Risk of cancer in patients with ankylosing spondylitis: a nationwide cohort study in Taiwan.

Objective: To estimate the incidence of cancer among patients with ankylosing spondylitis (AS) and compare this risk with that of the general population.Method: We obtained data from Taiwan's National Health Insurance database on 19 289 patients with a first diagnosis of AS registered between 2000 and 2012 with no history of cancer before the diagnosis of AS. Standardized incidence ratios (SIRs) for all cancers and for site-specific cancers were used to assess whether AS was associated with an increased risk of cancer.Results: During the follow-up period, 485 patients developed cancer. The incidence rate was therefore 256.3 per 100 000 person-years. Compared with the general population, patients with AS had an increased risk of cancer [SIR 1.33, 95% confidence interval (CI) 1.20-1.47]. The SIR of cancer was higher in older patients; the risk increased from 8 years after initial diagnosis. Among solid tumours, the risk of melanoma was the highest (SIR 4.64, 95% CI 1.93-11.15), followed by prostate (SIR 2.53, 95% CI 2.01-3.19), thyroid (SIR 2.09, 95% CI 1.45-3.00), and bone cancer (SIR 2.00, 95% CI 1.01-3.99). Among haematological cancers, the risk of leukaemia was the highest (SIR 1.94, 95% CI 1.21-3.12). By contrast, the risks of oesophageal and oral cancers decreased in patients with AS.Conclusion: This nationwide population-based cohort study demonstrated that patients with AS in Taiwan are at an increased risk of cancer, particularly melanoma; prostate, thyroid, and bone cancers; and haematological malignancies.

Longitudinal associations of active renal disease with irreversible organ damage accrual in systemic lupus erythematosus.

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 <50%/proteinuria >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 < 0.02). Active lupus nephritis was strongly associated with damage accrual in renal but not in non-renal organ domains (hazard ratios = 13.0 (95% CI: 6.58, 25.5) p < 0.001 and 0.96 (95% CI: 0.69, 1.32) p = 0.8, respectively). There was no effect of ethnicity on renal damage accrual, but Asian ethnicity was significantly associated with reduced non-renal damage accrual. CONCLUSION: Active lupus nephritis measured using the SLEDAI-2K domain cut-offs is associated with renal, but not non-renal, damage accrual in SLE.

Cancer risk among patients with systemic sclerosis: a nationwide population study in Taiwan.

OBJECTIVES: Systemic sclerosis (SSc) has been associated with high cancer risk. We compared the cancer risk among SSc patients with that among the general Taiwanese population. METHODS: The catastrophic illness registry of the Taiwan National Health Insurance Research Dataset (NHIRD) was used to identify patients diagnosed with SSc and cancer in Taiwan during 1996-2008. The standardized incidence ratio (SIR) for cancer was calculated, and mortality was ascertained using the data from the National Death Registry. RESULTS: Data analysis revealed that 2053 (472 men, 1581 women) Taiwanese individuals were diagnosed with SSc during the study period and 83 (30 men, 53 women) had cancer. The incidence of cancer was 6.9/1000 person-years. The most common cancer sites in male SSc patients were the lung (n = 10), oral cavity and pharynx (n = 8), and gastrointestinal tract (n = 4), and those in female patients were the breast (n = 11), lungs (n = 11), and blood (n = 6). Compared to the Taiwanese population of 1996, the all-cancer SIR for SSc was 1.63 [95% confidence interval (CI) 1.31-2.01]. Cancer risk was elevated for cancers of the lung (SIR 4.20), oral cavity and pharynx (SIR 3.67), and blood (SIR 3.50). A cancer diagnosis in SSc patients was associated with a hazard ratio (HR) of 2.15 (95% CI 1.30-3.53). Among cancer patients, a diagnosis of SSc was not associated with increased mortality. CONCLUSIONS: SSc patients are at high risk of developing cancer, especially of the lung, oral cavity and pharynx, and blood.

Antinuclear antibody status and risk of death in children and adolescents.

