To the Editor:

Radiographic axial spondyloarthritis (r-axSpA), also known as ankylosing spondylitis (AS), is a disease in which symptoms generally occur in the second or third decade of life. Inflammatory back pain, the quintessential AS clinical feature, is defined in part by early onset of symptoms and thus can exclude patients with late-onset disease.1,2 AxSpA onset ≥ 50 years of age is uncommon. Different studies have estimated the frequency of late-onset axSpA from 3% to 8%.3-6 Given the modest occurrence, late-onset axSpA studies have been limited, making our understanding incomplete. We sought to characterize the clinical presentation of late-onset AS by comparing it to early-onset disease.

The Prospective Study of Outcomes in Ankylosing Spondylitis (PSOAS) is a prospective longitudinal multicenter cohort study to evaluate AS outcomes. This study comprises 1253 patients who meet the modified New York (mNY) criteria for AS.7 Out of this cohort, we examined 33 patients with AS with late-onset disease (defined by age of self-reported symptom onset) at age ≥ 50 years and 411 patients with disease onset at age < 20 years at baseline. Radiographs of the pelvis, cervical spine, and lumbar spine were performed. Data collected included demographic factors (age, gender, exercise, smoking history, uveitis, peripheral arthritis, family history of AS), baseline laboratory data (HLA-B27 status, C-reactive protein [CRP], and erythrocyte sedimentation rate [ESR]), associated clinical factors (including disease activity as measured by the Bath Ankylosing Spondylitis Disease Activity Index [BASDAI]), and physical functional limitation (as measured by the Bath Ankylosing Spondylitis Functional Index [BASFI] scores).7

Univariable comparisons of clinical characteristics between categories were conducted using chi-square or Fisher exact test for categorical variables and Wilcoxon rank-sum test for nonnormal continuous variables. ANOVA and Kruskal-Wallis tests were used to compare groups stratified by HLA-B27 status.

Among the 1253 patients in the PSOAS cohort, there were 33 (2.6%) patients with disease onset at age ≥ 50 years and 411 (32.8%) patients with early disease onset at < 20 years of age (Table 1). We found important differences in clinical manifestations of the disease between those with late-onset compared to early-onset AS. The cervical modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) between those with late-onset disease (17/36, IQR 2-26) compared to early (0/36, IQR 0-12) was greater (P < 0.001), despite those with late-onset AS having much shorter disease duration (5 yrs, IQR 2-12) than those with early onset (21 yrs, IQR 13-34). Peripheral arthritis, defined as physician-reported joint swelling, was more common among those with late-onset disease (46.6% vs 29.5%, P = 0.05). In contrast, HLA-B27 positivity was lower in the late-onset AS group compared to the early-onset group (53.1% vs 86.7%, P < 0.001). No significant difference in uveitis prevalence was noted in patients with early-onset vs late-onset disease (34.4% vs 22.5%, P = 0.24). When stratified by HLA-B27 status, higher prevalence of uveitis was noted in patients who were HLA-B27 positive compared to those who were HLA-B27 negative, but only in patients with early-onset AS (Table 2). Similar levels of presenting disease activity and physical functional limitation were found between the 2 groups, as measured by BASDAI and BASFI.

Characteristics of patients with late-onset vs early-onset AS from the PSOAS cohort (n = 444).

Characteristics of patients from the PSOAS cohort with late-onset vs early-onset AS by HLA-B27 status (n = 439).

AS disease onset ≥ 50 years of age is rare, and we sought to compare it to early-onset disease. We found that late-onset AS had a different clinical presentation compared to early-onset disease in terms of peripheral arthritis, uveitis, radiographic cervical spine disease, and HLA-B27 frequency.

Previous studies of late-onset AS had similar findings in terms of peripheral arthritis, cervical symptoms (eg, pain, limited mobility), and HLA-B27 frequency in different patient populations.3-6,8,9 Unlike in previous studies, we did not find a statistically significant difference in uveitis, although this may be partly related to our small sample size. The potentially lower uveitis finding in late-onset AS may be explained in part by the shorter disease duration and overall lower HLA-B27 status in late-onset AS. We also did not observe differences in enthesitis or dactylitis as in some previous studies.5,10

Our study had limitations. Recall bias may have occurred in those with late-onset disease, where mild symptoms of earlier onset may not have been detected or reported, which would account for radiographic changes despite the shorter self-reported disease duration. Psoriatic arthritis with axial involvement (also known as psoriatic spondylitis that fulfilled mNY criteria), which could present later in life and potentially explain differences observed, was not well captured. How disease-specific patient-reported outcome constructs perform in these different subpopulations may also differ. The small sample of patients with late-onset AS may obscure the effect of HLA-B27 positivity. Also, the concern could be raised as to whether the higher cervical mSASSS scores found in our patients with late-onset AS reflected age-associated osteophytes. All imaging, however, was scored by a central musculoskeletal radiologist experienced in distinguishing differences between osteophytes and syndesmophytes, who was blinded to patient identity and age.

Late-onset AS remains an understudied subgroup of patients that may possess different clinical manifestations compared to those with typical AS. Further studies are needed to discover if these subgroups differ as well in their prognosis and response to therapy.

All authors meet the criteria for authorship, have read and approved all versions of this manuscript and its submission, and have given necessary attention to ensure the integrity of the work.

The Prospective Study of Outcomes in Ankylosing Spondylitis (PSOAS) cohort is supported by grants from the US Department of Health and Human Services, National Institutes of Health (NIH), National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS; P01-052915-06), and the Spondylitis Association of America. This work was supported by the Biostatistics/Epidemiology/Research Design (BERD) component of the Center for Clinical and Translational Sciences (CCTS), funded by the National Center for Advancing Translational Sciences (NCATS), awarded to the University of Texas Health Science Center at Houston (UL1TR003167). We acknowledge the support provided by the Biostatistics/Epidemiology/Research Design (BERD) component of the UTHealth Center for Clinical and Translational Sciences (CCTS) for this project. CCTS is mainly funded by the NIH Centers for Translational Science Award (UL1TR000371) by the National Center for Advancing Translational Sciences (NCATS). Management of data for this study was done using REDCap, and was partly supported by a grant from NCATS/NIH (UL1TR000445), awarded to Vanderbilt University. MMW is supported by the Intramural Research Program, NIAMS, NIH.

The authors declare no conflicts of interest relevant to this article.