Shan-Fu Yu

Incidental discovery of high systemic lupus erythematosus disease activity associated with cytomegalovirus viral activity

We try to find the association of cytomegalovirus (CMV) infection and anti-β2 glycoprotein 1 autoantibodies (anti-β2 GP1), a key antibody in antiphospholipid syndrome (APS), among systemic lupus erythematosus (SLE) and cerebral vascular accident (CVA) patients. This retrospective study enrolled serum samples obtained from 87 SLE and 97 CVA patients who have been checked for the existence of anti-β2 GP1. First, the prevalence rate of anti-CMV IgG and IgM in patients with and without anti-β2 GP1 were compared. Second, the prevalence of anti-CMV IgG and IgM were compared between SLE and CVA patients. Last, this study analyzed the clinical characteristics and disease activity in SLE patients with positive anti-CMV IgM and IgG. No difference existed in the prevalence rate of anti-CMV IgG and IgM between positive or negative anti-β2 GP1 serum samples in both SLE and CVA patients. However, the prevalence of anti-CMV IgM was significantly higher in the SLE group than in the CVA group. Severity of clinical features and SLEDAI scores were considerably higher in patients with positive anti-CMV IgM than in SLE patients with negative anti-CMV IgM. Very impressively, all IgM-positive SLE samples (9/9) carrying highest levels of anti-CMV IgG, indicated reactivation of the latent CMV infection. Hence, it suggests that CMV reactivation might contribute toward the disease flare in some SLE patients. In future, a prospective and longitudinal study is stongly indicated.

Adherence to anti-osteoporotic regimens in a Southern Taiwanese population treated according to guidelines: a hospital-based study.

This study was designed to investigate adherence to anti‐osteoporotic regimens in a population following therapeutic guidelines; and to assess whether this experience differs from that in other administrative surveys.

Preliminary study of a traditional Chinese medicine formula in systemic lupus erythematosus patients to taper steroid dose and prevent disease flare-up

Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease. Prolonged complete remission is rare. Most patients with SLE need long‐term treatment with glucocorticoid and immunomodulators. However, side effects because of the above medications are common. We evaluated the effect of adding‐on Dan‐Chi‐Liu‐Wei combination (DCLWC) on SLE patients with conventional therapy in tapering steroid and preventing disease flare‐up. This was a double‐blind and randomized controlled trial. Sixty‐six SLE patients were recruited into this study and 53 patients who fulfilled the 1997 revised criteria for the classification of SLE with an SLE disease activity index (SLEDAI) score of 2–12 and a steroid (measured with prednisolone) daily dose of less than 20 mg/d were enrolled. The patients were randomized into either an experimental or control group. We checked the urine analysis, hemogram, liver function, renal function, C3, C4, erythrocyte sedimentation rate, and anti‐dsDNA, evaluated the SLEDAI score, and recorded the steroid dose at 0 months, 3 months, and 6 months, respectively. After 6 months of study, the C4 and blood urea nitrogen level revealed a statistically significant difference in either group. There was a tendency toward a decreased SLEDAI score in the experimental group (p = 0.083) but not in the control group (p = 0.867). The steroid dose was not statistically significant in either group. Renal function and liver function revealed no statistically significant statistics changes in either group. Adding‐on DCLWC to conventional therapy for the treatment of SLE was safe and might have a borderline effect in decreasing disease activity, but it was not possible to taper the dosage of steroid after 6 months of clinical trial. Therefore, a long‐term follow‐up and a large‐scale study are necessary to confirm the effect of DCLWC.

