The clinically quiescent phase in early-diagnosed SLE patients: inception cohort study.

OBJECTIVES: The aims of this study were to evaluate the incidence of clinical quiescence in early-diagnosed SLE patients and to determine factors associated with a prolonged clinically quiescent phase. METHODS: We used an inception cohort of SLE patients seen between May 2007 and June 2012. All patients were assessed for clinical quiescence [modified SLEDAI 2000 (mSLEDAI-2K) score = 0, no new features of lupus activity o increase in treatment] then evaluated for the occurrence of flare (mSLEDAI-2K increase ≥4 and increased disease activity in one or more organ systems or an increase in treatment). RESULTS: Ninety-five patients (88 females) with a mean age of 33.22 years (s.d. 13.24) and mean disease duration 2.79 months (s.d. 3.19) at cohort entry were enrolled during a mean observation period of 3.04 years (s.d. 1.38). Sixty-six patients (69.5%) reached clinical quiescence within 11.31 months (s.d. 1.10) of enrolment. Thirty-six patients (54.5%) had a disease flare during the observation period. The clinically quiescent phase was 28.2 months (s.d. 3.4). Cox regression analysis revealed that age ≥25 years at diagnosis [hazard ratio (HR) 2.57 (95% CI 1.23, 5.40)] and continued antimalarial drug treatment [HR 2.80 (95% CI 1.40, 5.58)] were associated with a longer clinically quiescent phase. CONCLUSION: Most early-diagnosed SLE patients could have a good prognosis. Age at diagnosis ≥25 years or continued treatment with antimalarial drugs after reaching clinical quiescence may result in a longer clinically quiescent phase. More studies are needed to elucidate the mechanism of action for these protective effects.

Streptococcus agalactiae: an emerging cause of septic arthritis.

OBJECTIVE: Invasive Streptococcus agalactiae infection in nonpregnant women has been reported increasingly worldwide. This study reports the clinical features and outcome of S. agalactiae septic arthritis in Thai patients. METHODS: The medical records of cases with septic arthritis seen between July 1990 and December 2010 were reviewed. Only those with S. agalactiae were included in this study. RESULTS: From 244 cases of septic arthritis, 38 (15.57%, 13 men and 25 women) were caused by S. agalactiae, with 34 of them (89.48%) occurring between 2008 and 2010. Their mean age was 52.89 (SD, 18.95) years. Twenty-four of the 38 patients (63.16%) had 1 or more underlying disease that might predispose to joint infection. Fever and joint pain were the most common symptoms presented. Eleven cases (28.95%) presented monoarthritis, 15 (39.47%) oligoarthritis, and 12 (31.58%) polyarthritis, with a mean joint involvement of 3.34 (SD, 2.35) joints (range, 1-8). Cellulitis was seen in 27 cases (71.05%). Blood cultures were positive in 31 patients (81.58%). Thirty-five of the 38 synovial fluid specimens obtained were enough for cultures and stain smears, with 24 (68.57%) growing S. agalactiae and 19 (54.29%) showing gram-positive cocci. All isolates were sensitive to penicillin. Ten patients (26.31%) received arthroscopic drainage. The articular outcome was good in 11 patients, fair in 24, and poor in 3. There were no deaths. CONCLUSIONS: Streptococcus agalactiae is an emerging cause of septic arthritis in Thai patients. Physicians should be especially aware of this condition in patients presenting with acute oligopolyarthritis and prominent cellulitis.

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

BACKGROUND: Leukopenia is a common finding in systemic lupus erythematosus (SLE) and may contribute to severe infections. OBJECTIVES: The 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. METHODS: This 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. RESULTS: There 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). CONCLUSIONS: Leukopenia 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.

Association of HLA-DRB1*15:02 and DRB5*01:02 allele with the susceptibility to systemic sclerosis in Thai patients.

