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OBJECTIVES: To examine the influence of contextual factors upon the evaluation of skin thickness and stiffness by ultrasound and to assess the reliability of these parameters. METHODS: Ultrasound dermal thickness (by B-mode, 18MHz) and skin stiffness (by shear-wave elastography, 9MHz) were assessed in persons with systemic sclerosis (SSc) and in healthy controls. The influence of contextual factors upon repeated measures was evaluated: (i) room temperature (16-17ºC vs. 22-24ºC); (ii) time of day (morning vs. afternoon), and (iii) menstrual cycle phase (menstrual vs. ovulatory). Differences were analysed using the related-samples Wilcoxon signed-rank test. Inter- and intra-rater reliability of ultrasound skin thickness and stiffness were evaluated in the 17 skin Rodnan sites of 20 persons with SSc and 20 healthy controls, under stable contextual conditions. RESULTS: A significant increase in ultrasound dermal thickness was observed at the leg in the afternoon vs morning, in both patients and controls. Similar observations were made for skin stiffness at the leg (in SSc) and at the foot (in SSc and controls) in the afternoon. No significant changes were observed in association with room temperature and menstrual cycle. Intra- and inter-rater-reliability was good to excellent for ultrasound dermal thickness and stiffness, both in SSc and healthy controls. CONCLUSIONS: The timing of the ultrasound procedure within each day seems to influence the ultrasound measures at the legs and feet. Our study corroborates that ultrasound dermal thickness and skin stiffness are reliable domains to quantify skin involvement in SSc.
Assuntos
Técnicas de Imagem por Elasticidade , Escleroderma Sistêmico , Feminino , Humanos , Reprodutibilidade dos Testes , Pele/diagnóstico por imagem , Escleroderma Sistêmico/diagnóstico por imagem , Ultrassonografia , Técnicas de Imagem por Elasticidade/métodosRESUMO
BACKGROUND: Patients' objectives and experiences must be core to the study and management of chronic diseases, such as SSc. Although patient-reported outcomes are attracting increasing attention, evaluation of the impact of disease on the overall subjective well-being, equivalent to 'happiness', is remarkably lacking. OBJECTIVES: To examine the determinants of happiness and quality of life in patients with SSc, with emphasis on disease features and personality traits. METHODS: Observational, cross-sectional multicentre study, including 142 patients, with complete data regarding disease activity, disease impact, personality, health-related quality of life (HR-QoL) and happiness. Structural equation modelling was used to evaluate the association between the variables. RESULTS: The results indicated an acceptable fit of the model to the data. Perceived disease impact had a significant negative direct relation with HR-QoL (ß = -0.79, P < 0.001) and with happiness (ß = -0.52, P < 0.001). Positive personality traits had a positive relation with happiness (ß = 0.36, P = 0.002) and an important indirect association upon QoL (ß = 0.43) and happiness (ß = 0.23). Perceived disease impact is influenced by body image, fatigue and SSc-related disability to a higher degree (ß = 0.6-0.7) than by disease activity (ß = 0.28) or form (ß = 0.17). Impact of disease had a much stronger relation with HR-QoL than with happiness. CONCLUSIONS: The results suggest that treatment strategies targeting not only disease control but also the mitigation of relevant domains of disease impact (body image, fatigue, global disability) may be important to improve patients' experience of the disease. The reinforcement of resilience factors, such as positive psychological traits, may also play a contributory role towards better patient outcomes.
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Felicidade , Qualidade de Vida/psicologia , Escleroderma Sistêmico/psicologia , Idoso , Estudos Transversais , Feminino , Humanos , Análise de Classes Latentes , Masculino , Pessoa de Meia-Idade , Personalidade , Resiliência Psicológica , Índice de Gravidade de DoençaRESUMO
OBJECTIVES: To evaluate ultrasound Virtual Touch Imaging and Quantification (VTIQ) as a method for determining absolute skin stiffness in patients with systemic sclerosis (SSc). METHODS: Skin thickness, assessed by the modified Rodnan Skin Score (mRSS) and absolute skin stiffness, using VTIQ, were measured at all mRSS anatomical sites to quantify the shear wave velocity (in m/s) in 26 SSc patients and in 17 age- and gender-matched controls. Correlations between mRSS and absolute skin stiffness, and comparisons between patients and controls were analysed statistically using Mann-Whitney U tests and correlations between variables using Pearson's. P values <0.05 were considered significant. RESULTS: Shear wave velocity as a measure of skin stiffness was significantly higher in SSc than in controls in 11 out of 16 mRSS sites investigated. Shear-wave velocity was strongly correlated with the local mRSS in the following anatomical sites: forearm, hand, phalanx, and thigh. In the patient group, clinically unaffected skin could also be differentiated from healthy skin using shear-wave velocity. CONCLUSIONS: VTIQ represents an innovative and promising technique that provides, for the first time, a non-invasive, absolute quantification of skin stiffness. Further studies of VTIQ are required, but this early study supports the clinical and scientific potential of this new measure of skin involvement in SSc.