OBJECTIVES: The association between the presence of antinuclear antibodies (ANA) and mortality has been rarely reported. The present study explored the value of ANA as a predictor of overall survival in children and adolescents. METHODS: Patients younger than 20 years who underwent ANA testing in Chang Gung Memorial Hospital (CGMH) from 2000 to 2008 were enrolled in this study. Mortality was ascertained by using the National Death Registry of Taiwan. Positive ANA titres were categorized as low (1:40 to 1:80), medium (1:160 to 1:320), and high (≥ 1:640). RESULTS: A total of 13 345 subjects (6579 males, 6766 females) were enrolled during the 9-year study period. The overall prevalence of low, medium, and high ANA titres was 20.8% (n = 2774), 6.0% (n = 804), and 2.5% (n = 338), respectively. During 45,140 person-years of follow-up, 146 deaths were identified and the crude mortality rates were 3.8 and 3.0 per 1000 person-years for subjects with positive and negative ANA test results, respectively (p = 0.130). Compared with ANA-negative subjects, the adjusted hazard ratio (HR) for all-cause mortality among those with a high ANA titre was 5.18 [95% confidence interval (CI) 3.13-8.57]. A low-to-medium ANA titre was not associated with increased mortality. Among the 18 deaths in individuals with a high ANA titre, 14 were due to systemic lupus erythematosus (SLE). In comparison, five out of 34 deaths among those with low-to-medium titres of ANA and none of those with negative ANA were related to SLE. CONCLUSIONS: Children and adolescents with high ANA titres should receive greater attention and monitoring to prevent unfavourable outcomes because they have a higher mortality risk than those with negative ANA results.

Incidence, cancer risk and mortality of dermatomyositis and polymyositis in Taiwan: a nationwide population study.

BACKGROUND: Nationwide data on the epidemiology of dermatomyositis (DM) and polymyositis (PM) were limited. OBJECTIVES: This study was to estimate the incidence, occurrence of cancer and mortality of DM and PM in Taiwan. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Epidemiology and mortality of systemic sclerosis: a nationwide population study in Taiwan.

OBJECTIVES: There have been few nationwide population studies of systemic sclerosis (SSc). We describe the epidemiological features of SSc in Taiwan. METHODS: The catastrophic illness registry of the Taiwan National Health Insurance Research Dataset (NHIRD) and the National Death Registry of Taiwan were used to calculate estimates of the incidence, prevalence, and mortality of SSc. RESULTS: A total of 1479 persons (325 males, 1154 females) with incident SSc were enrolled in the study. The annual incidence of SSc in Taiwan was found to be 10.9 cases (4.7 males, 17.4 females) per million population. During 2002-2007, the mean prevalence was 56.3 cases per million population. There were 204 deaths (70 males, 134 females) during the study period; 1-, 2-, and 5-year survival rates were 94.9, 92.0, and 83.2%, respectively. SSc patients had a standardized mortality ratio (SMR) of 3.24 [95% confidence interval (CI) 2.82-3.71] for all-cause mortality, as compared with the national population in 2002. There was excess mortality from neoplasms (SMR 1.50, 95% CI 1.03-2.11), cardiovascular diseases (2.23, 1.52-3.16), kidney disease (4.67, 2.66-7.64), gastrointestinal diseases (2.50, 1.27-4.46), and pulmonary diseases (3.20, 1.89-5.09). In addition to male sex and older age, cancer and end-stage renal disease (ESRD) diagnosis were risk factors for death, with hazard ratios (HRs) of 2.71 (95% CI 1.27-5.76) and 2.59 (1.14-5.90), respectively. CONCLUSION: SSc patients had a threefold greater risk of all-cause mortality than the general population of Taiwan. Male sex, older age, diagnosis of cancer, and ESRD were risk factors for death.

Hyperuricaemia and accelerated reduction in renal function.

