Acute Eosinophilic Pneumonia
I. What every physician needs to know.
Acute eosinophilic pneumonia (AEP) is an idiopathic, acute, febrile illness characterized by non-productive cough, dyspnea, diffuse pulmonary infiltrates, and hypoxemia with eosinophilic infiltration of the pulmonary parenchyma. The diagnosis is made when bronchoalveolar lavage cell count reveals > 25% eosinophils in the absence of medication-related, infectious or atopic triggers. The treatment is systemic corticosteroids.
II. Diagnostic Confirmation: Are you sure your patient has Acute Eosinophilic Pneumonia?
Suspect acute eosinophilic pneumonia in previously healthy patients with progressive dyspnea over less than one month with diffuse parenchymal opacities on imaging.
A. History Part I: Pattern Recognition:
Patients with acute eosinophilic pneumonia present with an acute respiratory illness of less than four weeks; typically symptoms last fewer than seven days before the patient seeks medical attention. The most common symptoms are non-productive cough, dyspnea, and fever though malaise, night sweats, chills, myalgias, and pleuritic chest pain are possible as well.
Patients with AEP are typically previously healthy before the respiratory syndrome develops. Recent onset of cigarette smoking (for the first time or after a period of abstinence) can be a clinical clue that supports the diagnosis of AEP. The cause of this correlation is unknown, but researchers believe that AEP may be an acute hypersensitivity reaction to an inhaled antigen.
B. History Part 2: Prevalence:
Acute eosinophilic pneumonia is a rare, idiopathic disease. It can occur at any age, though most patients are in their third through fifth decades. Men are affected twice as frequently as women. As mentioned above, AEP is associated with smoking, particularly new smokers.
C. History Part 3: Competing diagnoses that can mimic Acute Eosinophilic Pneumonia.
Given that AEP is characterized by acute respiratory failure with fever and diffuse pulmonary infiltrates, the initial differential diagnosis is broad and includes severe community-acquired bacterial or viral pneumonia (including influenza), acute interstitial pneumonia, fulminant cryptogenic organizing pneumonia, diffuse alveolar haemorrhage, granulomatosis with polyangiitis, and acute respiratory distress syndrome.
When eosinophilia is identified on bronchoalveolar lavage or peripheral complete blood cell counts, the differential diagnosis evolves to include the following syndromes:
Eosinophilic granulomatosis with polyangiitis (Churg-Strauss disease);
Fungal pulmonary infections such as Coccidioides or invasive aspergillosis;
Parasitic infections such as ascariasis and strongyloidiasis;
Eosinophilic pneumonias due to drug exposure, toxins, or radiation;
Allergic bronchopulmonary aspergillosis;
Simple pulmonary eosinophilia (previously called Loeffler’s syndrome, a benign disorder with one or more migrating, self-resolving, typically peripheral pulmonary opacities);
Chronic eosinophilic pneumonia (CEP) is a disease with a longer course than AEP; it is characterized by systemic and pulmonary symptoms.
D. Physical Examination Findings.
Physical exam findings include hypoxemia, fever, tachypnea, non-productive cough, and bilateral diffuse rales. If pleural effusions are present, there is decreased tactile fremitus and increased dullness to percussion. Given the acute nature of respiratory failure in AEP, clubbing and signs of cor pulmonale are absent.
E. What diagnostic tests should be performed?
There are no physical exam findings that confirm the diagnosis; lab and radiographic studies are needed.
1. What laboratory studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?
Patients with AEP should receive the standard work-up for any individual with acute-onset, febrile respiratory failure:
Complete blood count with differential (Of note, patients with AEP typically have a peripheral blood neutrophilia – not eosinophilia – on presentation. Peripheral eosinophilia is a later development);
Complete metabolic panel;
Arterial or venous blood gas;
Influenza polymerase chain reaction (PCR);
Other tailored infectious studies (such as Coccidioides serology or strongyloides enzyme linked immunosorbent assay [ELISA]);
Anti-neutrophil cytoplasmic antibody;
Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP);
Immunoglobulin E (IgE) levels.
If the patient has pleural effusions, thoracentesis is helpful; fluid cell counts will show marked eosinophilia.
Bronchoalveolar lavage (BAL) is required to diagnose acute eosinophilic pneumonia. BAL will reveal > 25% eosinophils on cell count with negative infectious studies and negative cytology. Of note, expectorated sputum is not helpful in diagnosis; it may show eosinophilia but the sensitivity and specificity of expectorated sputum cell counts have not been formally evaluated.
Lung biopsy is not necessary to identify AEP but can be done if the diagnosis remains unclear. Pathology will reveal acute and organizing diffuse alveolar damage with marked number of interstitial and alveolar eosinophils.