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Técnicas de Imagem por Elasticidade/métodos , Escleroderma Sistêmico/diagnóstico por imagem , Pele/diagnóstico por imagem , Adulto , Idoso , Estudos de Casos e Controles , Elasticidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Valor Preditivo dos Testes , Prognóstico , Escleroderma Sistêmico/patologia , Índice de Gravidade de Doença , Pele/patologiaRESUMO
OBJECTIVE: To develop evidence-based recommendations for the non-pharmacological and pharmacological management of Raynaud's phenomenon (RP) and digital ulcers (DUs) in patients with systemic sclerosis and other immune-mediated connective tissue diseases (CTDs). METHODS: A task force comprising 21 rheumatologists, two surgeons (vascular and plastic), two nurses, and one patient representative was established. Following a systematic literature review performed to inform the recommendations, statements were formulated and discussed during two meetings (one online and one in-person). Levels of evidence, grades of recommendation (GoR), and level of agreement (LoA) were determined. RESULTS: Five overarching principles and 13 recommendations were developed. GoR ranged from A to D. The mean ± standard difference (SD) LoA with the overarching principles and recommendations ranged from 7.8±2.1 to 9.8±0.4. Briefly, the management of RP and DUs in patients with CTDs should be coordinated by a multidisciplinary team and based on shared decisions with patients. Nifedipine should be used as first-line therapy for RP and/or DUs. Sildenafil, tadalafil, and/or iloprost IV are second-line options for severe and/or refractory patients with RP and/or DUs. Sildenafil, tadalafil and/or Iloprost IV, should be prescribed for healing and prevention (also including bosentan) of DUs. In patients with RP and/or DUs, non-pharmacological interventions might be considered as add-ons, but there is limited quality and quantity of scientific evidence supporting their use. CONCLUSIONS: These recommendations will inform rheumatologists, specialist nurses, other healthcare professionals, and patients about a comprehensive and personalized management of RP and DUs. A research agenda was developed to address unmet needs, particularly for non-pharmacologic interventions.
Assuntos
Doenças do Tecido Conjuntivo , Dedos , Doença de Raynaud , Escleroderma Sistêmico , Úlcera Cutânea , Humanos , Doenças do Tecido Conjuntivo/complicações , Doenças do Tecido Conjuntivo/terapia , Dedos/irrigação sanguínea , Dedos/patologia , Portugal , Doença de Raynaud/terapia , Doença de Raynaud/etiologia , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/terapia , Úlcera Cutânea/terapia , Úlcera Cutânea/etiologiaRESUMO
BACKGROUND: The etiology of exercise-induced pulmonary hypertension (exPH) in systemic sclerosis (SSc) remains a complex task, as both left ventricle (LV) diastolic dysfunction and pulmonary vascular disease can contribute to its development. We determined the incidence of exPH in SSc and examined the association between pulmonary artery systolic pressure (PASP) and tissue Doppler-derived indexes of pulmonary capillary wedge pressure (PCWP). METHODS: Thirty-eight patients with SSc were studied, using a cycloergometer protocol; 10 were excluded due to resting PH or absence of tricuspid regurgitation (TR); TR and mitral E-wave velocities, LV outflow tract time-velocity integral and LV septal E'-wave were measured before and in peak exercise to calculate cardiac output (CO), PCWP and pulmonary vascular resistance (PVR). RESULTS: Mean age of diagnosis was 57.9 ± 8.9 years. At a mean workload of 64 ± 29 Watts, 48% of patients increased PASP ≥ 50 mmHg. PCWP, assessed by the E/e' ratio, did not change significantly during exercise (10.2 ± 3.1-10.0 ± 5.1; P = NS). Only 3 patients had elevations of the E/e' ratio ≥ 13 during exercise; 2 of them had an exercise PASP ≥ 50 mmHg, yielding a proportion of exPH due to elevated LV filling pressures of 2/11 (18%). Patients with exPH had lower DLCO and had more frequently the diffuse SSc. CONCLUSION: The elevation of PASP during exercise in most patients of this cohort seems to be related to a reduced pulmonary vascular reserve, and not to an increase in PCWP. Further studies are warranted to determine the therapeutic, as well as prognostic implications of these findings.
