Clinical presentation, course, and prognosis of patients with mixed connective tissue disease: A multicenter retrospective cohort.

OBJECTIVES: The objective of this study is to better characterize the features and outcomes of a large population of patients with mixed connective tissue disease (MCTD). METHODS: We performed an observational retrospective multicenter cohort study in France. Patients who fulfilled at least one diagnostic criterion set for MCTD and none of the criteria for other differentiated CTD (dCTD) were included. RESULTS: Three hundred and thirty patients (88% females, median [interquartile range] age of 35 years [26-45]) were included. The diagnostic criteria of Sharp or Kasukawa were met by 97.3% and 93.3% of patients, respectively. None met other classification criteria without fulfilling Sharp or Kasukawa criteria. After a median follow-up of 8 (3-14) years, 149 (45.2%) patients achieved remission, 92 (27.9%) had interstitial lung disease, 25 (7.6%) had pulmonary hypertension, and 18 (5.6%) died. Eighty-five (25.8%) patients progressed to a dCTD, mainly systemic sclerosis (15.8%) or systemic lupus erythematosus (10.6%). Median duration between diagnosis and progression to a dCTD was 5 (2-11) years. The presence at MCTD diagnosis of an abnormal pattern on nailfold capillaroscopy (odds ratio [OR] = 2.44, 95% confidence interval [95%CI] [1.11-5.58]) and parotid swelling (OR = 3.86, 95%CI [1.31-11.4]) were statistically associated with progression to a dCTD. Patients who did not progress to a dCTD were more likely to achieve remission at the last follow-up (51.8% vs. 25.9%). CONCLUSIONS: This study shows that MCTD is a distinct entity that can be classified using either Kasukawa or Sharp criteria, and that only 25.8% of patients progress to a dCTD during follow-up.

Anti-U1RNP antibodies are associated with a distinct clinical phenotype and a worse survival in patients with systemic sclerosis.

OBJECTIVES: To clarify the impact of anti-U1RNP antibodies on the clinical features and prognosis of patients with SSc. METHODS: We conducted a monocentric case-control, retrospective, longitudinal study. For each patient with SSc and anti-U1RNP antibodies (SSc-RNP+), one patient with mixed connective tissue disease (MCTD) and 2 SSc patients without anti-U1RNP antibodies (SSc-RNP-) were matched for age, sex, and date of inclusion. RESULTS: Sixty-four SSc-RNP+ patients were compared to 128 SSc-RNP- and 64 MCTD patients. Compared to SSc-RNP-, SSc-RNP+ patients were more often of Afro-Caribbean origin (31.3% vs. 11%, p < 0.01), and more often had an overlap syndrome than SSc-RNP- patients (53.1 % vs. 22.7%, p < 0.0001), overlapping with Sjögren's syndrome (n = 23, 35.9%) and/or systemic lupus erythematosus (n = 19, 29.7%). SSc-RNP+ patients were distinctly different from MCTD patients but less often had joint involvement (p < 0.01). SSc-RNP+ patients more frequently developed interstitial lung disease (ILD) (73.4% vs. 55.5% vs. 31.3%, p < 0.05), pulmonary fibrosis (PF) (60.9% vs. 37.5% vs. 10.9%, p < 0.0001), SSc associated myopathy (29.7% vs. 6.3% vs. 7.8%, p < 0.0001), and kidney involvement (10.9% vs. 2.3% vs. 1.6%, p < 0.05). Over a 200-month follow-up period, SSc-RNP+ patients had worse overall survival (p < 0.05), worse survival without PF occurrence (p < 0.01), ILD or PF progression (p < 0.01 and p < 0.0001). CONCLUSIONS: In SSc patients, anti-U1RNP antibodies are associated with a higher incidence of overlap syndrome, a distinct clinical phenotype, and poorer survival compared to SSc-RNP- and MCTD patients. Our study suggests that SSc-RNP+ patients should be separated from MCTD patients and may constitute an enriched population for progressive lung disease.

Prognostic value of automated assessment of interstitial lung disease on CT in systemic sclerosis.

