Clinical manifestations of ankylosing spondylitis in adults

Ankylosing spondylitis (AS), a form of spondyloarthritis (SpA), is a chronic inflammatory disease of the spine (axial skeleton) manifested by back pain and progressive stiffness of the spine; it can also involve the hips, shoulders, and peripheral joints. Extraarticular manifestations, including uveitis, may also be seen in patients with AS and other forms of SpA. AS typically develops in young adults, with a peak age of onset between 20 and 30 years.

The name “ankylosing spondylitis” is derived from the Greek root “ankylosis,” meaning stiffening of a joint, and “spondylos,” which refers to a vertebra. “Ankylosing spondylitis” thus refers to the inflammatory disorder associated with fibrous or bony bridging of joints in the spine, including the bridging of intervertebral discs.

NOMENCLATURE AND CLASSIFICATION CRITERIA

Ankylosing spondylitis (AS) is the prototypic form of spondyloarthritis (SpA), a family of disorders characterized by inflammation around the entheses (the sites of ligament insertion into bone) and an association with the human leukocyte antigen (HLA)-B27.

Classically, the diseases which comprise the SpA are AS, undifferentiated SpA, reactive arthritis, psoriatic arthritis, juvenile SpA, and arthritis/spondylitis associated with inflammatory bowel diseases (IBD).
SpA with predominantly axial involvement is also designated as “axial SpA,” and SpA with predominantly peripheral involvement is also designated as “peripheral SpA.” Axial SpA in the absence of plain radiographic changes of sacroiliitis is termed non-radiographic axial SpA, abbreviated as nr-axSpA.

Several different sets of classification criteria have been used to define the clinical spectrum of AS and axial SpA more generally; and the specific criteria set used for a particular study will influence the epidemiologic, clinical, and radiographic findings found among the study population. Since the mid-1980s, the modified New York classification criteria for AS has been used most often to define the classic form of axial SpA, historically termed AS. These criteria require the presence of specific abnormalities both clinically and upon plain radiography to meet classification criteria for AS. However, radiographic abnormalities may take several years to develop, and their recognition is subject to interobserver variation. Thus, it is likely that figures reported in the literature are an underestimation of true incidence and prevalence.
The spectrum of patients considered to have axial SpA, including AS, has also been defined by the 2009 Assessment of SpondyloArthritis International Society (ASAS) classification criteria, which do not necessarily require evidence of disease on plain radiography. Other classification criteria for SpA include the Amor criteria and the European Spondyloarthritis Study Group (ESSG) criteria sets.

EPIDEMIOLOGY

General population

The incidence and prevalence of ankylosing spondylitis (AS) in a population depend upon the ethnic group studied, the selection of subjects for evaluation, and the criteria for diagnosis. Estimates of the prevalence of AS in different studies range from zero to 1.4 percent [1-5]. In general, there is a clear correlation between the prevalence of AS in a given population and the prevalence of human leukocyte antigen (HLA)-B27 in that group, with the prevalence of AS being approximately 5 to 6 percent among people who are HLA-B27-positive. 

The prevalence of AS in the US was surveyed in the 1971 to 1975 National Health and Nutrition Examination Survey (NHANES) I study consisting of 6913 subjects of 25 to 74 years of age. The prevalence of AS was estimated to be 0.2 to 0.5 percent [7]. In the US, the prevalence of HLA-B27 varies among different ethnic communities; in a 2009 national survey, the prevalence rates of HLA-B27 in several groups were [8]:

• Mexican-Americans – 4.6 percent
• Whites who are non-Hispanic – 7.5 percent
• Blacks who are non-Hispanic – 1.1 percent

Familial risk depends partly upon the presence of HLA-B27. An individual's risk of developing AS is increased 5.6- to 16-fold if there is a first-degree relative with AS, and 10 to 20 percent of HLA-B27-positive individuals with affected first-degree relatives develop AS [9].

The actual male-to-female ratio is probably about 2:1 to 3:1 in AS. In a large Dutch cohort, more radiographic damage was found in the spine in men [10]. Men with non-radiographic axial spondyloarthritis (SpA) in a German cohort were at increased risk for developing radiographic sacroiliitis compared with women, and therefore at increased risk for evolution to AS [11]. Some cross-sectional studies have suggested that cervical involvement is more frequent in women, and lumbar involvement more frequent in men [12,13]; however, other studies, including longitudinal studies, have not found such a difference [10,14-16].