Assuntos
Ecocardiografia/métodos , Teste de Esforço/métodos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/etiologia , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/diagnóstico , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
Systemic sclerosis (SSc) is an immune-mediated disease wherein T cells are particularly implicated, presenting a poor prognosis and limited therapeutic options. Thus, mesenchymal-stem/stromal-cell (MSC)-based therapies can be of great benefit to SSc patients given their immunomodulatory, anti-fibrotic, and pro-angiogenic potential, which is associated with low toxicity. In this study, peripheral blood mononuclear cells from healthy individuals (HC, n = 6) and SSc patients (n = 9) were co-cultured with MSCs in order to assess how MSCs affected the activation and polarization of 58 different T cell subsets, including Th1, Th17, and Treg. It was found that MSCs downregulated the activation of 26 out of the 41 T cell subsets identified within CD4+, CD8+, CD4+CD8+, CD4-CD8-, and γδ T cells in SSc patients (HC: 29/42) and affected the polarization of 13 out of 58 T cell subsets in SSc patients (HC: 22/64). Interestingly, SSc patients displayed some T cell subsets with an increased activation status and MSCs were able to downregulate all of them. This study provides a wide-ranging perspective of how MSCs affect T cells, including minor subsets. The ability to inhibit the activation and modulate the polarization of several T cell subsets, including those implicated in SSc's pathogenesis, further supports the potential of MSC-based therapies to regulate T cells in a disease whose onset/development may be due to immune system's malfunction.
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INTRODUCTION: Despite years of experience with biological disease modifying anti-rheumatic drugs (bDMARD) in rheumatoid arthritis (RA), little is known about differences in infectious risk among bDMARDs. The aim of this study was to assess the incidence and type of infections in RA patients on bDMARDs and to determine possible predictors. METHODS: A retrospective multicenter cohort study that included patients registered in the Rheumatic Diseases Portuguese Registry (Reuma.pt) with RA, and exposed to at least one bDMARD until April 2021. RA patients under bDMARD and with at least one episode of severe infection (SI), defined as infection that requires hospitalization, use of parenteral antibiotics or that resulted in death, were compared to patients with no report of SI. Demographic and clinical data at baseline and at the time of each SI were collected to establish comparisons between different groups of bDMARDs. Comparisons between different bDMARDs were assessed and logistic regression was performed to identify predictors of SI. RESULTS: We included 3394 patients, 2833 (83.5%) female, with a mean age at RA diagnosis of 45.5±13.7 years. SI was diagnosed in 142 of the 3394 patients evaluated (4.2%), totaling 151 episodes of SI. At baseline, patients with SI had a significantly higher proportion of prior orthopedic surgery, asthma, interstitial lung disease, chronic kidney disease and corticosteroid use, higher mean age and longer median disease duration at first bDMARD. Nine patients died (6.0%). Ninety-two SI (60.9%) occurred with the first bDMARD, the majority leading to discontinuation of the bDMARD within 6 months (n=75, 49.7%), while 65 (43.0%) restarted the same bDMARD and 11 (7.3%) switched to another bDMARD (6 of them to a different mechanism of action). In the multivariate analysis, we found that chronic kidney disease, asthma, infliximab, corticosteroid use, interstitial lung disease, previous orthopedic surgery, higher Health Assessment Questionnaire and DAS284V-ESR are independent predictors of SI. CONCLUSION: This study described the incidence and types of SI among Portuguese RA patients on biologics, identifying several predictors of SI, both globally and with different bDMARDs. Physicians should be aware of the real-word infectious risk in RA patients on bDMARDs when making treatment decisions.
