Israel Medical Association Journal

Background: Previous studies have demonstrated the utility of exercise hemodynamics during right heart catheterization (RHC) in the diagnosis of diastolic dysfunction (DD). Little data exists regarding exercise hemodynamics during RHC in symptomatic systemic sclerosis (SSc) patients. 

Objectives: To assess the added diagnostic value of using exercise hemodynamics during RHC in assessment of patients with symptomatic SSc.

Methods: We performed 22 RHCs in 17 SSc patients with dyspnea and/or pulmonary arterial hypertension (PAH). Exercise was performed in 15 RHCs using isotonic arm exercises while holding a 1 kg weight in each hand. Measurements of pulmonary arterial pressure (PAP), pulmonary arterial wedge pressure (PAWP), and cardiac output (CO) were taken at rest and during peak exercise. 

Results: Normal resting RHC (PAP 22 ± 3 mmHg, PAWP 11 ± 3 mmHg) was found in seven cases. Of these, exercise induced elevation in PAP was found in three (38 ± 7 mmHg), and exercise induced elevation in PAWP was found in four (24 ± 6 mmHg). Elevated resting PAP was found in 15 (41 ± 11 mmHg) with minor changes in exercise. Of the 22 RHCs, elevation of the PAWP was found in 11 (50%), half of which were in response to exercise. 

Conclusions: In symptomatic SSc patients, exercise hemodynamics provides important information on diastolic dysfunction that is not available with non-invasive testing. Findings on exercise RHC can explain patient symptoms in up to 50% of cases. Earlier and more accurate diagnosis of patient symptoms can aid in tailoring the correct therapy for each.

Background: Evidence has shown that pregnancy failure (PF) in women with systemic sclerosis (SSc) consists mainly of preterm delivery (PD) and intrauterine growth restriction (IUGR). Thyroid dysfunction (TD) and Hashimoto's thyroiditis (HT) represent a common feature of SSc. Since TD has been associated with PF, its presence in SSc women may potentially affect pregnancy outcome. 

Objectives: To analyze the interplay between TD and PF in a cohort of SSc women. 

Methods: SSc women (n=77) and age-matched controls from the general obstetric population (n=50) were included. Clinical/biochemical/instrumental data exploring TD and the visceral involvement were collected in the context of a clinical practice setting. Pregnancy outcome was assessed by registering the history of primary infertility, recurrent spontaneous abortion, PD (≤ 37 gestational week), IUGR, and intrauterine fetal death. 

Results: A higher prevalence of PD/IUGR was recorded in the SSc cohort than the controls (P = 0.04). SSc women with PF showed a higher prevalence of diffuse SSc than women without PF (P = 0.03). Scl-70 positive SSc women had a higher prevalence of PF than women with anti-centromere positivity (P = 0.01). A higher prevalence of HT was recorded in SSc women with PF than in patients without (P = 0.04). 

Conclusions: Our findings support the evidence that women with SSc can have successful pregnancies despite a higher prevalence of PD/IUGR. Diffuse SSc and Scl-70 positivity may predispose SSc women to PF. Routine thyroid workup may be included in the multi-specialist monitoring of SSc women for the early detection of thyroid dysfunctions.

 

Systemic sclerosis (SSc) is characterized by extensive collagen deposition, microvasculopathy and autoantibodies. All three features can be promoted by activation of T cells and B cells. T cells are of Th2 type producing profibrotic cytokines IL-4 and IL-13 and inducing dendritic cell maturation that promotes Th2 response. B cells are overactivated and promote fibrosis by autoantibodies that activate fibroblasts or inhibit the degradation of extracellular matrix. They also promote fibrosis by cell-cell contact with fibroblasts or dendritic cells. B cells, through autoantibodies, may promote vasoconstriction and obliterative vasculopathy. They may also sustain activation of T cells by functioning as antigen-presenting cells. An immunoregulatory subset of B cells, namely IL-10-producing Bregs, is decreased in SSc. Finally, B cells have a critical role in animal models of SSc. All this evidence suggests an important role for B cells in the pathogenesis of SSc and makes B cells a potential target for therapeutic intervention in this disease. 

