RΗEUMATOLOGY CENTER limassol

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Dr. Maria Michailidou

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  General Considerations


Ankylosing spondylitis is regarded as the prototype of the spondyloarthropathies. Axial skeletal involvement predominates in ankylosing spondylitis, which invariably involves the sacroiliac joints and typically presents with the insidious onset of inflammatory low back pain during late adolescence or early adulthood. Onset of symptoms after the age of 40 is uncommon.


Although environmental factors are important in the development of ankylosing spondylitis, the environmental triggers appear to be ubiquitous, and genetic background is the major determinant of susceptibility to ankylosing spondylitis. The only known susceptibility gene, HLA-B27, confers a relative risk of close to 100 but probably accounts for only 10–50% of the overall genetic risk for ankylosing spondylitis.


The disease course varies considerably, ranging from mild disease with little impact on functional status to severe disease that produces substantial disability. The extent of spinal involvement is a major determinant of the impact of the disease on functional status. Unfortunately, there are no reliable predictors of long-term functional outcome early in the disease course.


Clinical Findings


Symptoms and Signs in ankylosing spondylitis


Axial Spine


The typical presenting symptom in ankylosing spondylitis is the insidious onset of inflammatory low back pain due to sacroiliitis. The pain is dull and located in the lower lumbar regions, although some describe a deep alternating buttock pain. The characteristic inflammatory nature of the pain differentiates it from mechanical back pain; most notably, the pain worsens with rest, improves with activity, and is accompanied by morning stiffness that lasts 30 minutes or longer. Patients often describe awakening from sleep and pacing in order to relieve nocturnal pain— a rare complaint in patients with mechanical back pain.


There may be few objective findings in patients with early disease, making diagnosis a challenge. Palpation and specific maneuvers can elicit pain in the sacroiliac joints, but these tests are relatively insensitive and nonspecific due to the number of other anatomic structures that overlap within the same area.


Involvement of the spine (spondylitis) is the major source of morbidity. Unlike rheumatoid arthritis, which only affects the cervical spine, ankylosing spondylitis can involve the lumbar, thoracic, and cervical spine. Over time the accumulation of pathologic changes can lead to loss of spinal mobility, particularly of the lumbar spine. The Schober test is the standard examination to assess impaired lumbar flexion. Two marks are made on the patient's back: one at the level of the sacral dimples (approximately at the fifth lumbar spinous process) and the other 10 cm above. The patient then bends forward as far as possible (ie, attempts to touch toes with knees extended), and the distance between the two marks is again measured. In normal individuals, the overlying skin will stretch to 15 cm; values less than this can be indicative of reduced lumbar mobility. Some clinicians prefer the modified Schober test in which marks are made 5 cm below and 10 cm above the sacral dimples; the distance between these marks increases from 15 cm to at least 20 cm with lumbar flexion. Reductions in lumbar lateral bending and rotation are also commonly observed. Spinal fusion results in irreversible impairments, but reductions in mobility also can be induced by pain or muscle spasm and, therefore, vary somewhat with time and treatment. With advancing disease, a characteristic posture often develops as the spine fuses in flexion, leading to loss of lumbar lordosis, exaggeration of thoracic kyphosis, an inability to extend the neck, and compensatory hip flexion deformities



Peripheral Joint Manifestations


Peripheral arthritis, typically monarticular or asymmetric oligoarticular, develops in approximately one-third of patients with ankylosing spondylitis and most often affects large joints of the lower extremities. Hip disease is a major source of morbidity.


Enthesitis


Involvement of insertion sites around the pelvis (the ischial tuberosities, iliac crests, and greater trochanters) is common and appears on radiographs as bony "whiskering" at these sites of attachment. Achilles tendinitis and enthesitis at the site of the insertion of the plantar fascia onto the calcaneus can cause unilateral or bilateral heel pain, although not as often as in reactive arthritis.









Ocular


The most common extra-articular manifestation of ankylosing spondylitis is acute anterior uveitis, and one-third of patients experience at least one episode. It is heralded by the acute onset of unilateral eye pain, photophobia, blurred vision, and increased lacrimation. Ciliary flush (an increased conjunctival injection at the rim of the iris) is a characteristic finding (The presence of cells and flare in the anterior uveal chamber detected by slit-lamp examination establishes the diagnosis. The need for specialized equipment and expertise necessitates prompt ophthalmologic consultation when this diagnosis is suspected. Anterior uveitis can precede the onset of ankylosing spondylitis by several years, and a history of anterior uveitis is a helpful diagnostic clue in a patient with inflammatory back pain or other symptoms of ankylosing spondylitis. Anterior uveitis is strongly associated with HLA-B27.


Other Organs


The majority of patients with ankylosing spondylitis have histologic evidence of inflammation on biopsy specimens of the small or large bowel. These changes are asymptomatic but may be of pathogenetic importance in view of the link between clinically overt inflammatory bowel disease and spondyloarthropathy and the apparent importance of colitis in the transgenic rat model of HLA-B27-associated disease.


Cardiac involvement in the form of ascending aortitis, aortic regurgitation, conduction abnormalities, and myocardial disease occurs in approximately 10% of patients with ankylosing spondylitis, and, like uveitis and axial disease, is strongly associated with HLA-B27. The prevalence of aortic regurgitation, which is the most common cardiac problem, increases with the duration of disease but remains < 10% even after 30 years of disease.