Association of tri-nucleotide (CAG and GGC) repeat polymorphism of androgen receptor gene in Taiwanese women with refractory or remission rheumatoid arthritis

We investigated the relationship between CAG and GGC repeat polymorphism of the androgen receptor (AR) gene and rheumatoid arthritis (RA) in female patients with different disease subtypes. This case-control study enrolled 215 women in three groups: RA patients refractory to standardized therapy (n = 51); RA patients at complete remission phase (n = 60); and healthy controls (n = 104). CAG and GGC repeat lengths were determined by automated fluorescence-based DNA fragment-sizing method. Demographic data, allele lengths, allele distribution, and zygosity status of CAG/GGC repeats were assessed for the three groups. Refractory RA patients tend to have a significantly younger onset age of RA and more elevated erythrocyte sedimentation rates than do remission RA patients. Mean and median values of CAG and GGC repeat lengths are similar in both RA and control patients. However, RA patients harboring any long CAG alleles with more than 23 repeats had an increased risk of a refractory course, whereas differences in risk were not observed between these patients and RA subtypes harboring any long GGC alleles with more than 16 repeats. In addition, the homozygous frequency of CAG but not GGC alleles was lower in refractory RA than in remission RA patients or in controls (p = 0.042). Neither CAG nor GGC repeat lengths had a significant relationship with rheumatoid factor reactivity. Our observations indicate that short CAG repeats of the AR gene with higher transactivation activity may have protective effects against refractory course of RA development and that homozygous frequency of CAG alleles may be involved in the disease remission subtype. In contrast, lack of association of GGC polymorphism and RA was also observed. Together, these data imply that CAG but not GGC alleles in the AR polymorphism may play an important role in modulating the disease pattern of RA among Taiwanese women.

EBV-encoded small RNA1 and nonresolving inflammation in rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by perpetuated inflammation in multiple joints. To date, there is no cure for RA, and the causal factor for non‐resolving inflammation in RA remains unclear. In this study, we initially observed expression of Epstein–Barr virus‐encoded small RNA1 (EBER1) in the synovial tissue of all five patients who showed nonresolving RA inflammation. By contrast, EBER1 was detected in the synovial tissue of only one out of seven patients with advanced osteoarthritis (OA; p < 0.01, Fishers exact test). To confirm this finding, we conducted a second study on synovial tissue samples taken from 23 patients with nonresolving RA inflammation and 13 patients with OA. All synovial samples from patients with nonresolving inflammation of RA showed positive expression of EBER1 (23/23, 100%), whereas none of the synovial samples from patients with OA showed expression of EBER1 (0/13, 0%; p < 0.001, by Fishers exact test). In vitro, transfection of RA synovial fibroblasts with EBER1 induced the production of interleukin‐6. Taken together, these data strongly suggest that nonresolving RA inflammation is strongly related to the presence of EBER1, which might be, at least partially, responsible for synovial fibroblast interleukin‐6 production.

The Diagnostic Value of Anti-CCP and Rheumatoid Factor for Patients with Refractory Rheumatoid Arthritis (RA) and RA in Remission

To compare the diagnostic value of antibodies to cyclic citrullinated peptides (anti-CCP) and rheumatoid factor (RF) for patients with refractory rheumatoid arthritis (RA) and RA in remission. Methods. A total of one hundred and forty three participants were enrolled: fifty one patients with RA refractory to standard methotrexate therapy, group I (Gr I, refractory RA); forty three RA patients in complete remission status for at least 3 months, group II (Gr II, RA in remission); and forty nine community-based healthy controls, group III (Gr III). Levels of anti-CCP and RF were measured for all of the subjects. The sensitivity and specificity of both tests were determined via these subjects. The receiver operating characteristic (ROC) analysis was used to display the pairs of sensitivity and specificity for different cut off points of anti-CCP and RF. False negative rate and the complementary diagnostic effect of both assays were also calculated and compared. Results. The sensitivity of anti-CCP and RF for Gr I were 84% and 78%, and 74% and 67% for Gr II, respectively. The specificity of anti-CCP and RF was 98% and 92% respectively. The ROC analysis disclosed that anti-CCP, compared to RF, provided the best combination of sensitivity and specificity for detecting either groups of RA. In addition, anti-CCP provided better complementary diagnostic effect for our RA patients when the results of opposite tests were negative (33% vs 11% in Gr I, and 29% vs 9% in Gr II) (p＜0.001). Conclusion. The detection of anti-CCP in the diagnosis of patients with refractory RA and RA in remission showed higher sensitivity and specificity than RF assay.

