Claire Danel

Characteristics of sirolimus-associated interstitial pneumonitis in renal transplant patients.

Background. Sirolimus, a promising new immunosuppressive drug for organ transplantation, is currently associated with side effects, such as thrombocytopenia and hyperlipidemia. Methods. Eight renal transplant recipients, who developed unexplained interstitial pneumonitis during sirolimus therapy, were extensively re-screened for all causes of pneumonitis. Results. Interstitial pneumonitis was constantly characterized by bilateral interstitial infiltrates on chest x-rays and lung computed tomography scans, with marked general symptoms in all patients but one. Bronchoalveolar lavage (BAL) disclosed lymphocytic alveolitis (mainly of the CD4 type) in seven patients and alveolar hemorrhage in one. Transbronchial lung biopsies, performed in two patients, showed bronchiolitis obliterans with organizing pneumonia combined with lymphocytic interstitial pneumonitis. Pulmonary infections were ruled out by specific stainings and cultures of BAL, bronchial aspirates, and blood cultures. After the elimination of all possible causes, sirolimus-induced pneumonitis was considered probable. Discontinuation of sirolimus in seven cases and dose reduction in the remaining case dramatically improved clinical and radiological status within a few weeks and led to complete resolution within 3 months. Conclusions. Sirolimus is very probably responsible for interstitial pneumonitis on the following grounds: (a) occurrence of pneumonitis during sirolimus therapy; (b) absence of any other causes; and (c) resolution within 3 months of sirolimus discontinuation or dose reduction. Sirolimus should now be added to the list of possible causes of pulmonary complications after renal transplantation. Discontinuation or dose reduction of sirolimus led to complete and lasting resolution of symptoms.

Smoking and interstitial lung disease. The effect of cigarette smoking on the incidence of pulmonary histiocytosis X and sarcoidosis.

: Cigarette smoking produces marked alterations in the lung parenchyma and in the population of immune and inflammatory cells present in the lower respiratory tract. These cigarette-induced changes appear to influence the incidence of two different interstitial lung diseases, histiocytosis X and sarcoidosis. Smoking is a strong risk factor for the development of pulmonary histiocytosis X, since the incidence of smoking is very high among patients with histiocytosis X: 90% of the patients with histiocytosis X were smokers; 46% of the controls were smokers (p less than .001). In contrast, smoking appears to reduce the incidence of sarcoidosis: 31% of the patients with sarcoidosis were smokers (p less than .05 compared to controls). In an effort to understand how cigarette smoking influences the incidence of these two disorders, we compared the numbers and types of immune and inflammatory cells recovered by bronchoalveolar lavage from nonsmoking and smoking controls and patients with histiocytosis X and sarcoidosis. Although nonsmoking patients with histiocytosis X did not have a significant increase in the number of alveolar macrophages recovered by lavage (p greater than .2 compared to normals), smoking patients had an increase in the number of alveolar macrophages similar to that observed in the control population. In contrast, the number of macrophages recovered from patients with sarcoidosis who smoked was considerably less than that observed in normal smokers (p less than .05 comparing patients with sarcoidosis and controls who smoked 1-20 cigarettes/day). This difference in the intensity of the cigarette-induced macrophage alveolitis observed in the two patient groups may be important in explaining the opposite effects of cigarette smoking on the incidence of histiocytosis X and sarcoidosis.

Bronchoalveolar Lavage in Sarcoidosis

Bronchoalveolar lavage (BAL) was performed in 1,188 patients suffering from sarcoidosis. After technical considerations, the authors analyze the results of BAL from a practical point of view concerning its value for the diagnosis of sarcoidosis and its prognostic value and its value for the selection of therapy, particularly for the decision as to steroid treatment. BAL helps in the diagnosis of sarcoidosis, but is not specific enough to provide this diagnosis on its own. The persistence of high alveolar lymphocytosis within the first year of evolution is strongly correlated with nonrecovery from pulmonary sarcoidosis at 2 years and thus with the evolution towards a chronic phase of the disease. On the other hand, BAL can provide basic information for a better understanding of the disease and permits immunocompetent cells and soluble factors to be recovered from the lung, which is useful for immunological studies.

Intérêt des biopsies transbronchiques et chirurgicales dans la prise en charge des pneumopathies interstitielles diffuses

Resume L’interpretation des prelevements pulmonaires dans le cadre des pneumopathies interstitielles diffuses (PID) est souvent difficile et requiert une expertise particuliere du pathologiste : en effet, dans la majorite des cas, et contrairement a la pathologie tumorale, le diagnostic de ces affections n’est pas purement pathologique et necessite toujours une correlation avec les donnees cliniques et radiologiques. La BTB et le LBA restent la premiere etape diagnostique dans l’investigation d’une PID. Dans un bon nombre de cas, l’association de ces deux techniques peu deleteres est suffisante pour orienter le diagnostic, ou meme l’affirmer, et reduire ainsi les indications chirurgicales qui sont devenues exceptionnelles. Apres un rappel sur la necessite d’une prise en charge rigoureuse de ces prelevements endoscopiques ou chirurgicaux et sur les difficultes specifiques de l’interpretation des lesions qui doivent etre connues des cliniciens, nous traiterons de la contribution de l’examen anatomopathologique dans le diagnostic et la surveillance de l’evolution et des complications des PID, en particulier chez les sujets traites, en insistant sur la necessite d’une collaboration etroite entre les differents intervenants pour optimiser l’approche diagnostique et la prise en charge de ces affections.

Contribution du lavage bronchoalvéolaire à la prise en charge des pneumopathies interstitielles diffuses

Resume Le lavage bronchoalveolaire (LBA) constitue un moyen peu invasif d’exploration du poumon distal, permettant le recueil du materiel cellulaire libre et du materiel acellulaire presents dans l’alveole. Il s’est impose au cours des deux dernieres decennies comme outil fondamental du diagnostic positif des pneumopathies infiltratives diffuses (PID), mais aussi et surtout de leur diagnostic differentiel. En effet, son apport a ete spectaculaire dans le diagnostic des infections pulmonaires, en particulier chez le patient immunodeprime. Dans la pathologie interstitielle non infectieuse, a l’oppose, la contribution diagnostique du LBA est limitee par l’absence de specificite des profils cellulaires observes. Elle reste cependant fondamentale dans le diagnostic differentiel des pneumopathies interstitielles idiopathiques, permettant d’exclure avec une grande fiabilite un certain nombre d’affections en particulier infectieuses et tumorales. Il represente de plus dans ce cadre un element de poids dans l’evaluation d’une possible pneumopathie iatrogene. En transformant l’abord diagnostique des PID, il a considerablement reduit les indications de biopsie pulmonaire chirurgicale.

Maladie de Castleman médiastinale : mise au point

Castleman disease is a rare lymph nodes disease whose name covers different clinical presentations. The most frequent histology is the hyaline vascular localized form. In this case, Castleman disease occurs in young adults, and is localized to the mediastinum in one third of the cases. The disease is often asymptomatic, but paraneoplasic pemphigus has been described. The management of this form of Castleman disease is based on complete surgical resection. Perioperative immunomodulating treatments may be discussed in case of paraneoplasic pemphigus, mostly when affecting the bronchial tree.