Séverine Feuillet

Paris Diderot University, Lutetia Parisorum, Île-de-France, France

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Publications (19)41.13 Total impact

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    ABSTRACT: OBJECTIVES: To evaluate the efficacy and safety of rituximab in patients with primary Sjögren's syndrome (pSS). METHODS: The AutoImmune and Rituximab registry has included 86 patients with pSS treated with rituximab, prospectivey followed up every 6 months for 5 years. RESULTS: Seventy-eight patients with pSS (11 men, 67 women), who already had at least one follow-up visit, were analysed. Median age was 59.8 years (29-83), median duration of disease was 11.9 years (3-32). Indications for treatment were systemic involvement for 74 patients and only severe glandular involvement in four patients. The median European Sjögren's Syndrome disease activity index (ESSDAI) was 11 (2-31). 17 patients were concomitantly treated with another immunosuppressant agent. Median follow-up was 34.9 months (6-81.4) (226 patient-years). Overall efficacy according to the treating physician was observed in 47 patients (60%) after the first cycle of rituximab. Median ESSDAI decreased from 11 (2-31) to 7.5 (0-26) (p<0.0001). Median dosage of corticosteroid decreased from 17.6 mg/day (3-60) to 10.8 mg/day (p=0.1). Forty-one patients were retreated with rituximab. Four infusion reactions and one delayed serum sickness-like disease resulted in rituximab discontinuation. Three serious infections (1.3/100 patient-years) and two cancer-related deaths occurred. CONCLUSIONS: In common practice, the use of rituximab in pSS is mostly restricted to patients with systemic involvement. This prospective study shows good efficacy and tolerance of rituximab in patients with pSS and systemic involvement.
    Annals of the rheumatic diseases 12/2012; · 8.11 Impact Factor
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    ABSTRACT: Abstract BACKGROUND:Precapillary pulmonary hypertension (PH) is a complication of pulmonary Langerhans cell histiocytosis (PLCH) associated with increased mortality. However, outcomes and efficacy of pulmonary arterial hypertension (PAH) therapies in patients with PH complicating PLCH (PLCH-PH) remain unknown. METHODS:Consecutive PLCH patients with PH confirmed by right heart catheterization were included in the study. Characteristics at baseline and during follow-up as well as survival were analyzed. RESULTS:29 patients were studied. Baseline characteristics of PLCH-PH patients were: 83% of patients in World Health Organization (WHO) functional class III-IV, mean 6-min walk distance of 355 ± 95 m, mean pulmonary arterial pressure (mPAP) of 45 ± 14 mm Hg, cardiac index of 3.2 ± 0.9 L.min(-1).m(-2) and pulmonary vascular resistance (PVR) of 555 ± 253 dyn.s.cm(-5). Use of PAH therapy in 12 patients was followed by improvement in mPAP (56 ± 14 and 45 ± 12 mm Hg, P = 0.03) and PVR (701 ± 239 and 469 ± 210 dyn.s.cm(-5), P = 0.01) between baseline and follow up evaluations. No significant oxygen worsening was observed in the treated group. The 1-, 3- and 5-year survival estimates of the 29 patients were 96%, 92% and 73%, respectively. Except a trend toward a better survival associated with the use of PAH therapy, WHO functional class was the only variable significantly associated with death. CONCLUSIONS:In this group of patients, PAH therapies improved hemodynamic without oxygen worsening or pulmonary edema. WHO functional class was the only prognostic factor identified. Prospective clinical trials focusing on this population of patients are warranted.
    Chest 03/2012; · 7.13 Impact Factor
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    ABSTRACT: Sarcoidosis is a multisystemic disease of unknown etiology characterized by a disproportionate Th1 granulomatous immune response in the organs involved. Plasmatic hypergammaglobulinemia and B cell accumulation in granulomatous lesions suggest the possible role of humoral immune responses in the pathogenesis of sarcoidosis. The purpose of this study is to describe B cell peripheral compartment in sarcoidosis. We analyzed blood B cell subsets and BAFF levels in 33 patients with chronic sarcoidosis (active sarcoidosis n = 18; inactive sarcoidosis n = 15) and 18 healthy donors. Active chronic sarcoidosis patients had significantly less circulating memory B cells (p<0.01), more transitional (p<0.01) and increased numbers of IL-10-producing regulatory B cells (p<0.05) compared with healthy donors and patients with inactive sarcoidosis. BAFF serum levels were significantly higher in patients with active sarcoidosis (p<0.01 versus healthy donors and inactive sarcoidosis patients) and strongly correlated with serum hypergammaglobulinemia (r = 0.53, p<0.01) and angiotensin converting enzyme levels (r = 0.61, p = <0.01). These data show that there is an altered B cell homeostasis in active sarcoidosis and suggest BAFF antagonist drugs as potential new treatments of this disease.