OBJECTIVE: Stratifying the risk of death in SSc-related interstitial lung disease (SSc-ILD) is a challenging issue. The extent of lung fibrosis on high-resolution CT (HRCT) is often assessed by a visual semiquantitative method that lacks reliability. We aimed to assess the potential prognostic value of a deep-learning-based algorithm enabling automated quantification of ILD on HRCT in patients with SSc. METHODS: We correlated the extent of ILD with the occurrence of death during follow-up, and evaluated the additional value of ILD extent in predicting death based on a prognostic model including well-known risk factors in SSc. RESULTS: We included 318 patients with SSc, among whom 196 had ILD; the median follow-up was 94 months (interquartile range 73-111). The mortality rate was 1.6% at 2 years and 26.3% at 10 years. For each 1% increase in the baseline ILD extent (up to 30% of the lung), the risk of death at 10 years was increased by 4% (hazard ratio 1.04, 95% CI 1.01, 1.07, P = 0.004). We constructed a risk prediction model that showed good discrimination for 10-year mortality (c index 0.789). Adding the automated quantification of ILD significantly improved the model for 10-year survival prediction (P = 0.007). Its discrimination was only marginally improved, but it improved prediction of 2-year mortality (difference in time-dependent area under the curve 0.043, 95% CI 0.002, 0.084, P = 0.040). CONCLUSION: The deep-learning-based, computer-aided quantification of ILD extent on HRCT provides an effective tool for risk stratification in SSc. It might help identify patients at short-term risk of death.

Mouth opening in systemic sclerosis: A longitudinal analysis from the French National Cohort Study.

BACKGROUND: Few studies have evaluated mouth opening (MO) in systemic sclerosis (SSc). None have studied MO trajectories. OBJECTIVE: To study MO trajectories in SSc. METHODS: This multicentre study included patients enrolled in the French national SSc cohort with at least one MO assessment, described patients based on MO baseline measure, modeled MO trajectories, and associated MO measures with SSc prognosis. RESULTS: We included 1101 patients. Baseline MO was associated with disease severity. On Kaplan-Meier analysis, MO < 30 mm was associated with worse 30-year-survival (p<0.01) and risk of pulmonary arterial hypertension (p<0.05). Individual MO trajectories were heterogenous among patients. The best model of MO trajectories according to latent-process mixed modeling showed that 88.8% patients had a stable MO trajectory and clustered patients into 3 groups that predicted SSc survival (p<0.05) and interstitial lung disease (ILD) occurrence (p<0.05). The model highlighted a cluster of 9.5% patients with diffuse cutaneous SSc (dcSSc) (p<0.05) and high but decreasing MO over 1 year (p<0.0001) who were at increased risk of poor survival and ILD. CONCLUSION: MO, which is a simple and reliable measure, could be used to predict disease severity and survival in SSc. Although MO remained stable in most SSc patients, dcSSc patients with high but decreasing MO were at risk of poor survival and ILD. This article is protected by copyright. All rights reserved.

In-depth characterization of pulmonary arterial hypertension in mixed connective tissue disease: a French national multicentre study.

OBJECTIVE: Pulmonary arterial hypertension (PAH) is a leading cause of death in MCTD. We aimed to describe PAH in well-characterized MCTD patients. METHODS: MCTD patients enrolled in the French Pulmonary Hypertension Registry with a PAH diagnosis confirmed by right heart catheterization were included in the study and compared with matched controls: MCTD patients without PAH, SLE patients with PAH and SSc patients with PAH. Survival rates were estimated by the Kaplan-Meier method and risk factors for PAH in MCTD patients and risk factors for mortality in MCTD-PAH were sought using multivariate analyses. RESULTS: Thirty-six patients with MCTD-PAH were included in the study. Comparison with MCTD patients without PAH and multivariate analysis revealed that pericarditis, polyarthritis, thrombocytopenia, interstitial lung disease (ILD) and anti-Sm antibodies were independent predictive factors of PAH/PH in MCTD. Estimated survival rates at 1, 5 and 10 years following PAH diagnosis were 83%, 67% and 56%, respectively. MCTD-PAH presentation and survival did not differ from SLE-PAH and SSc-PAH. Multivariate analysis revealed that tobacco exposure was an independent factor predictive of mortality in MCTD-PAH. CONCLUSION: PAH is a rare and severe complication of MCTD associated with a 56% 10-year survival. We identified ILD, pericarditis, thrombocytopenia and anti-Sm antibodies as risk factors for PAH in MCTD and tobacco exposure as a predictor of mortality in MCTD-PAH.

Heart and systemic sclerosis-findings from a national cohort study.