OBJECTIVES: Hyperuricaemia has been linked to reduced renal function, and evidence indicates that it may be associated with acceleration of the decline in glomerular filtration rate (GFR) and progression of chronic kidney disease (CKD). METHODS: We analysed a population of subjects who had undergone serum uric acid (SUA) and serum creatinine measurements in a hospital-based cohort. Initial and final serum creatinine measurements were used to calculate the estimated glomerular filtration rate (eGFR) and the annual decline in eGFR. Cox regression was used to investigate the relationship between SUA and CKD progression. RESULTS: A total of 63,785 subjects were enrolled in the study during a 12-year follow-up period. The mean age at the time of initial serum creatinine measurement was 50.0 ± 14.9 years. Hyperuricaemic subjects had a significantly larger annual eGFR decline, both in absolute terms (2.5 ± 9.5 mL/min/1.73 m(2) per year) and as a percentage (2.8 ± 11.6% per year), as compared to the normouricaemia group (1.3 ± 9.6 mL/min/1.73 m(2) per year, 1.1 ± 11.1% per year, p < 0.001). After adjustment for age, sex, status of diabetes mellitus (DM) and hypertension, baseline eGFR, azotaemia, hypercholesterolaemia, and hyperglycaemia, hyperuricaemia was associated with a hazard ratio (HR) of 1.28 [95% confidence interval (CI) 1.23-1.33, p < 0.001] for an accelerated eGFR decline ≥ 3 mL/min/1.73 m(2) per year and an HR of 1.52 (95% CI 1.46-1.59) for CKD progression at the end of follow-up. CONCLUSION: Hyperuricaemia was associated with an accelerated decline in eGFR and higher risk of CKD progression. Therefore, renal function should be monitored closely in patients with hyperuricaemia.

Gout and risk of non-alcoholic fatty liver disease.

OBJECTIVES: To investigate the association between gout and non-alcoholic fatty liver disease (NAFLD). METHODS: The study subjects were participants in a health-screening programme at Chang Gung Memorial Hospital from 2000 to 2006. Subjects were classified into eight groups based on serum urate (SU) level and gout status (≤ 4.9, 5.0-6.9, 7.0-8.9, and ≥ 9.0 mg/dL, without and with gout). The association between gout and NAFLD was assessed by multiple logistic regression. RESULTS: Among a total of 54 325 subjects, 1930 (3.6%) had gout and 6169 (11.3%) had NAFLD. The prevalence of NAFLD was significantly higher in subjects with gout (23.1%, n = 445) than in those without gout (10.9%, n = 5724, p < 0.001). Among subjects with NAFLD, the severity of NAFLD was higher in gout patients. Gout was associated with an increased risk for NAFLD [odds ratio (OR) 1.42, 95% confidence interval (CI) 1.25-1.60, p < 0.001], after adjustment for age, sex, presence of metabolic syndrome, and low estimated glomerular filtration rate (eGFR). With SU ≤ 4.9 mg/dL in the absence of gout as reference, the ORs (95% CI) for NAFLD, after adjustment for age, sex, presence of metabolic syndrome, and low eGFR, were, respectively, 2.16 (1.94-2.41), 3.98 (3.55-4.46), and 5.99 (5.19-6.90) for SU levels 2-4 in those without gout and 2.61 (1.39-4.91), 2.87 (2.04-4.04), 4.53 (3.70-5.56), and 6.31 (5.12-7.77) for SU levels 1-4 in those with gout. CONCLUSIONS: There was an independent association between gout and the risk for NAFLD. In addition, there was a dose-response relationship between SU and NAFLD in subjects with and without gout.

Synergic CSE1L/CAS, TNFR-1, and p53 apoptotic pathways in combined interferon-gamma/adriamycin-induced apoptosis of Hep G2 hepatoma cells.

Many cancers are chemotherapy-resistant. Chemotherapy combined with immunotherapy offers a potential avenue for the treatment of chemotherapy-resistant cancers. In this study, we investigated the apoptotic pathways induced by combined interferon-gamma/adriamycin treatment in Hep G2 cells. Our data showed that Hep G2 cells treated with combined interferon-gamma/adriamycin enhanced cell apoptosis in comparison with that of cells treated with adriamycin. Interferon-y increased TNFR-1, CSE1L/CAS (cellular apoptosis susceptibility protein), Bax, and Bad levels. Adriamycin increased p53 and Bax, but not TNFR- 1 and CAS levels. Interferon-y did not increase p53 accumulation; nevertheless it enhanced adriamycin-induced p53 accumulation. Overexpression of IRF-1 augmented the combined interferon-gamma/adriamycin-induced p53 accumulation. Interferon-gamma co-treatment increased the stability of p53 protein induced by adriamycin. Our data suggest that TNF-gamma may greatly enhance the combined interferon-gamma/chemotherapeutic drug-induced apoptosis of cancers. Our findings also indicate that CAS, TN-FR-1, p53, Bax, and Bad may be the targets for the interferon-y-based chemo-immunotherapy of the chemotherapy-resistant cancers.

