Chun Hsiung Chen

Factors associated with radiographic spinal involvement and hip involvement in ankylosing spondylitis.

OBJECTIVES To determine the factors associated with radiographic spinal involvement and hip involvement in ankylosing spondylitis (AS) and assess the influence of the damage seen in the radiographs on functional outcome in patients with AS. METHODS We included 531 consecutive patients and recorded the clinical, laboratory, and radiographic data. Based on the spinal radiographs, patients were classified into 3 categories: (1) no spinal involvement; (2) spinal involvement without fusion; and (3) spinal involvement with fusion. Hip involvement was assessed by the Bath Ankylosing Spondylitis Radiology Hip Index and defined by a score of at least 2. Logistic regression analyses were used to investigate the factors associated with the radiographic spine and hip involvements. RESULTS Ninety-eight (18.5%) patients had radiographic evidence of spinal fusion and 48 (9.0%) had radiographic evidence of hip involvement. Patients who had longer disease duration, elevated C-reactive protein levels, advanced sacroiliitis, and radiographic hip involvement were significantly more likely to have spinal fusion (P < 0.05). Elevated C-reactive protein levels and advanced sacroiliitis were also significantly associated with the presence of spinal involvement without fusion (P < 0.05). Early disease onset and more radiographic severity in the spine and sacroiliac joints were the predictors of radiographic hip involvement (P < 0.05). Patients with either spine or hip involvement had significantly higher Bath Ankylosing Spondylitis Functional Index scores (P < 0.001). CONCLUSION There is a relationship between radiographic sacroiliitis, spinal fusion, and hip involvement in patients with AS. Damage to the spine and hip seen radiographically can contribute to functional impairment.

Prevalence of spondyloarthritis in 504 Chinese patients with HLA‐B27‐associated acute anterior uveitis

Objectives: To estimate the prevalence of spondyloarthritis (SpA) and the clinical features of human leucocyte antigen (HLA)‐B27‐associated acute anterior uveitis (HLA‐B27 uveitis) in Chinese patients. Methods: We conducted a retrospective cohort study using a structured chart review to record the complete ocular history, including the onset of uveitis, month of uveitis attack, specific eye involvement, the time of first attack, and rheumatic manifestations from 1987 to 2004. A total of 504 patients with HLA‐B27 uveitis were consequently enrolled consecutively from the uveitis clinic of Taipei Veterans General Hospital. Results: In total, 1719 attacks of uveitis in 504 patients were recorded. Females tended to have a higher frequency of attack than males, and those with a disease course of less than 5 years showed more uveitis recurrence. The same eye attacks were observed in 156 of 332 patients (47%), more than the expected percentage compared with attacks with random‐eye occurrence (p<0.001). A significantly higher number of uveitis attacks occurred in winter. SpA‐related acute anterior uveitis (AAU) was found in 387 patients (76.8%). Ankylosing spondylitis (AS) occurred in 214 patients (42.5%), with a significantly higher prevalence in males than in females (p<0.001). Undifferentiated SpA (USpA)‐related AAU occurred in 150 patients (29.8%), with a significantly higher prevalence in females than in males (p<0.001). Patients with SpA had an earlier onset of uveitis (p = 0.01) and a greater number (⩾ 6) of attacks (p = 0.03). Conclusions: The prevalence of SpA was high in the Chinese population with HLA‐B27‐associated uveitis. The association with SpA indicated an earlier age of uveitis onset and a greater likelihood of having a higher number of uveitis attacks.

Association of acute anterior uveitis with disease activity, functional ability and physical mobility in patients with ankylosing spondylitis: a cross-sectional study of Chinese patients in Taiwan

