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Objective To examine longitudinal associations of active lupus nephritis with organ damage accrual in patients with systemic lupus erythematosus (SLE). Methods This study was performed using data from a large multinational prospective cohort. Active lupus nephritis at any visit was defined by the presence of urinary casts, proteinuria, haematuria or pyuria, as indicated by the cut-offs in the SLE Disease Activity Index (SLEDAI)-2K, collected at each visit. Organ damage accrual was defined as a change of SLICC-ACR Damage Index (SDI) score >0 units between baseline and final annual visits. Renal damage accrual was defined if there was new damage recorded in renal SDI domains (estimated glomerular filtration rate 3.5 g per 24 h/end-stage kidney disease). Time-dependent hazard regression analyses were used to examine the associations between active lupus nephritis and damage accrual. Results Patients ( N = 1735) were studied during 12,717 visits for a median (inter-quartile range) follow-up period of 795 (532, 1087) days. Forty per cent of patients had evidence of active lupus nephritis at least once during the study period, and active lupus nephritis was observed in 3030 (24%) visits. Forty-eight per cent of patients had organ damage at baseline and 14% accrued organ damage. Patients with active lupus nephritis were 52% more likely to accrue any organ damage compared with those without active lupus nephritis (adjusted hazard ratio = 1.52 (95% confidence interval (CI): 1.16, 1.97), p Conclusion Active lupus nephritis measured using the SLEDAI-2K domain cut-offs is associated with renal, but not non-renal, damage accrual in SLE.

Fcgamma receptors (FcgammaR) impact upon the development of inflammatory arthritis through immune complex stimulation and proinflammatory cytokine production. FcgammaRIIa, FcgammaRIotaIotaIotaa and FcRgammaIIIb polymorphisms were genotyped in 212 rheumatoid arthritis (RA) patients and 371 healthy control subjects using an allelic-specific polymerase chain reaction (PCR). No significant skewing in the distribution of FcgammaRIIa H/R131, FcgammaRIIIa F/V158 and FcgammaRIIIb NA1/NA2 was found between RA patients and healthy control subjects. However, a significant skewing distribution of the FcgammaRIIIa F/V158 polymorphism was observed between rheumatoid factor (RF)-positive versus RF-negative RA patients (P = 0.01). The low-affinity FcgammaRIIIa F158 allele seems to have a protective role in RF production, in comparison with the FcgammaRIIIa V158 allele (P = 0.004; OR = 0.485; 95% CI: 0.293-0.803). A high frequency of FcgammaRIIIa F/F158 was identified in RA patients with negative RF compared with RF-positive patients (for FF158 versus FV158 + VV158; P = 0.002; OR = 0.372; 95% CI: 0.194-0.713). In addition, no association was found between FcgammaRIIa H/R131, FcgammaRhoIIIa F/V158 and FcgammaRIIIb NA1/NA2 polymorphisms and other clinical parameters. The results of this study suggest that three activating FcgammaRs polymorphisms lack association with RA but FcgammaIIIa F/V158 polymorphism may influence RF production and IgG RF immune complex handling in Taiwanese RA patients.

Summary Apoptosis is important in the pathogenesis of systemic lupus erythematosus (SLE). Several genome-wide scan studies have suggested chromosome 1q as a genetic susceptibility locus for SLE. This study investigated the association of apoptosis-related genes on chromosome 1q, Fas ligand (FasL), interleukin (IL)-10 and poly(ADP-ribose) polymerase (PARP), promoter microsatellite multi-allelic polymorphisms with SLE susceptibility and clinical characteristics in Taiwan. This study recruited 237 SLE patients and 304 healthy controls. FasL, IL-10 and PARP promoter microsatellite polymorphisms were genotyped employing gene scan. IL-10, located on 1q31–32, emerged as a significant susceptibility gene locus in Taiwanese SLE (T4 statistic = 0·01). IL-10 CA21 allele was the most common allele of 15 identified in Taiwanese, displaying skewed distribution of susceptibility in Taiwanese SLE patients. Conversely, the IL-10 CA20 allele showed a protective effect of SLE susceptibility. Additionally, the IL-10 CA26 allele displayed a negative significant association with ascites and IL-10 CA25 allele increased the occurrence of the anti-cardiolipin IgM antibody. This study identified five alleles of FasL and nine alleles of PARP of microsatellite polymorphisms in Taiwanese patients. FasL and PARP alleles displayed no skewing distribution between Taiwanese SLE patients and controls. However, FasL GT15 and PARP CA17 allele demonstrated a high discoid rash presentation (T4 statistic 0·01 and 0·03, respectively) and PARP CA12 allele displayed a significant association with anti-cardiolipin IgM antibody production (T4 statistic 0·02). IL-10, FasL and PARP microsatellite polymorphisms exhibited significant associations with SLE susceptibility and/or clinical characteristics in Taiwanese patients. Thus, SLE is a complex and multiple genetics determined autoimmune disease. Chromosome 1q23–42 is an important genetic locus for further SLE subphenotype susceptibility study.

