Can hydralazine (apresoline) cause organizing pneumonia or a 'crazy paving' pattern on computed tomography (CT) scans?

Hydralazine and Organizing Pneumonia/Crazy Paving Pattern

While hydralazine is not specifically documented in the provided evidence as causing organizing pneumonia or crazy paving patterns, drug-induced organizing pneumonia is a well-recognized entity that can present with these CT findings, and hydralazine is a known cause of drug-induced lung disease (particularly lupus-related pneumonitis). The absence of hydralazine in the specific drug lists provided does not exclude it as a potential cause, as drug-induced pneumonitis can occur with numerous medications.

Understanding Drug-Related Pneumonitis Patterns

Drug-related pneumonitis (DRP) can manifest with multiple CT patterns, including organizing pneumonia (OP) and crazy paving appearance, and diagnosis relies heavily on temporal relationships between drug administration and symptom onset. 1

Organizing Pneumonia Pattern on CT

The organizing pneumonia pattern demonstrates: 1

• Multifocal patchy alveolar opacities with peribronchovascular and/or peripheral distribution
• May demonstrate reversed halo sign
• Consolidation in peribronchovascular and/or peripheral distribution, often with ground-glass opacity 1

Crazy Paving Pattern

The crazy paving pattern consists of: 1

• Ground-glass opacity with superimposed interlobular septal thickening and intralobular interstitial thickening
• This pattern is nonspecific and can result from various diseases including drug-induced pneumonitis 2
• Originally described in pulmonary alveolar proteinosis but now recognized in multiple conditions 1, 2

Documented Drug Causes of Organizing Pneumonia

The evidence identifies several drug classes that definitively cause organizing pneumonia: 3

• Salicylates (sulfasalazine, 5-ASA)
• Methotrexate (causing hypersensitivity pneumonitis or pulmonary fibrosis with organizing features)
• Anti-TNF monoclonal antibodies (paradoxically causing granulomatous inflammation compatible with organizing pneumonia)
• Thiopurines (associated with parenchymal lung disease including organizing pneumonia patterns)

Diagnostic Approach for Suspected Drug-Induced Organizing Pneumonia

When evaluating a patient on hydralazine with organizing pneumonia or crazy paving pattern, the key diagnostic steps include: 1

1. Establish temporal relationship between hydralazine initiation and symptom onset
2. Exclude infectious etiologies through bronchoscopy with bronchoalveolar lavage (BAL) 4
3. Exclude other causes including malignancy, connective tissue disease, and other drug exposures 3, 5
4. Consider surgical lung biopsy if diagnosis remains uncertain after non-invasive testing 4

Critical Pitfall to Avoid

Do not attribute respiratory symptoms solely to opportunistic infection in patients on multiple medications—drug-induced organizing pneumonia must be considered in the differential. 3 The diagnosis of drug-related pneumonitis is based on temporal relationships and exclusion of alternative causes, as CT patterns are typically nonspecific for any particular drug. 1

Management Considerations

If hydralazine-induced organizing pneumonia is suspected: 4, 6

• Discontinue the offending agent (hydralazine)
• Initiate oral corticosteroids (typically prednisone ~50 mg/day initially) as the mainstay of treatment
• Monitor for treatment response with follow-up imaging
• Watch for relapses, which are common even with appropriate treatment
• Assess for progression to fibrotic disease, which can occur in a subgroup of patients despite treatment

The prognosis varies significantly: secondary organizing pneumonia (drug-induced) has a 5-year survival rate of 44%, compared to 73% for cryptogenic organizing pneumonia. 6