Updated: Mar 25, 2009
Ankylosing spondylitis is a distinct disease entity characterized by inflammation of multiple articular and para-articular structures, frequently resulting in bony ankylosis. The term ankylosing is derived from the Greek word ankylos, meaning stiffening of a joint; the term spondylos means vertebra. Spondylitis refers to inflammation of one or more vertebrae. Ankylosing spondylitis usually is classified as a chronic and progressive form of seronegative arthritis.
Enthesopathy
The basic pathologic lesion of ankylosing spondylitis occurs at the entheses, which are sites of attachment to bone of ligaments, tendons, and joint capsules. Enthesopathy results from inflammation, with subsequent calcification and ossification at and around the entheses. Inflammation with cellular infiltration by lymphocytes, plasma cells, and polymorphonuclear leukocytes is associated with erosion and eburnation of the subligamentous bone. The process usually starts at the sacroiliac joints. Other enthesopathic sites include the iliac crest, ischial tuberosity, greater trochanter, patella, and calcaneum. In the paravertebral soft tissues, the lesion manifests as a formation of new bone within the outer layers of the annulus fibrosis of the intervertebral disk. The margins of the disk are invaded by hyperemic granulation tissue arising from the subchondral bone. This tissue replaces the disk fibers with new bone.
Synovial joints
In the synovial joints, a proliferative chronic synovitis indistinguishable from rheumatoid arthritis may occur; however, subchondral bone and cartilage are invaded by reactive tissue originating from the bone, which is a feature not encountered in rheumatoid arthritis. Capsular fibrosis and bony ankylosis tend to occur. Formation of bony bridges between adjacent vertebrae (syndesmophytes) and progressive ossification of extraspinal joint capsules and ligaments are characteristic of the disease. Unlike rheumatoid arthritis, pannus formation is not known to occur.
Genetics
The etiology of ankylosing spondylitis is unknown; however, a strong genetic influence exists. A family history of the disease is common in patients with ankylosing spondylitis. Approximately 90-95% of patients with ankylosing spondylitis have the tissue antigen human leukocyte antigen B27 (HLA-B27); by comparison, HLA-B27 is present in 7% of the general population. Because only 1% of individuals who have HLA-B27 develop ankylosing spondylitis, the disease is likely triggered by an unknown environmental factor in persons who are genetically predisposed.
It is estimated that ankylosing spondylitis affects approximately 0.1-0.2% of the general population.
Internationally, ankylosing spondylitis occurs with a frequency identical with that in the United States.
The life expectancy of patients with ankylosing spondylitis is the same as that of the general population, except for patients who are severely affected with the disease and in whom complications develop. The morbidity of ankylosing spondylitis may be considerable; it is estimated that fewer than 20% of patients with adult-onset disease develop significant morbidity. Most patients are able to maintain a normal lifestyle, and patients should be encouraged and counseled to do so. In fact, many mild cases may go undetected.
The prevalence of ankylosing spondylitis is lower in blacks and in certain North American Indian tribes.
Ankylosing spondylitis primarily affects young males. The male-to-female ratio is 4-10:1. The true prevalence in females may be higher than reported, and the disease may be more subtle and difficult to diagnose in female patients. Ankylosing spondylitis tends to follow a more mild and benign course in females.
Ankylosing spondylitis typically affects young males. The peak age of onset is 15-35 years; the mean age of onset is 26 years. In approximately 15-20% of patients, the disease begins in the second decade of life. In 10%, onset occurs after 39 years of age. Hip and peripheral joint involvement is more frequent and severe in juveniles than in adults.
The classic initial site of involvement of ankylosing spondylitis is the sacroiliac joint, followed by the thoracolumbar and lumbosacral junctions. As the disease progresses, the mid lumbar, upper thoracic, and cervical vertebrae are affected. Although considered characteristic, the disease does not always ascend up the spine. In general, atypical patterns occur more frequently in women; spinal disease without sacroiliac joint involvement is unusual in either sex.
