Imaging in Drug-Induced Lung Disease

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The number of drugs that adversely affect the respiratory system continues to increase, and their effects pose a great challenge to all physicians. A review in 1972 identified only 19 drugs with the potential to cause pulmonary disease; now, more than 350 (and counting) have been identified. Awareness of drug-induced pulmonary disease is increasing. The sole purpose of one clinical study group, the Groupe d’Etudes de la Pathologie Pulmonaire Iatrogene (GEPPI), is to provide information regarding individual cases, to collect and update literature on drug-induced lung disease, to publish updated lists of offending compounds, and to provide warnings when adverse effects of drugs are recognized. ^{[1, 2, 3, 4, 5, 6, 7, 8, 9, 10]}

Although conventional chest radiography is the first choice in imaging options in evaluating patients for pulmonary manifestations of drug toxicity, the limitations of the pattern approach often necessitate the use of other imaging techniques in addition to clinical and laboratory evaluation. In select cases, high-resolution computed tomography (HRCT) and radionuclide imaging have a role in detecting lung toxicity early, when it is still reversible, or in differentiating drug toxicity from other lung pathology. ^[11]

The major problem with all imaging is that drug-related lung toxicity has a nonspecific appearance, and similar patterns have been described with many interstitial lung diseases. Lung toxicity resulting from various drugs can induce similar changes. In patients taking drug combinations, the imaging findings alone may not reveal the culprit.

Early recognition of drug-induced lung disease is important because it can be reversed if appropriate therapy is instituted soon after the onset of symptoms. Lack of response to empiric antibiotic treatment and an imaging pattern of organizing pneumonia should raise suspicion of everolimus-induced pneumonitis in patients undergoing therapy with this drug. ^[12]

See the images below.

Conventional chest radiography is usually an initial investigation in patients with pulmonary and/or cardiac symptoms and may be the only imaging required. Although chest radiography is the first choice among imaging options in evaluating patients for pulmonary manifestations of drug toxicity, the limitations of the pattern approach often necessitate the use of other imaging techniques in addition to clinical and laboratory evaluation. Many pathologies, such as infections, sarcoidosis, lymphoma, and interstitial pneumonias, can mimic drug-induced lung disease.

Busulfan toxicity causes drug-induced pulmonary damage after prolonged exposure, usually after 3-4 years of therapy. Approximately 1-10% of patients taking the drug are affected. Conventional radiographic changes include diffuse linear opacities, which may occasionally become reticulonodular. Pneumocystis jiroveci pneumonia (PCP) and interstitial leukemic infiltrates can have similar appearances. The abnormalities in the lung parenchyma may partially or completely resolve after the drug is withdrawn.

Bleomycin lung toxicity occurs with doses larger than 300 mg in 3-6% cases, generally 1-3 months after the commencement of therapy (see the images below). Increasing age, conjoint radiation therapy, and high concentrations of oxygen are associated with high rates of lung toxicity. Radiographic changes include subpleural linear and/or nodular opacities at the lung bases.

Methotrexate lung toxicity is not dose related and is self-limiting despite continuing therapy. It is often associated with blood eosinophilia. ^[13] Radiographic changes include linear and/or reticulonodular opacities early in the process, followed by acinar filling. On occasion, transient mediastinal lymphadenopathy and pleural effusions occur.

Nitrofurantoin lung toxicity may appear in an acute stage or in a chronic stage. An acute presentation is more common than a chronic one and is often associated with fever and eosinophilia. The chronic form manifests as a pulmonary fibrotic process, often with no accompanying eosinophilia. Bilateral basal interstitial opacities are observed (see the image below).

Pulmonary granulomas are composed of macrophages reacting to various drugs, such as methotrexate and nitrofurantoin. A common form of granulomatous reaction is also seen after chronic aspiration of mineral oils, which leads to the formation of chronic basilar, often conglomerate, masses. ^[14]

A case of salazosulfapyridine-induced pneumonitis associated with multiple pulmonary nodules and lymphadenopathy has been reported. ^[15]

Heroin, propoxyphene, or methadone overdose is often associated with pulmonary edema with widespread airspace consolidation. Aspiration pneumonia may be a complication in more than one half of patients. Aspirin overdose may also cause pulmonary edema.