Assuntos
Antirreumáticos , Artrite Reumatoide , Asma , Produtos Biológicos , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Masculino , Estudos de Coortes , Portugal/epidemiologia , Artrite Reumatoide/tratamento farmacológico , Antirreumáticos/efeitos adversos , Produtos Biológicos/efeitos adversos , Asma/induzido quimicamente , Corticosteroides/uso terapêuticoRESUMO
INTRODUCTION/OBJECTIVES: The study aims to define the clinical and subclinical calcinosis prevalence, the sensitivity of radiographed site and clinical method for its diagnosis, and the phenotype of Portuguese systemic sclerosis (SSc) patients with calcinosis. METHOD: A cross-sectional multicenter study was conducted with SSc patients fulfilling Leroy/Medsger 2001 or ACR/EULAR 2013 classification criteria, registered in the Reuma.pt. Calcinosis was assessed through clinical examination and radiographs of hands, elbows, knees, and feet. Independent parametric or non-parametric tests, multivariate logistic regression, and sensitivity calculation of radiographed site and clinical method for calcinosis detection were performed. RESULTS: We included 226 patients. Clinical calcinosis was described in 63 (28.1%) and radiological calcinosis in 91 (40.3%) patients, of which 37 (40.7%) were subclinical. The most sensitive location to detect calcinosis was the hand (74.7%). Sensitivity of the clinical method was 58.2%. Calcinosis patients were more often female (p = 0.008) and older (p < 0.001) and had more frequently longer disease duration (p < 0.001), limited SSc (p = 0.017), telangiectasia (p = 0.039), digital ulcers (p = 0.001), esophageal (p < 0.001) and intestinal (p = 0.003) involvements, osteoporosis (p = 0.028), and late capillaroscopic pattern (p < 0.001). In multivariate analysis, digital ulcers (OR 2.63, 95% CI 1.02-6.78, p = 0.045) predicted overall calcinosis, esophageal involvement (OR 3.52, 95% CI 1.28-9.67, p = 0.015) and osteoporosis (OR 4.1, 95% CI 1.2-14.2, p = 0.027) predicted hand calcinosis, and late capillaroscopic pattern (OR 7.6, 95% CI 1.7-34.9, p = 0.009) predicted knee calcinosis. Anti-nuclear antibody positivity was associated with less knee calcinosis (OR 0.021, 95% CI 0.001-0477, p = 0.015). CONCLUSIONS: Subclinical calcinosis high prevalence suggests that calcinosis is underdiagnosed and radiographic screening might be relevant. Multifactorial pathogenesis may explain calcinosis predictors' variability. Key Points ⢠Prevalence of subclinical calcinosis in SSc patients is substantial. ⢠Hand radiographs are more sensitive to detect calcinosis than other locations or clinical method. ⢠Digital ulcers were associated with overall calcinosis, esophageal involvement and osteoporosis were associated with hand calcinosis, and late sclerodermic pattern in nailfold capillaroscopy was associated with knee calcinosis. ⢠Anti-nuclear antibody positivity may be a protective factor for knee calcinosis.
Assuntos
Calcinose , Osteoporose , Escleroderma Sistêmico , Feminino , Humanos , Estudos Transversais , Portugal , Calcinose/complicações , Calcinose/diagnóstico por imagem , Osteoporose/complicaçõesRESUMO
Evidence for the role of sex in the clinical manifestations of systemic sclerosis (SSc) patients is emerging. Some multicenter cohorts have shown that male SSc patients have more severe disease and worse survival. To assess the differences in clinical manifestations and survival in Portuguese SSc patients according to gender. Data from male and female adult SSc patients included in the Rheumatic Diseases Portuguese Register (Reuma.pt) were analysed and compared. Survival was calculated for patients included in Reuma.pt. within the first two years of diagnosis (inception cohort). In total, 1054 adult patients with SSc were included, 12.5% males. No differences in demographic features and comorbidities were found between the sexes, except for a higher rate of cigarette smokers among men. Diffuse cutaneous SSc and anti-topoisomerase antibodies were more prevalent in males than females. Additionally, male patients presented significantly more myositis, interstitial lung disease and gastric involvement. There were no differences in the patterns of drug use between the sexes. During follow-up, more deaths were reported in men than women (12.1% vs 7.3%, p = 0.04). The overall 1-, 3-, and 5-year survivals from diagnosis of the inception cohort (N = 469) for men vs women were 96.4% vs 98.2%, 93% vs 95.9%, and 75.8% vs 93.2%, respectively, with statistically significant differences (p < 0.01). This study confirms the existence of gender differences in clinical and immunological SSc features. Although SSc is less common in men than women, men have a more severe expression of skin and internal organ involvement and worse survival. Key Points ⢠There are differences in SSc disease manifestations between sexes. ⢠Males more commonly have diffuse cutaneous SSc, anti-topoisomerase antibodies, pulmonary and musculoskeletal involvement. ⢠In the inception cohort, men had worse survival rates than women.
