Clinical Challenges: Diagnosing Axial Spondyloarthritis

The diagnosis of axial spondyloarthritis (axSpA) can be highly challenging because its hallmark symptom — chronic back pain — is experienced by some 20% of adults at some point in their lives.

Yet axSpA only accounts for 0.5% to 1% of those cases, “so axSpA is lost within a sea of chronic back pain,” said Liron Caplan, MD, PhD, of the University of Colorado in Aurora.

The pain of axSpA is inflammatory and immune system-related rather than musculoskeletal or mechanical, which can be associated with causes ranging from trauma to degenerative disc disease. “There’s a lot of musculoskeletal back pain out there that has no clear relationship to the immune system,” Caplan told MedPage Today.

A second obstacle in the diagnosis of axSpA is that there is no reasonable objective biomarker available to narrow down the group of patients with this condition from among the larger pool of patients with chronic back pain. Unlike patients with rheumatoid arthritis who often have specific autoantibodies, such as rheumatoid factor and anti-cyclic citrullinated peptide, and elevated inflammatory markers, such as erythrocyte sedimentation rate and C-reactive protein, specific markers have remained elusive and inflammatory markers are not consistently elevated in axSpA.

The genetic marker HLA-B27 is common in patients with this condition, but its presence varies widely among the background population, being higher in northern regions and low in areas such as southern Africa.

An additional challenge in diagnosis is the possibility that the patient has not been referred to a rheumatologist. Because axSpA often is accompanied by nonspinal manifestations such as anterior uveitis, psoriasis, or inflammatory bowel disease (IBD), patients may have been seen by ophthalmologists, dermatologists, or gastroenterologists less experienced with the spinal disease.

“Patients are often not referred to a rheumatologist for many years, thus delaying their access to effective medications to control their pain and potentially alter their course of disease,” said Dalit Ashany, MD, of the Hospital for Special Surgery and Weill Cornell Medical College in New York City.

Clues to the Diagnosis

Family history is a major clue. “If you take 100 people who are just HLA-B27-positive, five of them will develop axSpA,” said Atul Deodhar, MD, of Oregon Health & Science University in Portland. “But if you have someone who is HLA-B27-positive and has a first-degree relative who has ankylosing spondylitis, the likelihood increases from 5% to 20%,” Deodhar said. Even a family history of the related autoimmune diseases (uveitis, IBD) is suggestive, he told MedPage Today.

The nature of the back pain also can be informative, being most severe in the morning, accompanied by stiffness, and worsening with rest.

Other clues include young age at symptom onset; the presence of enthesitis or peripheral arthritis, usually of the lower limbs; and a prompt response to nonsteroidal anti-inflammatory drugs. The Assessment of Spondyloarthritis International Society has recommended that a patient younger than 45 who has chronic back pain (persisting for 3 months or longer) and one or more of those features be referred to a rheumatologist.

The conventional approach to imaging has centered on radiographs of the sacroiliac joints, but it is now widely recognized that radiographic changes typically are not visible until actual joint damage has occurred, which often does not occur until years after the onset of symptoms, with a mean delay of 6.5 years in men and 8.8 years in women.

But imaging is becoming critical in the diagnosis, according to Caplan. “MRI in particular is increasingly recognized as an extremely useful imaging modality, particularly when used with newer sequences and read by someone with experience in the diagnosis of axSpA,” he said.

“Radiographs are a fast way of identifying advanced disease, so if that’s all that is available, it does have a role, though a limited one,” he added.

Monitoring the Disease

Following the diagnosis, patients must be routinely monitored to determine their prognosis and response to treatment.

Clinical monitoring can be straightforward using a composite index such as the Ankylosing Spondylitis Disease Activity Score (ASDAS), which consists of questions about axial pain, peripheral pain and inflammation, duration of morning stiffness, and global disease activity, which the patient rates on scales of 0 to 10. The patient’s overall disease activity then can be classified as inactive, with an ASDAS score below 1.3; low activity, with a score below 2.1; high activity, with a score between 2.1 and 3.5; or very high activity, with a score above 3.5.

A clinically important improvement is defined as a decrease of 1.1 points, while a major improvement is a decrease of 2 points. Flare is defined as an increase of 0.9 points or more since the time of last disease assessment.

Other monitoring instruments focus on overall physical function, using the Bath Ankylosing Spondylitis Functional Index, with scores ranging from 0 (indicating good function) to 10 (meaning poor function); and mobility of the spine, using the Bath Ankylosing Spondylitis Metrology Index.

The acute-phase reactants C-reactive protein and erythrocyte sedimentation rate also are often measured, but are elevated in fewer than half of patients and are helpful in monitoring disease only in a minority of patients with axSpA.

In 2019, treatment recommendations for axSpA were published by the American College of Rheumatology in conjunction with the Spondylitis Association of America and the Spondyloarthritis Research and Treatment Network. In this document, the expert panel conditionally recommended obtaining spinal or pelvic MRI to assess disease activity for patients who are undergoing biologic treatment. “Because physical and laboratory measures are often normal despite active axSpA, and because symptoms may be nonspecific, it may be difficult to know if a patient is experiencing inflammation that warrants a change in treatment,” they wrote.

They also conditionally recommended against obtaining routine radiographs of the spine, such as every 2 years, for patients on any type of therapy, explaining that while spinal radiographs can reveal developments such as spinal fusion, “there is no evidence that monitoring serial changes in spine radiographs at a regular interval leads to better patient outcomes.”

A Final Thought

“The most important thing is getting the word out to our healthcare practitioner colleagues and patients that there’s a lot we can do for this disease,” Caplan said. “If we remain vigilant to its presence and not overlook it in patients with back pain, we could avert 4 to 10 or more years of suffering by making an early diagnosis,” he concluded.

Nancy Walsh earned a BA in English literature from Salve Regina College in Newport, R.I.

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