Pannus inflammation in sacroiliitis following immune pathological injury and radiological structural damage: a study of 193 patients with spondyloarthritis.

BACKGROUND: The pathogenesis of sacroiliitis is unclear; therefore, we aimed to systematically study the immunopathology of sacroiliitis in patients with axial spondyloarthritis (axSpA), and explore the relationship between pannus formation, inflammation, and the structural damage caused by sacroiliitis. METHODS: Fine needle aspiration biopsy of the sacroiliac joint (SIJ) was performed in 193 patients with axSpA. Clinical, laboratory, and imaging data were collected at baseline and during the follow up. Immunohistochemistry analysis was performed to detect CD34+ microvessels, CD68+ osteoclasts/macrophages, vascular endothelial growth factor (VEGF), metalloproteinase-3 (MMP-3), tumor necrosis factor-α (TNF-α), and caspase-3. Autopsy subjects were used as controls. RESULTS: In early sacroiliitis (grade 0-1) all pathological features could be observed, with the most common being subchondral pannus formation. Among the 193 patients, 98 were followed up for 1-13 years (mean 3.6 years); 63.3% had radiological progression at the endpoint. Multiple regression analysis showed that cartilage pannus invasion (OR 2.99, P = 0.010) and endochondral ossification (OR 3.97, P = 0.049) at baseline were risk factors for radiological structural damage. Compared to SIJ controls, the subchondral microvessel density, number of CD68+ multinuclear osteoclasts, and the levels of VEGF, caspase-3, MMP-3, and TNF-α expressed at the interface of the bone and cartilage were significantly higher in patients with sacroiliitis. CONCLUSIONS: Subchondral fibrovascular tissue formation is the most important pathological feature in early sacroiliitis. The existence of cartilage pannus invasion or endochondral ossification at baseline can predict radiological structural damage during the follow up.

Changes in the Prevalence of Rheumatic Diseases in Shantou, China, in the Past Three Decades: A COPCORD Study.

This study aimed to clarify changes in the prevalence of rheumatic diseases in Shantou, China, in the past 3 decades and validate whether stair-climbing is a risk factor for knee pain and knee osteoarthritis (KOA). The World Health Organization-International League Against Rheumatism Community Oriented Program for Control of Rheumatic Diseases (COPCORD) protocol was implemented. In all, 2337 adults living in buildings without elevators and 1719 adults living in buildings with elevators were surveyed. The prevalence of rheumatic pain at any site and in the knee was 15.7% and 10.2%, respectively; both types of pain had a significantly higher incidence in residents of buildings without elevators than was reported by people who lived in buildings with elevators (14.9% vs. 10.6% and 11.32% vs. 8.82%, respectively) (both P < 0.0001). The prevalence of rheumatic pain in the neck, lumbar spine, shoulder, elbow, and foot was 5.6%, 4.5%, 3.1%, 1.4%, and 1.8%, respectively; these findings were similar to the data from the 1987 rural survey, but were somewhat lower than data reported in the urban and suburban surveys of the 1990s, with the exception of neck and lumbar pain. The prevalence of KOA, gout, and fibromyalgia was 7.10%, 1.08%, and 0.07%, respectively, and their prevalence increased significantly compared with those in previous studies from the 20th century. There were no significant differences in the prevalence of rheumatoid arthritis (RA) (0.35%) or ankylosing spondylitis (AS) (0.31%) compared to that reported in prior surveys. The prevalence of KOA was higher in for residents of buildings without elevators than that in those who had access to elevators (16-64 years, 5.89% vs. 3.95%, P = 0.004; 16->85 years, 7.64% vs. 6.26%, P = 0.162). The prevalence of RA and AS remained stable, whereas that of KOA, gout, and fibromyalgia has increased significantly in Shantou, China, during the past 3 decades. Stair-climbing might be an important risk factor for knee pain and KOA.

Prevalence and risk factors of osteoporosis in patients with ankylosing spondylitis: a 5-year follow-up study of 504 cases.