Systemic lupus erythematosus (SLE) in the elderly is uncommon and rarely reported with disease onset at age 65 and older. The aim of this study is to retrospectively analyze the influence of age at disease onset on the clinical features and prognosis of SLE. From 1988 to 1998, we encountered 21 lupus patients with disease onset at age 65 and older (all are included in group A). For comparison, 21 lupus patients with disease onset between 50 ± 64 years of age (group B)and 152 lupus patients with disease onset before 50 years of age (group C) were obtained by a simple random sampling method from the hospital registry. Clinical features as included in the 1982 ARA revised criteria for classification of SLE and survival rate were analyzed and compared among these three groups. Group A had a smaller female to male ratio, longer duration from disease onset to diagnosis, less malar rash, more discoid lupus, and shorter survival rate that group C. There was no statistically significant difference in clinical features and survival between groups A and B, as well as between female and male patients of these two groups. The main cause of death in group A was septic shock. In conclusion, the clinical features and prognosis of SLE were influenced by the age at disease onset. However, clinical features and prognosis of SLE were similar in both late-onset lupus groups.

Nationwide data on the epidemiology of dermatomyositis (DM) and polymyositis (PM) were limited.This study was to estimate the incidence, occurrence of cancer and mortality of DM and PM in Taiwan.Both the register of critical illness of the Taiwan National Health Insurance Research Dataset and the National Death Registry of Taiwan were used to calculate estimates of the incidence, cancer association, and mortality of DM and PM between 2003 and 2007.A total of 803 DM and 500 PM cases were identified between 2003 and 2007. Mean age at diagnosis was 44·0 ± 18·3 years for DM and 49·2 ± 15·9 years for PM. The overall annual incidences of DM and PM were 7·1 (95% CI 6·6-7·6) and 4·4 (95% CI 4·0-4·8) cases per million population. The incidence of both DM and PM increased with age and reached a peak at age 50-59 years. One hundred and eleven (13·8%) patients with DM and 31 (6·2%) patients with PM had cancers. The diagnosis of most cancers was made after the diagnoses of DM (n = 71; 64·0%) and PM (n = 21; 67·7%). Overall, the standardized incidence ratios (SIR) for cancer were 5·36 (4·12-6·87) and 1·80 (1·10-2·79) among patients with DM and PM; however, during the first year, SIRs for cancer were 24·55 (95% CI 18·62-31·79) and 9·17 (95% CI 14·82-15·93) in patients with DM and PM, respectively. The most common types of cancer were nasopharyngeal cancer for men and breast cancer for women. Patients with DM and PM had standardized mortality ratios of 7·68 (6·41-9·01) and 5·29 (4·28-6·48).This study reports robust estimates of important aspects of the epidemiology of both DM and PM in Taiwan. This highlights the rarity of these diseases, and their associated cancer risks and increased mortality.

Though proximal muscle weakness is characteristic of polymyositis, other agents may also lead to proximal muscle weakness, such as drugs, endocrine diseases, or infections. Here, we report a thirty year-old female suffering from proximal weakness which initially was thought to be a case of polymyositis with high serum creatine phosphokinase level. Very low thyroid hormone levels were found as the history inquiry revealed constipation, hoarseness and cold intolerance. The muscle biopsy showed no obvious inflammation. After thyroxine therapy, her muscle weakness recovered. Up to now, hypothyroid myopathy with muscle mitochondrial abnormalities shown by electron microscopic examination has not been reported in the medical literature in Taiwan. Hypothyroid myopathy, though it is rare, may be misdiagnosed as polymyositis clinically. Therefore, it is recommended that hypothyroid myopathy should be considered in the differential diagnosis of proximal muscle weakness.

