Ankylosing spondylitis

QU LIUXIN

SOUTHEAST UNIVERSITY ZHONGDA HOSPITAL

 Ankylosing spondylitis (AS, from Greek ankylos, bent; spondylos, vertebrae), a form of Spondyloarthritis, is a chronic, inflammatory arthritis. It affects joints in the spine and the sacroilium in the pelvis, causing eventual fusion of the spine. It is a member of the group of the spondyloarthropathies with a strong genetic predisposition. Complete fusion results in a complete rigidity of the spine, a condition known as bamboo spine.

Epidemiology
The sex ratio is 3:1 for men:women. the prevalence is 0.25%, but as it is a chronic condition the incidence (number of new cases) is fairly low.

Signs and symptoms

The typical patient is young, aged 18-30, with chronic pain and stiffness in the lower part of the spine, often with pain referred to one or other buttock or back of thigh from the sacroiliac joint early on. Pain is often severe on rest, and improves with physical activity. Men are affected more than women by a ratio about of 3:1. In 40% of cases, ankylosing spondylitis is associated with an inflammation of the eye (iridocyclitis), causing eye pain and photophobia. Another common symptom is generalised fatigue. As with all the seronegative spondarthropathies.

 When the condition presents before the age of 18 it is relatively likely to cause pain and swelling of large limb joints, particularly the knee. In pre-pubescent cases, pain and swelling may also manifest in the ankles and feet. The spine may be affected later on. AS is one of a cluster of conditions known as seronegative spondarthropathies in which the characteristic pathological lesion is an inflammation of the enthesis (the insertion of tensile connective tissue into bone). Other forms of spondarthropathy are associated with ulcerative colitis, Crohn's disease, psoriasis, and Reiter's syndrome (reactive arthritis) .

General symptoms
Symptoms include those related to inflammatory back pain, peripheral enthesitis, arthropathy, and constitutional and organ-specific extra-articular manifestations. Because ankylosing spondylitis is a systemic inflammatory disease, systemic features are common. Morning stiffness is characteristic, and fatigue is common. Fever and weight loss may occur during periods of active disease.

Inflammatory back pain

This is the most common symptom and the first manifestation in approximately 75% of patients. Symptoms associated with an inflammatory process include insidious onset occurring over months or years, generally with at least 3 months of symptoms before presentation. Symptoms include morning stiffness lasting at least 30 minutes, improvement of symptoms with moderate physical activity, and diffuse nonspecific radiation of pain into both buttocks. Patients often experience stiffness and pain that awakens them in the early morning, a distinctive symptom not generally found in patients with mechanical back pain.

 New criteria to define inflammatory back pain have been proposed; when 2 of the 4 criteria are present, they yield a sensitivity of 70.3% and specificity of 81.2%. These criteria include the following: Morning stiffness that lasts more than 30 minutes Improvement of back pain with exercise but not rest Nocturnal back pain during second half of the night only Alternating buttock pain

 Acute onset of pain, exacerbation of symptoms with activity, and radicular radiation of pain suggest a mechanical or degenerative process such as disc disease. The spinal disease starts in the sacroiliac joints (bilateral lumbosacral region). Most patients have mild chronic disease or intermittent flares with periods of remission. The spinal disease is rarely persistently active. Progression occurs from the lumbosacral region proximally, with ossification of the annulus fibrosus that results in fusion of the spine (bamboo spine).

Ankylosing process

Peripheral enthesitis and arthropathy

Peripheral musculoskeletal involvement occurs in 3050% of all patients. Peripheral enthesitis is the basic pathologic process, involving inflammation at the site of insertion of ligaments and tendons on to bone. This often progresses from erosion and osteitis to ossification, resulting in telltale radiological signs of periosteal new bone formation.

Joint involvement tends to occur most commonly in the hips, shoulders, and joints of the chest wall, including the acromioclavicular and sternoclavicular joints, and often occurs in the first 10 years of disease. Involvement of the hips and shoulders may result in joint damage with radiographic changes. Other peripheral joints are involved less frequently and to a milder degree, usually as an asymmetric oligoarthritis predominantly involving the lower extremities. Temporomandibular joints are occasionally involved.

