Prevalence and characteristics of inflammatory rheumatic diseases in patients with thalassemia.

Reports of inflammatory rheumatic diseases (IRD) in thalassemia are limited. This study aimed to determine the prevalence and clinical characteristics of IRD in patients with thalassemia disease. Consecutive adult patients with thalassemia disease, confirmed by hemoglobin typing, attending the Hematology Clinic between June 2019 and May 2021 were invited to join this study. All of them had their history taken and a physical examination for IRD. Those with IRD had their medical records reviewed. Sixty-three patients (transfusion-dependent in 50) were included in this study. There was α-, ß-, and co-inheritance of α- and ß-thalassemia in 22.22%, 73.02%, and 4.76% of the patients, respectively, with ß-thalassemia/Hb E disease in 53.97%. Twenty-three patients had IRD (rheumatoid arthritis in 9, gout in 6, systemic lupus erythematosus in 3, spondyloarthropathy in 2, and one patient each with dermatomyositis, overlap syndrome, and unclassified polyarthralgia). Clinical manifestations and laboratory findings were similar to IRD patients in general. In 40 patients without IRD, direct and indirect Coombs tests and antinuclear antibody (ANA) were positive in 51.72%, 27.59%, and 10.26%, respectively. When comparing among these 40 patients, between those with non-transfusion-dependent thalassemia (n = 10) and those with transfusion-dependent thalassemia (n = 30), the latter had non-significantly more positive direct Coombs (60.87% vs. 16.67%), indirect Coombs (30.43% vs. 16.67%), and ANA tests (13.33% vs. 0%). The prevalence of IRD in patients with thalassemia disease was rather high. Positive direct Coombs test and ANA were common in transfusion-dependent patients.

Acute parkinsonism in patients with systemic lupus erythematosus: a case report and review of the literature.

Purpose of the study: Parkinsonism in patients with systemic lupus erythematosus (SLE) is rare. This study reported a case of parkinsonism in SLE and reviewed the clinical features and outcomes of parkinsonism in SLE patients.Methods: English language literature of parkinsonism in SLE patients was reviewed.Results: There were 28 patients (19 adults and 9 children) with SLE and parkinsonism. Twenty-three patients were female. Of 26 patients whose disease duration was available parkinsonism occurred at SLE diagnosis and after SLE diagnosis in 6 and 20 patients, respectively. Twenty-five patients had active SLE. Hematologic, mucocutaneous and musculoskeletal systems were the 3 most common organs involved in SLE during parkinsonism onset. Rigidity, bradykinesia and resting tremor were the 3 most common parkinsonian symptoms. Compared with adults, child cases had significantly more psychosis (4 in 9 vs. 1 in 19, p = .026), seizures or psychosis (6 in 9 vs. 2 in 19, p = .005) and mutism (6 in 9 vs. none, p < .001). Brain magnetic resonance imaging (MRI) was abnormal in 13 of 24 patients. Eight of nine patients had abnormal single-photon emission computed tomography (SPECT) and 5 and 3 showed hypoperfusion and hyperperfusion, respectively. The outcomes were resolution, partial response and persistent symptoms in 17, 7 and 4 patients, respectively. The outcome was no different whether or not dopamine therapy was included to corticosteroids and/or immunosuppressive drugs.Conclusions: Parkinsonism in SLE usually occurs during active SLE disease. Good response to corticosteroid and/or immunosuppressive drugs supports the immunologic mechanism in the pathogenesis.

Disease Activity and Rate and Severity of Flares During Peripartum Period in Thai Patients With Systemic Lupus Erythematosus: An Age at Diagnosis and Disease Duration Matched Controlled Study.

