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Clinical spectrum of ankylosing spondylitis in Korea
Joint Bone Spine 77 (2010) 235–240
Original article
Clinical spectrum of ankylosing spondylitis in Korea Tae-Jong Kim a,b , Tae-Hwan Kim a,∗ a
Department of Rheumatology, The Hospital for Rheumatic Diseases, Hanyang University College of Medicine, 17 Haengdang-Dong, Sungdong-Gu, Seoul 133-792, Republic of Korea Department of Rheumatology, Research Institute of Medical Sciences, Chonnam National University Medical School and Hospital, 8 Hak-dong, Dong-ku, Gwangju 501-757, Republic of Korea b
a r t i c l e
i n f o
Article history: Accepted 4 November 2009 Available online 30 March 2010 Keywords: Ankylosing spondylitis Juvenile-onset ankylosing spondylitis HLAB-27
a b s t r a c t Objectives: The aim of this study was to determine the clinical profile of ankylosing spondylitis (AS) in Korea. Methods: A total of 732 men and 98 women with AS were recruited for the cross-sectional component of the Hanyang University ankylosing spondylitis (HYAS) Study. All participants completed extensive questionnaires about their medical and personal histories, and two rheumatologists concomitantly performed clinical evaluation and previous medical record reviews for all participants. Results: The mean age of onset (SD) was 20.9 (8.1) years. Three hundred and ninety-one patients (47.1%) were found to have a history of peripheral arthritis. Six hundred and four patients (73.9%) were found to have a history of hip joint involvement. Two hundred and thirty-six patients (28.7%) were found to be juvenile-onset AS (JoAS) patients. The frequency of uveitis differed between the sexes (28.2% of men vs 40.8% of women; p = 0.03; OR: 1.63; 95% CI: 1.05–2.53). Peripheral arthritis (p < 0.001; OR: 4.19; 95% CI: 2.98–5.88) and hip joint involvement (p < 0.001; OR: 2.76; 95% CI; 1.77–4.29) were more frequent in JoAS group. HLA-B27 positive cases had a significantly younger age of symptom onset (by 5.3 years), more uveitis, and a higher frequency of hip joint involvement than HLA-B27 negative patients. Conclusions: The clinical features of our patients are largely similar to those in other studies, with a few noticeable differences: 1) AS patients in Korea have a higher prevalence of peripheral arthritis and hip joint involvement; 2) female patients have more uveitis, and; 3) JoAS is common in our group. © 2010 Société franc¸aise de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.
1. Introduction
2. Methods
Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease of the spine that affects 0.2–0.8% of the population [1]. AS is characterized by inflammation of the axial skeleton, sacroiliac joints, and, to a lesser degree, peripheral joints and certain extra-articular organs, including the eyes, skin, and cardiovascular system [2]. Several studies have examined the clinical features of AS according to the subjects’ race and geographic locations [2–7]. However, a precise clinical spectrum of Korean AS patients has not been determined. Therefore, the aim of this study was to determine the clinical profile of AS patients in Korea. To understand the potential influences of gender, onset age, and HLA-B27 carrier status on AS characteristics, we analyzed differences in the clinical spectra of patients according to these criteria.
2.1. Patients
∗ Corresponding author. E-mail address: [email protected] (T.-H. Kim).
Patients were recruited between September 2006 to August 2007 for the cross-sectional component of the Hanyang University Ankylosing Spondylitis (HYAS) Study from subjects referred to the rheumatologic institution. A total of 732 men and 98 women who met the modified New York criteria for AS [8] were included in this study. We excluded those patients for whom data was missing. 2.2. Clinical data All participants completed extensive questionnaires about their medical and personal histories, and two rheumatologists (TJ Kim, TH Kim) concomitantly performed clinical evaluations and previous medical record reviews. Clinical data included age, sex, duration of disease, age at onset of AS symptoms, family history of AS, history of uveitis/iritis, peripheral arthritis, enthesitis, and HLA-B27 carrier status. To measure functional disability, participants were also asked to complete the Bath Ankylosing Spondylitis Functional Index (BASFI) [9].
1297-319X/$ – see front matter © 2010 Société franc¸aise de rhumatologie. Published by Elsevier Masson SAS. All rights reserved. doi:10.1016/j.jbspin.2009.11.015
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2.3. Definition of each data type Age at symptom onset was defined as the time when the initial symptom, whether it was an axial symptom, peripheral arthritis, or enthesitis, developed. Peripheral arthritis was defined as the presence of swelling and/or restricted range of motion, and/or previous swelling in at least one peripheral joint confirmed at that time (except hip or shoulder joints). Hip joint involvement was defined as the presence of pain localized in the groin, together with lameness [10]. Enthesitis was defined as swelling and/or pain of entheses such as the Achilles tendon or plantar fascia. When symptom onset occurred in individuals of less than 16 years of age, the disease was termed juvenile-onset AS (JoAS); otherwise, it was classified as adult-onset AS (AoAS). Familial history was defined as whether the subject had any first-degree relatives (parents, siblings, or offspring) who were AS patients. All cases of uveitis were diagnosed by an ophthalmologist, and the involved patterns were described as unilateral, bilateral, or alternative during the entire disease course. Heart abnormalities were detected by electrocardiography or cardiac echocardiography.
ratio was about 8:1. One hundred and fifty-seven (19.6%) of 802 patients had a familial history of AS. Three hundred and ninety-one patients (47.1%) were found to have a history of peripheral arthritis. Six hundred and four patients (73.9%) were found to have a history of hip joint involvement. 28.7% were found to have JoAS. Seven hundred and twenty-seven (94.8%) were HLA-B27 carrier. Two hundred and twenty-four (26.9%) patients had been treated with TNF blockers. Three hundred and forty-four patients (42.7%) were found to have enthesitis, which was the most common extra-articular symptom in this survey. Two hundred and forty-six patients (29.7%) were found to have a history of uveitis. The involvement of other extraarticular organs, such as heart, kidney, and colon, was relatively uncommon. The first symptoms observed at disease onset are shown in Table 2. Lower back pain or buttock pain was the most frequent onset symptom. In peripheral joint involvement, the knee joint was the most commonly affected joint, followed by the ankle joint. Enthesitis such as Achilles tendinitis (7.2%) and plantar fasciitis (2.3%) sometimes presented as the first symptom. Rarely, other symptoms such as neck pain, chest pain, uveitis, or thigh pain were also detected as initial disease symptoms.