Peripheral joint involvement tends to occur more frequently in cases of chronic ankylosing spondylitis. Radiographic changes are seen in more than 50% of patients with long-standing ankylosing spondylitis. The hip joint is affected most often; the glenohumeral and knee joints are involved in approximately 30% of patients. With time, diffuse articular disease occurs, with involvement of the hands, wrists, and feet.
Radiographic changes are seen at the pubic symphysis, often in combination with sacroiliitis. Other involved cartilaginous sites in the axial skeleton include the manubriosternal, acromioclavicular, and sternoclavicular joints. Enthesopathic changes are frequently seen at sites of tendinous and ligamentous attachments such as the ischial tuberosity, iliac crest, trochanters of the femur, and the inferior calcaneum.
History
The most common presenting symptom of patients with ankylosing spondylitis is low back pain. Usually, pain is centered over the sacrum; it may radiate to the groin and buttocks and down the legs. The typical patient is a young man who has repeated episodes of being wakened at night with back pain; the back pain is associated with spinal stiffness in the morning. Low back pain persists, even at rest. The pain pattern is characteristic of bilateral sacroiliitis.
With time, back pain progresses up the spine and affects the rib cage. Chest expansion becomes restricted as the costovertebral joints become involved. The patient must practice diaphragmatic breathing, which may be observed as ballooning of the abdomen during inspiration. The cervical spine is ankylosed late in the course of the disease, leading to restriction in neck movement and head rotation. Eventually, the spine is completely rigid, with loss of the normal curvatures and movement.
Physical examination
Loss of lateral flexion of the lumbar spine is the earliest objective sign of spinal involvement. Sacroiliitis may be detected by encountering a tenderness response during percussion over the sacroiliac joints and encountering a pain response by springing the pelvis. Several tests have been designed to measure spinal restriction that occurs with disease progression; these include touching the toes, applying the Schober test, and measuring chest expansion. Synovitis and restriction of joint motion may be encountered during examination of the peripheral joints. Tenderness over the entheses, especially the heel, should be sought.
Patients should be examined for the development of complications. Cardiovascular complications include aortic incompetence secondary to aortitis; rarer cardiovascular complications include conduction defects, cardiomyopathy, and pericarditis. In a minority of patients, a restrictive ventilatory pattern develops as a result of limited chest expansion.
Chest complications include apical fibrosis and cavitation. Anterior uveitis is the most common extra-articular manifestation of the disease; it affects approximately 20% of patients. Eye symptoms usually precede spinal symptoms; there is a temporal association between eye symptoms and peripheral arthritis.
Neurologic complications are rare and include radiculitis caused by nerves running over inflamed sacroiliac joints in early disease and spinal cord damage from traumatic fractures of the ankylosed spine in late disease. Amyloidosis is a rare complication of long-standing disease and may lead to renal failure.
Laboratory investigations
The erythrocyte sedimentation rate is elevated during the acute phase of the disease. Mild leukocytosis may occur. In chronic disease, a normochromic normocytic anemia may develop. Gamma-globulin levels may be raised. Rheumatoid factors are negative. Human leukocyte antigen typing shows the presence of B27 in as many as 95% of patients, although this test cannot be used diagnostically because only a small percentage of individuals with positive test results for HLA-B27 develop the disease.4
Treatment
Once a definitive diagnosis is established, a detailed explanation of the disease, including its implications, should be provided to the patient. Regular lifelong exercises are the mainstay of the treatment program. Adequate analgesics in the form of nonsteroidal anti-inflammatory drugs should be administered under supervision to control pain and stiffness and to allow the patient to continue exercising through pain. Severe hip involvement may require hip replacement surgery. Spinal surgery may be required to treat complications of long-standing spinal disease. For example, in the cauda equina syndrome in ankylosing spondylitis (CES-AS syndrome), surgery either by lumboperitoneal shunting or laminectomy may be required to improve neurologic dysfunction.