Spinal articular manifestations

Stiffness of the spine and kyphosis resulting in a stooped posture are characteristic of ankylosing spondylitis at advanced stages. Earlier in the course of the disease, indirect evidence of sacroiliitis and spondylitis may be observed, including tenderness of the sacroiliac joints (elicited by either direct pressure or indirect compression) or a limited range of spine motion. Some patients may have a deformity of the spine, most commonly with a loss of lumbar lordosis and accentuated thoracic kyphosis.

o The range of motion of the lumbar spine can be assessed using various methods, of which the Schober test is the most popular. This test is not specific for ankylosing spondylitis. Perform the Schober test by marking a 10-cm length of the lumbar spine (with patient in the erect position), starting at the fifth lumbar spinous process. Instruct the patient to maximally flex his or her spine. Remeasure the distance between the marks. Normal flexion increases the distance by at least 5 cm. Loss of chest expansion (<3-cm difference between minimum and maximum chest diameter) is usually found only in patients with late-stage disease and is generally not helpful in diagnosis.

Peripheral entheses and joints

Peripheral enthesitis occurs in approximately 33% of patients. These lesions are painful and tender upon examination and may be associated with swelling of the tendon or ligament insertion. The most common and characteristic peripheral sites of enthesitis are the insertion of the Achilles tendon on the calcaneus and the insertion of the plantar fascia on the calcaneus. Certain anatomic areas may be more prone to enthesitis due to biomechanical stress. Other areas of involvement are listed in Peripheral enthesitis and arthropathy. Carefully examine patients for tenderness upon palpation.

 Enthesitis and synovitis account for some of the peripheral joint involvement. Peripheral joint disease occurs in 33% of patients, most commonly in the hips. Hip involvement usually occurs in the first 10 years of the disease course and is typically bilateral. Other joints may be involved, including the shoulder girdle (glenohumeral, acromioclavicular, sternoclavicular joints), costovertebral joints, costosternal junctions, manubriosternal joints, symphysis pubis, and temporal mandibular joints.

Extraarticular manifestations
o Uveitis is the most common extra-articular manifestation, occurring in 20-30% of patients with ankylosing spondylitis. Of all patients with acute anterior uveitis, 30-50% have or will develop ankylosing spondylitis. The incidence is much higher in individuals who are HLA-B27 positive (84-90%). o Patients with uveitis may also have or may develop other spondyloarthropathies (SpAs), although less commonly, including reactive arthritis (5-10%), undifferentiated spondyloarthropathy (2-5%), and psoriatic arthritis (<1%). Isolated inflammatory bowel disease (IBD) is also associated with uveitis.

Cardiovascular involvement
o Cardiovascular involvement of clinical significance occurs in fewer than 10% of patients, typically those with severe longstanding disease. However, subclinical disease can be detected in many patients and may occur as an isolated clinical entity in association with HLA-B27.

Pulmonary involvement
o Restrictive lung disease may occur in patients with late-stage ankylosing spondylitis, with costovertebral and costosternal involvement causing limited chest expansion.

Renal involvement
o Amyloidosis is a very rare complication of ankylosing spondylitis in patients with severe, active, and long-standing disease. These patients generally have active spondylitis, active peripheral joint involvement, and an elevated erythrocyte sedimentation rate (ESR) and C-reactive protein level. This may result in renal dysfunction with proteinuria and renal insufficiency or failure.

Neurologic involvement
Neurologic complications may occur secondarily to fractures of a fused spine, which may be very difficult to detect with standard radiography. Patients are also prone to atlantoaxial subluxation, which may result in cervical myelopathy. Cauda equina syndrome may also occur in patients with severe long-standing disease.

Gastrointestinal involvement
Asymptomatic inflammation of the proximal colon and terminal ileum has been observed in as many as 60% of patients with ankylosing spondylitis and undifferentiated spondyloarthropathy. Patients with established ankylosing spondylitis only rarely develop Crohn disease or ulcerative colitis.

Causes
The cause of ankylosing spondylitis is unknown, but a combination of genetic and environmental factors works in concert to produce clinical disease.