A genetic study, particularly in HLA-DRs, has never been performed in Thai patients with systemic sclerosis (SSc). This study was performed to investigate the association between the HLA-DR series in Thai SSc patients. HLA-DR subtypes were determined in 50 Thai SSc patients and 99 healthy controls (HCs). All SSc patients met the ACR classification criteria for SSc. HLA-DR typing was performed using INNO-LiPA HLA-DRB Decoder kits (INNOGENETICS) and reconfirmed using MICRO SSP HLA DNA Typing kits (ONE LAMBDA). The allele frequency (AF) of HLA-DR*15, compared with HC, was significantly higher in all SSc patients (41.0 vs 21.7%, Pc = 0.0083) and SSc patients with anti-Scl70 antibody positive (anti-Scl70+) (47.1%, Pc = 0.0018). Among the HLA-DR*15 alleles, the AF of the DRB1*15:02 was increased significantly in all SSc patients (29.0 vs 12.6%, Pc = 0.0219) and SSc patients with anti-Scl70+ (32.4 vs 12.6%, Pc = 0.0196). The AF of the HLA-DRB5*01:02 allele was also increased in all SSc patients (27.0 vs 12.6%, Pc = 0.0166) and in SSc patients with anti-Scl70+ (29.4%, Pc = 0.0124). The AF of the DR*04 was significantly lower in the SSc patients (1.0 vs 9.6%, Pc = 0.0399). However, the AF of the DRB1*15:02 and DRB5*01:02 was not different among SSc patients with or without clinical manifestations (pulmonary fibrosis, digital pitting scar, sclerodactyly, myositis, and sicca symptoms). In addition, there was no significant association between clinical manifestations among individuals who carried HLA-DRB1*15:02 or DRB5*01:02. HLA-DRB1*15:02 and DRB5*01:02 alleles were significantly elevated in Thai SSc patients, especially in those with anti-Scl70+. The HLA-DRB1*04 was a protective allele against Thai SSc patients.

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 patient's 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.

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 (κ = 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.

Anti-agalactosyl IgG antibodies in Thai patients with rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis.

This study was performed to determine the prevalence of anti-agalactosyl IgG antibodies in Thai patients with RA, systemic lupus erythematosus (SLE) and systemic sclerosis (SSc), and determine the sensitivity and specificity of anti-agalactosyl IgG antibodies in the diagnosis of RA in comparison with IgM-rheumatoid factor (IgM-RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies. Serum samples were obtained from 100 patients with RA, 50 cases of SLE, 50 cases of SSc, and 100 healthy controls and analyzed for the presence of anti-agalactosyl IgG antibodies, IgM-RF and anti-CCP antibodies. A serum value greater than mean + 2 standard deviation of normal value of anti-agalactosyl IgG antibodies and anti-CCP antibodies was considered positive. The prevalence of anti-agalactosyl IgG antibodies in RA, SLE, and SSc patients was 88.0%, 14.0%, and 12.0%, respectively. The serum level of anti-agalactosyl IgG antibodies in patients with RA (227.10 +/- 353.64 AU/mL) was significantly higher than those in SLE (11.84 +/- 52.04 AU/mL), SSc (18.85 +/- 99.60 AU/mL), and healthy controls (2.14 +/- 1.97 AU/mL), (p < 0.001). There was a good correlation between the log serum level of anti-agalactosyl IgG antibodies and IgM-RF (r = 0.92, p < 0.001), anti-CCP antibodies and IgM-RF (r = 0.49, p < 0.001), and anti-agalactosyl IgG antibodies and anti-CCP antibodies (r = 0.55, p < 0.001). The sensitivity and specificity in the diagnosis of RA was 88.00% and 96.00% for anti-agalactosyl IgG antibodies, 90.00% and 99.00% for anti-CCP antibodies, and 91.00% and 95.00% for IgM-RF, respectively. The serum level of anti-agalactosyl IgG antibodies was significantly higher in RA than in SLE, SSc, and healthy controls. There was a good correlation between serum levels of anti-agalactosyl IgG antibodies, anti-CCP antibodies, and IgM-RF. These three tests had comparable sensitivity and specificity.

Acute rheumatic fever in adults: case report together with an analysis of 25 patients with acute rheumatic fever.

We reported the oldest acute rheumatic fever (ARF) patient with initial attack at the age of 90 years and experience with ARF in adults in 20 years of observation. The case files of all ARF patients treated by rheumatology unit, Chiang Mai University, were reviewed. Demographic data and clinical profile were recorded and compared between patients with initial attack and patients with recurrent attack. A total of 25 patients with ARF were included. There was no different incidence of arthritis and carditis between two groups. Initial attack patients have higher incidence of prolonged PR-interval (67 vs. 12%, P = 0.049) and longer duration of admission to diagnosis (5 vs. 2 days, P = 0.05). Thirty percent presented initial attack after 30 years of age. ARF is more common in adults than previously recognized. Therefore, clinicians should be aware of this condition and include it in their differential diagnosis of the febrile patients with arthritis.