People with chronic back pain — The prevalence of AS among working adults with chronic (greater than three months) low back pain was 4.6 percent in one study [17]. In another group with chronic back pain, the prevalence of either AS or undifferentiated SpA with axial involvement was 5 percent [18].

MUSCULOSKELETAL SYMPTOMS AND FINDINGS

Ankylosing spondylitis (AS) is characterized by involvement of the spine and sacroiliac (SI) joints, peripheral joints, and entheses, although extraskeletal organs may also be affected. Spinal and SI involvement typically results in inflammatory back pain. Skeletal involvement may also result in complications including fracture and neurologic compromise in some patients. The major musculoskeletal features include:

• Spinal and SI involvement
• Hip and shoulder ("root" joint) involvement
• Costovertebral, manubriosternal, sternoclavicular, and costochondral inflammation
• Inflammation of extraspinal entheses
• Peripheral arthritis

Low back pain — Almost all patients with AS report back pain, which frequently, but not invariably, has characteristics suggesting an inflammatory etiology. Inflammatory back pain typically exhibits at least four of the following five features [19]:

• Age of onset <40 li="" years="">
• Insidious onset
• Improvement with exercise
• No improvement with rest
• Pain at night (with improvement upon arising)

Inflammatory back pain, by this definition, is present in 70 to 80 percent of patients with AS, but also in 20 to 25 percent of the patients with mechanical causes of back pain [20]. Despite its prevalence among patients with AS, in a population study only a minority of individuals with symptoms characteristic of inflammatory back pain will have SpA [21].

Limited spinal mobility and chest expansion — Postural abnormalities, especially hyperkyphosis, may already become apparent within the first 10 years of disease in some patients. Increasing flexion deformity of the neck, increased thoracic kyphosis, loss of normal lumbar lordosis, and flexion deformities of the hips generate a characteristic stooped posture. Lateral lumbar flexion and the Schober test are the measurements for spinal mobility which are affected earliest.

Buttock pain — Buttock pain, especially alternating between the two sides, may be indicative of SI involvement. In a study of 101 patients with AS and 112 with mechanical low back pain, alternating buttock pain was present in 37 percent of patients with AS and only 12 percent of patients with mechanical low back pain [23].

Hip pain — Hip involvement, resulting in hip joint pain, is present in 25 to 35 percent of patients with AS and is associated with higher degrees of disability and a worse prognosis. The typical symptom is groin pain, but as with other disorders of the hip joint, pain may be referred to the medial thigh or even the knee. Flexion deformities of the hips may develop. Hip involvement may be more severe in patients with early onset of AS, axial, and entheseal disease; and such patients may be more likely to eventually require hip replacement surgery [24].

Peripheral arthritis — Patients with AS may experience pain, stiffness, and swelling of joints outside the spine. Peripheral arthritis occurs in approximately 35 to 50 percent of patients with AS over the course of disease, and the prevalence of peripheral arthritis within a cohort of patients with AS at a single time point in one study was about 20 percent [25,26].

In one cohort, 36 percent of patients available for follow-up 33 years after enrollment in the cohort had experienced arthritis outside the spine [22]; the most commonly affected joints, in order of frequency, were the shoulders, hips, and knees. In another study, which involved 147 patients, the most frequently involved peripheral joints were ankles (40 percent), hips (36 percent), knees (29 percent), shoulders (19 percent), and the sternoclavicular joints (14 percent) [27]. Patients may also report temporomandibular joint (TMJ) pain. TMJ involvement is very uncommon in our experience, but one report has suggested that it might be more common than usually reported [28].

Enthesitis — The enthesis is the region of attachment of tendons and ligaments to bone; enthesitis (inflammation of the enthesi is a classic feature of AS and other spondyloarthritides. Enthesitis manifests as pain, stiffness and tenderness of insertions, usually without much swelling, although swelling may be a prominent feature at large insertions of the lower limbs. Enthesitis may occur in approximately 40 to 70 percent of patients with AS at some time during the disease course [11,26]. Extraspinal areas that may be involved by enthesitis in patients with AS include the calcaneal attachments of the Achilles tendon and the plantar fascia, the shoulders, the costochondral junctions, the manubriosternal and sternoclavicular joints, and along the superior iliac crest. Tenderness at these and other entheseal sites is suggestive of enthesitis.