OBJECTIVES: The objective of this study was to assess the prevalence and risk factors of osteoporosis (OP) in patients with ankylosing spondylitis (AS). METHODS: Demographic and clinical data of 504 AS patients were collected. Bone mineral density (BMD) measurements of the lumbar spine, proximal femur and forearm were performed by dual-energy x-ray absorptiometry at baseline and follow-up. 106 cases of sex- and age-matched healthy volunteers were enrolled as normal controls. RESULTS: In contrast to normal controls, AS patients displayed a higher prevalence of both OP (9.7% vs. 0%) and osteopenia (57.5% vs. 34.9%). The prevalence of OP was significantly higher and the BMD were significantly lower in patients with elevated erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) than patients with normal ESR and CRP. Juvenile onset, morning stiffness lasting over 0.5 hours and elevated ESR levels were risk factors for bone loss at the lumbar spine; Male gender, older age, hip involvement and lack of regular treatment were risk factors for bone loss at the femur. 173 cases were followed up for 1 to 5 years, BMD changes per year at the lumbar spine, femur and forearm were 4.8%, 2.7%, and 2.6% respectively. There was no significant difference in annual BMD change between patients treated with or without low dose glucocorticoids (GCs). Hip involvement and persistent elevated ESR levels, but not GCs treatment, were associated with decreased BMD at both the lumbar spine and the femur during follow-up in longitudinal regression analysis. CONCLUSIONS: High disease activity and hip involvement are risk factors of bone loss in patients with AS. Low-dose GCs treatment in AS does not increase the risk of OP.

Ten years' experience with needle biopsy in the early diagnosis of sacroiliitis.

OBJECTIVE: To evaluate the usefulness of needle biopsy in the diagnosis of early sacroiliitis to improve the diagnostic level and outcome of ankylosing spondylitis (AS). METHODS: One hundred nine patients in whom early AS was highly suspected, but in whom only sacroiliitis of grade I or lower on radiography/computed tomography (CT) was seen, were recruited for study. CT-guided needle biopsy of the sacroiliac joints was performed, and the patients were followed up for 5-10 years. RESULTS: Of the 109 patients, magnetic resonance imaging (MRI) was used to confirm the presence or absence of sacroiliitis in 77 patients. Of these, 23 patients were determined to have sacroiliitis on MRI, and 54 had no sacroiliitis on MRI. Needle biopsy was performed on all 109 patients. Features of inflammation were found in 85 patients, which included all 23 patients with MRI evidence of sacroiliitis and 38 of the 54 patients without MRI evidence of sacroiliitis. No features of inflammation were found on needle biopsy in 24 of the patients, including the remaining 16 patients who did not have sacroiliitis on MRI. The sensitivity and specificity of MRI for the early diagnosis of sacroiliitis in these patients were 37.7% and 100%, respectively. Thirty-four patients with pathologic evidence of sacroiliitis were followed up for 5-10 years. At the study end point, 16 of these 34 patients continued to show grade I or lower changes on CT, and 18 had changes of grade II or higher. These 18 patients included 7 of the 8 patients with evidence of sacroiliitis on MRI and 6 of the 20 patients confirmed not to have MRI evidence of sacroiliitis at baseline. CONCLUSION: MRI, though of low sensitivity, is specific for the diagnosis of early sacroiliitis. Sacroiliitis can be detected earlier by needle biopsy than by MRI.

Epidemiologic study of soft tissue rheumatism in Shantou and Taiyuan, China.

