Prevalence of premature ovarian failure in systemic lupus erythematosus patients treated with immunosuppressive agents in Thailand.

BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disease that affects most women of reproductive age. The prevalence of premature ovarian failure (POF) in SLE patients is higher than that in the general population. However, the data on this condition are limited in Asian countries. OBJECTIVES: To determine the prevalence and associated factors of POF in SLE patients who received immunosuppressive therapy. METHODS: Women aged 18-40 years who were diagnosed with SLE according to the 1997 revised criteria for the classification of SLE or patients with biopsy-proven lupus nephritis were evaluated. All patients had received at least one of the following immunosuppressive agents: cyclophosphamide (CYC), azathioprine, mycophenolate mofetil, chlorambucil or cyclosporine for more than six months. POF was diagnosed in those who had sustained amenorrhea for more than six consecutive months, with a level of estradiol ≤ 110 pmol/L (30 pg/mL) and follicle stimulating hormone ≥40 IU/L. RESULTS: Ninety two SLE patients were included in this study. Mean age at enrollment was 30 ± 6.9 years and disease duration was 103 ± 67.5 months. The mean Systemic Lupus International Collaborating Clinics/ American College of Rheumatology (SLICC/ACR) damage index was 1.7 ± 1.7. Seventy five patients (82%) had lupus nephritis. Sixty four patients (70%) received CYC. Eleven patients (12%) with POF were observed. For the binary logistic regression model, CYC cumulative dosage of more than 10 g was the only independent risk factor of POF (hazard ratio 17.0, 95% CI 1.96-147.72, p = 0.01). CONCLUSIONS: From our data, 12% of SLE patients developed POF. A cumulative dose of CYC of more than 10 g was the only risk factor for POF. To prevent these events, systematic evaluation and early recognition of POF should be promoted in the care of SLE patients.

Transcutaneous electrical nerve stimulation for knee osteoarthritis.

BACKGROUND: Osteoarthritis (OA) is a disease that affects synovial joints, which mainly causes degeneration and destruction of hyaline cartilage. To date, no curative treatment for OA exists. The primary goals for OA therapy are to relieve pain, maintain or improve functional status, and minimize deformity. Transcutaneous electrical nerve stimulation (TENS) is a noninvasive modality in physiotherapy that is commonly used to control both acute and chronic pain arising from several conditions. A number of trials evaluating the efficacy of TENS in OA have been published. OBJECTIVES: To assess the effectiveness of TENS in the treatment of knee OA. The primary outcomes of interest were those described by the Outcome Measures in Rheumatology Clinical Trials (OMERACT) 3, which included pain relief, functional status, patient global assessment, and change in joint imaging for studies of one year or longer. The secondary objective was to determine the most effective mode of TENS application in pain control. SEARCH STRATEGY: We searched MEDLINE, EMBASE, CINAHL, HEALTHSTAR, PEDro, Current Contents and the Cochrane Controlled Trial Register using the Cochrane Musculoskeletal Group search strategy for trials up to and including December 1999. We also hand-searched reference lists and consulted content experts. SELECTION CRITERIA: Two independent reviewers selected the trials that met predetermined inclusion criteria. DATA COLLECTION AND ANALYSIS: Two independent reviewers extracted the data using standardized forms and assessed the quality of randomization, blinding and dropouts. A third reviewer was consulted to resolve any differences. For dichotomous outcomes, relative risks (RR) were calculated. For continuous data, weighted mean differences (WMD) or standardized mean difference (SMD) of the change from baseline were calculated. A fixed effects model was used unless heterogeneity of the populations existed. In this case, a random effects model was used. MAIN RESULTS: Seven trials were eligible to be included in this review. Six used TENS as the active treatment while one study used acupuncture-like TENS (AL-TENS). A number of 148 and 146 patients were involved in the active TENS treatment and placebo, respectively. Three studies were cross-over studies and the others were parallel group, randomized controlled trials (RCTs). Median methodological quality of these studies was two. Pain relief from active TENS and AL-TENS treatment was significantly better than placebo treatment. Knee stiffness also improved significantly in active treatment group compared to placebo. Different modes of TENS setting (High Rate and Strong Burst Mode TENS) demonstrated a significant benefit in pain relief of the knee OA over placebo. Subgroup analyses showed a heterogeneity in the studies with methodological quality of three or more and those with repeated TENS applications. REVIEWER'S CONCLUSIONS: TENS and AL-TENS are shown to be effective in pain control over placebo in this review. Heterogeneity of the included studies was observed, which might be due to the different study designs and outcomes used. More well designed studies with a standardized protocol and adequate number of participants are needed to conclude the effectiveness of TENS in the treatment of OA of the knee.

