What are the possible causes of diffuse ground glass opacities on computed tomography (CT) imaging, suggestive of pulmonary edema, in a 32-year-old female patient with a recent history of pulmonary embolism (PE), now off anticoagulant, presenting with pleuritic chest pain, normal D-dimer, normal computed tomography pulmonary angiogram (CTPA), and no history of coronary or cardiac problems?

Differential Diagnosis of Diffuse Ground Glass Opacities in a Young Patient with Recent PE

In this 32-year-old patient with pleuritic chest pain, normal cardiac workup, and diffuse ground glass opacities (GGOs) on CT, the most likely diagnoses to consider are organizing pneumonia, hypersensitivity pneumonitis, atypical infection, drug-related pneumonitis, or pulmonary infarction from undetected subsegmental emboli—with organizing pneumonia being particularly high on the differential given the acute presentation with pleuritic pain and diffuse GGO pattern. 1

Primary Diagnostic Considerations

Organizing Pneumonia (OP)

• Organizing pneumonia characteristically presents with patchy consolidation or GGO in predominantly peripheral or peribronchovascular distribution, often with pleuritic chest pain. 1
• This diagnosis should be strongly considered in your patient given the acute presentation with pleuritic pain and diffuse GGOs without cardiac abnormalities. 1
• The subpleural distribution pattern, if present on the CT, would further support this diagnosis. 1

Hypersensitivity Pneumonitis (HP)

• HP demonstrates small, poorly defined centrilobular nodules with widespread GGO, particularly in nonsmokers. 1, 2
• Obtain a detailed exposure history to organic antigens (birds, mold, hot tubs, humidifiers, occupational exposures) as this is the key diagnostic step. 3
• Look for the "three-density pattern" (hypoattenuating, normal, and hyperattenuating lobules in close proximity) on CT, which is highly specific for fibrotic HP. 1, 2
• Consider obtaining inspiratory and expiratory CT views to assess for mosaic attenuation and air-trapping, which supports HP diagnosis. 3

Atypical Infections

• Viral pneumonias (influenza, COVID-19, cytomegalovirus) and atypical bacterial infections can present with diffuse GGOs. 4
• COVID-19 pneumonia characteristically shows multiple patchy subpleural GGOs with a "paving stone-like" appearance (GGO with interlobular septal thickening). 1
• Obtain sputum cultures, viral respiratory panel, and consider COVID-19 testing if not already done. 3

Drug-Related Pneumonitis

• Review all medications started within the past 3-12 weeks, as drug-related pneumonitis can present with various interstitial pneumonia patterns including GGOs. 2, 3
• Common culprits include molecular targeting agents, immune checkpoint inhibitors, amiodarone, nitrofurantoin, and methotrexate. 2

Pulmonary Infarction from Subsegmental PE

• Although CTPA was reported as negative, isolated subsegmental filling defects may require further imaging tests to confirm or exclude PE. 5
• Approximately 75% of patients with pulmonary emboli and pleural effusion have pleuritic chest pain. 6
• The mechanism of GGO in PE context could be increased interstitial fluid from ischemia or release of vasoactive cytokines. 6
• Consider lower extremity compression ultrasound to evaluate for DVT, which if positive, would confirm venous thromboembolism even without visible PE on CTPA. 5

Pulmonary Edema (Non-Cardiac)

• Isolated GGOs without fibrotic features are usually associated with inflammatory cells in the alveolar septum or lumen (alveolitis), but can also represent pulmonary edema. 1, 2
• Non-cardiogenic causes to consider include:
  • Negative pressure pulmonary edema (NPPE): presents with extensive centrally accentuated consolidations with surrounding GGO, but typically occurs perioperatively. 7
  • Neurogenic pulmonary edema
  • High-altitude pulmonary edema (obtain travel history)
  • Capillary leak syndromes

Alveolar Hemorrhage

• Presents with bilateral patchy GGOs in middle and lower lung zones. 2
• Check for hemoptysis (even occult), anemia, and consider autoimmune workup (ANCA, anti-GBM antibodies) if suspected. 2

Recommended Diagnostic Algorithm

Immediate Steps:

1. Obtain detailed exposure history: occupational exposures, birds, mold, hot tubs, recent travel, new medications (within 3-12 weeks). 3
2. Review the CT pattern carefully:
   • Distribution (peripheral/subpleural vs. diffuse vs. centrilobular) 1
   • Associated findings (interlobular septal thickening, "paving stone" appearance, centrilobular nodules, mosaic attenuation) 1, 3
3. Laboratory workup:
   • Complete blood count (assess for anemia suggesting hemorrhage)
   • Comprehensive metabolic panel (already normal per your report)
   • Inflammatory markers (ESR, CRP)
   • Autoimmune panel if clinically indicated (ANA, ANCA, anti-GBM)
   • Respiratory viral panel including COVID-19
   • Consider procalcitonin to assess bacterial infection likelihood

Secondary Evaluation:

1. Pulmonary function tests with DLCO: The extent of GGO on CT correlates with physiologic impairment. 1, 2
2. Consider bronchoscopy with BAL:
   • BAL lymphocyte differential >20% supports HP diagnosis. 3
   • Cell differential can help distinguish between infection, hemorrhage, and inflammatory processes. 3
3. Repeat lower extremity compression ultrasound: A positive proximal DVT would confirm venous thromboembolism even with negative CTPA. 5

Critical Pitfalls to Avoid

• Do not assume infectious etiology without considering HP, especially in nonsmokers with exposure history. 3
• Do not overlook recent medication changes, as drug-related pneumonitis can occur 3-12 weeks after drug initiation. 3
• Extensive GGO (>30% of lung involvement) argues against idiopathic pulmonary fibrosis and should prompt consideration of alternative diagnoses such as NSIP, organizing pneumonia, or HP. 1, 3
• Do not dismiss the possibility of subsegmental PE despite negative CTPA, particularly given the recent PE history and pleuritic chest pain. 5

Empiric Treatment Consideration

If organizing pneumonia is strongly suspected based on imaging pattern (peripheral/subpleural GGOs) and clinical context (acute presentation with pleuritic pain, no clear alternative diagnosis), consider an empirical high-dose corticosteroid trial with expected improvement within 48-72 hours. 1 However, this should only be initiated after excluding active infection through appropriate testing.