BACKGROUND: Soft tissue rheumatism is a group of common rheumatic disorders reported in many countries. For investigating the prevalence rate of soft tissue rheumatism in different population in China, we carried out a population study in Shantou rural and Taiyuan urban area. METHODS: Samples of 3915 adults in an urban area of Taiyuan, Shanxi Province, and 2350 in a rural area of Shantou, Guangdong Province were surveyed. Modified International League of Association for Rheumatology (ILAR)-Asia Pacific League of Association for Rheumatology (APLAR) Community Oriented Program for Control of Rheumatic Diseases (COPCORD) core questionnaire was implemented as screening tool. The positive responders were then all examined by rheumatologists. RESULTS: Prevalence rate of soft tissue rheumatism was 2.0% in Taiyuan, and 5.3% in Shantou. Rotator cuff (shoulder) tendinitis, adhesive capsulitis (frozen shoulder), lateral epicondylitis (tennis elbow), and digital flexor tenosynovitis (trigger finger) were the commonly seen soft tissue rheumatism in both areas. Tatarsalgia, plantar fasciitis, and De Quervain's tenosynovitis were more commonly seen in Shantou than that in Taiyuan. Only 1 case of fibromyalgia was found in Taiyuan and 2 cases in Shantou. The prevalence of soft tissue rheumatism varied with age, sex and occupation. CONCLUSIONS: Soft tissue rheumatism is common in Taiyuan and Shantou, China. The prevalence of soft tissue rheumatism was quite different with different geographic, environmental, and socioeconomic conditions; and varying with age, sex, and occupation. The prevalence of fibromyalgia is low in the present survey.

Rheumatic diseases in China.

INTRODUCTION: Epidemiological studies of rheumatic diseases have been conducted during the past 20 years in China. The aim of this study was to clarify prevalence rates of common rheumatic diseases in China. METHODS: Relevant reports of population-based surveys conducted from 1980 to 2006 were retrieved. Studies using the World Health Organization-International League of Associations for Rheumatology COPCORD (Community Oriented Program for Control of Rheumatic Diseases) protocol and those that did not employ this protocol but were published in recognized journals were identified and analyzed. RESULTS: Thirty-eight surveys including 241,169 adults from 25 provinces/cities were pooled for analysis. The prevalence of rheumatic complaints ranged from 11.6% to 46.4%, varying by locality, study protocol and age of the people surveyed. Prevalence of symptomatic osteoarthritis (OA) varied from 5.1% to 20.8%, with common sites of involvement being the lumbar spine, knee joint and cervical spine. Compared with rates of radiographic and symptomatic knee OA in the USA, elderly men in Beijing exhibited similar prevalence rates and elderly women exhibited a higher prevalence. The prevalence of hip OA and hand OA was much lower in Chinese than in Caucasian populations, but both kinds of OA were more common in coal miners. The prevalence of ankylosing spondylitis ranged from 0.2% to 0.54% among Han ethnic Chinese and were lower among mixed ethnic populations. The prevalence of psoriatic arthritis ranged from 0.01% to 0.1%, and that of reactive arthritis was 0.02%; undifferentiated spondyloarthropathy was identified in 0.64% to 1.2% of the individuals included in the surveys. The prevalence of rheumatoid arthritis (RA) ranged from 0.2% to 0.93%, with the highest rate being reported from a Taiwan urban area. In mainland China there were no significant differences in prevalence of RA between the northern and southern parts of China, or between different ethnic groups. The prevalence of hyperuricemia increased after the 1980s. The prevalence of gout was found to have increased in recent decades from 0.15% to 1.98%, apart from in the Taiwan aborigines, among whom the highest prevalence rate of 11.7% was recorded. The prevalence of primary Sjögren's syndrome in Beijing was 0.77% by the Copenhagen criteria and 0.33% by the San Diego criteria. The prevalence of soft tissue rheumatism was 2.5% to 5.7%. Fibromyalgia was seldom observed in China. CONCLUSION: Rheumatic diseases are common in China. The prevalence of rheumatic complaints varied with the locality surveyed. The prevalence of OA is comparable with that in Western countries but varies in terms of joint involvement. The prevalence of ankylosing spondylitis is similar to that in Caucasians. Except in Taiwan, the prevalence of RA in China is lower than that in developed countries. The prevalence of hyperuricemia and gout increased after the 1980s, but it remains lower than that in developed countries. More studies are required to evaluate prevalence rates among minority groups in the west and northwest parts of China, and further study is needed to address fibromyalgia in China.

