Ankylosing Spondylitis and Other Spondyloarthropathies

Spondyloarthropathy is a group of seronegative inflammatory rheumatic diseases of the spine. The phrase “seronegative” specifically denotes the absence of rheumatoid factor and antinuclear antibodies in the patient’s circulation. The main forms of seronegative spondyloarthropathy are ankylosing spondylitis, reactive arthritis (such as Reiter’s syndrome), psoriatic arthritis and spinal illnesses linked to inflammatory bowel diseases, such as Crohn's disease or ulcerative colitis.

Spondyloarthropathy is characterized by back pain and stiffness. In some cases, there are systemic manifestations affecting the eyes, gastrointestinal tract, and skin. Spondyloarthropathy is associated with joint inflammation and cartilage destruction, which leads to immobility in the musculoskeletal system. Although not detectable with routine blood tests for common antibodies, spondyloarthropathy, especially ankylosing spondylitis, is associated with a higher prevalence of the human leukocyte antigen B27 (HLA-B27) gene.

Structure and Function

Spondyloarthropathy results in joint inflammation and cartilage destruction, which results in pain and loss of motion at the affected joint. In the spine, inflammation of the annulus surrounding the nucleus pulposus of the intervertebral disc leads to subsequent bone formation within the disc. Bone can form between the intervertebral discs too, producing so-called syndesmophytes. Ultimately, syndesmophytes can bridge one vertebral body to those adjacent to it, leading to ankyloses (fusion) of the spine.

Figure 1: The spine in ankylosing spondylitis with osteophytes bridging adjoining vertebral bodies. (Courtesy of Wikipedia)

Inflammation of the attachment of the longitudinal ligaments also promotes soft-tissue ossification which contributes to the fusion of otherwise normally mobile segments. Spondyloarthropathy can induce synovitis affecting the facet joints between adjacent articular processes.
There is a strong susceptibility to spondyloarthropathy in people with the human leukocyte antigen B27 (HLA-B27) phenotype. Human leukocyte antigens are part of the major histocompatibility complex. Their function is to present antigens to cytotoxic T cells. Thus, HLA-B27 likely predisposes individuals to develop spondyloarthritis via an auto-immune reaction initiated by a response to an environmental factor or infectious pathogen. The exact mechanism, however, remains unknown.
In ankylosing spondylitis, the sacroiliac joint and the pubic symphysis are the most commonly affected joints in the body. Further inflammation leads to ascending fusion of the lumbar, thoracic and cervical vertebrae, ultimately resulting in a “bamboo spine” appearance on x-ray.

Figure 2: A radiograph showing ankylosing spondylitis with well-formed syndesmophytes, as denoted by the red stars. These osteophytes are said to resemble the culms, or rings, of bamboo, shown in the image to the right. Thus, the radiographic appearance of ankylosing spondylitis is termed “bamboo spine.” (Case courtesy of Frank Gaillard,, rID: 7163)

Reactive arthritis, as the name suggests, is thought to occur in response to an exogenous insult, such as an infection. Common pathogens include viruses and bacteria such as chlamydia, yersinia, salmonella, shigella, and campylobacter. While reactive arthritis can affect the spine, it can also commonly affect other joints of the body.
Psoriatic arthritis occurs in patients with psoriasis. In a small set of patients, the classic skin findings associated with psoriasis may be absent at the onset of joint symptoms. Nonetheless, many of these patients will eventually develop the characteristic rash.
Patients with inflammatory bowel disease often have spondyloarthropathy. In a 20-year prospective cohort study of approximately 500 patients with ulcerative colitis or Crohn’s disease, ankylosing spondylitis developed in about 5% of patients, with an additional 20% reporting back pain without objective findings in the spine. Notably, the symptoms of the underlying bowel disease were reportedly worse in patients who had spondyloarthropathy compared to those who did not.

Patient Presentation

The prototypical presentation of ankylosing spondylitis is a male in his 20s complaining of lower back pain and stiffness of insidious onset. This pain is worse in the morning and improves with activity, in contrast to osteoarthritis, which is relieved with rest and worsens with activity.
On physical exam, decreased spine motion in the anterior-posterior plane is most evident. The Schober test (Figure 3) can be used to evaluate lumbar stiffness.