Acute anterior uveitis (AAU) is the most frequently extra-articular manifestation of ankylosing spondylitis (AS). To investigate whether AAU has an association with disease activity, functional ability and physical mobility in AS patients, 146 Chinese AS patients in Taiwan were enrolled in a cross-sectional study. These patients fulfilled the 1984 modified New York criteria and visited the Outpatient Department of the Veterans General Hospital-Taipei from April 2004 to July 2005. Patients completed questionnaires assessing disease activity [Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)], functional ability [Bath Ankylosing Spondylitis Functional Index (BASFI)] and patient’s global assessment [Bath Ankylosing Spondylitis Patient Global Score (BAS-G)]. Meanwhile, physical examinations were performed, including Schober test, finger-to-floor, lateral spinal flexion, occiput-to-wall and chest expansion. The history of AAU was accepted only if diagnosed by an ophthalmologist. The prevalence of AAU in this Chinese AS cohort was 15.8% (23/146). Patients with AAU had a significantly higher BASDAI than those without [absolute differences=0.96, 95% confidence intervals (CI): 0.35∼1.88]. Additionally, patients with AAU had significantly increased BASFI than those without (absolute differences=1.46, 95% CI: 0.33∼2.59). Moreover, there was advanced limitation of physical motility in patients with AAU, including finger-to-floor, occiput-to-wall distances and Schober test, (95% CI: 3.89∼16.95 and p=0.046, respectively). Disease duration mildly correlated with BASFI (r=0.24, p=0.003) but not with BASDAI (p=0.838). There was no difference of disease duration between patients with and without AAU (p=0.343). These results suggested that the presence of AAU in AS patients may be associated with higher disease activity, poor functional ability and advanced physical impairment.

Clinical, Functional, and Radiographic Differences Among Juvenile-onset, Adult-onset, and Late-onset Ankylosing Spondylitis

Objective. The aim of our study was to compare the clinical, functional, and radiographic outcomes at different ages of onset in patients with ankylosing spondylitis (AS). Methods. A total of 546 patients were enrolled consecutively and classified into 3 groups based on their age at symptom onset: (1) juvenile-onset AS (age ≤ 16 years; JoAS); (2) adult-onset AS (> 16 but < 40 years; AoAS); and (3) late-onset AS (≥ 40 years; LoAS). We compared the differences among the 3 groups. OR for disease outcomes were calculated and adjusted for sex, HLA-B27, and disease duration. Results. There were 67 patients (12.3%) with JoAS, 460 (84.2%) with AoAS, and 19 (3.5%) with LoAS. Male sex and HLA-B27 were associated with a younger age at onset (p < 0.001). Compared to patients with AoAS, patients with JoAS were more likely to present with peripheral arthritis, while patients with JoAS and LoAS were less likely to have back pain at the onset of AS (p < 0.05). After controlling for multiple covariates, JoAS was found to be associated with a worse functional outcome and global assessment, and a high serum immunoglobulin A level (p < 0.05). Patients with JoAS had less lumbar spinal radiographic severity (p < 0.05). There were no statistical differences in clinical or functional outcome between the LoAS and AoAS groups. None of the LoAS patients had radiographic hip involvement. Conclusion. Sex and HLA-B27 are significantly associated with age at onset of AS. Both JoAS and LoAS have their distinctive symptoms/signs at onset and different disease outcomes.

Immunohistological features of hip synovitis in ankylosing spondylitis with advanced hip involvement

Division of Allergy-Immunology-Rheumatology, Veterans General Hospital, and National Yang-Ming University, Buddhist Tzu Chi General Hospital, Taipei Branch, Department of Nursing, National Taipei College of Nursing, Division of Allergy-ImmunologyRheumatology, Wan Fang Hospital, Department of Pathology and Laboratory Medicine, and Department of Orthopaedics, Veterans General Hospital, Taipei, Taiwan

Association of cigarette smoking with Chinese ankylosing spondylitis patients in Taiwan: A poor disease outcome in systemic inflammation, functional ability, and physical mobility

We investigated the association between smoking and the disease activity, functional ability, physical mobility, and systemic inflammation in Chinese ankylosing spondylitis (AS) patients. Seventy five male Chinese AS patients in Taiwan were enrolled in the cross-sectional study. These patients fulfilled the 1984 modified New York criteria. Patients completed the questionnaires, containing the demographic data, disease activity, functional ability (BASFI), and patient’s global assessment. Meanwhile, physical examinations were performed to determine the patient’s physical mobility. Acute-phase reactants, erythrocyte sedimentation rate (ESR), and C-reactive protein levels were also measured in the AS patients. Smoking habits with smoking duration and smoking intensity (pack–years of smoking) were recorded. Among these physical mobility parameters, modified Schober’s index (p < 0.001), cervical rotation (p = 0.034), later lumbar flexion (p = 0.002), chest expansion (p = 0.016), and occiput-to-wall distances (p = 0.003) were significantly impaired in smoking AS patients (n = 35) as compared to non-smoking (n = 40). Systemic inflammation parameter, ESR was significantly higher in smoking AS patients than non-smoking (p = 0.03). The odds ratio of advanced modified Schober’s index, lateral lumbar flexion, fingertip-to-floor distance, chest expansion, and occiput-to-wall were significantly elevated in smoking AS patients as compared to non-smoking. Moreover, the smoking intensity correlated significantly with BASFI (r = 0.481, p = 0.005), cervical rotation (r = −0.401, p = 0.031), fingertip-to-floor distance (r = 0.485, p = 0.004), and occiput-to-wall distance (r = 0.473, p = 0.005) in the 35 smoking AS patients. The cigarette smokers in the Chinese AS patients have increased systemic inflammation and poor physical mobility. In addition, the higher smoking intensity in the AS smokers is associated with poor disease outcome, including functional ability and physical mobility. Thus, it is quite important for the physician to emphasize the association of smoking with poor disease prognosis in AS, and patients should be strongly recommended to avoid smoking cigarette.

