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Current
Rheumatology Reviews
ISSN: 1573-3971
Current Rheumatology Reviews
Volume 4, Number 2, May 2008
Contents
Spondyloarthritis in Asia
Guest Editor: Chung-Tei Chou
Editorial Pp. 80
Spondyloarthritis in Asian Countries – An Overview
Pp. 81-86
Chung-Tei Chou
[Abstract]
Epidemiology of Spondyloarthritis in Asian Countries
and Regions Pp. 87-90
Zetao Liao, Chao Li and Jieruo Gu
[Abstract]
The Association Between Genes and SpA in Asian
Pp. 91-94
Chung-Tei Chou
[Abstract]
HLA and Non-HLA Genes in Ankylosing Spondylitis and
Seronegative Spondyloarthritis in Asia Pp. 95-98
Hwee Siew Howe
[Abstract]
The Role of HLA-B27 in the Pathogenesis of Ankylosing
Spondylitis Pp. 99-102
Wen-Chan Tsa
[Abstract]
HLA-B27 Uveitis is the Most Common Type of Uveitis
in Ethnic Chinese Pp. 103-104
Yu-Mei Chung
[Abstract]
Features of Undifferentiated Spondyloarthropathy
and Juvenile Spondyloarthropathy Among Asian Populations
Pp. 105-110
Tae-Jong Kim and Tae-Hwan Kim
[Abstract]
The Prevalence and Significance of Uveitis in
Ankylosing Spondylitis and Other Spondyloarthropathies
Pp. 111-114
Horng-An Chen and Chung-Tei Chou
[Abstract]
Clinical Features of Psoriatic Arthritis in Korea
Pp. 115-119
Yeong Wook Song, Hyo Jin Choi and Jai Il Youn
[Abstract]
Patient Attitudes Toward Western Medicine and
the Future of Chinese Medicine for Spondyloarthritis
Pp. 120-123
James Cheng-Chung Wei, Yi-Chang Su, Hung-Chou Chang, Ming-Shiou
Jan, Ruey-Hong Wong and Chung-Tei Chou
[Abstract]
Imaging Characteristics of Spondyloarthropathy
Pp. 124-130
Hung-Ta Wu, Chung-Tei Chou, Hong-Jen Chiou and
Cheng-Yen Chang
[Abstract]
Management of Spondyloarthropathy in Asian Countries
Pp. 131-134
Chunhua Yang and Feng Huang
[Abstract]
Abstracts
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Editorial
Spondyloarthritis (SpA) is a common rheumatic disorder.
It consists of ankylosing spondylitis (AS), reactive arthritis
(ReA), psoriatic arthritis (PsA), inflammatory bowel disease
(IBD), juvenile chronic arthritis (JCA), and undifferentiated
spondyloarthritis (USpA), etc. Presenting differences from
rheumatoid arthritis, SpA is characterized by axial and sacroiliac
joint involvement, anterior uveitis, enthesopathy, dactylitis,
positive HLA-B27 and high family tendency. Many studies to
explore the prevalence, genetic marker, pathogenesis, clinical
features, radiologic image, pathology and management have
been largely conducted in the Western countries. By the clinical
application of biologic therapy, it becomes more understandable
for etiology and pathogenesis in SpA. As a matter of fact,
the majority of studies are performed in the Western countries
and fewer in Asian countries.
Asia has a very large population in the world. Recently, a
review of the literature disclosed that Asian investigators
have published more and more researches in SpA.
In this regard, I invited several authors from different Asian
countries to contribute a special issue of ‘Spondyloarthritis
in Asia”, and wish it can provide the knowledge and
understanding of SpA in Asian people.
Chung-Tei Chou
Division of Allergy-Immunology-Rheumatology
Veterans General Hospital
Taipei 112
Taiwan
E-mail: ctchou1007@gmail.com
[Back to top]
Spondyloarthritis in Asian Countries – An Overview
Chung-Tei Chou
Spondyloarthritis (SPA) is a group of chronic arthritis,
characterized by inflammatory back pain, peripheral arthritis
and enthesitis. Since 1973, HLA-B27 has been known as an important
genetic marker for AS and other SPA. In recent 10 years, after
the clinical application of tumor necrosis factor-alpha (TNF-α)
for SPA, a lot of researches including epidemiology, genetic
and family, immunology and serology, pathology and treatment
have been done, particularly in the US and European countries.
As a matter of fact, Asian countries own a big population
in the world, and fortunately, many studies focusing on the
SPA in Asian have been published in the last 15 years. This
special issue will review most of the researches for SPA that
have been done in Asian people.