2.4. Statistical analyses Clinical comparisons were performed using t-tests for continuous measures that were normally distributed. Wilcoxon’s rank sum tests were performed for continuous measures that were not normally distributed, and 2 tests were used for categorical measures. A p-value < 0.05 was considered statistically significant. Logistic regression analysis was performed to adjust for age or disease duration. 3. Results 3.1. Demographic features The clinical characteristics of the subjects are presented in Table 1. The mean age (SD) of the AS patients was 33.2 (10.1) years. The mean onset age (SD) was 20.9 (8.1) years. The male to female
Although the disease duration at the time of study entry was nearly the same between the genders, women had a later age of disease onset (p = 0.05; OR: 1.03; 95% CI: 1.00–1.06). Women reported family histories of AS more frequently than men (p = 0.01; OR: 1.86; 95% CI: 1.14–3.03). The frequency of uveitis was statistically different between the sexes (28.2% of men vs 40.8% of women; p = 0.03; OR: 1.63; 95% CI: 1.05–2.53). There were no statistically significant differences in joint involvement, enthesitis, or HLA-B27 positivity between male and female patients (Table 3). Functional limitations as measured by the BASFI were not statistically different between men and women. A comparison of first symptoms between genders, failed to reveal any significant differences in onset symptoms.
3.3. Comparison between JoAS and AoAS
Table 1 Demographic features of AS patients. Features
Cases
Age, mean ± SD (years) Age at onset, mean ± SD (years) Duration of disease, mean ± SD (years) Male, n (total, %) Familial history, n (total, %) Peripheral arthritis, n (total, %) Hip joint involvement, n (total, %) JoAS, n (total, %) HLA-B27, n (total, %) TNF blocker use, n (total, %)
33.2 ± 10.1 20.9 ± 8.1 12.1 ± 8.1 732 (830, 88.2) 157 (802, 19.6) 391 (826, 47.1) 604 (817, 73.9) 236 (823, 28.7) 727 (767, 94.8) 224 (830, 26.9)
Extra-articular manifestation Enthesitis, n (total, %) Uveitis, n (total, %) Disease duration, mean (SD) (years) Unilateral (%) Bilateral (%) Alternative (%) Frequency, mean (SD) (years) One episode (%) Two episodes (%) Three episodes (%) Four episodes (%) Five episodes and more (%) Cardiac involvement, n (total, %) Renal involvement, n (total, %) Inflammatory bowel disease, n (total, %)
344 (805, 42.7) 246 (829, 29.7) 15.1 (7.8) 63.6 11.8 24.6 3.7 (4.3) 33.5 24.6 11.6 9.4 20.9 13 (806, 1.6) 32 (806, 3.9) 9 (806, 1.1)
JoAS: juvenile-onset ankylosing spondylitis.
3.2. Comparison of clinical features between men and women
There was no difference in sex distribution between the groups (Table 4). At the time of the survey, the JoAS group had more enthesitis (p < 0.001; OR: 1.89; 95% CI: 1.38–2.61) than the AoAS group. Peripheral arthritis (p < 0.001; OR: 4.19; 95% CI: 2.98–5.88) and hip joint involvement (p < 0.001; OR: 2.76; 95% CI: 1.77–4.29) were more frequent in the JoAS group. However, there were no significant differences in uveitis, BASFI, or HLA-B27 between the two groups. Comparison of symptoms at onset between the JoAS and AoAS group, revealed that lower back pain or buttock pain were more frequent in the AoAS group, but hip, knee, and ankle arthritis were more frequent in the JoAS group.
Table 2 The initial presenting symptom at disease onset. Initial symptom/sign
Number (%)
Low back pain or Buttock pain Hip joint involvement Knee joint arthritis Achilles tendinitis Ankle joint arthritis Plantar fasciitis Tarsal joint arthritis Shoulder joint pain Others
391 (47.1) 132 (15.8) 115 (13.7) 60 (7.2) 35 (4.2) 19 (2.3) 14 (1.7) 12 (1.4) 60 (7.2)
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Table 3 Comparisons between men and women with AS. Clinical features
Male (n = 720)
Female (n = 97)
p-value, OR (95% CI)
Age, mean ± SD Age at onset, mean ± SD Disease duration, mean ± SD Familial history, n (%) Enthesitis, n (%) Peripheral arthritis, n (%) Uveitis, n (%) Hip joint involvement, n (%) Shoulder involvement, n (%) BASFI, Mean ± SD HLA-B27, n (%)
32.9 ± 9.9 20.6 ± 8.0 12.1 ± 8.1 130 (18.3) 297 (41.9) 341 (46.8) 206 (28.2) 534 (75.2) 385 (56.2) 1.8 ± 1.9 638 (94.9)
35.4 ± 9.9 23.3 ± 8.9 11.9 ± 8.1 27 (29.3) 47 (48.5) 50 (51.0) 40 (40.8) 70 (72.9) 53 (60.9) 1.8 ± 2.0 89 (93.7)
0.02 0.05a , 1.03 (1.00-1.06) NS 0.01a , 1.86 (1.14-3.03) NS NS 0.03a , 1.63 (1.05-2.53) NS NS NS NS
Initial symptom/sign LBP or buttock pain, n (%) Hip joint involvement, n (%) Knee arthritis, n (%) Achilles tendonitis, n (%) Ankle arthritis, n (%) Plantar fasciitis, n (%)
342 (46.7) 128 (17.5) 106 (14.5) 50 (6.8) 29 (4.0) 18 (2.5)
46 (46.9) 14 (14.3) 9 (9.2) 12 (12.2) 3 (3.1) 1 (1.0)
NS NS NS NS NS NS
NS: not significant; BASFI: Bath Ankylosing Spondylitis Functional Index; LBP: low back pain. a Age-adjusted p-value.
3.4. Comparison between HLA-B27 positive and negative patients A comparison of HLA-B27 positive and negative groups (Table 5) demonstrated that HLA-B27 positive cases had a significantly younger age of symptom onset (by 5.3 years, p = 0.002), with more uveitis (p = 0.001) and hip joint involvement (p < 0.001) than HLAB27 negative patients. However, there was no difference in BASFI between the two groups. 4. Discussion In our study, the mean age at AS disease onset was the early twenties, with an onset after the age of 45 very rare; these findings are consistent with the published literature [2,11]. We also found that AS was eight times more common in men than in women, in contrast to Khan and van der Linden’s report [2], where it was only three times more common in men than women. There was a relatively greater degree of underdiagnosis of the disease in female than male patients. This may be because women have more peripheral arthritis, and implies that women with AS are initially being misdi-
agnosed and treated for seronegative rheumatoid arthritis instead of AS [12]. Another possibility is that women tend to have a higher threshold for seeking medical counseling than men because of a tendency to consider their back pain an insignificant symptom of their daily lives. A third possibility is that the slower and relatively incomplete progression to spinal ankylosis in female patients results on a decrease in pain over time, compared to male patients [13]. Peripheral joint involvement is a presenting feature in only 10–20% of patients and occurs during the disease course in 30–40% of patients [14]. In our patients group, 47.1% had peripheral arthritis, which was higher prevalence than reported by Kahn [15]. The proportion of hip joint involvement (73.9%) in our study was much higher than previous reports (24–41%) [3,6,16]. Our study revealed that Korean patients with AS have a higher frequency of peripheral arthritis and hip joint involvement. Furthermore, we noticed some differences in clinical features depending on the presence or absence of peripheral arthritis: patients with peripheral arthritis were younger than the patients without arthritis, and also had a higher frequency of enthesitis.
