Hope in ankylosing spondylitis
Finally, we have drugs that can make a real difference
Vol.17, No.08, October 2009

The first description of AS is credited to Bernard Conner, a 17th-century Irish physician. But AS has also gone by the eponyms of Marie-Strumpell’s or Von Bechterew’s disease, after the 19th-century doctors who also contributed to its description. We know today that the powerful Egyptian warrior pharaoh Ramses II, whose mummy survives, was an early sufferer.

AS is a chronic inflammatory disease that primarily affects the axial skeleton and progressively limits spinal mobility. Sacroiliitis is the hallmark. The etiology is unknown, but there’s a strong genetic predisposition associated with the human leukocyte antigen (HLA)-B27 tissue type.

AS is one of the most important causes of back pain leading to permanent disability. It’s a treatable disorder, but the average delay to diagnosis exceeds 8 years. Recent criteria for inflammatory back pain (IBP) in adults < 50 years old (Table 1) have been proposed to allow early diagnosis.

Clinical characteristics

AS begins insidiously, in late adolescence and early adulthood, with back pain and stiffness due to inflammation of the sacroiliac joints, the spine and sites of bony attachment of ligaments. Hip and shoulder joints and, to a lesser extent, the peripheral joints may be involved. Some patients may exhibit acute anterior uveitis. The ratio of men to women is 2:1.

Complete physical and musculoskeletal examinations are mandatory. Table 2 lists 6 tests that suggest axial involvement.

Laboratory findings

No test is diagnostic. B27 is present in approximately 90% of patients (though only a small minority of people with this tissue type develop AS). Erythrocyte sedimentation rate and C-reactive protein are often elevated. Anemia may be present. Rheumatoid factor and antinuclear antibodies are generally absent. The synovial fluid is inflammatory.

Radiographic findings

The earliest radiological changes of sacroiliitis are blurring of the cortical margins of the subchondral bone, followed by erosions and sclerosis. Progression of the erosions leads to “pseudowidening” of the joint space; as fibrous and then bony ankylosis develops, the joints may become obliterated. The lesions are usually symmetric.

Progression of the disease leads to lumbar straightening, and to reactive sclerosis, caused by osteitis of the anterior corners of the vertebral bodies with subsequent erosion, leading to “squaring” of their bodies. Progressive ossification leads to formation of marginal syndesmophytes, visible on plain films as bony bridges connecting successive vertebral bodies anteriorly and laterally. MRI and CT scans can detect abnormalities at an earlier stage than plain radiography.

A breakthrough in treatment

An exercise program is mandatory, to preserve posture, thoracic expansion and range of motion.

Hip arthroplasty is the most common surgery. It’s performed with success in destructive hip disease. Occasionally, correction of extreme flexion deformities of the spine or of atlantoaxial subluxation is indicated. These surgeries are performed in rare cases only, and can be risky.

Anti-inflammatory drugs may reduce pain and increase mobility. Radiographic progression is slower in patients taking these drugs daily than in those taking them only as needed. Many patients will see symptoms and underlying progression continue despite NSAID treatment.

Sulfasalazine has shown modest benefit, primarily for peripheral arthritis. Methotrexate hasn’t demonstrated any usefulness in AS.

There is, however, a dramatic response to anti-TNF-α therapy. Patients with AS treated with infliximab, etanercept, adalimumab or more recently golimumab have shown rapid, profound, and sustained reductions in all clinical and laboratory measures. It’s yet to be determined whether radiographic progression is slowed.

Infliximab is given as an intravenous infusion while etanercept, adalimumab and golimumab are given by subcutaneous injection. The tumour necrosis factor blocking agents have a good safety profile, when weighed against their efficacy, but the following side effects have been reported: serious infections, including disseminated tuberculosis; hematologic disorders, such as pancytopenia; demyelinating disorders; exacerbation of congestive heart failure; systemic lupus erythematosus–related autoantibodies and clinical features; hypersensitivity to infusion or injection site reactions; and severe liver disease.

Increased incidence of malignancy is of concern. The FDA has just issued a warning of such risk in children, but it hasn’t been observed in adult patients treated for up to 5 years.

The high cost of TNF blockers is an obstacle to their widespread use. They aren’t considered first line therapy and various criteria must usually be met before reimbursement is allowed in private and public regimes. In essence, the patient must have failed conservative treatment.

Monique Camerlain, MD, FRCPC, and Myhal Daniel MD, CSPQ are on staff with the Service de Rhumatologie at the Centre Hospitalier Universitaire de Sherbrooke, QC.

Table 1 - Proposed criteria for inflammatory back pain

From Rudwaleit et al. Arthritis Rheum 2006;54:678-81

  • morning stiffness of more than 30 minutes
  • improvement of back pain with exercise, aggravation with rest
  • awakening during the second half of the night because of back pain
  • alternating buttock pain

If two of the above four parameters are present, IBP is present. Sensitivity 70.3%, specificity 81.2%.

Table 2 - Tests to assess sacroiliac tenderness and progression of spinal disease
  • Occiput-to wall test. Demonstrates loss of cervical range of motion
  • Decreased chest expansion: normal expansion, at the 4th intercostal space, is about 5 cm.
  • Schober’s test. A mark is drawn at the level of the posterior superior iliac spine and another 10 cm above in the midline. With normal forward flexion the distance increases by 5 cm.
  • Pelvic compression. Compression with the patient lying on his side will cause pain in the sacroiliac joints
  • Gaenslen’s test: The patient lies on his back and draws a leg on his chest while the other is dropped over the side of the table. The sacroiliac joint on the side of the dropped leg is painful.
  • Patrick’s test. The heel is placed on the opposite knee. Pressure is applied on the flexed knee, the hip being in flexion, abduction and external rotation. Pain is elicited in the contralateral sacroiliac joint.

References

  1. Khan M.A. Ankylosing Spondylitis, the facts. Oxford University Press 2002 p 7
  2. West S.G. Rheumatology Secrets. Hanley & Belfus, 1997 p 213-214
  3. Taurog, Joel D, “Chapter 318. The Spondyloarthritides” (Chapter). Fauci AS, Braunwald E, Kasper DL, Hauser SL, Longo DL, Jameson JL, Loscalzo J: Harrison’s Principles of Internal Medicine, 17th Edition: http://www.access medicine.com/content.aspx?aID=2862753
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