Increased respiratory drive relates to severity of dyspnea in systemic sclerosis.

BACKGROUND: Dyspnea may be a presenting symptom in progressive systemic sclerosis (SSc). Respiratory drive (mouth occlusion pressure, MOP, at rest and during CO2 rebreathing, 7% CO2, 93% O2) is a major determinant of dyspnea and may relate to the magnitude of dyspnea. METHODS: In a prospective design, MOP at 0.1 sec (P0.1) was measured in 73 SSc patients while breathing room air and during CO2 rebreathing. An abnormal V'E/P0.1 is defined as < 8 L/min/cm H2O. Dyspnea scores were assessed by a shortness of breath questionnaire (UCSD dyspnea scale). RESULTS: Mean P0.1 in patients with normal V'E/P0.1 (n = 45) was 1.1 ± 0.04 and 1.6 ± 0.08 cm H2O in patients with abnormal V'E/P0.1 (n = 28), p <0.001. ∆P0.1/∆PetCO2 differed significantly between these groups (0.45 versus 0.75 cm H2O/mmHg, P < 0.001), but no significant difference was present in ∆V'E/∆PetCO2. V'E/P0.1 showed the highest significant correlation with the UCSD dyspnea score (r = -0.76, p <0.001). UCSD cut-off value for abnormal V'E/P0.1 was 8.5 (sensitivity 93%, specificity 96%, area under the curve 0.98). CONCLUSIONS: In SSc patients an abnormal V'E/P0.1 better relates to the severity of dyspnea than traditional lung function parameters and can easily be assessed at first outpatient consultation.

Health-care utilization in Dutch systemic sclerosis patients.

This study aims to examine healthcare utilization and its determinants among patients with systemic sclerosis (SSc). A cross-sectional survey among all patients with SSc visiting an outpatient clinic of an academic hospital in the Netherlands was done. Assessments included sociodemographic characteristics and a survey on healthcare utilization including a registration of contacts with healthcare services since onset of disease, contacts, and number of visits with healthcare services over the last 12 months. A total healthcare utilization score of all visits over the last 12 months was computed and classified as high and low care utilization according to the median. In addition, the Short Form-36 and the Scleroderma Health Assessment Questionnaire (SHAQ) were administered. Logistic regression analysis was used to determine the relationship between high and low healthcare utilization as dependent variable and sociodemographic and disease characteristics as independent variables. Sixty-four patients returned the questionnaires. Over the last 12 months, 83% of the patients had had contact with one or more physicians. On average, patients reported 3.9 visits (SD, 2.9) to a rheumatologist and 6.9 visits (SD, 9.3) to other medical specialists over the last 12 months. The median total health-care utilization was six visits over the last 12 months. Multivariate regression showed that a higher SHAQ score was significantly associated with higher health-care utilization. Patients with SSc visited a considerable number of various health-care providers. Patients with more functional disability were using more healthcare.

Communication between human mast cells and CD4(+) T cells through antigen-dependent interactions.

Mast cells (MCs) are immune cells residing in tissues where pathogens are first encountered. It has been indicated that MCs might also be involved in setting the outcome of T-cell responses. However, little is known about the capacity of human MCs to express MHC class II and/or to capture and present antigens to CD4(+) T cells. To study the T-cell stimulatory potential of human MCs, CD34(+) stem cell derived MCs were generated. These cells expressed HLA-DR when stimulated with IFN-γ, and, importantly, presented peptide and protein for activation of antigen-specific CD4(+) T cells. The interplay between MC and T cell led to increased HLA-DR expression on MCs. MCs were present in close proximity to T cells in tonsil and expressed HLA-DR and CD80, indicating their ability to present antigens to CD4(+) T cells in T-cell areas of human LNs. Our data show that MCs can present native antigens to human CD4(+) T cells and that HLA-DR expressing MCs are present in tonsil tissue, indicating that human MCs can directly activate T cells and provide a rationale to study the potential of MCs to prime and/or skew human T-cell responses.

Diagnosis and mortality prediction in pulmonary hypertension: the value of the electrocardiogram-derived ventricular gradient.

PURPOSE: The aim of this study was to investigate the use of the electrocardiogram-derived ventricular gradient, projected on the x-axis (VGx), for detection of pulmonary hypertension (PH) and for prediction of all-cause mortality in PH patients. METHODS: In patients referred for PH screening (n = 216), the VGx was calculated semiautomatically from the electrocardiogram and was defined as abnormal when less than 24 mV · ms. The VGx of PH patients was compared with the VGx of patients without PH. The association between a reduced VGx and mortality was investigated in PH patients. RESULTS: Patients with PH (n = 117) had a significantly reduced VGx: 14 ± 27 vs 45 ± 23 mV · ms, P < .001. Furthermore, a severely reduced VGx (<0 mV · ms) was associated with increased mortality in PH patients: hazard ratio, 1.025 (95% confidence interval, 1.006-1.045; P = .012) per mV·ms VGx decrease. CONCLUSION: Reduced VGx is associated with the presence of PH and, more importantly, within PH patients, a severely reduced VGx predicts mortality.

Left ventricular dysfunction assessed by speckle-tracking strain analysis in patients with systemic sclerosis: relationship to functional capacity and ventricular arrhythmias.