Restriction in chest wall motion from enthesitis or bony fusion commonly produces mild impairment of pulmonary function; characteristic spirometry findings include a slight reduction of vital and total lung capacity and normal diffusion capacity. Most patients, however, are asymptomatic, and clinically significant pulmonary disease is uncommon. A rare pulmonary finding in ankylosing spondylitis is the development of apical fibrobullous disease that radiographically resembles reactivation of tuberculosis and that can become a site for bacterial or fungal infections.


Of the neurologic consequences of spondyloarthritis, the most important is spinal fracture, which often goes unrecognized and leads to neurologic compromise in about one-third of cases (see the following section, Complications). Cauda equina syndrome can develop in long-standing ankylosing spondylitis and is associated with large subarachnoid diverticula on magnetic resonance imaging.


Rare manifestations of the spondyloarthropathies include the late development of secondary amyloidosis. An association of ankylosing spondylitis with retroperitoneal fibrosis has been suggested.


Laboratory Findings in ankylosing sponylitis


Routine laboratory investigations often reveal a mild, normocytic, normochromic anemia, reflective of chronic disease. Only about half of patients with active disease will have elevations of the erythrocyte sedimentation rate or C-reactive protein. These inflammatory markers appear to correlate more with peripheral arthritis than the activity of axial skeleton disease. There is no association with rheumatoid factor or antinuclear antibodies.


No laboratory test is diagnostic of ankylosing spondylitis or the other spondyloarthropathies. Inheritance of HLA-B27 is strongly associated with these diseases, but testing for HLA-B27 has limited usefulness in clinical practice. Several key facts should inform the use and the interpretation of this test. First, inheritance of HLA-B27 is not sufficient to produce spondyloarthropathy. The great majority of HLA-B27-positive persons (95% in some studies) do not have a spondyloarthropathy, and indiscriminate testing for HLA-B27 will produce many more false-positive tests for spondyloarthropathy than true positives. Second, inheritance of HLA-B27 is not absolutely essential for the development of a spondyloarthropathy (. Third, the strength of the association between HLA-B27 and disease varies according to the presence of axial involvement and the specific spondyloarthropathy (. Fourth, there are important ethnic differences in the prevalence of HLA-B27 in normal populations. Finally, although HLA-B27 confers an increased relative risk of spondyloarthropathy in most ethnic groups studied, ethnicity influences the prevalence of HLA-B27 in disease populations. For example, HLA-B27 is present in 8% of the general white population, and 90% of whites with ankylosing spondylitis are HLA-B27 positive. In contrast, HLA-B27 is present in 2% of the African American population and in 50% of African Americans with ankylosing spondylitis. Therefore, in a patient with symptoms suggestive of ankylosing spondylitis, the absence of HLA-B27 substantially decreases the probability of disease if the patient is white but not if the patient is African American.


Nonsteroidal Anti-Inflammatory Drugs


Almost all patients are prescribed at least one nonsteroidal anti-inflammatory drug (NSAID) during the course of the disease. These agents can provide significant reductions in pain, although many patients require additional pharmacologic agents. Of the NSAIDs currently available, indomethacin is commonly mentioned as the most effective, although this is mainly based on anecdotal clinical experience. As in other rheumatic diseases, there can be a wide individual variation in response to a given agent, and it is reasonable to prescribe what is most effective with the least amount of toxicity for each individual patient.


Disease-Modifying Antirheumatic Drugs (DMARDs)


NSAIDs alone do not control the symptoms of many patients. Sulfasalazine has established efficacy in treating the peripheral arthritis of ankylosing spondylitis but does not appear to be of benefit for disease of the axial skeleton. The typical therapeutic dose is 2–3 g/d in divided doses. Methotrexate is sometimes used; the rationale for this is based mainly on its efficacy in rheumatoid arthritis, as controlled studies are lacking.


Intravenous bisphosphonates have recently been demonstrated to effectively treat the pain and inflammation of both the peripheral and axial disease of spondyloarthropathy. Pamidronate is typically given as a 30–60-mg intravenous dose monthly for 6 months. Acute arthralgia, myalgia, and fever after the first infusion are not uncommon, but reactions are generally mild and usually decrease with continued treatment.


Etanercept and infliximab, both anti-tumor necrosis factor (TNF) therapies, have dramatic and rapid efficacy in the therapy of the ankylosing spondylitis and the other spondyloarthropathies. The main toxicities include injection site or infusion reactions and a slight increase in minor uncomplicated infections. Serious toxicities, although uncommon, include reactivation of tuberculosis, the induction of demyelinating disease, and possibly an increase in lymphoproliferative diseases. Since the long-term safety of these agents is still relatively unknown, treatment should not be undertaken lightly and patients should be properly advised of potential risks.


Other Pharmacologic Therapies


Systemic glucocorticoids are not commonly used and can worsen osteopenia. In certain cases, intra-articular glucocorticoid injection into the sacroiliac joint can provide short-term symptomatic relief. However, the anatomy of the joint is extremely complicated, and radiographic guidance for this procedure is required.


Surgical Therapy


The deformities that result from extensive disease of the spine can lead to disabling decreases in the field of vision and ambulation. Corrective surgeries of spinal alignment, however, are major procedures and have limited indications. Typically, osteotomy with fixation is performed, with corrections of the lumbar spine being most common. Neurologic complications and perioperative mortality are not insignificant with these procedures.


Hip involvement requires artificial replacement in approximately 5% of patients with ankylosing spondylitis. The outcome of total hip arthroplasty is good, with long-term joint survival of 60% at 20 years. The occurrence of postoperative heterotopic bone formation is increased in those undergoing repeat hip surgery and those with more spinal ankylosis.





ANKYLOSING SPONDYLITIS

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