Diagnostic criteria
Specific criteria for the diagnosis of ankylosing spondylitis were developed at rheumatic disease conferences in Rome and New York; these criteria have come to be referred to as the Rome criteria (1963) and the New York criteria (1968), respectively. Although the criteria generally have been accepted as useful, limitations have been recognized, and overlaps exist among clinical and radiologic features of various seronegative spondyloarthropathies. The British Society for Rheumatology recommends that the so-called modified New York criteria be used to diagnose ankylosing spondylitis. Sacroiliitis is the hallmark of ankylosing spondylitis and is a requisite for the diagnosis under these sets of criteria.
Classification of functioning and health
The Assessment of SpondyloArthritis International Society (ASAS) has created 2 Core Sets (comprehensive and brief) for the classification of functioning and health in patients who have ankylosing spondylitis. The Comprehensive International Classification of Functioning and Health (ICF) Core Set includes 80 categories consisting of body functions, body structures, activities and participation, and environmental factors. The Brief ICF Core Set has 19 categories.5
Radiographs are the single most important imaging technique for the detection, diagnosis, and follow-up monitoring of patients with ankylosing spondylitis. Overall bony morphology and subtle calcifications and ossifications may be demonstrated well radiographically. The diagnosis may be reliably made if the typical radiographic features of ankylosing spondylitis are present.
CT is useful in selected situations (eg, in equivocal cases of sacroiliitis and in cases in which subtle radiographic changes are present) and in the evaluation of complications.
MRI is useful in assessing early cartilage abnormalities and bone marrow edema.6,7,8,9
Radiographs are limited in detecting early sacroiliitis and in demonstrating subtle changes in the posterior elements of the vertebrae.
CT is useful in evaluating sacroiliitis, but normal variations of the sacroiliac joints may simulate the findings of inflammation. CT is not ideal for imaging long segments of the spine because of its high radiation dose.
MRI is limited by its relatively poor ability to detect calcification, ossification, and cortical bony changes.
Scintigraphy has been used to detect early sacroiliitis, but there are conflicting reports as to its accuracy.
[Reiter Syndrome, Musculoskeletal]
Diffuse Idiopathic Skeletal Hyperostosis
Gout
Psoriatic Arthritis
Rheumatoid Arthritis, Spine
Spondylodiskitis
Enteropathic arthropathies
Osteitis condensans ilii
Radiographs are a reliable means with which to make a diagnosis, particularly if typical radiographic features are present.
The sacroiliitis associated with ankylosing spondylitis should be differentiated from sacroiliitis caused by other diseases. Bilateral symmetric sacroiliac joint disease may be found in conditions such as psoriasis, Reiter disease, enteropathic arthropathy, hyperparathyroidism, and osteitis condensans ilii.
Ankylosing spondylitis also may present as a bilateral asymmetric sacroiliitis, mimicking psoriasis, Reiter disease, rheumatoid arthritis, and gouty arthritis. Unilateral distribution of sacroiliac disease also may be found in infective arthritis; therefore, it is important that radiographic features be carefully analyzed to look for signs of various diseases and that radiographic features be correlated with the overall pattern of bony involvement and the clinical findings.
Spinal abnormalities found in ankylosing spondylitis may be encountered in other diseases, such as enteropathic arthropathy, psoriasis, and Reiter disease. Careful analysis and classification of bony outgrowths in the vertebrae are helpful in differentiating the various conditions. In addition to ankylosing spondylitis, syndesmophytes are found in alkaptonuria. Flowing anterior ossification is a feature of diffuse idiopathic skeletal hyperostosis, whereas paravertebral ossification is present in both psoriasis and Reiter disease.
Spinal pseudoarthrosis in ankylosing spondylitis often produces marked diskovertebral destructive changes that may resemble infective spondylodiskitis. The presence of posterior element fracture or defect is an important distinguishing clue.