[Back to top]
Epidemiology of Spondyloarthritis in Asian Countries
and Regions
Zetao Liao, Chao Li and Jieruo Gu
There are race-related differences in the prevalence
of AS/SpA. Asian and Pacific regions contain many countries
and regions, and many different races and nations. The purpose
of this article is to summarize the epidemiology data from
these contries, to describe the clinical features of Asian
AS/SpA patients, and to compare the clinic and genetic difference
between different races. The prevalence of AS/SpA in Chinese
and Thai are similar to that in Caucasian, while that of Japanese
is much lower because of low prevalence of HLA-B27. The sporadic
USpA has different genetic predisposition compared with familial
USpA. Patients with Juvenile onset ankylosing spondylitis
(JAS) have fewer and milder spinal symptoms and more peripheral
joint involvement than those with adult onset ankylosing spondylitis
(AAS). The Middle East Arab patients have more tendency to
present with AS and have family history, compared to South
Asian patients. The native Indonesian AS patients tend to
have HLA-B2705 subtype while most of Indonesian Chinese patients
have B2704 subtype. Different designed questionnaires are
used in the above prevalence surveys. We suggest that validation
and evaluation of these questionnaires should be carried out
in the future epidemiology study.
[Back to top]
The Association Between Genes and SpA in Asian
Chung-Tei Chou
Spondyloarthritis is a family of chronic arthritis, characterized
by inflammatory back pain, peripheral arthritis and enthesitis.
The relationship between HLA-B27 and AS was found by a British
investigator in 1973, which considerably differentiated this
disease from rheumatoid arthritis. Obviously, the prevalence
of ankylosing spondylitis (AS) is correlated with the B27
positive rate in general population. In the Asian countries,
the B27 antigen frequency in Vietnamese, Thais, Malaysians
and Indonesians ranged from 5% to 12%, which is close to or
higher than in the Chinese population. In contrast, lower
prevalence of HLA-B27 was found in Japanese (<1%) and Polynesians,
including Taiwan aborigines (<2%). Al-though the B2705
and B2704 are the major subtypes in Asian people, the relationship
between the prevalence of these subtypes and AS in Asians
has not been demonstrated. Until now, only B2706 was considered
as a “protective gene” for AS in Thai people.
In addition to B27, a study of 41 B27-negative Taiwanese (Han
Chinese) AS patients showed both B60 and B61 significantly
increased susceptibility to AS in HLA-B27 negative patients.
Also, IL1 gene cluster (IL1F10.3, IL1RN VNTR, etc) was associated
with AS in Chinese. The recent study in both psoriasis (PSO)
and psoriatic arthritis (PSA) in Taiwanese demonstrated HLA-B27
was significantly higher in PSA and HLA-A30, -CW6, DR7 in
PSO compared with healthy control. Besides, PSO patients with
the HLA-B27 and/or -CW12 have higher risk to become PSA. For
USpA, the B27 frequency was 64.3% in Chinese USpA patients
and 78% in Korean patients. Our group showed B27, DR12 and
B60 were significantly increased in USpA patients than in
control.
[Back to top]
HLA and Non-HLA Genes in Ankylosing Spondylitis and
Seronegative Spondyloarthritis in Asia
Hwee Siew Ho
Genetic susceptibility to ankylosing spondylitis, the
prototype of the seronegative spondyloarthropathies is strongly
associated with the major histocompatibility antigen HLA-B27.
However besides HLA-B27, there are other genes, both MHC and
non-MHC, that predispose to susceptibility and severity of
disease. Studies on the genetic epidemiology of these diseases
in Asia have shown similar findings to those elsewhere; with
most showing strong association of HLA-B27 with ankylosing
spondylitis, no difference in HLA B27 subtypes between patients
and controls, some association of IL-1 gene cluster, TNF and
LMP polymorphisms with ankylosing spondylitis, association
of HLADR8 with acute anterior uveitis, and no association
with TAP and TGF polymorphisms. Genetic predisposition to
disease severity has not been reported from Asian studies.
As most studies from the region have been of small sample
size, future studies should be designed to obtain adequate
levels of significance, and the results of genome wide linkage
scans may be useful in guiding future studies into the genetic
background of these diseases.
[Back to top]
The Role of HLA-B27 in the Pathogenesis of Ankylosing
Spondylitis
Wen-Chan Tsa
HLA-B27 has been well-known for its strong association
with spondyloarthropathy for more than 30 years. Much effort
has been put forth to uncover the mysterious linkage of this
gene with that disease spectrum. With its unique structural
characteristic, this molecule was found to bind to a limited
number of peptides with arginine at the p2 position, and be
weakly associated with β2-microglobulin,
which in turn, causes HLA-B27 to appear as a free heavy chain
homodimer on the cell surface. These two characteristics have
led researchers to propose two important hypotheses trying
to explain the role of this molecule in the pathogenesis of
spondyloarthropathy: the arthritogenic peptide theory and
the unfolded protein response theory. Other researchers have
noticed that the presence of HLA-B27 can modulate the bacteriahost
interaction and evoke signal transduction. Genes other than
HLA-B27 continued to be the focus of other researchers, although
data were not so consistent. Molecular mimicry was proposed
as a mechanism for disease pathogenesis not long after the
linkage of HLA-B27 with ankylosing spondylitis was found.
