Interstitial pneumonia possibly due to a novel anticancer drug, TS-1: first case report.

A newly approved oral fluoropyrimidine, TS-1, is a dihydropyrimide dehydrogenase (DPD)-inhibiting fluoropyrimidine (DIF) drug. We describe a case of interstitial pneumonia probably caused by TS-1. A peripheral blood lymphocytes stimulating test (DLST) with TS-1 demonstrated a substantial positive reaction. So far only three cases of TS-1-induced interstitial pneumonia have been reported but the relationship between interstitial pneumonia and TS-1 was demonstrated only in this case. Considering that interstitial pneumonia has also been reported with 5-FU, it is necessary in the future to clarify which component of this drug is directly related to interstitial pneumonia.

Elevated serum soluble CD44 level in sarcoidosis.

Sarcoidosis is a chronic multi-organ granulomatous disease of unknown etiology. Several studies have suggested an involvement of immunologic background in sarcoidosis. The lymphocyte surface marker CD44 is a multifunctional molecule which mediates the adhesion of lymphocytes to the extracellular matrix. Recently, we developed a system to quantitate soluble CD44 (sCD44) which we employed to determine serum and bronchoalveolar lavage fluid (BALF) levels of sCD44 to obtain further insights into immunologic aspects of sarcoidosis. Serum sCD44 levels were measured in 13 consecutive patients with sarcoidosis and 56 normal healthy controls using enzyme-linked immunoabsorbent assay. BALF sCD44 levels were also measured in 11 patients with sarcoidosis and 10 normal healthy controls. In patients with sarcoidosis, the serum sCD44 level was significantly higher than that of normal controls (348.5+/-164.2 ng/ml vs 145.4+/-22.9 ng/ml; p<0.001). Also BALF sCD44 levels tended to be higher in sarcoidosis than in normal controls (23.7+/-13.4 ng/ml vs 18.1+/-8.4 ng/ml), but no statistically significant difference was recognized. We also found that there was a positive correlation between the serum sCD44 and angiotensin converting enzyme (r=0.78). Our data indicate that sCD44 may be related to immunologic background and may be a useful new marker of sarcoidosis.

Sarcoidosis induced by interferon therapy for chronic myelogenous leukaemia.

A 31-year-old male was diagnosed as having chronic myelogenous leukaemia and has been treated with hydroxyurea and interferon-alpha since February 1995. After 16 months, he complained of low-grade fever and a cough. Bilateral hilar lymph node enlargement was detected on the chest X-ray film and multiple subcutaneous erythematous nodules appeared. A skin biopsy revealed subcutaneous sarcoid granuloma. Two months after the cessation of interferon therapy, the subcutaneous nodules and the hilar lymph node enlargement resolved. It is possible that continuous interferon administration can promote granuloma formation in sarcoidosis by activating T cells and macrophages.

Elevation of antibodies to cytomegalovirus and other herpes viruses in pulmonary fibrosis.

The aim of this study was to determine whether latent viral infection is associated with idiopathic pulmonary fibrosis (IPF), an interstitial lung disease whose aetiology remains to be elucidated. Cytomegalovirus (CMV) immunoglobulin G (IgG) and complement fixation (CF), Epstein-Barr (EB) viral capsid antigen (VCA) IgG, herpes simplex virus (HSV) IgG, adenovirus CF, and parainfluenza 3 virus haemagglutinin inhibition (HI) titres were measured in the serum from patients with pulmonary diseases. The study included five subject groups: 35 normal controls (aged (mean +/- SD) 38 +/- 17 yrs); 43 IPF (63 +/- 10 yrs), seven collagen vascular disease-related interstitial pneumonitis (CVD-IP) (62 +/- 12 yrs); 22 sarcoidosis (36 +/- 14 yrs); and 17 emphysema (66 +/- 11 yrs). Levels of CMV IgG in IPF (87.6 +/- 51.7) and CVD-IP (101.2 +/- 69.9) were significantly elevated compared to those in the control (30.9 +/- 24.1), sarcoidosis (34.4 +/- 38.3) and emphysema groups (40.3 +/- 24.6), whereas CMV immunoglobulin M (IgM) was generally below the limit of detection. Similarly, CMV CF titres in IPF and CVD-IP were elevated compared to those in other diseases. EB VCA IgG titres in IPF, CVD-IP and emphysema and HSV IgG in IPF were also elevated. In contrast, adenovirus CF and parainfluenza 3 HI titres demonstrated no significant difference among all of the groups investigated. Increases in cytomegalovirus immunoglobulin G and complement fixation titres with negative cytomegalovirus immunoglobulin M suggest that latent cytomegalovirus infection may be more prominent in idiopathic pulmonary fibrosis or collagen vascular disease-related interstitial pneumonitis. Together with the elevation of Epstein-Barr virus viral capsid antigen and herpes simplex virus immunoglobulin G in idiopathic pulmonary fibrosis and/or collagen vascular disease-related interstitial pneumonitis, it is rational to assume that these viruses may be implicated in the development of pulmonary fibrosis. Further study is necessary to investigate the relationship between latent viral infection and pulmonary fibrosis.

