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.

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.

The reliability, validity and responsiveness of the Thai version of Systemic Lupus Erythematosus Quality of Life (SLEQOL-TH) instrument.

OBJECTIVES: The English version of the Systemic Lupus Erythematosus Quality of Life Questionnaire (SLEQOL) is a validated disease-specific quality of life instrument. The aim of this study was to evaluate the psychometric properties of the Thai version of the SLEQOL (SLEQOL-TH). METHODS: Two independent translators translated the SLEQOL into Thai. The back translation of this version was performed by two other independent translators. The final version, SLEQOL-TH, was completed after resolving the discrepancies revealed by the back translation. One hundred and nine patients with SLE were enrolled to test the reliability, construct validity, floor and ceiling effects, and sensitivity to the changes of the SLEQOL-TH at six months. The differential item functioning (DIF) between the Thai and English versions was analyzed using the partial gamma. RESULTS: The internal consistency of the SLEQOL-TH was satisfactory with the overall Cronbach's alpha of 0.86. The test-retest reliability of the SLEQOL-TH was acceptable with the intra-class correlation coefficient of 0.86. Low correlations between the SLEQOL-TH and SLEDAI were observed. The total score of the SLEQOL-TH was moderately responsive to changes in quality of life, with a standardized response mean of 0.50. When comparing the SLEQOL-TH from Thai SLE patients with the original SLEQOL version obtained from Singapore SLE patients, 11 out of 40 items showed a moderate to large DIF. CONCLUSIONS: The SLEQOL-TH has acceptable psychometric properties and shows construct validity. In comparison with the English version of SLEQOL, there are some items that showed DIF. The applicability of the SLEQOL-TH in real-life clinical practice and clinical trials needs to be determined.

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.

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.

A modified Delphi exercise to determine the extent of consensus with OMERACT outcome domains for studies of acute and chronic gout.

OBJECTIVES: To reach consensus with recommendations made by an OMERACT Special Interest Group (SIG). METHODS: Rheumatologists and industry representatives interested in gout rated and clarified, in three iterations, the importance of domains proposed by the OMERACT SIG for use in acute and chronic gout intervention studies. Consensus was defined as a value of less than 1 of the UCLA/RAND disagreement index. RESULTS: There were 33 respondents (61% response rate); all agreed the initial items were necessary, except "total body urate pool". Additional domains were suggested and clarification sought for defining "joint inflammation" and "musculoskeletal function". Items that demonstrated no clear decision were re-rated in the final iteration. There were six highly rated items (rating 1-2) with four slightly lower rating items (rating 3) for acute gout; and 11 highly rated items with eight slightly lower ratings for chronic gout. CONCLUSIONS: Consensus is that the following domains be considered mandatory for acute gout studies: pain, joint swelling, joint tenderness, patient global, physician global, functional disability; and for chronic gout studies: serum urate, gout flares, tophus regression, health-related quality of life, functional disability, pain, patient global, physician global, work disability and joint inflammation. Several additional domains were considered discretionary.

The efficacy, safety and carry-over effect of diacerein in the treatment of painful knee osteoarthritis: a randomised, double-blind, NSAID-controlled study.

OBJECTIVE: To evaluate the efficacy, safety and carry-over effect of diacerein, in comparison to piroxicam, in the treatment of Thai patients with symptomatic knee osteoarthritis (OA). DESIGN: This was a double-blind, randomised, piroxicam-controlled, parallel-group study. A 7-day non-steroidal anti-inflammatory drug washout period was followed by a 16-week treatment period with either diacerein 100mg/day or piroxicam 20mg/day, and an 8-week treatment-free observation period. The primary efficacy criterion was pain on Western Ontario and McMaster University Osteoarthritis (WOMAC) A. The secondary criteria included WOMAC B, C and total WOMAC, paracetamol intake, Short Form-36 questionnaire and global judgements on efficacy and tolerability by patients and investigators. RESULTS: Of 171 randomised patients, 150 completed the study and 161 were analysed in the intent-to-treat population (diacerein: 82, piroxicam: 79). Pain (WOMAC A) decreased to a similar extent in both groups at Week 16 (diacerein: -69.7%+/-31.5%; piroxicam: -74.1+/-26.2%; P=n.s.). On treatment discontinuation, pain increased in the piroxicam group at Weeks 20 (-47%+/-47.8%) and 24 (-26.8%+/-60.6%) while improvements persisted in the diacerein group at Weeks 20 (-66.9%+/-35.9%) and 24 (-69.5%+/-33.7%), with a significant difference in favour of diacerein at Weeks 20 and 24, demonstrating the carry-over effects of the drug. The incidence of adverse events was similar in both groups but more patients from the piroxicam group dropped out of the study due to these events. CONCLUSIONS: Diacerein was as effective as piroxicam in reducing pain and improving function but, unlike piroxicam, displayed a carry-over effect and a better safety profile.