Leflunomide for treating rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory joint disease. Leflunomide, as an inhibitor of pyrimidine synthesis, has a different mechanism of action than other existing disease modifying anti-rheumatic drugs (DMARD). OBJECTIVES: To determine the efficacy and toxicity of leflunomide compared to placebo or other DMARDs in the treatment of RA. SEARCH STRATEGY: We conducted a search in MEDLINE, EMBASE, Current Contents and the Cochrane Controlled Trial Register for trials up to December 2001. We also hand-searched reference lists and consulted content experts. SELECTION CRITERIA: Two independent reviewers selected the trials that met predetermined inclusion criteria. DATA COLLECTION AND ANALYSIS: Two independent reviewers extracted data and assessed methodologic quality using standardized forms. MAIN RESULTS: Six trials were included in this review. Using the ACR20 improvement criteria, there was an absolute difference in improvement of 28% (95% confidence interval: 21 - 35%) favouring leflunomide (232 out of 413 leflunomide treated patients compared to 89 out of 311 placebo patients met the criteria). There was no difference in ACR20 response rate between the patients treated with leflunomide and SSZ or MTX at 6 and 12 months. Other clinical outcomes were improved significantly in the leflunomide group compared to placebo but not different from SSZ or MTX. Withdrawals due to adverse events with leflunomide were 10% greater than placebo (70 out of 416 compared to 18 out of 311 respectively). Important adverse events included gastrointestinal symptoms, elevated liver function tests, alopecia, and infections. Overall adverse events and withdrawals in the leflunomide group were not significantly different from SSZ or MTX. REVIEWER'S CONCLUSIONS: Leflunomide appears to improve all clinical outcomes and delay radiologic progression at both 6 and 12 months of treatment compared to placebo. Its efficacy and adverse events at 2 years of treatment are comparable to SSZ and MTX. Long-term efficacy and toxicity remains to be established.

Edwardsiella tarda bacteremia and septic arthritis in a patient with diabetes mellitus.

Edwardsiella tarda is an uncommon pathogen in the family Enterobacteriaceae which usually infects patients with underlying diseases. Its habitats include fresh water, a variety of animals and human feces. We report a case of E. tarda bacteremia and septic arthritis with underlying diabetes mellitus, the first found in Thailand.

IL-1beta, IL-6 and TNF-alpha in synovial fluid of patients with non-gonococcal septic arthritis.

Interleukin-1 beta (IL-1beta), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) are the main proinflammatory cytokines responsible for the inflammatory process and cartilage destruction of inflammatory arthropathies. The present study sequentially measured the concentrations of these cytokines and their proportions of detectable levels in the synovial fluid (SF) of 23 patients with non-gonococcal (GC) septic arthritis before and after treatment. Persistently high concentrations and proportions of IL-6 and TNF-alpha were found up to day 7 of treatment, while SF IL-1beta concentration declined significantly after day 7 (p = 0.036). SF IL-1beta and TNF-alpha correlated with each other significantly and with SF WBC counts (p < 0.01). Positive correlations between SF IL-1beta concentration and joint effusion (p < 0.01) and between SF TNF-alpha concentration and joint tenderness (p < 0.001) were observed. SF IL-1beta and TNF-alpha were significantly higher in patients with local complications of septic arthritis. In conclusion, high levels of IL-1beta, IL-6 and TNF-alpha were detected in SF of patients with non-GC septic arthritis. Only IL-1beta decreased significantly after day 7 of treatment, but IL-6 and TNF-alpha concentrations were persistently high. SF IL-1beta and TNF-alpha may be useful in predicting the outcome and complications of patients with this disease.

Practice pattern variation among internal medicine specialists in the prevention of glucocorticoid-induced osteoporosis.

Osteoporosis is a serious side effect of long-term glucocorticoid (GC) use, but there is little success at prevention. We sought to identify academic physicians' awareness of glucocorticoid-induced osteoporosis (GIOP) risk and the patient and provider characteristics that determine GIOP management. A retrospective chart review of 365 patients seen at The University of Alabama at Birmingham by 4 rheumatologists, 3 pulmonologists, and 3 gastroenterologists was performed. Of these, 59.2% were women and 69.3% were Caucasians. Only 110 patients (30.1%) received any type of GIOP prevention intervention. The patients receiving GIOP prevention were older (58.7 +/- 13.8 vs. 49.8 +/- 16.7 years; p < 0.001); had longer duration of GC use (91.9 +/- 84.9 vs. 50.0 +/- 57.7 months; p < 0.001); and, for women, were more likely post-menopausal (81.5% vs. 18.5% premenopausal; p < 0.001). Fracture history was more common in those who received GIOP management (18 vs. 9 cases; p < 0.001). Calcium was the most commonly prescribed prevention strategy (84.5%). Recommendation of risk factor modification was seldom documented. Using multivariate logistic regression, rheumatologists were 4 times more likely to recommend GIOP prevention than the other two specialists. To improve the education in GIOP prevention strategies for specialists who commonly prescribe long-term GC, regular meetings and guidelines provided by experts in this field should be conducted. Both risk factors modification and pharmacological intervention for GIOP prevention should be started at the time of first GC prescription or as early as possible.