Table 4 Comparisons between juvenile-onset and adult-onset AS. Clinical features
JoAS (n = 236)
AoAS (n = 581)
p-value, OR (95% CI)
Sex (M/F) Age, mean ± SD Age at onset, mean ± SD Disease duration, mean ± SD Familial History, n (%) Enthesitis, n (%) Peripheral arthritis, n (%) Uveitis, n (%) Hip joint involvement, n (%) Shoulder involvement, n (%) BASFI, Mean ± SD HLA-B27, n (%)
215/21 28.3 ± 8.6 13.1 ± 2.5 15.0 ± 8.0 54 (23.7) 123 (53.9) 171 (72.5) 83 (35.2) 204 (87.6) 133 (60.7) 1.85 ± 2.1 221 (97.8)
510/71 35.0 ± 9.8 24.0 ± 7.5 10.9 ± 7.9 102 (17.8) 220 (38.2) 218 (37.3) 160 (27.3) 399 (69.8) 304 (55.1) 1.80 ± 1.9 500 (93.5)
NS < 0.001 < 0.001 < 0.001 NS < 0.001a , 1.89 (1.38-2.61) < 0.001a , 4.19 (2.98-5.88) NS < 0.001a , 2.76 (1.77-4.29) NS NS NS
Initial symptom/sign LBP or buttock pain, n (%) Hip joint involvement, n (%) Knee arthritis, n (%) Achilles tendonitis, n (%) Ankle arthritis, n (%) Plantar fasciitis, n (%)
46 (19.5) 61 (25.8) 71 (30.1) 24 (10.2) 19 (8.1) 5 (2.1)
341 (58.1) 81 (13.8) 44 (7.5) 37 (6.3) 13 (2.2) 14 (2.4)
< 0.001 < 0.001 < 0.001 NS < 0.001 NS
NS: not significant; JoAS: juvenile-onset ankylosing spondylitis; AoAS: adult-onset ankylosing spondylitis; BASFI: Bath Ankylosing Spondylitis Functional Index; LBP: low back pain. a Disease duration adjusted p-value.
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Table 5 Comparison of the clinical features between HLA-B27 positive and negative groups. Clinical features
HLA-B27 positive (n = 727)
HLA-B27 negative (n = 40)
p-value
Age, mean ± SD Age at onset, mean ± SD Disease duration, mean ± SD Male, n (%) JoAS, n (%) Enthesitis, n (%) Peripheral arthritis, n (%) Uveitis, n (%) Hip joint involvement, n (%) Shoulder involvement, n (%) BASFI, Mean ± SD
32.9 ± 9.8 20.5 ± 7.9 12.3 ± 8.0 638 (94.9) 221 (30.7) 307 (43.5) 352 (48.6) 228 (31.4) 547 (77.6) 394 (58.1) 1.8 ± 1.9
33.8 ± 12.6 25.8 ± 9.9 11.1 ± 10.3 34 (85.0) 5 (12.5) 18 (47.4) 19 (47.5) 3 (7.5) 20 (50) 19 (54.3) 1.6 ± 1.6
NS 0.002 NS NS 0.013 NS NS 0.001 <0.001 NS NS
Initial symptom/sign LBP or buttock pain, n (%) Hip joint involvement, n (%) Knee arthritis, n (%) Achilles tendonitis, n (%) Ankle arthritis, n (%) Plantar fasciitis, n (%)
332 (45.7) 130 (17.9) 105 (14.4) 56 (7.7) 29 (4.0) 17 (2.3)
20 (50.0) 2 (5.0) 7 (17.5) 2 (5.8) 1 (2.5) 1 (2.5)
NS 0.03 NS NS NS NS
NS: not significant; JoAS: juvenile-onset ankylosing spondylitis; BASFI: Bath Ankylosing Spondylitis Functional Index; LBP: low back pain.
Although AS typically presents in the late teens or early twenties, it can present in childhood. Among patients with AS, the prevalence rates for juvenile-onset vary from 9 to 21% in Western populations [15,17]. However, according to our study, the prevalence of JoAS is higher (28.7%) in Korea than that reported for Western JoAS. Between 20–30% of patients with AS have been found to suffer from uveitis attacks [18,19], and the uveitis associated with AS is usually unilateral. An attack of uveitis has been suggested to cause a breakdown in the blood–aqueous barrier [20]. This phenomenon could promote recurrence in the same eye. In our study, most uveitis was unilateral, and among the uveitis patients, more than one episode of uveitis was generally observed, consistent with a previous report [21]. The mean frequency of attacks (SD) was 3.7 (4.3) times. Extra-articular organ involvement is rarely observed in AS patients. The prevalence of aortic incompetence was reported to be 10.1% in patients who had had spondylitis for 30 years, compared with 1% in those who had the disease for only 5 years [22]. The incidence of atrioventricular conduction block was shown to increase with the duration of the disease from 0.6% after 5 years of disease to 8.5% after 30 years [22]. In this survey, 13 patients (1.6%) had cardiac defects, and eight of those patients had cardiac conduction abnormalities. Renal involvement has been reported in approximately 10% of AS patients [23]. In our study, 32 patients (3.9%) had renal problems. However, we did not perform renal function monitoring at regular intervals, so the observed nephropathy may be due to a number of undiagnosed cases. The prevalence of inflammatory bowel disease (IBD) in AS has been reported to be between 2.6% (three out of 118 patients) and 3.8% (three out of 79 patients) [24]. In this survey, nine subjects (1.1%, one with Crohn’s disease, the remainder with ulcerative colitis) had IBD. Although a number of patients suffered from bowel discomfort, it was difficult to confirm IBD using colonoscopy, which may be the reason for the discrepancies between studies. In AS patients from Brazil, the predominant initial presenting symptoms were inflammatory back pain (61.9%) and peripheral arthritis (22.4%) [3]. Baek et al. [25] reported that chronic back pain was the presenting symptom in approximately 75% of AS patients in Korea. It is clear from the results of our study and others that pain in the low back or buttock is the most frequent onset symptom in AS. Among the peripheral joints, the knee joint was the most commonly affected site, followed by the ankle joint. Enthesitis such as Achilles tendonitis (7.2%) and plantar fasciitis (2.3%) were also