BACKGROUND/OBJECTIVE: The aim of this study was to compare disease activity and rate and severity of flares between pregnant and nonpregnant systemic lupus erythematosus (SLE) patients. METHODS: Medical records of pregnant SLE patients seen between January 1993 and June 2017 were reviewed. Nonpregnant SLE controls were matched by age at diagnosis and disease duration before pregnancy. Systemic lupus erythematosus disease activity and flares were determined by the cSLEDAI (clinical Systemic Lupus Erythematosus Disease Activity Index) and Safety of Estrogens in Lupus Erythematosus National Assessment-SLEDAI Flare Index, respectively. Disease activity was measured from 6 months before conception (-6 months) until the postpartum period. The repeated measures mixed model, Cox regression, and cumulative hazard plots were used for statistical analysis. RESULTS: Ninety pregnancies occurred in 77 patients. The cSLEDAI scores from -6 months to the postpartum period were comparable between the pregnancy and control group, but slightly yet significantly higher in the controls at conception (mean ± SEM, 3.57 ± 0.45 vs 1.90 ± 0.36; p = 0.019). When compared with the controls, during the pregnancy and postpartum period, the pregnancy group did not have significantly higher incidence of flare (41.11% vs 28.89%, p = 0.086 and 7.78% vs 11.11%, p = 0.445, respectively) or flare category (severe flare) (75.68% vs 53.85%, p = 0.070 and 85.71% vs 70.00%, p = 0.603, respectively). The flare incidence rate (95% confidence interval)/100 patient-months in the pregnancy and control group was 6.75 (4.89-9.32) and 4.34 (2.96-6.38), respectively, giving the adjusted hazards for flare (95% confidence interval) of 1.54 (0.91-2.61) (p = 0.110). CONCLUSIONS: There was no overall significant increase in SLE disease activity, flare incidence, and flare severity in pregnant SLE patients when compared with their properly matched nonpregnant SLE controls.

Associations between physicians' global assessment of disease activity and patient-reported outcomes in patients with systemic lupus erythematosus: A longitudinal study.

OBJECTIVE: To determine longitudinal associations between Physician Global Assessment (PGA) and patient-reported outcomes (PROs) in patients with systemic lupus erythematosus (SLE). METHODS: Patients attending a rheumatology clinic between 2013 and 2017 completed specific (SLEQOL) and generic (SF36) health-related quality of life (HRQoL) surveys and rated their global rating of change (GRC) at each visit. PGA, SLEDAI-2K and SLE Flare Index (SFI) were also captured on all visits. Generalised estimating equations (GEE) methods were used to examine longitudinal associations of PGA with PROs and clinical indicators. RESULTS: 337 patients were followed for a median [IQR] of 3.2 [1.6, 3.4] years (2,059 visits). High PGA (>1) was strongly associated with high SLEDAI-2K scores, the presence of flares and poor PROs. Odd ratios (OR) [95% CI] of PGA > 1 in patients with SLEDAI-2K >4 & <10 and SLEDAI-2K ≥10, compared to SLEDAI-2K ≤ 4, were 3.46 [2.36, 5.08], p < 0.001 and 6.39 [4.30, 9.49], p < 0.001, respectively. OR [95% CI] of PGA > 1 in patients with mild-to-moderate or severe flares were 2.09 [1.62, 2.71], p < 0.001 and 4.42 [3.21, 6.07], p < 0.001, respectively. Mental components of both SLEQOL (mood, self-image) and SF36 (MCS) surveys demonstrated significant associations with high PGA. After adjusting for SLEDAI-2K, one-point increase in PGA was associated with reductions in SLEQOL total score and SF36-MCS by 2.33 (regression coefficient (RC) [95% CI] = -2.33 [-3.77, -0.88], p = 0.002), and 4.16 (RC [95% CI] = -4.16 [-5.19, -3.13], p < 0.001) points, respectively. Associations of some physical components (SLEQOL-symptoms, and SF36-PCS) with PGA attenuated when adjusted for SLEDAI-2K. Patients who rated low scores of GRC, which indicate health deterioration, were twice as likely to have PGA > 1 (OR [95%CI] 1.99 [1.25, 3.16], p = 0.004). CONCLUSION: High PGA was strongly associated with poor mental health, high disease activity and flares. This study confirms the value of PGA as an efficient assessment tool for SLE.

Incidence and predictors of interstitial lung disease (ILD) in Thai patients with early systemic sclerosis: Inception cohort study.

