Ankylosing spondylitis (AS) is a common chronic systemic inflammatory disease. Its prevalence is almost as common as rheumatoid arthritis (1, 2). The sacroiliac (SI) joints are one of the earliest sites involved, and sacroiliitis is crucial for the diagnosis of AS. However, the methods currently used, including radiography, computed tomography (CT), scintigraphy, and ultrasonography, are of little help in the diagnosis of early sacroiliitis (3–5). The diagnosis of AS is thus usually delayed (6, 7). Magnetic resonance imaging (MRI) can detect periarticular bone marrow edema (BME) before sacroiliitis of grade II or higher can be identified by CT (8), thus greatly improving the diagnosis of early sacroiliitis. However, the sensitivity is limited (9, 10).
Since 1999, investigators in our department have been studying the usefulness of needle biopsy in the pathologic diagnosis of early sacroiliitis (9). Our most recent findings are reported herein.
- Top of page
- PATIENTS AND METHODS
- AUTHOR CONTRIBUTIONS
A total of 109 patients, 63 male and 46 female, were enrolled. The average age was 23.2 years (range 9–43 years), and the average age at disease onset was 19.2 years (range 5–41 years). The average disease duration was 4.0 years (range 0.3–20 years). Axial joint involvement as the first manifestation was seen in 65 patients, peripheral arthralgia/arthritis in 42 patients, and febrile attack in 2 patients. HLA–B27 typing was done in 100 patients, 56.0% of whom were positive. The erythrocyte sedimentation rate (ESR) was elevated in 50 patients, and the C-reactive protein (CRP) level was elevated in 41 patients. Sacroiliitis assessed by radiography/CT was found to be grade I or lower in all of the patients at study entry.
MRI results at baseline.
MRI of the SI joints was performed in 77 of the 109 patients at baseline (Table 1). Of these 77 patients, definite BME was found in 23 patients, and equivocal BME (only 1 signal noted on a single slice) in 2 patients. Definite unilateral minor erosion was found in 5 patients, of which 4 were accompanied by definite BME signals. Only 1 patient had no BME signal on MRI. Equivocal erosion was found in 18 patients; this was accompanied by definite BME in 8 patients. No definite BME signals accompanied the erosion in the other 10 patients. No fat deposition or sclerosis was found. Thus, 23 patients fulfilled the definition of sacroiliitis on MRI, and the other 54 had no sacroiliitis on MRI.
Table 1. Needle biopsy results in 109 patients in whom AS was highly suspected, and outcome at the 5–10-year followup
| ||Baseline||Study end point†|
|No. with MRI at baseline||CT grade at study end point|
|Pathologic early sacroiliitis||No pathologic sacroiliitis*||Total||Grade I or lower||Grade II||Grade III||Total|
| No sacroiliitis||38||16||54||20||14||4||2||20|
Biopsy findings in the SI joints.
Needle biopsy was performed on all 109 patients. Components of the SI joints obtained by needle biopsy revealed subchondral bone marrow in 82 patients, subchondral bone plate in 90 patients, cartilage in all 109 patients, synovium in 15 patients, and ligament in 19 patients. Pathologic features of sacroiliitis in these patients were as follows: 1) subchondral BME, with mononuclear cells commonly seen in proliferating connective tissue infiltrates, such as histiocytes/macrophages, lymphocytes, and plasmacytes, and pannus formation was present in 79 patients; 2) subchondral bone plate disruption combined with pannus invasion in 83 patients; 3) cartilage pannus invasion in 80 patients; 4) synovitis in 5 patients; and 5) enthesitis in 4 patients. The common pathologic changes were subchondral erosion of the bone plate, sequestration and sclerosis, or cartilage degeneration, erosion, fibrosis, and ossification (Figure 1). Thus, pathologic early sacroiliitis was diagnosed by needle biopsy in 85 patients (78%), and no pathologic changes in the remaining 24 patients (22%) (Table 1).
Figure 1. Pathologic features of sacroiliitis in hematoxylin and eosin–stained sacroiliac (SI) joint tissues obtained by needle biopsy. A, SI joint section showing granulation tissue (a) and subchondral bone plate destruction (b). B, SI joint section showing disappearance of the subchondral bone plate (c) and pannus invasion in the cartilage. C, SI joint section showing enthesitis, with dense connective tissue (ligament) and inflammatory cell invasion (e). d = bone tissue. Inset shows a higher-magnification view of the boxed area. N = neutrophilic leukocyte; P = plasmacyte; Ly = lymphocyte; E = eosinophilic granulocyte. D, SI joint section showing synovitis, with hyperplasia of synovial lining cells (f) and hyperplasia of loose connective tissues and interstitial edema (g). Bars = 50 μm in A and C; 20 μm in B and D; and 10 μm in inset.