    PLoS ONE 01/2012; 7(8):e43588. · 3.53 Impact Factor
  • S Feuillet, A Tazi
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    ABSTRACT: Acute interstitial pneumonia (AIP) encompasses a spectrum of pulmonary disorders characterized by involvement of the lung interstitium and distal airways (bronchioles and alveoli). The onset of respiratory symptoms is acute, most often within two weeks. Most AIP take place de novo, but sometimes represent an acute exacerbation of chronic lung disease. The clinical presentation of AIP comprises rapidly progressive dyspnoea, associated sometimes with cough, fever, myalgia and asthenia. Chest radiography shows diffuse pulmonary opacities. The associated hypoxemia may be severe enough to cause acute respiratory failure. Underlying aetiologies are numerous and variable, particularly in relation to the underlying immune status of the host. Various histopathological entities may be responsible for AIP although diffuse alveolar damage is the predominant pattern. The diagnostic approach to a patient presenting with AIP is to try to determine the most likely underlying histopathological pattern and to search for a precise aetiology. It relies mainly on a meticulous clinical evaluation and accurate biological investigation, essentially guided by the results of bronchoalveolar lavage performed in an area identified by abnormalities on high resolution computed tomography of the lungs. Initial therapeutic management includes symptomatic measures, broad-spectrum antibiotic treatment adapted to the clinical context, frequently combined with systemic corticosteroid therapy.
    Revue des Maladies Respiratoires 06/2011; 28(6):809-22. · 0.50 Impact Factor
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    ABSTRACT: Multisystem autoimmune diseases occurring after allogeneic hematopoietic stem cell transplantation are infrequent, late-onset manifestations that resemble well-defined collagen vascular disorders. Because the lung is frequently involved in the course of connective tissue disorders, we focused on lung manifestations occurring in autoimmune diseases following allogeneic stem cell transplantation. In the present series, we report 6 patients with systemic lupus erythematous, mixed connective tissue disease, Sjögren syndrome, polymyositis, and ANCA-positive vasculitis who presented with a spectrum of pulmonary manifestations affecting the airways, lung parenchyma, and probably respiratory muscles. We identified 3 different histopathologic patterns of interstitial pneumonia consistent with the underlying autoimmune disorder: lymphocytic interstitial pneumonia and non-specific interstitial pneumonia in 2 patients with Sjögren syndrome and diffuse alveolar damage in 1 patient with ANCA-positive vasculitis. These lung manifestations had poor prognoses. Further studies are needed to determine the optimal therapy for these complications.
    Medicine 02/2011; 90(2):146-57. · 4.35 Impact Factor
  • Gastroenterology 01/2011; 140(5). · 12.82 Impact Factor
  • S. Feuillet, A. Tazi
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    ABSTRACT: Acute interstitial pneumonia (AIP) encompasses a spectrum of pulmonary disorders characterized by involvement of the lung interstitium and distal airways (bronchioles and alveoli). The onset of respiratory symptoms is acute, most often within two weeks. Most AIP take place de novo, but sometimes represent an acute exacerbation of chronic lung disease. The clinical presentation of AIP comprises rapidly progressive dyspnoea, associated sometimes with cough, fever, myalgia and asthenia. Chest radiography shows diffuse pulmonary opacities. The associated hypoxemia may be severe enough to cause acute respiratory failure. Underlying aetiologies are numerous and variable, particularly in relation to the underlying immune status of the host. Various histopathological entities may be responsible for AIP although diffuse alveolar damage is the predominant pattern. The diagnostic approach to a patient presenting with AIP is to try to determine the most likely underlying histopathological pattern and to search for a precise aetiology. It relies mainly on a meticulous clinical evaluation and accurate biological investigation, essentially guided by the results of bronchoalveolar lavage performed in an area identified by abnormalities on high resolution computed tomography of the lungs. Initial therapeutic management includes symptomatic measures, broad-spectrum antibiotic treatment adapted to the clinical context, frequently combined with systemic corticosteroid therapy.
