Suparaporn Wangkaew

Objectives: Laboratory detection of myositis-specific autoantibodies (MSAs) utilizes ELISA and multianalyte line blot assays (LBA). We sought to evaluate the concordance and reliability of these two commercial assays. Methods: Serum samples from patients with idiopathic inflammatory myopathies (IIMs) were obtained from seven countries across the Asia-Pacific region. Anti-Jo-1, anti-EJ, anti-PL-7, anti-PL-12, anti-MDA5, anti-Mi-2 and anti-TIF1-γ antibodies were centrally measured with commercial ELISA and LBA kits. The positive percentage agreement (PPA), negative percentage agreement (NPA) and Cohen’s kappa were calculated by comparing the two assays. Sera with discordant results were subjected to ‘gold-standard’ immunoprecipitation (IP) assays. Results: Serum samples obtained from 485 patients with IIMs, including 180 with DM, 44 with amyopathic DM, seven with JDM, 197 with PM or immune-mediated necrotizing myopathy and 57 with IBM, were subjected to ELISA and LBA. The PPA was the highest for anti-Jo-1 at 0.98, followed by 0.94 for anti-PL-7, 0.93 for anti-EJ, 0.93 for anti-MDA5, 0.89 for anti-TIF1-γ, 0.78 for anti-PL-12 and 0.67 for anti-Mi-2, whereas the NPA was high (ranging from 0.97 to 1 for all MSAs). Kappa values exceeded 0.80 for anti-Jo-1, anti-EJ, anti-MDA5 and anti-TIF1-γ, whereas anti-PL-7, anti-PL-12 and anti-Mi-2 exhibited low values. IP assays using sera with discordant results revealed a high rate of false positives for anti-PL-7 and anti-Mi-2 in LBA. Conclusion: Discrepancies in the measurement results were observed between commercially available ELISA and LBA, especially for anti-PL7 and anti-Mi-2. ELISA is more accurate than LBA.

Background/Objectives: Predictors of ischemic vascular complications (IVCs)—including coronary artery disease (CAD), ischemic stroke, and digital gangrene—in patients with early SSc remain insufficiently defined. Therefore, we aim to determine the incidence, risk factors, and mortality associated with IVCs in early SSc. Methods: An inception cohort of patients with early SSc at the Rheumatology Clinic, Maharaj Nakorn Chiang Mai Hospital, Thailand, was studied from January 2010 to December 2023. Clinical, laboratory, and cardiopulmonary assessments were performed at baseline and annually thereafter. Results: A total of 146 patients (83 female, 119 DcSSc) were enrolled, with a mean disease duration of 11.5 ± 8.9 months from the first non-Raynaud’s phenomenon (NRP). The mean follow-up was 8.0 ± 3.9 years. Seventeen patients (11.6%) developed IVCs, three CAD, four ischemic stroke, eight digital gangrene, and two digital gangrene plus CAD. The median time to first IVCs was two years. The overall incidence rate of IVCs from the NRP was 1.44 per 100 person-years (95% CI 0.89–2.32). Independent factors associated with IVCs included baseline (BL) digital ulcer, traumatic ulcer, LVEF < 50%, elevated pro-BNP, and any atrial fibrillation. BL pro-BNP and dyslipidemia were independently associated with CAD, whereas BL pro-BNP and any atrial fibrillation were associated with ischemic stroke. BL digital ulcer, traumatic ulcer, and any LVEF < 50% were associated with digital gangrene. All-cause mortality was higher among patients with IVCs than those without (9 [52.9%] vs. 37 [28.7], p = 0.043). Conclusions: In this study, IVCs were uncommon in early SSc, but were associated with increased mortality. Digital ulcers, traumatic ulcers, atrial fibrillation, impaired LVEF, and elevated pro-BNP identified the patients at higher risk of IVCs.

