Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
AIM: To describe the main characteristics and the treatment of cryptococcosis in patients with sarcoidosis. DESIGN: Multicenter study including all patients notified at the French National Reference Center for Invasive Mycoses and Antifungals. METHODS: Retrospective chart review. Each case was compared with two controls without opportunistic infections. RESULTS: Eighteen cases of cryptococcosis complicating sarcoidosis were analyzed (13 men and 5 women). With 2749 cases of cryptococcosis registered in France during the inclusion period of this study, sarcoidosis accounted for 0.6% of all the cryptococcosis patients and for 2.9% of the cryptococcosis HIV-seronegative patients. Cryptococcosis and sarcoidosis were diagnosed concomitantly in four cases; while sarcoidosis was previously known in 14/18 patients, including 12 patients (67%) treated with steroids. The median rate of CD4 T cells was 145 per mm(3) (range: 55-1300) and not related to steroid treatment. Thirteen patients had cryptococcal meningitis (72%), three osteoarticular (17%) and four disseminated infections (22%). Sixteen patients (89%) presented a complete response to antifungal therapy. After a mean follow-up of 6 years, no death was attributable to cryptococcosis. Extra-thoracic sarcoidosis and steroids were independent risk factors of cryptococcosis in a logistic regression model adjusted with the sex of the patients. CONCLUSIONS: Cryptococcosis is a significant opportunistic infection during extra-thoracic sarcoidosis, which occurs in one-third of the cases in patients without any treatment; it is not associated to severe CD4 lymphocytopenia and has a good prognosis.
ISSN: 1460-2725

hal-00873410
https://hal.archives-ouvertes.fr/hal-00873410
DOI : 10.1093/qjmed/hct052
PUBMED : 23515400

Éditeur(s) : HAL CCSD Elsevier Masson
Résumé : International audience
INTRODUCTION: Light chain deposition disease is a rare clinical entity characterized by deposition of monoclonal immunoglobulin light chains in organs. The kidneys are almost always affected, while the lung manifestations that have been reported, including nodular or diffuse disease, especially cystic lesions, are unusual. CASE REPORT: We report the case of a 60-year-old man with a diffuse infiltrative lung disease characterized by numerous apical cysts. The diagnosis of light chain deposition cystic lung disease was obtained by surgical lung biopsy. Light chain deposits in the salivary glands were the only extrapulmonary manifestation. Despite 12 chemotherapy cycles, the patient's lung function and radiological appearances worsened. CONCLUSION: This is the fourth case describing a cystic lung disease due to light chain deposition in the literature. It highlights the need for comprehensive investigations so as not to miss this rare cause of cystic lung disease, which appears to be related to a primary pulmonary lymphoproliferative disorder. The only treatment that appears to be effective is lung transplantation.
ISSN: 0761-8425

hal-00873356
https://hal.archives-ouvertes.fr/hal-00873356
https://hal.archives-ouvertes.fr/hal-00873356/document
https://hal.archives-ouvertes.fr/hal-00873356/file/DA_pots_chaines_lA_gA_res_non_amyloides_version_finale.pdf
DOI : 10.1016/j.rmr.2013.02.003

