Waraporn Sukitawut

Sensitivity and specificity of ANA and anti-dsDNA in the diagnosis of systemic lupus erythematosus: a comparison using control sera obtained from healthy individuals and patients with multiple medical problems.

BACKGROUND Antinuclear antibodies (ANA) and anti-double stranded DNA (anti-dsDNA) are often tested as a screening tool in patients with suspected systemic lupus erythematosus or connective tissue diseases. ANA can be seen in healthy controls (HC) and patients with multiple medical problems (MMP). OBJECTIVE To determine the sensitivity and specificity of ANA and anti-dsDNA in SLE patients, using sera from HC and MMP patients. METHODS Serum samples from HC, MMP and SLE patients, 100 in each group, were analyzed for the presence of ANA and anti-dsDNA, by indirect immunofluorescent assay, using a HEp-2 cell and Crithidia luciliae as substrates, respectively. RESULTS The prevalence of ANA at a titer of ≥1:80 and ≥ 1:160 was 8% and 4%, respectively, in HC; and it was 12% and 6% respectively, in MMP patients. The prevalence of anti-dsDNA was 0% in HC and 3% in MMP patients. When using HC sera for the diagnosis of SLE, the sensitivity of ANA at a titer of ≥ 1:80 and ≥ 1:160 was 98% and 90%, respectively, with specificity of 92% and 96%, respectively. The specificity decreased to 88% and 94%, respectively, when using sera from MMP patients. The specificity of anti-dsDNA was 100% and 97%, when using sera from HC and MMP patients, respectively. CONCLUSION ANA and anti-dsDNA gave high sensitivity and high specificity in patients with SLE, even when using MMP patients sera as controls. Physicians should take care in interpreting ANA and anti-dsDNA results in MMP patients who do not have signs or symptoms of SLE or connective tissue diseases.

Usefulness of pleural effusion antinuclear antibodies in the diagnosis of lupus pleuritis

We performed this study to determine sensitivity and specificity of pleural effusion antinuclear antibodies (ANA) at a titer of ≥1 : 160, and the ratio of pleural effusion to serum ANA of ≥1, to distinguish between pleural fluid from lupus pleuritis and other causes. A prospective study of 54 patients with pleural effusion (12 lupus pleuritis, seven parapneumonic effusion, 26 malignancy-associated pleural effusions, nine transudative effusions) was performed. ANA at a titer of ≥1 : 160 were found in 11 of 12 lupus pleuritis samples, and in four of 42 pleural effusions from non-systemic lupus erythematosus (SLE) patients. The pleural effusion ANA at a titer of ≥1 : 160 gave a sensitivity of 91.67% for lupus pleuritis, with a specificity of 83.33% when compared with all other pleural effusions, 90.91% when compared with exudative effusion (parapneumonic effusion and malignancy-associated effusion) and 55.56% when compared with the transudative pleural effusion group. Using the ratio of pleural effusion to serum ANA of ≥1, the sensitivity and the specificity decreased to 75.00% and 78.57%, respectively. This study provides further evidence that the pleural effusion ANA at a titer of ≥1 : 160 is a sensitive and specific diagnostic biomarker for lupus pleuritis in patients with lupus. However, pleural effusion ANA can occasionally be found in other conditions.

Associated factors and psychotherapy on sleep disturbances in systemic lupus erythematosus

Sleep disturbance is a common problem in systemic lupus erythematosus (SLE) patients. This study was performed to determine the prevalence of sleep disturbance in SLE, the factors that might be associated with sleep disturbance, and the correlation between changes in clinical parameters and sleep quality over time. Fifty-six female SLE patients from a total of 497 SLE patients (11.3%) agreed to join the study. The demographic data were recorded at baseline and the clinical data, the Pittsburgh Sleep Quality Index (PSQI) and other standardized assessment tools, disease activity index, quality of life (QoL), damage index, depression, anxiety and fatigue score, were assessed three times: the first visit was at baseline, the second time was one month later, and the third time was three months after the baseline. Thirty-one of these 56 patients (55.36%) were found to have sleep disturbances. All were females with their mean ± SD age of 37.5 ± 12.3 years, and disease duration at study entry of 8.6 ± 7.3 years. There was no association between sleep disturbances and demographic data, disease activity, clinical symptoms, the presence of autoantibodies and current steroid use. In multiple logistic regression analyses, only moderate to severe depression was the independent determinant of sleep disturbances, p = 0.036. During the three-month observation, with the treatment, the changing of total PSQI score showed a significantly positive correlation with depression, anxiety, pain and QoL. Sleep disturbances in Thai SLE patients were not uncommon but a correctable condition. Depression was strongly associated with sleep disturbances. Awareness of underlying depression as well as sleep disturbances in SLE patients and treating them properly improve QoL in SLE.

