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Thursday, June 4, 2009

Ankylosing spondylitis

Ankylosing spondylitis is a chronic inflammatory disorder of multiple articular and para-articular structures that principally involves the axial skeleton. It usually affects the sacroiliac joints and the spinal facet joints of the vertebrae. It sometimes involves the appendicular skeleton as well, such as the joints of the greater trochanter, patella, and calcaneum. Other extraspinal manifestations include iritis/uveitis and pulmonary involvement. The basic pathologic lesion of ankylosing spondylitis occurs at the entheses, which are sites at which ligaments, tendons, and joint capsules attach to bone. In the outer layers of the annulus fibrosis of the intervertebral disks, the condition manifests as a formation of new bone. The name of the disease is derived from Greek; "ankylos" means stiffening of a joint, and "spondylos" means vertebra. The disease is classified as a chronic and progressive form of seronegative arthritis. Ankylosing spondylitis affects men 4-10 times more frequently than women, and the symptoms generally appear in those aged 15-35 years. More than 90% of whites with ankylosing spondylitis have the HLA-B27 gene, but 6-8% of those with this gene do not develop the disease.

Symptoms of ankylosing spondylitis include back pain and stiffness, peripheral joint and chest pain, sciatica, anorexia, weight loss, and low-grade fever. The back pain associated with this condition is typically transient at first, but it eventually becomes persistent. It is usually worse in the mornings and resolves with exercise. A typical patient may also complain of waking up with back pain at night. The pain is usually centered over the sacrum, but it may radiate to the groin, buttocks, and down the legs. With time, the back pain usually progresses up the spine and affects the rib cage, resulting in a restriction of chest expansion and diaphragmatic breathing (observed as ballooning of the abdomen during inspiration) as the costovertebral joints become affected. The cervical spine is ankylosed late in the course of the disease, leading to restriction in neck movement and head rotation. Without treatment, the spine eventually becomes completely rigid, with loss of the normal curvatures and movement.

On physical examination, the loss of lateral flexion of the lumbar spine is the earliest objective sign of spinal involvement. The sacroiliitis may be detected by eliciting a tenderness response during percussion over the sacroiliac joints. Objective tests to quantify spinal restriction include touching the toes, the Schober test, and measurement of chest expansion. Additional physical findings include restriction of motion in the peripheral joints and tenderness over the enthuses. The physical exam should also include evaluation for signs of potentially serious cardiovascular and pulmonary complications, such as aortic incompetence secondary to aortitis, conduction defects of the heart, cardiomyopathy, pericarditis, apical fibrosis of the lungs, bronchiectasis, cavitation of the chest, and development of a restrictive ventilatory pattern. Other associated conditions include the development of inflammatory bowel disease, uveitis (in up to 20% of patients), radiculitis secondary to inflamed nerves, and, rarely, amyloidosis.

Specific criteria for the diagnosis of ankylosing spondylitis include the Rome criteria (developed in 1963) and the New York criteria (developed in 1968). Although these criteria have been generally accepted as useful, limitations are recognized and overlaps exist among the clinical and radiologic features of various seronegative spondyloarthropathies. Sacroiliitis is the hallmark of ankylosing spondylitis and is a requisite for the diagnosis under both sets of criteria. Other conditions, such as psoriasis, Reiter disease, enteropathic arthropathy, hyperparathyroidism, and osteitis condensans ilii, may also result in bilateral symmetric sacroiliac joint disease and should be considered in the differential diagnosis. Ankylosing spondylitis may also present with asymmetric sacroiliitis, which may be more characteristic of other conditions, such as psoriasis, Reiter disease, rheumatoid arthritis, and gouty arthritis. Radiographically, diffuse idiopathic skeletal hyperostosis (DISH) has a similar appearance to ankylosing spondylitis; however, DISH typically occurs at a later age and does not involve the sacroiliac joint.

The radiographic changes usually first appear in the sacroiliac joints, followed by the thoracolumbar and lumbosacral spine; this is in line with the natural progression of the disease. The disease then proceeds cephalad up the spine; however, the cervical spine may also be affected without involvement of the thoracic or lumbar spine. Radiographically evident peripheral-joint abnormalities are seen in more than 50% of patients. Abnormalities can also be seen in the symphysis pubis and in the manubriosternal, sternoclavicular, and temporomandibular joints. Spinal findings include osteitis, syndesmophytosis, diskovertebral erosions and destruction (Romanus lesions), and disk calcification. Radiographically, joint involvement appears as joint-space narrowing, periostitis, osseous erosion, and minimal periarticular osteoporosis (less than that seen with rheumatoid arthritis). Sacroiliac joint involvement is usually bilateral and symmetric.

Common laboratory findings are an elevated erythrocyte sedimentation rate (during the acute phase), a positive HLA-B27 histocompatibility antigen, mild leukocytosis, normochromic normocytic anemia (anemia of chronic disease), and negative results for rheumatoid factor.

The general principles of managing chronic arthritis also apply to ankylosing spondylitis. Among the various nonsteroidal anti-inflammatory drugs (NSAIDs) available to treat the disease, indomethacin may be the most effective. The lowest dose that provides pain relief should be used in order to avoid potentially serious complications, such as gastritis, peptic ulcer disease, and renal insufficiency. Sulfasalazine can be useful if peripheral arthritis is substantial, but it may be less effective when spinal and sacroiliac pain are the most prominent symptoms. In the majority of patients, the symptoms persist for life, although in some cases remission does occur.

Physical therapy and exercise can help prevent axial immobility. Specifically, spinal extension and deep-breathing exercises maintain spinal mobility, encourage erect posture, and promote chest expansion. Maintaining an erect posture and sleeping on a firm mattress with a thin pillow can help reduce thoracic kyphosis. Severe hip or spinal involvement may require surgical repair. Antitumor necrosis factor (anti-TNF) agents, such as infliximab and etanercept, are relatively new but often very effective therapeutic agents that may be considered for patients with pain refractory to other interventions.

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