OBJECTIVES: Heart involvement is one of the leading causes of death in systemic sclerosis (SSc). The prevalence of SSc-related cardiac involvement is poorly known. Our objective was to investigate the prevalence and prognosis burden of different heart diseases in a nationwide cohort of patients with SSc. METHODS: We used data from a multicentric prospective study using the French SSc national database. Focusing on SSc-related cardiac involvement, we aimed to determine its incidence and risk factors. RESULTS: Over the 3528 patients with SSc 312 (10.9%) had SSc-related cardiac involvement at baseline. They tended to have a diffuse SSc subtype more frequently, more severe clinical features, and presented more cardiovascular risk factors. From the 1646 patients available for follow-up analysis, SSc-related cardiac involvement was associated with an increased risk of death. There was no significant difference in overall survival between SSc-related cardiac involvement, ischaemic heart disease or pulmonary arterial hypertension. Regarding survival analysis, 98 patients developed SSc-related cardiac involvement at five years (5-year event rate: 11.15%). Regarding reduced LVEF < 50% and left ventricular diastolic dysfunction, the 5-year event rate was 2.49% and 5.84% respectively. Pericarditis cumulative incidence at five years was 3%. Diffuse SSc subtype was a risk factor for SSc-related cardiac involvement and pericarditis. Female sex was associated with less left ventricular diastolic dysfunction incidence. CONCLUSIONS: Our results describe the incidence and prognostic burden of SSc-related cardiac involvement at a large scale, with gender and diffuse SSc subtype as risk factors. Further analyses should assess the potential impact of treatment on these various cardiac outcomes.

The association between air pollution and the severity at diagnosis and progression of systemic sclerosis-associated interstitial lung disease: results from the retrospective ScleroPol study.

OBJECTIVE: To investigate the association of air pollution exposure with the severity of interstitial lung disease (ILD) at diagnosis and ILD progression among patients with systemic sclerosis (SSc)-associated ILD. METHODS: We conducted a retrospective two-center study of patients with SSc-associated ILD diagnosed between 2006 and 2019. Exposure to the air pollutants particulate matter of up to 10 and 2.5 µm in diameter (PM10, PM2.5), nitrogen dioxide (NO2), and ozone (O3) was assessed at the geolocalization coordinates of the patients' residential address. Logistic regression models were used to evaluate the association between air pollution and severity at diagnosis according to the Goh staging algorithm, and progression at 12 and 24 months. RESULTS: We included 181 patients, 80% of whom were women; 44% had diffuse cutaneous scleroderma, and 56% had anti-topoisomerase I antibodies. ILD was extensive, according to the Goh staging algorithm, in 29% of patients. O3 exposure was associated with the presence of extensive ILD at diagnosis (adjusted OR: 1.12, 95% CI 1.05-1.21; p value = 0.002). At 12 and 24 months, progression was noted in 27/105 (26%) and 48/113 (43%) patients, respectively. O3 exposure was associated with progression at 24 months (adjusted OR: 1.10, 95% CI 1.02-1.19; p value = 0.02). We found no association between exposure to other air pollutants and severity at diagnosis and progression. CONCLUSION: Our findings suggest that high levels of O3 exposure are associated with more severe SSc-associated ILD at diagnosis, and progression at 24 months.

Health-related quality of life in patients with mixed connective tissue disease: a comparison with matched systemic sclerosis patients.

OBJECTIVES: Health-Related Quality of Life (HRQoL) in adult patients with mixed connective tissue disease (MCTD) has not been described so far. Therefore, we performed an explorative study to evaluate HRQoL in MCTD patients. METHODS: MCTD patients fulfilling the Kahn criteria and participating in the prospective follow-up cohort for MCTD of the Leiden University Medical Center were included; and matched to systemic sclerosis (SSc) patients based on age, sex and disease duration. Data on disease characteristics and HRQoL (SF36 and EQ-5D) were collected annually. HRQoL was compared between MCTD and SSc patients at baseline. Factors associated with HRQoL in MCTD were identified using linear regression and change in HRQoL over 3 years using linear mixed models. RESULTS: Thirty-four MCTD patients (121 visits) and 102 SSc patients (424 visits) were included. At baseline, MCTD patients presented with interstitial lung disease, cardiac involvement, synovitis and myositis more frequently compared to SSc patients, while use of immunosuppressive medication was less frequent. In both groups, mean SF36 scores were lower than in the general Dutch population. The SF36 subscore "general health perception" was impacted most in both groups (MCTD: 38.5 [SD:7.0], SSc: 39.9 [SD:8.9]). During follow-up, SF36 scores improved in MCTD patients, while EQ5DNL remained stable. No specific characteristics were identified that associated with baseline HRQoL or change in HRQol over time. CONCLUSIONS: Like in SSc, HRQoL in MCTD is significantly impaired, especially the general health perception of patients. Evaluation in larger prospective cohorts is needed to identify characteristics that impact HRQol most.