initial presenting symptoms. Rarely, neck pain, chest pain, uveitis, or thigh pain was detected as initial symptoms. AS appears to manifest 2 to 4 years later in women than men [26]. Despite the disease duration at the time of study, entry being nearly equal between the genders, our data also showed that AS developed later in women than in men, consistent with previous reports. It is known that females are more susceptible to rheumatoid disease. Thus gender appears to be an important risk factor, with relatives of male patients having the greatest cumulative risk of rheumatoid arthritis [27]. However, AS affects mainly men, with relatives of female patients more at risk [28]. Women have a greater family prevalence of AS than men [29], and this finding is reflected by our results. Previous clinical studies [30,31] reported a significantly higher prevalence of peripheral arthritis in women. However, we did not find differences in peripheral joint, hip, or shoulder joint involvement between genders. Most studies [26,32] showed that there were no differences in uveitis between genders, but uveitis in females was more common in this study, similar to Marks et al.’s report [31]. It has been demonstrated that the disease course of AS is more benign and the radiologic progression is slower in women than in men [29,33]. However, the functional outcomes were the same in this study. After adjusting for radiographic spinal damage, women were found to report worse functioning than men at any given level of radiographic damage [29], Additional analyses of functional measures in men and women are required to assess radiologic damages. There were no differences in onset symptoms between genders. Although AoAS and JoAS share many common features, they also differ in many respects. A greater portion of patients with JoAS have enthesitis than patients with AoAS [33]. JoAS patients have more peripheral arthritis, whereas AoAS patients have a greater prevalence of spinal disease [34,35]. Hip joint involvement is significantly higher in JoAS than in AoAS patients [34]. Our study confirmed that patients with JoAS more frequently have symptoms such as enthesitis, peripheral arthritis, and hip joint involvement. Furthermore, it has been reported that more patients with AoAS have positive family histories than those with JoAS [34]. This could be partly related to the fact that this disease manifests late and that siblings of children with JoAS may not yet show symptoms of the disease [34]. These results did not occur in our study. Differences in functional outcome according to the age of onset have also been reported. In a study that compared JoAS with AoAS patients, JoAS patients were shown to have worse functional outcomes [36]. In
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another study, no difference was observed between AoAS and JoAS patients [37]. In our study, there was no significant difference in functional outcome between the AoAS and JoAS groups. Different sample sizes and the dearth of a common definition of outcomes makes direct comparisons between studies difficult. In addition, several phenotypic manifestations of JoAS exist that may account for differences in determining functional outcomes. Compared with adults, patients with JoAS more commonly have initial symptoms in joints outside of the trunk. Because the diagnosis of JoAS relies on the same criteria as used for its adult counterpart, the early diagnosis of JoAS tends to be difficult. Therefore, there is a need to develop and standardize diagnostic criteria for JoAS. It has been reported that HLA-B27 positive cases have an earlier age of onset [38,39] than HLA-B27 negative cases and are more likely to develop acute anterior uveitis [40,41]. Consistent with these previous findings, we found a significant association between an earlier age of symptom onset and higher uveitis frequency, and between an earlier symptom onset and HLA-B27 presence. Furthermore, we found that hip joint involvement was more frequent in the HLA-B27 positive group. Thus, it is clear that the HLA-B27 antigen plays an important role in the pathogenesis of AS. This study had some limitations. It was based on subjects referred to our hospital for rheumatic diseases. Moreover, questioning patients about symptom onset is fraught with recall bias. A prospective study of patients from the date of symptom onset is the only way to prevent recall bias. Although spinal mobility should be measured using the Bath Ankylosing Spondylitis Metrology Index (BASMI), a validated quantitative index that reflects axial segmental involvement [42], these measurements were not performed in this study. Physicians now commonly use patient-derived instruments such as Bath Ankylosing spondylitis Disease Activity Index (BASDAI) as a “gold standard” for measuring disease activity, whereas there is no appropriate evidence that patients and physicians perceive disease activity similarly. BASDAI is entirely patient-reported, therefore reflecting only a part of the entire construct of disease activity [43]. For this reason, we did not analyze disease activity (BASDAI) findings in this study. However, strengths of this study include the large number of patients, diagnosed and confirmed by two specialized rheumatologists. The clinical features of our patients appear largely similar to those in other studies, with the following noticeable differences: 1) AS patients in Korea have a higher prevalence of peripheral arthritis and hip joint involvement; 2) female patients have more uveitis; 3) JoAS appears to be more common in Korea. Conflict of interest statement This study was supported by a grant of the Korea Healthcare technology R & D project, Ministry for Health, Welfare and Family Affairs, Republic of Korea (A084794). References [1] Braun J, Bollow M, Remlinger G, et al. Prevalence of spondylarthropathies in HLA-B27 positive and negative blood donors. Arthritis Rheum 1998;41:58–67. [2] Khan MA, van der Linden SM. A wider spectrum of spondyloarthropathies. Semin Arthritis Rheum 1990;20:107–13. [3] Sampaio-Barros PD, Bertolo MB, Kraemer MH, et al. Primary ankylosing spondylitis: patterns of disease in a Brazilian population of 147 patients. J Rheumatol 2001;28:560–5. [4] Mau W, Zeidler H, Mau R, et al. Clinical features and prognosis of patients with possible ankylosing spondylitis. Results of a 10-year follow-up. J Rheumatol 1988;15:1109–14. [5] Boyer GS, Templin DW, Goring WP. Evaluation of the European Spondylarthropathy Study Group preliminary classification criteria in Alaskan Eskimo populations. Arthritis Rheum 1993;36:534–8.