Amiodarone therapy is associated with alveolar and interstitial infiltrates, peripheral consolidation, and pleural thickening adjacent to the consolidation. The lung consolidation tends to have increased density because of the iodine content.

Ground-glass opacity may be observed in drug- or radiation-induced lung disease. Ground-glass opacification is much better defined with high-resolution computed tomography (HRCT) than with radiography. Ground-glass opacity is commonly observed in patients with early diffuse pulmonary infiltrative diseases. Ground-glass pulmonary opacification is a nonspecific finding but nevertheless an important sign of disease. It is also a useful sign of an active and treatable component in some diffuse pulmonary diseases, including drug toxicity.

The diagnosis of drug-induced lung disease is often made on the basis of a history of drug exposure, histologic evidence of lung injury, and the exclusion of other causes of lung injury. The main value of HRCT is in the depiction of parenchymal abnormalities in symptomatic patients who have normal or questionable findings on chest radiography. (See the images below.) ^{[16, 17, 18, 19, 20, 21, 22, 23]}

Approximately 10% of patients receiving cytotoxic drugs develop drug-induced lung reactions. ^[24] Any chemotherapeutic drug can adversely affect the lung, but the drugs most commonly implicated in lung toxicity are bleomycin, methotrexate, carmustine, busulfan, and cyclophosphamide. ^{[25, 26, 27, 28, 29, 30, 31, 32]}

Interstitial pneumonitis and fibrosis, hypersensitivity reaction, acute respiratory distress syndrome (ARDS), and cryptogenic organizing pneumonia (COP) or bronchiolitis obliterans organizing pneumonia (BOOP) are the most common types of lung reaction related to chemotherapy. ^{[33, 34, 35]}

HRCT findings in chemotherapeutic drug-induced lung reactions reflect the histologic findings. The most consistent findings in chemotherapy-induced (particularly bleomycin-induced) lung reaction include interstitial pneumonitis and fibrosis, which result in ground-glass attenuations, focal areas of consolidation, and irregular and linear attenuations that predominantly involve the lower zones of the lungs. Hypersensitivity lung reaction complicating chemotherapy resembles other types of hypersensitivity pneumonitis, which cause ground-glass opacities and poorly defined centrilobular nodules. Bilateral extensive airspace consolidation can also occur, particularly as a reaction to methotrexate. ^[36]

ARDS may occur within days after induction of chemotherapy, and it may cause bilateral and predominantly dependent airspace consolidation. BOOP is a less common reaction to chemotherapeutic drugs, particularly bleomycin. ^[36] BOOP commonly results in peribronchial or subpleural areas of consolidation.

Amiodarone is the most common drug related to cardiovascular pulmonary abnormalities. It affects as many as 6% of individuals receiving the drug. ^[37]

HRCT shows diffuse interstitial thickening or, infrequently, nodular areas of subpleural consolidation (BOOP). On occasion, patients present with the acute onset of dyspnea and fever, which cause areas of dependent consolidation.

Amiodarone contains iodine. Therefore, lung parenchymal opacities have increased attenuation (82-174 HU). This finding is suggestive, but it is not pathognomonic of amiodarone-induced pulmonary toxicity.

Nitrofurantoin, amphotericin B, sulfonamides, and sulfasalazine are known to cause lung toxicity. Antibiotic-related lung disease includes interstitial pneumonitis and fibrosis, hypersensitivity reaction, ARDS, and BOOP. Nitrofurantoin is responsible for lung toxicity in less than 1% of patients receiving the drug; however, it remains an important cause of adverse drug reaction. The most common presentation is that of an acute hypersensitivity reaction.