OBJECTIVES: To determine and compare the prevalence of interstitial lung disease (ILD), the severity of high-resolution computed tomography (HRCT) score and incidence rate (IR) of ILD between the two subsets of early-SSc (systemic sclerosis) patients. We also determined the factors associated with ILD. METHODS: We used an inception cohort of early-SSc patients seen between January 2010 and June 2014. All patients underwent HRCT at study entry and annually thereafter. RESULTS: One hundred and thirteen patients (66 females and 89 diffuse cutaneous SSc [dcSSc]) with a mean ± SD age of 53.4 ± 8.4 years and mean disease duration of 12.9 ± 10.3 months at cohort entry were enrolled. At enrollment, patients with dcSSc had a higher prevalence of ILD (78.7% vs. 45.8%, p = 0.002), and a higher total HRCT score (10.3 ± 9.5 vs. 4.4 ± 5.6, p = 0.001) compared with limited cutaneous SSc (lcSSc). DcSSc patients had a higher IR of ILD than lcSSc patients (58.8 vs.17.3 per 100 person-years, p < 0.001). Univariable analysis revealed that male gender, presence of anti-Scl 70 and absent anti-centromere antibody was significant predictors of ILD. In Cox-regression analysis, a positive anti-centromere [hazard ratio (HR) 0.09 95% confidence interval (95% CI 0.01-0.73)] was a protective factor. CONCLUSIONS: DcSSc patients had more severe HRCT scores and higher IR of ILD compared with lcSSc patients. Male gender, presence of anti-Scl 70, and absent anti-centromere antibody predicted the future development of ILD in early-SSc patients.

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.

Effect of Antituberculous Drugs on Serum Uric Acid and Urine Uric Acid Excretion.

OBJECTIVES: The aim of this study was to determine the effect of antituberculous drugs on serum uric acid (SUA), urine uric acid (UUA) excretion, and renal function. METHODS: Patients with tuberculosis requiring a 6-month treatment course of antituberculous drugs (isoniazid, rifampicin, pyrazinamide, and ethambutol for 2 months, followed by isoniazid and rifampicin for a further 4 months) were included in this study. Serum uric acid, 24-hour UUA excretion, uric acid clearance (UACl), serum creatinine, and creatinine clearance were determined at baseline and at the end of the second week, second month, and fourth month. RESULTS: Sixteen of 50 patients completed the study. Their mean ± SD baseline SUA and UACl was 4.44 ± 1.72 mg/dL and 8.77 ± 7.03 mL/min per 1.73 m, respectively. At the second week, a significant increase in SUA (9.78 ± 3.21 mg/dL, P < 0.001) and significant decrease in UACl (3.50 ± 2.50 mL/min per 1.73 m, P = 0.001) were noted. These changes persisted through the second month, but returned to baseline value at the fourth month. Thirteen patients (81.25%) had hyperuricemia. The 24-hour UUA followed the same pattern as that of UACl but showed no statistical significance. There were no changes in serum creatinine or creatinine clearance. One patient had arthralgia, and another developed tuberculous arthritis. CONCLUSIONS: The hyperuricemic effect of pyrazinamide and ethambutol was due primarily to a decrease in UACl, which was reversible, and had no negative effect on the renal function. Arthralgia was uncommon and required no specific treatment.

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.

Effects of green tea extract on serum uric acid and urate clearance in healthy individuals.