Background: Available data regarding clinical characteristics of systemic sclerosis-associated myopathy (SSc-M) patients comparing different subgroups of muscle pathology are limited. We aimed to compare clinical and laboratory findings among different subgroups of Thai patients with SSc-M. Methods: From January 2010 to December 2019, 27 patients with suspected SSc-M underwent a muscle biopsy. Twenty-three patients with available frozen muscle biopsy specimens for repeating immunohistochemical stained for reviewing were included. There were three subgroups of pathological findings, including immune-mediated necrotizing myopathy (IMNM), non-specific myopthy (NsM), and polymyositis (PM). No fibrosing myopathy was observed. Baseline clinical data and laboratory findings were compared within those three inflammatory myopathies. Results: Of the 23 SSc-M, there were 14 females and 19 DcSSc with a mean age and disease duration of SSc of 53.6±7.7 years and 16.4±23.6 months, respectively. Their mean duration from weakness to muscle biopsy was 3.6±6.0 months. There were 14 (60.9%) patients with IMNM, 6 (26.1%) with NsM, and 3 (13.0%) with PM. At the biopsy date, IMNM had a greater prevalence of severe muscle weakness (42.6% vs. 0% vs. 0%) and arthritis (87.5% vs. 50% vs. 0%) than the NsM and PM groups. There was no significant difference among the three inflammatory patterns regarding baseline clinical characteristics, including age, gender, SSc subtype, disease duration, other organ involvements and median values of CK and ESR levels. Conclusion: In this study, we found that the pathological findings of Thai SSc-M were IMNM, NsM, and PM. No fibrosing myopathy was observed. SSc with IMNM tended to have more severe baseline muscle weakness and arthritis than the other inflammatory patterns.

Available data including the incidence, predictors and long-term outcome of early systemic sclerosis patients associated with suspected cardiomyopathy(SSc-CM) is limited. Therefore, we aimed to study the incidence, predictors and survival of SSc-CM. An inception cohort study was conducted for early SSc patients seen at the Rheumatology Clinic, Maharaj Nakorn Chiang Mai Hospital, Thailand, from January 2010 to December 2019. All patients were determined for clinical manifestations and underwent echocardiography and HRCT at enrollment and then annually. SSc-CM was determined and classified using echocardiography. 135 early SSc patients (82 female,108 DcSSc) were enrolled. With the mean follow-up period of 6.4 years, 32 patients developed SSc-CM. The incidence of SSc-CM was 5.3 per 100-person years. The multivariate Cox regression analysis showed that baseline anti-topoisomerase I-positive (Hazard ratio[HR] 4.86, p = 0.036), dysphagia (HR 3.35, p = 0.001), CK level ≥ 500 U/L(HR 2.27, p = 0.045) and low oxygen saturation (HR 0.82, p = 0.005) were predictors of SSc-CM. The survival rates after SSc-CM diagnosis at 1, 5 and 10 years were 90.3%, 73.1%, and 56.1%, respectively. In this study cohort, the incidence of SSc-CM was 5.3 per 100-person years, and tended to have low survival. The presence of anti-topoisomerase I antibody, dysphagia, CK level ≥ 500 U/L, and low oxygen saturation were independent baseline predictors for developing SSc-CM.

Background Inception cohort data regarding the incidence of cardiopulmonary complications in early systemic sclerosis (SSc) patients comparing those with and without elevated baseline creatine kinase (CK) are limited. This study aimed to compare the incidence of cardiopulmonary complications and survival between the two subgroups. Methods We used an inception cohort study of early SSc patients seen at the Rheumatology Clinic, Maharaj Nakorn Chiang Mai Hospital, Thailand, from January 2010 to December 2019. All patients were assessed for clinical manifestations and CK levels and underwent echocardiography and HRCT at the study entry and annually thereafter. Results A total of 144 SSc patients (84 female, 115 diffuse cutaneous SSc (DcSSc)) with a mean disease duration of 11.9 ± 9.2 months were enrolled. At cohort entry, their mean ± SD CK levels were 364.3 ± 598.0 U/L. The participants were then divided into two subgroups: (i) 29 SSc with elevated CK (baseline CK ≥ 500 U/L); (ii) 115 SSc with non-elevated CK. At enrollment, the elevated CK group was characterized by a higher proportion of male gender, DcSSc subtype, arthritis, and weakness; shorter disease duration; and higher MRSS compared with non-elevated CK. At the last visit, with a mean ± SD follow-up duration of 6.2 ± 2.7 years, the elevated CK group showed a higher cumulative prevalence of weakness, dysphagia, LVEF < 50%, and suspected myocardial disease; higher incidence of LVEF < 50%, suspected myocardial disease, and ILD; and shorter survival time. Conclusion It was found in our study cohort that elevated baseline serum CK in early SSc, of which majority were DcSSc subtype, is associated with more severe clinical presentation, higher incidence of cardiopulmonary complications, and shorter survival time compared with the non-elevated CK subgroup. Key Points • In early SSc patients, elevated baseline serum creatine kinase was confirmed to be associated with a high incidence of cardiac and ILD complications, and poor long-term survival time. • Careful evaluation of baseline serum CK levels in all early-diagnosed SSc patients is crucial in general clinical practice.