    Revue Des Maladies Respiratoires - REV MAL RESPIR. 01/2011; 28(6):809-822.
  • European Respiratory Review 03/2010; 19(115):86-8.
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    ABSTRACT: Immunocompromised patients with influenza are at higher risk of pneumonia and death. However, risk factors for progression to pneumonia still need evaluation. Retrospective study in immunocompromised patients with influenza-related respiratory infections. Risk factors for pneumonia were identified by multivariable logistic regression. We identified 100 immunocompromised patients infected with influenza (68 hematological malignancies, 11 HIV, 21 iatrogenic immunosuppression). Immunofluorescence was positive in 95% of patients, mainly on nasopharyngeal aspirates (84%). Influenza A virus was involved in 80% of patients. Associated infection was documented in 34 patients. All patients presented with upper respiratory tract infection and 53 progressed to pneumonia. Thirty-two patients were critically ill, 11 received mechanical ventilation, and 10 died. All the patients who died had pneumonia. Patients with pneumonia were older (46y (36-63) vs. 33y (13-51), P=0.003) and more often had influenza A (89% vs. 70%, P=0.04) and associated infection (56% vs. 9%, P<0.0001). Factors independently associated with progression to pneumonia were influenza A (OR 5.54, 95% CI [1.16-26.47]) and hematological malignancies (OR 3.85, 95% CI [1.1-14.5]). In our cohort of hospitalized immunocompromised patients, influenza progresses to pneumonia in more than half the patients. Patients with hematological malignancies and influenza A infection are at higher risk for pneumonia and should be included in preemptive antiviral therapy trials.
    Respiratory medicine 02/2010; 104(7):1050-6. · 2.33 Impact Factor
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    ABSTRACT: Pulmonary Langerhans-cell histiocytosis in adults is a rare condition of unknown etiology characterized by the accumulation of Langerhans cells organized in granulomas involving the distal bronchioles and destroying their walls. It occurs in young subjects who smoke, with frequency peaking between 20 and 40 years. High-resolution thoracic CT is essential for diagnosis; in typical forms it shows a combination of nodules, cavitary nodules, thick-walled cysts, and thin-walled cysts. Diagnostic certainty requires a surgical lung biopsy, by videothoracoscopy, but only if a specialist considers it indicated. It is difficult to predict the disease course for any given patient. A prospective multicenter cohort study currently underway should provide more information about the natural history of this disease. Management is empirical, for efficacy has not been proved for any treatment. Stopping smoking is especially important to prevent the added development of chronic obstructive pulmonary disease (COPD), cardiovascular complications, or the onset of bronchopulmonary cancer, the frequency of which appears elevated in these patients. Oral corticosteroids are used to treat disease progression, especially in the symptomatic mainly nodular forms, but their efficacy for respiratory function has not been shown. Vinblastine, the reference treatment for multisystem forms of Langerhans-cell histiocytosis, is not indicated for pulmonary involvement in adults. Better knowledge of the pathogenic mechanisms involved in this condition should eventually make it possible to develop innovative treatment strategies. The creation of the national reference center for Langerhans-cell histiocytosis has given new momentum to clinical and pathophysiologic research on this orphan disease.
    La Presse Médicale. 01/2010; 39(1):107–115.