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[30] Kidd B, Mullee M, Frank A, et al. Disease expression of ankylosing spondylitis in males and females. J Rheumatol 1988;15:1407–9. [31] Marks SH, Barnett M, Calin A. Ankylosing spondylitis in women and men: a case-control study. J Rheumatol 1983;10:624–8. [32] Gran JT, Ostensen M, Husby G. A clinical comparison between males and females with ankylosing spondylitis. J Rheumatol 1985;12:126–9. [33] Lee JH, Jun JB, Jung S, et al. Higher prevalence of peripheral arthritis among ankylosing spondylitis patients. J Korean Med Sci 2002;17:669– 73. [34] Aggarwal A, Hissaria P, Misra R. Juvenile ankylosing spondylitis – is it the same disease as adult ankylosing spondylitis? Rheumatol Int 2005;25:94–6. [35] Burgos-Vargas R. Juvenile-onset spondyloarthropathies: therapeutic aspects. Ann Rheum Dis 2002;61(Suppl. 3):iii33–9. [36] Garcia-Morteo O, Maldonado-Cocco JA, Suarez-Almazor ME, et al. Ankylosing spondylitis of juvenile-onset: comparison with adult-onset disease. 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[39] Rudwaleit M, Haibel H, Baraliakos X, et al. The early disease stage in axial spondylarthritis: results from the German Spondyloarthritis Inception Cohort. Arthritis Rheum 2009;60:717–27. [40] Khan MA, Kushner I, Braun WE. Comparison of clinical features in HLA-B27 positive and negative patients with ankylosing spondylitis. Arthritis Rheum 1977;20:909–12. [41] Saari M, Vuorre I, Kaila J, et al. Family studies of ocular manifestations in arthritis. Can J Ophthalmol 1978;13:144–51.
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Original article
Clinical spectrum of ankylosing spondylitis in Korea Tae-Jong Kim a,b , Tae-Hwan Kim a,∗ a
Department of Rheumatology, The Hospital for Rheumatic Diseases, Hanyang University College of Medicine, 17 Haengdang-Dong, Sungdong-Gu, Seoul 133-792, Republic of Korea Department of Rheumatology, Research Institute of Medical Sciences, Chonnam National University Medical School and Hospital, 8 Hak-dong, Dong-ku, Gwangju 501-757, Republic of Korea b
a r t i c l e
i n f o
Article history: Accepted 4 November 2009 Available online 30 March 2010 Keywords: Ankylosing spondylitis Juvenile-onset ankylosing spondylitis HLAB-27
a b s t r a c t Objectives: The aim of this study was to determine the clinical profile of ankylosing spondylitis (AS) in Korea. Methods: A total of 732 men and 98 women with AS were recruited for the cross-sectional component of the Hanyang University ankylosing spondylitis (HYAS) Study. All participants completed extensive questionnaires about their medical and personal histories, and two rheumatologists concomitantly performed clinical evaluation and previous medical record reviews for all participants. Results: The mean age of onset (SD) was 20.9 (8.1) years. Three hundred and ninety-one patients (47.1%) were found to have a history of peripheral arthritis. Six hundred and four patients (73.9%) were found to have a history of hip joint involvement. Two hundred and thirty-six patients (28.7%) were found to be juvenile-onset AS (JoAS) patients. The frequency of uveitis differed between the sexes (28.2% of men vs 40.8% of women; p = 0.03; OR: 1.63; 95% CI: 1.05–2.53). Peripheral arthritis (p < 0.001; OR: 4.19; 95% CI: 2.98–5.88) and hip joint involvement (p < 0.001; OR: 2.76; 95% CI; 1.77–4.29) were more frequent in JoAS group. HLA-B27 positive cases had a significantly younger age of symptom onset (by 5.3 years), more uveitis, and a higher frequency of hip joint involvement than HLA-B27 negative patients. Conclusions: The clinical features of our patients are largely similar to those in other studies, with a few noticeable differences: 1) AS patients in Korea have a higher prevalence of peripheral arthritis and hip joint involvement; 2) female patients have more uveitis, and; 3) JoAS is common in our group. © 2010 Société franc¸aise de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.
1. Introduction
2. Methods
Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease of the spine that affects 0.2–0.8% of the population [1]. AS is characterized by inflammation of the axial skeleton, sacroiliac joints, and, to a lesser degree, peripheral joints and certain extra-articular organs, including the eyes, skin, and cardiovascular system [2]. Several studies have examined the clinical features of AS according to the subjects’ race and geographic locations [2–7]. However, a precise clinical spectrum of Korean AS patients has not been determined. Therefore, the aim of this study was to determine the clinical profile of AS patients in Korea. To understand the potential influences of gender, onset age, and HLA-B27 carrier status on AS characteristics, we analyzed differences in the clinical spectra of patients according to these criteria.
2.1. Patients
∗ Corresponding author. E-mail address: [email protected] (T.-H. Kim).
Patients were recruited between September 2006 to August 2007 for the cross-sectional component of the Hanyang University Ankylosing Spondylitis (HYAS) Study from subjects referred to the rheumatologic institution. A total of 732 men and 98 women who met the modified New York criteria for AS [8] were included in this study. We excluded those patients for whom data was missing. 2.2. Clinical data All participants completed extensive questionnaires about their medical and personal histories, and two rheumatologists (TJ Kim, TH Kim) concomitantly performed clinical evaluations and previous medical record reviews. Clinical data included age, sex, duration of disease, age at onset of AS symptoms, family history of AS, history of uveitis/iritis, peripheral arthritis, enthesitis, and HLA-B27 carrier status. To measure functional disability, participants were also asked to complete the Bath Ankylosing Spondylitis Functional Index (BASFI) [9].
1297-319X/$ – see front matter © 2010 Société franc¸aise de rhumatologie. Published by Elsevier Masson SAS. All rights reserved. doi:10.1016/j.jbspin.2009.11.015
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2.3. Definition of each data type Age at symptom onset was defined as the time when the initial symptom, whether it was an axial symptom, peripheral arthritis, or enthesitis, developed. Peripheral arthritis was defined as the presence of swelling and/or restricted range of motion, and/or previous swelling in at least one peripheral joint confirmed at that time (except hip or shoulder joints). Hip joint involvement was defined as the presence of pain localized in the groin, together with lameness [10]. Enthesitis was defined as swelling and/or pain of entheses such as the Achilles tendon or plantar fascia. When symptom onset occurred in individuals of less than 16 years of age, the disease was termed juvenile-onset AS (JoAS); otherwise, it was classified as adult-onset AS (AoAS). Familial history was defined as whether the subject had any first-degree relatives (parents, siblings, or offspring) who were AS patients. All cases of uveitis were diagnosed by an ophthalmologist, and the involved patterns were described as unilateral, bilateral, or alternative during the entire disease course. Heart abnormalities were detected by electrocardiography or cardiac echocardiography.
ratio was about 8:1. One hundred and fifty-seven (19.6%) of 802 patients had a familial history of AS. Three hundred and ninety-one patients (47.1%) were found to have a history of peripheral arthritis. Six hundred and four patients (73.9%) were found to have a history of hip joint involvement. 28.7% were found to have JoAS. Seven hundred and twenty-seven (94.8%) were HLA-B27 carrier. Two hundred and twenty-four (26.9%) patients had been treated with TNF blockers. Three hundred and forty-four patients (42.7%) were found to have enthesitis, which was the most common extra-articular symptom in this survey. Two hundred and forty-six patients (29.7%) were found to have a history of uveitis. The involvement of other extraarticular organs, such as heart, kidney, and colon, was relatively uncommon. The first symptoms observed at disease onset are shown in Table 2. Lower back pain or buttock pain was the most frequent onset symptom. In peripheral joint involvement, the knee joint was the most commonly affected joint, followed by the ankle joint. Enthesitis such as Achilles tendinitis (7.2%) and plantar fasciitis (2.3%) sometimes presented as the first symptom. Rarely, other symptoms such as neck pain, chest pain, uveitis, or thigh pain were also detected as initial disease symptoms.