We aimed to investigate patients with early diffuse cutaneous systemic sclerosis (dcSSc) with regard to: 1. the association between skin thickness progression rate (STPR) at baseline visit and incidence rate of cardiopulmonary complications; 2. comparison of the mortality rate between patients with skin improvers and those with skin non-improvers. An inception cohort of early dcSSc patients seen at the Rheumatology Clinic, Maharaj Nakorn Chiang Mai Hospital, Thailand, was selected. All patients were assessed for clinical manifestations, and modified Rodnan skin score (mRSS) and underwent echocardiography, and HRCT at study entry and then annually. One hundred and four dcSSc patients (57 of whom were females and 91 anti-topoisomerase I-positive) with a mean disease duration of 11.1±8.6 months were enrolled. Forty-two patients had rapid STPR [RPsp], 38 intermediate STPR [IMsp] and 24 slow STPR [SLsp]. At enrolment, the RPsp group had a significantly shorter disease duration, more prevalent anti-topoisomerase-I-positive, higher mRSS, more prevalent creatine kinase≥500 IU/L and higher NT-proBNP levels compared to the IMSp and SLsp groups. During a mean observation period of 4.5±2.0 years, the RPsp group had a significantly higher incidence rate of LVEF< 50% (6.06 vs. 0 per 100 person- years, p=<0.01) and interstitial lung disease (ILD) (69.69 vs. 34.66 per 100 person-years, p=0.012) than the SLsp group. Skin non-improvers had a signif- icantly higher mortality rate than skin improvers (28.6% vs. 5.8 %, p= 0.004). In this early dcSSc study cohort it was found that skin change determined by STPR at the baseline visit was a useful surrogate marker for cardiac and ILD complications. It was also found that skin improvers assessed 1-year later were a useful surrogate marker of mortality.

Background Data regarding longitudinal association between changes (Δ: time2-time1) in the widest esophageal diameter (WED) and Δ HRCT score in early SSc-ILD patients is limited. We therefore investigated the association of ΔWED with Δ HRCT score and predictors of a worse Δ HRCT score in those patients. Methods We used an inception cohort of early SSc-ILD patients with availability for two HRCT records at enrollment and 1-year follow-up.The extent of ground glass, reticulation, bronchiectasis, and honeycombing was scored and then aggregated to produce a total HRCT score. The WED was measured at four levels and the maximum value was used. The Δ maximum WED, Δ mean WED, and Δ tHRCT score were analyzed. Results We recruited 75 early SSc-ILD patients and found a significant correlation of Δ tHRCT score with a Δ maximum WED (rho = 0.34, p < 0.01) and Δ mean WED (rho = 0.26, p < 0.05). There were 34 patients with a worsening Δ tHRCT (Δ > 0), 17 with stability (Δ = 0), and 24 with improvement (Δ < 0). Patients with a worsening ILD had a significantly shorter disease duration, lower prevalence of tendon friction rub, higher cumulative prednisolone dose, and larger ΔWED than those with stable and improved Δ tHRCT scores. Multivariate ordinal logistic regression identified a larger Δ mean WED (OR 1.21, 95% CI 1.03–1.42, p = 0.02) as a predictor of worsening HRCT score, while presence of tendon friction rub was associated with a lower risk (OR 0.18, 95% CI 0.04–0.77, p = 0.021). Conclusion Our study cohort found that a worsening esophageal diameter was a predictor of progression of lung fibrosis determined by HRCT score in early SSc-ILD. A further study regarding esophageal dilation progression different in early versus longstanding SSc-ILD is needed. Key Points •In early SSc-ILD patients, we demonstrated that a worsening esophageal diameter was a predictor of progression of HRCT score at 1-year follow-up. •Further study regarding the association of worsening of the esophageal dilatation with the progression of ILD comparing between early versus late SSc-ILD is needed.