New evidences seem encouraging. Now there are several endogenous
and exogenous peptides sharing a similar molecular structure
that are claimed to bind to HLA-B27. Needless to say, in the
near future, a tremendous amount of evidence will hasten the
day when we finally unravel the mystery of HLA-B27 and disease
pathogenesis.
[Back to top]
HLA-B27 Uveitis is the Most Common Type of Uveitis
in Ethnic Chinese
Yu-Mei Chung
HLA-B27-associated uveitis is the most common type of
endogenous uveitis in the ethnic Chinese population. The typical
presentation of HLA-B27 uveitis is acute anterior uveitis
(AAU). AAU has been defined as a sudden onset of pain, redness,
and photophbia associated with anterior chamber cells and
flare ≥
1+, the duration of which is less than 3 months. Recurrence
of AAU with an alternating unilateral attack is an important
characteristic. Same eye attacks occur at greater than the
expected percentage as compared with attacks with a random
eye occurrence. A high number of attacks clustered in the
cold winter season is found. HLA-B27 uveitis is strongly associated
with spondyloarthritis (SpA). SpA was confirmed in 387 of
504 patients (76.8%) with HLA-B27 uveitis in our clinic from
1987 to 2004. Among them, ankylosing spondylitis occurred
in 42.5%, with a significantly higher frequency in males than
female. Undifferentiated SpA occurred in 29.8%, with a significantly
high incidence in females. Reactive arthritis occurred in
2.2%, psoriatic arthritis in 2.0%, and enteropathic arthritis
in 0.4%. A comparison of patients with and without SpA revealed
a significantly younger age at the first attack of uveitis
in patients with SpA.
[Back to top]
Features of Undifferentiated Spondyloarthropathy
and Juvenile Spondyloarthropathy Among Asian Populations
Tae-Jong Kim and Tae-Hwan Kim
The spondyloarthropathies (SpA) are defined as inflammatory
arthropathies characterised by sacroiliac involvement and
a relationship to HLA-B27. Undifferentiated spondyloarthropathy
(USpA) includes the forms that do not meet the criteria for
the established categories of SpA. The clinical spectrum of
USpA is therefore wide, due to the various combinations of
clinical and radiological manifestations of SpA. In a European
population study, USpA was found to be the second most common
clinical entity in the SpA group. However few studies have
been published on USpA, since it has usually been overlooked
due to inadequate classification criteria. Juvenile onset
spondyloarthropathy (JSpA) is a term that refers to a group
of HLA-B27-associated inflammatory disorders affecting children
under the age of 16 years. Unlike adult SpA, there is higher
prevalence of peripheral arthritis/enthesitis and lower axial
symptoms. Although USpA is common, and juvenile ankylosing
spondylitis (JAS) has different clinical features and a different
prognosis from adult ankylosing spondylitis (AAS), few studies
in Asia on these entities have been published. This paper
reviews the literature on USpA and JSpA (particularly JAS)
among Asian populations, and compares it to Western population
studies.
[Back to top]
The Prevalence and Significance of Uveitis in
Ankylosing Spondylitis and Other Spondyloarthropathies
Horng-An Chen and Chung-Tei Chou
Uveitis is defined as inflammation in the uveal tract,
which is the middle layer of the eye. In chronic and recurrent
cases, visual acuity can be affected. Anterior uveitis is
the most common form of uveitis and is the most frequent extraarticular
manifestation of ankylosing spondylitis (AS) patients. Conversely,
AS and other spondyloarthropathies (SpA) are the most common
underlying diseases associated with anterior uveitis. Both
anterior uveitis and spondyloarthropathy have a genetic association
with the HLA-B27 allele. Uveitis can be the initial clinical
manifestation of SpA patients and may contribute to the diagnosis
of previously unknown SpA diseases. The pattern and prevalence
of uveitis differ among the various SpA diseases. Uveitis
is not only the ocular inflammation of SpA disease, but is
also associated with various characteristics of the disease
entity; it has a systemic importance beyond intra-ocular inflammation,
and physicians must be aware of the significance to facilitate
the early diagnosis and treatment of uveitis and related SpA
illness.
