Ankylosing Spondylitis and Other Spondyloarthropathies

Spondyloarthropathyis 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 asReiter'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 system icmanifestations affecting the eyes, gastrointestinal tract, and skin. Spondyloarthropathy is associated with jointinflammation and cartilage destruction, which leads to immobility in the musculoskeletal system. Although not detectable with routine blood tests forcommon antibodies, spondyloarthropathy, especially ankylosing spondylitis, isassociated with a higher prevalence of the human leukocyte antigen B27(HLA-B27) gene.

Structure and Function

Spondyloarthropathy results in joint inflammation andcartilage destruction, which results in pain and loss of motion at the affectedjoint. In the spine, inflammation of the annulussurrounding the nucleus pulposus of the intervertebral disc leads to subsequentbone 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 toankyloses (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 ligamentsalso 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 inpeople with the human leukocyte antigen B27 (HLA-B27) phenotype. Humanleukocyte antigens are part of the major histocompatibility complex. Their function is to present antigens to cytotoxic T cells. Thus, HLA-B27 likely predisposesindividuals to develop spondyloarthritis via an auto-immune reaction initiatedby a response to an environmental factor or infectious pathogen. The exactmechanism, 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 toascending fusion of the lumbar, thoracic and cervical vertebrae, ultimatelyresulting 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, isthought 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. Whilereactive 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. None the less, many of these patients will eventually develop the characteristic rash.

Patients with inflammatory bowel disease often havespondyloarthropathy. In a 20-year prospective cohortstudy 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 whohad spondyloarthropathy compared to those who did not.

Patient Presentation

The prototypical presentation of ankylosing spondylitis is amale 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 theanterior-posterior plane is most evident. The Schober test (Figure 3) can beused 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 supinepatient's hip in a position of flexion, abduction and externalrotation, 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 isassociated 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 islimited, 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 recalla history of recent viral or bacterial infection 1 to 3 weeks prior to theonset 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, suchas 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 thepatients have a history of psoriatic rash (Figure 5) prior to the appearance ofarthritis, some develop the rash and arthritis concurrently and others presentwith 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 unilateraleye pain, blurred vision, photophobia and lachrymation (increased tearproduction).

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 erythrocytesedimentation rate (ESR) or C-reactive protein (CRP) levels are suggestive of inflammation, but are nonspecific. The testsfor rheumatoid factor (RF) and anti-nuclear antibody (ANA) are, by definition, normalin seronegative spondyloarthropathy. The synovial fluid may also show anincreased preponderance of white blood cells, particularly neutrophils, but this finding is also nonspecific.

While there is a strong correlation to the HLA-B27 gene, onlya scant minority (1-2%) of those with the HLA-B27 gene ever develop spondyloarthropathies. The prevalence of the HLA-B27 genevaries by race, ethnicity and geographic location. In the United States, theestimated prevalence is about 7% among Caucasians but less than 1% among AfricanAmericans. 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 definitivediagnosis.

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 arecharacteristic 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 thatconnect the vertebral bodies (as shown above).

MRI is the best modality for early detection of ankylosingspondylitis, as it can detect inflammation around the sacroiliac joints on the T2-weighted images.


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

Ankylosing spondylitis affects males approximately 3 to 4times more frequently than it affects females. The typical age of onset isadulthood. 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 thanankylosing spondylitis: approximately 0.1% in the US are affected. As withankylosing spondylitis, male patients make up the majority of cases of reactivearthritis, and the typical age of onset is also in early adulthood. The HLA-B27gene is present in ~80% of patients.

Psoriatic arthritis is found in about 0.3% of Americans. Unlikeanky losing spondylitis and reactive arthritis, psoriatic arthritis has a laterage of onset (about 40 years of age) and an equal distribution among males andfemales.

As noted above, about 25% of patients with inflammatorybowel disease will have some form of spondyloarthropathy, but most cases do notfeature sacroiliac erosions or ankylosis.