Risk factors associated with rheumatic complaints: a WHO-ILAR COPCORD study in Shantou, Southeast China.

OBJECTIVE: To validate the differences of the prevalence of rheumatic symptoms between the north and south part of China and to investigate the associated risk factors for rheumatic complaints in Shantou, China. METHODS: Four samples together comprising 10,638 people > or = 16 years of age were surveyed in 1987, 1992, 1995, and 1999. The protocol of the ILAR-China Collaborative Study or the WHO-ILAR COPCORD Core Questionnaire was implemented. Data on rheumatic symptoms that were part of these surveys were collected and analyzed. RESULTS: The prevalence rate of rheumatic complaints was increasing in the Shantou area during the recent decade (in 1987 11.6%, 1992 12.5%, 1995 16.0%, and 1999 19.8%). However, it was still lower than the rate in Beijing, China, in 1987 (40.0%). Rheumatic symptoms were more prevalent in women than in men, and were more frequently seen in the elderly than in young people. The most frequently involved site was the low back followed by the knee and neck. Lumbar pain was more frequent among rural residents, while neck pain was more prevalent in the urban school-age population group. The prevalence of knee pain was significantly higher in people living in multi-story buildings without elevators compared with those living in single-story houses. The peak value of bone mineral density (BMD) in the Shantou population was 0.839 +/- 0.085 g/cm2 in men, and 0.723 +/- 0.064 g/cm2 in women, significantly higher than that reported in 13 other provinces and cities of China including Beijing. The sense of seeking a physician's care was higher in the population with a higher prevalence of rheumatic symptoms than that in the group with a lower prevalence of complaints. However, no significant difference was found in the rate of disability among the different population samples. CONCLUSION: The prevalence rate of rheumatic complaints was lower in Shantou than in Beijing. Socioeconomic status, environmental differences (e.g., Shantou in the southern and Beijing in the northern part of China), sex, age, occupation, ergonomics, BMD, and awareness of seeking medical care might all be risk factors associated with the prevalence of rheumatic complaints.

[Study on the associated risk factors of rheumatic pain: a ILAR-China, WHO COPCORD Shantou study].

OBJECTIVE: To validate the difference on the prevalence of rheumatic symptoms between north and south parts of the country and to study the associated risk factors of rheumatic complaints in Shantou city, China. METHODS: A total number of 10 638 people at above 16 years of age from four samples, were surveyed in 1987, 1992, 1995, and 1999. Protocol of International League Against Rheumatism (ILAR)-China collaborative study or WHO-ILAR community oriented program for control of rheumatic disease(COPCORD) core questionnaire was implemented. Data on related rheumatic symptoms were collected and analyzed. RESULTS: The prevalence rate of rheumatic complaints had been increasing in Shantou area during the last decade (in 1987 11.6%, 1992 12.5%, 1995 16.0% and 1999 19.8%) but still lower than that seen in Beijing, China in 1987(40.0%). Rheumatic symptoms were more prevalent in females than in males, in elderly than in young people with most frequently involved site happened in low back area, followed by knee and neck. Lumbar pain was more frequent among rural residents, while neck pain was more prevalent in urban school students. Prevalence of knee pain was significantly higher in people living in multi-storey buildings without elevator than those living in single-storey houses. The peak values of Bone Mineral Density in Shantou population were (0.839 +/- 0.085) g/cm2 in men, and (0.723 +/- 0.064) g/cm2 in women, significantly higher than that reported in 13 other provinces and cities including Beijing. The sense of seeking for medical help was higher in population with higher prevalence of rheumatic symptoms than that in lower complaints group. However, no significant difference was found in the rates of disability among the different populations. CONCLUSION: The prevalence rate of rheumatic complaints was lower in Shantou than that in Beijing. Socio-economic status, environment, sex, age, occupation, ergonomics, bone mineral density, and awareness of seeking medical care might have been the associated risk factors to the prevalence of rheumatic complaints.

[Needle biopsy of spondyloarthropathy: pathological features and clinical significance].