Imaging Studies
Standard radiography
Radiographic studies are most helpful in establishing a diagnosis. In ankylosing spondylitis, sacroiliitis is usually bilateral, symmetric, and gradually progressive over years. The lesions progress from blurring of the subchondral bone plate to irregular erosions of the margins of the sacroiliac joints (pseudowidening) to sclerosis, narrowing, and finally fusion. Erosions of the subchondral bone of the sacroiliac joint are generally seen earlier in the lower portion of the joint (because this portion is lined by synovium) and on the iliac side (due to the thinner cartilage covering this side of the joint).

 The spondylitis of ankylosing spondylitis starts in the lumbar or thoracolumbar spine and progresses proximally in a continuous fashion. The radiographic signs of ankylosing spondylitis 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 these bodies, resulting in loss of the normal concave contour of the anterior surface of the vertebral bodies. 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). Ossification of the annulus fibrosus leads to the radiographic appearance of syndesmophytes, which, in ankylosing spondylitis, are typically marginal. Over time, development of continuous (bridging) syndesmophytes may result in a bamboo spine, which is essentially fused.

Radiography
Sacroiliitis occurs early in the course of ankylosing spondylitis and is regarded as a hallmark of the disease. Radiographically, the earliest sign is indistinctness of the joint. The joints initially widen before they narrow. Subchondral bony erosions on the iliac side of the joint are seen (see Image 1); these are followed by subchondral sclerosis and bony proliferation.

 Image 1

Bilateral sacroiliitis. Frontal radiograph shows bilateral sacroiliac joint erosions and iliac side subchondral sclerosis.

 With eventual bony fusion, the sclerosis resolves (see Image 2). At the end stage, the sacroiliac joint may be seen as a thin dense line, or it may not be visible at all. Sacroiliitis typically is symmetric, although it may be asymmetric in the early stages of the disease. In the spine, the early stages of spondylitis are manifested as small erosions at the corners of the vertebral bodies. The areas are surrounded by reactive sclerosis and have been termed the shiny corner sign or Romanus lesion (see Image 3).

Image 2

Bilateral chronic sacroiliitis. Frontal radiograph shows complete fusion of both sacroiliac joints.

 Romanus lesions. Lateral radiograph shows anterior corner erosions at the T12 and L1 vertebral bodies. The typical shiny corner sign (or Romanus lesion) is present (arrows).

Image 3

 Squaring of the vertebral body is another characteristic feature of ankylosing spondylitis; it is caused by a combination of corner erosions and periosteal new bone formation along the anterior aspect of the vertebral body. This is best seen in the lumbar spine, in which the anterior cortex of the vertebral body normally is concave. This is followed by syndesmophyte formation; this term refers to the process in which ossification of the outer fibers of the annulus fibrosis leads to bridging of the corners of one vertebra to another (see Image 4). Ossification of the adjacent paravertebral connective tissue fibers also occurs. Posterior interspinous ligament ossification, combined with linking of the spinous process, produces an appearance of a solid midline vertical dense line on frontal radiographs (see Image 5).

Image 4
Vertebral body squaring. Lateral radiograph shows squaring of L3 and L4 vertebral bodies, L3-L4 anterior syndesmophyte, and lumbar facet joint fusion.

Image 5
Interspinous ossification. Frontal radiograph shows T12-L2 lateral syndesmophytes and interspinous ligament ossification extending from the T12 to L1 and L2 to L4 levels.

 The apophyseal and costovertebral joints frequently are affected by erosions and eventually undergo fusion (see Image 6). Complete fusion of the vertebral bodies by syndesmophytes and other related ossified areas produces bamboo spine (see Image 7). Calcifications of the disk may occur at single or multiple levels; they are usually associated with apophyseal joint ankylosis and adjacent syndesmophytes (see Image 8).

Image 6
Vertebral fusion. Lateral radiograph shows solid ankylosis of all cervical facet joints from C2 downwards. Extensive anterior and posterior syndesmophytes is noted.

Image 7
Bamboo spine. Frontal radiograph shows complete fusion of the vertebral bodies. Extensive facet joint ankylosis and posterior ligamentous ossification produce the trolley track appearance.