Association of rheumatoid factor production with FcgammaRIIIa polymorphism in Taiwanese rheumatoid arthritis.

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.

Association of apoptosis-related microsatellite polymorphisms on chromosome 1q in Taiwanese systemic lupus erythematosus patients.

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.

The -844C/T polymorphism in the Fas ligand promoter associates with Taiwanese SLE.

FasL expression is critical in T-cell activation-induced apoptosis, which is involved in lupus pathogenesis. This study identified two SNPs in the FasL promoter regions from -1145 to -45 by genomic DNA sequencing. The -844C/T polymorphism was previously described by its location in and affect on the CCAAT/enhancer-binding protein beta (C/EBPB beta)-binding site and the other (-1094A/C, a novel polymorphism) was located at the NF-kappaB transcription-binding site. FasL gene promoter polymorphisms were genotyped in 260 systemic lupus erythematosus (SLE) patients and 280 healthy controls using MassArray matrix-assisted laser desorption ionization-time-of-flight (MALDI-TOF) mass spectrometry. The distribution of FasL promoter -844C/C genotype, predominant in Taiwanese, was skewed in Taiwanese SLE patients (odds ratio: 1.53; P-value=0.014). FasL promoter -844C/T polymorphism genotype distributions of Taiwanese, African Americans, and Caucasians differed. Moreover, no particular clinical association of -844C/T and -1094A/C polymorphisms with SLE was found in patients in Taiwan. This study confirmed that -844C/C genotype is associated with lupus susceptibility. The -1094A/C polymorphism is not significantly associated with lupus disease susceptibility, albeit the role of NF-kappaB pathway in FasL promoter activation remains unclear. Fas/FasL pathway may contribute to SLE polygenic disease entity.

Involvement of hypoxia-inducible factor-1-alpha in multidrug resistance induced by hypoxia in HepG2 cells.

Aim of the study was to explore the influence of hypoxia on multidrug resistance related genes and the potential role of hypoxia-inducible factor-1-alpha (HIF-1alpha) in formation of multidrug resistance in HepG2 human hepatocellular carcinoma cell line. HepG2 cells were subjected to hypoxia in a cohort of exposed time. A cell model stably expressing HIF-1alpha was established by liposome-mediated transfection of plasmid pcDNA3/HIF-1alpha into HepG2 cells. Apoptosis of HepG2 cells exposed to hypoxia or transfected by plasmid pcDNA3/HIF-1alpha was detected by Flow Cytometry after administration of chemotherapeutic drug (5-Fu). Real-time fluorescent quantitative PCR and Western-blot technique were used to analyze the expressions of multidrug resistance related genes mdr1, MRP1 and LRP at mRNA and protein level, respectively. Apoptosis Index of HepG2 cells exposed to hypoxia stepped down as exposed time extended after administration of 5-Fu. The expression of mdr1, MRP1 and LRP gene and protein revealed a hypoxic time-dependent induction and was synchronous with the alterations of HIF-1alpha in HepG2 cells exposed to hypoxia. The expressions of these multidrug resistance related genes were remarkably increased in HIF-1alpha transfected HepG2 cells as compared to empty vector transfected cells. Apoptosis index of HIF-1alpha transfected cells was obviously less than that of control cells when they were simultaneously exposed to 5-Fu for 24hrs. In conclusion, ambient hypoxia might be one of the causes for the formation of multidrug resistance in HepG2 human hepatocellular carcinoma cell line. Hypoxia-elicited multidrug resistance related protein expression might be a pathway for resistance of HepG2 cells to chemotherapeutics and HIF-1alpha might be involved in this process.

Intermittent elevation of serum urate and 24-hour urinary uric acid excretion.