Patients do not usually receive pulmonary function testing due to their acute presentation, but pulmonary function tests (PFTs) reveal a restrictive pattern in AEP.
2. What imaging studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?
Chest x-ray should be ordered on all patients with acute respiratory symptoms. AEP will manifest in a variety of ways, from subtle reticulonodular changes to diffuse ground-glass alveolar and/or interstitial opacities. The distribution of opacities is widespread, unlike chronic eosinophilic pneumonia in which opacities are typically localized in the lung periphery. Bilateral pleural effusions may be present as well. See Figure 1.
High-resolution chest computed tomography (CT) should also be ordered and will almost always show bilateral ground glass or reticular opacities. There may also be interlobular septal thickening and bilateral pleural effusion(s). See Figure 2.
F. Over-utilized or “wasted” diagnostic tests associated with this diagnosis.
There are no commonly over-utilized tests for acute eosinophilic pneumonia.
III. Default Management.
A. Immediate management.
Patients with acute eosinophilic pneumonia typically receive empiric broad-spectrum antibiotics plus supportive care with supplemental oxygen and possibly mechanical ventilation on admission. However, once infectious causes are ruled out, systemic glucocorticoid therapy serves as the foundation of treatment. Without steroids, most patients experience progressive respiratory failure, though those with milder initial disease may experience spontaneous remission following smoking cessation without glucocorticoid therapy.
The optimal dose and length of glucocorticoid treatment is unknown. Initial therapy is usually based on severity of respiratory compromise: intravenous methylprednisolone (60 to 125 milligram [mg] every 6 hours) is used for profound hypoxemia whereas oral prednisone (40 to 60 mg daily) is used for milder cases.
No other immunomodulatory medications are currently used for acute eosinophilic pneumonia.
B. Physical Examination Tips to Guide Management.
Continuous reassessment of respiratory status is crucial in the management of AEP. Patients with progressive respiratory failure require more aggressive supportive measures (such as mechanical ventilation) and glucocorticoid treatment in the form of high dose, intravenous systemic glucocorticoids.
C. Laboratory Tests to Monitor Response To, and Adjustments in, Management.
Treatment adjustments should be made based on respiratory status, which may include arterial blood gases.
D. Long-term management.
Once infection is ruled out, antibiotics should be stopped. Patients with severe respiratory failure should receive intravenous methylprednisolone until their respiratory status improves. At that point, patients should continue on 40 to 60 mg of prednisone per day for two weeks, after which they can undergo a weekly glucocorticoid taper. A longer treatment course may be required for patients who experience severe respiratory failure with delayed resolution of symptoms and imaging abnormalities.
E. Common Pitfalls and Side-Effects of Management.
If patients with acute eosinophilic pneumonia receive high-dose steroids for more than three weeks, clinicians need to prevent steroid-related complications such as osteoporosis (using calcium and vitamin D), Pneumocystis jiroveci infection (using trimethoprim-sulfamethoxazole), and peptic ulcer disease (using proton pump inhibitors).
IV. Management with Co-Morbidities.
A. Renal Insufficiency.
No change in standard management.
B. Liver Insufficiency.
No change in standard management.
C. Systolic and Diastolic Heart Failure.
Clinicians should monitor patients for fluid retention and hypertension while on high-dose glucocorticoids.
D. Coronary Artery Disease or Peripheral Vascular Disease.
Clinicians should monitor patients for hypertension while on high-dose glucocorticoids.
E. Diabetes or other Endocrine issues.
Clinicians should monitor patients for hyperglycemia while on high-dose glucocorticoids.
No change in standard management.
G. Immunosuppression (HIV, chronic steroids, etc.).
Clinicians should monitor patients for infections and use trimethoprim-sulfamethoxazole to prevent Pneumocystis jiroveci infection.
H. Primary Lung Disease (COPD, Asthma, ILD).
No change in standard management. Prior lung disease is usually not present in patients with AEP.
I. Gastrointestinal or Nutrition Issues.
No change in standard management.
J. Hematologic or Coagulation Issues.
No change in standard management.
K. Dementia or Psychiatric Illness/Treatment.
Clinicians should monitor patients for mood changes while on high-dose glucocorticoids.
V. Transitions of Care.
A. Sign-out considerations While Hospitalized.
Patients require close monitoring of respiratory status and intubation if profound hypoxemia develops.
B. Anticipated Length of Stay.
Length of stay depends upon the patient’s clinical response to steroids after infection is ruled out. Patients need to be on oral steroids before discharge.
C. When is the Patient Ready for Discharge.
Patients are typically ready for discharge when they are on oral steroids and decreased supplemental oxygen. Some patients may need supplemental oxygen at discharge. Physical therapy evaluation can help identify patients who will benefit from inpatient rehabilitation prior to transfer home.