[Back to top]
Clinical Features of Psoriatic Arthritis in Korea
Yeong Wook Song, Hyo Jin Choi and Jai Il Youn
This study was undertaken to assess the prevalence of
psoriatic arthritis (PsA) in Korean psoriasis patients and
to evaluate its clinical features. The authors evaluated 504
patients with psoriasis who visited the dermatology clinic
at Seoul National University Hospital. Fifty-three of these
patients (10.5%) were diagnosed as having PsA. Plaque-type
psoriasis was the most common in both the PsA and psoriasis
only groups, and pustular psoriasis was more frequent in the
PsA group (19.0%) than in the psoriasis only group (4.3%,
p=0.001). Nail change was more common in the PsA group (54.3%
vs 35.3%, respectively; p=0.015). Dactylitis and enthesopathy
were observed in 8.5% and 9.1% of PsA patients, respectively.
Psoriasis was followed by arthritis in 73.6% of PsA patients,
with a mean interval of 12.2 ± 10.1 (mean ±
SD) years, and spondylitis (43.4%) was the most predominant
disease type. HLA-B27 was detected in 21.1% of patients in
the PsA group.
In conclusion, plaque-type psoriasis was most common in PsA
patients, and nail change was more common in PsA patients
than in patients with psoriasis only. Spondylitis was the
most predominant form of arthritis.
[Back to top]
Patient Attitudes Toward Western Medicine and
the Future of Chinese Medicine for Spondyloarthritis
James Cheng-Chung Wei, Yi-Chang Su, Hung-Chou Chang, Ming-Shiou
Jan, Ruey-Hong Wong and Chung-Tei Chou
Spondyloarthritis (SpA) and ankylosing spondylitis (AS)
have a significant social and economic impact on ethnic Chinese
patients. Western medicine, especially NSAIDs and disease-modifying
anti-rheumatic drugs (DMARDs), are standard mainstream therapies
for patients with SpA and AS. However, patient compliance
with these medications is poor, due to the fear of side effects.
In spite of their poor functional status and disease activity,
less than 40% of AS patients are regularly treated.
Complementary and alternative medicine (CAM) is very popular
in Asian countries like China, Korea, Japan, India and Taiwan.
A Korean survey in university hospital rheumatology clinics
showed that 155 patients (68.5%) reported using at least one
form of CAM during the previous 12 months. Herbal remedies
and acupuncture were the most frequently used categories of
CAM. Compared to conventional Western treatments, CAM is seen
to have advantages in terms of a lower incidence of adverse
reactions, greater patient choice, psychological comfort,
and an increased quality of the patient/therapist relationship.
Common symptoms treated by CAM were pain (80%), decreased
functioning (43%), and lack of energy (24%).
Tripterygium wilfordii Hook. f. (Lei Gong Teng), Tetrandrine
(Tet), acupuncture and Tai Chi are some examples of potential
Chinese medicine treatments for spondyloarthritis. CAM usage
is a worldwide trend. However, further study, including basic
research and well-designed clinical trials, is warranted.
Patients should be instructed to discuss treatment strategies
for their disease, and the use of CAM, with their rheumatologists.
[Back to top]
Imaging Characteristics of Spondyloarthropathy
Hung-Ta Wu, Chung-Tei Chou, Hong-Jen Chiou and
Cheng-Yen Chang
Seronegative spondyloarthropathy is a group of diseases
composed of ankylosing spondylitis, psoriatic arthropathy,
Reiter’s syndrome, arthritis of inflammatory bowel disease,
and undifferentiated spondyloarthropathy. These diseases share
similar but variable radiological features. Spondyloarthropathy
is reported to be related to HLA- B27, and is characterized
by sacroiliitis, spondylitis, enthesis, and bone proliferation.
In this report, features of spondyloarthropathy focusing on
imaging characters are reviewed.
[Back to top]
Management of Spondyloarthropathy in Asian Countries
Chunhua Yang and Feng Huang
Spondyloarthropathy (SpA) comprises a family of chronic
inflammatory arthritis disorders, and ankylosing spondylitis
(AS) is regarded as the most frequent and severe subtype of
SpA. The prevalence of SpA in Chinese is about 0.2-0.3%. Information
about the management of SpA is limited in Asian countries.
Non-steroidal anti-inflammatory drugs (NSAIDs) are still the
medication of choice for relieving the spinal pain and morning
stiffness of SpA. Traditional NSAIDs are relatively cheap
and more readily available than selective COX-2 inhibitors
in Asian countries. Diseasemodifying agents widely used in
SpA include sulfasalazine (SSZ), thalidomide, methotrexate
(MTX) and leflunomide. SSZ and MTX are the most frequently
used in patients with SpA, even though there are few clinical
trials to verify their efficacy. Thalidomide is potentially
useful in treating severe and refractory AS patients. Tumor
necrosis factor (TNF) inhibitors have been shown to be effective
in the treatment of AS, but more attention needs to be given
to potential tuberculosis (TB) infection. Traditional herbal
medicine and acupuncture are also used in relieving pain and
improving function in SpA patients in some Asian countries.
This review will discuss the current therapeutic strategies
for SpA.
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