Differential Diagnosis

As most of the spondyloarthropathies affect younger patients, traumatic injuries should be ruled out initially. Aside fromtrauma 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 geneticpredis position. The defining features that help identify osteoarthritis are radiographic findings consistent with joint space narrowing, osteophyte formation, bonysclerosis, back pain that worsens as the day progresses, and the lack of inflammatory markers on blood testing.

Rheumatoid arthritis is much more common thanseronegative spondyloarthropathies and thus when inflammatory markers on bloodtesting are elevated and the patient's back pain improves as the dayprogresses, rheumatoid arthritis must be considered. Notably, rheumatoidarthritis in the limbs is commonly symmetric, whereas peripheral jointinvolvement in spondyloarthropathies is often asymmetric. Most importantly,patients with spondyloarthropathy will test negative for rheumatoid factor and anti-nuclearantibody.

Diffuse Idiopathic Skeletal Hyperostosis ("DISH") isalso a condition that can cause enthesophytes and markedly decreased range of motion of the spine. This can be differentiated from ankylosing spondylitis by thelocation and shape of the bony outgrowths on radiographs. Syndesmophytes arebony fusions within the joint space itself, while enthesophytes occur outside the annulus fibrosus (Figure 8). Another key distinction is that DISH has nosacroiliac joint involvement and is a disease of older men; DISH is rarely seenin 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 evenminor 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 manwith no history of trauma presents with insidious lower back pain, ankylosingspondylitis must not be missed. The red flags suggesting ankylosingspondylitis include lower back pain in a young patient with no history of recent trauma or repetitive stress, symptoms that improve during the day orwith activity, and the gradual migration of the pain from the lumbosacralregion to the neck over time. In addition,radiographs of the pelvis have the characteristic pattern of sacroiliac jointfusion.

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 spinefractures and neurologic injury with low energy trauma. Diagnostic vigilanceand a high index of suspicion for fracture must be maintained when evaluating apatient with known ankylosing spondylitis after trauma. CT and/or MRI areneeded and the patient should be immobilized in their preinjury alignment pending diagnosis and treatment. Acute neck pain in a patient withlong-standing ankylosing spondylitis should be immobilized and evaluated with more advanced imaging such as CT and MRI scans to exclude a fracture, even without ahistory of severe trauma.

Treatment Options and Outcomes

Treatment for spondyloarthropathiesbegins with traditional NSAIDs or COX-2 inhibitors. Physical therapy can alsobe prescribed to maintain mobility and reduce pain. NSAIDs should be taken withcaution in patients with spondyloarthropathy associated inflammatory boweldisease.

Seronegative spondyloarthropathies, in general, are chronic and insidious diseases. Reactive arthritis may be the exception, as most casesare 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 progressivearthritis.

For patients who do not respond sufficiently to NSAIDs/COX-2inhibitors (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 theinteraction between inflammatory cells and include agents such as infliximab oretanercept, which are TNF-alpha inhibitors, or IL-12 inhibitors. DMARDs includemethotrexate, cyclosporine, azathioprine, and sulfasalazine. DMARDs produce the irimmunosuppressive effects by suppressing the growth and maturation of inflammatory cells.

Debilitating kyphotic deformities in ankylosing spondylitiscan 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 forspinal fractures, most commonly in the mid-cervical or the cervicothoracic junction or lower at the thoracolumbar junction. While stable fractures with noaccompanying epidural hemorrhage can be treated with traction or haloimmobilization devices alone, instability, hemorrhage and neurological changes suggesta need for surgical intervention. The most common technique involvesdecompression at the site of injury to remove the hematoma, followed by spinalfusion to stabilize the area. In some cases, osteotomies are necessary tocorrect 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 patientswith ankylosing spondylitis is more than 10 times greater than that of the generalpopulation.

There are no known preventive measures for seronegative spondyloarthropathies. Although viral or bacterial infections are associatedwith reactive arthritis in HLA-B27 positive patients, any small infection maylead 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 focuson increasing flexibility with low impact such Pilates or Tai Chi may improvefunction.

Key Terms

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


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

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