Session Information
Date: Monday, November 9, 2015
Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
Background/Purpose:
The association of HLA-B27 with spondyloarthritis is well-established. Under
the International League of Associations for Rheumatology (ILAR) criteria most
children with spondyloarthritis are classified as enthesitis-related arthritis
(ERA). It is unknown if the clinical features vary between children with ERA
who are HLA-B27 positive (pos) versus HLA-B27 negative (neg). Therefore, we
aimed to test whether ERA manifests differently in these serologically distinct
populations.
Methods:
We
performed a retrospective multicenter cohort study that included subjects from
5 pediatric rheumatology centers who were diagnosed with ERA from 1989-2012. Baseline
visit for patients was defined as the first rheumatology appointment at which
the patient exhibited enthesitis, arthritis or acute, symptomatic uveitis. To be
included in the study, patients had to have a documented HLA-B27 test result
and had to fulfill the ILAR criteria for ERA within the first 6 months from baseline
visit. Patient data collected included the following: demographics, clinical features,
patient reported outcomes, and medications prescribed both at the time of diagnosis
of ERA and over the following 12 months. Differences in clinical and demographic
characteristics by HLA-B27 status were assessed using the Mann-Whitney or
chi-squared test, as appropriate.
Results:
Data was collected from 301 children and a total of 296 were included in the
study. Patients were predominantly male (69%) and Caucasian (83%). Median age
at diagnosis was 12 years (IQR: 10-14) and 53% were HLA-B27 pos. HLA-B27
positivity was associated with male gender (p<0.01) and older age at
diagnosis (p=0.03). Symptom duration at time of diagnosis was shorter in the
HLA-B27 neg group with a median of 6 versus 7 months, respectively (p=0.04). Table
1 shows the ILAR criteria, clinical features and patient reported outcomes at
the time of diagnosis as well as the incidence of arthritis and enthesitis
throughout the duration of the study, and compared between HLA-B27 pos and neg
groups. Not only did a greater proportion of HLA-B27 neg patients have
enthesitis at diagnosis (78% vs. 59%; p<0.01), but these children also had greater
tender entheses counts at diagnosis (p<0.01) and a greater number of
affected entheses during the first year after diagnosis (p<0.01). Sacroiliac
tenderness and uveitis were not associated with HLA-B27 status. Disease
activity scores and patient reported outcomes were not significantly different between
the two groups.
Conclusion:
In this retrospective cohort, the clinical phenotype of children with ERA
differed significantly based on HLA-B27 status. In comparison to HLA-B27 pos
children, HLA-B27 neg children are younger, more likely to be female, and have
more peripheral enthesitis. Future studies should address differences in
response to therapy and outcomes between these 2 groups.
|
Table. Patient Characteristics Based on HLA-B27 Status |
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|
|
All (n=296) |
HLA-B27 pos (n=158) |
HLA-B27 neg (n=138) |
P-value*
|
|
ILAR ERA criteria, N (%) |
||||
|
|
||||
|
Arthritis |
260 (88) |
143 (91) |
117 (85) |
0.13 |
|
Enthesitis |
201 (68) |
93 (59) |
108 (78) |
<0.01 |
|
Sacroiliac joint tenderness and/or inflammatory spinal pain
|
92 (31) |
45 (28) |
47 (34) |
0.30 |
|
Acute, symptomatic uveitis |
17 (6) |
10 (6) |
7 (5) |
0.67 |
|
Onset of arthritis in a male > 6 years |
172 (58)
|
107 (68)
|
65 (47)
|
<0.01
|
|
Family history of HLA-B27 pos associated disease† in a first degree relative
|
42 (14)
|
23 (15)
|
19 (14)
|
0.85
|
|
Clinical Features and Patient Reported Outcomes at Diagnosis, Median (IQR) |
||||
|
Active Joint Count |
2 (1, 4) |
2 (1, 4)
|
2 (1, 3)
|
0.04
|
|
Tender Entheses Count |
2 (0, 4) |
1 (0, 3)
|
2 (1, 4)
|
<0.01
|
|
Physician disease activity (VAS 0 – 10) |
2.0 (2.0, 3.2) |
2.0 (2.0, 3.0) |
2.6 (2.0, 3.5) |
0.09 |
|
Juvenile Spondyloarthritis Disease Activity Index (JSpADA) (0 – 8) |
2.0 (1.0, 3.0) |
2.0 (1.0, 3.0) |
2.0 (1.0, 3.0) |
0.79 |
|
Function (CHAQ) (0 – 3) |
0.4 (0.0, 1.0) |
0.4 (0.0, 1.0) |
0.4 (0.0, 1.0) |
0.44 |
|
Patient/parent pain (VAS 0 – 10) |
4.0 (2.0, 7.0) |
4.0 (2.0, 7.0) |
4.0 (2.0, 6.0) |
0.48 |
|
Patient/parent disease activity (VAS 0 – 10) |
4.0 (2.0, 6.0) |
4.0 (2.0, 6.0) |
3.5 (2.0, 6.0) |
0.42 |
|
Enthesitis/Arthritis Throughout Study Duration, Median (IQR)
|
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|
Maximum tender entheses count at any visit
|
2 (1, 4) |
2(0, 4) |
3(2, 6) |
<0.01 |
|
Maximum active joint count at any visit
|
3(2, 5) |
3(2, 5) |
2(1, 4) |
0.04 |
|
Total active joints^ |
3 (2, 6) |
4 (2, 7) |
3 (2, 5) |
0.02 |
|
Total tender entheses^ |
2 (1,5) |
2 (0, 4) |
4 (2, 7) |
<0.01 |
|
Legend. *Differences between HLA-B27 categories were compared using the Mann-Whitney or chi-squared test, as appropriate. † HLA-B27 pos associated disease defined as including: ankylosing spondylitis; inflammatory bowel disease; reactive arthritis or acute anterior uveitis. ^Number of unique joints with arthritis and unique affected entheses over the first year after diagnosis. ILAR: International League of Associations for Rheumatology; HLA: human leukocyte antigen; IQR: interquartile range; CHAQ: childhood health assessment questionnaire. Number of patients with patient-reported outcomes varied due to the retrospective nature of the study. The total number of patients available for each assessment at diagnosis was as follows: Physician disease activity (N=156); CHAQ (N=149); Patient/parent pain (N=160); Patient/parent disease activity (N=123). |
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To cite this abstract in AMA style:
Gmuca S, Brandon T, Xiao R, Pagnini I, Wright TB, Beukelman T, Morgan-DeWitt E, Weiss PF. Phenotypic Differences Between HLA-B27 Positive and Negative Children with Enthesitis-Related Arthritis [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/phenotypic-differences-between-hla-b27-positive-and-negative-children-with-enthesitis-related-arthritis/. Accessed .« Back to 2015 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/phenotypic-differences-between-hla-b27-positive-and-negative-children-with-enthesitis-related-arthritis/