Patient demographics and enrollment
Fifty-two AS outpatients who were admitted to the department of rheumatology and the department of adult joint reconstruction surgery in our institute from February 2018 to June 2019 were enrolled in this study. The inclusion criteria were as follows: (1) diagnoses of AS were made according to the 1984 modified New York criteria【27】; (2) the age of the patients ranged from 18 to 45 years. Exclusion criteria that any selected patients with any of the followings: (1) systemic diseases of the muscular of nervous systems, (2) history of congenital or childhood disease, surgery, deep infection, trauma, and tumor of hip; (3) lower extremity replacement or amputation other hip joint; (4) MRI contraindications (e.g. pacemaker, metal implants, pregnancy, claustrophobia).
The subjects’ demographics and clinical characteristics included gender, body mass index (BMI), age at outpatient visit, age at onset of AS, duration of AS, diagnosis delay, family history, medication status and extra-articular manifestations (EAMs) (current or past) including uveitis, psoriasis and inflammatory bowel disease (IBD). Disease activity was assessed respectively using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 【28】and Ankylosing Spondylitis Disease Activity Score(ASDAS) 【29】. The functional status was assessed using the Bath ankylosing spondylitis functional index (BASFI) 【30】. The patient-reported outcomes (PROs) were assessed by using the Ankylosing Spondylitis Quality of Life (ASQoL) scales 【31】and the short form-12(SF-12) 【32】. The use of the medications including NSAIDs and DMARDs was recorded, and the patients who had taken treatment agents for one year or longer were considered as sustained users. These data for clinical characteristics were collected and evaluated independently by two rheumatologists (L.H.C. and M.S.L.) who had not participated in radiographic evaluations conducted from a face-to-face questionnaire and medical records. The Harris hip scoring (HHS) system 【33】 was directly evaluated by orthopedic surgeons (Z.L. and H.Y.) at the time of outpatient consultation. On the 100-point scale, a score of 90 points or more is defined as an excellent outcome; 80 to 89 points, a good outcome; 70 to 79 points, a fair outcome; and 70 points or less, a poor outcome.
Laboratory data such as human leukocyte antigen (HLA-B27) status, serum erythrocyte sedimentation rate (ESR), high sensitive C reactive protein (CRP) and CRP level were also measured at enrollment.
The results of these clinical and laboratory parameters are provided in Table 1.
Table 1
Patient demographics, clinical and laboratory parameters of AS patients on different stages of hip involvement
|
Total AS patients
|
Group A(n = 21)
|
Group B(n = 42)
|
Group C(n = 25)
|
P value
|
Adjusted P value
|
A-B
|
A-C
|
B-C
|
Male gender, n (%)
|
72(81.8%)
|
20(95.2%)
|
33(78.6%)
|
19(76.0%)
|
0.175
|
|
|
|
Age at outpatient visit (years)
|
30.00(25.25,34.75)
|
32.00(30.00,39.00)
|
30.00(25.50-34.25)
|
28.50(25.00–35.00)
|
0.147
|
|
|
|
Age at onset (years)
|
23.00(19.00,26.00)
|
25.00(23.00,28.00)
|
22.00(18.00,27.25)
|
21.50(17.00,24.00)
|
0.005*
|
0.093
|
0.004*
|
0.390
|
Disease duration (years)
|
6.50(2.00,10.50)
|
6.00(2.00,11.00)
|
6.00(2.00,9.00)
|
7.00(2.00,11.00)
|
0.812
|
|
|
|
Diagnosis delay (years)
|
2.00(0.25,8.00)
|
1.00(0.00,6.00)
|
2.00(0.00,8.00)
|
2.00(1.00,10.50)
|
0.233
|
|
|
|
Family history, n (%)
|
27(30.7%)
|
6(28.6%)
|
9(21.4%)
|
12(48.0%)
|
0.081
|
|
|
|
EAMs, n (%)
|
14(15.9%)
|
1(4.8%)
|
7(16.7%)
|
6(24.0%)
|
0.213
|
|
|
|
Uveitis, n (%)
|
3(3.4%)
|
0(0.0%)
|
0(0.0%)
|
3(12.0%)
|
0.033*
|
\
|
0.239
|
0.048*
|
IBD, n (%)
|
7(8.0%)
|
1(4.8%)
|
5(11.9%)
|
1(4.0%)
|
0.595
|
|
|
|
Psoriasis, n (%)
|
4(4.4%)
|
0(0.0%)