HRCT shows airspace consolidation with a basal predominance and pleural effusions, which is a pattern consistent with noncardiogenic pulmonary edema. ^[38] Chronic pneumonitis and fibrosis occur infrequently and are usually related to prolonged therapy over years. Chronic pneumonitis and fibrosis may mimic idiopathic pulmonary fibrosis on HRCT, with bilateral, predominantly basilar reticular opacities. On occasion, a BOOP-like reaction may also be seen.

Illicit drug abuse is now regarded as the most common cause of drug-related lung toxicity. ^[39] Pulmonary talcosis is a known complication of intravenous drug abuse. HRCT shows diffuse micronodularity resulting from a foreign-body granulomatous response. These micronodules may become confluent, forming conglomerate parahilar masses, which tend to have high attenuation because of their talc content. Ground-glass attenuation has also been described. Intravenous methylphenidate abuse may result in talcosis and in severe panlobular emphysema. ^[40]

Intravenous heroin and cocaine abuse is a known cause of acute pulmonary edema occurring within a few hours of injection. The effect is presumably related to direct alveolar capillary injury. ^[37]

Aspirin is the most common anti-inflammatory drug associated with adverse reactions. An ARDS-type syndrome has been described with salicylate toxicity. Methotrexate is increasingly used as an anti-inflammatory agent to treat many disorders. A low-dose regimen is typically used; nevertheless, pulmonary toxicity has been reported in approximately 4% of patients. Pulmonary reaction to methotrexate is commonly subacute, with a hypersensitivity-like reaction. HRCT shows changes of interstitial pneumonitis and occasionally centrilobular nodules or a localized nodular airspace consolidation.

The main value of HRCT is in the depiction of parenchymal abnormalities in symptomatic patients who have normal or questionable findings on chest radiography. HRCT is superior to radiography in depicting the presence and distribution of parenchymal abnormalities. One study reported abnormal findings on HRCT in all patients and abnormal findings on radiography in 74%. ^[41] Abnormalities most commonly overlooked on radiography include ground-glass opacities and mild fibrosis.

Findings on HRCT associated with drug-induced lung disease can mimic many other pulmonary pathologies, such as infection, pulmonary fibrosis, and disease recurrence. The diagnosis should be suspected in patients receiving one or more drugs known to be potentially damaging to the lung and in those with radiologic findings consistent with interstitial pneumonitis and fibrosis, hypersensitivity reaction, ARDS, or BOOP.

Although ultrasonography has no direct role in the management of drug-induced lung disease, it does have a role in the confirmation of pleural effusions and assessment for pleural intervention.

Richman et al found diffuse gallium-67 (⁶⁷ Ga) localization in both lungs in 2 patients with interstitial pneumonitis associated with bleomycin therapy. ^[42] Clinical symptoms and the results of laboratory evaluation of pulmonary status were correlated with scintigraphic findings in these 2 patients, whereas discrepancies between scintigraphic and radiographic findings were observed.

Khan et al described a patient receiving a cardiac transplant who presented with a fever of undetermined etiology. ^[43] The patient had been taking multiple medications, including phenytoin. A chest radiograph and CT scan revealed no active disease. A⁶⁷ Ga study showed diffuse intense uptake in both lungs. A bronchoscopic biopsy confirmed hypersensitivity pneumonitis. Phenytoin was withdrawn, and a corticosteroid was started in therapeutic doses. A follow-up⁶⁷ Ga study obtained 25 days after the baseline study demonstrated marked improvement in the lungs, with concurrent clinical recovery. This case illustrates the usefulness of⁶⁷ Ga imaging in the detection of drug-induced pneumonitis and in the follow-up of response to therapy.

Brown et al described a case of pulmonary granulomatosis in a user who habitually injected methylphenidate (Ritalin) intravenously. ^[44] Symptomatic and objective improvement occurred with corticosteroid therapy.⁶⁷ Ga lung scans showed increased accumulation of the radionuclide; a diffusely increased concentration of⁶⁷ Ga was observed in both lungs. The abnormal accumulation of⁶⁷ Ga was reduced, the arterial oxygen pressure and the diffusing capacity for carbon monoxide were improved, and the infiltrate was reduced on the chest radiograph 2 months after the start of therapy.