The added value of a European Reference Network on rare and complex connective tissue and musculoskeletal diseases: insights after the first 5 years of the ERN ReCONNET.

In order to address the main challenges related to the rare diseases (RDs) the European Commission launched the European Reference Networks (ERNs), virtual networks involving healthcare providers (HCPs) across Europe. The mission of the ERNs is to tackle low prevalence and RDs that require highly specialised treatment and a concentration of knowledge and resources. In fact, ERNs offer the potential to give patients and healthcare professionals across the EU access to the best expertise and timely exchange of lifesaving knowledge, trying to make the knowledge travelling more than patients. For this reason, ERNs were established as concrete European infrastructures, and this is particularly crucial in the framework of rare and complex diseases in which no country alone has the whole knowledge and capacity to treat all types of patients.It has been five years since their kick-off launch in Vilnius in 2017. The 24 ERNs have been intensively working on different transversal areas, including patient management, education, clinical practice guidelines, patients' care pathways and many other fundamental topics. The present work is therefore aimed not only at reporting a summary of the main activities and milestones reached so far, but also at celebrating the first 5 years of the ERN on Rare and Complex Connective Tissue and Musculo-skeletal Diseases (ReCONNET), in which the members of the network built together one of the 24 infrastructures that are hopefully going to change the scenario of rare diseases across the EU.

Cluster analysis reveals eosinophilia and fibrosis as poor prognostic markers in 128 patients with eosinophilic fasciitis.

BACKGROUND: Eosinophilic fasciitis (EF) is an extremely rare disease with polymorphic presentation and prognosis. OBJECTIVE: To further investigate EF features. METHODS: We performed a retrospective multicentre study of EF patients from 2013 to 2019, clustered patients using multivariate correspondence analysis, and sought prognosis factors. RESULTS: One hundred twenty-eight patients were included. Sixty-nine (50%) patients had skin sclerosis, and eosinophil count was increased in 71 (55%) patients. Multivariate correspondence analysis identified 3 clusters: a "mild," a "late-onset and hypereosinophilic," and a "fibrotic" cluster. Of 109 patients who followed up for more than 1 year, 49 (45%) presented a relapse, and 48 (44%) had sequelae. Multivariate analysis revealed that eosinophilia (hazard ratio = 1.56; P = .02) and fibrosis (hazard ratio = 4.02; P = .002) were predictive factors of relapse, whereas edema (odds ratio = 0.31; P = .03), relapse (odds ratio = 3.00; P = .04) and fibrosis (odds ratio = 1) were predictive factors of sequelae. Following relapse, treatment modifications consisted of an increase in glucocorticoids in 40 (82%) patients and the addition of methotrexate in 31 (63%) patients. These modifications led to clinical improvement and glucocorticoid withdrawal in 37 (76%) and 22 (45%) patients. LIMITATIONS: Retrospective study. CONCLUSION: EF patients can be divided into 3 homogenous clusters, which, along with fibrosis and eosinophilia, are prognosis factors of relapse and sequelae.

Skewed peripheral B- and T-cell compartments in patients with ANCA-associated vasculitis.

OBJECTIVES: To characterize lymphocytes dysregulation in patients with granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). METHODS: Using flow cytometry, we analysed B- and T-cell subsets in peripheral blood from 37 untreated patients with active disease (29 GPA and 8 MPA) and 22 healthy controls (HCs). RESULTS: GPA patients had increased Th2 (1.8 vs 1.0%, P = 0.02), Th9 (1.1 vs 0.2%, P = 0.0007) and Th17 (1.4 vs 0.9%, P = 0.03) cells compared with HC. Patients with MPO-ANCAs had significantly more CD21- B cells than HC or PR3-ANCA patients (6.9 vs 3.3% and 4.4%, P = 0.01). CD69 expressing B cells were significantly higher in GPA and MPA (3.0 and 5.9 vs 1.4%, P = 0.02 and P = 0.03, respectively) compared with HC, whereas B-cell activating factor-receptor expression was decreased in GPA and MPA (median fluorescence intensity ratio 11.8 and 13.7 vs 45.1 in HC, P < 0.0001 and P = 0.003, respectively). Finally, IL-6-producing B cells were increased in GPA vs HC (25.8 vs 14.9%, P < 0.0001) and decreased in MPA vs HC (4.6 vs 14.9%, P = 0.005), whereas TNF-α-producing B cells were lower in both GPA and MPA patients compared with controls (15 and 8.4 vs 30%, P = 0.01 and P = 0.006, respectively). CONCLUSION: Skewed T-cell polarization towards Th2, Th9 and Th17 responses characterizes GPA, whereas B-cell populations are dysregulated in both GPA and MPA with an activated phenotype and a decreased B-cell activating factor-receptor expression. Finally, inflammatory B cells producing IL-6 are dramatically increased in GPA, providing an additional mechanism by which rituximab could be effective.

