Fulminant Pneumocystis carinii pneumonia in 4 patients with dermatomyositis.

Between 1989 and 1996, 4 cases of Pneumocystis carinii pneumonia (PCP) were observed in patients seronegative for the human immunodeficiency virus who were receiving corticosteroid therapy for dermatomyositis in our institution. These cases were considered unusual in light of the short delay of their onset after initiation of immunosuppressive therapy and their fulminant course: 3 of these patients died of PCP occurring during the first month of treatment with prednisone. In all 4 patients lymphopenia was observed before the initiation of corticosteroid treatment and low CD4 and CD8 cell counts were evident at the time of PCP. These observations support the view of an increase in both the severity and incidence of PCP in patients without human immunodeficiency virus infection and question the need for a primary prophylaxis in patients with connective tissue diseases receiving high-dose corticosteroid therapy.

Evidence for a cytotoxic T-lymphocyte alveolitis in human immunodeficiency virus-infected patients.

A T8 lymphocyte alveolitis occurs in HIV-positive patients, even in the absence of any lung infections or tumors. Using the monoclonal antibody (MAb) D44, the CD8+ T cells can be further subdivided into two functional subsets of cytotoxic T lymphocytes (CTL; CD8+, D44+) and suppressor T cells (CD8+, D44-). A dual fluorescence analysis of alveolar and peripheral lymphocytes has been used in HIV-positive patients without lung infections or tumors to reveal a dramatic increase in alveolar T8 lymphocytes (83%), compared to peripheral values (52%), which was mainly composed (89%) of CD8+ D44+ CTLs. Functional studies confirmed the cytolytic activity of these phenotypically defined alveolar CTLs on autologous alveolar macrophages used as target cells, excluding a natural killer-like activity. An immuno-enzyme analysis concomitantly revealed the co-expression of the p18 HIV antigen and the CD4 molecule on the autologous alveolar macrophages. These data suggest that CTL alveolitis occurs during HIV infection and is directed against HIV-infected alveolar macrophages which are presumably the targets of the locally recruited lung CTLs.

Leukocyte migration inhibition in amiodarone-associated pneumonitis.

Amiodarone-associated pneumonitis is now a well-known clinical entity, but the mechanism for the induction of the pulmonary disease is ill defined. In four patients with this disorder, evidence was obtained for elaboration of a lymphokine, leukocyte inhibitory factor (LIF), by peripheral blood lymphocytes after incubation with amiodarone in the direct leukocyte migration inhibition test. Control lymphocytes from normal subjects, as well as from patients receiving amiodarone but without pneumonitis, failed to elaborate LIF in the presence of the drug in this test. This production of LIF suggests that pneumonitis associated with amiodarone therapy is also associated with a specific cellular immune response to the drug.

Leukocyte migration inhibition in methotrexate-induced pneumonitis. Evidence for an immunologic cell-mediated mechanism.

Methotrexate-induced pneumonitis is a well-known clinical entity, but the mechanism for the induction of the pulmonary disease is ill defined. In three patients with this disorder, evidence was obtained for elaboration of a lymphokine, leukocyte inhibitory factor (LIF), by peripheral blood lymphocytes after incubation with methotrexate (MTX) in the direct leukocyte migration inhibition test. Control lymphocytes from normal subjects, as well as from patients receiving methotrexate but without pneumonitis, failed to elaborate LIF in the presence of the drug in this test. Along with these results, we obtained bronchoalveolar lavage (BAL) cell data displaying high grade lymphocyte alveolitis with a lymphocyte subset inverted ratio. This production of LIF suggests that pneumonitis associated with methotrexate therapy is also associated with a specific cellular immune response to the drug.

Pleural T-lymphocyte subsets in amiodarone-associated pleuropneumonitis.

Two male patients presented with lung disorders with all the characteristics of amiodarone-related pneumonitis. Bilateral exudative pleural effusions were associated with pneumonitis. High lymphocytosis was present in the pleural fluid with a ratio of T-lymphocyte subsets close to that found in peripheral blood; in the blood T-lymphocyte subset ratio was nearly normal. By contrast, and as is usual in similar cases, lymphocytic alveolitis with T-lymphocyte subset imbalance was found in bronchoalveolar lavage fluid. These findings, never published so far to our knowledge, would favor a compartmentalization of the immune response inside the lung.

Amiodarone-induced hypersensitivity pneumonitis. Evidence of an immunological cell-mediated mechanism.

Interstitial pneumonitis developed in a patient who had received a cumulative dose of 985 g of amiodarone in nine years. No other cause for pneumonitis was found. The following findings favor an immunologic mechanism of hypersensitivity due to amiodarone: positive skin and basophil degranulation tests with amiodarone; lymphocytosis and inverted ratio of helper/suppressor T lymphocytes in bronchoalveolar lavage fluid; secretion of leukocyte inhibitory factor, as shown by the inhibition of migration of peripheral blood leukocytes; and positive lymphoblastic transformation in the presence of amiodarone.