Raised chondroitin sulfate epitopes and hyaluronan in serum from rheumatoid arthritis and osteoarthritis patients.

OBJECTIVES: Serum hyaluronan (HA) and chondroitin sulfate (CS) epitopes WF6 and 3B3 (+) were determined to investigate disease association in patients with osteoarthritis (OA), rheumatoid arthritis (RA) and healthy controls. METHODS: Specific assays for HA and CS epitopes WF6 and 3B3 (+) were established and applied to a cross-sectional study of serum samples from patients (96 OA, 57 RA and 50 healthy controls). RESULTS: Both CS epitopes were increased in serum of many OA and RA patients and average levels were significantly above in healthy controls. In contrast serum HA was increased in RA, but only in few OA patients. CONCLUSIONS: CS epitopes WF6 and 3B3 (+) are raised in serum of patients with both OA and RA and were thus distinct from serum HA. The results suggest that OA may be detected systemically as well as RA. The range of levels of CS epitopes detected in OA and RA was wide and correlation with any aspect of disease activity is yet to be determined.

Correlation between serum hyaluronan and disease activity and severity in Thai patients with rheumatoid arthritis.

Serum hyaluronan (HA) concentration was quantified using an ELISA-based assay with biotinylated hyaluronan binding proteins, and correlated with the clinical and laboratory variables in 100 consecutive rheumatoid arthritis (RA) patients (mean +/- SD age and duration of disease of 50.1 +/- 12.5 and 7.9 +/- 6.6 years respectively). Thirty-four patients received prednisonole at an average dose of 5.0 mg/day. The correlations were good between the serum HA level and the joint swollen scores (r = 0.26, p = 0.04), joint space narrowing scores (r = 0.25, p = 0.03), joint erosion scores (r = 0.26, p = 0.03), and erythrocyte sedimentation rate (r = 0.31, p < 0.01) in RA patients who did not take prednisolone. These correlations were diminished in those who received prednisolone, although their disease was more severe. It might be possible that corticosteroids could decrease inflammation of the joint, thus interfering with the correlations. It was concluded that the serum HA level is a useful marker for the activity and severity of disease in patients with RA.

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.

Depression in Thai patients with rheumatoid arthritis.

A wide spectrum of behavioral and psychological disturbances, in particular depression, has been described as a prevalent problem in patients with rheumatoid arthritis (RA). The investigators proposed to evaluate the correlations of depressive symptoms and the disease activity of RA in Thai patients. A variety of aspects of disease activity included in the assessment were the number of swollen joints, the number of tender joints, overall tenderness of the joints (assessed by using the Ritchie Articular Index), overall pain (assessed by using the visual analog scale for pain), joint functional class, and disease duration. The 24-item Hamilton Rating Scale for Depression (HRSD) was the measure used to determine the severity of depressive symptoms. The correlations of HRSD scores and the data relevant to the disease activity were evaluated by using Pearson correlation test. A total of 75 female and 4 male patients participated in this study. Their mean age and mean duration of disease were 49.81 and 7.48 years, respectively. The mean score of HRSD was significantly correlated with those of the number of swollen joints, the number of tender joints, the Ritchie Articular Index, the visual analog scale for pain, and the joint functional class. In conclusion, depression is highly correlated with some respects of the disease activity of RA, especially the number of swollen joints and joint functional class. The results of the present study are not much different from those of previous studies conducted in western countries. Careful evaluation of the disease activity of RA will be helpful in detecting the depression comorbidity in Thai patients suffering from this disease.

Arthritis in leukemia.

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. Adegree 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.

Pregnancy outcome in Thai patients with systemic lupus erythematosus.

The outcome of 48 pregnancies from 42 patients with systemic lupus erythematosus was studied. Their mean age and the duration of the disease were 28.47 and 4.42 years, respectively. The conception occurred when the disease was inactive or quiescent in 45 and active in 3. Four pregnancies were terminated by criminal abortion. Flares occurred in 16 pregnancies. The kidney and mucocutaneous system were the 2 organs that flared most commonly. The fetal outcomes were term delivery in 18 (40.90%), prematurity in 17 (38.64%), spontaneous abortion in 6 (13.64%) and still birth in 3 (6.82%). There was no statistical difference in pregnancy loss and successful delivery between pregnant patients with and without flares. Concerning 35 successful live births, those pregnancies without flares had significantly more full term deliveries (p < 0.02), higher gestational age (p < 0.002) and more birth weight (p < 0.001) than those with flares. Small for gestational age was seen in 20%. Pregnancy with active renal disease had a poor fetal outcome. There were no cases of congenital anomalies or neonatal lupus. Maternal complications were more common in patients with flares.