OBJECTIVE: Systemic sclerosis (SSc) is a connective tissue disease characterized by vascular inflammation and fibrosis. Visceral involvement, including cardiac manifestations, can lead to severe clinical complications, such as congestive heart failure, arrhythmias, and sudden death. Conventional echocardiography parameters have limited sensitivity to detect subtle myocardial dysfunction in patients with SSc. The aim of this study was to assess, using novel speckle-tracking strain analysis, the presence of myocardial dysfunction in patients with SSc, and to investigate its relationship to functional capacity and ventricular arrhythmias. METHODS: A total of 104 patients with SSc (mean ± SD age 54 ± 12 years, 77% female) were included and underwent cardiopulmonary exercise testing, 24-hour electrocardiography (EKG) Holter monitoring, and transthoracic echocardiography. For comparison, 37 matched healthy control subjects were included. RESULTS: The total patient population consisted of 51 patients with limited cutaneous SSc and 53 with diffuse cutaneous SSc. Peak VO(2) was a mean ± SD 91 ± 20% predicted, and 28 patients had abnormal findings (ventricular tachycardia or ventricular ectopics >100/day) on EKG Holter monitoring. Patients with SSc, as compared with controls, had impaired global longitudinal and circumferential strains (mean ± SD -18.2 ± 1.8% versus -21.3 ± 1.7% and -18.2 ± 2.3% versus -21.3 ± 2.1%, respectively; each P < 0.01), but there was no difference in the left ventricular ejection fraction between patients and controls (mean ± SD 63.5 ± 7.2% versus 64.6 ± 4.4%; P = 0.20). In patients with SSc, global longitudinal and circumferential strains each correlated with the peak VO(2) (r = -0.46 and r = -0.41, respectively; both P < 0.01), and multivariate analysis confirmed the independent association of each strain measure with the peak VO(2). Compared to SSc patients with normal results on EKG Holter monitoring, SSc patients with abnormal results showed impaired global longitudinal strains (-18.5 ± 1.5% versus -17.1 ± 2.1%; P < 0.01) and circumferential strains (-18.7 ± 2.0% versus -17.3 ± 2.5%; P = 0.01), and each strain measure was independently associated with abnormal Holter findings. CONCLUSION: Speckle-tracking strain analysis can detect subtle myocardial dysfunction in patients with SSc. Importantly, decreased global longitudinal and circumferential strains are associated with lower functional capacity and rhythm disturbances in patients with SSc.

Increased incidence of pregnancy complications in women who later develop scleroderma: a case control study.

INTRODUCTION: Studies have shown that fetal progenitor cells persist in maternal blood or bone marrow for more than 30 years after delivery. Increased trafficking of fetal cells occurs during pregnancy complications, such as hypertension, preeclampsia, miscarriage and intra-uterine growth restriction (IUGR). Women with these pregnancy complications are significantly more often HLA-class II compatible with their spouses. Women who later develop scleroderma also give birth to an HLA-class II child more often. From these prior studies we hypothesized that preeclampsia and other pregnancy complications could be associated with increased levels of fetal cell trafficking, and later be involved in the development of scleroderma. METHODS: This study was a retrospective multi-centre matched case-control study. One-hundred-and-three women with systemic sclerosis (SSc) and 103 women with no history of SSc or other autoimmune disease were given a questionnaire regarding complications during pregnancy, such as hypertension, intra-uterine growth restriction (IUGR) and miscarriage. Conditional logistic regression analysis was used to assess associations. RESULTS: We found a statistically significantly increased incidence of having had a pregnancy history of hypertension or a fetus with IUGR in women who subsequently developed SSc compared to healthy controls. We found an odds ratio of 2.6 (95% confidence interval (CI): 1.1 to 4.6) for hypertensive complications during pregnancy and an odds ratio of 3.9 (95% CI: 1.2 to 12.3) for intra-uterine growth restriction for women with SSc compared to healthy controls. CONCLUSIONS: This is the first study to show an association between hypertensive complications during pregnancy or IUGR and the development of SSc at a later age. We speculate that the pregnancy abnormalities may have resulted in increased fetomaternal trafficking, which may have played a role in the increased incidence of SSc. Further studies are indicated to examine this putative relationship.

Mast cells are the main interleukin 17-positive cells in anticitrullinated protein antibody-positive and -negative rheumatoid arthritis and osteoarthritis synovium.

INTRODUCTION: Mast cells have been implicated to play a functional role in arthritis, especially in autoantibody-positive disease. Among the cytokines involved in rheumatoid arthritis (RA), IL-17 is an important inflammatory mediator. Recent data suggest that the synovial mast cell is a main producer of IL-17, although T cells have also been implicated as prominent IL-17 producers as well. We aimed to identify IL-17 expression by mast cells and T cells in synovium of arthritis patients. METHODS: Synovial samples of anticitrullinated protein antibody-positive (ACPA+) and ACPA-negative (ACPA-) RA and osteoarthritis (OA) patients were stained for IL-17 in combination with CD117 (mast cells), CD3 (T cells) and CD68 (macrophages). Concentrations of IL-17 in synovial fluid were determined by ELISA. RESULTS: The number of IL-17+ cells in synovium was comparable in all groups. Although the vast majority of IL-17+ cells are mast cells, no difference in the percentage of IL-17+ mast cells was observed. Nonetheless, levels of IL-17 in synovial fluid were increased in ACPA+ RA patients compared to ACPA- RA and OA patients. CONCLUSIONS: The synovial mast cell is the main IL-17+ cell in all three arthritis groups analyzed. These data are relevant for studies aimed at blocking IL-17 in the treatment of arthritis.