2.4. Statistical analyses Clinical comparisons were performed using t-tests for continuous measures that were normally distributed. Wilcoxon’s rank sum tests were performed for continuous measures that were not normally distributed, and 2 tests were used for categorical measures. A p-value < 0.05 was considered statistically significant. Logistic regression analysis was performed to adjust for age or disease duration. 3. Results 3.1. Demographic features The clinical characteristics of the subjects are presented in Table 1. The mean age (SD) of the AS patients was 33.2 (10.1) years. The mean onset age (SD) was 20.9 (8.1) years. The male to female
Although the disease duration at the time of study entry was nearly the same between the genders, women had a later age of disease onset (p = 0.05; OR: 1.03; 95% CI: 1.00–1.06). Women reported family histories of AS more frequently than men (p = 0.01; OR: 1.86; 95% CI: 1.14–3.03). The frequency of uveitis was statistically different between the sexes (28.2% of men vs 40.8% of women; p = 0.03; OR: 1.63; 95% CI: 1.05–2.53). There were no statistically significant differences in joint involvement, enthesitis, or HLA-B27 positivity between male and female patients (Table 3). Functional limitations as measured by the BASFI were not statistically different between men and women. A comparison of first symptoms between genders, failed to reveal any significant differences in onset symptoms.
3.3. Comparison between JoAS and AoAS
Table 1 Demographic features of AS patients. Features
Cases
Age, mean ± SD (years) Age at onset, mean ± SD (years) Duration of disease, mean ± SD (years) Male, n (total, %) Familial history, n (total, %) Peripheral arthritis, n (total, %) Hip joint involvement, n (total, %) JoAS, n (total, %) HLA-B27, n (total, %) TNF blocker use, n (total, %)
33.2 ± 10.1 20.9 ± 8.1 12.1 ± 8.1 732 (830, 88.2) 157 (802, 19.6) 391 (826, 47.1) 604 (817, 73.9) 236 (823, 28.7) 727 (767, 94.8) 224 (830, 26.9)
Extra-articular manifestation Enthesitis, n (total, %) Uveitis, n (total, %) Disease duration, mean (SD) (years) Unilateral (%) Bilateral (%) Alternative (%) Frequency, mean (SD) (years) One episode (%) Two episodes (%) Three episodes (%) Four episodes (%) Five episodes and more (%) Cardiac involvement, n (total, %) Renal involvement, n (total, %) Inflammatory bowel disease, n (total, %)
344 (805, 42.7) 246 (829, 29.7) 15.1 (7.8) 63.6 11.8 24.6 3.7 (4.3) 33.5 24.6 11.6 9.4 20.9 13 (806, 1.6) 32 (806, 3.9) 9 (806, 1.1)
JoAS: juvenile-onset ankylosing spondylitis.
3.2. Comparison of clinical features between men and women
There was no difference in sex distribution between the groups (Table 4). At the time of the survey, the JoAS group had more enthesitis (p < 0.001; OR: 1.89; 95% CI: 1.38–2.61) than the AoAS group. Peripheral arthritis (p < 0.001; OR: 4.19; 95% CI: 2.98–5.88) and hip joint involvement (p < 0.001; OR: 2.76; 95% CI: 1.77–4.29) were more frequent in the JoAS group. However, there were no significant differences in uveitis, BASFI, or HLA-B27 between the two groups. Comparison of symptoms at onset between the JoAS and AoAS group, revealed that lower back pain or buttock pain were more frequent in the AoAS group, but hip, knee, and ankle arthritis were more frequent in the JoAS group.
Table 2 The initial presenting symptom at disease onset. Initial symptom/sign
Number (%)
Low back pain or Buttock pain Hip joint involvement Knee joint arthritis Achilles tendinitis Ankle joint arthritis Plantar fasciitis Tarsal joint arthritis Shoulder joint pain Others
391 (47.1) 132 (15.8) 115 (13.7) 60 (7.2) 35 (4.2) 19 (2.3) 14 (1.7) 12 (1.4) 60 (7.2)
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Table 3 Comparisons between men and women with AS. Clinical features
Male (n = 720)
Female (n = 97)
p-value, OR (95% CI)
Age, mean ± SD Age at onset, mean ± SD Disease duration, mean ± SD Familial history, n (%) Enthesitis, n (%) Peripheral arthritis, n (%) Uveitis, n (%) Hip joint involvement, n (%) Shoulder involvement, n (%) BASFI, Mean ± SD HLA-B27, n (%)
32.9 ± 9.9 20.6 ± 8.0 12.1 ± 8.1 130 (18.3) 297 (41.9) 341 (46.8) 206 (28.2) 534 (75.2) 385 (56.2) 1.8 ± 1.9 638 (94.9)
35.4 ± 9.9 23.3 ± 8.9 11.9 ± 8.1 27 (29.3) 47 (48.5) 50 (51.0) 40 (40.8) 70 (72.9) 53 (60.9) 1.8 ± 2.0 89 (93.7)
0.02 0.05a , 1.03 (1.00-1.06) NS 0.01a , 1.86 (1.14-3.03) NS NS 0.03a , 1.63 (1.05-2.53) NS NS NS NS
Initial symptom/sign LBP or buttock pain, n (%) Hip joint involvement, n (%) Knee arthritis, n (%) Achilles tendonitis, n (%) Ankle arthritis, n (%) Plantar fasciitis, n (%)
342 (46.7) 128 (17.5) 106 (14.5) 50 (6.8) 29 (4.0) 18 (2.5)
46 (46.9) 14 (14.3) 9 (9.2) 12 (12.2) 3 (3.1) 1 (1.0)
NS NS NS NS NS NS
NS: not significant; BASFI: Bath Ankylosing Spondylitis Functional Index; LBP: low back pain. a Age-adjusted p-value.
