- One of the most common drug-induced pulmonary diseases
- Toxicity occurs in <1% of all users of drug
- Acute Nitrofurantoin Toxicity: unclear mechanism (studies have shown prolonged lymhocyte transformation factor and migration inhibition factor production)
- Chronic Nitrofurantoin Toxicity: induction of oxygen radicals by parenchymal cells
- Acute Nitrofurantoin Toxicity: proliferation of fibroblasts/lymhoplasmocytic infiltrate (IgA-laden plasma cells)/DIP-like features
- Importantly, absence of eosinophilia in lung tissue (despite peripheral eosinophilia)
- Chronic Nitrofurantoin Toxicity: mimics idiopathic pulmonary fibrosis
Pulmonary Adverse Effects
- Onset: few hrs to several days after initiation of nitrofurantoin
- Incidence is 1 in 550-5400
- More common in females (possibly due to increased use of drug in females for UTI’s)
- Not dose-related (can occur after single dose)
- CBC: peripheral leukocytosis and eosinophilia (33% of cases)
- Elevated ESR (50% of cases)
- CXR/Chest CT
- Basilar-predominant alveolar and/or interstitial infiltrates: may be unilateral or asymmetric
- Pleural Effusion: usually unilateral
- 20% of acute cases have infiltrate with effusion
- 3% of acute cases have isolated effusion
- PFT’s: obstruction
- Pleural Fluid: may demonstrate pleural eosinophilia in some cases
- Fever (usually present)
- Dyspnea (usually present)
- Cough (66% of cases)
- Bronchospasm (see Obstructive Lung Disease): may occur in the absence of parenchymal or pleural manifestations in some cases
- Pleuritic Chest Pain (33% of cases)
- Rales (most cases)
- Supportive care
- Not clear that corticosteroids are effective -> probably not indicated
- Re-challenge is contraindicated
- Chronic nitrofurantoin toxicity is less common than acute nitrofurantoin toxicity
- Onset: 6 months-years after start of continuous or intermittent use of nitrofurantoin
- More common in females
- CXR/Chest CT
- Diffuse interstitial infiltrates
- Pleural Effusion: 10% of chronic cases have effusion (no chronic cases have effusion without infiltrates)
- PFT’s: restriction without obstruction
- FOB-BAL: lymphocytosis
- OLB: inflammatory cells and fibrosis
- Fever and eosinophilia are less common than in acute toxicity
- Insidious onset of fever and cough
- Withdraw Nitrofurantoin: wait 2-4 mo to see if resolves (by CT + PFT’s) without steroids -> if not, then initiate a trial of corticosteroids
- Few reported cases: present with pleuropulmonary disease with positive ANA
- May appear as nodular infiltrates
Other Adverse Effects
- 71% of all reactions are severe enough to require hospitalization
- 1% of all cases were fatal: 4/49 with chronic fibrosis toxicity and 2/398 with acute toxicity
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