|
2(4.8%)
|
2(8.0%)
|
0.570
|
|
|
|
Use of NSAIDs, n (%)
|
82(93.2%)
|
19(90.5%)
|
39(92.9%)
|
24(96.0%)
|
0.327
|
|
|
|
Use of DMARDs, n (%)
|
36(40.9%)
|
8(38.1%)
|
17(40.5%)
|
11(44.0%)
|
0.922
|
|
|
|
BMI
|
25.95(22.86,29.09)
|
27.12(23.12,29.93)
|
25.81(22.86,29.36)
|
25.95(19.59,28.98)
|
0.752
|
|
|
|
HLA-B27 positivity, n (%)
|
80(90.9%)
|
21(100.0%)
|
38(90.5%)
|
21(84.0%)
|
0.165
|
|
|
|
ESR (mm)
|
25.50(13.00,38.00)
|
13.00(10.00,24.50)
|
25.00(13.00,39.25)
|
29.00(25.00,41.25)
|
< 0.001*
|
0.016*
|
< 0.001*
|
0.296
|
CRP (mg/L)
|
14.80(9.30,27.80)
|
13.20(6.60,15.56)
|
14.30(5.28,27.80)
|
24.20(12.70,53.80)
|
0.003*
|
0.610
|
0.003*
|
0.032*
|
hsCRP(mg/L)
|
13.54(4.60,28.17)
|
7.70(4.93,20.44)
|
12.20(3.42,29.49)
|
25.96(8.83,34.24)
|
0.031*
|
0.869
|
0.031*
|
0.179
|
ALB (g/L)
|
45.50(43.00,47.45)
|
44.90(41.30,46.80)
|
46.30(43.95,47.70)
|
43.90(43.00,46.65)
|
0.134
|
|
|
|
HGB(g/L)
|
142.00(133.00,150.00)
|
145.00(141.00-159.00)
|
143.00(131.50–152.00)
|
141.00(130.00-149.00)
|
0.123
|
|
|
|
BASDAI
|
3.20(1.80,5.35)
|
2.00(1.40,3.00)
|
3.40(1.65,5.25)
|
4.60(3.20,5.80)
|
< 0.001*
|
0.070
|
< 0.001*
|
0.023*
|
BASFI
|
1.60(0.73,2.60)
|
0.70(0.60,1.30)
|
1.80(0.80,2.90)
|
2.00(1.60,2.83)
|
< 0.001*
|
0.001*
|
< 0.001*
|
0.214
|
ASQOL
|
6.00(2.00,8.00)
|
2.00(2.00,3.00)
|
6.00(2.75,8.00)
|
7.00(6.00,11.75)
|
0.001*
|
0.011*
|
0.001*
|
0.541
|
ASDAS-ESR
|
2.35(1.83,3.10)
|
1.79(1.05–1.96)
|
2.44(1.90–3.48)
|
2.93(2.35–3.55)
|
< 0.001*
|
< 0.001*
|
< 0.001*
|
0.443
|
ASDAS-CRP
|
2.45(1.61,3.23)
|
1.54(1.43,1.98)
|
2.52(1.79,3.46)
|
2.63(2.37,3.42)
|
< 0.001*
|
< 0.001*
|
< 0.001*
|
0.538
|
SF-12PCS
|
42.20(27.70,52.20)
|
50.10(39.00,55.40)
|
42.20(28.38,50.40)
|
32.10(22.80,51.83)
|
0.020*
|
0.092
|
0.020*
|
1.000
|
SF-12MCS
|
42.75(27.50,53.50)
|
52.20(40.00,54.75)
|
42.35(29.45,53.50)
|
31.90(25.40,51.75)
|
0.038*
|
0.279
|
0.032*
|
0.675
|
HHS
|
86.00(67.00,94.75)
|
95.00(93.00,96.00)
|
77.00(54.00,89.75)
|
69.00(51.50,87.00)
|
< 0.001*
|
< 0.001*
|
< 0.001*
|
0.875
|
BARSI
|
2.00(1.00,3.00)
|
1.00(1.00,1.00)
|
2.00(1.00,2.00)
|
3.00(3.00,4.00)
|
< 0.001*
|
0.002*
|
< 0.001*
|
< 0.001*
|
HIMRISS
|
29.63(15.25,43.00)
|
14.50(11.38,22.25)
|
29.38(17.00,40.94)
|
38(31.13,64.38)
|
< 0.001*
|
0.009*
|
< 0.001*
|
0.103
|
*P < 0.05, AS = ankylosing spondylitis, EAMs = extra-articular manifestations, IBD = inflammatory bowel disease, NSAIDs = nonsteroidal anti-inflammatory drugs, DMARDs = disease modifying anti-rheumatic drugs, BMI = bone mass density, HLA-B27 = human leucocyte antigen-B 27, ESR = erythrocyte sedimentation rate, CRP = C reactive protein, hsCRP = high sensitive C reactive protein, ALB = albumin, HGB = hemoglobin, BASDAI = Bath ankylosing spondylitis disease activity index, BASFI = Bath ankylosing spondylitis functional index, ASQOL = ankylosing spondylitis quality of life, ASDAS = Ankylosing Spondylitis Disease Activity Score, SF-12 PCS = short form-12 physical component summary, SF-12 MCS = short form-12 mental component summary, HHS = Harris hip score, BASRI-Hip = the bath ankylosing spondylitis radiology hip index |
Group A represents the hips with no hip involvement (HHS ≥ 80 and BASRI ≤ 1), group B represents the hips with mild hip involvement (BASRI = 2 or BASRI ≤ 1 and HHS ≤ 79) and Group C represents the hips with advanced hip involvement (BASRI ≥ 3) |
The value of continuous variables was presented as median and quartile (25–75%) and the categorical variables were based on presented as number plus percentage |
Radiographic Classification System
The anteroposterior (AP) radiographs of the pelvis and MRI imaging were obtained on the same day on an outpatient basis. We excluded 8 patients whose radiographs were of inadequate quality and kept a total of 44 patients for review and analysis.