3.4. Comparison between HLA-B27 positive and negative patients A comparison of HLA-B27 positive and negative groups (Table 5) demonstrated that HLA-B27 positive cases had a significantly younger age of symptom onset (by 5.3 years, p = 0.002), with more uveitis (p = 0.001) and hip joint involvement (p < 0.001) than HLAB27 negative patients. However, there was no difference in BASFI between the two groups. 4. Discussion In our study, the mean age at AS disease onset was the early twenties, with an onset after the age of 45 very rare; these findings are consistent with the published literature [2,11]. We also found that AS was eight times more common in men than in women, in contrast to Khan and van der Linden’s report [2], where it was only three times more common in men than women. There was a relatively greater degree of underdiagnosis of the disease in female than male patients. This may be because women have more peripheral arthritis, and implies that women with AS are initially being misdi-
agnosed and treated for seronegative rheumatoid arthritis instead of AS [12]. Another possibility is that women tend to have a higher threshold for seeking medical counseling than men because of a tendency to consider their back pain an insignificant symptom of their daily lives. A third possibility is that the slower and relatively incomplete progression to spinal ankylosis in female patients results on a decrease in pain over time, compared to male patients [13]. Peripheral joint involvement is a presenting feature in only 10–20% of patients and occurs during the disease course in 30–40% of patients [14]. In our patients group, 47.1% had peripheral arthritis, which was higher prevalence than reported by Kahn [15]. The proportion of hip joint involvement (73.9%) in our study was much higher than previous reports (24–41%) [3,6,16]. Our study revealed that Korean patients with AS have a higher frequency of peripheral arthritis and hip joint involvement. Furthermore, we noticed some differences in clinical features depending on the presence or absence of peripheral arthritis: patients with peripheral arthritis were younger than the patients without arthritis, and also had a higher frequency of enthesitis.
Table 4 Comparisons between juvenile-onset and adult-onset AS. Clinical features
JoAS (n = 236)
AoAS (n = 581)
p-value, OR (95% CI)
Sex (M/F) Age, mean ± SD Age at onset, mean ± SD Disease duration, mean ± SD Familial History, n (%) Enthesitis, n (%) Peripheral arthritis, n (%) Uveitis, n (%) Hip joint involvement, n (%) Shoulder involvement, n (%) BASFI, Mean ± SD HLA-B27, n (%)
215/21 28.3 ± 8.6 13.1 ± 2.5 15.0 ± 8.0 54 (23.7) 123 (53.9) 171 (72.5) 83 (35.2) 204 (87.6) 133 (60.7) 1.85 ± 2.1 221 (97.8)
510/71 35.0 ± 9.8 24.0 ± 7.5 10.9 ± 7.9 102 (17.8) 220 (38.2) 218 (37.3) 160 (27.3) 399 (69.8) 304 (55.1) 1.80 ± 1.9 500 (93.5)
NS < 0.001 < 0.001 < 0.001 NS < 0.001a , 1.89 (1.38-2.61) < 0.001a , 4.19 (2.98-5.88) NS < 0.001a , 2.76 (1.77-4.29) NS NS NS
Initial symptom/sign LBP or buttock pain, n (%) Hip joint involvement, n (%) Knee arthritis, n (%) Achilles tendonitis, n (%) Ankle arthritis, n (%) Plantar fasciitis, n (%)
46 (19.5) 61 (25.8) 71 (30.1) 24 (10.2) 19 (8.1) 5 (2.1)
341 (58.1) 81 (13.8) 44 (7.5) 37 (6.3) 13 (2.2) 14 (2.4)
< 0.001 < 0.001 < 0.001 NS < 0.001 NS
NS: not significant; JoAS: juvenile-onset ankylosing spondylitis; AoAS: adult-onset ankylosing spondylitis; BASFI: Bath Ankylosing Spondylitis Functional Index; LBP: low back pain. a Disease duration adjusted p-value.
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Table 5 Comparison of the clinical features between HLA-B27 positive and negative groups. Clinical features
HLA-B27 positive (n = 727)
HLA-B27 negative (n = 40)
p-value
Age, mean ± SD Age at onset, mean ± SD Disease duration, mean ± SD Male, n (%) JoAS, n (%) Enthesitis, n (%) Peripheral arthritis, n (%) Uveitis, n (%) Hip joint involvement, n (%) Shoulder involvement, n (%) BASFI, Mean ± SD
32.9 ± 9.8 20.5 ± 7.9 12.3 ± 8.0 638 (94.9) 221 (30.7) 307 (43.5) 352 (48.6) 228 (31.4) 547 (77.6) 394 (58.1) 1.8 ± 1.9
33.8 ± 12.6 25.8 ± 9.9 11.1 ± 10.3 34 (85.0) 5 (12.5) 18 (47.4) 19 (47.5) 3 (7.5) 20 (50) 19 (54.3) 1.6 ± 1.6
NS 0.002 NS NS 0.013 NS NS 0.001 <0.001 NS NS
Initial symptom/sign LBP or buttock pain, n (%) Hip joint involvement, n (%) Knee arthritis, n (%) Achilles tendonitis, n (%) Ankle arthritis, n (%) Plantar fasciitis, n (%)
332 (45.7) 130 (17.9) 105 (14.4) 56 (7.7) 29 (4.0) 17 (2.3)
20 (50.0) 2 (5.0) 7 (17.5) 2 (5.8) 1 (2.5) 1 (2.5)
NS 0.03 NS NS NS NS
NS: not significant; JoAS: juvenile-onset ankylosing spondylitis; BASFI: Bath Ankylosing Spondylitis Functional Index; LBP: low back pain.