Elevated levels of several cytokines including interleukin-1beta (IL-1beta) have been detected in airway fluid of asthmatic patients. Inhalation of IL-1beta induced a bronchial hyper-reactivity to contractile agonists. However, the implication of IL-1beta in the pathogenesis of bronchial hyper-reactivity is not completely understood. Therefore, we investigated the effect of IL-1beta on bradykinin (BK)-induced inositol phosphate [Ins(X)P] accumulation and Ca2+ mobilization, and up-regulation of BK receptor density in canine cultured tracheal smooth-muscle cells (TSMCs). Treatment of TSMCs with IL-1beta potentiated BK-induced Ins(X)P accumulation and Ca2+ mobilization. However, there was no effect on the Ins(X)P response induced by endothelin-1, 5-hydroxytryptamine or carbachol. Treatment with platelet-derived growth factor B-chain homodimer (PDGF-BB) also enhanced the BK-induced Ins(X)P response. These enhancements by IL-1beta and PDGF-BB might be due to an up-regulation of BK B(2) receptor density (B(max)), since [(3)H]BK binding to TSMCs was inhibited by the B(2)-selective agonist and antagonist, BK and Hoe 140, but not by B(1)-selective reagents. The enhancing effects of IL-1beta and PDGF-BB on Ins(X)P accumulation, Ca2+ mobilization and B(max) were attenuated by PD98059 [an inhibitor of activation of mitogen-activated protein kinase (MAPK) kinase, MEK] and cycloheximide (an inhibitor of protein synthesis), suggesting that IL-1beta may share a common signalling pathway with PDGF-BB via protein synthesis. Furthermore, overexpression of dominant negative mutants, H-Ras-15A and Raf-N4, significantly suppressed the up-regulation of BK receptors induced by IL-1beta, indicating that Ras and Raf may be required for activation of these kinases. These results suggest that the augmentation of BK-induced responses produced by IL-1beta might be, at least in part, mediated through activation of the Ras/Raf/MEK/MAPK pathway in TSMCs.

Bacterial lipopolysaccharide (LPS) was found to induce inflammatory responses and to enhance bronchial hyperreactivity to several contractile agonists. However, the implication of LPS in the pathogenesis of bronchial hyperreactivity was not completely understood. Therefore, in this study, we investigated the effect of LPS on mitogen-activated protein kinase (MAPK) activation associated with potentiation of bradykinin (BK)-induced inositol phosphates (IPs) accumulation and Ca(2+) mobilization in canine cultured tracheal smooth muscle cells (TSMCs). LPS stimulated phosphorylation of p42/p44 MAPK in a time- and concentration-dependent manner using a Western blot analysis against a specific phosphorylated form of MAPK antibody. Maximal stimulation of the p42 and p44 MAPK isoforms occurred after 7 min-incubation and the maximal effect was achieved with 100 microg ml(-1) LPS. Pretreatment of TSMCs with LPS potentiated BK-induced IPs accumulation and Ca(2+) mobilization. However, there was no effect on the IPs response induced by endothelin-1, 5-hydroxytryptamine, and carbachol. In addition, pretreatment with PDGF-BB enhanced BK-induced IPs response. These enhancements by LPS and PDGF-BB might be due to an increase in BK B(2) receptor density (B(max)) in TSMCs, characterized by competitive inhibition of [(3)H]-BK binding using B(1) and B(2) receptor-selective reagents. The enhancing effects of LPS and PDGF-BB were attenuated by PD98059, an inhibitor of MAPK kinase (MEK), suggesting that the effect of LPS may share a common signalling pathway with PDGF-BB in TSMCs. Furthermore, overexpression of dominant negative mutants, H-Ras-15A and Raf-N4, significantly suppressed p42/p44 MAPK activation induced by LPS and PDGF-BB, indicating that Ras and Raf may be required for activation of these kinases. These results suggest that the augmentation of BK-induced responses produced by LPS might be, at least in part, mediated through activation of Ras/Raf/MEK/MAPK pathway in TSMCs.

The term chondrocalcinosis is often used to describe the radiological or pathological features of calcified joint cartilage, and it usually indicates the deposition in cartilage of calcium pyrophosphate dihydrate. The prevalence of chondrocalcinosis increases with age, with dramatic increases occurring in the decades past age 60. In younger patients with chondrocalcinosis, either clinical evidence of associated metabolic diseases leading to the chondrocalcinosis or familial disease occurrence usually can be detected. We report a 42-year-old Chinese woman with ankylosing spondylitis and arthritis involving multiple peripheral joints. Severe chondrocalcinosis was detected incidentally in this patient, however, subsequent studies revealed no associated metabolic disease or familial susceptibility and the clinical features of this patient were different from those of ankylosing chondrocalcinosis (pseudoankylosing spondylitis). The cause of chondrocalcinosis in this patient remains unknown, but joint damage and repair could have been initiating or aggravating factors of the chondrocalcinosis.

Suppurative coxitis induced by salmonella is rarely reported in the literature. Furthermore, reconstruction with a total hip arthroplasty (THA) in such patients has never been reported. However, in this study, we present 4 cases; 2 normal male patients and 2 female patients with underlying systemic lupus erythematosus (SLE). The ages range from 26 to 61 years. All 4 cases revealed growth of group B salmonella from the cultures of synovial fluid. They all received THA after the infections were eradicated. The functional assessment of pain, range of motion, walking ability together with the radiographic assessment were used according to the new hip score system. After a minimum follow-up of 2 years, all of the reconstructed hips showed good to excellent results since no infections recurred during this period. Although the long-term results are uncertain, the short-term clinical advantage of THA in the treatment of quiescent salmonella coxitis is encouraging.

