Elsevier

Clinics in Chest Medicine

Volume 25, Issue 3, September 2004, Pages 479-519
Clinics in Chest Medicine

Drug-induced and iatrogenic infiltrative lung disease

https://doi.org/10.1016/j.ccm.2004.05.006Get rights and content

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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:

  • Interstitial pneumonitis with (eg, with methotrexate, interferons, or bacille Calmette-Guérin[BCG]-therapy) or without (eg, with chrysotherapy, or β-blockers) granulomas (Fig. 1)

  • Eosinophilic pneumonia (eg, with minocycline, NSAIDs, or angiotensin-converting enzyme inhibitors (ACEI) (Fig. 2)

  • 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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References (88)

  • A.H. Limper

    Chemotherapy-induced lung disease

    Clin Chest Med

    (2004)
  • W. van Mieghem et al.

    Amiodarone and the development of ARDS after lung surgery

    Chest

    (1994)
  • B.K. Gehlbach et al.

    The pulmonary manifestations of left heart failure

    Chest

    (2004)
  • M.I. Schwarz et al.

    Drug-induced diffuse alveolar hemorrhage syndromes and vasculitis

    Clin Chest Med

    (2004)
  • G.R. Epler

    Drug-induced bronchiolitis obliterans organizing pneumonia

    Clin Chest Med

    (2004)
  • I.Y. Nizami et al.

    Idiopathic bronchiolitis obliterans with organizing pneumonia. An acute and life-threatening syndrome

    Chest

    (1995)
  • R.C. Bone et al.

    Desquamative interstitial pneumonia following long-term nitrofurantoin therapy

    Am J Med

    (1976)
  • J.N. Allen

    Drug-induced eosinophilic lung disease

    Clin Chest Med

    (2004)
  • J.J. Erasmus et al.

    High-resolution CT of drug-induced lung disease

    Radiol Clin North Am

    (2002)
  • M.C. Ott et al.

    Pulmonary toxicity in patients receiving low-dose amiodarone

    Chest

    (2003)
  • B. Coudert et al.

    Amiodarone pneumonitis: bronchoalveolar lavage findings in 15 patients and review of the literature

    Chest

    (1992)
  • C.W. Bedrossian et al.

    Amiodarone pulmonary toxicity: cytopathology, ultrastructure, and immunocytochemistry

    Ann Diagn Pathol

    (1997)
  • B.R. O'Driscoll et al.

    Late carmustine lung fibrosis. Age at treatment may influence severity and survival

    Chest

    (1995)
  • U.B. Prakash et al.

    Pulmonary complications from ophthalmic preparations

    Mayo Clin Proc

    (1990)
  • N.F.J. Adkinson et al.

    Task force report: future research needs for the prevention and management of immune-mediated drug hypersensitivity reactions

    J Allergy Clin Immunol

    (2002)
  • Pneumotox® website

  • P. Camus et al.

    Drug-induced infiltrative lung disease

    Eur Respir J

    (2001)
  • D.B. Flieder et al.

    Pathologic characteristics of drug-induced lung disease

    Clin Chest Med

    (2004)
  • P. Camus et al.

    Amiodarone pulmonary toxicity

    Clin Chest Med

    (2004)
  • D.A. White

    Drug-induced pulmonary infection

    Clin Chest Med

    (2004)
  • J.M. Kremer et al.

    Clinical, laboratory, radiographic, and histopathologic features of methotrexate-associated lung injury in patients with rheumatoid arthritis

    Arthritis Rheum

    (1997)
  • P. Camus

    Drug-induced infiltrative lung diseases

  • P. Camus

    Drug history and remote exposure to drugs. A cause of lung disease?

    Eur Respir J

    (2000)
  • P.M. Kopko et al.

    Transfusion-related lung injury

    Br J Haematol

    (1999)
  • D.A. Zisman et al.

    Drug-induced pneumonitis: the role of methotrexate

    Sarcoidosis Vasc Diffuse Lung Dis

    (2001)
  • C. Fuhrman et al.

    Spectrum of CD4 to CD8 T-cell ratios in lymphocytic alveolitis associated with methotrexate-induced pneumonitis

    Am J Respir Crit Care Med

    (2001)
  • R. Clearkin et al.

    Methotrexate pneumonitis in a patient with rheumatoid arthritis

    Postgr Med J

    (1997)
  • S. Imokawa et al.

    Methotrexate pneumonitis: review of the literature and histopathological findings in nine patients

    Eur Respir J

    (2000)
  • U. Costabel et al.

    Bronchoalveolar lavage in drug-induced lung disease

    Clin Chest Med

    (2004)
  • L. Donaldson et al.

    Acute amiodarone-induced lung toxicity

    Intensive Care Med

    (1998)
  • E. Liverani et al.

    Amiodarone-induced adult respiratory distress syndrome after nonthoracotomy subcutaneous defibrillator implantation

    J Intern Med

    (2001)
  • M.Y. Rady et al.

    Preoperative therapy with amiodarone and the incidence of acute organ dysfunction after cardiac surgery

    Anesth Analg

    (1997)
  • P. Bristedt et al.

    Pulmonary edema following intravenous injection of nonionic low-osmolar contrast medium - Appearance on HRCT - A case report

    Acta Radiol

    (1998)
  • P.M. Kopko et al.

    Pulmonary injury from transfusion-related acute lung injury

    Clin Chest Med

    (2004)
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    Space constraints did not allow for the inclusion of a reference on each statement. Specific queries on this and other aspects are welcome on Pneumotox at http://www.pneumotox.com.

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