Elevated baseline serum creatine kinase in Thai early systemic sclerosis patients is associated with high incidence of cardiopulmonary complications and poor survival: an inception cohort study.

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.

Incidence, predictors, and survival of pulmonary hypertension determined by echocardiography in Thai patients with early systemic sclerosis (SSc): inception cohort study.

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.

Rapid skin thickness progression rate is associated with high incidence rate of cardiopulmonary complications in patients with early diffuse cutaneous systemic sclerosis: inception cohort study.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Comparison of clinical presentation and incidence of cardiopulmonary complications between male and female Thai patients with early systemic sclerosis: inception cohort study.

OBJECTIVES: To determine the prevalence of clinical manifestations and incidence rate of cardiopulmonary complications in a comparison between men and women with early SSc. METHODS: An inception cohort of early-SSc patients at the Rheumatology Clinic, Maharaj Nakorn Chiang Mai Hospital, between January 2010 and June 2016, was used. All patients were assessed for clinical manifestations and underwent ECG, echocardiography, and HRCT at the study entry and then annually. RESULTS: One hundred and fifteen patients (46 male, 90 dcSSc) with a mean (SD) disease duration of 11.6 months (8.8) at cohort entry were enrolled during a mean (SD) observational period of 3.8 years (1.6). At enrollment, the male group had a higher prevalence of dcSSc subtype (91.3% vs. 69.5%, p = 0.006), hypo-hyperpigmentation (84.8% vs. 65.2%, p = 0.021), myositis (26.1% vs. 10.1%, p = 0.024), and right ventricular dysfunction [RVD] (8.7% vs. 0%, p = 0.024) compared with women. At the last visit, the male group had a higher cumulative prevalence of digital ulcers (47.8% vs. 27.5%, p = 0.026), telangiectasia (93.5% vs. 69.6%, p = 0.002), joint contracture (69.6% vs. 43.5%, p = 0.006), tendon friction rub (39.1% vs. 20.3%, p = 0.027), LVEF < 50% (21.7% vs. 8.7%, p = 0.048), and RVD (34.8% vs. 7.2%, p < 0.001). The male group had a significantly higher incidence rate of RVD (8.21 vs. 1.99 per 100 person-years, p = 0.006) and interstitial lung disease [ILD] (65.25 vs. 40.36 per 100 person-years, p = 0.022) compared to women. CONCLUSIONS: In this study cohort, it was found that men with SSc had more severe clinical manifestations and higher incidence rate of RVD and ILD compared to women. Increased awareness of cardiopulmonary complications in men even in early phase of SSc is crucial. KEY POINTS: • Male patients with SSc have more severe disease manifestations compared to women. • Even in the early phase of the disease, men were found to have higher incidence rates of right ventricular dysfunction and interstitial lung disease than women. • Increased awareness regarding cardiopulmonary complications in men with early SSc is crucial for effective management of these complications.

Clinical Manifestation and Incidence of Cardiopulmonary Complications in Early Systemic Sclerosis Patients with Different Antibody Profiles.

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.

Differences in clinical presentation and incidence of cardiopulmonary involvement in late-onset versus early-onset systemic sclerosis: inception cohort study.

INTRODUCTION: Data regarding the incidence rate (IR) of cardiopulmonary involvement in comparison between late-onset SSc and early-onset SSc are limited. OBJECTIVE: To compare the prevalence of clinical manifestations and the IR of cardiopulmonary involvement compared between the two subgroups. METHODS: An inception cohort of SSc patients seen at the Rheumatology Clinic, Maharaj Nakorn Chiang Mai Hospital, between January 2010 and June 2016, was used. All patients were assessed for clinical manifestations and underwent electrocardiograph, echocardiography and high-resolution computed tomography at the study entry and every 12 months thereafter. RESULT: One hundred and fifteen patients (69 female and 90 diffuse cutaneous SSc [dcSSc]) with a mean (SD) disease duration of 11.6 months (8.8) at cohort entry were enrolled during a mean (SD) observation period of 3.8 years (1.6). Patients were classified into two groups: age ≥ 50 years (late onset) and age < 50 years (early onset). The late-onset group included 78 patients (67.8%). At enrollment, the late-onset group had higher prevalence of digital pitting scars (60.3% vs. 35.1%, P = 0.012), dry eye symptoms (17.9% vs. 2.7%, P = 0.035), and hypertension (20.5% vs. 5.4%, P = 0.037) compared to the early-onset group. In the last visit, it was found that the late-onset group had higher cumulative prevalence of joint contracture (61.5% vs. 37.8%, P = 0.017) compared to the early-onset group. The late-onset group had no significant IR of left ventricular ejection fraction < 50% (3.04 vs. 4.45 per 100 person-years, P = 0.486), right ventricular dysfunction (5.17 vs. 2.73 per 100 person-years, P = 0.269), interstitial lung disease (49.45 vs. 42.03 per 100 person-years, P = 0.462), and systolic pulmonary arterial pressure ≥ 50 mmHg (2.57 vs. 1.07 per 100 person-years, P = 0.267) compared to the early-onset group. CONCLUSION: Our study cohort found that digital pitting scar, xerophthalmia, hypo-hyperpigmentation, joint contracture, and hypertension are more prevalent in late-onset SSc than early-onset SSc. However, no significant differences regarding the IR of cardiopulmonary involvement between the two subgroups, the majority of which were dcSSc, in the early phase of the disease.