Autoantibody and Biopsy Grading Are Associated with Expression of ICAM-1, MMP-3, and TRAIL in Salivary Gland Mononuclear Cells of Chinese Patients with Sjögren’s Syndrome

Objective. Sjögren’s syndrome (SS) is an inflammatory autoimmune disease. We investigated important factors associated with the expression of inflammation-related molecules in minor salivary gland (MSG) mononuclear cells in patients with SS. Methods. Thirty-four patients with SS with a MSG biopsy grading of either grade III (10 patients) or grade IV (24 patients) were enrolled. The age, sex, autoantibodies, cell infiltration, and intercellular adhesion molecule-1 (ICAM-1), matrix metalloproteinase-3 (MMP-3), tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), or CXCR3 expression were also analyzed. Results. Ten of the 34 patients with SS were diagnosed with secondary SS; in these patients, the diagnosis of rheumatoid arthritis was confirmed in 8 and systemic lupus erythematosus in 2. TRAIL and ICAM-1 were overexpressed in patients with antinuclear antibodies (ANA) > 1:160, compared to those with titer < 1:160 (45.1 ± 4.4 vs 41.2 ± 3.9, p = 0.021, and 15.2 ± 5.7 vs 10.8 ± 3.3, p = 0.018, respectively). Higher erythrocyte sedimentation rate (ESR; ≥ 20) was associated with higher TRAIL expression and CD20 cell infiltration in contrast to lower ESR (< 20; p < 0.05). ICAM-1, TRAIL, and MMP-3 were expressed more predominantly in anti-SSA-positive than in anti-SSA-negative patients with SS. There was a significant difference in CD20 cell infiltration and MMP-3 expression between primary SS and secondary SS. Biopsy of a grade IV showed a significantly increased expression of TRAIL (44.9 ± 4.5 vs 40.8 ± 3.6, p = 0.013) and MMP-3 (62.7 ± 6.3 vs 54.4 ± 7.3, p = 0.003) in mononuclear cells as compared to those of grade III. Conclusion. In our study, pathologic grading with a higher grade (grade IV) and the presence of SSA or a higher titer of ANA were significantly associated with the overexpression of TRAIL, MMP-3, or ICAM-1 in the salivary gland mononuclear cells in patients with SS.

A large ulcer and cutaneous small‐vessel vasculitis associated with syphilis infection

Cutaneous vasculitis (CV) is a condition with cutaneous manifestations and possible systemic involvement. The causative factors or associated diseases are usually drugs, infection, collagen vascular disease, or malignancy. Syphilis as a cause of cutaneous vasculitis is rare. We report the case of a large cutaneous ulcer and small‐vessel vasculitis associated with syphilis infection. We suggest that in apparently idiopathic CV or a chronic ulcer refractory to treatment, screening should be performed to detect any underlying infection such as syphilis. It is important to have a rapid and accurate diagnosis because the lesions are very contagious, but may be rapidly and completely cured by early administration of antibiotic treatment.