Effect of minidose aspirin on renal function and renal uric acid handling in healthy young adults

Minidose aspirin (60–325 mg/day) has been widely used in the prevention and treatment of cardiovascular and cerebrovascular diseases. However, studies on the effects of minidose aspirin on renal handling of uric acid and renal function are limited. We studied the effect of aspirin at 60 mg/day (n = 18) and 300 mg/day (n = 14) on uric acid handling and renal function in healthy subjects. The subjects were evaluated weekly during 2 weeks of aspirin therapy, and again 1 week after aspirin was discontinued. Aspirin at both dosages decreased the fractional excretion of uric acid. However, aspirin at 300 mg/day, but not 60 mg/day, significantly decreased uric acid clearance and creatinine clearance by the end of the second week of aspirin therapy. Despite these changes, serum uric acid and serum creatinine remained constant. The uric acid clearance, but not the creatinine clearance, returned to baseline value 1 week after aspirin therapy was discontinued. As aspirin at 60 mg/day showed no suppressive effect on renal function, it may be better for long-term use.

Adult onset Still's disease: clinical features and outcome in 16 Thai patients.

The clinical features of adult onset Still’s disease (AOSD) have rarely been described in Thai patients. We report the clinical manifestations, laboratory findings, and outcome of 16 Thai patients with AOSD, and compare these findings with those of the western and other oriental series. Fourteen patients (87.5%) had the onset of their disease between 16–35 years of age. The most common features presented were fever (100%), arthralgia and myalgia (100%), significant weight loss (84.6%), arthritis (81.3%), skin rashes (68.8%), sore throat (62.5%), elevated erythrocyte sedimentation rate (100%), leukocytosis (93.8%), and liver dysfunction (75%). Pleuro-pericarditis and abdominal pain were uncommon. All but 2 patients required corticosteroids to control their systemic disease activity. The clinical course of 13 patients, who were followed for more than 12 months, was monocyclic systemic disease in four cases, polycyclic systemic disease in five, chronic articular monocyclic systemic in one, and chronic articular polycyclic systemic in three. When compared with western and other oriental series, the AOSD in Thai patients shared similar clinical features and laboratory findings, suggesting that mechanisms of pathogenesis may be similar in patients from widely different genetic backgrounds and geographic locations. Corticosteroids were frequently required and dramatically effective.

Lack of CTGF*-945C/G Dimorphism in Thai Patients with Systemic Sclerosis.

An association between connective tissue growth factor (CTGF) gene dimorphism at –945 (CTGF*-945C/G) and systemic sclerosis (SSc) has been reported with inconclusive results. We performed this study to determine whether such an association exists among Thai patients with SSc. DNA samples were taken from 50 Thai SSc patients (diffuse SSc in 39 and limited SSc in 11) and 99 healthy controls for determination of CTGF*-945C/G dimorphism by polymerase chain reaction (PCR) using specific oligonucleotide primers. The associations between the genotype frequencies, clinical manifestations and auto-antibodies were determined as well. When compared with the controls, SSc patients had no significantly higher frequencies of the GG genotype (44.0% vs 39.4%, p = 0.60), G allele (63.0% vs 65.2%, p = 0.80) or G phenotype (82.0% vs 90.9%, p = 1.0). There was no association between the presence of the GG genotype and clinical manifestations (pulmonary fibrosis, sclerodactyly, digital pitting scars, telangiectasia and pulmonary arterial hypertension), or the presence of auto-antibodies (anti-Scl-70, anti-SSA/Ro, and anti-RNP). In conclusion, we found no association between CTGF*-945C/G dimorphism and Thai SSc patients.

Comparison of proteinuria determination by urine dipstick, spot urine protein creatinine index, and urine protein 24 hours in lupus patients.

Background:A simple, convenient, and accurate method for detecting urine protein excretion in lupus nephritis is crucial. Objectives:The objectives of the study were to determine the sensitivity and the specificity of the qualitative urine dipstick test value to detect 0.50 g or greater of the quantitative 24-hour urine protein (24-hUP) in lupus patients, to evaluate an overall agreement of the dipstick test results and the magnitude of 24-hUP, and to examine the correlation between the spot urine protein creatinine index (S-UPCI) and the 24-hour UPCI with that of the 24-hUP. Methods:A prospective study was conducted in 92 patients with lupus. All dipstick test values from 5 dipstick assays (Bayer, Roche, Meditest USA, Standard Diagnostics, and Arkray) and the S-UPCI were obtained within 6 hours of the 24-hUP collection. Of 149 urine samples, only 39% were collected properly and were used for analysis. Results:The sensitivity and specificity of a ≥2+ dipstick test result to detect 0.50 g or greater 24-hUP were 56-% to 80% and 67% to 92%, respectively. The agreement of the urine dipstick test values and the magnitude of 24-hUP was fair (&kgr; = 0.23-0.32). The correlation between the S-UPCI and the 24-hUP was 0.83 (P < 0.0001), and that of the 24-hour UPCI and the 24-hUP was 1 (P < 0.0001). Using 24-hUP 2 g/d or less, the bias ±1.96 SD of the difference of S-UPCI and 24-hUP was 0.23 (SD, 0.96) g. Conclusions:A ≥2+ dipstick test is relatively sensitive to detect significant proteinuria, but it is poorly correlated with quantitative 24-hUP. The S-UPCI and the 24-hUP can be used interchangeably for follow-up in lupus nephritis patients with proteinuria of less than 2 g/d.

