Ankylosing Spondylitis and Undifferentiated Spondyloarthropathy Workup

Updated: Jun 14, 2022
  • Author: Lawrence H Brent, MD; Chief Editor: Herbert S Diamond, MD  more...
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Approach Considerations

Radiographic studies are most helpful in establishing a diagnosis of ankylosing spondylitis (AS). [90] Computed tomography (CT) and magnetic resonance imaging (MRI) may be useful in selected patients but, for reasons of expense, are not typically part of routine evaluation. For full discussion, see Imaging in Ankylosing Spondylitis.

European League Against Rheumatism (EULAR) guidelines for the use of imaging in the diagnosis and management of spondyloarthritis in clinical practice, issued in April 2015, recommend conventional radiography of the sacroiliac (SI) joints as the first imaging method to diagnose sacroiliitis as part of axial spondyloarthritis in the majority of cases. Magnetic resonance imaging (MRI) of the SI joints is an alternative in certain cases, such as young patients and those with short duration of symptoms. [91]

EULAR also recommends MRI of the SI joints for patients in whom clinical features and conventional radiography findings are not diagnostic, but axial spondyloarthritis is still suspected. On MRI, findings to consider include both active inflammatory lesions (primarily bone marrow edema) and structural lesions (eg, bone erosion, new bone formation, sclerosis and fat infiltration). [91]

EULAR does not generally recommend imaging modalities other than conventional radiography and MRI for diagnosing axial spondyloarthropathy. CT may provide additional information on structural damage if conventional radiography is negative and MRI cannot be performed. Scintigraphy and ultrasound (US) are not recommended for diagnosis of sacroiliitis as part of axial spondyloarthropathy.

EULAR recommends initial conventional radiography of the lumbar and cervical spine to detect syndesmophytes in patients with AS. MRI may also be used to predict development of new radiographic syndesmophytes. [91]

Power Doppler ultrasonography can be used to document active enthesitis. In addition, this technology may be useful to assess changes in inflammatory activity at entheses during institution of new therapies. [10]

The diagnosis of AS is not dependent on laboratory data; no laboratory tests are specific for AS. Biopsy and histologic analysis are not indicated for individuals with AS.


Laboratory Studies

Approximately 15% of patients with AS present with a normochromic normocytic anemia of chronic disease. The erythrocyte sedimentation rate (ESR) or the C-reactive protein (CRP) level is elevated in approximately 75% of patients and may correlate with disease activity in some, but not all, patients; these values may also be used as markers of response to treatment. [92, 93]

Alkaline phosphatase (ALP) is elevated in 50% of patients; this indicates active ossification but does not correlate with disease activity. Creatine kinase (CK) is occasionally elevated but is not associated with muscle weakness. The serum immunoglobulin A (IgA) level may be elevated, correlating with elevated acute-phase reactants.

Of white patients with AS, 92% are HLA-B27 positive; the percentage is lower in patients of other ethnic backgrounds. Determining HLA-B27 status is not a necessary part of the clinical evaluation and is not required to establish the diagnosis. However, in patients suspected of having a spondyloarthropathy, determining HLA-B27 status may help support the diagnosis, especially in populations with a low prevalence of HLA-B27.



Radiographic evidence of inflammatory changes both in the sacroiliac (SI) joints and in the spine are useful in the diagnosis and ongoing evaluation of the disease process. [9] This disease generally begins in the distal portions of the spine and progresses more proximally with time in a continuous fashion.

Involvement of the SI joint is a requirement for the diagnosis of AS. Sacroiliitis is an inflammatory condition leading to bony erosions and sclerosis of the joints (see the image below).

The sacroiliitis seen in AS is usually bilateral, symmetric, and gradually progresses over years. The lesions progress from blurring of the subchondral bone plate to irregular erosions of the margins of the SI joints (pseudo-widening) to sclerosis, narrowing, and finally fusion. Erosions of the subchondral bone of the SI joint are generally seen earlier in the lower portion of the joint (because this portion is lined by synovium) and on the iliac side (because of the thinner cartilage covering this side of the joint).

