Quiz Ref ID Systemic sclerosis is a heterogeneous autoimmune connective tissue disease characterized by vasculopathy, autoantibody formation, low-grade inflammation, and fibrosis in skin and internal organs, with varying geographical prevalence (50-300 per million persons per year) and incidence (2.3-22.8 per million persons per year).^1,2 Previous studies have shown that systemic sclerosis is amenable to treatment with autologous hematopoietic stem cell transplantation (HSCT).^3-9 Improvement of skin involvement and functional ability was consistently observed, although some studies showed that HSCT can also ameliorate vasculopathy, improve skin and lung involvement, and correct immune abnormalities.^10-13 The benefits of HSCT must be weighed against the risk of serious toxicities due to organ involvement in systemic sclerosis.¹⁴ It is still unclear whether HSCT prolongs survival in systemic sclerosis. We therefore conducted a randomized clinical trial called ASTIS (Autologous Stem Cell Transplantation International Scleroderma) to compare safety and efficacy of HSCT vs 12 successive monthly intravenous pulses of cyclophosphamide.

Histiocytoses are rare disorders of unknown origin with highly heterogeneous prognosis. BRAF mutations have been observed in Langerhans cell histiocytosis (LCH). We investigated the frequency of BRAF mutations in several types of histiocytoses. Histology from 127 patients with histiocytoses were reviewed. Detection of BRAFV600 mutations was performed by pyrosequencing of DNA extracted from paraffin embedded samples. Diagnoses of Erdheim-Chester disease (ECD), LCH, Rosai-Dorfman disease, juvenile xanthogranuloma, histiocytic sarcoma, xanthoma disseminatum, interdigitating dendritic cell sarcoma, and necrobiotic xanthogranuloma were performed in 46, 39, 23, 12, 3, 2, 1, and 1 patients, respectively. BRAF status was obtained in 93 cases. BRAFV600E mutations were detected in 13 of 24 (54%) ECD, 11 of 29 (38%) LCH, and none of the other histiocytoses. Four patients with ECD died of disease. The high frequency of BRAFV600E in LCH and ECD suggests a common origin of these diseases. Treatment with vemurafenib should be investigated in patients with malignant BRAFV600E histiocytosis.

Objective: To describe the response to first‐line immunosuppressive therapy with or without pulmonary vasodilators in pulmonary arterial hypertension (PAH) associated with systemic lupus erythematosus (SLE) or mixed connective tissue disease (MCTD).Methods: Twenty‐three consecutive patients with SLE‐ or MCTD‐associated PAH treated with first‐line immunosuppressive therapy either alone (n = 16) or in combination with pulmonary vasodilators (n = 7) were evaluated according to clinical and hemodynamic criteria before and after immunosuppressive therapy. Responders were defined as patients in New York Heart Association (NYHA) functional class I or II with hemodynamic improvement after the last pulse of cyclophosphamide.Results: Among the 16 patients treated with first‐line immunosuppressive therapy alone, 8 (50%) were responders. These patients had a significantly improved NYHA functional class, 6‐minute walking distance, and mean pulmonary artery pressure. Patients in NYHA functional class I or II and/or a cardiac index >3.1 liters/minute/m² at baseline were more likely to benefit from immunosuppressive therapy. Six of the 8 nonresponders subsequently improved with pulmonary vasodilators. Among the 7 patients who were initially treated with immunosuppressive therapy and pulmonary vasodilators, 4 (57.1%) were responders.Conclusion: PAH associated with SLE or MCTD may respond to a treatment combining cyclophosphamide and glucocorticoids. Patients who could benefit from this immunosuppressive therapy could be those who have less severe disease at baseline. For patients with more severe disease, pulmonary vasodilators should be started, possibly in combination with immunosuppressants. In any case, clinical and hemodynamic evaluations are mandatory to monitor the response and adapt the treatment. These retrospective and uncontrolled data need to be confirmed by randomized controlled trials.

Objective: Pulmonary arterial hypertension (PAH) is a severe, life‐limiting complication of systemic sclerosis (SSc). Guidelines recommend early detection and management of SSc‐PAH. However, little is known about the impact of detection programs on patients with SSc‐PAH. This study was undertaken to assess the clinical characteristics of patients with SSc‐PAH at diagnosis and their long‐term outcomes.Methods: Two incident cohorts of patients with SSc‐PAH from the same management era (2002/2003) were studied. The first cohort (designated the routine practice cohort) included consecutive adult patients with symptomatic SSc in whom a diagnosis of PAH was made by right‐sided heart catheterization (RHC) at the time of recruitment into the French PAH Registry. The second cohort (designated the detection cohort) comprised consecutive patients with SSc who entered a systematic PAH detection program and were subsequently found to have PAH on RHC. Clinical characteristics at diagnosis of PAH and subsequent 8‐year mortality were compared between the cohorts.Results: There were 16 patients in each cohort. At the time of PAH diagnosis, patients in the detection cohort had less advanced pulmonary vascular disease compared with patients in the routine practice cohort, as evidenced by more patients being in New York Heart Association class I and class II, a lower mean pulmonary artery pressure and pulmonary vascular resistance index, and a higher cardiac output. Patients in the detection cohort were less likely to receive diuretics and warfarin, but there was no difference in exposure to PAH‐specific therapies between the cohorts. The 1‐, 3‐, 5‐, and 8‐year survival rates were 75%, 31%, 25%, and 17%, respectively, in the routine practice cohort compared with 100%, 81%, 73%, and 64%, respectively, in the detection cohort (P = 0.0037).Conclusion: Compared with patients in routine clinical practice, PAH detection programs in SSc are able to identify patients with milder forms of the disease, allowing earlier management.

Objectives: To assess the prevalence and patterns of cardiac abnormalities as detected by cardiac magnetic resonance imaging (MRI) in systemic sclerosis (SSc). Methods: Fifty-two consecutive patients with SSc underwent cardiac MRI to determine morphological, functional, perfusion at rest and delayed enhancement abnormalities. Results: At least one abnormality on cardiac MRI was observed in 39/52 patients (75%). Increased myocardial signal intensity in T2 was observed in 6 patients (12%), thinning of left ventricle (LV) myocardium in 15 patients (29%) and pericardial effusion in 10 patients (19%). LV and right ventricle (RV) ejection fractions were altered in 12 patients (23%) and 11 patients (21%), respectively. LV diastolic dysfunction was found in 15/43 patients (35%). LV kinetic abnormalities were found in 16/52 patients (31%) and myocardial delayed contrast enhancement was detected in 11/52 patients (21%). No perfusion defects at rest were found. Patients with limited SSc had similar MRI abnormalities to patients with diffuse SSc. Seven of 40 patients (17%) without pulmonary arterial hypertension had RV dilatation. Conclusions: This study shows that MRI is a reliable and sensitive technique for diagnosing heart involvement in SSc and for analysing its mechanisms, including its inflammatory, microvascular and fibrotic components. Compared with echocardiography, MRI appears to provide additional information by visualising myocardial fibrosis and inflammation. RV dilatation appeared to be non-specific for pulmonary arterial hypertension but could also reflect myocardial involvement related to SSc. Further studies are needed to determine whether cardiac MRI abnormalities have an impact on the prognosis and treatment strategy.