Although AS typically presents in the late teens or early twenties, it can present in childhood. Among patients with AS, the prevalence rates for juvenile-onset vary from 9 to 21% in Western populations [15,17]. However, according to our study, the prevalence of JoAS is higher (28.7%) in Korea than that reported for Western JoAS. Between 20–30% of patients with AS have been found to suffer from uveitis attacks [18,19], and the uveitis associated with AS is usually unilateral. An attack of uveitis has been suggested to cause a breakdown in the blood–aqueous barrier [20]. This phenomenon could promote recurrence in the same eye. In our study, most uveitis was unilateral, and among the uveitis patients, more than one episode of uveitis was generally observed, consistent with a previous report [21]. The mean frequency of attacks (SD) was 3.7 (4.3) times. Extra-articular organ involvement is rarely observed in AS patients. The prevalence of aortic incompetence was reported to be 10.1% in patients who had had spondylitis for 30 years, compared with 1% in those who had the disease for only 5 years [22]. The incidence of atrioventricular conduction block was shown to increase with the duration of the disease from 0.6% after 5 years of disease to 8.5% after 30 years [22]. In this survey, 13 patients (1.6%) had cardiac defects, and eight of those patients had cardiac conduction abnormalities. Renal involvement has been reported in approximately 10% of AS patients [23]. In our study, 32 patients (3.9%) had renal problems. However, we did not perform renal function monitoring at regular intervals, so the observed nephropathy may be due to a number of undiagnosed cases. The prevalence of inflammatory bowel disease (IBD) in AS has been reported to be between 2.6% (three out of 118 patients) and 3.8% (three out of 79 patients) [24]. In this survey, nine subjects (1.1%, one with Crohn’s disease, the remainder with ulcerative colitis) had IBD. Although a number of patients suffered from bowel discomfort, it was difficult to confirm IBD using colonoscopy, which may be the reason for the discrepancies between studies. In AS patients from Brazil, the predominant initial presenting symptoms were inflammatory back pain (61.9%) and peripheral arthritis (22.4%) [3]. Baek et al. [25] reported that chronic back pain was the presenting symptom in approximately 75% of AS patients in Korea. It is clear from the results of our study and others that pain in the low back or buttock is the most frequent onset symptom in AS. Among the peripheral joints, the knee joint was the most commonly affected site, followed by the ankle joint. Enthesitis such as Achilles tendonitis (7.2%) and plantar fasciitis (2.3%) were also
initial presenting symptoms. Rarely, neck pain, chest pain, uveitis, or thigh pain was detected as initial symptoms. AS appears to manifest 2 to 4 years later in women than men [26]. Despite the disease duration at the time of study, entry being nearly equal between the genders, our data also showed that AS developed later in women than in men, consistent with previous reports. It is known that females are more susceptible to rheumatoid disease. Thus gender appears to be an important risk factor, with relatives of male patients having the greatest cumulative risk of rheumatoid arthritis [27]. However, AS affects mainly men, with relatives of female patients more at risk [28]. Women have a greater family prevalence of AS than men [29], and this finding is reflected by our results. Previous clinical studies [30,31] reported a significantly higher prevalence of peripheral arthritis in women. However, we did not find differences in peripheral joint, hip, or shoulder joint involvement between genders. Most studies [26,32] showed that there were no differences in uveitis between genders, but uveitis in females was more common in this study, similar to Marks et al.’s report [31]. It has been demonstrated that the disease course of AS is more benign and the radiologic progression is slower in women than in men [29,33]. However, the functional outcomes were the same in this study. After adjusting for radiographic spinal damage, women were found to report worse functioning than men at any given level of radiographic damage [29], Additional analyses of functional measures in men and women are required to assess radiologic damages. There were no differences in onset symptoms between genders. Although AoAS and JoAS share many common features, they also differ in many respects. A greater portion of patients with JoAS have enthesitis than patients with AoAS [33]. JoAS patients have more peripheral arthritis, whereas AoAS patients have a greater prevalence of spinal disease [34,35]. Hip joint involvement is significantly higher in JoAS than in AoAS patients [34]. Our study confirmed that patients with JoAS more frequently have symptoms such as enthesitis, peripheral arthritis, and hip joint involvement. Furthermore, it has been reported that more patients with AoAS have positive family histories than those with JoAS [34]. This could be partly related to the fact that this disease manifests late and that siblings of children with JoAS may not yet show symptoms of the disease [34]. These results did not occur in our study. Differences in functional outcome according to the age of onset have also been reported. In a study that compared JoAS with AoAS patients, JoAS patients were shown to have worse functional outcomes [36]. In
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another study, no difference was observed between AoAS and JoAS patients [37]. In our study, there was no significant difference in functional outcome between the AoAS and JoAS groups. Different sample sizes and the dearth of a common definition of outcomes makes direct comparisons between studies difficult. In addition, several phenotypic manifestations of JoAS exist that may account for differences in determining functional outcomes. Compared with adults, patients with JoAS more commonly have initial symptoms in joints outside of the trunk. Because the diagnosis of JoAS relies on the same criteria as used for its adult counterpart, the early diagnosis of JoAS tends to be difficult. Therefore, there is a need to develop and standardize diagnostic criteria for JoAS. It has been reported that HLA-B27 positive cases have an earlier age of onset [38,39] than HLA-B27 negative cases and are more likely to develop acute anterior uveitis [40,41]. Consistent with these previous findings, we found a significant association between an earlier age of symptom onset and higher uveitis frequency, and between an earlier symptom onset and HLA-B27 presence. Furthermore, we found that hip joint involvement was more frequent in the HLA-B27 positive group. Thus, it is clear that the HLA-B27 antigen plays an important role in the pathogenesis of AS. This study had some limitations. It was based on subjects referred to our hospital for rheumatic diseases. Moreover, questioning patients about symptom onset is fraught with recall bias. A prospective study of patients from the date of symptom onset is the only way to prevent recall bias. Although spinal mobility should be measured using the Bath Ankylosing Spondylitis Metrology Index (BASMI), a validated quantitative index that reflects axial segmental involvement [42], these measurements were not performed in this study. Physicians now commonly use patient-derived instruments such as Bath Ankylosing spondylitis Disease Activity Index (BASDAI) as a “gold standard” for measuring disease activity, whereas there is no appropriate evidence that patients and physicians perceive disease activity similarly. BASDAI is entirely patient-reported, therefore reflecting only a part of the entire construct of disease activity [43]. For this reason, we did not analyze disease activity (BASDAI) findings in this study. However, strengths of this study include the large number of patients, diagnosed and confirmed by two specialized rheumatologists. The clinical features of our patients appear largely similar to those in other studies, with the following noticeable differences: 1) AS patients in Korea have a higher prevalence of peripheral arthritis and hip joint involvement; 2) female patients have more uveitis; 3) JoAS appears to be more common in Korea. Conflict of interest statement This study was supported by a grant of the Korea Healthcare technology R & D project, Ministry for Health, Welfare and Family Affairs, Republic of Korea (A084794). References [1] Braun J, Bollow M, Remlinger G, et al. Prevalence of spondylarthropathies in HLA-B27 positive and negative blood donors. Arthritis Rheum 1998;41:58–67. [2] Khan MA, van der Linden SM. A wider spectrum of spondyloarthropathies. Semin Arthritis Rheum 1990;20:107–13. [3] Sampaio-Barros PD, Bertolo MB, Kraemer MH, et al. Primary ankylosing spondylitis: patterns of disease in a Brazilian population of 147 patients. J Rheumatol 2001;28:560–5. [4] Mau W, Zeidler H, Mau R, et al. Clinical features and prognosis of patients with possible ankylosing spondylitis. Results of a 10-year follow-up. J Rheumatol 1988;15:1109–14. [5] Boyer GS, Templin DW, Goring WP. Evaluation of the European Spondylarthropathy Study Group preliminary classification criteria in Alaskan Eskimo populations. Arthritis Rheum 1993;36:534–8.
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