Éditeur(s) : HAL CCSD Elsevier Masson
Résumé : National audience
Introduction Les télomérases sont les enzymes assurant la synthèse des télomères, séquences d’ADN essentiels dans la protection des chromosomes. Les mutations des télomérases sont responsables, entre autres, d’anomalies hématologiques, pulmonaires (fibrose pulmonaire idiopathique) et hépatiques. Il n’y a que peu de données dans la littérature concernant les résultats des transplantations pulmonaires chez ces patients mutés. Cas clinique Nous rapportons le cas d’un jeune homme de 39 ans, souffrant de syndrome myélodysplasique associé à une fibrose pulmonaire, permettant de poser le diagnostic de téloméropathie (mutation de la sous-unité ARN ou TERC ; r.182delG, pseudoknot area). L’insuffisance médullaire est sévère : leucopénie à 1,3 G/L dont 0,54 G/L de PNN, anémie macrocytaire (Hb à 10,3 g/dL ; VGM à 120 fL) et thombopénie à 27 G/L. Le syndrome restrictif est également sévère avec une CPT à 60 % et une CVF à 82 % de la valeur prédite (% pred). Il s’associe à une altération de la membrane alvéolo-capillaire (DLCO corrigée sur l’hémoglobine à 31 % pred). Le patient a été récusé à la fois pour la transplantation médullaire et pour la transplantation pulmonaire malgré son jeune âge. La prise en charge est donc palliative : réhabilitation respiratoire, oxygénothérapie, puis nintedanib. Discussion Dans la littérature, les transplantations médullaires chez les patients présentant une mutation des télomérases s’associent à une dégradation de la fonction respiratoire, en lien avec la toxicité des traitements immunosuppresseurs, même en l’absence d’atteinte pulmonaire initiale. Par ailleurs, les complications infectieuses et hématologiques post-transplantations pulmonaires chez ces patients mutés semblent plus fréquentes et nécessitent souvent une adaptation des traitements anti-rejets. Ces risques post-transplantations paraissent plus importants en présence d’une thrombopénie sévère préopératoire. Ces données sont cependant limitées à trois études rétrospectives de petites tailles. Au total, ce jeune patient a été jugé inéligible à la transplantation médullaire et à la transplantation pulmonaire, respectivement à cause de l’insuffisance respiratoire et de l’insuffisance médullaire. Il est émis l’hypothèse que l’allègement de la thérapie immunosuppressive pourrait améliorer le devenir des patients mutés transplantés, sans majorer le risque de rejet, illustrant le concept d’immunosénescence. Mais cette hypothèse reste à être validée. Ce cas clinique souligne l’importance de reconnaître les signes évocateurs de téloméropathie, dans la mesure où le diagnostic impacte la prise en charge de la fibrose pulmonaire
ISSN: 0761-8425

hal-01334065
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01334065
DOI : 10.1016/j.rmr.2016.04.018

Éditeur(s) : HAL CCSD Elsevier Masson
Résumé : International audience
INTRODUCTION: Hydroxyurea is an antimetabolite drug used in the treatment of myeloproliferative disorders. Common adverse effects include haematological, gastrointestinal cutaneous manifestations, and fever. Hydroxyurea-induced pneumonitis is unusual. CASE REPORT: A female patient was treated with hydroxyurea for polycythemia vera. She was admitted 20 days after commencing treatment with a high fever, productive cough, clear sputum and nausea. A chest CT-scan showed diffuse ground-glass opacities. Microbiological investigations were negative. The symptoms disappeared a few days after discontinuation of the drug and rechallenge led to a relapse of symptoms. CONCLUSION: Our case and 15 earlier cases of hydroxyurea-induced pneumonitis are reviewed. Two patterns of this disease may exist: an acute febrile form occurring within 1 month of introduction of hydroxyurea and a subacute form without fever. Even if uncommon, one should be aware of this complication of hydroxyurea.
Revue des Maladies Respiratoires

hal-01072996
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01072996
DOI : 10.1016/j.rmr.2013.09.001
PUBMED : 24878159

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
OBJECTIVE: The WEGENT trial and other short-term studies suggested that azathioprine or methotrexate could effectively maintain granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) remission. Whether differences in relapse or adverse event rates would appear after discontinuation of those 2 maintenance regimens and longer follow-up remains unknown. METHODS: Long-term outcomes for the patients enrolled in the WEGENT trial were analyzed according to their randomization group. Parameters at trial entry were evaluated as potential prognostic factors for death, relapse or damage in multivariate models. RESULTS: Data were returned for 88.8% of the 126 original participants. Median [95% confidence interval] followup was 11.9 [11.3-12.5] years. For the azathioprine and methotrexate arms, respectively, the 10-year overall survival rates were 75.1% [64.8-86.9] and 79.9% [70.3-90.8] (P = 0.56), and relapse-free survival rates 26.3% [17.3-40.1] and 33.5% [23.5-47.7] (P = 0.29). No between-arm differences were observed for relapse, adverse events, damage, survival rates without severe side effects and survival rates without relapse and severe side effects. Considering only the 97 GPA patients, no between-arm survival differences were observed. Relapse-free survival was shorter for GPA than MPA patients but the multivariate analysis retained anti-PR3-ANCA-positivity, and not GPA, as being independently associated with relapse. CONCLUSION: This long-term analysis confirms that azathioprine and methotrexate are comparable options for maintaining GPA or MPA remission. Despite good overall survival, relapses, adverse events and damage remain matters of concern and further studies are needed to reduce them.
ISSN: 2326-5205

hal-01217989
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01217989
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01217989/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01217989/file/Long-term%20outcomes%20of%20the%20WEGENT%20trial_accepted.pdf
DOI : 10.1002/art.39450