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    ABSTRACT: Pulmonary Langerhans-cell histiocytosis in adults is a rare condition of unknown etiology characterized by the accumulation of Langerhans cells organized in granulomas involving the distal bronchioles and destroying their walls. It occurs in young subjects who smoke, with frequency peaking between 20 and 40 years. High-resolution thoracic CT is essential for diagnosis; in typical forms it shows a combination of nodules, cavitary nodules, thick-walled cysts, and thin-walled cysts. Diagnostic certainty requires a surgical lung biopsy, by videothoracoscopy, but only if a specialist considers it indicated. It is difficult to predict the disease course for any given patient. A prospective multicenter cohort study currently underway should provide more information about the natural history of this disease. Management is empirical, for efficacy has not been proved for any treatment. Stopping smoking is especially important to prevent the added development of chronic obstructive pulmonary disease (COPD), cardiovascular complications, or the onset of bronchopulmonary cancer, the frequency of which appears elevated in these patients. Oral corticosteroids are used to treat disease progression, especially in the symptomatic mainly nodular forms, but their efficacy for respiratory function has not been shown. Vinblastine, the reference treatment for multisystem forms of Langerhans-cell histiocytosis, is not indicated for pulmonary involvement in adults. Better knowledge of the pathogenic mechanisms involved in this condition should eventually make it possible to develop innovative treatment strategies. The creation of the national reference center for Langerhans-cell histiocytosis has given new momentum to clinical and pathophysiologic research on this orphan disease.
    La Presse Médicale 12/2009; 39(1):107-15. · 0.87 Impact Factor
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    ABSTRACT: Although it has not been evaluated prospectively, the usual treatment for obstructive airway disease after allogeneic hematopoietic stem cell transplantation, which is related to graft versus host disease, consists of intensification of systemic immunosuppressive therapy. However, this treatment has a limited efficacy and is associated with a significant number of serious adverse effects, particularly infectious. Alternative treatments are therefore required. Recently, clinical and functional improvement in patients with obstructive airway disease following allogenic hematopoietic stem cell transplantation treated with inhaled combined Budesonide/Formoterol has been retrospectively reported. The present prospective multi-centered, randomised double-blind trial is designed to evaluate the efficacy of the combination of budesonide/formoterol (400/12 microg 2 inhalations bid) versus placebo in patients with moderate to severe obstructive airway disease, not requiring initiation or intensification of systemic immunosuppressive therapy for extra thoracic graft versus host disease. The primary outcome will be the improvement of FEV1 at 1 month of treatment. The secondary outcomes will be the clinical and functional pulmonary improvements at 6 months. The leading hypothesis is that patients treated with inhaled combined Budesonide/Formoterol will show significant improvement of their clinical symptoms and pulmonary functional testing.
    Revue des Maladies Respiratoires 09/2009; 26(7):794-800. · 0.50 Impact Factor
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    ABSTRACT: A. Bergeron, K. Chagnon, S. Feuillet, S. Chevret, A. Tazi Background Although it has not been evaluated prospectively, the usual treatment for obstructive airway disease after allogeneic hematopoietic stem cell transplantation, which is related to graft versus host disease, consists of intensification of systemic immunosuppressive therapy. However, this treatment has a limited efficacy and is associated with a significant number of serious adverse effects, particularly infectious. Alternative treatments are therefore required. Recently, clinical and functional improvement in patients with obstructive airway disease following allogenic hematopoietic stem cell transplantation treated with inhaled combined Budesonide/Formoterol has been retrospectively reported. Methods The present prospective multi-centered, randomised double-blind trial is designed to evaluate the efficacy of the combination of budesonide/formoterol (400/12µg 2 inhalations bid) versus placebo in patients with moderate to severe obstructive airway disease, not requiring initiation or intensification of systemic immunosuppressive therapy for extra thoracic graft versus host disease. The primary outcome will be the improvement of FEV1 at 1 month of treatment. The secondary outcomes will be the clinical and functional pulmonary improvements at 6 months. Expected Results The leading hypothesis is that patients treated with inhaled combined Budesonide/Formoterol will show significant improvement of their clinical symptoms and pulmonary functional testing.
    Revue Des Maladies Respiratoires - REV MAL RESPIR. 01/2009; 26(7):794-800.
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    ABSTRACT: The Epstein-Barr virus (EBV) associated Post-Transplant Lymphoproliferative Disorders (PTLD) are increasingly recognized as a fatal complication of hematological stem cell transplantation (HSCT). Thoracic involvement, that may be isolated or part of a disseminated disease, usually encompasses pulmonary nodules or masses and mediastinal lymph node enlargement. The current case study presents 2 patients who underwent HSCT, one allogenic and the other autologous, who developed an exceptional endobronchial EBV related PTLD. The first patient had a fleshy white endobronchial mass resulting in a right upper lobe atelectasis and the second had an extensive necrotising mucosa from trachea to both basal bronchi without any significant change of lung parenchyma on the CT scan. In both cases, the diagnosis was made by bronchial biopsies. Physicians should be aware of an endobronchial pattern of EBV associated PTLD after HSCT to permit quick diagnosis and therapeutic intervention.