Pulmonary arterial hypertension in Thai patients with systemic sclerosis.

OBJECTIVE: Study the clinical features of pulmonary arterial hypertension (PAH) in Thai patients with systemic sclerosis (SSc), and compare these features between those with limited (lc) SSc and diffuse (dc) SSc. MATERIAL AND METHOD: The medical records of SSc patients attending the Division of Rheumatology, Chiang Mai University were reviewed. PAH was defined by pulmonary arterial systolic pressure (PASP) > 35 mmHg, determined by Doppler echocardiography. RESULTS: Among 275 patients with SSc, 66 had Doppler echocardiography measurement. Thirty-nine patients (59.1%) had PAH. Among the PAH-SSc patients, 36 (92.3%) presented with dyspnea on exertion, and 37 (94.8%) were in a New York Heart Association functional class of II and III. Twenty-four of 39 patients (61.5%) had interstitial lung disease. Diffuse SSc patients had a significantly higher proportion of males, and shorter disease duration between SSc and PAH diagnosis than lcSSc patients. CONCLUSION: PAH was not uncommon in Thai patients with SSc. Interstitial lung disease might have been the cause associated with over half of these cases. Annual routine Doppler echocardiography screening for PAH in patients with SSc may detect preclinical PAH, and lead to early management and improved functional outcome.

Validation of the Thai version of a screening questionnaire for detection of systemic lupus erythematosus.

OBJECTIVE: The present study was performed to assess the sensitivity and specificity of the translation questionnaire for Systemic Lupus Erythematosus (SLE) in Thai speaking populations. MATERIAL AND METHOD: The 10- item questionnaire was applied to out-patients at the rheumatology clinic of the Chiang Mai University Hospital. One hundred and thirty-nine SLE, 109 Rheumatoid Arthritis (RA), and 35 Scleroderma (Scl) patients, as well as 88 Healthy Controls (HC) were enrolled into the present study. RESULTS: All subjects completed the questionnaire within 2 minutes. A positive response to three or more questions of the questionnaire gave a sensitivity and specificity of 92.81% and 76. 39%, respectively, and was comparable to the original version. CONCLUSION: This Thai-version of the screening questionnaire should be applied in the general population to determine the prevalence of SLE.

Sicca symptoms in Thai patients with rheumatoid arthritis, systemic lupus erythematosus and scleroderma: a comparison with age-matched controls and correlation with disease variables.

This study was performed to determine the prevalence of ocular and oral sicca symptoms in Thai patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and scleroderma (Scl). The ocular symptoms and sign (the Schirmer's 1 test) and the oral sicca symptoms and sign (the Saxon's test) in each of 50 RA, SLE and Scl patients were compared with their age-matched controls. The correlation between the presence of sicca symptoms and signs with their clinical activity was also determined. Ocular sicca symptoms were found more common in patients with RA (38% vs 18%, p < 0.05), SLE (36% vs 14%, p < 0.05) and Scl (54% vs 16%, p < 0.01), and oral sicca symptoms were found more common in SLE (22% vs 0%, p < 0.01), and Scl (16% vs 4%, p < 0.05) than their controls. However, only RA patients had a significantly higher proportion of positive Schimer-1 test compared with their controls (p < 0.01). There was no strong correlation between sicca symptoms or signs and other clinical or laboratory variables (age, disease duration, disease activity, disease severity, and antibody to Ro and La antigens) in these three groups. In conclusion, sicca symptoms were seen significantly more common in Thai patients with connective tissue diseases, but the symptoms did not show a good correlation with the clinical and laboratory variables.

A clinical study of crystal-proven gouty arthritis in a university hospital.

The clinical features of 567 patients with crystal proven gout (489 males, 78 females) seen in a University Hospital in northern Thailand was reviewed. The mean age at onset and mean duration of disease was 60.0 +/- 11.7 years and 5.2 + 4.8 years, respectively. Recurrent attacks accounted for 94 per cent. The knee and ankle were the 2 most common joints affected during the first attack and each one was seen in 55.6 per cent of cases. During a recurrent attack, the ankle, knee and first metatarsophalangeal joint were the 3 most common joints affected and were seen in 94.5 per cent, 81.2 per cent and 80.2 per cent of cases, respectively. Thirty-six per cent of the patients had tophi. Hypertension, hyperlipidemia, diabetes mellitus and ischemic heart disease were commonly associated diseases. Thirty-five per cent had renal calculi, and fifty-four per cent had renal insufficiency. Of 59 patients who tested with normal renal function, twelve per cent were hyperexcretor. The clinical features of gout seen in the university hospital in northern Thailand were similar to those reported in Bangkok, but with a higher incidence of tophaceous gout, renal failure and renal calculi.