The prevalence of enthesitis across one cohort at a single point in time was about 20 percent [11,26]; the frequency is probably dependent upon the duration of the disease. The heel is the most frequently involved site, with enthesitis present in 22 percent of patients at this site in one cross-sectional study [27]. Ultrasound techniques are frequently used in studies of enthesitis, but interpretation of these data has been limited by the great variation in acquisition methods, and there is no consensus regarding the threshold to be used in clinical practice [29]. Magnetic resonance imaging (MRI) is also used for the detection of osteitis at the entheseal insertion to the bone and soft tissue edema at the enthesis and adjacent areas.
Inflammation at the insertion of the supraspinatus tendon into the greater tuberosity of the humerus may be associated with shoulder pain and limited mobility of the affected shoulder or shoulders.

Dactylitis — Dactylitis (sausage digits) is characterized by diffuse swelling of toes or fingers. In one report of 1072 AS patients, dactylitis was present in 8 percent [30]. In two other AS studies, dactylitis at any time during disease was reported in 6 percent of patients [11,26], while prevalent dactylitis was seen in only 2 percent at a single time point [11].

EXTRAARTICULAR COMORBIDITIES

Patients with ankylosing spondylitis (AS) can exhibit a range of disease manifestations in extraskeletal organ systems. For some of these, a causal relationship with AS is more likely, such as pulmonary or cardiac involvement, while for others the relationship is less clear and may be more complex. Examples of the latter include uveitis, inflammatory bowel disease (IBD), and psoriasis, for which prevalence is disproportionally increased in patients with AS compared with the general population; these conditions may affect quality of life and function. Additionally, other problems, such as some neurologic manifestations, may be complications of changes due to the disease process. Renal disease may rarely occur, either as a comorbidity or a complication of the disease or its treatment.

Patients with AS also sometimes complain of constitutional symptoms, including considerable fatigue. Poor sleep is common, and is thought to be related in part to pain caused by active disease. Fever is an infrequent manifestation of AS in adults.

Acute anterior uveitis — Unilateral uveitis is the most common extraarticular complication of AS, occurring in 25 to 40 percent of patients [31-33]. Uveitis typically presents as acute unilateral pain, photophobia, and blurring of vision. Uveitis may be the first problem to require medical evaluation and should alert clinicians to the possibility of AS. About 50 percent of patients with acute recurrent unilateral anterior uveitis have a form of spondyloarthritis (SpA) [34]. The activity and severity of the eye disease are not correlated with the activity and severity of the articular disease. However, the occurrence of uveitis is associated with longer AS disease duration and the presence of human leukocyte antigen (HLA)-B27 [33].

Recurrence is common despite the effectiveness of local therapy, but seldom leads to permanent impairment of vision. In one study of 148 patients with HLA-B27-associated uveitis performed before the availability of tumor necrosis factor (TNF) inhibitors, the median duration of an attack was six weeks, and there were a median number of three recurrences for patients with more than 12 months of follow-up [35]. Cataracts and glaucoma can also occur. They are associated with posterior synechiae, increased intraocular pressure, and cystoid macular edema. 

Inflammatory bowel disease — Ileal and colonic mucosal ulcerations, which are almost always asymptomatic, can be detected by histological examination in 50 to 60 percent of patients with AS [36,37]. A minority of those with histologic inflammation develop clinically apparent IBD, whether Crohn’s disease or ulcerative colitis. Overt IBD occurs in approximately 5 to 10 percent of patients with AS, and about 4 to 10 percent of patients with IBD have concomitant findings of AS [33,38,39]. A considerable proportion of IBD patients have asymptomatic radiographic sacroiliitis [40]; the association between HLA-B27 and AS is weaker in the presence of established IBD, compared with AS alone [41]. However, the clinical presentation is very similar.

Psoriasis — Psoriasis is present in up to approximately 10 percent of patients with AS [33,38]. Patients with concomitant psoriasis have more frequent peripheral joint involvement and possibly a more severe AS disease course compared with AS patients without psoriasis [42]. Some experts have suggested that all psoriatic arthritis should be classified is part of the spondyloarthritis family, but this remains a matter of debate [43].

Psychosocial status — AS can adversely affect psychological health and socioeconomic status in addition to causing pain and disability. Taken together, these factors influence the patient’s overall quality of life, and they are collectively responsible for the intensity of pain, fatigue, and sleep disturbance [44,45].