Limited evidence suggests that ⁶⁷Ga scanning may be useful in evaluating drug-induced pneumonitis and pulmonary granulomatous disease. Although ⁶⁷Ga scanning and positron-emission tomography scanning are not primary modalities for the diagnosis of lung toxicity, they are commonly used in follow-up imaging of patients with various malignancies; therefore, it is important to recognize the findings of lung toxicity on these images. ⁶⁷Ga uptake may occur in other types of granulomatous disease, such as sarcoids, infections, and lymphomas.

Babu KS, Marshall BG. Drug-induced airway diseases. Clin Chest Med. 2004 Mar. 25(1):113-22.

Camus P, Bonniaud P, Fanton A, et al. Drug-induced and iatrogenic infiltrative lung disease. Clin Chest Med. 2004 Sep. 25(3):479-519, vi.

Camus PH, Foucher P, Bonniaud PH, Ask K. Drug-induced infiltrative lung disease. Eur Respir J Suppl. 2001 Sep. 32:93s-100s. [Medline].

Erasmus JJ, McAdams HP, Rossi SE. Drug-induced lung injury. Semin Roentgenol. 2002 Jan. 37(1):72-81. [Medline].

Fraser RS, Mueller NL, Colman N, Pare PD. Drugs. In: Fraser RS, Mueller NL, Colman N, Pare PD, eds. Diagnosis of Diseases of the Chest. 4th ed. Philadelphia, PA:. WB Saunders. 1999: 2537-83.

Huggins JT, Sahn SA. Drug-induced pleural disease. Clin Chest Med. 2004 Mar. 25(1):141-53.

Limper AH, Rosenow EC. Drug-induced interstitial lung disease. Curr Opin Pulm Med. 1996 Sep. 2(5):396-404. [Medline].

Lock BJ, Eggert M, Cooper JA. Infiltrative lung disease due to noncytotoxic agents. Clin Chest Med. 2004 Mar. 25(1):47-52.

Morelock SY, Sahn SA. Drugs and the pleura. Chest. 1999 Jul. 116(1):212-21. [Medline].

Ozkan M, Dweik RA, Ahmad M. Drug-induced lung disease. Cleve Clin J Med. 2001 Sep. 68(9):782-5, 789-95. [Medline].

Graves MW, Kiratli PO, Mozley D, et al. Scintigraphic diagnosis of a right to left shunt in end-stage lung disease. Respir Med. 2003 May. 97(5):549-54. [Medline].

Sulkowska K, Palczewski P, Miszewska-Szyszkowska D, Durlik M, Golebiowski M, Malkowski P. Early everolimus-induced pneumonitis in a renal transplant recipient: A case report. Ann Transplant. 2012 Dec 31. 17(4):144-8. [Medline].

Allen JN. Drug-induced eosinophilic lung disease. Clin Chest Med. 2004 Mar. 25(1):77-88.

Vital Durand D, Durieu I, Rousset H. [Toxic or drug-induced granulomatous reactions]. Rev Med Interne. 2008 Jan. 29(1):33-8. [Medline].

Kasai S, Tokuda H, Yoshikawa M, Nishine H, Nishiyama H. [A case of salazosulfapyridine-induced pneumonitis presenting with multiple pulmonary nodules and lymphadenopathy]. Nihon Kokyuki Gakkai Zasshi. 2006 Dec. 44(12):928-32. [Medline].

Antonio GE, Wong KT, Hui DS, et al. Thin-section CT in patients with severe acute respiratory syndrome following hospital discharge: preliminary experience. Radiology. 2003 Sep. 228(3):810-5. [Medline].

Cleverley JR, Screaton NJ, Hiorns MP, et al. Drug-induced lung disease: high-resolution CT and histological findings. Clin Radiol. 2002 Apr. 57(4):292-9. [Medline].