Éditeur(s) : HAL CCSD Elsevier Masson
Résumé : International audience
Alveolar proteinosis (AP) is a rare disease characterized by alveolar accumulation of surfactant components, which impairs gas exchange. AP is classified into three groups: auto-immune AP defined by the presence of plasma autoantibodies anti-GM-CSF, the most frequent form (90 % of all AP); secondary AP, mainly occurring as a consequence of haematological diseases, or following on from toxic inhalation or infections, and genetic AP, which affects almost exclusively children. AP diagnosis is suspected where chest CT-scan demonstrates interstitial lung disease with a crazy paving aspect; and confirmed by bronchoalveolar lavage, which has a milky appearance and contains periodic acid Schiff positive proteinaceous alveolar deposits. The use of surgical lung biopsy to confirm AP is less frequent nowadays. In this context, positive antibodies against GM-CSF indicates an auto-immune etiology of the AP. Concerning management, whole lung lavage is the gold standard therapy. In refractory AP, new treatments are available such as subcutaneous or inhaled GM-CSF supplementation, or rituximab infusions. The clinical course is unpredictable. Spontaneous improvement or even cure can occur, and the 5-year actuarial survival is 95 %. The most frequent complications are infectious etiology.
La protéinose alvéolaire pulmonaire (PAP) est une maladie rare caractérisée par l’accumulation alvéolaire de composants du surfactant qui gêne les échanges gazeux. Les PAP sont séparées en trois groupes : les PAP auto-immunes caractérisées par la présence d’anticorps sériques anti-GM-CSF qui sont les plus fréquentes ; les PAP secondaires à une maladie sous-jacente, le plus souvent hématologique, mais aussi à l’inhalation de toxiques et à des infections ; enfin, les PAP d’origine génétique. Le diagnostic de PAP est évoqué sur le scanner thoracique avec une pneumopathie infiltrante diffuse ayant un aspect classique de crazy paving, puis confirmé par l’aspect laiteux du lavage bronchoalvéolaire, et la présence de matériel lipoprotéinacé PAS positif. La confirmation du diagnostic de PAP par biopsie pulmonaire chirurgicale est désormais rarement nécessaire. La positivité des anticorps sériques anti-GM-CSF signe le caractère auto-immun de la maladie. Le traitement de référence des PAP auto-immunes est le « grand lavage pulmonaire thérapeutique ». En cas de maladie réfractaire, d’autres traitements sont disponibles, tels que le GM-CSF en injection sous-cutanée ou en aérosol et le rituximab. L’évolution de la maladie est imprévisible. Une évolution spontanément favorable ou même une guérison spontanée peuvent survenir et la survie actuarielle à 5 ans est de 95 %. Les principales complications sont infectieuses.
ISSN: 0761-8425

hal-01085907
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01085907
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01085907/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01085907/file/Prot%C3%A9inose%20alv%C3%A9olaire%20pulmonaire_accepted.pdf
DOI : 10.1016/j.rmr.2014.08.009

Éditeur(s) : HAL CCSD
Résumé : International audience
Idiopathic pulmonary fibrosis (IPF) is the most frequent chronic idiopathic interstitial pneumonia in adults. The management of rare diseases in France has been organised by a national plan for rare diseases, which endorsed a network of expert centres for rare diseases throughout France. This article is an overview of the executive summary of the French guidelines for the management of IPF, an initiative that emanated from the French National Reference Centre and the Network of Regional Competence Centres for Rare Lung Diseases. This review aims at providing pulmonologists with a document that: 1) combines the current available evidence; 2) reviews practical modalities of diagnosis and management of IPF; and 3) is adapted to everyday medical practice. The French practical guidelines result from the combined efforts of a coordination committee, a writing committee and a multidisciplinary review panel, following recommendations from the Haute Autorité de Santé. All recommendations included in this article received at least 90% agreement by the reviewing panel. Herein, we summarise the main conclusions and practical recommendations of the French guidelines.
Eur Respir Rev

hal-01063982
https://hal.archives-ouvertes.fr/hal-01063982
DOI : 10.1183/09059180.00001814
PUBMED : 24881074

Éditeur(s) : HAL CCSD Elsevier Masson
Résumé : CCBY
National audience
ISSN: 0761-8425

hal-01117879
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01117879
PUBMED : 24314711
DOI : 10.1016/j.rmr.2013.09.007