In small studies, symptoms of pain and fatigue in patients with AS were associated with structural differences in certain regions in white and grey matter of the brain compared with controls, as shown on MRI, along with measures of emotional strength and spinal mobility [46]. A sense of helplessness (a feeling of an inability to actively cope with the disease), was an important contextual factor identified in both longitudinal and cross-sectional studies that affected health-related quality of life and functional measures [47-49].

Cardiovascular disease — AS is associated with an increased risk of both aortic regurgitation and cardiovascular disease overall:

• The estimated frequencies of aortic regurgitation and conduction disturbances are both increased but vary considerably, ranging from 6 to 10 percent for aortic regurgitation, and from 3 to 33 percent for conduction disturbances [50-53].
• There is also an increased risk of other cardiovascular diseases in AS. In a cross-sectional study during 2001 and 2002, involving 1843 patients with AS and 7372 controls (matched for age, gender, and geography), there were statistically significant increases among patients with AS in the prevalence of cardiovascular disease, heart failure, and peripheral vascular disease (prevalence ratios of 1.7, 95% CI 1.3-2.3; 1.6, 95% CI 1.2-2.2; and 1.8, 95% CI 1.2-2.6, respectively) [54]. There were nonsignificant trends suggesting a possible increase in ischemic heart disease and atherosclerosis. The prevalence of hypertension and hyperlipidemia was also significantly greater among the patients with AS. A 2011 metaanalysis of longitudinal studies found a statistically nonsignificant trend suggesting a possible increase in the risk of myocardial infarction in patients with AS and increased risk of the metabolic syndrome [55].
• Pulmonary disease — Pulmonary compromise can occur in patients with AS due to restrictive changes caused by the musculoskeletal disease and to changes in the lungs themselves, including interstitial, nodular, and parenchymal abnormalities.
• Restrictive pulmonary disease is related largely to diminished chest wall and spinal mobility. In one study where this was seen, pulmonary function tests (PFTs) were compared between patients with AS and matched controls; 18 percent of patients with AS, but none of the controls, showed a restrictive pattern [56]. Vital capacity is decreased and functional residual capacity is increased.
• A small percentage of patients, with estimates ranging from 1.3 to 15 percent, have evidence of other pulmonary changes such as apical pulmonary fibrosis by plain radiography [57-60]. The apical fibrosis is usually asymptomatic and associated with a long duration of disease.
• Abnormalities detected on a high-resolution computed tomography (CT) are much more common than findings on plain radiography. These include a mosaic pattern, subpleural nodules, and parenchymal bands, and may be present even early in the disease [59,60].
• Fibrotic disease and cigarette smoking may be risk factors for spontaneous pneumothorax, a complication that is otherwise rare in AS [61].

The causes of these intrinsic pulmonary abnormalities are unknown. There is a lack of evidence for alveolitis, as bronchoalveolar lavage is generally unremarkable [58]. However, in one report transbronchial biopsies revealed interstitial fibrosis of variable degree in 5 out of 12 patients, indicating that the radiologic appearance of apical fibrosis may actually reflect a more generalized process [58].

COMPLICATIONS

Several types of complications can occur in patients with ankylosing spondylitis (AS), most frequently as a consequence of longstanding disease. These include low bone mass, fractures, and neurologic compromise due to changes in the spine. Renal complications are rare.

Osteopenia

Low bone mineral density (BMD) and bone loss have been documented in patients with AS, and are evident within the first 10 years of disease [62-64]. In more than half of patients with longstanding and persistently active disease, BMD is decreased at both the spine and the hip [65,66]. However, with advanced disease, dual photon absorptiometry (DEXA) measurement of bone mineral density of the spine may provide falsely high values because of the superimposed effect of syndesmophytes and periosteal bone formation [67]. However, estimation of bone density in the presence of syndesmophytes may be facilitated by dual-energy quantitative computed tomography (CT) scanning of the spine; and in using this technique, it has been shown that patients with syndesmophytes have lower bone mass than those without this finding [68]. Osteopenia or frank osteoporosis may predispose to fracture, especially in the spine.

Fractures in axial SpA

Patients with ankylosed spines can develop vertebral fractures with minimal (and sometimes no recollected) trauma [69]. Additionally, hyperkyphosis of the spine is common in patients with longstanding AS, and many of these patients have anterior wedging of the thoracic vertebrae [70].