Bilateral symmetric sacroiliitis in a patient with Bilateral symmetric sacroiliitis in a patient with AS showing blurring of the margins of the joints and pseudo-widening.
Bilateral symmetric sacroiliitis in a patient with Bilateral symmetric sacroiliitis in a patient with AS with narrowing and sclerosis of the joints.
Bilateral sacroiliac joint fusion in a patient wit Bilateral sacroiliac joint fusion in a patient with AS.

The radiographic signs of AS are due to enthesitis, particularly of the annulus fibrosus. Early radiographic signs include squaring of the vertebral bodies caused by erosions of the superior and inferior margins of the vertebral bodies, resulting in loss of the normal concave contour of the anterior surface of the vertebral bodies (see the images below). The inflammatory lesions at vertebral entheses may result in sclerosis of the superior and inferior margins of the vertebral bodies, called shiny corners (Romanus lesion).

Enthesitis at the site of the insertion of the ann Enthesitis at the site of the insertion of the annulus fibrosis on the corners of the vertebral bodies, shiny corner (Romanus) lesions.

Ossification of the annulus fibrosus leads to the radiographic appearance of syndesmophytes, which in AS are typically marginal. Over time, the development of continuous (bridging) syndesmophytes may result in complete fusion (bamboo spine), which is essentially fused (see the images below).

Anteroposterior radiograph of spine of a patient w Anteroposterior radiograph of spine of a patient with AS.


Anteroposterior (left) and lateral (right) radiogr Anteroposterior (left) and lateral (right) radiographs of a patient with AS.
Anteroposterior radiograph of spine of a patient w Anteroposterior radiograph of spine of a patient with AS. Ossification of annulus fibrosus can be observed at multiple levels, which has led to fusion of spine with abnormal curvature.
This radiograph of the lumbar spine of a patient w This radiograph of the lumbar spine of a patient with end-stage AS shows bridging syndesmophytes, resulting in bamboo spine.
This radiograph of the cervical spine of a patient This radiograph of the cervical spine of a patient with AS shows fusion of the vertebral bodies due to bridging syndesmophytes.

Spinal disease associated with inflammatory bowel disease (IBD) is similar to AS with bilateral symmetric sacroiliitis and gradually ascending spondylitis and marginal syndesmophytes. On the other hand, reactive arthritis (ReA) and psoriatic arthritis (PsA) typically exhibit asymmetric sacroiliitis and discontinuous spondylitis with nonmarginal syndesmophytes.

Radiographs of other areas may show evidence of enthesitis with osteitis or arthropathy. Radiographs of the pelvis may show ossification of various entheses, such as the iliac crest, ischial tuberosity, and femoral trochanter, which is termed whiskering. Occasionally, the symphysis pubis develops erosive changes (osteitis pubis).

Peripheral entheses may develop radiographic changes, including erosion, periosteal new bone formation, and finally, ossification, especially in the feet at the insertion of the Achilles tendon and the plantar fascia on the calcaneus.

Peripheral joint involvement is most common in the hips and shoulders and may result in uniform joint space narrowing, cystic or erosive changes, deformation, and subchondral sclerosis without osteopenia (see the image below). Heterotopic bone formation may occur after total joint replacement, especially in the hip. Ultimately, peripheral joints may undergo ankylosis. See the radiographs below for an example.

Radiographs of hand (top) and arm (bottom) of a pa Radiographs of hand (top) and arm (bottom) of a patient with peripheral involvement of AS. Fusion of joint spaces and deformity can be observed.

Patients with AS are vulnerable to cervical spine fractures. Long-standing pain may mask the symptoms of a fracture. On radiographs, the distorted anatomy, ossified ligaments, and artifacts may obscure the fracture.