Initial disease modifying antirheumatic drugs and prednisolone prescriptions for patients with rheumatoid arthritis: a 15-year study.

OBJECTIVE: To compare patterns and time trends of initial disease-modifying antirheumatic drugs (DMARDs) and prednisolone prescriptions for patients with rheumatoid arthritis (RA) by the rheumatologists at King Chulalongkorn Memorial Hospital, Bangkok, Thailand over a 15-year period, as well as their side effects. METHOD: Medical records of all patients with RA seen at the Rheumatology Clinic from January 1983 to June 1997 with a duration of follow-up of 6 months or more were reviewed. Information on the disease, initial DMARDs prescriptions and their side effects, prednisolone use, dosage and side effect(s) were focused and compared among three 5-year periods (1983-1987, 1988-1992 and 1993-1997). RESULTS: 236 patients were included in this study. There were 44, 82 and 110 patients in the first, second and third period, respectively. Methotrexate (MTX) was the most frequently prescribed DMARD in all time periods. Dapsone and intramuscular (i.m.) gold were prescribed in the first period while antimalarial drugs and sulfasalazine (SSZ) were increasingly used in the second and third periods. Combination treatment of DMARDs was first used in the third period. Side effects from MTX were observed in patients with a longer duration of treatment (p < 0.05). Patients prescribed combined DMARDs did not develop more side effects compared with those who had monotherapy. Prednisolone was prescribed in 57.2 per cent of the patients, most being newly prescribed at the clinic. Mean starting dose of prednisolone was 8.9 mg per day. 64 patients took prednisolone together with non-steroidal antiinflammatory drugs (NSAIDs). Gastrointestinal side effects did not increase in these patients. CONCLUSION: MTX was the most frequently prescribed DMARDs regardless of the time period. Antimalarial drugs, SSZ and combination of DMARDs (most were MTX + chloroquine) have been prescribed more in the last 5 years, while dapsone, auranofin and i.m. gold were rarely used as initial DMARDs. Low dose prednisolone was prescribed in more than half of the patients with RA. Side effects from DMARDs and prednisolone found in this study were comparable to previous reports.

Streptococcal arthritis in Thai adults: case series and review.

The incidence, clinical spectrum, types of streptococci in Thai adults with streptococcal arthritis in Chulalongkorn Hospital are similar to Western reports. The most frequently found organism was group A Streptococcus and the second was group G. Most of the patients were elderly who usually had underlying medical and/or joint diseases. There were 3 patients with underlying lepromatous leprosy which has never been reported before, while mixed types of streptococcal infection in the same joint, mixed types of streptococcal infection in the same patient and a patient with group C lumbar spondylodiskitis were also found. The most reliable diagnostic test is synovial fluid culture. All streptococcal isolates in our review were sensitive to penicillin and the clinical responses correlated with antibiotic sensitivity tests. Intravenous antibiotics and adequate drainage are the treatment of choice. The duration of treatment ranged from 4 to 6 weeks and most patients responded well. The overall mortality rate depended on host factors, organism virulence and treatment administered.

Clinical features of septic arthritis of sternoclavicular joint.

We studied 21 patients with septic arthritis of the sternoclavicular joint at Chulalongkorn University Hospital between January 1987 and January 1997. There were 15 males (71.4%) and 6 females (28.6%). The mean age was 47.4 years with a range of 16 to 69. More than half of the patients (57.1%) were aged more than 50 years and most had associated diseases including diabetes mellitus and cirrhosis. Almost all of the younger age group had a history of intravenous drug abuse. All of the patients had fever and sternoclavicular joint pain. Most of the patients (66.7%) had monoarticular arthritis, whereas, the others had oligoarticular arthritis. Staphylococcus aureus was the most commonly or identified organism in the patients. Retrosternal abscess was seen by computerized tomography in 6 patients (28.6%). All patients received parenteral antibiotics, and 5 patients (23.8%) required surgical drainage of a retrosternal abscess. Eighteen patients recovered but there were 3 (14.3%) deaths. All of these had retrosternal abscesses. The major cause of death was septic shock. Septic arthritis of the sternoclavicular joint is an uncommon disease in Thai clinical practice. Although uncommon, retrosternal abscess is a life threatening complication.