Image 8
Disk calcification. Lateral radiograph shows L2-L3 and L3-L4 disk calcifications, as well as L2-L4 anterior syndesmophytes.

 For patients with established ankylosing spondylitis, fractures usually occur at the thoracolumbar (see Image 9) and cervicothoracic junctions. Upper cervical spine fractures and atlantoaxial subluxation rarely are seen. Fractures typically are transverse, extend from anterior to posterior, and frequently pass through the ossified disk. They have been termed chalk stick fractures (see Image 10). Pseudoarthrosis is seen radiographically as areas of diskovertebral destruction and adjacent sclerosis. The changes, which are referred to as the Andersson lesion, may resemble disk infection, although pseudoarthrosis usually develops secondarily to a previously undetected fracture or at an unfused segment. Therefore, an important imaging feature is the involvement of the posterior elements, seen as a linear hypodense area with sclerotic borders (see Image 11).

Image 9
Thoracolumbar junction fracture. Lateral radiograph shows features of established ankylosing spondylitis. A T12 vertebral body fracture is noted, with disruption of the ossified anterior longitudinal ligament (arrow). An old L1 compression fracture is present.

Image 10
Chalk stick fracture. Lateral radiograph shows a fracture through the ankylosed cervical spine, producing a gap at the C6-C7 disk.

Image 11
Pseudoarthrosis. Lateral radiograph shows a T11-T12 diskovertebral lesion with adjacent sclerosis (Andersson lesion; arrow). Posterior element defect is present (arrowheads). The patient also has a severe kyphotic deformity.

Magnetic resonance imaging and computed tomography scanning

MRI or CT scanning of the sacroiliac and peripheral joints may reveal evidence of early sacroiliitis, erosions, and enthesitis that are not apparent on standard radiographs. MRI using fat-saturating techniques such as short tau inversion recovery (STIR) or MRI with gadolinium are sensitive for inflammatory lesions of enthesitis. However, they are not part of the routine evaluation of patients because of the expense of these studies. Because of the insensitivity of standard radiography in the clinical setting of acute back pain in advanced ankylosing spondylitis, an MRI and a CT scan may be useful in diagnosis of a spinal fracture in patients with late-stage spinal disease.

 Bilateral sacroiliitis. Axial CT scan shows erosions and iliac side subchondral sclerosis of both sacroiliac joints.

 Pseudoarthrosis. Reconstructed midsagittal CT image shows an L1-L2 diskovertebral lesion with adjacent sclerosis.

 Bilateral facet joint ankylosis. Axial CT scan shows complete fusion of both T12L1 facet joints.

 Lateral lumbar spine X-ray demonstrating in ankylosing spondylitis.

 X-ray showing bamboo spine in a patient with ankylosing spondylitis.

 Magnetic resonance images of sacroiliac joints. Shown are T1-weighted semi-coronal magnetic resonance images through the sacroiliac joints (a) before and (b) after intravenous contrast injection. Enhancement is seen at the right sacroiliac joint (arrow, left side of image), indicating active sacroiliitis. This patient had psoriatic arthritis, but similar changes can occur in ankylosing spondylitis.

Diagnosis
There is no direct test to diagnose AS. A clinical examination and X-ray studies of the spine, which show characteristic spinal changes and sacroiliitis, are the major diagnostic tools. A drawback of X-ray diagnosis is that signs and symptoms of AS have usually been established as long as 8-10 years prior to X-ray-evident changes occurring on a plain film X-ray, which means a delay of as long as 10 years before adequate therapies can be introduced. Options for earlier diagnosis are tomography and magnetic resonance imaging of the sacroiliac joints, but the reliability of these tests is still unclear.

 During acute inflammatory periods, AS patients will usually show an increase in the blood concentration of C-reactive protein (CRP) and an increase in the erythrocyte sedimentation rate (ESR). Variations of the HLA-B gene increase the risk of developing ankylosing spondylitis, although it is not a diagnostic test. Those with the HLA-B27 variant are at a higher risk than the general population of developing the disorder. HLA-B27, demonstrated in a blood test, can occasionally help with diagnosis but in itself is not diagnostic of AS in a person with back pain. Over 95% of people that have been diagnosed with AS are HLAB27 positive, although this ratio varies from population to population.