Intrathoracic Kaposi's sarcoma. CT findings.

AIM: To describe the thin CT scans findings in AIDS patients with intrathoracic Kaposi's sarcoma (KS). MATERIAL AND METHODS: Fifty-three CT scans of patients with KS were retrospectively reviewed. The diagnosis of intrathoracic KS was established histologically (n = 17) or on the association of skin KS and the visualization of characteristic endobronchial lesions (n = 36). CT scans were performed with thin slices (2 mm) obtained at 10-mm intervals, and a 512 x 512 reconstruction matrix. No patients had Pneumocystis carinii pneumonia within the 3 months preceding the CT scan examination. RESULTS: Numerous nodules (n = 42), tumoral masses (n = 28), bronchovascular pathways thickening (n = 35), and pleural effusions (n = 28) were the most frequent patterns. Septal lines (n = 15), ground-glass opacities (n = 3), and mediastinal adenopathies (n = 8) were not frequent. CONCLUSION: Numerous nodules, tumoral masses, bronchovascular pathways thickening, and bilateral pleural effusions were the main signs of intrathoracic KS; their association (66%) is very characteristic. An opportunistic infection or mycobacteriosis must be sought if the thin CT scans reveal ground-glass opacities and/or mediastinal adenopathies.

Leukocyte migration inhibition in propranolol-induced pneumonitis. Evidence for an immunologic cell-mediated mechanism.

About 20 cases of beta blocker-associated pneumonitis have been published in the mid-70s, and a case of interstitial pneumonitis has been attributed to propranolol. The pathogenesis of these cases of pneumonitis with or without pleural effusion is not clear. A 59-year-old man developed pneumonitis which showed all the characteristics of a drug-associated pneumonitis due to propranolol: BAL demonstrated a lymphocytosis, the variations of which closely correlated with a provocation test. The LIF appeared to be released by the patient's peripheral blood lymphocytes when cultured with optimal doses of propranolol. Production of LIF by the patients' lymphocytes suggests the existence of a drug-specific cellular immune response in propranolol-associated pneumonitis.

Bronchoalveolar lavage cell data in amiodarone-associated pneumonitis. Evaluation in 22 patients.

To assess the value of bronchoalveolar lavage (BAL) for diagnosis, understanding, and treatment of amiodarone-associated pneumonitis, we examined the results of BAL total and differential cell counts and phenotyping of lymphocytes in 22 patients with this lung disorder and in 33 normal subjects. Overall, the total cell count was found to be almost the same as that seen in control subjects; the macrophage population was significantly reduced, and the lymphocyte, neutrophil, and eosinophil populations were increased in absolute number and percentage. When results were analyzed individually, BAL data appeared to be distributed according to two patterns. In the first pattern, there was no abnormal lymphocytosis. In the second pattern a lymphocyte alveolitis was found in percentage and in absolute number. This lymphocyte alveolitis was present either alone or associated with neutrophil alveolitis or with eosinophil alveolitis. In the first pattern, despite the normal level of the lymphocyte population, the percentage of CD4 T-lymphocytes and the CD4:CD8 T-lymphocyte ratio were significantly lowered. In the second pattern the CD8 T-lymphocyte count was increased in absolute number and percentage, with a low CD4:CD8 ratio. In six patients relavaged two to four months after amiodarone withdrawal, there was a significant fall in alveolar lymphocytosis, but the progressive increase in the neutrophil population over time seemed to be associated with the seriousness and progression of the disease. Finally, these findings closely resembled those obtained in patients with hypersensitivity pneumonitis due to inhalation of organic dust and suggest that an underlying immunologic cell-mediated mechanism may play a role in this iatrogenic pulmonary disease.

Bronchoalveolar lavage cell data in 19 patients with drug-associated pneumonitis (except amiodarone)

We examined bronchoalveolar lavage (BAL) cell data from 19 patients with a lung disorder presenting clinical, radiologic, functional, and course characteristics of drug-associated interstitial pneumonitis. In each of them, one of 13 different drugs was incriminated and no other cause was found. In one case due to bleomycin, a neutrophil and eosinophil alveolitis was present. In the other 18, the common denominator was a lymphocyte alveolitis, either pure (n = 6) or associated with neutrophilia (n = 5), eosinophilia (n = 3), or neutrophilia and eosinophilia (n = 4). In addition, in all patients, an inverted CD4/CD8 lymphocyte ratio was observed. In eight patients who underwent another BAL, lymphocyte alveolitis decreased but was persistent in two of them two to four months after cessation of treatment with the drug incriminated, whereas interstitial pneumonitis had resolved clinically. In five patients, after resolution of pneumonitis and after an almost normal BAL cell profile was obtained, resumption of treatment with the suspected drug for two to four weeks induced a rise in lymphocyte population in a third BAL. In conclusion, apart from one case of bleomycin lung, the most striking feature of drug-associated alveolitis in this series was expansion of lymphocyte population and imbalance in lymphocyte subsets. When a provocation test was performed, variations in alveolar lymphocyte levels paralleled withdrawal and readministration of the drug responsible for alveolitis. These data could be of value in diagnosing and understanding drug-induced lung disorders.