An evaluation of the association of leukopenia and severe infection in patients with systemic lupus erythematosus.

BackgroundLeukopenia is a common finding in systemic lupus erythematosus (SLE) and may contribute to severe infections. ObjectivesThe objectives of this study were to determine the prevalence of leukopenia in SLE patients and examine the association between these conditions and severe infections noting the risk factor of severe infections. MethodsThis study was a prospective inception lupus cohort of newly diagnosed SLE patients seen between May 2007 and June 2011. Only cases that had been observed for a minimum of 1 year or died during the study were included. ResultsThere were 89 SLE patients (92% females), with their mean (SD) age and disease duration at the study entry of 31.7 (12.2) years and 2.4 (2.9) months. Leukopenia was found at the diagnosis in 51.6% of the cases. The cumulative prevalence of leukopenia, lymphopenia, and neutropenia was observed in 57.3%, 96.6%, and 60.7%, respectively. Persistent lymphopenia, noted continuously for more than or equal to 75% of the observation period, was found in 41.6%, but there was no persistent neutropenia. The incidence rate of severe infection was 12.4 per 100 patient-years. There was no difference of severe infection–free survival rate between patients who ever and never had leukopenia. In the multivariate analysis, using cyclophosphamide was the independent predictor for severe infection in SLE (hazard ratio, 2.73; 95% confidence interval, 1.10–6.77). ConclusionsLeukopenia was common in SLE but usually not persistent. In this study, the presence of leukopenia at any time was not the risk factor for severe infection in SLE. Cyclophosphamide was the important predictor for severe infection in SLE.

The genetic contribution of HLA‐DRB5*01:01 to systemic lupus erythematosus in Thailand

Human leucocyte antigen (HLA) study in patients with systemic lupus erythematosus (SLE) has been investigated in various countries, but the results are still inconclusive. This study was performed to investigate the association between HLA‐DR and SLE in patients in northern Thailand. HLA‐DR subtyping was performed in 70 patients with SLE and 99 normal healthy controls living in northern Thailand using the INNO‐LiPA HLA‐DR Decoder kit (Innogenetics) and MICRO SSP HLA DNA Typing kit (One Lambda) for reconfirmation. The allele frequency (AF) of DRB5*01:01 in SLE was significantly higher than in the controls [25.7% vs. 14.6%, P = 0.012, Pc = 0.048, OR = 2.02 (95%CI = 1.17–3.48)]. The AF of DRB1*15:01 and DRB1*16:02 showed a nonsignificant tendency to be higher in SLE (10.7% vs. 8.1%, and 17.9% vs. 11.1%). Interestingly, the DRB5*01:01 allele linked to DRB1*16:02 in 47.2% of SLE and 37.9% of controls, and the prevalence of the DRB1*16:02‐DRB5*01:01 haplotype was higher in the patients with SLE [12.1% vs. 5.6%, P = 0.044, OR = 2.35 (95%CI = 1.06–5.19)]. The DRB1*16:02 linked to DRB5*02:02 and *02:03 in 18.2% and 31.8% of controls, respectively, and linked to DRB5*02:03 in 32.0% of SLE patients. The frequency of DRB1*03:01 and *15:02 alleles was not increased in Thai SLE. There was no significant association between DRB5*01:01 and any auto‐antibodies or clinical manifestations of SLE. DRB5*01:01 is associated with Thai SLE, and the association is stronger than that of DRB1*15:01. The genetic contribution of DRB5*01:01 is due partially to the linkage disequilibrium between DRB1*16:02 and DRB5*01:01 in the northern Thai population.

Arthritis in leukemia

&NA; The clinical features of 19 patients who had arthritis and leukemia were reviewed and compared with those without arthritis. There was leukemic arthritis (characterized by absence of other evident causes and response to chemotherapy) in 14, septic arthritis in 4, and hemarthrosis in 1. Among those with leukemic arthritis, there was acute leukemia in 11 and chronic leukemia in 3. The arthritis presented before, simultaneously with, and after the diagnosis of leukemia in 5, 4, and 5 cases, respectively. Acute symmetrical polyarthritis mimicking rheumatoid was the most common presentation. The knee, wrist, and ankle were most commonly involved. A degree of pain, which was out of proportion to the degree of inflammation, could be seen occasionally. Synovial fluid blast cells were identified in 33% of cases. The leukemic arthritis responded well to chemotherapy. Septic arthritis was an initial presentation of leukemia in 2 patients. There was no significant difference in hematologic parameters or in mortality rate between those with and without arthritis. In conclusion, symmetric polyarthritis mimicking rheumatoid and septic arthritis could be an initial presentation of leukemic arthritis. One should have a high index of suspicion in patients with acute arthritis, especially if there is already anemia and pain is out of proportion to swelling.