Download figure to PowerPoint
Of the 85 patients with pathologic early sacroiliitis, at baseline, MRI was performed on 61 of them. Among these patients, 23 (37.7%) had sacroiliitis on MRI, and 38 did not. Of the 24 patients without inflammatory changes, MRI was performed in 16 patients, and no evidence of sacroiliitis was found in any of them. That is, pathologic early sacroiliitis was present in all of the patients with MRI evidence of sacroiliitis. And among the 54 patients in whom sacroiliitis was not detected by MRI, 38 of them still had pathologic early sacroiliitis. Therefore, in our study, the specificity and sensitivity of MRI for the diagnosis of early sacroiliitis was 100% and 37.7%, respectively (Cohen's κ = 0.65 [95% confidence interval 0.44–0.76] for the reliability of detection by MRI and histopathologic techniques).
The proportions of male patients and patients with juvenile onset (age <16 years) were significantly higher in the group with pathologic early sacroiliitis than in the group without pathologic sacroiliitis (Table 2). The mean age at disease onset was significantly younger and the mean disease duration was significantly shorter in patients with pathologic early sacroiliitis than in those without pathologic sacroiliitis. Fever as the first manifestation of symptoms was seen in 2 patients with pathologic early sacroiliitis. The percentage of patients with peripheral arthralgia/arthritis as the first manifestation was equivalent in both groups. The levels of ESR and CRP and the proportion with decreased BMD were significantly higher in patients with pathologic early sacroiliitis than in those without pathologic sacroiliitis. The percentage of patients positive for HLA–B27 (61.0%) was also higher in those with pathologic early sacroiliitis, but was lower than the percentage of patients in our previous study (93.3%) whose AS was diagnosed according to the New York criteria (6).
Table 2. Baseline clinical features of patients with pathologic early sacroiliitis and patients without pathologic sacroiliitis*
| ||Pathologic early sacroiliitis (n = 85)||No pathologic sacroiliitis (n = 24)|
|No. male/female (male:female ratio)||58/27 (1:0.47)†||5/19 (1:3.8)|
|No. with axial/peripheral joint onset||51/32||14/10|
|Mean age at onset, years||17.7†||24.4|
| Axial joint onset||19.2‡||24.2|
| Peripheral joint onset||15.8†||25.3|
|Mean disease duration, years||3.4†||6.4|
| Axial joint onset||3.7‡||6.6|
| Peripheral joint onset||3.1||5.4|
|No. (%) with juvenile onset||38 (44.7)†||4 (16.7)|
|HLA–B27 positive, no. positive/no. tested (%)||47/77 (61.0)||9/23 (39.1)|
|Elevated ESR, no. positive/no. tested (%)||45/74 (60.8)†||5/24 (20.8)|
|Elevated CRP, no. positive/no. tested (%)||37/70 (52.8)†||4/24 (16.7)|
|Decreased BMD, no. positive/no. tested (%)|| || |
| Lumbar spine||15/38 (39.5)||2/12 (16.7)|
| Hip||25/38 (65.8)†||3/12 (25.0)|
|Sacroiliitis on MRI, no. positive/no. tested (%)||23/61 (37.7)†||0/16 (0)|
The 24 patients without pathologic sacroiliitis were followed up for 0.3–8.5 years, after which time a diagnosis of AS or other spondylarthropathies was excluded in all of them.
All of the 85 patients with pathologic early sacroiliitis were treated with conventional antirheumatic drugs. By the end of 2009, 44 patients had been followed up for 5–10 years. At this end point, 40 patients (90.9%) had no symptoms, and in the remaining 4 patients, symptoms were at an acceptable level. No adverse events related to the needle biopsy were noted.
Followup CT scan of the SI joints in patients with pathologic early sacroiliitis.
Among the 44 patients who had been followed up for 5–10 years, CT scans of the SI joints were obtained in 34 of them at the study end point (Table 1). The other 10 patients declined to undergo CT scans for financial reasons. Among the 34 patients examined, 16 (47.1%) remained in grade I or lower sacroiliitis and 18 (52.9%) had grade II or higher sacroiliitis. Among the 18 patients with grade II or higher sacroiliitis on CT, 10 had grade II bilateral sacroiliitis, and 8 had bilateral grade III sacroiliitis on CT. All 18 patients (52.9%) fulfilled the diagnosis of AS according to the modified New York criteria (18).
