PARIS — Earlier diagnosis of ankylosing spondylitis has emerged as a high priority—and MRI is vital in accomplishing it, according to Dr. Martin Rudwaleit.
The average interval between onset of symptoms of ankylosing spondylitis (AS)—chiefly inflammatory low back pain—and the time of diagnosis is 6–10 years. This is unacceptable given the pain and progressive disability patients are subjected to during these long years of delay, he said.
Moreover, AS, a disease with an estimated prevalence of about 0.5%, has its onset predominantly in young adulthood. Symptoms occur by age 30 in 80% of cases and by age 45 in 95%. So the lengthy delays in diagnosis, which often involve extensive work absenteeism and deteriorating quality of life, take place during what would ordinarily be among the most productive years of life.
A major reason for the long delay in diagnosis is that the standard diagnostic criteria for AS used for nearly the past quarter century—the 1984 modified New York criteria—require unequivocal radiographic evidence of sacroiliitis. Because x-ray changes are a late-disease manifestation, they typically don't appear until years after symptom onset.
Long before the classic radiographic findings are evident, however, active inflammatory lesions are present on MRI, stressed Dr. Rudwaleit, a rheumatologist at the University Hospital Charité, Berlin.
Bone marrow edema located periarticularly, adjacent to the sacroiliac joint space, indicates active inflammatory osteitis. This is the most important MRI finding in establishing the diagnosis of AS, he added.
Another big reason for the long delay in diagnosis is that the core clinical features required under the modified New York criteria—namely, restricted spinal mobility and restricted chest expansion—are, like the radiographic changes, late-disease manifestations. Similarly, the distinctive postural changes often considered pathognomonic for AS aren't apparent until the disease is well along.
Dr. Rudwaleit and coworkers have proposed a new diagnostic algorithm for AS. It focuses on identifying disease in the preradiographic stages and relies upon MRI and HLA-B27 testing (Ann. Rheum. Dis. 2004;63:535-43). The criteria are now undergoing minor alterations in a multicenter validation study, in which 650 patients with chronic low back pain have been enrolled to date.
“We think diagnosis of axial spondyloarthritis without radiographic changes is feasible in daily clinical practice,” he said at the annual European Congress of Rheumatology.
As part of the effort to develop improved diagnostic criteria, he and his coworkers have devised a simpler method for differentiating inflammatory from mechanical low back pain. The distinction is critical because inflammatory low back pain is the earliest and most important symptom of AS. The diagnostic challenge arises from the fact that AS accounts for only 5% of chronic low back pain.
By analyzing the clinical histories of 101 patients with confirmed AS and 112 others with mechanical low back pain, Dr. Rudwaleit and coworkers identified four parameters that best discriminated between the two: morning stiffness of more than 30 minutes' duration, improvement of back pain with exercise but not with rest, nighttime awakening due to back pain during only the second half of the night, and alternating buttock pain. When any two of these four criteria were met, the sensitivity and specificity for inflammatory back pain were 70% and 81%, respectively (Arthritis Rheum. 2006;54:569-78).
But the presence of inflammatory back pain doesn't suffice to make the diagnosis of AS; that requires additional criteria, ideally including a positive MRI, which has the greatest sensitivity and specificity of the various diagnostic criteria, according to Dr. Rudwaleit.
He and his coworkers have developed a method of calculating AS probability derived by multiplying the likelihood ratios (LRs) of the individual AS parameters. For example, a positive MRI carries an LR of 9.0 based upon its high sensitivity and specificity. If a patient has a positive MRI plus inflammatory back pain, which has an LR of 3.1, plus heel pain, with an LR of 3.4, and elevated acute phase reactants, with an LR of 2.5, the resultant LR product is 237, indicating a greater than 90% probability of AS.
The MRI findings are so important in diagnosing early AS that Dr. Rudwaleit considers a clearly positive MRI to be a prerequisite for anti-tumor necrosis factor therapy. Anti-TNF agents have proved highly effective in AS. There is hope that their early use can prevent or at least retard disease evolution. The definitive evidence for this isn't in yet, but it's an exciting possibility that has added further impetus to efforts to diagnose AS earlier.
STIR MRIs (right top, bottom) show inflammation next to the sacroiliac joints (white) not seen on x-ray (left). Images courtesy Dr. Martin Rudwaleit