Ellis SJ, Cleverley JR, Müller NL. Drug-induced lung disease: high-resolution CT findings. AJR Am J Roentgenol. 2000 Oct. 175(4):1019-24. [Medline]. [Full Text].

Erasmus JJ, McAdams HP, Rossi SE, et al. High-resolution CT of drug-induced lung disease. Radiol Clin North Am. 2002 Jan. 40(1):61-72. [Medline].

Shah RM, Miller W. Widespread ground-glass opacity of the lung in consecutive patients undergoing CT: Does lobular distribution assist diagnosis?. AJR Am J Roentgenol. 2003 Apr. 180(4):965-8. [Medline]. [Full Text].

Tanaka N, Newell JD, Brown KK, et al. Collagen vascular disease-related lung disease: high-resolution computed tomography findings based on the pathologic classification. J Comput Assist Tomogr. 2004 May-Jun. 28(3):351-60.

Zompatori M, Rimondi MR. Diffuse ground-glass opacity of the lung. A guide to interpreting the high-resolution computed tomographic (HRCT) picture [in Italian]. Radiol Med (Torino). 1994 Nov. 88(5):576-81. [Medline].

Lee HN, Kim MY, Koo HJ, Kim SS, Yoon DH, Lee JC, et al. Thin-Section CT Characteristics and Longitudinal CT Follow-up of Chemotherapy Induced Interstitial Pneumonitis: A Retrospective Cohort Study. Medicine (Baltimore). 2016 Jan. 95 (2):e2460. [Medline].

Rosenow EC III, Limper AH. Drug-induced pulmonary disease. Semin Respir Infect. 1995 Jun. 10(2):86-95. [Medline].

Cannon GW. Methotrexate pulmonary toxicity. Rheum Dis Clin North Am. 1997 Nov. 23(4):917-37. [Medline].

Alexandrescu DT, Dutcher JP, O’Boyle K, et al. Fatal intra-alveolar hemorrhage after rituximab in a patient with non-Hodgkin lymphoma. Leuk Lymphoma. 2004 Nov. 45(11):2321-5. [Medline].

Garrido M, O’Brien A, González S, Clavero JM, Orellana E. Cryptogenic organizing pneumonitis during oxaliplatin chemotherapy for colorectal cancer: case report. Chest. 2007 Dec. 132(6):1997-9. [Medline].

Ohnishi K, Sakai F, Kudoh S, Ohno R. Twenty-seven cases of drug-induced interstitial lung disease associated with imatinib mesylate. Leukemia. 2006 Jun. 20(6):1162-4. [Medline].

Buttin BM, Moore MJ. Thalidomide-induced reversible interstitial pneumonitis in a patient with recurrent ovarian cancer. Gynecol Oncol. 2008 Jan 10. [Medline].

Nishino M, Brais LK, Brooks NV, Hatabu H, Kulke MH, Ramaiya NH. Drug-related pneumonitis during mammalian target of rapamycin inhibitor therapy in patients with neuroendocrine tumors: a radiographic pattern-based approach. Eur J Cancer. 2016 Jan. 53:163-70. [Medline].

Farr KP, Kallehauge JF, Møller DS, Khalil AA, Kramer S, Bluhme H, et al. Inclusion of functional information from perfusion SPECT improves predictive value of dose-volume parameters in lung toxicity outcome after radiotherapy for non-small cell lung cancer: A prospective study. Radiother Oncol. 2015 Oct. 117 (1):9-16. [Medline].

Diederich S. Chest CT for suspected pulmonary complications of oncologic therapies: how I review and report. Cancer Imaging. 2016 Apr 11. 16:7. [Medline].

Pipavath S, Godwin JD. Imaging of the chest: idiopathic interstitial pneumonia. Clin Chest Med. 2004 Dec. 25(4):651-6, v-vi.