OBJECTIVES: Serum urate concentrations fluctuate throughout the day, and may be subject to variation with time. However, monthly variation of urinary uric acid excretion has not been investigated. This prompted us to investigate serum urate and 24-h urinary uric acid excretion in healthy men. METHODS: Serum urate and creatinine and 24-h urinary uric acid and creatinine were measured at monthly intervals throughout a 12-month period in 12 healthy men (aged 23-61 yr) from July 2002 to June 2003. RESULTS: The mean age of the 12 healthy men was 35.3+/-10.5 yr (median 33, range 23-61), and they had mean serum urate concentration 7.1+/-1.1 mg/dl (range 4.6-10.4), mean serum creatinine 1.0+/-0.1 mg/dl (range 0.8-1.3) and mean 24-h urinary uric acid excretion 651+/-189 mg/day/1.73 m(2) (median 623, range 389-1565). Approximately 20.1 and 20.7% of the measurements displayed above normal serum urate level and daily urinary uric acid excretion of more than 800 mg, respectively. CONCLUSIONS: The data presented here demonstrate individual variations in serum urate levels and 24-h urinary uric acid excretions in healthy men with serial measurement. Transient hyperuricaemia and hyperuricosuria are more common than expected, and both transitory and monthly variations are important factors to consider when evaluating the influence of other factors upon serum urate levels and urinary uric acid excretion. Further studies are needed to confirm these results using larger populations.

Fcgamma receptor IIa, IIIa, and IIIb polymorphisms of systemic lupus erythematosus in Taiwan.

OBJECTIVE: To determine whether the distribution of Fcgamma receptor IIa, IIIa, and IIIb polymorphisms confers a risk factor for disease susceptibility, and correlates with the clinical characteristics and serological parameters of patients with SLE in Taiwan. METHODS: Genotyping of Fcgamma receptors IIa H/R131, IIIa F/V158, and IIIb NA1/NA2 was performed in 302 patients with SLE and 311 healthy blood donor controls. The distribution of Fcgamma receptor IIa, IIIa, and IIIb genotypes in patients and controls was analysed. Frequencies of three Fcgamma receptor polymorphisms were also compared between lupus patients with and without different clinical manifestations and autoantibodies. RESULTS: No significant skewing in the distribution of Fcgamma RIIa H/R131, Fcgamma RIIIa F/V158, and Fcgamma RIIIb NA1/NA2 was found between patients and controls in Taiwan. The following clinical associations were found: Fcgamma RIIIb NA1/NA1 protected against neuropsychiatric lupus (p = 0.028) but conferred susceptibility to discoid rash (p<0.005); increased Fcgamma RIIIa V/V158 was associated with infections (p = 0.039); increased Fcgamma RIIa H/H131 was associated with earlier onset of lupus (p = 0.01). CONCLUSION: Fcgamma receptor IIa, IIIa, and IIIb polymorphisms may be responsible for the development of distinct manifestations of lupus patients in Taiwan, but there is no significantly skewed distribution in the susceptibility to lupus as a whole.

Gout complicated with necrotizing fasciitis--report of 15 cases.

OBJECTIVE: To analyse the clinical features and outcomes of gout complicated with necrotizing fasciitis. METHODS: From the database of our hospital, we identified 15 hospitalized cases of gout complicated with necrotizing fasciitis from 1987 to 2001. The medical records of the patients were analysed in detail. RESULTS: Mean patient age was 54.7 +/- 12.8 yr. Fever was found in only 10 (66.7%) patients, while the remaining five patients were afebrile on presentation. The peripheral blood white count was raised in only nine (60%) patients. The median time from the onset of symptoms to hospital visit was 4 days (range 2 to 25). Formation of bullae occurred in 60% of patients. Six patients had previous wound infection, two patients had concomitant septic arthritis and the remaining seven patients had no obvious source of infection. Diabetes mellitus and iatrogenic Cushing syndrome were each found in three patients. The identified causative microorganisms were Gram-positive cocci (eight cases) and Gram-negative bacilli (four cases); but in three patients the causative organisms were unknown. Thirteen patients received surgery, including amputation in four cases. Finally, six patients suffered septic shock, three of whom died as a result. CONCLUSIONS: Necrotizing fasciitis in gout patients represents a surgical and medical emergency, and is associated with a high mortality rate. Prompt diagnosis and treatment is imperative and may be lifesaving. Early diagnosis requires a high level of suspicion, even in patients without fever or leucocytosis.

Gout in systemic lupus erythematosus and overlap syndrome - a hospital-based study.