Disease duration in patients with different grades of sacroiliitis on CT.
At the end point, the mean disease duration in the 16 patients with grade I or lower sacroiliitis on CT was 11.0 years (range 6.5–22 years). In the group with grade II sacroiliitis, the average disease duration was only 9.4 years (range 5.5–12 years), and in the group with grade III sacroiliitis, it was 6.9 years (range 5.5–9 years). Thus, the mean disease duration in this group of patients was shortest in the group with the highest grade of change: grade III < grade II < grade 0–I.
Comparison of clinical features between the group with grade II or higher sacroiliitis and the group with grade I or lower sacroiliitis on baseline CT.
The proportions of patients with sacroiliitis on MRI, an increased BME score, and elevated CRP level at baseline were significantly higher in those with grade II or higher sacroiliitis on CT than in those with grade I or lower sacroiliitis on CT (Table 3). The proportions of patients who were male, had juvenile-onset disease, peripheral arthralgia/arthritis as the first manifestation, required a wheelchair, were HLA–B27 positive, had an elevated ESR, had decreased BMD, and had a low rate of therapeutic compliance tended to be higher in the group with grade II or higher sacroiliitis on CT, although the difference was not statistically significant. With regard to the difference between patients with grade III and grade II sacroiliitis, the proportion of patients who were male, had juvenile-onset disease, required a wheelchair, were HLA–B27 positive, and had an increased BME score tended to be higher in the group with grade III sacroiliitis, and the mean age at onset, mean disease duration, and rate of therapeutic compliance tended to be lower in this group than in the group with grade II sacroiliitis, although the difference was not statistically significant. Thus, the outcome of patients with more severe disease was worse than the outcome in those with less severe disease.
Table 3. Comparison of baseline clinical features by CT grade at study end point*
|Baseline||Sacroiliitis of grade II or higher on CT||CT changes of grade I or lower (n = 16)|
|Grade III (n = 8)||Grade II (n = 10)||Total (n = 18)|
|No. male/female (male:female ratio)||6/2 (1:0.3)||6/4 (1:0.7)||12/6 (1:0.5)||10/6 (1:0.6)|
|No. (%) with juvenile onset||5 (62.5)||5 (50.0)||10 (55.6)||8 (50.0)|
|Age at onset, mean ± SD years||13.0 ± 4.5||17.8 ± 7.2||15.4 ± 5.7||17.1 ± 6.6|
|Disease duration, mean ± SD years||2.3 ± 3.5||3.7 ± 3.0||3.0 ± 3.3||5.1 ± 3.8|
|Fingers-to-floor distance, mean ± SD cm||9.5 ± 9.1||8.5 ± 15.0||9.1 ± 10.3||8.3 ± 11.1|
|No. (%) with axial joint onset||3 (37.5)||5 (50.0)||8 (44.4)||10 (62.5)|
|No. (%) with peripheral joint onset||4 (50.0)||5 (50.0)||9 (50.0)||6 (37.5)|
|HLA–B27 positive, no. positive/no. tested (%)||5/5 (100.0)||7/9 (77.8)||12/14 (85.7)||10/15 (66.7)|
|Elevated ESR, no. positive/no. tested (%)||5/8 (62.5)||6/10 (60.0)||11/18 (61.1)||6/16 (37.5)|
|Elevated CRP, no. positive/no. tested (%)||5/8 (62.5)||7/10 (70.0)||12/18 (66.7)†||5/16 (31.3)|
|MRI findings|| || || || |
| Sacroiliitis, no. positive/no. tested (%)||1/3 (33.3)||6/10 (60.0)||7/13 (53.8)‡||1/15 (6.7)|
| BME score, mean ± SEM||21.7 ± 19.3||6.6 ± 4.8||13.1 ± 17.6‡||0.6 ± 2.1|
|Decreased BMD, no. positive/no. tested (%)|| || || || |
| Lumbar spine||2/5 (40.0)||1/3 (33.3)||3/8 (37.5)||3/10 (30.0)|
| Hip||5/5 (100.0)||1/3 (33.3)||6/8 (75.0)||5/10 (50.0)|
Correlations between sacroiliitis on MRI at baseline, clinical features at baseline, and prognosis.