Human leukocyte antigen-G in ankylosing spondylitis and the response after tumour necrosis factor-α blocker therapy

OBJECTIVE To investigate the role of HLA-G in AS. METHODS Serum levels of soluble HLA-G (sHLA-G) were measured in 80 AS patients and 30 healthy controls. The expression of HLA-G on the peripheral blood mononuclear cell (PBMC) surface was investigated in the same 80 AS patients and 40 healthy controls by flow cytometry. The response of HLA-G after 3 months of TNF-alpha blocker therapy (adalimumab) was evaluated in 14 AS patients. We evaluated Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Patient Global Score (BAS-G), physical mobility, ESR and CRP levels. RESULTS Serum levels of sHLA-G were significantly lower in 80 AS patients than 30 healthy controls [mean (s.d.) 22.47 (26.8) vs 34.78 (32.01) U/ml, P = 0.028], and correlated significantly with modified Schober index (r = 0.326; P = 0.009), chest expansion (r = 0.319; P = 0.011), lateral lumbar flexion (r = 0.377; P = 0.002), cervical rotation (r = 0.396; P = 0.004), whereas inversely correlated with fingertip-to-floor distance (r = -0.282; P = 0.026) and tragus-to-wall distance (r = -0.270; P = 0.031). The expression of HLA-G on PBMCs was significantly higher in 80 AS patients than 40 healthy controls [mean (s.d.) 18.5 (6.10)% vs 15.41 (4.84)%; P = 0.012], and correlated significantly with ESR (r = 0.421; P < 0.001) and CRP (r = 0.419; P < 0.001). The expression of HLA-G on PMBCs decreased significantly after 3 months of adalimumab therapy [third month vs baseline, 13.46 (5.38)% vs 19.87 (7.31)%; P = 0.016]. CONCLUSIONS Lower serum levels of sHLA-G contribute to susceptibility to AS, and predispose to poor spinal mobility. The expression of HLA-G on PMBCs is up-regulated in AS, correlates with acute phase reactants and decreases after TNF-alpha blocker therapy, suggesting an index of disease activity.

Adult Still's disease patient developed thrombotic microangiopathy with diffuse digital gangrene

Adult onset Still’s disease (AOSD) is frequently manifested by the appearance of fever, skin rash, arthritis, sore throat, leucocytosis, hypertransaminasaemia, or hepatosplenomegaly (1). Severe lifethreatening complications, such as fulminant liver failure, acute respiratory distress syndrome, haemophagocytic syndrome, disseminated intravascular coagulation (DIC), or thrombotic microangiopathy (TMA) have been reported (2–4). We report here the case of an ASOD patient with pulmonary arterial hypertension (PAH) who developed TMA with diffuse digital gangrene in 2005 while the AOSD was still active. After immediate, aggressive treatment with pulse methylprednisolone and plasma exchange, progression of digital gangrene stopped, haemolytic anaemia and thrombocytopaenia gradually recovered. Our 42-year-old female was diagnosed with AOSD in October 1998 with the manifestations of arthritis, salmon-like skin rash, fever (up to 39.8 C̊), hyperferritinaemia (1134; normal 9–90 ng/mL), splenomegaly, and leucocytosis [white blood cell (WBC) count: 23.3610/L], fulfilling the diagnostic criteria proposed by Yamaguchi et al (1). At that time serum rheumatoid factor (RF) and anti-nuclear antibodies (ANA) were negative. Infection, malignancy, or other autoimmune diseases including Sjögren’s syndrome, systemic lupus erythematosus (SLE), and rheumatoid arthritis were also excluded after extensive studies. The patient then took prednisolone and nonsteroidal anti-inflammatory drugs (NSAIDs) irregularly but the disease activity of AOSD always remained active. Because of progressive exertional dyspnoea, pulmonary arterial hypertension (PAH) was diagnosed in April 2003, with right ventricle systolic pressure of 80 mmHg as determined by echocardiography. Other aetiologies that might contribute to the development of PAH were excluded, including anti-phospholipid syndrome (APS), in which serum anti-cardiolipin antibodies and lupus anticoagulant were negative. She was then treated with methotrexate (15 mg/week), prednisolone (10–15 mg/day), Bosentan (250 mg/day), and furosemide. On 28 April 2005, the digits of all four limbs suddenly became gangrenous (Figure 1) and the patient was drowsy the next day. At that time her vital signs were 35.5 C̊, 106/63 mmHg (blood pressure), 120/min (pulse rate), and 26/min (respiratory rate). WBC count was 10.6610/L and platelet count was 87610/L. Haemoglobin fell from 11.1 to 9.1 g/dL within 2 days after the digital gangrene developed. Urinalysis showed mild proteinuria. C-reactive protein was 12 mg/dL and erythrocyte sedimentation rate was 47 mm/h. A peripheral blood smear revealed many fragmented