The negative association between gout and rheumatoid arthritis is widely accepted, and gout is also speculated to be rare in systemic lupus erythematosus (SLE), as only a few sporadic cases have been reported. From 1985 to 2001 we encountered 15 lupus patients at Chang-Gung Memorial Hospital, including two with lupus-scleroderma and one with lupus-scleroderma-polymyositis overlap syndrome coexisting with gout. This study retrospectively analyses the clinical and laboratory characteristics of these patients. A lower female predominance is found, and most patients developed gout after the onset of SLE, although gout preceded SLE in two cases. Measurement of serum uric acid and 24-h urine uric acid found all of the patients to be hyperuricaemic and underexcretors of uric acid. Furthermore, most of the patients (14/15) were receiving diuretics. Also, many had hypertension and serious cardiovascular diseases. Renal impairment during gouty attacks seemed to be a predisposing factor for developing end-stage renal disease. Gouty arthritis usually occurred during relative SLE inactivity, podagra was frequent, and tophi were found in a few patients. Compared with the unselected population of SLE patients, the cases studied here had a higher incidence of chronic arthritis, malar rash, haematologic disorder, photosensitivity, serositis and neurologic disorder. Renal disease in the patients sampled was frequently membranous nephropathy.

Concomitant septic and gouty arthritis--an analysis of 30 cases.

OBJECTIVES: To analyse the clinical features and outcomes of gouty patients with concomitant septic arthritis in a medical centre. METHODS: From the hospital database, we collected 30 hospitalized cases with concomitant septic arthritis and gouty arthritis from 1987 to 2001. All patients had positive bacterial culture and monosodium urate crystals in the affected joints. Medical records of the patients were analysed in detail. RESULTS: The mean age of patients was 52.8+/-12.5 yr. One-third of patients were afebrile at presentation, 30% had a normal blood leucocyte count and 10% had a synovial fluid leucocyte count less than 6000/mm3. The knee joint was the most common site of involvement, followed by the ankle, shoulder and wrist joints. Most patients had long-standing disease and subcutaneous tophi. Subcutaneous tophi rupture with secondary wound infection is the most common route of infection. Causative micro-organisms were Staphylococcus aureus (16 cases, 7 of whom were oxacillin-resistant), Streptococcus sp. (5 cases), Pediococcus sp. (1 case), and Gram-negative bacilli (9 cases). Fourteen patients received surgical debridement, among them two patients had an arthrodesis owing to severe joint destruction and one received above-knee amputation. Two patients died. One died of septic complications and the other died of acute myocardial infarction. CONCLUSIONS: Septic arthritis coexistent with gout presented a diagnostic difficulty. An early diagnosis requires a high level of suspicion. Prompt aspiration and analysis of the synovial fluid is imperative, regardless of the absence of fever or leucocytosis. Culture of the aspirated synovial fluid is warranted in gouty attack, even when it has a low white cell count or the Gram stain reveals no organisms.

Younger age of onset of gout in Taiwan.

OBJECTIVE: To study the clinical features of gout in the community and in medical centres, and to describe the recent changes in gout in Chinese patients. METHODS: We analysed retrospectively the clinical features of 1079 Chinese gout patients seen by a rheumatologist between 1993 and 2000. These included 558 patients from a private clinic and 521 patients from a medical centre. The data were compared with those in previous reports of large Caucasian and non-Caucasian series. RESULTS: The mean age of onset was 41.6 yr and the mean disease duration before first visit was 4.2 yr. For medical centre patients, the mean age of onset was 43.0 yr and mean disease duration before the first visit was 4.8 yr. For private clinic patients, the mean age of onset was 40.2 yr and mean disease duration before the first visit was 3.6 yr. Young patients with gout, with onset before age 30, constituted 23.3 and 26.7% of the medical centre and private clinic patients respectively. Female patients constituted 10.6 and 5.6% respectively, the family history was positive in 27.1 and 28.7%, and urolithiasis occurred in 11.5 and 10.9%. Tophi were found in 21.1% of medical centre and 12.7% of private clinic patients. The mean time from first gouty attack to visible tophi was 6.6 yr in those who developed tophi. CONCLUSIONS: The age at onset of gout was much earlier than in previous reports. Twenty-five per cent of patients had their first gouty attack before age 30. The first attack frequently occurred between the third and fifth decades (68.2%) rather than between the fourth and sixth decades, as reported in previous papers. The incidence of gout in females had increased (8.0% of the patients were female) and the incidence of tophi was high (16.8%). Besides, our patients had more frequent gouty attacks and the interval from the first attack to visible tophi was shorter than in previous reports of the disease in Caucasians.