Objectives We investigated the incidence, predictors, and survival of pulmonary hypertension (PH) determined by Doppler echocardiography in Thai patients with early SSc (systemic sclerosis), in which the majority were diffuse cutaneous SSc (DcSSc) with anti-topoisomerase I-positive. Methods We used an inception cohort study of patients with early SSc seen at the Rheumatology Clinic, Maharaj Nakorn Chiang Mai Hospital. All patients were assessed for clinical data and underwent Doppler echocardiography at the study entry and then annually. Results A total of 133 patients (81 female, 106 DcSSc, 103 anti-topoisomerase I-positive) with a mean disease duration of 11.9 months were recruited. During the mean observational period of 4.2 years, 14 patients developed PH concurrent with ILD and 6 with left heart disease. The incidence rate for the development of PH was 3.95 per 100 person years. The multivariate Cox regression analysis indicated higher NYHA class (HR 6.90, 95% CI 2.28–20.94, p = 0.001), telangiectasia (HR 4.18, 95% CI 1.25–13.92, p = 0.020), and enlarged LA diameter (HR 1.16, 95% CI 1.05–1.28, p = 0.005) as predictors of PH. Raynaud’s phenomenon (HR 0.22, 95% CI 0.06–0.84, p = 0.026) and high oxygen saturation (HR 0.80, 95% CI 0.65–0.99, p = 0.047) were protective factors. The survival rate after PH diagnosis at 1, 3, and 5 years were 88.9%, 82.3%, and 48.0%, respectively. Conclusions In this study cohort, the majority had early DcSSc, the incidence of PH was modest, and all cases developed concomitantly with ILD or left heart disease, resulting in poor survival. The presence of higher NYHA class, telangiectasia, and enlarged LA diameter was predictors of secondary PH. Further study regarding the treatment strategies for PH associated with ILD and left heart disease in SSc is needed. Key Points • In this cohort of early SSc in which the main subtype was DcSSc, the incidence of PH was modest and all PH was secondary PH associated with ILD and left heart disease, resulting in poor survival. • The presence of higher NYHA functional class, telangiectasia, and enlarged LA diameter was baseline predictors of developing secondary PH. • Effective treatment strategies for secondary PH due to ILD and cardiac involvement in SSc patients are urgently needed.

To determine the prevalence of clinical manifestations and incidence rate of cardiopulmonary complications in a comparison between men and women with early SSc.

Background: There has been no prior inception cohort study comparing clinical manifestations and incidence rate (IR) of cardiopulmonary involvement among early systemic sclerosis (SSc) patients by difference in autoantibody profiles. We compared the differences in the clinical presentation at study entry and cumulative organ complications at last visit, as well as the IR of cardiopulmonary complications between anti-topoisomerase I antibody-positive SSc patients (pATA), ATA-negative (nATA), and the positive anti-centromere antibody patients (pACA). Methods: An inception cohort of early diagnosis SSc patients (disease duration ≤ 3 years) seen at the Rheumatology Clinic, Maharaj Nakorn Chiang Mai Hospital, between January 2010 and June 2016, was studied. SSc patients who had follow-up duration as less than 1 year and those diagnosed with an overlap syndrome were excluded. All participants underwent electrocardiography (ECG), echocardiography, and high-resolution computed tomography (HRCT) at the study entry and then annually. Results: A total of 114 patients (90 diffuse cutaneous SSc (dcSSc), 69 women) with mean (standard deviation, SD) disease duration of 11.7 (8.8) months at cohort entry and an observational period of 3.8 (1.6) years, were recruited. There were 89 patients (78.1%) with pATA, 18 (15.8%) with nATA, and 7 (6.1%) with pACA. At enrollment, both pATA and nATA groups had a higher prevalence of dcSSc subtype, and interstitial lung disease (ILD) when compared with the pACA group. At the last visit, the pATA group had a higher cumulative prevalence of digital ulcers, joint contracture and tendon friction rub than the other groups. Both the pATA and nATA groups had a significantly higher IR of ILD compared to the pACA group (54.9 and 57.8 vs. 6.3 per 100 person-years). During the study period, no suspected myositis, systolic pulmonary artery pressure (sPAP) ≥ 50 mm Hg or cardiac complications was observed in the pACA group. Conclusions: In our study cohort, the majority of which were dcSSc subtype with pATA, it was found that the presence of SSc-specific autoantibodies was associated with a distinctive clinical presentation and cumulative internal organ involvement, even in the early phase of the disease. Cardiopulmonary complications were rarely seen in the pACA group; whereas ILD complications were very common in both the pATA and nATA groups. A further study into the association of autoantibodies in nATA patients with ILD complications is needed. J Clin Med Res. 2019;11(7):524-531 doi: https://doi.org/10.14740/jocmr3849