A retrospective case series of 32 patients with AS and cervical spine fractures revealed that in 19 patients (59.4%), a fracture was not identified on plain radiographs. [94] Only 5 patients (15.6%) presented immediately after the injury. Of the 15 patients (46.9%) who were initially neurologically intact, 3 patients had neurologic deterioration before admission. Early diagnosis with appropriate radiologic investigations may prevent possible long-term neurologic cord damage.

Patients with a fused spine are prone to fractures, which may be hard to diagnose with standard radiography. CT scanning or MRI may be required to document the presence of a fracture in patients with late-stage spinal disease (see the images below). Patients with a history of AS who report any recent trauma or an increased level of back or neck pain should be fully evaluated for the possibility of a vertebral fracture and subsequent spinal instability (see the image below).

Radiograph shows vertebral fracture in a patient w Radiograph shows vertebral fracture in a patient with AS.

MRI and CT

MRI or CT scanning of the SI joints, spine, and peripheral joints may reveal evidence of early sacroiliitis, erosions, and enthesitis that are not apparent on standard radiographs. [11, 12] MRI using fat-saturating techniques such as short tau inversion recovery (STIR) or MRI with gadolinium is sensitive for inflammatory lesions of enthesitis. [95, 96] The so-called MR corner sign, characterized by inflammatory lesions at the corners of vertebral bodies, is common in the thoracolumbar region of the spine in patients with AS. [97]

Investigations of patients with AS using serial MRI over time has shown a link between inflammatory lesions and the later development of syndesmophytes. [98] MRI can be used as an adjunct to evaluate the inflammatory changes and to assess neural compromise (see the image below). However, MRI and CT are not part of the routine evaluation of AS patients, because of their relatively high cost.

Sagittal MRI of thoracolumbar spine of a patient w Sagittal MRI of thoracolumbar spine of a patient with AS. Syndesmophytes and anterior corner lesions can be seen.

In patients with inflammatory back pain who have normal plain radiographs, MRI imaging of the pelvis (sacroiliac joints) may be very useful to confirm a diagnosis of axial SpA. This is illustrated in the images below, which are of a patient with nr-axSpA who presented with inflammatory back pain and had an excellent response to NSAIDs.

This 15-year-old female patient presented with rec This 15-year-old female patient presented with recent onset of right-sided low back pain. Plain radiography findings were normal.
MRI of the same patient whose radiography findings MRI of the same patient whose radiography findings were normal (previous image). She underwent further evaluation, including MRI. The MRI (short tau inversion recovery [STIR]) showed increased sinal intensity in the right sacroiliac joint, revealing sacroiliitis. Other laboratory study findings were essentially normal. The patient was started on indomethacin and rapidly improved.

Patients who develop bowel or bladder dysfunction should be evaluated immediately with MRI to assess for possible cauda equina syndrome secondary to spinal stenosis. Cauda equina syndrome is a surgical emergency necessitating decompression within 48 hours to prevent permanent loss of function.

Computerized tomography (CT) can be used to assess bony changes in patients with AS.  It is not routinely used because of its cost and radiation exposure.

CT scan of the pelvis in a patient with AS showing CT scan of the pelvis in a patient with AS showing ankylosis of the sacroiliac joints.
CT scan of the L-spine in a patient with AS showin CT scan of the L-spine in a patient with AS showing bony syndesmophytes.

Histologic Findings

Histopathologic evaluation is not generally part of the diagnostic workup in patients with ankylosing spondylitis.

The basic pathologic lesion is inflammation at the enthesis (enthesitis), which occurs at the site of insertion of ligaments and tendons into bone. The histologic picture is that of chronic inflammation with CD4+ and CD8+ T lymphocytes and macrophages. Early AS lesions include subchondral granulation tissue that erodes the joint. Over time, fibrosis and ossification occur, which can be seen radiographically as periostitis and ossification at sites of enthesitis, particularly the SI joints, spine, and heels.