OBJECTIVE: To study the pathological features of sacroiliitis, aiming at improving the early diagnosis of ankylosing spondylitis (AS). METHODS: CT guided needle biopsy of sacroiliac joint (SIJ) was performed in 96 cases of spondyloarthropathy (SpA) patients with 3 autopsy materials of non-SpA sacroiliac joints serving as control. Pathological features were studied by two independent observers. Clinical data were collected and analyzed. RESULTS: No pathological change was noticed in the control group. Among the 96 cases of SpA, pathological changes were found in 76 cases, including bone marrow inflammation, pannus formation, subchondral bony plate destruction, cartilage degeneration/erosion, synovitis, and enthesitis. The aforementioned first 4 findings were present in 45 cases of grade 0/I CT sacroiliitis. In the synovial specimens obtained, synovitis was seen in some cases of grade I and all of >/= grade II CT sacroiliitis,while no inflammatory change was noticed in all cases of grade 0 CT sacroiliitis. Frequency rate of cartilage erosion and ossification in grade 0/I CT sacroiliitis was the lowest in comparison with the other groups. Moreover, in cases of grade 0/I CT sacroiliitis, cartilage erosion only present at the bony plate side, while the joint cavity side was not affected. The inflammatory index was significantly lower in cases of grade IV CT sacroiliitis than that in the other groups. Enthesitis only presented in some cases of >/= grade II CT sacroiliitis. Among the 65 undifferentiated spondyloarthropathy patients, 45 were diagnosed as AS after SIJ pathological examination. The mean disease duration of these 45 cases was significantly shorter than that in cases of >/= grade II CT sacroiliitis. CONCLUSIONS: Inflammatory changes of SIJ did exist in cases of the < grade II CT sacroiliitis. Sacroiliitis probably initiated with bone marrow inflammation, followed by pannus formation, subchondral bony plate destruction, and cartilage degeneration/erosion, eventually leading to fibrosis, ossification and joint fusion. Synovitis and enthesitis were not the very early changes of sacroiliitis. Pathological examination was beneficial to the early diagnosis and differential diagnosis of ankylosing spondylitis.

Antitumor immunopreventive and immunotherapeutic effect in mice induced by hybrid vaccine of dendritic cells and hepatocarcinoma in vivo.

AIM: To develop atumor vaccine by fusion of H22 hepatocarcinoma cells and DC, and to study its protective and therapeutical effect against H22 cell. METHODS: H22-DC vaccine was produced by PEG fusion of H22 and DC induced by cytokine released from splenic mononuclear cells, sorted by CD11c magnetic microbead marker. It was injected through the tail vein of the mice and the H(22)-DC oncogenesis was detected in the liver, spleen and lung. In order to study the therapeutical and protective effect of H(22)-DC against tumor H(22), two groups were divided: immune group and therapeutic group. Immune group was further divided into P, D, HD and H subgroups, immunized by PBS, DC, H(22)-DC and inactivated H(22), respectively, and attacked by H(22) cell. The tumor size, tumor weight, mice survival time and tumor latent period were recorded and statistically analyzed; Therapeutical group was divided into three subgroups of P, D and HD, and attacked by H(22), then treated with PBS, DC, and H(22)-DC, respectively. Pathology and flow cytometry were also applied to study the mechanism how the H(22)-DC vaccine attacked on the H(22) cell. RESULTS: 1. No oncogenesis was found in spleen, lung and liver after H22-DC injection. 2. Hybrid vaccine immunized mice had strongest CTL activity. 3. In the immune group, latent period was longer in HD subgroup than that in P, H and D subgroup; and tumor size and weight were smaller in HD subgroup than that in P, H and D subgroup. 4. In therapeutic group, tumor size was smaller in HD subgroup than that in P, D subgroup. CONCLUSION: 1. H22-DC tumor vaccine is safe without oncogenesis in vivo. 2. Hybrid vaccine can stimulate potent specific CTL activity against H22. 3. H22-DC vaccine has distinctive prophylatic effect on tumor H22 and can inhibit the tumor growth.