    Clinical Medicine: Case Reports 01/2009; 2:11-5.
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    ABSTRACT: Non infectious pulmonary complications which frequently occur in the late follow-up of haemopoietic stem cell transplant (HSCT) recipients account for an increase in mortality and morbidity. Different histological entities have been described among which bronchiolitis obliterans is the most common. Because of the absence of prospective epidemiological studies and the difficulties in obtaining surgical lung biopsies from these frail patients little is known about these conditions. Although their pathogenesis is poorly understood they probably result from a chronic pulmonary graft versus host disease (GVHD). The introduction of or increase in systemic immunosuppressive treatment, usually indicated for controlling extra-thoracic manifestations of GVHD, may lead to the resolution of an organising pneumonia but is usually ineffective in the treatment of bronchiolitis obliterans. Current prospective cohort studies together with randomised prospective studies evaluating more targeted treatments should help determine the frequency, the risk factors and the precise characteristics of the different entities of late non-infectious pulmonary diseases following HSCT and should also improve their management. Furthermore, the recent demonstration of lung abnormalities in animal models of chronic GVHD, similar to those observed in humans, should allow a better understanding of the pathogenesis. The prevalence of these diseases is increasing throughout the world. More precise analysis, the identification of risk factors and study of the pathophysiological mechanisms involved should allow better understanding and management than at present.
    Revue des Maladies Respiratoires 03/2008; 25(2):173-83. · 0.50 Impact Factor
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    ABSTRACT: IntroductionNon infectious pulmonary complications which frequently occur in the late follow-up of haemopoietic stem cell transplant (HSCT) recipients account for an increase in mortality and morbidity. Different histological entities have been described among which bronchiolitis obliterans is the most common.Background Because of the absence of prospective epidemiological studies and the difficulties in obtaining surgical lung biopsies from these frail patients little is known about these conditions. Although their pathogenesis is poorly understood they probably result from a chronic pulmonary graft versus host disease (GVHD). The introduction of or increase in systemic immunosuppressive treatment, usually indicated for controlling extra-thoracic manifestations of GVHD, may lead to the resolution of an organising pneumonia but is usually ineffective in the treatment of bronchiolitis obliterans.ViewpointsCurrent prospective cohort studies together with randomised prospective studies evaluating more targeted treatments should help determine the frequency, the risk factors and the precise characteristics of the different entities of late non-infectious pulmonary diseases following HSCT and should also improve their management. Furthermore, the recent demonstration of lung abnormalities in animal models of chronic GVHD, similar to those observed in humans, should allow a better understanding of the pathogenesis.Conclusion The prevalence of these diseases is increasing throughout the world. More precise analysis, the identification of risk factors and study of the pathophysiological mechanisms involved should allow better understanding and management than at present.
    Revue des Maladies Respiratoires 02/2008; 25(2):173-183. · 0.50 Impact Factor
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    ABSTRACT: Bronchiolitis obliterans (BO) is the most frequent late-onset noninfectious pulmonary complication following an allogeneic hematologic stem cell transplantation attributed to chronic lung graft-versus-host disease. Its management is usually a great challenge when considering both the diagnosis and the treatment. The definite diagnosis relies on histological examination; however, lung biopsies are rarely available. The diagnosis must then be retained for converging arguments based on clinical and radiological features and pulmonary function testing. However, clinical, radiological and functional characteristics of patients with BO may be various, leading to difficulties in diagnosis. Furthermore, the treatment of BO is currently a controversial issue, and its evaluation is limited by not knowing the natural history. Herein, through a demonstrative case study, we discuss the diagnostic and therapeutic approach for a patient with a biopsy-proven BO following allogeneic stem cell transplantation.
  • Revue des Maladies Respiratoires. 29:A22–A23.
  • Revue des Maladies Respiratoires. 29:A40.