Figure 3: The Schober test is performed as follows: while standing behind the patient, the examiner identifies the line between the two iliac crests, shown here as red diamonds. The examiner then makes two marks on the skin over the lumbar spine, 15cm apart, one 5cm below the iliac line and one 10cm above it. (Both shown as blue circles). The patient is then asked to bend forward while keeping the knees straight, as if to touch the toes. The distance between the two marked points is measured again [panel at right]. If the distance of the two points does not increase by at least 5cm, lumbar stiffness is diagnosed.

Pain with the FABER maneuver (Figure 4) can help localize symptoms to the sacroiliac joint. This test is performed by placing the supine patient’s hip in a position of flexion, abduction and external rotation, and having the examiner press on the flexed knee toward the pelvis, thereby loading the sacroiliac joint.

Figure 4: The FABER maneuver (courtesy study on sacroiliac joint diagnostics. Manuelle Medizin 56, 239–248 (2018). Here, the examiner’s left hand places a force on the patient’s left SI joint. Pain localizing to the SI joint is considered a positive response.

Advanced ankylosing spondylitis is associated with a disabling thoracolumbar kyphotic deformity in more than 30% of cases. In advanced cases, ankylosis of the rib case and thoracic spine will limit chest wall expansion. Total chest wall expansion of less than 2.0 cm (normal is about 3 to 5 cm) is considered diagnostic. When chest wall expansion is limited, the patient may experience shortness of breath.
Patients with reactive arthritis classically have a triad of findings: conjunctivitis, urethritis and arthritis. (Arthritis often occurs later in the course than the other two symptoms.) In many cases, patients can recall a history of recent viral or bacterial infection 1 to 3 weeks prior to the onset of symptoms.

A distinctive feature of reactive arthritis is dactylitis, in which one or two fingers or toes becomes diffusely swollen. A small fraction of patients (< 10%) present with cardiac manifestations of the disease, such as aortic regurgitation or pericarditis.
Psoriatic arthritis most commonly affects the limbs, but in about 40% of cases, the cervical spine or the sacroiliac joint can be affected. Most of the patients have a history of psoriatic rash (Figure 5) prior to the appearance of arthritis, some develop the rash and arthritis concurrently and others present with arthritis first.

Figure 5. Skin manifestation of psoriasis. (Courtesy Wikipedia)

Enthesopathies involving the Achilles tendon, patellar tendon and plantar fascia are often seen.

Extra-articular manifestations are common with spondyloarthropathies. Uveitis (Figure 6) is the most frequent extra-articular manifestation of ankylosing spondylitis, occurring in ~25% of patients. This manifests as acute unilateral eye pain, blurred vision, photophobia and lachrymation (increased tear production).

Figure 6: Chronic anterior uveitis with dilated conjunctival blood vessels and deformed pupil due to anterior synechiae (adhesions of the iris). (Courtesy of Ocular manifestations of rheumatic diseases. Int Ophthalmol 40, 503–510 (2020).

Objective Evidence

Laboratory findings

There are no specific serological tests for seronegative spondyloarthropathies. Elevation of the erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) levels are suggestive of inflammation, but are nonspecific. The tests for rheumatoid factor (RF) and anti-nuclear antibody (ANA) are, by definition, normal in seronegative spondyloarthropathy. The synovial fluid may also show an increased preponderance of white blood cells, particularly neutrophils, but this finding is also nonspecific.

While there is a strong correlation to the HLA-B27 gene, only a scant minority (1-2%) of those with the HLA-B27 gene ever develop spondyloarthropathies. The prevalence of the HLA-B27 gene varies by race, ethnicity and geographic location. In the United States, the estimated prevalence is about 7% among Caucasians but less than 1% among African Americans. Only 10% of patients with spondyloarthropathies test negative for the HLA-B27 gene. Taken together, testing for the HLA-B27 gene is neither sensitive nor specific enough to make a definitive diagnosis.

