Current Rheumatology Reviews - Volume 4, Issue 2, 2008

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.

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.

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.

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%). Although 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.

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.

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.

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.

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.

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.

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.

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.

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.

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.