In one study, the risk of a clinical vertebral fracture was significantly increased in patients with AS, compared with matched controls (odds ratio 3.3, 95% CI 1.5-7.0), although the risks of forearm or hip fractures were not [71]. Estimates of the lifetime incidence of clinical vertebral fracture in patients with AS range from 4 to 18 percent [72]. Cervical fractures that can be visualized by magnetic resonance imaging (MRI) or CT may often not be visualized on plain radiographs.

Neurologic manifestations

Neurologic symptoms can occur by several mechanisms, including cord or spinal nerve compression due to fracture of the ankylosed spine or atlantoaxial subluxation. Additionally, subclinical neuropathy, myelopathy, and myopathy are common but rarely symptomatic [73].

• Spinal cord injury – Spinal cord injury is 11 times more common in AS than in the general population and affects the cervical spine, including the lower cervical spine, more often than the thoracic and lumbar spine [74]. About 65 percent of spinal fractures are associated with neurological complications, although the initial complaints are often subtle and might be missed without a high index of suspicion [75]. The morbidity of spinal injury is very high, causing paraparesis or tetraparesis in some patients [72].
• Atlantoaxial subluxation – Clinically significant spontaneous subluxation of the atlantoaxial joint (C1-C2) occurs in patients with AS and can lead to spinal cord compression if it is not recognized and stabilized. In one study of 103 patients, for example, anterior or posterior atlantoaxial subluxation was observed in 21 and 2 percent of individuals, respectively [76]. In a two-year follow-up, progression of anterior subluxation was observed in about 50 percent. In other reports, clinically significant spontaneous subluxation occurred in approximately 2 percent of individuals. This problem is managed in a fashion similar to that in rheumatoid arthritis.
• Cauda equina syndrome – The cauda equina syndrome is a rare complication of AS, typically reported in patients with longstanding disease who have marked ankylosis of the spine [72,77,78]. The symptoms are those of damage to the lumbosacral nerve roots, probably caused by arachnoiditis. Patients may complain of abnormalities in cutaneous sensation and motor function, problems with bladder and bowel control, and impotence.

Renal disease

Renal disease is very uncommon in AS, but non-specific glomerulopathy, immunoglobulin A (IgA) nephropathy, and renal amyloidosis may be seen [79-81]. In a cohort of 681 patients with AS abnormal findings on urinalysis were seen in 8 percent, including proteinuria and/or hematuria. Patients with proteinuria exceeding 1000 mg per day underwent renal biopsy. The biopsies showed nonspecific glomerulopathy (3 patients), IgA nephropathy (2 patients), and amyloidosis (1 patient) [79]. This spectrum of renal diseases is in agreement with an earlier review of literature [80]. Renal amyloidosis is rare [79,82,83]. 

PREGNANCY

Ankylosing spondylitis (AS) does not appear to adversely affect pregnancy. The relationship between the activity of AS and pregnancy has been evaluated by questionnaire in patients from the United States, Canada, and 10 European countries, in whom no adverse effects upon fertility, pregnancy outcome, or the neonate were identified [84]. Disease activity was improved, remained unchanged, or had worsened in equal numbers of patients. A postpartum flare was experienced in about 60 percent of patients, particularly in the peripheral joints.

LABORATORY FINDINGS

Laboratory findings in ankylosing spondylitis (AS) are generally nonspecific. An elevated acute phase response may be present, including an elevated erythrocyte sedimentation rate (ESR) and elevated C-reactive protein (CRP), in about 50 to 70 percent of patients with active disease; thus, a normal ESR and CRP do not exclude AS [11,26,85]. The ESR and CRP do not correlate well with axial disease activity, but might correlate better with active peripheral arthritis. A normochromic normocytic anemia is occasionally seen, most typically in patients with very active disease [85,86].

The level of serum bone-specific alkaline phosphatase may be elevated in severe disease, and serum levels of immunoglobulin A (IgA) are commonly elevated above the normal range [87]. Synovial fluid findings are typical of inflammatory arthritis, with an increased white blood cell count that is predominated by polymorphonuclear leukocytes. Human leukocyte antigen (HLA)-B27 is present, but not invariably so, in most patients with AS (90 to 95 percent of patients of European ancestry), and commonly present in other forms of spondyloarthritis compared with the prevalence in the general population.

MUSCULOSKELETAL IMAGING

Radiographic changes from joint and spine involvement with ankylosing spondylitis (AS) usually become evident over time. Evidence of AS can sometimes be demonstrated by magnetic resonance imaging (MRI) before damage is evident on plain radiography.