Radiographic findings

In patients with suspected ankylosing spondylitis, full-length AP and lateral plain radiographs of the spine and pelvis should be obtained.
Sacroiliac erosions and joint space changes are characteristic and are the first radiographic features observed (Figure 7).

Figure 7: Inflammation with widening of the sacroiliac joints (sacroiliitis) is seen bilaterally in the panel to the left (Case courtesy of Dr Mark Holland,, rID: 23359); on the right, a CT scan shows sacroiliac joint erosion with regional sclerosis of subchondral bone (Case courtesy of Lukas, Cédric et al. RMD open vol. 4,1 e000586. 12 Jan. 2018, doi:10.1136/rmdopen-2017-000586)

Another common finding is the presence of syndesmophytes that connect the vertebral bodies (as shown above).
MRI is the best modality for early detection of ankylosing spondylitis, as it can detect inflammation around the sacroiliac joints on the T2-weighted images.


The prevalence of the spondyloarthropathies varies widely by disease type, patient race and geography.

Ankylosing spondylitis affects males approximately 3 to 4 times more frequently than it affects females. The typical age of onset is adulthood. The HLA-B27 gene is present in ~90% of patients. Overall, about 0.2% of patients in the USA are affected.

Reactive arthritis is slightly less prevalent than ankylosing spondylitis: approximately 0.1% in the US are affected. As with ankylosing spondylitis, male patients make up the majority of cases of reactive arthritis, and the typical age of onset is also in early adulthood. The HLA-B27 gene is present in ~80% of patients.

Psoriatic arthritis is found in about 0.3% of Americans. Unlike ankylosing spondylitis and reactive arthritis, psoriatic arthritis has a later age of onset (about 40 years of age) and an equal distribution among males and females.

As noted above, about 25% of patients with inflammatory bowel disease will have some form of spondyloarthropathy, but most cases do not feature sacroiliac erosions or ankylosis.

Differential Diagnosis

As most of the spondyloarthropathies affect younger patients, traumatic injuries should be ruled out initially. Aside from trauma which can be gleaned from a thorough history, there are other causes of non-traumatic injuries that may present in a similar manner to seronegative spondyloarthropathies.

While rare in young patients, osteoarthritis may be present, especially in the context of repetitive trauma, overuse or genetic predisposition. The defining features that help identify osteoarthritis are radiographic findings consistent with joint space narrowing, osteophyte formation, bony sclerosis, back pain that worsens as the day progresses, and the lack of inflammatory markers on blood testing.

Rheumatoid arthritis is much more common than seronegative spondyloarthropathies and thus when inflammatory markers on blood testing are elevated and the patient’s back pain improves as the day progresses, rheumatoid arthritis must be considered. Notably, rheumatoid arthritis in the limbs is commonly symmetric, whereas peripheral joint involvement in spondyloarthropathies is often asymmetric. Most importantly, patients with spondyloarthropathy will test negative for rheumatoid factor and anti-nuclear antibody.

Diffuse Idiopathic Skeletal Hyperostosis (“DISH”) is also a condition that can cause enthesophytes and markedly decreased range of motion of the spine. This can be differentiated from ankylosing spondylitis by the location and shape of the bony outgrowths on radiographs. Syndesmophytes are bony fusions within the joint space itself, while enthesophytes occur outside the annulus fibrosus (Figure 8). Another key distinction is that DISH has no sacroiliac joint involvement and is a disease of older men; DISH is rarely seen in patients younger than 50 years of age.

Figure 8: T2-weighted coronal MRI image with fat signal saturation, showing bone marrow edema in the upper and middle thirds of sacroiliac joints (arrows). (Image courtesy of Rev. Bras. Reumatol. 57 (5) Sep-Oct 2017,

Red Flags

The most concerning spondyloarthropathy is ankylosing spondylitis, as it can severely reduce the patient’s life expectancy and quality of life. Restriction of chest wall movement, decreased mobility, and heightened susceptibility to fracture after even minor trauma are the major sources of morbidity and mortality. (Reactive arthritis and psoriatic arthritis, while painful, usually do not affect the patient’s life expectancy.) Thus, when a young man with no history of trauma presents with insidious lower back pain, ankylosing spondylitis must not be missed. The red flags suggesting ankylosing spondylitis include lower back pain in a young patient with no history of recent trauma or repetitive stress, symptoms that improve during the day or with activity, and the gradual migration of the pain from the lumbosacral region to the neck over time. In addition, radiographs of the pelvis have the characteristic pattern of sacroiliac joint fusion.

