Ankylosing Spondylitis

Also known as: Axial Spondyloarthritis, Bekhterev's Disease

ICD-9 Code: 720.0.
ICD-10 Code: M08.1

What is it?

AS is a common inflammatory condition associated with inflammatory axial and peripheral arthritis, enthesitis and other manifestations. Involvement of the axial skeleton is prominent, often beginning in the sacroiliac joints and ascending to involve the remaining spine.

What causes it?

AS has a strong genetic component; >90% of white patients are HLA-B27 positive, and a significant minority have a positive family history for AS. AS develops in 1% to 2% of HLA-B27–positive individuals. There is a 20% risk of AS in HLA-B27–positive first-degree relatives of patients with AS. The role of HLA-B27 in the etiopathogenesis of AS. It has been postulated that arthritogenic bacteria that resemble HLA-B27 may cause disease through molecular mimicry. Alternatively, properties of HLA-B27 might affect T cell repertoire and hence antigen presentation. The role of the misfolding of B27 and its potential association with the development of AS has also generated interest. There are >100 known subtypes of B27.  B*2705 is the most common. Most are associated with AS, with the notable exception of B*2706.

The spondyloarthropathies (SpA) typically demonstrate enthesitis early, followed by erosive changes, osteitis, and, ultimately, fibrous ankylosis. Synovial biopsy changes have some similarities but also some clear distinction from those seen in RA. AS and the other SpA share a propensity for inflammation at the entheses (sites of tendon or ligament attachment to bone), with resultant reactive bone formation.

Who gets it?

Epidemiologic studies suggest that the prevalence of AS in caucasian population is between 0.5 and five cases per 1,000 persons. The age- and gender-adjusted incidence rate in Rochester, MN, is 7.3 per 100,000 person- years. HLA-B27 and AS are less prevalent in African Americans. AS commonly affects young men more frequently than women, with an estimated male:female ratio ranging from 2.5:1 to 5:1. AS in women is often underdiagnosed. Women with AS may have a delayed disease onset, less hip involvement, less aggressive axial disease, more peripheral arthritis, severe osteitis pubis, and a higher incidence of isolated cervical spine disease. Peak age at onset of AS is between 15 and 30 years. Onset is rare after age 50. Juvenile spondylitis, a minority subset of juvenile arthritis, includes those with onset of AS between the ages of 9 and 16 years.

What are the symptoms?

Symptoms often begin in young adulthood. The insidious onset of inflammatory low back pain or stiffness is often the initial symptom of AS. Bilateral symmetric sacroiliitis is highly suggestive of AS. Although sacroiliitis begins at an early age, it may take as long as 10 years to become evident by conventional radiography. Patients usually complain of prolonged morning stiffness that may only relieved by increased activity or anti-inflammatory medications. Often these young patients actively pursue sports and physical activity as a means of alleviating their symptoms. Constitutional complaints of fever, anorexia, and weight loss may be seen. With progressive axial involvement, pain and stiffness result in difficulty with ambulation and activities of daily living. Fusion of the axial spine occurs in an ascending fashion, with early lumbar and late cervical spine involvement.

An asymmetric oligoarticular, inflammatory, peripheral arthritis is seen in 30% of patients with AS. Synovitis of the hip can be destructive and may lead to concentric loss of joint space, especially in men. Involved peripheral joints include the ankles, wrists, shoulders, elbows, and small joints of the hands or feet. Radiographically, peripheral articular changes may be erosive and similar to RA.

Extraarticular disease in AS primarily affects the eye. Ocular involvement is seen in as many as 40% of patients and is more frequently observed in HLA-B27–positive individuals. Uveitis, particularly iritis/anterior uveitis presents as acute, unilateral, orbital pain with photophobia and progressive loss of vision if untreated.