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Esclerodermia Difusa , Escleroderma Sistêmico , Adulto , Estudos de Coortes , Feminino , Humanos , Masculino , Portugal/epidemiologia , Esclerodermia Difusa/diagnóstico , Escleroderma Sistêmico/diagnóstico , Fatores SexuaisRESUMO
BACKGROUND: Systemic sclerosis (SSc) is a rare connective tissue disorder with heterogeneous manifestations and outcomes. Besides differences in disease characteristics among distinct ethnic groups and geographical regions, several questions regarding the impact of the disease and the effectiveness of treatments remain unanswered. To address these questions, the Rheumatic Diseases Portuguese Register (Reuma.pt) launched a specific protocol for the prospective follow-up of SSc patients. OBJECTIVES: To describe the baseline characteristics, disease subsets, treatments used and survival of SSc patients registered in Reuma.pt/SSc. METHODS: Data from adult patients with SSc included in Reuma.pt up to November 2020 were analysed. Demographic features, SSc subsets, fulfilment of classification criteria, main clinical and immunological features, comorbidities, treatments used and survival data were described and compared between diffuse cutaneous (dc) and limited cutaneous (lc) disease subsets. Survival was calculated for patients included in Reuma.pt within the first two years of diagnosis. RESULTS: In total, 1054 patients were included, 87.5% female, with a mean age at diagnosis of 52.7 +/- 14.8 years. The most common subset was lcSSc (56.3%), followed by dcSSc (17.5%), preclinical SSc (13%), overlap syndrome (9.8%) and SSc sine scleroderma (3.3%). Raynaud's phenomenon (93.4%) and skin thickening (76.9%) were the most frequently observed clinical manifestations. Gastrointestinal (62.8% versus 47.8%), pulmonary (59.5% versus 23%) and cardiac (12.8% versus 6.9%) involvements were significantly more prevalent in dcSSc than lcSSc. Ninety per-cent of patients were Antinuclear antibody positive, 52.5% were Anti-centromere antibody positive and 21% anti-topoisomerase positive, with significant differences between lcSSc and dcSSc. One-third of patients were treated with immunomodulators, 53.6% with vasodilators, 23% with glucocorticoids and 2.3% with biologics. During follow-up, 83 deaths (7.9%) were reported. The overall 1-, 2- and 5-year survivals were 98.0%, 96.8% and 92.6%, respectively, without significant differences between lcSSc and dcSSc. CONCLUSION: Reuma.pt/SSc data highlights the importance of registries in improving knowledge about rare and complex diseases, such as SSc. Clinical features of Portuguese SSc patients are similar to those of other populations. In recently diagnosed patients, 5-year survival is over 92%. To the best of our knowledge, this is the first study showing that clinical features of Portuguese SSc are similar to those of other cohorts.
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Síndrome CREST , Doenças do Tecido Conjuntivo , Esclerodermia Difusa , Escleroderma Sistêmico , Dermatopatias , Adulto , Anticorpos Antinucleares , Feminino , Humanos , Masculino , Estudos Prospectivos , Sistema de Registros , Esclerodermia Difusa/diagnóstico , Escleroderma Sistêmico/diagnósticoRESUMO
Pain is a common feature of most rheumatic diseases and it is often the main reason for the patient to seek for a clinical appointment. Chronic pain has a major impact on patient's quality of life, being frequently associated with functional incapacity, sleep and mood disorders. This leads to absenteeism and heavy consumption of health resources, both representing huge burdens on national economy. Managing musculoskeletal pain is pivotal but can be challenging. The use of the available pharmaceutical armamentarium should be parsimonious. Opioids are strong analgesic drugs that mostly act through their agonist action on µ-receptors in the central nervous system. Opioid-related side effects are not negligible and are mediated through both central and peripheral opioid receptors. The use of opioids is well established in the treatment of oncologic pain but their role in the management of musculoskeletal pain is still controversial. Inflammatory rheumatic diseases, osteoarthritis, osteoporotic fractures, chronic low back pain and fibromyalgia represent diverse major rheumatic conditions that frequently lead to chronic pain. In order to standardize and optimize management of musculoskeletal chronic pain in these prevalent diseases, the Portuguese Rheumatology Society elaborated this position paper. The objectives were: a) to define the importance of pain assessment and classification; b) to guide patient selection, appropriate choice of opioids, their management, and raise awareness of their adverse effects; c) to review the existent data on possible indications of opioid therapy on rheumatic diseases.