Acute aortic valvulitis as an initial presentation of systemic lupus erythematosus.

Valvular involvement in patients with systemic lupus erythematosus (SLE) is not uncommon but patients rarely present with it. The mitral valve is most commonly involved. We report a 36-year-old man who had an episode of acute fever, arthritis, and acute aortic insufficiency with a small vegetation at the tip of the aortic valve mimicking infective endocarditis, proven later to be due to SLE. SLE should be considered as one of the uncommon causes of acute aortic insufficiency.

Calcium pyrophosphate dihydrate crystal deposition: a clinical and laboratory analysis of 91 Thai patients.

The clinical features and laboratory findings of 91 Thai patients (33 males and 58 females) with CPPD crystal deposition disease were studied. Their average age was 71.54 years. Acute monoarthritis and oligoarthritis were the two most common forms of presentation and were seen in 89 per cent of cases. The knee, wrist and ankle were the three most common joints involved. Associated diseases were common and included hypertension (30 cases), renal insufficiency (23 cases), chronic obstructive pulmonary disease (17 cases), coronary heart disease (13 cases) and diabetes mellitus (12 cases). Eleven patients had malignancies. Five patients had concomitant gout and CPPD crystal deposition disease. The knee and the wrist were the two most common sites of chondrocalcinosis. Of 67 patients who had thyroid function tested, 2 had hyperthyroidism and 5 had hypothyroidism. Hypomagnesemia was seen in 19 per cent. None had hypercalcemia, hypophosphatasia, hemochromatosis or hyperparathyroidism. In contrast to the western series, acute arthritis in our series responded well to oral colchicine alone.

Childhood Churg-Strauss syndrome.

Churg-Strauss syndrome or allergic granulomatosis and angiitis is a vasculitis that is found in adults, but is extremely rare in children. We describe a 14-year-old boy who presented with prolonged fever, weight loss, sinusitis, myalgia and arthralgia, testicular pain, pulmonary infiltrations, pericardial effusion, peripheral neuropathy, and eosinophilia. Muscle biopsy showed necrotizing arteritis with eosinophil infiltration. His clinical course was complicated by several seizures secondary to cerebral vasculitis and severe asthma, resulting in death. The clinical features and outcomes of childhood Churg-Strauss syndrome are reviewed.

Cardiovascular autonomic nervous system dysfunction in patients with rheumatoid arthritis and systemic lupus erythematosus.

Although peripheral and central nervous system involvement have been well recognized in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), autonomic nervous system (ANS) involvement has rarely been studied, and has shown conflicting results. We performed cardiovascular ANS assessment in 34 RA and 37 SLE patients, using standard cardiovascular reflex tests. The results in each patient were compared with age- and sex-matched healthy controls. Forty-seven percent of the RA patients and 19% of the SLE patients had symptoms suggesting ANS dysfunction. The heart rate variation in response to deep breathing was significantly decreased in both the RA and SLE patients (p = 0.001). This diminished heart rate response showed no correlation with the disease duration, the number of swollen joints, the Ritchie articular index, ESR, or rheumatoid factor in the RA group, or the disease duration, the SLEDAI score or ESR in the SLE group. The clinical significance of the diminished cardiovascular ANS response needs to be investigated.

Anti Ro/SSA positive undifferentiated connective tissue disease in a mother with a newborn with complete congenital heart block: a case report.

An association between complete congenital heart block (CCHB) and anti-Ro/SSA antibody is well recognized but has never been reported in Thailand. We report here a 37-year-old female who was admitted because of massive epistaxis secondary to immune thrombocytopenia. She had given birth to a child with CCHB 2 years previously, when she was healthy. Antinuclear antibody and anti-Ro/SSA were positive in her sera, but were negative in her son. The relationship between anti-Ro/SSA antibody and outcome of mothers with infants with CCHB is reviewed.

Ruptured mycotic abdominal aortic aneurysm in a patient with systemic lupus erythematosus.

Abdominal pain, a common condition, has been reported in up to 37|X% of-patients with systemic lupus erythematosus (SLE) (1). There are many possible causes including peritonitis, pancreatitis, mesenteric vasculitis, thrombosis of the mesenteric vessels, intra-abdominal infections, or side effects of the medications used in the treatment of the disease, especially non-steroidal anti-inflammatory drugs (1-3). However, ruptured mycotic aneurysm of the abdominal aorta has rarely been mentioned as a cause of abdominal pain in SLE (1-3). We recently saw a patient with SLE who had an acute surgical abdomen, which proved to have been caused by a rupture of a mycotic abdominal aortic aneurysm.