Diffuse alveolar hemorrhage associated with proteinase 3-specific anti-neutrophil cytoplasmic antibodies.

A 31-year-old man was referred to our hospital for the management of progressive diffuse alveolar hemorrhage associated with renal dysfunction. Leukocytoclastic vasculitis was shown by skin biopsy and crescentic glomerulonephritis was also detected, in addition to positivity for proteinase 3-specific anti-neutrophil cytoplasmic antibodies (PR3-ANCA). The patient was diagnosed as a rare case of PR3-ANCA-positive pulmonary-renal vasculitic syndrome without granulomatous lesions. There was a good response to combination therapy with steroids and cyclophosphamide.

[Subsets of lymphocytes in bronchoalveolar-lavage fluid from patients with idiopathic bronchiolitis obliterans organizing pneumonia].

Lymphocyte activation may be involved in interstitial inflammatory processes in the lungs. We analyzed lymphocytes in bronchoalveolar lavage fluid obtained from 5 patients with idiopathic bronchiolitis obliterans organizing pneumonia and from 7 control subjects. Lymphocytes were analyzed by two-flow cytometry. Differential cell counts showed that the percentage and the number of lymphocytes was higher in the patients (32.9 +/- 21.9%, 12.8 +/- 8.32 x 10(4) cells/ml) than in the controls (8.31 +/- 3.66%, 0.69 +/- 0.39 x 10(4) cells/ml, p < 0.05). In particular, the patients had many more CD8+ S6F1+ lymphocytes (which are considered to be activated cytotoxic T lymphocytes; 32.2 +/- 11.8%, 42.0 +/- 26.5 x 10(3) cells/ml) than did the controls (6.31 +/- 1.69%, 0.42 +/- 0.25 x 10(3) cells/ml, p < 0.01). These data indicate that activated cytotoxic T lymphocytes may be important in the pathogenesis of bronchiolitis obliterans organizing preumonia.

[Lymphocyte subsets in bronchoalveolar lavage fluid from patients with idiopathic interstitial pneumonia].

Lymphocyte activation may be involved in interstitial inflammatory processes in the lungs. We analyzed lymphocytes in bronchoalveolar lavage fluid obtained from 15 patients with idiopathic interstitial pneumonia (IIP) and from 7 controls. Clinical criterial were used to divide the patients with IIP into two groups: acute (n = 5) and chronic (n = 10). Lymphocytes in the bronchoalveolar lavage fluid were analyzed with a flow-cytometric two-color system. Differential cell counts showed that percentages and numbers of lymphocytes were significantly higher in patients with acute IIP (44.2 +/- 25.2%, 12.3 +/- 8.18 x 10(4)/ml) than in controls (8.31 +/- 3.66%, 0.69 +/- 0.39 x 10(4)/ml, p < 0.05) and in patients with chronic IIP (8.44 +/- 6.11%, 1.58 +/- 1.08 x 10(4)/ml, p < 0.05). In particular, percentages and numbers of CD8+ S6F1+ lymphocytes, which are regarded as activated cytotoxic T lymphocytes were markedly higher in patients with acute IIP (32.3 +/- 16.0%, 39.6 +/- 37.1 x 10(3)/ml), than in controls (6.31 +/- 1.69%, 0.42 +/- 0.25 x 10(3)/ml, p < 0.05) and in patients with chronic IIP (10.6 +/- 6.16%, 1.88 +/- 1.42 x 10(3)/ml, p < 0.05). These data suggest that patients with acute IIP differ from those with chronic IIP in the percentage and the number of lymphocytes in bronchoalveolar lavage fluid, and that activated cytotoxic T lymphocytes may play an important role in the pathogenesis of acute IIP.