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Analgésicos Opioides/uso terapêutico , Dor Crônica/tratamento farmacológico , Dor Musculoesquelética/tratamento farmacológico , Medição da Dor/métodos , Doenças Reumáticas/tratamento farmacológico , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/efeitos adversos , Anti-Inflamatórios não Esteroides/uso terapêutico , Dor Crônica/diagnóstico , Esquema de Medicação , Redução da Medicação/métodos , Fibromialgia/tratamento farmacológico , Humanos , Dor Lombar/tratamento farmacológico , Dor Musculoesquelética/diagnóstico , Osteoartrite/tratamento farmacológico , Fraturas por Osteoporose/tratamento farmacológico , Seleção de Pacientes , Portugal , Reumatologia , Sociedades MédicasRESUMO
OBJECTIVE: To identify and synthesize the best available evidence on the use of ultrasound to assess skin involvement in systemic sclerosis (SSc). METHODS: We conducted a systemic review of the literature on PubMed Medline and Embase, using the vocabulary terms ("systemic sclerosis OR scleroderma") AND ("ultrasonography" OR "elasticity imaging techniques") AND ("skin" OR "dermis"). Two independent reviewers selected articles, collected data from studies, and carried out a manual search of the references from the studies included. This search was further enhanced by a review of bibliographic references extrapolated from these studies. The quality of the evidence was assessed by the Effective Public Health Practice Project system. RESULTS: A total of 30 studies were identified, enrolling 1,171 SSc patients, predominantly middle-aged (mean age 55.5 years) females (88.8%). The ultrasound skin measurements that were reported included thickness in 28 studies and/or echogenicity (7 studies), and/or stiffness (6 studies), and/or vascularity (1 study). The main comparator was the global and site-specific modified Rodnan skin thickness score. Reported interrater and intrarater reproducibility appeared to be excellent, but this reproducibility was assessed by a small number of studies. Moreover, there were no published evaluations of construct or criterion validity of skin ultrasound assessment. The responsiveness to change of ultrasound elastography has not been assessed. CONCLUSION: Published reports have strong limitations and are highly heterogeneous, hindering the evidence to support the use of skin ultrasound assessment in clinical practice. Further studies, with modern devices and appropriate methodology, are needed to establish the real value of skin ultrasound assessment in the early diagnosis and monitoring of SSc patients.
Assuntos
Escleroderma Sistêmico/diagnóstico por imagem , Humanos , UltrassonografiaRESUMO
BACKGROUND: Pulmonary arterial hypertension (PAH) complicates the course of systemic sclerosis (SSc) and is associated with poor prognosis. The elevation of systolic pulmonary arterial pressure (sPAP) during exercise in patients with SSc with normal resting haemodynamics may anticipate the development of PAH. Exercise echocardiography (ExEcho) has been proposed as a useful technique to identify exercise-induced increases in sPAP, but it is unclear how to clinically interpret these findings. In this systematic review, we summarize the available evidence on the role of exercise echocardiography to estimate exercise-induced elevations in pulmonary and left heart filling pressures in patients with systemic sclerosis. METHODS: We conducted a systematic review of the literature using MEDLINE, Cochrane Library and Web of Knowledge, using the vocabulary terms: ('systemic sclerosis' OR 'scleroderma') AND ('exercise echocardiography') AND ('pulmonary hypertension'). Studies including patients with SSc without a prior diagnosis of PAH, and subjected to exercise echocardiography were included. All searches were limited to English and were augmented by review of bibliographic references from the included studies. The quality of evidence was assessed by the Effective Public Health Practice Project system. RESULTS: We identified 15 studies enrolling 1242 patients, who were mostly middle-aged and female. Several exercise methods were used (cycloergometer, treadmill and Master's two step), with different protocols and positions (supine, semi-supine, upright); definition of a positive test also varied widely. Resting estimated sPAP levels varied from 18 to 35 mm Hg, all in the normal range. The weighted means for estimated sPAP were 22.2 ± 2.9 mmHg at rest and 43.0 ± 4.3 mmHg on exercise; more than half of the studies reported mean exercise sPAP ≥40 mmHg. The assessment of left ventricular diastolic function on peak exercise was reported in a minority of studies; however, when assessed, surrogate variables of left ventricular (LV) diastolic dysfunction were associated with higher sPAP on exercise. CONCLUSIONS: We found very high heterogeneity in the methods, the protocols and the estimated sPAP response to exercise. LV diastolic dysfunction was common and was associated with greater elevation of sPAP on exercise.