Extra-haematological manifestations related to human parvovirus B19 infection: retrospective study in 25 adults.

BACKGROUND: To describe extra-haematological manifestations associated with human parvovirus B19 (HPV-B19) infection. METHODS: We conducted a nationwide multicentre study to retrospectively describe the characteristics and outcome of extra-haematological manifestations in French adults. RESULTS: Data from 25 patients followed from 2001 to 2016 were analysed. Median age was 37.9 years (range: 22.7-83.4), with a female predominance (sex ratio: 4/1). Only 3 patients had an underlying predisposing condition (hemoglobinopathy or pregnancy). The most common manifestations were joint (80%) and skin (60%) involvement. Four patients (16%) had renal involvement (endocapillary proliferative or membranoproliferative glomerulonephritis, focal segmental glomerulosclerosis). Three patients (12%) had peripheral nervous system involvement (mononeuritis, mononeuritis multiplex, Guillain-Barré syndrome) and 2 (8%) presented muscle involvement. Other manifestations included hemophagocytic lymphohistiocytosis (n = 1), myopericarditis and pleural effusion (n = 1), and lymphadenopathy and splenomegaly mimicking lymphoma with spleen infarcts (n = 1). Immunological abnormalities were frequent (56.5%). At 6 months, all patients were alive, and 54.2% were in complete remission. In 2 patients, joint involvement evolved into rheumatoid arthritis. Six patients (24%) received intravenous immunoglobulin (IVIg), with a good response in the 3 patients with peripheral nervous system involvement. CONCLUSIONS: HPV-B19 infection should be considered in a wide range of clinical manifestations. Although the prognosis is good, IVIg therapy should be discussed in patients with peripheral nerve involvement. However, its efficacy should be further investigated in prospective studies.

Impact of disease activity on health-related quality of life in systemic lupus erythematosus - a cross-sectional analysis of the Swiss Systemic Lupus Erythematosus Cohort Study (SSCS).

BACKGROUND: To assess the impact of disease activity on health-related quality of life (HRQoL) in systemic lupus erythematosus (SLE). METHODS: Cross-sectional study of patients included in the Swiss SLE Cohort Study between April 2007 and June 2014. HRQoL outcomes were based on the Medical Outcome Study Short Form 36 (SF-36). Disease activity was assessed by the SLE Disease Activity Index score with the Safety of Estrogens in SLE National Assessment modification (SELENA-SLEDAI) and by the physican's global assessment (PGA). RESULTS: Of the 252 patients included, 207 (82%) were women. Median [interquartile range (IQR)] age was 43 [32-57] years. SLE was active in 125 patients (49.6%). Median [IQR] mental component summary (MCS) in active vs inactive SLE was 40.0 [30.2-51.0] compared to 47.3 [39.2-52.8] (p < 0.01) and median [IQR] physical component summary (PCS) 43.7 [37.0-52.8] compared to 49.1 [38.4-55.6], respectively (p < 0.05). Increase in SELENA-SLEDAI or increase in PGA were negatively correlated with PCS and/or MCS. After adjusting for gender, age and disease duration, disease activity impacted on both PCS and MCS and all subscales except general health. Active lupus nephritis and musculoskeletal involvement were associated with physical limitations and emotional problems, increased bodily pain and poor social functioning. Low complement and/or presence of anti-dsDNA antibodies were associated with increased fatigue and reduced mental health. CONCLUSIONS: In patients with SLE, HRQoL is reduced in those with active disease. Impact of disease activity on HRQoL dimensions depends on SELENA-SLEDAI system components.

Mechanisms of action of intravenous immunoglobulin.