Daba MH, El-Tahir KE, Al-Arifi MN, Gubara OA. Drug-induced pulmonary fibrosis. Saudi Med J. 2004 Jun. 25(6):700-6.

Lee-Chiong T, Matthay RA. Drug-induced pulmonary edema and acute respiratory distress syndrome. Clin Chest Med. 2004 Mar. 25(1):95-104.

Copper JA. Drug-induced lung disease. Adv Intern Med. 1997. 42:231-68. [Medline].

Aronchick JM, Gefter WB. Drug-induced pulmonary disorders. Semin Roentgenol. 1995 Jan. 30(1):18-34. [Medline].

Rosenow EC III. Drug-induced pulmonary disease. Dis Mon. 1994 May. 40(5):253-310. [Medline].

Rosenow EC III, Myers JL, Swensen SJ, Pisani RJ. Drug-induced pulmonary disease. An update. Chest. 1992 Jul. 102(1):239-50. [Medline].

Wolff AJ, O”Donnell AE. Pulmonary effects of illicit drug use. Clin Chest Med. 2004 Mar. 25(1):203-16.

Padley SP, Adler B, Hansell DM, Muller NL. High-resolution computed tomography of drug-induced lung disease. Clin Radiol. 1992 Oct. 46(4):232-6. [Medline].

Richman SD, Levenson SM, Bunn PA, et al. 67Ga accumulation in pulmonary lesions associated with bleomycin toxicity. Cancer. 1975 Dec. 36(6):1966-72. [Medline].

Khan AS, Dadparvar S, Brown SJ, et al. The role of gallium-67-citrate in the detection of phenytoin-induced pneumonitis. J Nucl Med. 1994 Mar. 35(3):471-3. [Medline].

Brown DG, Aguirre A, Weaver A. 67Gallium scanning in talc-induced pulmonary granulomatosis. Chest. 1980 Apr. 77(4):561-5. [Medline].

Ali Nawaz Khan, MBBS, FRCS, FRCP, FRCR Consultant Radiologist and Honorary Professor, North Manchester General Hospital Pennine Acute NHS Trust, UK

Ali Nawaz Khan, MBBS, FRCS, FRCP, FRCR is a member of the following medical societies: American Association for the Advancement of Science, American Institute of Ultrasound in Medicine, British Medical Association, Royal College of Physicians and Surgeons of the United States, British Society of Interventional Radiology, Royal College of Physicians, Royal College of Radiologists, Royal College of Surgeons of England

Disclosure: Nothing to disclose.

Klaus L Irion, MD, PhD Consulting Staff, The Cardiothoracic Centre Liverpool NHS Trust, The Royal Liverpool University Hospital, UK

Klaus L Irion, MD, PhD is a member of the following medical societies: American Roentgen Ray Society, Radiological Society of North America

Disclosure: Nothing to disclose.

Chitra P Nagarajaiah, MBBS, MRCP Acute Medicine Specialist Registrar, City Hospital of Birmingham, UK

Chitra P Nagarajaiah, MBBS, MRCP is a member of the following medical societies: Royal College of Physicians

Disclosure: Nothing to disclose.

Bernard D Coombs, MB, ChB, PhD Consulting Staff, Department of Specialist Rehabilitation Services, Hutt Valley District Health Board, New Zealand

Disclosure: Nothing to disclose.

Eugene C Lin, MD Attending Radiologist, Teaching Coordinator for Cardiac Imaging, Radiology Residency Program, Virginia Mason Medical Center; Clinical Assistant Professor of Radiology, University of Washington School of Medicine

Eugene C Lin, MD is a member of the following medical societies: American College of Nuclear Medicine, American College of Radiology, Radiological Society of North America, Society of Nuclear Medicine and Molecular Imaging

Disclosure: Nothing to disclose.

Kitt Shaffer, MD, PhD 

Kitt Shaffer, MD, PhD is a member of the following medical societies: American Roentgen Ray Society

Disclosure: Nothing to disclose.

Imaging in Drug-Induced Lung Disease

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