OBJECTIVE: The objective of this study was to investigate the hypouricemic effects of green tea extract (GTE) in healthy individuals. METHODS: This study comprised 1-week control, 2-week interventional, and 1-week follow-up periods. Participants were assigned randomly at the interventional period to consume GTE at 2 (GTE2), 4 (GTE4), or 6 (GTE6) g/d. Levels of serum uric acid (SUA), uric acid clearance, and serum antioxidant power (using trolox equivalent antioxidant capacity assay) were measured at both ends of each study period. RESULTS: Of 30 participants, 11, 11, and 8 received GTE2, GTE4, and GTE6, respectively. After 2 weeks of consumption, the mean SUA level tended to decrease in all groups, with no statistical significance. Serum uric acid reduction was greatest in GTE2 (from 4.81 ± 0.81 mg/dL to 4.64 ± 0.92 mg/dL, 3.53%). Uric acid clearance decreased significantly in GTE2 (from 11.37 ± 6.41 mL/min per 1.73 m to 7.44 ± 2.74 mL/min per 1.73 m, 34.56%, P < 0.05) and GTE4 (from 8.36 ± 3.41 mL/min per 1.73 m to 5.78 ± 2.33 mL/min per 1.73 m, 30.86%, P < 0.05). Serum antioxidant capacity (TEAC) increased significantly in GTE6 (from 32.77 ± 3.39 mg/mL to 35.41 ± 3.17 mg/mL, 8.06%, P < 0.05). There was no significant change in creatinine clearance. Gastrointestinal adverse events were common, but usually mild, with no medical treatment required. CONCLUSIONS: Green tea extract may modestly lower SUA level and decreases uric acid clearance. Green tea extract also significantly elevated serum antioxidant capacity with a positive dosage effect. The effect of GTE on SUA in healthy individuals was short term. The effects of GTE on urate handling in patients with hyperuricemia or gout need to be determined.

The relevance of high-resolution computed tomographic findings and pulmonary arterial hypertension in systemic sclerosis-associated interstitial lung disease.

OBJECTIVE: To compare the high-resolution computed tomographic (HRCT) findings between systemic sclerosis-associated interstitial lung disease (SSc-ILD) with and without pulmonary arterial hypertension (PAH), as well as to correlate the calculated HRCT scores and the estimated systolic pulmonary artery pressure (sPAP). MATERIAL AND METHOD: The medical records of all SSc-ILD patients who presented at the Rheumatology Clinic, Chiang Mai University Hospital were retrospectively reviewed Patients with the availability of echocardiography performed within six months of the corresponding HRCT were included The extent of ground glass, lung fibrosis, and honeycombing were scored The maximum diameter of the main pulmonary artery (MPAD) and ascending aortic diameter (AD) were measured The PAH was defined by sPAP >45 mmHg. RESULTS: Fifty patients with SSc-ILD diagnosed with HRCT were included Echocardiography identified 19 (38.0%) patients with PAH. The SSc-ILD with PAH had significantly higher mean (SD) lung fibrosis (9.9 [3.6] vs. 7.8 [3.5], p = 0.03), and CT-total scores (20.5 [6.9] vs. 14.9 [6.2], p<0. 01) than those without PAH. In the total group, the CT-total score correlated positively with sPAP (r = 0.384, p<0.01). No significant correlation of MPAD or MPAD/AD with sPAP was found. CONCLUSION: SSc-ILD with PAH had more severe lung fibrosis than those without PAH The calculated total HRCT score may be useful to identify PAH in SSc-ILD.

A comparative study of serum and synovial fluid levels of uric acid between patients with gout and other arthritides.

BACKGROUND: The urate levels and the correlations of urate levels between the serum and synovial fluid (SF) of many arthritic diseases have not been well described. OBJECTIVE: Compare urate levels in the serum and SF of gouty arthritis, calcium pyrophosphate dihydrate deposition disease (CPPD), rheumatoid arthritis (RA), septic arthritis, ankylosing spondylitis (AS), and osteoarthritis (OA) patients. MATERIAL AND METHOD: Paired samples of serum and SF from 95 patients comprised of 33 patients with gout, 22 with CPPD, 18 with RA, nine with septic arthritis, three with AS, and 10 with OA were collected simultaneously for urate measurement by photometric test. RESULTS: Ninety-five patients, including 53 males, with mean (SD) age of 64.1 (15.3) years were recruited. In gout, serum and SF urate levels were significantly higher than those of CPPD, RA, septic arthritis, AS, and OA ( p 0..01). In all the study population, the serum/SF ratios of urate levels of gout were not different across all groups. However, after excluding 24 patients with creatinine >1.5 mg/dl, the serum/SF ratios of urate were significantly lower in gout compared with the others ( 0.02). There were strongly positive correlations between serum and SF urate levels in gout similar to CPPD, RA, septic arthritis, AS, an dOA (r = 0.81-0.91, p 0O.01). CONCLUSION: Despite the highest level of serum and SF urate across all groups, the serum/SF urate ratio in gout patients was the lowest, which suggests that SF urate levels are uniquely higher than their serum. In addition, the levels of serum urate of the entire groups strongly reflect their SF levels.