Examination of the spine may reveal restricted spinal movement from axial stiffness, fusion, and paraspinal muscular spasm. Often the earliest finding is a loss of normal lumbar lordosis and resultant “flattening” of the lumbar spine. Left untreated, progressive axial inflammation may lead to a fixed forward flexion posture, most evident in the hip and neck. Chest expansion, as measured by the inspiratory minus expiratory chest circumference, normally exceeds 5 cm. Patients with AS demonstrate diminished expansion (<4 cm). Cervical spine mobility can be serially assessed by measuring the occiput (or tragus) to wall distance.

Lumbar spine mobility is assessed by the Schober test (with the patient standing upright with heels together, a 10-cm span is marked from the fifth lumbar vertebra cephalad. Upon maximal forward flexion, the distance between marks is remeasured. Normal spinal flexion expands the surface area over the flexed spine to >15 cm. Flexion in patients with spondylitis may be limited.

Uncommon Findings: Thoracocervical kyphoscoliosis, aortitis, aortic insufficiency, aortic root dilation, and conduction defects (heart block) are uncommon. Others include mitral valve disease, myocardial dysfunction, pericarditis, pulmonary fibrosis, and amyloidosis.

Complications: Minor or incidental trauma may result in serious spinal fractures in those with ankylosis of the spine. Such fractures may result in spinal cord damage and carry a high mortality rate. Fractures may be identified on plain radiographs, bone scans, or MRI. Other rare complications of AS include cauda equina syndrome, osteoporotic compression fractures, spondylodiscitis, restrictive lung disease, apical fibrosis, cardiac conduction defects, and aortic insufficiency.

How is it diagnosed?

Elevated ESR or CRP levels and anemia of chronic disease may be seen. Mild elevations of alkaline phosphatase and IgA levels may also be seen. Serologies for autoantibodies are typically absent. HLA-B27 determination is not necessary to establish the diagnosis but may help establish the diagnosis in equivocal  cases. HLA-B27 is found in ~90% of white but only 50% of African- American patients with AS.

Imaging: Radiographs are often normal early in the disease and demonstrate normal mineralization before the onset of ankylosis. Once present, ankylosis results in marked immobility and subsequent generalized osteoporosis. Sacroiliitis is evidenced by early erosions and pseudo-widening and, later, by sclerosis or fusion of the inferior, synovium-lined portion of the sacroiliac joint. These findings may be observed on plain radiographs of the pelvis but MRI can detect diagnostic changes earlier. Axial radiographic findings also include vertebral enthesitis (manifest as “shiny corners’’), marginal bridging syndesmophytes, fusion of the posterior facet joints, and “squaring” of lumbar and thoracic vertebrae. Collectively, these findings may produce the classic appearance of a “bamboo spine.” Axial damage or fibrosis tends to have a bilateral symmetric distribution.

Diagnostic Criteria: Several diagnostic criteria have been developed over the years (Table 2).

Keys to Diagnosis: AS must be distinguished from other causes of mechanical or degenerative low back pain. AS is suggested by (1) young age at onset, (2) strong family history of low back pain, (3) presence of inflammatory low back pain (lasting >3 months, with prolonged morning stiffness and improved by activity or exercise), (4) limited spinal mobility on examination, (5) elevated ESR or CRP, and, if needed, (6) HLA-B27 positivity.

Table 2 Diagnostic Criteria for Ankylosing Spondylitis
Rome Criteria, 1961 Clinical criteria1.Low back pain and stiffness for >3 mo, not relieved by rest 2. Pain and stiffness of the thoracic region 3. Limited motion in the lumbar spine 4. Limited chest expansion 5. History or evidence of iritis or its sequelae Radiologic criterion 6. Radiographs showing characteristic bilateral sacroiliac changes Definite AS = grade 3–4 bilateral sacroiliitis and 1 clinical criterion or at least 4 clinical criteria
Modified New York, 19841. Low back pain for at least 3 months; duration improved by exercise and not relieved by rest 2. Limitation of the lumbar spine in sagittal and frontal planes 3. Chest expansion decreased relative to normal values for age and sex 4. Bilateral sacroiliitis grades 2–4 5. Unilateral sacroiliitis grades 3–4 Definite AS = unilateral grade 3–4 sacroiliitis or bilateral sacroiliitis grades 2–4 and 1 clinical criterion

