Mesalazine-induced multi-organ hypersensitivity.

Mesalazine therapy for ulcerative colitis has been reported to be effective and safe. Rare cases of mesalazine-induced renal, pancreatic, myo-pericardial, pleuro-pulmonary and haematological toxicity have been described separately. We report a case characterized by the simultaneous presence of fever, pericarditis, peripheral eosinophilia, eosinophilic pneumonia, anaemia and haematuria (together with proteinuria and leukocyturia) due to mesalazine treatment in a patient with ulcerative colitis. No clinical response had been obtained with corticosteroids and various antibacterial agents. When mesalazine treatment was suspended, all symptoms rapidly and totally disappeared, confirming the direct responsibility of this drug in causing these adverse events. We conclude that mesalazine can induce multi-organ hypersensitivity, which must always be considered as a possible adverse effect during treatment with this drug. To resolve this adverse event it is essential to discontinue mesalazine treatment.

Chitotriosidase analysis in bronchoalveolar lavage of patients with sarcoidosis.

BACKGROUND: Sarcoidosis is a systemic granulomatous disease characterised by T-helper cell/macrophage alveolitis. Activated macrophages release mediators, such as cytokines, chemokines, oxygen radicals, and enzymes. In a previous paper we found higher levels of chitotriosidase, a macrophage derived enzyme, in serum of patients with sarcoidosis than in controls. Serum chitotriosidase levels were correlated with sarcoidosis radiological stages. Human chitotriosidase is involved in the pathogenesis of many lysosomal storage disorders and is selectively expressed in chronically activated tissue macrophages. METHODS: In the present study we determined chitotriosidase concentrations in bronchoalveolar lavage of patients with newly diagnosed pulmonary sarcoidosis (divided into two groups according to clinical parameters) and of controls with an ELISA test. RESULTS: Significantly different chitotriosidase concentrations were found in BAL of patients than controls, especially in patients with progressing disease. CONCLUSION: Chitotriosidase but not angiotensin converting enzyme concentrations correlated with sarcoidosis radiological stages, and also with the degree of lung infiltrate seen by CT-scan, suggesting that the former enzyme (detected locally and sistemically) may play a role in the pathogenesis of the disease. Further studies with a greater number of patients are needed to confirm this hypothesis and to determine whether chitotriosidase may be a marker of the severity of sarcoidosis.

Chitotriosidase activity in patients with interstitial lung diseases.

BACKGROUND: In previous papers, we found significantly higher activity of chitotriosidase, a macrophage derived enzyme, in serum and BAL of patients with sarcoidosis, especially in those with progressing disease and lung involvement, than in controls. Locally and systemically produced chitotriosidase activity was correlated with radiological stage and also with degree of lung infiltration, suggesting that this enzyme may play a role in the pathogenesis of sarcoidosis and may be used as a marker of disease severity. AIM: To analyse chitotriosidase activity in serum and bronchoalveolar lavage of patients with idiopathic pulmonary fibrosis and pulmonary fibrosis associated with systemic sclerosis and to compare it with chitotriosidase activity in controls and sarcoidosis patients. METHODS: Chitotriosidase activity was determined by a fluorometric assay. RESULTS: The results showed that serum chitotriosidase activity was only elevated in sarcoidosis patients; in patients with idiopathic pulmonary fibrosis and pulmonary fibrosis associated with systemic sclerosis it was in the normal range. On the contrary, in BAL of sarcoidosis and idiopathic pulmonary fibrosis patients the activity was significantly higher than in controls. CONCLUSION: Serum chitotriosidase is a potential marker of sarcoidosis severity; it increases in sarcoidosis in relation to radiological stage and degree of lung infiltration. The increase in chitotriosidase activity in BAL of sarcoidosis and idiopathic pulmonary fibrosis patients suggests that the enzyme could be involved in fibrogenesis in diffuse lung diseases. Further research is needed to understand the role of chitotriosidase in the pathogenesis of sarcoidosis and its involvement in fibrotic remodelling in certain diffuse lung diseases.