Taking advantage of the "World Apheresis Association/Société Française d'Hémaphérèse" meeting held in Paris in April 2016, this article reviews the current knowledge on the mechanisms of action of intravenous immunoglobulins. Immunoglobulins are a plasma-derived drug, which have been initially used as a replacement therapy for patients with antibody deficiency. Since 1980 they have also been used for their anti-inflammatory and immunomodulating efficacy in auto-immune diseases. Herein, we review the requirements for their production and composition before giving a specific attention to their mechanisms of action including substitution and immunomodulation.

Differential impact of systemic lupus erythematosus and rheumatoid arthritis on health-related quality of life.

PURPOSE: This study examined and compared health-related quality of life (QoL) in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). METHODS: We included patients from two multicentric cohorts, the Swiss SLE cohort study (SSCS) and the Swiss Clinical Quality Management Program for RA (SCQM-RA). Patients were matched by age, sex and disease duration using the propensity score. Disease activity was assessed by SELENA-SLEDAI in SLE and by DAS-28 in RA. QoL was captured by the short-form 36 (SF-36). The primary outcomes were physical component summary (PCS) and mental component summary (MCS) of the SF-36. Generalized estimating equation models were used to assess evolution over time. RESULTS: We analyzed 267 SLE patients and 267 matched RA patients. More patients with RA had active disease and more patients with SLE had immunosuppressant therapies at baseline. The median [interquartile range (IQR)] MCS and PCS scores were 45.1 [33.7-52.6] and 45.6 [38.0-53.0] in SLE and 48.8 [37.6-56.7] and 34.7 [26.8-43.0] in RA, respectively (ps < 0.001). Over one year the differences persisted, although PCS and MCS increased in RA (ps < 0.001) but not in SLE in the univariate analysis. The differences in MCS and PCS scores between RA and SLE remained qualitatively similar after adjustment for patient characteristics, treatment, and activity disease. CONCLUSIONS: SLE and RA both affect QoL. Patients with SLE have lower MCS, whereas patients with RA have lower PCS. These differences remained over 1 year of follow up, suggesting fundamental dissimilarities between SLE and RA in their impact on QoL.

Organizing pneumonia and occupational and environmental risk factors: a case-control study.

OBJECTIVES: A single-center case-control study was carried out to investigate the relationship between occupational and environmental exposure and organizing pneumonia (OP). METHODS: Thirty-seven cases of OP, including 25 cases of cryptogenic OP, and 111 controls were included. Occupational exposure was assessed retrospectively by an industrial hygienist and an occupational physician, through semi-quantitative estimates of exposure. An exposure score was calculated for each subject, based on probability, intensity, daily frequency, and duration of exposure for each period of employment. The final cumulative exposure score was obtained by summing exposure scores for all periods of employment. RESULTS: Significant associations with all-cause OP were observed for exposure to tetrachloroethylene (OR 13.33, CI 95% 1.44-123.5) and silica (OR 6.61, CI 95% 1.16-37.71). A significant association with cryptogenic OP was observed only for tetrachloroethylene (OR 31.6, CI 95% 1.64-610.8). No associations were found for environmental exposure. CONCLUSION: Despite its low statistical power, this work suggests that occupational risk factors could be involved in OP.

Patients' views and needs about systemic sclerosis and its management: a qualitative interview study.

BACKGROUND: Systemic sclerosis (SSc) is a chronic connective-tissue disease responsible for reduced life expectancy, disability and a decreased quality of life. In order to optimize patients-physicians relationship and care strategy we aimed to survey views of patients on SSc and its management to reveal potential hurdles and improve health care strategies. METHODS: A qualitative study combined semi-structured interviews, focus groups, and a direct observation of an information session was performed between November 2008 and January 2009. RESULTS: Twenty-five patients with SSc were included. They encounter difficulties to have a clear representation of their disease. Physical, psychological, and social repercussions of SSc may lead to a psychological distress and different coping strategies, which widely differ among interviewed patients. Patients' views on their therapeutic journey and the management of their disease highlighted strong expectations about patient-physician relationship. These expectations were numerous, complex and sometimes ambivalent. Patients expected physicians to be human and attentive but also involved in research in the field and to provide psychological and affective support to help them to accept the uncertainty of disease evolution and lack of curative treatment. They also expected more individualized management, improvements in diagnosis and follow-up organization, more efforts in education and information, comprehensive behaviors and support from working colleagues and relatives, and increased funding from the health care system. CONCLUSIONS: Our results suggest that SSc management could be optimized, particularly with more attention to the patient-practitioner relationship. Patient profiles should be more precisely defined in terms of coping strategies and treatment preferences to propose more individualized options.