ABSTRACT

Interstitial lung fibrosis is the most common form of drug-induced respiratory disease; but it only represents 3% of all the cases of interstitial lung disease (ILD). The most important risk factors associated are advanced age, rheumatoid lung involvement, previous use of disease modifying drugs and hypoalbuminemia. ILD is caused by fibrogenic agents that enhance the widespread thickness of the alveolar wall and the extracellular matrix generating the development of a restrictive lung defect. The lung injury is an idiosyncratic reaction although some factors have been described as important mediators of the fibrosis, for example the tumor necrosis factor alpha (TNF-a) and the transforming growth factor beta (TGF-b). Establishing a unique histopathologic pattern of ILD induced by methotrexate (MTX) is a difficult task, the most common findings are interstitial inflammation, fibrosis, giant cells, eosinophils, and type II pneumocytes hyperplasia. ILD due to MTX presents either acutely or subacutely with cough, fever, dyspnea and pulmonary infiltrates leading to respiratory failure. It is mainly a diagnosis of exclusion, as it is hard to distinguish from infection or exacerbations from pre-existing lung disease. The diagnosis rests on the temporal association between exposure to MTX and the development of respiratory signs and symptoms. The fact that the histopathologic changes don’t seem to be related with the dose or length of therapy with MTX suggest that these changes are not caused by MTX.

KEYWORDS

Interstitial pulmonary fibrosis, interstitial lung disease (ILD), interstitial inflammation, pneumonitis, methotrexate (MTX), lung toxicity.

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