Acute myocardial infarction is an important and sometimes fatal complication of systemic lupus erythematosus (SLE). We describe a case of acute myocardial infarction in a 23-year-old woman with SLE. Angiography revealed coronary ectasia in the left main and proximal circumflex coronary arteries, as well as a stenotic lesion in the left anterior descending artery. The possible pathophysiology is discussed.

To study the effect of 3,4',5-trihydroxystibene-3-beta-mono-D-glucoside (Polydatin, Pol) on rabbit arterial thrombosis.Rabbit arterial thrombosis was induced by vascular endothelial damage with trypsin.It was showed that the moist weights of the thrombus were 6.6 +/- 1.8 and 4.8 +/- 1.6 mg in Pol 5 and 10 mg.kg-1 groups, respectively, which was lighter than that in control (10.9 +/- 1.9 mg, P0.05, P0.01); the platelet aggregation was inhibited simultaneously. In vitro, Pol 0.30-1.15 mmol.L-1 reduced TXA2 produced in platelets. It did not affect the production of PGI2 in cultured human umbilical vein endothelial cells.Thrombosis was abated by Pol. The selective inhibition of production of TXA2 rather than PGI2, is one of the mechanisms involved.

From 1977 till 1991, the diagnosis of systemic lupus erythematosus was made on 137 children aged 18 years or under in Chang Gung Memorial Hospital. The medical records were reviewed and the clinical data were analysed with emphasis on the morbidity and mortality of this disease. The clinical and laboratory characteristics were similar to the findings from most other reports. Renal failure accounted for 8% of the initial presentation. The non-infectious complications were, in the order of frequencies, hypertension, avascular necrosis of femoral head, cataract, encephalopathy, and venous thrombosis. Sepsis, cutaneous infection and urinary tract infection were the frequently encountered infectious complications. The major causes of death in childhood onset systemic lupus erythematosus were sepsis (42%) and renal failure (30.7%). Forty patients were lost to follow-up. The 5-year survival rate, calculated by life-table, was 76.3%.

A 40-year-old Chinese woman with systemic lupus erythematosus (SLE) developed labile blood pressure 3 years after her onset of high blood pressure. Pheochromocytoma was subsequently found and removed. Postoperatively her hypertension improved without change in her SLE activity. Our case demonstrates pheochromocytoma can be a cause of hypertension in SLE.

A 21-year-old woman had suffered from repeated vasculitis and panniculitis with fever and chills after following mosquito bites since age 7. These manifestations were confirmed with a direct mosquito bite test during her admission to another hospital at age 17. The patient presented to our hospital with progressive dyspnea, productive cough and intermittent fever for one week. In addition to the bilateral infiltrative lesions on chest roentgenography, hepatosplenomegaly with an abnormal liver function test, pancytopenia, and elevated IgE were also detected. Blood and sputum cultures grew no microorganisms. Epstein-Barr virus-IgM, Cytomegalovirus-IgM and Mycoplasma pneumonia antibodies were all negative. Bone marrow aspiration and biopsy revealed histiocytosis with hemophagocytosis. No atypical histiocyte was found. The patient was put on dexamethasone treatment with improvement. Unfortunately, symptoms relapsed two weeks later. A repeated bone marrow aspiration and biopsy revealed a picture similar to the previous one. Despite antibiotic administration and ventilator support, a rapidly deteriorated course terminated in the patient's death by respiratory failure. Mosquito bite allergies were reported to be associated with malignant histiocytosis in Japan. However, atypical histiocytes were not found in our case upon repeated bone marrow aspirations, biopsies and skin biopsies. Mature histiocytes with hemophagocytosis were prominent instead. Reactive histiocytosis was thus favored rather than malignant histiocytosis. Although opportunistic infection cannot be excluded, we propose that a mosquito bite allergy with consequent histiocytic activation by antigen, immune complex or IgE is the possible pathogenetic mechanism for hemophagocytic histiocytosis in this patient.

We present the first report of neonatal lupus erythematosus from Taiwan. A female baby, born to a mother with documented systemic lupus erythematosus (SLE), developed cutaneous lupus lesions after phototherapy for hyperbilirubinemia. She had additional clinical features of hemolytic anemia and thrombocytopenia. Detailed serological and immunogenetic studies were performed. Transplacental passage of both anti-SSA/Ro and anti-SSB/La antibodies were demonstrated and their disappearance at the age of 6 months correlated with regression of clinical symptoms. This patient inherited human leukocyte antigen (HLA) A11, Bw60 Cw3, DR2 and Aw33, Bw57, Cw7, DRw6 from her father and mother, respectively. A long-term follow-up is required for observing whether she will develop SLE in the future.