Effect of long-term hydroxychloroquine on vascular events in patients with systemic lupus erythematosus: a database prospective cohort study

Objectives The incidence of thromboembolism in patients with SLE is higher than that in the general population. HCQ, widely used to treat lupus, may have vascular protective effects. The aim of this study was to determine whether long-term HCQ exposure is associated with decreased thromboembolism risk in SLE. Methods We designed a prospective cohort study within an SLE population based on the National Health Insurance Research Database in Taiwan. We divided participants into HCQ and control groups according to HCQ prescription during the first year. These groups were defined by medication possession ratio (MPR) ⩾80% and MPR = 0%, respectively. Patients with an MPR between 0 and 80% were excluded. The primary outcome was a composite vascular event, including acute coronary syndrome, ischaemic stroke, pulmonary embolism, deep vein thrombosis and peripheral arterial disease 1 year after inclusion. We excluded patients from the cohort if they had outcomes within the first year. Results A total of 8397 patients were eligible for analysis. After propensity-score matching, we included 1946 patients in each group. During a mean follow-up of 7.4 years, the number of events was 139 in the HCQ group (7.1%) and 149 in the control group (7.7%). The risk of vascular events in the HCQ group was similar to that in the control group (hazard ratio = 0.91; 95% CI: 0.72, 1.15). Further subgroup analyses confirmed no statistically significant differences between the groups. Conclusion Long-term HCQ appears to have no vascular protective effect in patients with SLE.

Is Long-Term Anti-Osteoporotic Treatment Associated with Greater Risk of Cancer in People with Severe Vertebral Fractures? A Hospital-Based Cohort Study.

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Androgen receptor genetic variants in male patients with ankylosing spondylitis in Taiwan

Ankylosing spondylitis (AS) is a chronic rheumatic disorder with gender differences. The aim of study was to investigate the association between polymorphisms of the androgen receptor (AR) gene and the susceptibility to AS in Taiwanese men of Han Chinese descent.

Clinical and Abdominal Computerized Tomography Characteristics of Patients with Image-Defined Lupus Mesenteric Vasculitis

Objective: Lupus mesenteric vasculitis (LMV) is a rare but challenging diagnostic issue related to patients with systemic lupus erythematosus (SLE). Early recognition by means of clinical signs, laboratory parameters and abdominal computerized tomography (CT) can help in differential diagnosis. The aim of this study was to describe the clinical characteristics, images features and discover possible risk factors of patients with LMV.Methods: Seventeen patients with history of SLE at Kaohsiung Chang Gung Memorial Hospital from 2004 to 2012 were identified according to clinical symptoms and fulfilling at least three of the following signs on abdominal CT scan: bowel wall thickening, bowel distention, target sign, comb sign, and fat attenuation. We recorded the clinical symptoms, laboratory data, and compared with 22 control lupus patients who experienced abdominal pain but LMV was excluded after abdominal CT survey.Results: The most frequent clinical symptoms of the 17 patients were abdominal pain, nausea/vomiting, and diarrhea. The abdominal CT findings were mainly bowel wall thickening, bowel distention and the comb sign. There were no significant differences between baseline and LMV onset in the hemogram, C-reactive protein, complement, and anti-double stranded DNA antibody. Patients with positive anti-β2 glycoprotein I antibody had a greater tendency to develop LMV than the control group (OR = 6.33, 95% CI = 1.06-37.78, p=0.04).Conclusions: We identified the frequent clinical symptoms and abdominal CT features present in patients with LMV. Of all the laboratory parameters and serologic markers, anti-β2 glycoprotein I antibody was found to be a risk factor that is associated with LMV.