CT may be useful in selected patients in whom ankylosing spondylitis is suggested and in whom initial sacroiliac joint radiographs findings are normal or equivocal. Features such as joint erosions, subchondral sclerosis (see Image 15), and bony ankylosis are visualized better on CT than on radiographs; however, some normal variants of the sacroiliac joint may simulate the features of sacroiliitis.10,11,12
CT supplements bone scintigraphy in evaluating areas of increased uptake, particularly in the spine. Bony lesions, such as pseudoarthrosis (see Images 16-17), fractures, spinal canal stenosis, and facet inflammatory disease (see Image 18), are detected well using CT, particularly with reformatted coronal, sagittal, or oblique images. Other useful applications include the assessment of atlantoaxial instability, costovertebral disease, manubriosternal disease, dural ectasia (see Image 19), and paraspinal muscle atrophy.
Multidetector CT (MDCT) is superior to radiographs and MRI in showing more injuries, and it yields more information on fracture morphology. In patients with advanced ankylosing spondylitis, MDCT is the imaging modality of choice for the evaluation of fractures of the cervical spine. It complements MRI, which better shows spinal cord and soft tissue injuries.
Features such as joint erosions, subchondral sclerosis, and bony ankylosis at the sacroiliac joint and the lumbar vertebral facet joints are visualized better on CT scans than on radiographs. CT is accurate for the diagnosis of complications such as spinal pseudoarthrosis, fractures, and vertebral scalloping from dural ectasia.
On CT, some normal variants of the sacroiliac joint may simulate the features of sacroiliitis.
MRI may have a role in the early diagnosis of sacroiliitis. Detection of synovial enhancement on MRI has been found to correlate with disease activity, as measured by laboratory inflammatory markers. MRI has been found to be superior to CT in the detection of cartilage changes, bone erosions, and subchondral bone changes. MRI is also sensitive for the assessment of activity in relatively early disease. Affected sites include the diskovertebral junction and the peripheral joints. In general, areas of increased T2 signal correlate with the presence of edema or vascularized fibrous tissue.13,14,15,16,17,18,19,20,21,22,23
In established disease, MRI detects pseudoarthrosis, diverticula associated with cauda equina syndrome, and spinal canal stenosis. In patients with complications of fracture or pseudoarthrosis, MRI is useful for the assessment of spinal canal compromise and cord injury (see Images 20-21). MRI may be used to assess the integrity of intervertebral disks and spinal ligaments in cases involving spinal fractures. MRI is considered to be mandatory for patients with neurologic symptoms, especially for those who experience a symptom-free interval and for those who experience neurologic deterioration after established spinal cord injury.
MRI has been found to have a role in monitoring the treatment of patients with active ankylosing spondylitis. The degree of spinal inflammation may be detected before and after therapy with drugs such as the tumor necrosis factor-alpha receptor fusion protein etanercept and the interleukin 1 receptor antagonist anakinra.
Advantages of MRI include direct visualization of cartilage abnormalities, detection of bone marrow edema, improved detection of erosions, and the absence of ionizing radiation.
Yu et al have found MRI to be more sensitive than either radiography or CT in detecting early cartilage changes and bone marrow edema of the sacroiliac joints.24
Although sensitive in the detection of sacroiliitis, MRI is not specific for diagnosing ankylosing spondylitis as the cause of sacroiliitis.
Bone scintigraphy may be helpful for patients with suggested ankylosing spondylitis in whom radiographic findings are normal or equivocal. Qualitative assessment of the accumulation of radionuclides in the sacroiliac region may be difficult because of normal uptake in the location. Quantitative analysis may be more useful in these patients. Ratios of sacroiliac joint to sacral uptake of 1.3:1 or more are considered abnormal (see Image 22).25,26
Scintigraphy has high sensitivity but low specificity for the diagnosis of sacroiliitis. Several factors potentially affect calculation of the sacroiliac joint to sacrum ratio. These factors include a prominent sacral tubercle that may produce increased uptake in the sacrum and the influence of age and sex on radionuclide uptakes in the sacroiliac joints and sacrum. In patients with advanced disease, the radionuclide uptake may not appear abnormal.