Analysis of carbonylated proteins in bronchoalveolar lavage of patients with diffuse lung diseases.

Diffuse lung diseases (DLD) are a heterogeneous group of diseases with different etiopathogenesis, clinical course, and prognosis. It has been demonstrated that oxidative stress can contribute to the pathogenesis of these diseases. In the present study we measured carbonylated protein concentrations in the BAL of patients with sarcoidosis, pulmonary fibrosis associated with systemic sclerosis, idiopathic pulmonary fibrosis, and for the first time in patients with chronic eosinophilic pneumonia and extrinsic allergic alveolitis. Our aim was to further investigate oxidation products in diffuse lung diseases. Oxidatively modified protein concentrations were increased in the BAL of patients than in that of controls (0.22 nmol/mg protein vs 0.05 nmol/mg protein; p < 0.001) and in each group of disease versus controls, suggesting that proteins that have become dysfunctional by oxidation could play a role in the pathogenesis of diffuse lung diseases. Further studies in a greater number of patients are needed to understand the contribution of oxidatively modified proteins to the pathogenesis of DLD and, in particular, to the development of extrinsic allergic alveolitis where the highest levels of carbonylated proteins were found.

Cytokine profile and proteome analysis in bronchoalveolar lavage of patients with sarcoidosis, pulmonary fibrosis associated with systemic sclerosis and idiopathic pulmonary fibrosis.

The aim of this study was to analyze the type of immune response (Th1, Th2) and protein composition of bronchoalveolar lavage (BAL) of patients with sarcoidosis, pulmonary fibrosis associated with systemic sclerosis (SSc) and idiopathic pulmonary fibrosis (IPF). Flow cytometry analysis of intracellular cytokines revealed different patterns: in IPF and SSc Th2 profiles were predominant, whereas in sarcoidosis Th1 prevailed. The proteomic analysis of BAL fluid (BALF) showed that there were quantitative differences between the three diseases. These were more evident between sarcoidosis and IPF, confirming our previous observations, whereas SSc had an intermediate profile between the two, however with some peculiarities. Comparison of BALF protein maps, constructed with the same quantity of total proteins, enabled us to identify the main profiles of the three diseases: an increase in plasma protein prevalent in sarcoidosis and also present in SSc, though for fewer proteins with respect to IPF and a greater abundance of low molecular weight proteins, mainly locally produced, in IPF. These findings are in line with the different pathogenesis of these diseases: IPF is considered a prevalently fibrotic disorder limited to the lung, with intense local production of functionally different proteins, whereas sarcoidosis and SSc are systemic immunoinflammatory diseases.

Bronchoalveolar lavage fluid protein composition in patients with sarcoidosis and idiopathic pulmonary fibrosis: a two-dimensional electrophoretic study.

We used two-dimensional (2-D) electrophoresis to analyze the protein composition of fluid recovered by bronchoalveolar lavage (BALF) from patients with sarcoidosis and idiopathic pulmonary fibrosis, two forms of interstitial lung disease with different cellular composition and cytokine profile in BALF. They are also characterized by different pathogenesis and clinical evolution, idiopathic pulmonary fibrosis being less favorable than sarcoidosis due to rapidly progressive pulmonary fibrosis. Thirty-eight proteins or protein fragments, never previously assigned in BALF samples, were identified by various methods including mass fingerprinting of tryptic digests. Comparison of the BALF protein maps of the two groups of patients showed 32 spots with statistically significant disease-related variations in relative abundance. In sarcoidosis we found an increase in the amount of several plasma proteins, while in idiopathic pulmonary fibrosis we observed a statistically significant increase in low-molecular-weight proteins, many of which are involved in inflammatory processes (such as MIF and calgranulin) or antioxidant response (such as antioxidant peroxysomal enzyme and thioredoxin peroxidase 2). 2-D electrophoresis allowed us to identify new BALF proteins and to characterize protein composition in patients with sarcoidosis and idiophatic pulmonary fibrosis. Comparison of the gels of the two diseases showed that they differ in BALF protein profiles as they do in type of immune response.