Comparison of Clinical Features, Treatment and Outcomes of Lupus Nephritis Between Patients With Late- and Early-Onset Systemic Lupus Erythematosus: A Controlled Study.

Background: Studies have found that late-onset systemic lupus erythematosus (SLE) patients (age at diagnosis ≥ 50 years) had less severe disease and milder clinical course, but with higher organ damage and mortality rate than early-onset ones (age at diagnosis < 50 years). Unfortunately, direct comparison of renal manifestations and treatment outcomes between late- and early-onset SLE patients has been determined rarely. This study aimed to compare lupus nephritis (LN) manifestations, treatment, and outcomes between late- and early-onset in SLE patients. Methods: Medical records of SLE patients in a lupus cohort at a tertiary care university hospital, seen between January 1994 and June 2020, were reviewed. Late- and early-onset patients were matched with year at SLE diagnosis at a ratio of 1:2 (62 and 124 patients, respectively). Those with LN were identified and analyzed. Results: At SLE onset and end of the study, LN was identified in 29 and 33 late-onset patients, respectively, and 58 and 90 early-onset patients, respectively. At the end of the study, there were 39 and 214 LN flares in late- and early-onset patients, respectively: giving an incident rate (IR) (95% confidence interval (CI))/100 person-years of LN and active LN flares of 2.00 (0.75 - 5.33) vs. 6.11 (4.32 - 8.64), P = 0.020, and 5.78 (2.75 - 12.12) vs. 18.28 (13.93 - 24.00), P = 0.001, respectively. Late-onset patients received a higher proportion of moderate- to high-dose corticosteroids, but fewer immunosuppressive drugs. In all LN flares, no difference existed between the two groups in serum creatinine, degree of proteinuria, and proportion of patients with nephrotic range proteinuria or rapidly progressive glomerulonephritis, and outcomes in terms of complete, partial or no-remission were similar between them. Mortality rate was higher in late-onset patients (27.27% vs. 6.67%, P = 0.004). Conclusion: This matched controlled study of year at SLE diagnosis showed that late-onset SLE patients had lower prevalence of LN and LN flares. Although they received fewer immunosuppressive drugs, their renal manifestations and treatment outcomes were no different from those in early-onset patients.

Prevalence of thyroid dysfunctions and thyroid autoantibodies in Thai patients with systemic lupus erythematosus: An age- and sex-matched controlled study.

BACKGROUND/OBJECTIVE: To determine the prevalence of thyroid dysfunctions and thyroid autoantibodies in Thai systemic lupus erythematosus (SLE) patients, and compare them with age- and sex-matched healthy controls (HCs). Associations between thyroid dysfunctions and SLE disease activity, and associated factors for thyroid dysfunctions in SLE also were determined. METHOD: One hundred SLE patients, without apparent clinical thyroid disease, attended the Rheumatology Clinic between November 2021 and October 2022, were enrolled into this study. HCs were matched to SLE cases by age and sex (ratio of 1:1). Clinical manifestations, SLE disease activity and medication received were collected in all SLE patients. Thyroid function tests and thyroid autoantibodies (anti-thyroglobulin: anti-TG and anti-thyroid peroxidase: anti-TPO) were collected from all participants. RESULTS: When compared with HCs, SLE patients had higher prevalence of thyroid dysfunctions, hypothyroidism and euthyroid sick syndrome (28% vs. 7%, p < .001, and 12% vs. 2%, p = .010, and 6% vs. 0%, p = .013, respectively). Prevalence of isolated hypothyroxinemia was higher numerically in SLE patients (9% vs. 3%, p = .074). Prevalence of anti-TG or anti-TPO was no different between SLE patients and HCs (16% vs. 18%, p = .707). There was no association between SLE disease activity and abnormal thyroid functions or thyroid autoantibodies. Family history of thyroid disease and prednisolone use (>10 mg/day) were associated factors for thyroid abnormalities with adjusted OR (95% CI) of 6.13 (1.58-23.75), p = .009 and 4.00 (1.37-11.70), p = .011, respectively. CONCLUSION: Thyroid dysfunctions were more prevalent in SLE patients. Family history of thyroid disease and prednisolone use (>10 mg/day) were independent associated factors of thyroid abnormalities.