ASAS classification criteria for axial spondyloarthrisis; 2009

in patients with back pain for 3 months or more and an age at onset <45 years: Classification requires -

1. Sacroiliitis on imaging (active inflammation on MRI) plus 1 or more SpA features

or

2. HLA-B27 + 2 or more SpA features

SpA features include:

inflammatory back pain

arthritis

enthesitis

uveitis

dactylitis

psoriasis

inflammatory bowel disease

good response to NSAIDs

family history of SpA

HLA-B27

increased CRP

Differential Diagnosis: The differential diagnosis includes other SpA (enteropathic arthritis, reactive arthritis, psoriatic spondylitis), osteitis condensans ilii, diffuse idiopathic skeletal hyperostosis (DISH), and other causes of hyperostosis (e.g., fluorosis, hypervitaminosis A).

How is it treated?

The goal of treatment is to reduce pain and stiffness and maintain posture and mobility, all in an effort to maintain functional status and optimize quality of life. Ideally, progression of disease could be halted. Both nonpharmacologic and pharmacologic measures should be used in all.

Nonpharmacologic: Patients should be educated about the disorder and the importance of joint protection, appropriate exercise, intermittent rest, physical therapy, and dietary and vocational counseling. Patients with axial disease should engage in lifelong physical therapy to maintain posture and prevent slow deformity. Patient support can be found through patient support organizations worldwide.

—NSAIDs: NSAIDs are effective in controlling several manifestations of AS, including inflammatory back pain/ stiffness, peripheral arthritis, and enthesitis. These agents modify symptoms and , especially at higher doses and with regular use, may actually slow the progression of radiographic disease progression. NSAIDs are the mainstay of therapy for most patients.

—Corticosteroids: Systemic corticosteroids are seldom used in the SpA. They can be effective in controlling localized disease when used by intraarticular injection (i.e., mono-or oligoarthritis), topical management of ocular complications (conjunctivitis or uveitis), and, on occasion, intralesionally to control enthesitis. Uncontrolled reports suggest beneficial effects of intraarticular corticosteroids administered by guided arthrocentesis into the sacroiliac joints.

—Disease-modifying antirheumatic drugs (DMARDs): For patients with peripheral inflammatory arthritis, the addition of a DMARD (e.g., sulfasalazine, MTX) could be considered. These agents may have a delayed onset of action (2–4 months). Randomized, placebo-controlled trials of sulfasalazine (or MTX) indicate efficacy in patients with peripheral arthropathy and enthesopathy. Unfortunately, DMARDs (including SSZ, MTX, leflunomide) have not been shown to be effective in controlling the axial symptoms. Other DMARDs (azathioprine, gold salts, antimalarials, cyclosporine) have not been well studied in AS. Limited studies suggest the benefit of pamidronate in controlling axial symptoms. TNF inhibitors have revolutionized the treatment of axial AS. Multiple studies with all 5 available TNF inhibitors have shown dramatic improvement in diverse signs and symptoms of AS. Interestingly, it is still not clear that TNF inhibitors can alter the radiographic progression of axial disease in AS.

Surgery: Surgical intervention in AS is primarily reserved for those with advanced peripheral arthritis, usually affecting the hip or knee. Total joint replacement may be indicated when pain and immobility markedly interfere with the patient’s lifestyle. The success of arthroplasty may be limited by post-surgical heterotopic bone formation. Surgical stabilization of spinal fractures should be undertaken with extreme caution. Correction of spinal deformities caused by advanced, aggressive ankylosis is not advised.

What is the outlook?

The clinical course and disease severity are highly variable. Inflammatory back pain and stiffness are prominent early in the disease, whereas chronic, aggressive disease may produce pain and marked axial immobility or deformity. Early-onset age and diagnosis portend a more severe outcome.

Adapted from: RheumaKnowledgy