Extra-Musculoskeletal Manifestations in Axial Spondyloarthritis

The chronic back pain of axial spondyloarthritis (axSpA) may be accompanied after diagnosis by three primary extra-musculoskeletal manifestations — uveitis, psoriasis, or inflammatory bowel disease (IBD). These manifestations can also precede a long delay in axSpA diagnosis.

“Axial spondyloarthritis, an immune-mediated inflammatory disease, not only affects the axial and peripheral skeleton, but also has other systemic extra-musculoskeletal manifestations in various other organs such as the eyes, gut, and skin,” said Atul Deodhar, MD, of Oregon Health & Science University (OHSU) in Portland.

Around 20% of people with axSpA have symptoms affecting joints or organs in addition to the axial skeleton, reported Deodhar and Mohamad Bittar, MD, MS, also of OHSU, in a recent review in JAMA. These can include peripheral inflammatory arthritis, enthesitis, or dactylitis (sausage digits).

Up to 45% of axSpA patients experience acute anterior uveitis in their lifetime, Deodhar and Bittar stated, with several studies showing the prevalence of uveitis at about 25%. About 10% to 15% of axSpA patients have psoriasis, and 8% have IBD, they added.

“Rheumatologists should consider co-management of axSpA patients with an ophthalmologist, gastroenterologist, or dermatologist depending upon which extra-musculoskeletal manifestation is present,” Deodhar told MedPage Today.

“The presence of one or more of these manifestations in patients with chronic back pain helps in making the initial diagnosis of axSpA, and later also informs choice of therapy,” he added.

Because sacroiliitis or spondylitis may be observed in both psoriatic and IBD-associated arthritis, it can sometimes be difficult to identify whether a disease is primarily axSpA with comorbid psoriasis or IBD, or primarily psoriatic disease or IBD with concomitant axial inflammation, Deodhar and Bittar noted.

Guidelines from the Assessment of Spondyloarthritis International Society and the European Alliance of Associations for Rheumatology (ASAS-EULAR) reflect the role extra-articular manifestations may play in axSpA treatment. The ASAS-EULAR recommendations advise that if there is a history of recurrent uveitis or active IBD, preference should be given to a monoclonal antibody against tumor necrosis factor (TNF). In patients with significant psoriasis, an interleukin (IL)-17 inhibitor may be preferred.

Effects on Disease Burden

Extraskeletal manifestations can significantly affect axSpA disease burden, observed Elaine Husni, MD, MPH, of the Cleveland Clinic.

“Awareness of these comorbidities allows rheumatologists to provide holistic care and tailor treatment strategies effectively,” she told MedPage Today.

For axSpA patients with acute anterior uveitis, “early detection and interdisciplinary care can prevent permanent eye complications and optimize patient outcomes,” Husni pointed out. Acute anterior uveitis, which often presents with ocular pain, erythema, and photophobia, may be associated with vision loss.

Manifestations of IBD include not only Crohn’s disease and ulcerative colitis but subclinical gut inflammation, she added. “Rheumatologists must remain vigilant for these manifestations to ensure comprehensive care and timely gastroenterological referral,” she said.

Psoriasis may be underdiagnosed, too: 13% of axSpA patients reported having psoriasis symptoms with a positive self-screening in a recent study, but only half of those patients had a confirmed prior psoriasis diagnosis in their medical records.

In a prospective observational cohort study of 2,419 people with axSpA across the U.K., one in three patients (32%) had at least one extraskeletal manifestation — uveitis, IBD, or psoriasis — before receiving biological therapy. Of these, 84.1% had one manifestation, 15.3% had two, and 0.5% of the participants had all three.

Uveitis was most common; in multivariable analyses, acute anterior uveitis was directly associated with the presence of human leukocyte antigen (HLA)-B27 and inversely associated with smoking. IBD and psoriasis were less common and were inversely associated with HLA-B27.

Screening to Improve Diagnoses

A 2024 scoping review led by Joerg Ermann, MD, of Brigham and Women’s Hospital and Harvard Medical School in Boston, highlighted that the extra-articular manifestations of spondyloarthritis (SpA), a group of inflammatory disorders that includes axSpA, may precede articular features by several years and sometimes are the first reason patients seek medical care.

Patients in ophthalmology, dermatology, and gastroenterology clinics with acute anterior uveitis, psoriasis, or IBD may have undiagnosed SpA, Ermann and colleagues noted. Diagnoses of SpA, particularly axSpA, are frequently delayed by several years and screening for SpA in patients with psoriasis, uveitis, or IBD may lead to earlier diagnosis and improved outcomes, they wrote in Arthritis Care & Research.

The group assessed screening tools for SpA and identified 13 tools for people with psoriasis, two for people with uveitis, and three for people with IBD. All were questionnaires except one physician-applied algorithm for uveitis. The tools varied in length (average completion time was 5 minutes) as well as scoring, threshold scores, and content.

The researchers found substantial heterogeneity in the spectrum of clinical SpA features included in the tools and in other design aspects.

“Although these tools show promise for use within a specific target population, none are generalizable to all patients with extra-musculoskeletal manifestations at risk of SpA,” Ermann and co-authors concluded. “Future studies should explore the utility of a generic patient-oriented SpA screening tool that can be applied to patients with psoriasis, uveitis, or IBD; is easy to use and comprehend, and captures all clinical domains of SpA.”