Human immunodeficiency virus-related lymphocytic alveolitis.

We observed 276 HIV-infected patients to determine the frequency, degree, and clinical presentation of the lymphocytic alveolitis in different stages of HIV disease, and also to identify the lymphocyte subsets involved. In 154 patients with proved lung infections or tumors (group A), bronchoalveolar lavage fluid showed lymphocytosis in 78 percent of cases. In 122 subjects (31 AIDS and 91 HIV-infected non-AIDS patients) without evidence of lung tumor or infection (group B), lymphocytic alveolitis was seen in 72 percent of cases. In 61 of 88 (69 percent) group B lymphocytic patients, we observed respiratory symptoms or diffuse interstitial opacities; however, we also observed such alveolitis in 27 of 46 (59 percent) group B patients free of respiratory symptoms and abnormality of chest x-ray film. This alveolitis was seen not only in AIDS or ARC patients but also at earlier stages of HIV infection. T-lymphocyte analysis showed a large majority (40 to 93 percent) of CD8 positive lymphocytes in the 37 patients tested. A dual fluorescence analysis revealed, in 18 subjects, that those cells were phenotypically cytotoxic (CD8 + D44 +). These findings suggest that, regardless of HIV-infection stages and of opportunistic lung infections, a CD8-positive T-lymphocyte alveolitis may be present in HIV-infected patients and could be responsible for cough, dyspnea, interstitial pneumonitis, and abnormalities of pulmonary function tests.

[Lymphocytic alveolitis in the early stages of HIV infection: correlation with biological and prognostic factors]. / Alvéolites lymphocytaires aux stades précoces de l'infection par le VIH: corrélations avec les facteurs biologiques de pronostic.

Broncho-alveolar lavage was performed to assess the degree of pulmonary lymphocytic alveolitis in 32 asymptomatic patients who were infected with the Human Immunodeficiency Virus (VIH). The patients were stages II and III of the CDC classification and the aim of the study was to determine the frequency, nature and prognostic role of the findings. 62.5% of the subjects (20/32) presented with a lymphocytic alveolitis which consisted predominantly of CD8 lymphocyte (64.3 +/- 3.5%), in the absence of an opportunistic infection or broncho-pulmonary tumours. Two sub-populations of alveolar CD8 were shown at comparable levels, a) sub-population CD8+D44+ (22.1 +/- 5%), in whom we showed the possession of cytotoxic activity in particular specific for VIH; b) sub-population CD8+CD57+ (19.6 +/- 3%) which we have shown to be capable in vitro of inhibiting the effector phase of cytotoxic activity of CD8+D44+ alveolar cells specific for VIH. In this group of 32 patients the occurrence of an alveolitis was not correlated with the usual prognostic factors of infection by VIH measured simultaneously with broncho-alveolar lavage (the level of CD4+ blood lymphocytes, and the beta 2-plasma microglobulins and the presence of p24 antigenaemia). In addition the level of CD4 lymphocytes supperior to 400/mm3 and of beta 2-microglobulins less then 3 mg/l whether a lymphocytic alveolitis was there or not confirmed the relatively poorly developed state of the VIH infection in these asymptomatic patients. Also the occurrence of a lymphocytic alveolitis did not seem to be linked to progression of the disease in the group of patients studied.(ABSTRACT TRUNCATED AT 250 WORDS)

[Pulmonary pathology of drug origin]. / La pathologie pulmonaire d'origine médicamenteuse.

Over the past ten years, there has been an impressively growing number of reports about drug-induced pneumonitis (DIP) due to more than one hundred different drugs. The most troublesome question is how to establish with certainty the diagnosis. Usually, five criteria are necessary. 1) The administration of a drug on a more or less long term basis. 2) Newly occurrence of an interstitial pneumonitis (defined on symptomatology, radiological features, pulmonary function test results). 3) Elimination of all other causes of pneumonitis (haemodynamic, infectious, systemic, environmental diseases). 4) Broncho-alveolar lavage (BAL) cell data showing in most cases a lymphocyte alveolitis with an inverted CD4/CD8 ratio. In a certain number of ambiguous circumstances, coupling a provocation test with a sequentially performed BAL could firmly establish the diagnosis. 5) Rapid resolution within a few days or months of the pneumonitis as early as the incriminated drug administration is stopped. Nevertheless sometimes one or more of these criteria are not met, mainly when the pneumonitis is a fibrosis directly induced by a fibrosing toxic mechanism.