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The Journal of Rheumatology 2014; 41:10; doi:10.3899/jrheum.131462
Personal non-commercial use only. The Journal of Rheumatology Copyright © 2014. All rights reserved.
Is HLA-B27 Increased in Patients Diagnosed with
Undifferentiated Arthritis? Results from the Leiden
Early Arthritis Cohort
Floris van Gaalen, Rosaline van den Berg, Inge Verhoog, Joris Schonkeren,
Annette van der Helm-van Mil, Tom Huizinga, and Désirée M. van der Heijde
ABSTRACT. Objective. Undifferentiated arthritis (UA) is a common form of arthritis. According to the
Assessment of Spondyloarthritis international Society (ASAS) criteria for peripheral spondy-
loarthritis (pSpA), HLA-B27 can be used to help classify patients with pSpA. We tested whether
HLA-B27 is increased in patients diagnosed with UA.
Methods. Prevalence of HLA-B27 was compared between healthy controls and patients with UA.
SpA features were compared between HLA-B27-positive and -negative UA, and SpA.
Results. We found 10.1% of UA (38/375) versus 7.2% (403/5584) of controls were HLA-B27-posi-
tive (OR 1.5, 95% CI 1.0–2.1; p = 0.037). HLA-B27-positive patients with UA had more SpA
features than HLA-B27-negative patients (mean 1.6, SD 1.0, and 0.9 SD 0.6; p < 0.001), but patients
with SpA had significantly more SpA features (mean 4.5, SD 1.5; p < 0.001). Family history and
preceding infection were features more common in HLA-B27-positive than in HLA-B27-negative
UA (15.8% vs 1.3%, p = 0.04 and 15.8% vs 2.6%, p = 0.04). After HLA-B27 testing, 21 additional
patients (5.6%) with UA could potentially have been classified with pSpA according to the ASAS
criteria.
Conclusion. HLA-B27 is more common in patients with UA than in controls. However, the yield of
HLA-B27 testing in UA is low. Our results suggest that HLA-B27 testing should be reserved for
patients with additional SpA features. (First Release Aug 15 2014; J Rheumatol 2014; 41:1948–51;
doi:10.3899/jrheum.131462)
Key Indexing Terms:
HLA-B27 GENETIC RISK FACTORS
SPONDYLOARTHRITIS UNDIFFERENTIATED ARTHRITIS
From the Department of Rheumatology, Leiden University Medical
Centre, Leiden, the Netherlands.
The work of F. van Gaalen is supported by Tracer, a Centre for
Translational Molecular Medicine project.
F. van Gaalen, MD, PhD; R. van den Berg, MSc; I. Verhoog, BSc;
J. Schonkeren, BSc; A. van der Helm-van Mil, MD, PhD; T. Huizinga,
MD, PhD; D.M. van der Heijde, MD, PhD, Department of Rheumatology,
Leiden University Medical Centre.
Address correspondence to Dr. F. van Gaalen, Department of
Rheumatology, Leiden University Medical Centre, C4-R, PO Box 9600,
Leiden 2300 R, The Netherlands. E-mail: f.a.van_gaalen@lumc.nl
Accepted for publication June 18, 2014.
Spondyloarthritis (SpA) refers to a group of common related
rheumatic diseases, including ankylosing spondylitis,
psoriatic arthritis, reactive arthritis, inflammatory bowel
disease (IBD)-related spondylitis and arthritis, and undiffer-
entiated SpA. The clinical presentation of SpA is hetero-
geneous, and no single distinguishing feature exists for all
forms of SpA
1
. However, various clinical laboratory and
imaging features suggestive of SpA are known and form the
building blocks for classification criteria for SpA and
diseases in the SpA spectrum.
SpA can be distinguished by its clinical presentation as
predominantly axial SpA (axSpA; e.g., inflammation of the
spine and/or sacroiliac joints) or peripheral SpA (pSpA; e.g.,
arthritis, dactylitis, and/or enthesitis) and classified with 2
criteria sets developed by the Assessment of Spondylo-
Arthritis international Society (ASAS). In patients with
early arthritis, the ASAS pSpA criteria performed well with
a good specificity at a reasonable sensitivity
2
.
According to the ASAS criteria for pSpA, HLA-B27 can
be used to help classify patients with pSpA
3
. While in adults
HLA-B27 is better known for its association with axSpA
rather than pSpA
4
, we recently showed that in a large cohort
of patients presenting with arthritis, HLA-B27 was signifi-
cantly more common in patients with SpA than in patients
without SpA
2
.
Undifferentiated arthritis (UA) is defined as an inflam-
matory arthritis in which no definitive diagnosis can be
made. Inception cohorts from Europe and North America
have shown that UA is common and may even be seen more
frequently than rheumatoid arthritis (RA). Estimates of the
percentage of patients diagnosed with UA range from 23%
to 81% of early arthritis cohorts
5
. UA spans a wide spectrum
of conditions with various natural courses. Some patients
will have a benign, self-limiting disease course while others
will experience disease persistence including development
of destructive arthritis
6
. There are limited data on the preva-
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