Causes of death and prognostic factors in Thai patients with systemic lupus erythematosus.

From a cohort study of 349 Thai patients (337 females [F] and 12 males [M]) with systemic lupus erythematosus (SLE), 52 patients (51 F, 1 M) died. Their 5- and 10-year survival rates were 84.0% and 74.9%, respectively. Seventy-nine percent of deaths occurred within the first year of diagnosis. Infection contributed to 27 deaths (51.9%). The lung and the urinary system were the 2 most common sites of infection. There were 18 SLE-related deaths (34.6%), and 7 non-SLE related deaths (13.5%). In a multivariate analysis of all causes of death, serositis, hematologic abnormality, central nervous system (CNS) and renal involvement were significantly associated with poor survival, while photosensitivity and arthritis were significantly associated with longer survival. Among SLE-related death, serositis and CNS involvement were significantly associated with poor survival, and arthritis was associated with longer survival. In conclusion, infection was the most common cause of death in Thai SLE patients. CNS and visceral involvement were associated with a poor outcome.

Serum muscle enzymes, muscle pathology and clinical muscle weakness: correlation in Thai patients with polymyositis/dermatomyositis.

The clinical correlation between serum muscle enzymes, muscle pathology and muscle weakness was studied in 100 Thai patients (22 males and 78 females) with polymyositis (PM) and dermatomyositis (DM). Their mean +/- SD age and duration of disease were 45.0 +/- 13.9 years and 6.3 + 13.4 months, respectively. There was idiopathic PM in 37 cases, idiopathic DM in 13, PM/DM associated with malignancy in 5 and PM associated with connective tissue disease in 45. Serum muscle enzymes including creatine phosphokinase, lactate dehydrogenase and aspartate aminotransferase were elevated in 87 per cent, 92 per cent, and 82 per cent of cases, respectively. Abnormal electromyographic findings that were compatible with inflammatory myopathy were found in 76 per cent of cases. Seventy-seven per cent had an abnormal muscle biopsy that was consistent with polymyositis. There was a significant correlation between serum muscle enzymes and muscle pathology (p < 0.01). The degree of muscle weakness correlated better with the degree of muscle destruction (p = 0.01) than the degree of muscle inflammation (p = 0.03). The erythrocyte sedimentation rate showed no correlation with serum muscle enzymes, muscle pathology or muscle weakness.

Erythema nodosum as a manifestation of HIV infection.

Various musculoskeletal syndromes have been well described in patients infected with the human immunodeficiency virus (HIV). Surprisingly, erythema nodosum, an inflammation of the adipose tissue of the skin, has rarely been described. We report a 24-year-old known case of HIV infection, who developed fever and multiple tender subcutaneous nodules that were proven to be erythema nodosum. The patient also had polymyositis. She responded well to a high dose of corticosteroids. Erythema nodosum should be listed as possible the rheumatic manifestation of HIV infection.

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.

Causes of death and poor survival prognostic factors in thai patients with systemic sclerosis.

Causes of death and poor prognostic factors for patients with systemic sclerosis (SSc) were studied in 222 cases. Their mean age at the onset and duration of disease was 48.9 +/- 12.0 years and 23.3 +/- 29.3 months, respectively. Fifty-three per cent were diffuse subtype. Patients with diffuse SSc had more digital pitting scars and more muscle, heart, lung, and esophageal involvement than those with limited subtypes (p < or = 0.02). One hundred and six patients were lost to follow-up. With a median follow-up duration of 25 months, 31 of the remaining 116 patients (26.7%) died. SSc related death occurred in 18 cases, in which the lung, heart and kidney (renal crisis) were the major causes. Infection contributed to the remaining 13 deaths. When compared with living patients, using a univariate analysis, factors associated with a reduced survival rate were age of > 45 years at the onset, diffuse skin thickness, and lung, gastrointestinal tract, heart, kidney and muscle involvement (p < or = 0.001). In the multivariate analysis, only age of > 45 years at onset and cardiac involvement remained poor prognostic factors (p = 0.04 and 0.001, respectively).