New York Criteria (1984) Low back pain with inflammatory characteristics Limitation of lumbar spine motion in sagittal and frontal planes Decreased chest expansion Bilateral sacroiliitis grade 2 or higher Unilateral sacroiliitis grade 3 or higher Definite ankylosing spondylitis when the fourth or fifth criterion mentioned presents with any clinical criteria

Rome Criteria (1961) Low back pain and stiffness for >3 months that is not relieved by rest Pain and stiffness in the thoracic region Limited motion in the lumbar spine Limited chest expansion History of uveitis Diagnosis of ankylosing spondylitis when any clinical criteria present with bilateral sacroiliitis grade 2 or higher

Differential Diagnoses
Lumbar Disc Disease Lumbar Spondylosis Psoriatic Arthritis

Reactive Arthritis

Treatment
No cure is known for AS, although treatments and medications are available to reduce symptoms and pain. Physical therapy and exercise, along with medication, are at the heart of therapy for ankylosing spondylitis. Physiotherapy and physical exercises are clearly to be preceded by medical treatment in order to reduce the inflammation and pain and are commonly followed by a physician. This way the movements will help in diminishing pain and stiffness, while exercise in an active inflammatory state will just make the pain worse. Medical professionals and experts in AS have widely speculated that maintaining good posture can reduce the likelihood of a fused or curved spine which occurs in a significant percentage of diagnosed persons.

Medication
There are three major types of medications used to treat ankylosing spondylitis. Anti-inflammatory drugs, which include NSAIDs such as aspirin, ibuprofen, phenylbutazone, indomethacin, naproxen and COX-2 inhibitors, which reduce inflammation, and consequently pain. DMARDs such as cyclosporin, methotrexate, sulfasalazine, and corticosteroids, used to reduce the immune system response through immunosuppression;

Corticosteroids
Oral corticosteroids are occasionally helpful in controlling symptoms; however, use them only for short-term management. No evidence has shown that corticosteroids alter the outcome of the disease, and they increase the tendency toward spinal osteoporosis. Local corticosteroid injections are useful for symptomatic sacroiliitis, peripheral enthesitis, and arthritis, although the response is not typically as rapid as in patients with rheumatoid arthritis.

TCM
Acupuncture and moxibustion Orthopaedic manipulations Tuina Herbs: baijiezi 10, lujiaojiao 15, mahuanggen 6, shudi 10, jiangtan 15, chaihu 10, jianghuang 10, gegen 15, zhigancao 5

Physical therapy
All physical therapies must be approved in advance by a rheumatologist, since movements that normally have great benefits to one's health may harm a patient with AS; massages and physical manipulations should only be practiced by therapists familiar with this disease. Some of the therapies that have been shown to benefit AS patients include: Physical therapy/Physiotherapy, shown to be of great benefit to AS patients; Slow movement muscle extending exercises like stretching, yoga, climbing, tai chi, Pilates method, etc.

 Physical therapy, including an exercise program and postural training, is important to maintain function. Spinal extension and deep-breathing exercises help maintain spinal mobility, encourage erect posture, and promote chest expansion. Maintaining an erect posture during daily activities and sleeping on a firm mattress with a thin pillow also tend to reduce the tendency toward thoracic kyphosis. Water therapy and swimming are excellent activities to maintain mobility and fitness. Swimming, one of the preferred exercises since it involves all muscles and joints in a low gravity environment.

Prognosis
AS can range from mild to progressively debilitating and from medically controlled to refractive. Unattended cases of AS normally lead to knee pain and may be accompanied by dactylitis or enthesitis, which may result in a misdiagnosis of normal rheumatism. Typical signs of progressed AS are the visible formation of syndesmophytes on X-rays and abnormal bone outgrowths similar to osteophytes affecting the spine. The fusion of the vertebrae paresthesia is a complication due to the inflammation of the tissue surrounding nerves. Organs commonly affected by AS, other than the axial spine and other joints, are the heart, lungs, colon, and kidney. Other complications are aortic regurgitation, Achilles tendinitis.

Thank you for your attention !