pain.
2. Cervical involvement results in large anterior osteophytes that can cause dysphagia and stridor.
3. Ossification of the posterior longitudinal ligament can lead to myelopathy, and large segmental ossification makes the spine vulnerable to fractures as in ankylosing spondylitis. These fractures are similarly unstable and often require surgery.
4. DISH is associated with extraspinal ossification at several joints, including an increased risk of heterotopic ossification following total hip arthroplasty.
Top Testing Facts
1. In RA, anterior ADI >3.5 mm is considered abnormal; however, the posterior ADI has more prognostic value. An anterior ADI >9 to 10 mm or posterior ADI <14 mm is associated with an increased risk of neurologic injury and usually requires surgery.
2. In RA, surgical intervention should be attempted before the onset of Ranawat class IIIB myelopathy because neurologic improvement is limited once the condition reaches this degree of severity.
3. Patients with ankylosing spondylitis have decreased chest expansion relative to other people.
4. Any patient with ankylosing spondylitis who presents with a sudden onset of back or neck pain must be worked up for a fracture. Rapid neurologic deterioration can occur as a result of spinal instability or hematoma formation.
5. The earliest radiographic sign of ankylosing spondylitis is erosion on the iliac side of the sacroiliac joint. Ankylosing spondylitis has a predilection for bilateral sacroiliitis and marginal thin-flowing syndesmophytes, leading to the characteristic "bamboo spine" appearance.
6. Approximately 10% of patients with psoriatic arthritis develop a spondyloarthropathy. Medical treatment is similar to that for patients with RA. Surgical indications are similar to those for patients with RA who have cervical disease or ankylosing spondylitis and a kyphotic deformity.
7. Asymmetric sacroiliitis and nonmarginal syndesmophytes differentiate Reiter syndrome from ankylosing spondylitis.
8. In contrast to ankylosing spondylitis, DISH is characterized by large, nonmarginal syndesmophytes with involvement of at least four contiguous vertebral bodies, and there is no involvement of the sacroiliac joints.
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