Sacroiliac joints

An abnormal appearance of the sacroiliac (SI) joint using an appropriate imaging technique is a hallmark of AS. Radiographic findings progress from subtle joint space narrowing and sclerosis to erosive change, and may result eventually in bony ankylosis (fusion). Plain radiography and MRI are the principal techniques used to assess the SI joints; additional methods that have been used to detect abnormalities include computed tomography (CT), scintigraphy, ultrasonography, and conventional tomography. Scintigraphy lacks specificity for SI, and conventional tomography involves substantial radiation exposure; thus, neither are generally used clinically.

Plain radiographs of the pelvis/SI joints — The initial radiographic changes of AS occur in the SI joints in about 95 percent of patients. In general, radiographic damage is slow to develop. Plain radiographs may be normal or may only reveal slight or suspicious changes during the first few years of disease, but usually will become abnormal within the first decade [14]. In a study of 228 patients with newly diagnosed axial spondyloarthritis (SpA), radiographic changes of the SI joints typical of AS were found in 33 percent of patients with symptoms for less than one year, about 47 percent of patients with symptoms for one to six years, and in 68 percent of those with symptoms for between six and nine years [88].

Changes characteristic of sacroiliitis can be well visualized with anteroposterior (AP) views of the pelvis. However, the SI joints are not as clearly visualized on plain radiography as are other joints, such as the knees or digits, and more subtle findings can be missed. This is because the direction of the SI joint is oblique relative to the coronal plane, being nearer to the central axis posteriorly than anteriorly. In addition, the direction is also oblique relative to the sagittal plane, being nearer the central axis inferiorly than superiorly. The surfaces on both the sacral and the iliac sides are also irregular in shape. X-ray films should be of good quality, as under-penetrated films can be misread.

With a high-quality film of the AP view of the pelvis, the joint spaces of both the right and the left SI joints can be well seen. The right and left sides should be read separately. The most obvious abnormalities as disease becomes more advanced are fusion and large erosions. Erosions are seen as obvious craters, usually associated with widening of the joint space. In advanced disease of the joint, when an SI joint is fused, the joint space disappears, so that the bone is continuous between the sacrum and the ilium. On the x-ray film, the joint space becomes a thin, narrow line. Presence of either fusion or obvious erosion even on one of the two SI joints is consistent with AS. The presence of sclerosis of the SI joint is a sign indicating possible AS, but is not diagnostic by itself.
Sacroiliitis has been divided into five grades, primarily for use in epidemiologic and clinical research:

• Grade 0: normal (image 2)
• Grade 1: suspicious changes (image 3)
• Grade 2: minimal abnormality – small localized areas with erosions or sclerosis, without alteration in the joint width (image 3)
• Grade 3: unequivocal abnormality – moderate or advanced sacroiliitis with one or more of the following: erosions, evidence of sclerosis, widening, narrowing, or partial ankylosis (image 4A-B)
• Grade 4: total ankylosis (image 5A-B)

By expert consensus it has been deemed that definite sacroiliitis is present in patients with bilateral changes of at least grade 2 in severity or at least unilateral changes of at least grade 3 severity. [89]. In practice, clinicians can regard the x-ray changes to be diagnostic of sacroiliitis if there is ankylosis or if there are obvious erosions. Other examples of the various grades are available in the slide library of the Assessment of Spondyloarthritis International Society.

Additional changes typical but not diagnostic of AS that may be seen on plain radiography of the pelvis include erosions and osteitis at the ischial tuberosities, iliac crests, symphysis pubis, femoral trochanters, and hip. Radiographs from these sites typically show destructive changes without much new bone formation. The severity of radiographic hip involvement correlates with more severe spinal disease [14].

MRI of the SI joints — The most characteristic change of active sacroiliitis on MRI is termed "bone marrow edema" (BME), which is a hyperintense signal in the bones adjacent to the affected joints, as seen in the STIR (short tau inversion recovery) images or the T2-weighted images with fat absorption. MRI views that are most helpful in AS, according to expert consensus, are the semi-coronal views parallel to the axes of the SI joints. Administration of contrast medium is normally not necessary to visualize these changes. BME can also be present in other causes of chronic low back pain, such as degenerative spine disease, where it may be present in up to 20 percent of such patients [90].

MRI changes other than BME, including structural changes such as erosions, fatty degeneration, and sclerosis visualized by T1-weighted images, can also be present; these findings can be useful in clinical assessment.