Among the 34 patients who underwent SI joint CT at the study end point, MRI of the SI joints had been performed in 28 of them at baseline. Of these 28 patients, 8 had sacroiliitis, whereas the other 20 patients did not (Table 1). As compared with the group without sacroiliitis on MRI, the group with sacroiliitis on MRI had a significantly higher proportion of patients with juvenile-onset disease and a significantly younger mean age at disease onset (Table 4). Despite the lack of statistical significance, the mean disease duration tended to be longer, the clinical symptoms and laboratory findings appeared to be more severe, and the prevalence of HLA–B27 tended to be higher in patients with sacroiliitis on MRI than in those without.
Table 4. Clinical features of patients with and those without evidence of sacroiliitis on MRI*
| ||No MRI sacroiliitis (n = 20)||MRI sacroiliitis (n = 8)|
|Baseline|| || |
| No. male/female (male:female ratio)||13/7 (1:0.54)||5/3 (1:0.6)|
| Age, mean ± SD years||23.2 ± 7.2||15.9 ± 2.4†|
| Age at onset, mean ± SD years||19.3 ± 6.3||11.4 ± 4.0†|
| Disease duration, mean ± SD years||4.0 ± 3.9||4.6 ± 3.6|
| No. (%) with juvenile onset||7 (35.0)||7 (87.5)‡|
| No. (%) with axial joint onset||12 (60.0)||3 (37.5)|
| No. (%) with peripheral joint onset||8 (40.0)||4 (50.0)|
| Fingers-to-floor distance, mean ± SD cm||10.6 ± 14.1||6.5 ± 8.1|
| No. (%) with HLA–B27||12 (70.6)§||6 (75.0)|
| No. (%) with elevated ESR||9 (45.0)||4 (50.0)|
| No. (%) with elevated CRP||7 (35.0)||5 (62.5)|
| BMD decrease, no. positive/no. tested (%)|| || |
| Lumbar spine||2/12 (16.7)||3/5 (60.0)|
| Hip||6/12 (50.0)||4/5 (80.0)|
|End point|| || |
| Sacroiliitis of grade II or higher, no. positive/no. tested (%)||6/20 (30.0)||7/8 (87.5)†|
At the end point of the 5–10-year followup, of the 8 patients with sacroiliitis detected by MRI at baseline, only 1 (12.5%) continued to show grade I or lower changes of sacroiliitis on CT (see, for example, images from patient 1 in Figure 2A). The other 7 patients (87.5%) had grade II or higher sacroiliitis on CT at the study end point (6 with grade II, and 1 with grade III) (see, for example, images from patient 2 in Figure 2B). Of the 20 patients with MRI-negative sacroiliitis at baseline, 14 (70%) continued to show grade I or lower sacroiliitis on CT (see, for example, patient 3 in Figure 2C), and only 6 (30%) had grade II or higher sacroiliitis on CT (4 had grade II and 2 had grade III) (see, for example, patient 4 in Figure 2D). These results showed that the outcome of patients with sacroiliitis on MRI at baseline was worse than that in those without.
Figure 2. Followup evaluation by magnetic resonance imaging (MRI) and computed tomography (CT) at 5–10 years (study end point) in 4 representative patients with pathologic sacroiliitis. Arrows point to the indicated features of interest. A, Patient 1. Bone marrow edema (BME) of the left sacroiliac (SI) joint (score of 8) is evident on baseline MRI (A1). Subchondral bone plate destruction and pannus infiltration (a) and replacement of bone marrow by granulation tissue (b) are seen on needle biopsy (A2). Followup MRI shows more serious BME (score of 20) (A3). Grade I or lower sacroiliitis is evident on CT at followup (A4). B, Patient 2. BME of the right SI joint (score of 5) is evident on baseline MRI (B1). Subchondral bone plate destruction and intertrabecular pannus formation (a) are seen on needle biopsy (B2). Followup MRI shows more serious BME (score of 16) (B3). Grade II sacroiliitis is evident on CT at followup (B4). C, Patient 3. No BME is evident on baseline MRI (C1). Subchondral bone plate destruction (a) and intertrabecular pannus formation (b) are seen on needle biopsy (C2). Followup MRI shows no BME (C3). Grade I or lower sacroiliitis is evident on CT at followup (C4). D, Patient 4. No BME is evident on baseline MRI (D1). Subchondral bone plate destruction (a) and intertrabecular pannus formation (b) are seen on needle biopsy (D2). Followup MRI shows BME (score of 15) (D3). Grade III sacroiliitis is evident on CT at followup (D4). Hematoxylin and eosin–stained biopsy sections (A2–D2); bars = 50 μm.
