Drug-induced and iatrogenic infiltrative lung disease☆
Section snippets
Drugs that cause infiltrative lung disease
Drugs that often cause ILD include Am, antibiotics, nonsteroidal anti-inflammatory drugs (NSAIDs), chemotherapeutic agents (bleomycin, busulfan, chlorambucil, cyclophosphamide, methotrexate, mitomycin, nitrosoureas), and nitro-bearing drugs (nitrofurantoin, nilutamide). Recently, all-transretinoic acid (ATRA), colony-stimulating factors (CSFs), interferons, docetaxel, gefitinib, gemcitabine, irinotecan, vinorelbine, cytokines, and proteins (eg, plasma fraction, intravenous immunoglobulins
Diagnostic criteria
A high index of suspicion is needed. The criteria for the diagnosis of DI ILD are discussed in the following sections.
Acute life-threatening drug-induced infiltrative lung disease
Drugs can produce respiratory emergencies, including widespread pulmonary infiltrates, with compromise of gas exchange and life-threatening respiratory failure [13]. This may correspond to acute:
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Interstitial pneumonitis with (eg, with methotrexate, interferons, or bacille Calmette-Guérin[BCG]-therapy) or without (eg, with chrysotherapy, or β-blockers) granulomas (Fig. 1)
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Eosinophilic pneumonia (eg, with minocycline, NSAIDs, or angiotensin-converting enzyme inhibitors (ACEI) (Fig. 2)
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Diffuse
Amiodarone pneumonitis-amiodarone pulmonary toxicity
Am is a antiarrhythmic benzofuran drug with an imposing adverse effect profile. APT was first recognized in the early 1980s in the United States. During chronic treatment, Am and its main metabolite, desethylamiodarone (DEAm), accumulate extensively in organs and achieve toxic concentrations in tissues. Two molecules of iodine are present for each molecule of Am or DEAm. Am and DEAm interfere with the catabolism of lung phospholipids, which also accumulate in lung. Am and DEAm efflux slowly
Organizing pneumonia or bronchiolitis obliterans organizing pneumonia
DI OP/bronchiolitis obliterans organizing pneumonia (BOOP) is a distinctive pattern of lung response to drugs that is characterized by alveolar fibrosis as the dominant histopathologic feature [39]. OP has many causes other than drugs [62], however, which makes evaluation of drug causality difficult. DI OP was reported initially as a severe and often fatal lung disease in patients who were treated with the early antihypertensive drugs, hexamethonium and mecamylamine [2]. After these drugs were
Infiltrative lung disease related to drug- or radiation-induced vascular injury
The use of leukotriene receptor antagonists (LTRA) in the treatment of asthma recently was associated with the development of the CSS [2]. Patients present with peripheral eosinophilia, diffuse pulmonary infiltrates, rarely DAH, in the context of suggestive extrapulmonary involvement (cardiomyopathy, muscle pain, mononeuritis and, less often, digestive or dermatologic changes). Symptoms occur a few weeks or months into treatment with the LTRA. Corticosteroid tapering may trigger the onset of
Exogenous lipoid pneumonia
Exogenous lipoid pneumonia (Fig. 13) is a complication of chronic exposure to mineral oil. Classically, contamination occurs during long-term ingestion of paraffin at night to combat constipation [74]. Less common exposures include inhalation of lipid formulation of amphotericin B and cyclosporin, application of mineral oil in the nasal cavity or on the face, the compulsive use of lipsticks, application of oily material on chest wounds, repeated use of oil-containing eyedrops [75], suicide
Drug-induced sarcoidosis
Most cases of DI sarcoidosis (not just granulomas) are associated with treatments with IFN-α or -β or pegylated IFN, whether or not ribavirin is combined with IFN in the treatment of hepatitis C infection [79]. IFN-induced sarcoidosis develops after a few months into treatment. Rarely, sarcoidosis develops after withdrawal of IFN. IFN can produce a relapse of previously-diagnosed sarcoidosis. Patients may complain of fatigue, breathlessness, or cough; these manifestations can be obscured by the
Drug hypersensitivity syndrome
Drug hypersensitivity syndrome (DHS) is an idiosyncratic reaction that is defined by the clinical triad of fever, rash, and such organ involvement as hepatitis, myocarditis, nephritis, or pneumonitis or pulmonary infiltrates. DHS also is known as “drug rash with eosinophilia and systemic symptoms”, the “sulfone syndrome,” “glandular fever,” or “anticonvulsant- or carbamazepine hypersensitivity syndrome,” depending on the causative drug and context [80]. Typically, the disease develops within
Drug-induced lupus erythematosus
DI lupus has been reported with approximately 60 chemically- and pharmacologically-unrelated drugs [8], [83], [84], including Am, ACEI, anticonvulsants (carbamazepine, ethosuximide, phenytoin, primidone, trimethadone, and valproate, but not benzodiazepines or phenobarbital), anti-TNF agents, β-blockers (mainly acebutolol), chlorpromazine, oral contraceptives, recombinant cytokines or antibodies, dihydralazine, IFN, mesalazine, methyldopa, minocycline, nitrofurantoin, propylthiouracil, statins,
Pleuropulmonary reactions
Parenchymal changes, such as pulmonary infiltrates or subpleural foci of rounded atelectasis, can develop in patients who have DI primary pleural fibrosis (eg, ergot-induced [85], or in DI lupus [83]). The disease is then referred to as “pleuropneumonitis.” The parenchymal changes may be nonspecific.
Infiltrative lung disease that results from irradiation to the chest
Thoracic irradiation causes dose-related reversible changes in the lung that are characterized by a dry cough and the pathologic changes of bizarre type II cells, hyaline membranes, edema, and eventually, fibrosis. It was later realized that the pathologic changes that were induced by alkylating agents were similar [12]. Most commonly, radiation lung injury develops in patients who receive therapy for lung or breast carcinoma, Hodgkin's disease or non-Hodgkin's lymphomas, or total body
Acknowledgements
The editorial assistance of Sarah Barth (Elsevier) and Sarah Mell (Capital City Press) is gratefully acknowledged.
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