 

Systemic sclerosis (SSc) is a heterogeneous chronic autoimmune disease that it is very difficult to diagnose in the early phase, resulting in a critical delay in therapy which is often begun when internal organ involvement is already irreversible. The ACR or LeRoy criteria have a low sensitivity for the early phases; these criteria were replaced by the ACR/EULAR 2013 criteria which improved the disease classification. Therefore, the SSc diagnosis may be delayed for several years after the onset of Raynaud’s phenomenon (RP) and even after the onset of the first non-RP symptom. RP, antinuclear antibodies (ANA) positivity, and puffy fingers were recently indicated as “red flags” (by the VEDOSS project) – that is, the main elements for suspicion of SSc in the very early phase of the disease. Confirming the diagnosis requires further tests, particularly nailfold videocapillaroscopy and evaluation of specific disease antibodies (anti-centromere and anti-topoisomerase I). In this way, the VEDOSS project identified patients in the very early phase of disease enabling a ‘‘window of opportunity’’ whereby the physician can act with effective drugs to block or at least slow the progression of the disease. The principal challenge in the fight against SSc is to detect valid predictors of disease evolution in order to treat patients in the early stage of disease. While waiting to find valid predictors, a close follow-up of the patients with the VEDOSS red flags is essential, as is a close collaboration between rheumatologists and general practitioners in order to identify all potential SSc patients as soon as possible.

Background: Systemic sclerosis (SSc) is a chronic disease with prominent vasculopathy, inflammation, production of autoantibodies, and tissue fibrosis. Periodontitis is a chronic inflammatory oral condition manifesting as microbial infection, inflammation and destruction of the alveolar bone. In both conditions tumor necrosis factor-alpha (TNFα) and other pro-inflammatory cytokines play an important role in pathogenesis. 

Objectives: To assess the periodontal status in SSc patients and compare these parameters to TNFα level in gingival crevicular fluid (GCF) of SSc patients and healthy controls.

Methods: Twenty SSc patients and 20 controls underwent periodontal examination, including probing depth (PD), plaque index (PI), gingival index (GI), bleeding on probing (BOP), and measurement of TNFα levels in collected GCF. 

Results: SSc patients had a greater PD (3.74 ± 0.32 mm vs. 3.35 ± 0.31 mm, P > 0.003), GI (1.53 ± 0.34 vs. 1.12 ± 0.54, P > 0.049), and non-significantly higher BOP than controls. TNFα levels in GCF were higher in SSc patients (1.63 ± 0.36 vs. 1.15 ± 0.34 pg/ml, P = 0.001). Periodontitis parameters correlated with several SSc variables; PI in particular was higher in patients with longer disease duration, sclerodactyly, more severe skin involvement, and SSc activity score.

Conclusions: Patients with SSc have higher indices of periodontal inflammation and higher TNFα level in GCF than did healthy individuals. These changes probably reflect the complexity of factors that influence oral health in SSc. Common pathologic pathways may be responsible for the association between SSc and periodontitis, which requires further study.

 

Abstract

Background: Scleroderma lung disease (ILD-SSc) is treated mainly with cyclophosphamide (CYC). The effectiveness of CYC was judged after 12–24 months in most reports.

Objectives: To analyze the effect of monthly intravenous CYC on pulmonary function tests including forced vital capacity (FVC) and diffusing lung capacity (DLCO), as well as Rodnan skin score (mRSS), during long-term follow-up.

Methods: We retrospectively collected the data on 26 ILD-SSc patients who began CYC treatments before 2007. Changes in FVC, DLCO and mRSS before treatment, and at 1, 4 and 7 years after completion of at least six monthly intravenous CYC treatments for ILD-SSc were analyzed.

Results: Mean cumulative CYC dose was 8.91 ± 3.25 G. More than 30% reduction in FVC (0%, 8%, and 31% of patients), DLCO (15%, 23%, 31%), and mRSS (31%, 54%, 62%) at years 1, 4 and 7 was registered. During the years 0–4 and 4–7, annual changes in FVC, DLCO and mRSS were 3.2 vs. 0.42% (P < 0.040), 4.6 vs. 0.89% (P < 0.001), and 1.8 vs. 0.2 (P = 0.002). The greatest annual FVC and DLCO reduction over the first 4 years correlated with mortality (P = 0.022). There were no differences in the main variables regarding doses of CYC (< 6 G and > 6 G).

Conclusions: In patients with ILD-SSc, CYC stabilized the reduction of FVC during treatment, but this effect was not persistent. The vascular characteristic of ILD-SSc (DLCO) was not affected by CYC treatment. CYC rapidly improved the mRSS. This effect could be achieved with at least 6 G of CYC. Higher rates of annual reduction in FVC and DLCO in the first 4 years indicate the narrow window of opportunity and raise the question regarding ongoing immunosuppression following CYC infusions.