Delay in diagnosis of juvenile-onset ankylosing spondylitis results in significant functional impairment

A delay in diagnosis of juvenile-onset ankylosing spondylitis (JoAS) may have profound consequences, according to a study published in the June 15, 2005 issue of Arthritis & Rheumatism. JoAS patients end up with more functional impairment than those diagnosed with adult-onset ankylosing spondylitis (AoAS), with females faring worse than their male counterparts, the new research suggests.

“It’s important to understand that with AS, there is a large delay between when patients develop symptoms and when they actually receive a diagnosis for the disease. This is because traditionally the diagnostic criteria have included the need for x-ray changes, which take many years to develop, and it’s also because of the many myths surrounding the disease, such as women don’t get it, you can’t get it after age 40, it doesn’t occur in childhood, or if you don’t have the [HLA B47] gene, you can’t get it,” first author Dr Millicent Stone (University of Toronto and St Michael’s Hospital, ON) tells rheumawire in an interview. “This research certainly helps to dispel some of those myths.”Largest group of JoAS patients ever reportedThe study is the first in North American AS patients comparing functional outcome between adults and children and is so far the largest published to date. “The emerging messages from these results are that you really need to diagnose and have a high level of awareness of the possibility of this disease, especially in children, and to treat it earlier,” Stone tells rheumawire. She notes that clinicians should suspect AS if a child is very stiff, symptoms last longer than six weeks, and there is possible involvement of the hips, knees, or leg tendons. Stone also says that physicians need to be keen in spotting inflammation-type back painpain and stiffness that improve with exercise. “The worst thing you can do is send these patients to bed,” she says.Stone et al undertook a cross-sectional study of 326 JoAS patients (defined as those developing symptoms before age 16) who responded to a survey conducted by the Spondylitis Association of America, which also commissioned the study. This group was compared with 2021 AoAS (symptom development after age 16) patients who also participated in the study. A validation cohort of 255 AS patients, whose AS was confirmed by a treating physician, was used to substantiate the findings of the survey group.Clinical and demographic features were compared between the two groups using simple and multiple logistic regression analyses, and functional impairment was measured using the Bath Ankylosing Spondylitis Functional Index (BASFI). At the time the survey was conducted, JoAS patients had mean disease duration of 18.3+0.70 years compared with 13.4+23 years for AoAS patients (p<0.001). Delay in diagnosis differed significantly between the two groups15.3+0.79 years for JoAS patients compared with 7.6+0.2 years for those with AoAS (p<0.001). "Furthermore, women with JoAS were more likely to have severe functional impairment, as defined by a BASFI score >50, earlier in the disease course as compared with men,” the researchers write. Still, the distribution of BASFI scores between the two groups was not huge, with JoAS patients having a mean score of 51.3+1.5, with an interquartile range of 72 to 30, compared with AoAS patients (46.4+0.57; interquartile range of 66-25). Noting that so far there have been no studies performed to assess small differences in the BASFI scores, the researchers said that, in looking at 10 mean BASFI subscales, those relating to the lumbar spine and cervical spine showed the greatest difference between the two groups. “The clinical relevance of this may be that patients with JoAS have more severe axial symptoms than those with AoAS,” the researchers write. Among the other findings, 171 JoAS patients classified as having severe functional impairment were also found to have the greatest delay in diagnosis compared with JoAS patients without severe impairment16.7+0.9 vs 11.9+0.8 years, respectively. Peripheral joint symptoms were more prevalent in JoAS patients than their adult counterparts46.6% vs 33.2% (p<0.001). Disease duration and lower income also appeared strongly associated with poorer outcome, the researchers noted.The weakness of the study, the authors point out, comes from the limits inherent in a cross-sectional analysis, and despite a large sample size representing a good sampling of 48 US states, there was only a 30% response rate to the survey. Moreover, the study design does not allow for a "definitive conclusion about prognostic indicators of outcome," they write. Other weaknesses were the fact that the patients were self-reporting as well as possible misdiagnoses. However, there were no differences between the study patients and those in the validation cohort, so this is unlikely to be a real concern, Stone points out. More treatment options now The physician's toolbox for treating AS has more options now than it did several years ago, Stone comments. Physiotherapy, of course, is still the mainstay of treatment and is effective for about 50% of patients. Stone now divides her time between Toronto and the Royal National Hospital for Rheumatic Diseases in Bath, UK, where she directs the AS physiotherapy program. Her team in Bath is developing a specific AS Pilates program. "Pilates strengthens the spine, so it's a very suitable exercise when delivered and managed by people who know about AS," she tells rheumawire.The other tools now available to clinicians include MRI (which can pick up changes in the spine before damage occurs), anti-inflammatory drugs, and, most recently, TNF blockers. "We've been using TNF blockers for AS in Canada since 2000," Stone says. "They're an exciting new treatment for AS and are being used in children with good results," says Stone. The drugs work well in AS because these patients don't have a lot of comorbidities such as those found in rheumatoid-arthritis patients, so they tend to have a less serious side-effect profile, she notes. Clinical data show that about 70% of patients have a mild to moderate response to the treatment, 50% have a very good response, and 20% to 30% have a dramatic response. Stone emphasizes that she is not advocating TNF-blocker use in all patients; however, those patients who are more likely to develop disabilities, such as those with childhood onset as reported in this study, and those with elevated inflammatory markers of disease activity would be good candidates for this therapeutic option. "The important points in the study are that we've shown again there is a delay in diagnosis of AS and that this delay is huge in people who develop symptoms younger than 16 years of age," Stone says. And while the researchers acknowledge that the question remains whether earlier treatment of AS results in the prevention of disease progression, suggesting future studies to address the issue, Stone concludes, "Clinicians need to be aware of symptoms and red flags that may suggest these 'growing pains' may not be growing pains but something worse, such as AS, and have a heightened awareness that we do need to treat people earlier." (Source: Stone M, Warren RW, Bruckel J, et al. Juvenile-onset ankylosing spondylitis is associated with worse functional outcomes than adult-onset ankylosing spondylitis. A cross-sectional analysis. Arthritis Rheum 2005; 53:445-451: Pubmed: Joint and Bone: July 2005.)