D. Arranging for Clinic Follow-up.
1. When should clinic follow up be arranged and with whom.
Patients diagnosed with acute eosinophilic pneumonia should follow-up with a pulmonologist approximately two weeks after discharge.
2. What tests should be conducted prior to discharge to enable best clinic first visit.
Ambulatory oxygen saturation testing should be completed prior to discharge.
3. What tests should be ordered as an outpatient prior to, or on the day of, the clinic visit.
No specific tests should be ordered prior to outpatient follow up, though repeat imaging (chest x-ray or CT) may help define clinical improvement.
E. Placement Considerations.
Physical therapy evaluation can help identify patients who will benefit from inpatient rehabilitation prior to transfer home. Some patients may need supplemental oxygen at discharge, whether going home or to a facility.
F. Prognosis and Patient Counseling.
Most patients have complete resolution of acute eosinophilic pneumonia disease after one course of steroids. Smoking cessation is crucial. Relapse is uncommon.
VI. Patient Safety and Quality Measures.
A. Core Indicator Standards and Documentation.
B. Appropriate Prophylaxis and Other Measures to Prevent Readmission.
Cottin, V, Cordier, JF. “Eosinophilic Pneumonias”. . vol. 60. 2005. pp. 841-857. (This article reviews eosinophilic pneumonias, including chronic eosinophilic pneumonia, acute eosinophilic pneumonia, Churg-Strauss syndrome, parasitic pneumonias, and ABPA.)
Akuthota, P, Weller, PF. “Eosinophilic Pneumonias”. . vol. 25. 2012. pp. 649-660. (This article reviews infectious and non-infectious causes of eosinophilic pneumonias.)
Philit, F. “Idiopathic Acute Eosinophilic Pneumonia: A Study of 22 Patients”. . vol. 166. 2002. pp. 1235-1239. (This article is a multicenter retrospective study that characterizes AEP in order to characterize and improve its diagnostic criteria.)
Schorr, AF. “Acute Eosinophilic Pneumonia Among US Military Personnel Deployed in or Near Iraq”. . vol. 292. 2014. pp. 2997-3005. (This is a case series of AEP in a deployed military population that identified new-onset smoking as a possible link.)
Allen, JN. “Acute Eosinophilic Pneumonia as a Reversible Cause of Non-infectious Respiratory Failure”. NEJM. vol. 321. 1989. pp. 569-574. (This article was the first to describe AEP based on four patient case series.)
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- Acute Eosinophilic Pneumonia
- I. What every physician needs to know.
- II. Diagnostic Confirmation: Are you sure your patient has Acute Eosinophilic Pneumonia?
- A. History Part I: Pattern Recognition:
- B. History Part 2: Prevalence:
- C. History Part 3: Competing diagnoses that can mimic Acute Eosinophilic Pneumonia.
- D. Physical Examination Findings.
- E. What diagnostic tests should be performed?
- 1. What laboratory studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?
- 2. What imaging studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?
- F. Over-utilized or “wasted” diagnostic tests associated with this diagnosis.
- III. Default Management.
- A. Immediate management.
- B. Physical Examination Tips to Guide Management.
- C. Laboratory Tests to Monitor Response To, and Adjustments in, Management.
- D. Long-term management.
- E. Common Pitfalls and Side-Effects of Management.
- IV. Management with Co-Morbidities.
- A. Renal Insufficiency.
- B. Liver Insufficiency.
- C. Systolic and Diastolic Heart Failure.
- D. Coronary Artery Disease or Peripheral Vascular Disease.
- E. Diabetes or other Endocrine issues.
- F. Malignancy.
- G. Immunosuppression (HIV, chronic steroids, etc.).
- H. Primary Lung Disease (COPD, Asthma, ILD).
- I. Gastrointestinal or Nutrition Issues.
- J. Hematologic or Coagulation Issues.
- K. Dementia or Psychiatric Illness/Treatment.
- V. Transitions of Care.
- A. Sign-out considerations While Hospitalized.
- B. Anticipated Length of Stay.
- C. When is the Patient Ready for Discharge.
- D. Arranging for Clinic Follow-up.
- 1. When should clinic follow up be arranged and with whom.
- 2. What tests should be conducted prior to discharge to enable best clinic first visit.
- 3. What tests should be ordered as an outpatient prior to, or on the day of, the clinic visit.
- E. Placement Considerations.
- F. Prognosis and Patient Counseling.
- VI. Patient Safety and Quality Measures.
- A. Core Indicator Standards and Documentation.
- B. Appropriate Prophylaxis and Other Measures to Prevent Readmission.