HLA Association among Thai Patients with Diffuse and Limited Cutaneous Systemic Sclerosis.

This study aimed to clarify the association of HLA Class I and II with dcSSc and lcSSc in Thais. HLA typing for 11 gene loci (Class I: HLA-A, B and C, and Class II [HLA-DR, DP and DQ]) was carried out using the Next Generation DNA Sequencing method (three fields) in 92 Thai patients with systemic sclerosis (55 dcSSc, 37 lcSSc) and 135 healthy controls (HCs). The distribution of HLA alleles in patients with dcSSc and lcSSc was compared. When compared with HCs, the AF of A*24:02:01, A*24:07:01, B*27:04:01 and B*27:06 showed an increasing trend in lcSSc patients without statistical significance. DRB1*15:02:01, DRB5*01:02:01, DQA1*01:01:01, DQB1*05:01:24, DPA1*02:01:01 and DPB1*13:01:01 increased significantly in dcSSc patients. DQB1*05:01:24 and DPB1*13:01:01 also increased significantly in lcSSc patients, but less significantly than in dcSSc patients. The association of DPB1*05:01:01 with lcSSc was significantly protective. HLA-A*24:02:01, B*27:06 and C*03:04:01 formed a three-locus haplotype that also constituted an eight-locus haplotype with DRB1*15:02:01, DQA1*01:01:01, DQB1*05:01:24, DPA1*02:01:01 and DPB1*13:01:01. There was a possibility that HLA Class I would play a role in the pathogenesis of lcSSc, while Class II played more of a role in the dcSSc in Thai patients.

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.

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.

Comparison of clinical features, disease activity, treatment and outcomes between late-onset and early-onset patients with systemic lupus erythematosus. A sex- and year at diagnosis-matched controlled study.

BACKGROUND: Several studies have compared the clinical features and outcomes of late- and early-onset systemic lupus erythematosus (SLE) patients. However, these previous studies were uncontrolled. The current study aimed to compare late- and early-onset SLE patients while controlling for sex and year at diagnosis (± 1 year). METHODS: The medical records of SLE patients in a lupus cohort from January 1994 to June 2020 were reviewed. Late-onset patients were identified as those with an age at diagnosis ≥ 50 years. The early-onset patients (age at diagnosis < 50 years) were matched by sex and year at diagnosis with the late-onset patients at a ratio of 2:1. Clinical manifestations, disease activity (mSLEDAI-2K), organ damage scores, treatment, and mortality were compared between the two groups. RESULTS: The study comprised 62 and 124 late- and early-onset patients, respectively, with a mean follow-up duration of 5 years. At disease onset, when comparing the early-onset patients with the late-onset patients, the latter group had a higher prevalence rate of serositis (37.0% vs. 14.5%, p < 0.001) and hemolytic anemia (50.0% vs. 33.9%, p = 0.034) but lower prevalence rate of malar rash (14.5% vs. 37.1%, p = 0.001), arthritis (41.9% vs. 62.1%, p = 0.009), leukopenia (32.3% vs. 50.0%, p = 0.022) and lymphopenia (50.0% vs. 66.1%, p = 0.034). The groups had similar SLE disease activity (7.41 vs. 7.50), but the late-onset group had higher organ damage scores (0.37 vs. 0.02, p < 0.001). The rates of treatment with corticosteroids, antimalarial drugs, or immunosuppressive drugs were not different. At their last visit, the late-onset patients still had the same pattern of clinically significant differences except for arthritis; additionally, the late-onset group had a lower rate of nephritis (53.2% vs. 74.2%, p = 0.008). They also had a lower level of disease activity (0.41 vs. 0.57, p = 0.006) and received fewer antimalarials (67.7% vs. 85.5%, p = 0.023) and immunosuppressive drugs (61.3% vs. 78.2%, p = 0.044), but they had higher organ damage scores (1.37 vs. 0.47, p < 0.001) and higher mortality rates/100-person year (3.2 vs. 1.1, p = 0.015). After adjusting for disease duration and baseline clinical variables, the late-onset patients only had lower rate of nephritis (p = 0.002), but still received fewer immunosuppressive drugs (p = 0.005) and had a higher mortality rate (p = 0.037). CONCLUSIONS: In this sex- and year at diagnosis-matched controlled study, after adjusting for disease duration and baseline clinical variables, the late-onset SLE patients had less renal involvement and received less aggressive treatment, but had a higher mortality rate than the early-onset patients.