Although sensitive for the detection of active disease in the spine, increased radionuclide accumulation is not specific for the diagnosis of ankylosing spondylitis.
Abnormal radionuclide uptake in the sacroiliac joints and other spinal locations may not be specific for ankylosing spondylitis. Correlation with other radiologic and clinical findings is important.
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ankylosing spondylitis, spondylitis, spondyloarthritis, spondyloarthropathy, rheumatoid spondylitis, bony ankylosis, vertebral inflammation, seronegative arthritis, sacroiliac, facet joint, paravertebral soft tissue, peripheral arthritis, iritis
Wilfred CG Peh, MD, MBBS, FRCP(Glasg), FRCP(Edin), FRCR, Clinical Professor, Faculty of Medicine, National University of Singapore; Senior Consultant Radiologist, Alexandra Hospital, Singapore
Wilfred CG Peh, MD, MBBS, FRCP(Glasg), FRCP(Edin), FRCR is a member of the following medical societies: American Roentgen Ray Society, British Institute of Radiology, International Skeletal Society, Radiological Society of North America, Royal College of Physicians, and Royal College of Radiologists
Disclosure: Nothing to disclose.
Michael A Bruno, MD, Associate Professor, Departments of Radiology and Medicine, Pennsylvania State University College of Medicine; Director, Radiology Quality Management Services, Milton S Hershey Medical Center, Pennsylvania State University College of Medicine
Michael A Bruno, MD is a member of the following medical societies: American College of Radiology, American Roentgen Ray Society, Association of University Radiologists, Radiological Society of North America, Society of Nuclear Medicine, and Society of Skeletal Radiology
Disclosure: Nothing to disclose.
Bernard D Coombs, MB, ChB, PhD, Consulting Staff, Department of Specialist Rehabilitation Services, Hutt Valley District Health Board, New Zealand
Disclosure: Nothing to disclose.
Wilfred CG Peh, MD, MBBS, FRCP(Glasg), FRCP(Edin), FRCR, Clinical Professor, Faculty of Medicine, National University of Singapore; Senior Consultant Radiologist, Alexandra Hospital, Singapore
Wilfred CG Peh, MD, MBBS, FRCP(Glasg), FRCP(Edin), FRCR is a member of the following medical societies: American Roentgen Ray Society, British Institute of Radiology, International Skeletal Society, Radiological Society of North America, Royal College of Physicians, and Royal College of Radiologists
Disclosure: Nothing to disclose.
Robert M Krasny, MD, Consulting Staff, Department of Radiology, Resolution Imaging Medical Corporation
Robert M Krasny, MD is a member of the following medical societies: American Roentgen Ray Society and Radiological Society of North America
Disclosure: Nothing to disclose.
Felix S Chew, MD, MBA, EdM, Professor, Department of Radiology, Vice Chairman for Radiology Informatics, Section Head of Musculoskeletal Radiology, University of Washington
Felix S Chew, MD, MBA, EdM is a member of the following medical societies: American Roentgen Ray Society, Association of University Radiologists, and Radiological Society of North America
Disclosure: Nothing to disclose.
Related eMedicine topics
Ankylosing Spondylitis and Undifferentiated Spondyloarthropathy (from Rheumatology)
Ankylosing Spondylitis (from Neurology)
Rheumatoid Spondylitis
Clinical guidelines
Adalimumab, etanercept and infliximab for ankylosing spondylitis. National Institute for Health and Clinical Excellence (NICE) - National Government Agency [Non-U.S.]. 2008 May. 47 pages. NGC:006523
Clinical trials
Efficacy of AIN457 in Adults (18-65 Years) With Moderate to Severe Ankylosing Spondylitis
Study Evaluating Etanercept for the Treatment of Active, Severe, and Advanced Axial Ankylosing Spondylitis
Examination of Radiographic Progression, Efficacy and Safety of Long-Term Treatment With Infliximab in Patients With Ankylosing Spondylitis
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