Download figure to PowerPoint
- Top of page
- PATIENTS AND METHODS
- AUTHOR CONTRIBUTIONS
An early accurate diagnosis and appropriate treatment are crucial for the best outcome of AS (19). Although a few cases of AS with normal SI joints have been reported (20), it remains quite rare. Therefore, sacroiliitis has been a crucial criterion in all of the criteria for the diagnosis/classification of AS (12, 18, 21).
MRI, using the SPIR/STIR technique, may reveal sacroiliitis before the structural changes become evident (grade II or higher sacroiliitis) and, thus, may offer an opportunity for early diagnosis (14). The significance of periarticular BME seen on MRI has been verified in some pathologic studies (22, 23). Nevertheless, the question remains: Is MRI the best way to detect early sacroiliitis?
In these study patients, the specificity of MRI in detecting early sacroiliitis was very high (100%), but the sensitivity was only 37.7%. Pathologic sacroiliitis was found not only in all patients with MRI-positive sacroiliitis, but also in 70.4% (38 of 54) of those with MRI-negative sacroiliitis, which suggests that pathologic sacroiliitis might already exist prior to its earliest possible detection by MRI. Therefore, pathologic examination of tissues obtained by needle biopsy can detect sacroiliitis earlier than MRI. Although needle biopsy is an invasive method, there are no important nerves or blood vessels around the site, and the procedure is safe, simple, and can be used in clinical practice.
With regard to the reason pathologic early sacroiliitis could not be detected by MRI, we think it might be due to insufficient disease severity (Table 4). This was further supported by the results of the 5–10-year followup, where at the study end point, grade II or higher sacroiliitis occurred in 87.5% of patients with MRI-positive sacroiliitis (7 of 8 patients) and only 30% of patients with MRI-negative sacroiliitis (6 of 20 patients).
The results of followup in our patients were similar to those of a 10-year followup of 88 patients with “suspicious AS” described by Mau et al (24). At the study end point, AS was diagnosed in 59% of the patients and excluded in 22%. However, the diagnosis in our study patients was made sooner, which allowed the earlier institution of appropriate treatment and avoided unnecessary treatment in those without sacroiliitis.
Few studies evaluating the natural course of sacroiliitis have been done. Retrospective analysis of 370 patients in our department in the 1990s (6) showed that the mean disease duration in 121 patients with grade II and grade III sacroiliitis was 4.4 years and 6.3 years, respectively. In the present study, the average disease duration when grade II and grade III sacroiliitis was identified by CT was 9.4 years and 6.9 years, respectively, which was longer than that of our previous report (9.4 and 6.9 years versus 4.4 and 6.3 years). This might be due to our early diagnosis and treatment, which could slow the disease progression.
As to the reason why the mean disease duration at the study end point in patients with grade III sacroiliitis on CT was shorter than that in the patients with grade II sacroiliitis (6.9 versus 9.4 years), and the mean disease duration in patients with grade II sacroiliitis was shorter than that in patients with grade I or lower sacroiliitis in this study, we think the following factors should be considered: the difference in disease severity between the different patient groups at baseline, the genetic heterogeneity of the patients per se (25, 26), and the effect of earlier treatment.
In conclusion, our study revealed that MRI possesses high specificity in the diagnosis of early sacroiliitis. However, the sensitivity of MRI in the diagnosis of early sacroiliitis is not sufficient. Needle biopsy can detect sacroiliitis earlier than MRI, and it is helpful for gaining time for early treatment and better outcome. Further studies should be done to verify whether the difference in prognosis in patients with pathologic early sacroiliitis is due to the early treatment or to the heterogeneity of the disease per se.
- Top of page
- PATIENTS AND METHODS
- AUTHOR CONTRIBUTIONS
All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors approved the final version to be published. Dr. Zeng had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Study conception and design. Gong, Zeng.
Acquisition of data. Gong.
Analysis and interpretation of data. Gong, Zheng, Chen, Xiao, Wu, Liu, Zeng.
- Top of page
- PATIENTS AND METHODS
- AUTHOR CONTRIBUTIONS
We thank Professor Yanqing Ding (Director, Department of Pathology, Southern Medical University, Guangzhou, China), Professor Haibin Chen (Director, Department of Histology and Embryology, Shantou University Medical College), and Professor Naizheng Zhang (former president of the Chinese Association of Rheumatology; Peking Union Hospital, Beijing, China) for their guidance throughout the study.