Éditeur(s) : HAL CCSD Elsevier Masson
Résumé : International audience
Antisynthetase syndrome is an inflammatory myopathy frequently associated with pulmonary manifestations, especially interstitial lung diseases, and uncommonly pulmonary hypertension. In the context of a suggestive clinical and radiological picture, positive anti-RNA synthetase antibodies confirm the diagnosis. Anti-Jo1, anti-PL7, and anti-PL12 antibodies are the more commonly encountered. The presence of a number of extra-thoracic manifestations in association with pulmonary disease may suggest the diagnosis. These include: myalgia or muscular deficit, Raynaud's phenomenon, polyarthritis, fever, mechanics hands. Serum creatine kinase levels are usually increased. Electromyogram, muscular magnetic resonance imaging or muscle pathology are not mandatory to make the diagnosis. There is a high variability in symptoms and severity, between patients but also during the course of the disease in the same patient. The presence of an interstitial lung disease is a major prognostic factor and an indication for more intensive treatment, principally with systemic corticosteroids with or without immunosuppressive drugs. Improving respiratory physicians’ knowledge of this disease, which is often revealed by its pulmonary manifestations, should help diagnosis, therapeutic management, and possibly prognosis.
Le syndrome des antisynthétases correspond à une myopathie inflammatoire fréquemment associée à une atteinte pulmonaire, surtout parenchymateuse (pneumopathie infiltrante diffuse) et plus rarement vasculaire (hypertension pulmonaire). Devant un tableau clinique et radiologique évocateur, la présence d’anticorps anti-ARNt synthétases signe le diagnostic. Les plus fréquents de ces auto-anticorps sont les anti-Jo1, les anti-PL7 et les anti-PL12. De nombreuses manifestations cliniques extrathoraciques associées à l’atteinte pulmonaire peuvent orienter le diagnostic : myalgies ou déficit musculaire, phénomène de Raynaud, polyarthrite, fièvre et « mains de mécaniciens ». Une augmentation des créatine-phospho-kinases est quasi constante. Le recours à l’électromyogramme, à l’imagerie musculaire par résonance magnétique ou à l’histologie n’est pas systématique. Néanmoins, il existe une grande variabilité des symptômes et de leur sévérité d’un patient à l’autre ou au long de l’évolution de la maladie. L’atteinte pulmonaire est un facteur pronostic majeur et incite à traiter de manière intensive les patients, principalement par corticothérapie systémique, voire d’emblée par association corticoïdes et immunosuppresseurs. Mieux connaître cette pathologie qui est souvent de révélation pneumologique permettrait d’améliorer le diagnostic et la prise en charge thérapeutique, voire même le pronostic.
ISSN: 0761-8425

hal-01085369
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01085369
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01085369/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01085369/file/Manifestations%20pulmonaires%20du%20syndrome%20des%20antisynth%C3%A9tases_accepted.pdf
DOI : 10.1016/j.rmr.2014.07.013

Éditeur(s) : HAL CCSD Elsevier Masson
Résumé : International audience
Introduction: Hydroxyurea is an antimetabolite widely used in the treatment of myeloproliferative diseases. Usual side effects are mainly hematological, gastrointestinal, neurological disorders and induced-fevers. More rarely, hydroxyurea-induced pneumonitis are reported. Case report: We report a case of a patient treated for polycythemia vera. She was admitted 20 days after introduction of hydroxyurea for a high fever, productive cough and clear sputum associated with nausea. Chest CT-scan found diffuse bilateral ground-glass opacities. The microbiological investigations were negative. Symptoms disappeared few days after discontinuation of treatment. Its reintroduction led to recurrence of symptoms. Conclusion: This additional case completes the 15 cases of hydroxyurea-induced pneumonitis described in the literature. Two forms of this disease seem to exist: an acute form with fever occurring in the month following introduction of hydroxyurea; and a chronic form without fever. Even if it is uncommon, pulmonologists should be aware of this complication.
ISSN: 0761-8425

hal-00916333
https://hal.archives-ouvertes.fr/hal-00916333
https://hal.archives-ouvertes.fr/hal-00916333/document
https://hal.archives-ouvertes.fr/hal-00916333/file/hydroxyurA_e_version_rA_visA_e.pdf
DOI : 10.1016/j.rmr.2013.09.001