Potential roles of air pollutants on the induction and aggravation of rheumatoid arthritis: From cell to bedside studies.

Rheumatoid arthritis (RA) is an involving chronic systemic inflammatory disease which mainly affects the joints. Several factors including genetic, environment and infections have been acknowledged as being involved in the pathogenesis and aggravation of RA. Air pollution, particularly particulate matter is widely recognized as a cause of health problems. This review is to summarize and discuss the association between air pollutants and the development or the aggravation of RA based on evidence from in vitro, in vivo and clinical studies. The results from the review found that air pollutants can stimulate immunological processes and stimulate inflammatory mediators and autoantibodies productions, both in intro and in vivo studies. In addition, air pollutants can induce RA and aggravate RA disease activity. Unfortunately, there also are some discrepancies in the results, which might be due to the type cell line and the concentration of air pollutants used in the in vitro and in vivo studies, as well as the concentration and duration of exposure in human studies. These findings suggest that future studies focused on elucidating these mechanisms using advanced techniques and identifying reliable biomarkers to assess individual susceptibility and disease activity should be carried out. Longitudinal studies, intervention strategies, and policy implications also should be explored. A comprehensive understanding on these association will facilitate targeted approaches for prevention and management of air pollutant-induced RA and improve health outcome.

Non-loading versus loading low-dose colchicine in acute crystal-associated arthritis: A double-blinded randomized controlled study.

INTRODUCTION: This study aimed to compare the efficacy of non-loading versus loading low-dose colchicine in patients with acute crystal-associated arthritis. MATERIALS AND METHODS: All in-patients who were admitted to Chiang Mai University Hospital with non-arthritis disease and developed acute crystal-associated arthritis during admission (within 48 h after arthritis onset) were invited to join this study. The patients were randomized into two groups. Patients in Group I (non-loading group) and Group II (loading group) received colchicine at 1.2 and 2.4 mg in the first 24 h, respectively. The primary outcome was the patients' pain response at 24 h after treatment. RESULTS: Of 80 patients, 49 were acute gouty arthritis, and 31 acute calcium pyrophosphate (CPP) arthritis. The mean [95% CI] pain score was no different between Groups I and II at the baseline level (6.46[5.72-7.19] vs. 6.654[5.85-7.44], p = .867) and at 24 h (3.13[2.43-3.82] vs. 3.18[2.42-3.93], p = .907). The proportion of patients with ≥50% pain reduction was not different (57.50% vs. 55.00%, p = .822). Sensitivity analysis among patients with a baseline pain score of ≥4 showed the same pattern of response. Mild diarrhea was common and comparable in both groups. Subgroup analysis according to renal function (eGFR < 60 vs. ≥60 mL/min/1.73 m2 ) or type of crystals (acute gouty arthritis vs. acute CPP arthritis) also showed the same pattern of response. CONCLUSION: Non-loading low-dose colchicine was as effective as loading low-dose colchicine in patients with acute crystal-associated arthritis, regardless of renal function or type of crystals.