Among patients with known spondyloarthropathy, the syndesmophytes present render the spine brittle and minimally compliant. Thus, patients with ankylosing spondylitis are highly susceptible to unstable spine fractures and neurologic injury with low energy trauma. Diagnostic vigilance and a high index of suspicion for fracture must be maintained when evaluating a patient with known ankylosing spondylitis after trauma. CT and/or MRI are needed and the patient should be immobilized in their preinjury alignment pending diagnosis and treatment. Acute neck pain in a patient with long-standing ankylosing spondylitis should be immobilized and evaluated with more advanced imaging such as CT and MRI scans to exclude a fracture, even without a history of severe trauma.

Treatment Options and Outcomes

Treatment for spondyloarthropathies begins with traditional NSAIDs or COX-2 inhibitors. Physical therapy can also be prescribed to maintain mobility and reduce pain. NSAIDs should be taken with caution in patients with spondyloarthropathy associated inflammatory bowel disease.

Seronegative spondyloarthropathies, in general, are chronic and insidious diseases. Reactive arthritis may be the exception, as most cases are either self-limited or relapsing-remitting. The majority of reactive arthritis patients have severe symptoms lasting weeks to months that eventually disappear. However, about 15% of patients may develop chronic or progressive arthritis.

For patients who do not respond sufficiently to NSAIDs/COX-2 inhibitors (or for those who have complications compelling their cessation), biological response modifiers and disease-modifying antirheumatic drugs (DMARDs) may be considered. Biological response modifiers aim to block the interaction between inflammatory cells and include agents such as infliximab or etanercept, which are TNF-alpha inhibitors, or IL-12 inhibitors. DMARDs include methotrexate, cyclosporine, azathioprine, and sulfasalazine. DMARDs produce their immunosuppressive effects by suppressing the growth and maturation of inflammatory cells.

Debilitating kyphotic deformities in ankylosing spondylitis can be treated with an osteotomy and fusion (Figure 9).

Figure 9: Kyphosis in ankylosing spondylitis is decreased from 72 degrees preoperatively (left) to 25 degrees (right) with a mini‐open pedicle subtraction osteotomy. (Courtesy of BMC Musculoskeletal Disorders 22, 101 (2021).

Patients with advanced spondyloarthropathies are at risk for spinal fractures, most commonly in the mid-cervical or the cervicothoracic junction or lower at the thoracolumbar junction. While stable fractures with no accompanying epidural hemorrhage can be treated with traction or halo immobilization devices alone, instability, hemorrhage and neurological changes suggest a need for surgical intervention. The most common technique involves decompression at the site of injury to remove the hematoma, followed by spinal fusion to stabilize the area. In some cases, osteotomies are necessary to correct severe kyphotic deformities.

Risk Factors and Prevention

Spondyloarthropathy is a risk factor for spinal fracture and spinal cord injury. Indeed, the incidence of spinal cord injury among patients with ankylosing spondylitis is more than 10 times greater than that of the general population.
There are no known preventive measures for seronegative spondyloarthropathies. Although viral or bacterial infections are associated with reactive arthritis in HLA-B27 positive patients, any small infection may lead to the development of arthritis, making it difficult to prevent.

It is particularly important that patients with spondyloarthropathy, especially ankylosing spondylitis, stop smoking. The disease itself can cause shortness of breath, in addition to the dyspnea that smoking may cause.
For patients with spondyloarthropathy, exercises that focus on increasing flexibility with low impact such Pilates or Tai Chi may improve function.

Key Terms

Seronegative spondyloarthropathy, ankylosing spondylitis, reactive arthritis, bamboo-spine


Perform a comprehensive history and physical exam in patients presenting with back pain. Recognize the x-ray findings in spondyloarthropathy.

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