Spine

A series of radiographic changes characteristic of AS can develop progressively over the course of disease [14]:

• Squaring of the vertebral bodies due to anterior and posterior spondylitis is an early radiographic sign of inflammatory and destructive spinal involvement due to axial SpA.
• Changes that are more easily distinguished and found at later stages of AS include syndesmophytes, ankylosis of the facet joints, and calcification of the anterior longitudinal ligament.
• The abnormality that is most easily recognizable is the bamboo spine in late ankylosing spondylitis.

Anterior atlantoaxial (C1-C2) subluxation is also be visualized by use of plain radiographs taken in flexion and extension of the cervical spine. Other findings that may also be apparent on radiographs of the spine are spondylodiscitis and fractures [91].

MRI of the lumbar spine may show changes in the absence of abnormalities on plain radiographs, and infrequently even in the absence of SI joint inflammation [92]. Spinal changes in the absence of significant SI joint inflammation were more frequent in a study population of patients with clinically active, longstanding, non-radiographic axial SpA (nr-axSpA) [93]. Abnormalities seen in AS and other SpA that experts consider consistent with inflammatory change in the spine include anterior/posterior spondylitis in at least three sites on a STIR sequence [94]. The MRI views should be sagittal and should include the STIR or the T2-weighted images with fat absorption sequences. Another characteristic lesion on MRI of the spine is fatty change, which may be present in several corners of the vertebral bodies, especially in younger adults and in the presence of a ‘healthy’ disc, seen on T1-weighted sequences.

Entheses

Ultrasonography is increasingly being used for the detection and assessment of enthesitis, such as Achilles tendonitis. Findings in 2011 of an expert task force, based upon a systematic review of published data, were that the utility of ultrasound in assessing enthesitis required further validation, despite a growing body of literature [29]. Major problems included a lack of standardization of techniques, the diversity of equipment used in different studies, and a lack of consensus for the definitions of enthesitis and treatment response.

SUMMARY AND RECOMMENDATIONS

• Estimates of the prevalence of ankylosing spondylitis (AS) vary from 0 to 1.4 percent, depending upon the ethnic group, the prevalence of human leukocyte antigen (HLA)-B27, the selection of subjects for evaluation, and the criteria for diagnosis. The prevalence may be underestimated because of the difficulty in establishing the diagnosis clinically and radiographically; it is increased to approximately 5 to 6 percent in subjects who are HLA-B27 positive. The prevalence of AS or axial spondyloarthritis (SpA) among adults with chronic back pain is about 5 percent. 
• The symptoms of AS include inflammatory back pain, buttock pain, limited spinal mobility, limited chest expansion, hip and shoulder pain, and enthesitis. Patients may have peripheral arthritis, dactylitis, and constitutional features. Inflammatory low back pain is characterized by age of onset <40 .="" li="">
• Extraarticular involvement may include anterior uveitis, psoriasis, and symptomatic as well as asymptomatic inflammatory bowel diseases (IBD). Additional extraarticular features include cardiovascular disease, including aortic regurgitation and conduction abnormalities; pulmonary disease, especially restricted chest expansion and apical pulmonary fibrosis; and manifestations of psychosocial distress. Complications of AS may include osteopenia, neurologic manifestations of cord or spinal nerve compression due to spinal fracture or atlantoaxial subluxation, and other rare neurologic events.
• Laboratory findings are generally nonspecific, and may include the presence of HLA-B27 and occasionally a normochromic normocytic anemia. An elevated acute phase response may be present, including an elevated erythrocyte sedimentation rate (ESR) and elevated C-reactive protein (CRP), but the ESR and CRP do not correlate well with axial disease activity, and a normal ESR and CRP do not exclude AS or active disease. 
• Imaging abnormalities characteristic of AS include sacroiliitis and spondylitis, which can be seen on plain radiographs in more advanced disease. However, they are only detected during early disease, when plain radiographs may be normal or may have only minimal changes, by the finding of bone marrow edema (BME) and other changes on magnetic resonance imaging (MRI). Ultrasonography may be helpful in the detection of enthesitis but requires further standardization and validation. 

Authors: David T Yu, MD, Astrid van Tubergen, MD, PhD

Section Editor: Joachim Sieper, MD

Deputy Editor: Paul L Romain, MD

All topics are updated as new evidence becomes available and our peer review process for UptoDate is complete. Literature review current through: Apr 2014. | This topic last updated: Mar 13, 2014.

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