• Drugs toxicity has complex pathogenesis that varies depending on the drug
  
• Onset of symptoms, variable
  
• Radiography – varied and nonspecific
  
• CT/HRCT can be helpful for toxicity from certain drugs, e.g., amiodarone, steroids, methysergide, mineral oil, vitamin D, talc
  
• Presentation: varied, dyspnea, cough, eosinophilia
  
• Many have decreased diffusing capacity
  
• Prognosis, variable
  
• Mortality from respiratory failure

General Imaging findings

• Nonspecific
  
• Sometimes normal CXR and abnormal CT/HRCT
  
• Patterns
  
  • Pulmonary edema
    
  • ARDS
    
  • Fleeting peripheral opacities (‘eosinophilic pneumonia like”)
    
  • Granulomas
    
  • Alveolar opacities
    
  • Cavitation (vasculitis)
    
  • Interstitial lung disease and honeycombing
    
  • Fine calcification
    
  • Systemic lupus erythematosis, drug induced
    
  • Pleural and pericardial effusions
    
  • Pleural effusions/fibrosis
    
  • Hilar/mediasinal lymphadenopathy
    
  • Pneumothorax (Cocaine, Nitroureas)
    
  • Pneumomediastinum (Cocaine)
    
  • Pulmonary artery hypertension (Talc, Fenfluramine)

CT/HRCT

• HRCT can show early abnormalities when radiograph is normal
  
  • Shows distribution of interstitial, ground glass, airspace opacities or honeycombing
    
• High density CT deposits in lung and liver
  
• Amiodarone – contains 37% iodine by weight
  
  • Multiple peripheral opacities
    
  • Reticulonodular opacities
    
  • Fibrosis, honeycombing
    
• Fine calcification
  
  • Vitamin D
    
  • CXR may be normal
    
  • HRCT may show calcification before radiography
    
  • Bone scanning agents may show uptake
    
• Lipoid pneumonia
  
  • Mineral oil ingestion
    
  • Low attenuation opacities – fat density
    
• Micronodules, basal predominance
  
  • Talc
    
    • Ground glass opacities
      
    • Pulmonary artery hypertension
      
• Mediasinal lipomatosis/extrapleural fat
  
  • Steroids
    
  • Fat attenuation best seen with CT
    

• Pulmonary edema,
  
• ARDS
  
• Pneumonia
  
• Aspiration
  
• UIP
  
• Lymphoma,
  
• Differentiation: always consider history of drug use

• Pathogenesis is complex
  
  • Pulmonary edema
    
  • Heroin, cocaine
    
  • Aspirin
    
  • Contrast media
    
  • Cytosine arabinoside
    
  • Mitomycin – hemolytic uremic syndrome
    
  • Tricyclic antidepressants – edema, ARDS
    
  • Hydrochlorothiazide
    
  • Interleukin-2
    
• Direct toxic damage to lung - diffuse alveolar damage
  
  • Cytoxan, bleomycin, methotrexate, busulfan, carmustine
    
    • Bleomycing
      
      • Multi focal rounded opacities may simulate metastases
        
  • Oxygen
    
• Pleura/mediastinal fibrosis
  
  • Methysergide
    
  • Ergotamine
    
  • Ergonovine
    
• Pleural effusions
  
  • Methotrexate procarcazine
    
  • Nitrofuradantoin
    
• Hypersensitivity reaction (Type I or III)
  
  • Bleomycin, methotrexate, procarbazine
    
• Neural or humoral mechanisms
  
  • Asthma – propranolol, neostigmine, aspirin
    
• Autoimmune response, systemic lupus erythematosis, drug-induced
  
  • Procainamide, hydralazine, isoniazide, phenytoin, and many other drugs
    
• Vasculitis
  
  • Sulfonamides, penicillin, cromolyn sodium
    
• Pulmonary hemorrhage
  
  • Anticoagulants, estrogens, penicillamine, and others
    
• Drug induced phospholipidoses
  
  • Amiodarone
    
• Constrictive bronchiolitis
  
  • Penicillamine
    
  • Sulfasalazine
    
• Pulmonary calcification
  
  • Vitamin D
    
  • Calcium in milk alkali syndrome
    
• Chronic pleural effusions/fibrosis
  
  • Bromcriptine
    
• Hilar/mediasinal lymphadenopathy
  
  • Methorexate
    
  • Phenytoin
    
• Granulomas
  
  • Methotraxate
    
  • Nitrofurantoin
    
  • Mineral oils
    
  • Talc

• Age and gender, variable
  
• Approximately 40 commonly used drugs may cause lung disease
  
• Aspirin, Mitomycin
  
  • Asthma
    
• Methotrexate – onset, weeks after start of treatment
  
• Fever, cough, dyspnea
  
• Eosinophilia
  
• Fibrosis
  
• Treated with steroids
  
• Mortality – 10%
  
• Bleomycin – onset 3 months after start of treatment
  
• Diffusing capacity most sensitive test
  
• With early detection – lung disease may be reversible
  
• Cytosine arabinoside – onset 2 – 21 days after start of treatment
  
• Recovery after discontinuance of drug
  
• Some develop respiratory failure
  
• ALL-TRANS Retinoic Acid – onset 5-15 days
  
• Fever, respiratory distress, anasarca, cardiac decompensation, hypotension
  
• Diffuse pulmonary opacities
  
• Treated with steroids
  
• Potentially fatal
  
• Amiodarone – onset 6 months after start of treatment
  
• 5% incidence of pulmonary toxicity
  
• Dyspnea
  
• Decreased diffusing capacity
  
• Fatality < 20%
  
• Gold – onset < 3 months after start of treatment
  
• Fever, proteinuria, skin rash
  
• Eosinophilia
  
• Resolves with discontinuation of drug
  
• Dilantin – 1 week – 30 years
  
• Rash, hepatosplenomegaly, eosinophilia, lymphadenopathy
  
• Pseudolymphoma, adenopathy, fever, skin rash, eosinophilia, hepatosplenomegaly
  
• Risk for lymphoma – Hodgkin’s, nonHodgkin’s lymphoma
  
• Fenfluramines
  
• Pulmonary artery hypertension, valvular heart disease
  
• Nitrofurantoin
  
• Acute, onset - 1 day to 1 month after start of treatment
  
  • Fever, chest pain, dyspnea, rash, cough, arthralgia
    
  • Complete response after discontinuation of drug
    
• Chronic – onset, 6 months
  
  • Fibrosing alveolitis
    
  • If prolonged exposure, may not reverse with withdrawal of drug
    
  • 10% mortality

Rosenow EC, 3rd, Myers JL, Swensen SJ, et al. Drug-induced pulmonary disease. An update Chest 102:239-250, 1992
Rossi SE, Erasmus JJ, McAdams HP, et al. Pulmonary drug toxicity: radiologic and pathologic manifestations Radiographics 20:1245-1259, 2000