Evaluation of functional ability of Thai patients with rheumatoid arthritis by the use of a Thai version of the Health Assessment Questionnaire.

METHODS: The Health Assessment Questionnaire (HAQ) was translated into Thai and its validity and applicability were assessed in 22 Thai patients with active rheumatoid arthritis (RA) before and after 6 months of treatment with disease-modifying anti-rheumatic drugs (DMARDs). The activities in three subcategories of the Thai HAQ were modified, including Eating, Hygiene and ACTIVITIES: Two common activities in Thai people were incorporated into the items in the Grip and Arising domains. RESULTS: Significant improvements in mean HAQ scores and other parameters were observed after DMARD therapy. Mean HAQ scores correlated significantly with tender joint count, patient global and physician global assessments, and grip strength. CONCLUSIONS: The Thai HAQ met validity requirements and can be used in the measurement of functional capacity of Thai RA patients.

The prevalence of dyslipoproteinemia in Thai patients with systemic lupus erythematosus.

Fasting blood samples taken from 93 pairs of outpatient systemic lupus erythematosus (SLE) women and matched controls were assessed for total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL)- and low-density lipoprotein (LDL)-cholesterol. The demographic data, clinical manifestations, Mexican-SLE Disease Activity Index (MEX-SLEDAI), Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index and medication prescribed in the SLE patients were reviewed. A significant elevation of TG levels was observed in the SLE patients compared to controls (mean+/-SD 113.3+/-59.5 versus 77.7+/-45.7 mg/dL, P < 0.001). The HDL-c level was also significantly lower in SLE patients than controls (mean+/-SD 49.7+/-12.7 versus 65.0+/-14.8 mg/dL, P < 0.001). The percentage of samples with low HDL-c (<35 mg/dL) was higher in the SLE group (9.7%) than controls (0%; P = 0.002). The LDL-c and TC levels were comparable in both groups. The use of antimalarial drugs was negatively associated with TC (OR 0.22, 95%CI 0.08-0.61) and LDL-c levels (OR 0.27, 95%CI 0.09-0.80). The increased prevalence of dyslipoproteinemia in SLE patients in this report has confirmed the results of previous studies and emphasized the importance of controlling this modifiable cardiovascular risk factor by the combination of lifestyle modification and medical treatments.

Number needed to treat (NNT): implication in rheumatology clinical practice.

OBJECTIVE: To calculate the number needed to treat (NNT) and number needed to harm (NNH) from the data in rheumatology clinical trials and systematic reviews. METHODS: The NNTs for the clinically important outcome measures in the rheumatology systematic reviews from the Cochrane Library, issue 2, 2000 and in the original randomised, double blind, controlled trials were calculated. The measure used for calculating the NNT in rheumatoid arthritis (RA) interventions was the American College of Rheumatology 20% improvement or Paulus criteria; in osteoarthritis (OA) interventions, the improvement of pain; and in systemic sclerosis (SSc) interventions, the improvement of Raynaud's phenomenon. The NNH was calculated from the rate of withdrawals due to adverse events from the treatment. RESULTS: The data required for the calculation of the NNT were available in 15 systematic reviews and 11 original articles. For RA interventions, etanercept treatment for six months had the smallest NNT (1.6; 95% confidence interval (CI) 1.4 to 2.0), whereas leflunomide had the largest NNH (9.6; 95% CI 6.8 to 16.7). For OA treatment options, only etodolac and tenoxicam produced significant pain relief compared with placebo (NNT=4.4; 95% CI 2.4 to 24.4 and 3.8; 95% CI 2.5 to 7.3, respectively). For SSc interventions, none were shown to be efficacious in improving Raynaud's phenomenon because the 95% CI of the NNT was infinite. CONCLUSIONS: The NNT and NNH are helpful for clinicians, enabling them to translate the results from clinical trials and systematic reviews to use in routine clinical practice. Both NNT and NNH should be accompanied by a limited 95% CI and adjusted for the individual subject's baseline risk.

A novel single nucleotide polymorphism and five probable haplotypes in the 5' flanking region of the IL-6 gene in African-Americans.

In order to identify novel single nucleotide polymorphisms (SNPs), we sequenced a 940 bp region of the 5' flanking region of the IL-6 gene in 63 normal African-Americans. We identified a biallelic (G/C) SNP at position -573 relative to the transcription start site (-573C allele frequency 0.095). This SNP, together with SNPs at -598 and -174, allows identification of five probable haplotypes. Haplotypes containing the -174C allele, which has been associated with lower plasma IL-6 levels, were uncommon (4%). These haplotypes may influence IL-6 gene transcription and thus may contribute to racial differences in the prevalence of inflammatory diseases.