The BASRI hip system was adopted to assess the severity of radiological involvement in the hip joint【13】, and it classified the status of the hip joints into a five-point scale from 0 to 4 (0 = normal, no change; 1 = suspicious, possible focal joint space narrowing; 2 = minimal, circumferential joint space narrowing > 2 mm; 3 = moderate, circumferential joint space narrowing ≤ 2mm, or bone-on-bone apposition of ≤ 2 cm; 4 = severe, bone deformity or bone-on-bone apposition of < 2 cm or total hip re-placement).
MRI scans on enrolled patients’ both hips were performed on a 3.0 T MR system (Siemens MAGNETOM Skyra, Siemens Company) using the following imaging parameters: a transverse T1-Weighted Spin Echo (T1 TSE) sequence, a transverse T2 TSE + Fat-Sat sequence, a coronal T1 TSE sequence, a coronal T2 TSE + Fat-Sat sequence, and trans-verse and coronal fat-saturated. All sequences used a 380mm field of view, a 3.5mm slice thickness, a 0.7mm slice interval, a 384 448 matrix, and several excitations (AVERAGE) of 2.
HIMRISS has three features: bone marrow lesions (BMLs), synovitis and effusion. BML is defined as an area of hyper-intensity within the bone in STIR sequence. The BML scoring on either femoral head or acetabulum side was graded according to the method which was described by Maksymowych et al【34】. The range of BML scoring is 0-100. Effusion and synovitis are scored together depending on the maximum depth of the fluid (0 = 0‐1.9 mm, 1 = 2‐3.9 mm, 2 = ≥ 4 mm) on the same central, anterior and posterior slices. The range of total effusion scoring is 0‐30. Therefore, the final HIMRISS scoring range is 0‐130.
Reading exercises
Considering the possible effect of the raters’ experiences on evaluating the hips, we chose four raters with different levels of training and experiences. A senior rheumatologist (L.H.C.) who is an attending physician with 16 years of clinical experience, an adult hip surgeon (Z.L.) who is a vice director with 15 years of clinical experience, and two musculoskeletal radiologists (Z.J., X.P.) who are residents with 4 years and 9 years of clinical experience respectively participated in grading the MRI imaging.
All raters were not informed about patient demographics and clinical parameters. Firstly, they learned the scoring rule through a PowerPoint file of Outcome Measures in Rheumatology (OMERACT) 11【24】individually. Then a training session was held where they agreed on a criteria for radiographic evaluation that was based on five MRI images.
Next, another 88 MRI images from the PACS (Picture Archiving and Communication System) workstation which were not included in the evaluation were collected by the first author (M.S.L.) and were sent to the raters. Then they graded the MRI images in random sequences in different workrooms (exercise 1). Three months later, they repeated their works (exercise 2) without knowing the previous results to assess the reliability of test-retest.
Statistical analysis
Data were statistically analyzed using SPSS software for Windows (version 23.0; IBM, Armonk, NY, USA). Descriptive analyses for categorical variables were shown as percentages and frequencies and for continuous variables they were based on mean and standard deviation (SD) or median and quartile (25–75 %) if the data were skewed. The values of femoral BML, acetabular BML, synovitis effusion were summed up as the HIMRISS values for the single hip, and the mean values by all readers obtained in exercise 2 were taken as the final HIMRISS scores. The inter-rater and intra-rater reliability of HIMRISS were calculated using intraclass correlation coefficient (ICC). The correlations of HIMRISS with clinical continuous variables and with ordinal variables were determined by correlation coefficient (r) in Pearson correlation analysis and Spearman rank correlation analysis respectively. We classified hips into no hip involvement group(HHS ≥ 80 and BASRI ≤ 1)(Group A), mild hip involvement subgroup (BASRI = 2 or BASRI ≤ 1 and HHS ≤ 79) (Group B) and moderate to advanced hip involvement subgroup (BASRI ≥ 3) (Group C) based on HHS of involved hip and BASRI-hip score. Demographic features, clinical characteristics and radiographic parameters were compared using ANOVA (including post hoc analysis) and nonparametric Kruskal-Wallis test among these subgroups. Bonferroni method was taken to adjust the significance level in multiple comparisons. All reported P values were two-tailed with an alpha of 0.05.
Ethics and registration
All procedures involving human participants carried out in the studies were in accordance with the ethical standards of the institutional and/or national research committee and the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This study was approved by the Beijing Jishuitan Hospital Institutional Review Board (project number S-305/2007), and the informed consent was obtained from each participant before the enrollment of this study.