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Eosinophilic Pneumonia Last Updated: September 7, 2006 |
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| Synonyms and related keywords: EP, primary eosinophilic pneumonia, primary EP, secondary eosinophilic pneumonia, secondary EP, eosinophilic lung disease, pulmonary eosinophilia, pulmonary infiltrates-with-eosinophilia syndrome, PIE, acute eosinophilic pneumonia, AEP, chronic eosinophilic pneumonia, CEP, drug-induced lung disease, parasite-induced lung disease, eosinophils, Ascaris lumbricoides, Strongyloides stercoralis, amiodarone, nitrofurantoin, idiopathic eosinophilic pneumonia, pulmonary tuberculosis, PTB
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AUTHOR INFORMATION
| Section 1 of 10   |
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| Author: Ali Jawa, MD, MPH, Department of Internal Medicine, Assistant Professor of Medicine, Section of Endocrinology, Diabetes and Metabolism, Allama Iqbal Medical College Coauthor(s): Klaus-Dieter Lessnau, MD, FCCP, Clinical Assistant Professor of Medicine, New York University School of Medicine; Medical Director, Pulmonary Physiology Laboratory, Department of Medicine, Section of Pulmonary Medicine, Lenox Hill Hospital |
| Ali Jawa, MD, MPH, is a member of the following medical societies:
American Association of Clinical Endocrinologists,
American Diabetes Association,
American Federation for Medical Research, and
Endocrine Society |
| Editor(s): Michael Peterson, MD, Chief of Medicine, Vice-Chair of Medicine, University of California at San Francisco; Endowed Professor of Medicine, University of California at San Francisco-Fresno; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine;
Daniel R Ouellette, MD, Consultant to the US Army Surgeon General; Assistant Professor, Department of Internal Medicine, Division of Pulmonary Disease, University of Texas Health Sciences Center at San Antonio;
Timothy D Rice, MD, Associate Professor, Departments of Internal Medicine and Pediatrics and Adolescent Medicine, Saint Louis University School of Medicine;
and Zab Mosenifar, MD, Professor of Medicine, University of California at Los Angeles School of Medicine; Director, Division of Pulmonary/Critical Care Medicine, Executive Vice Chair, Department of Medicine, Cedars-Sinai Medical Center |
Disclosure
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INTRODUCTION
| Section 2 of 10   |
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Background: The term eosinophilic pneumonia (EP) refers to a heterogenous group of lung diseases characterized by pulmonary eosinophilia and infiltrates, with or without increased peripheral eosinophils in the blood. Primary, or idiopathic, EP includes acute eosinophilic pneumonia (AEP) and chronic eosinophilic pneumonia (CEP). Secondary EPs include drug-induced lung disease and parasite-induced lung disease. EP can lead to irreversible damage to the lungs. Pathophysiology: Eosinophils accumulate in the lung parenchyma. They have been described as "angry-looking" cells because they contain cytotoxic substances such as basic eosinophilic protein. The roles of CD4+ helper cells and cytokines, especially interleukin-5, in eosinophil accumulation are being evaluated. Frequency:
- In the US: EP is a rare orphan lung disease. Precise incidence rates are unknown but are probably less then 0.1 case per 100,000 population per year.
- Internationally: Precise incidence rates are unknown but are also probably less then 0.1 case per 100,000 population per year. AEP reportedly occurs at an increased rate in deployed military populations.
Mortality/Morbidity:
- AEP sometimes develops into a life-threatening disease.
- CEP causes progressive symptoms over weeks, months, or years and rarely resolves spontaneously. CEP has been reported after radiation therapy for breast cancer.
Race: Idiopathic AEP and CEP have primarily been described in whites, though idiopathic EP has also been reported in the African American population and other ethnic/racial groups.
Sex:
- AEP has no reported predilection for either sex.
- CEP has a reported female-to-male ratio of 2:1.
Age:
- AEP has been reported in children and adults.
- CEP involves patients of all ages, with peak prevalence in the fifth decade of life.
History: Acute eosinophilic pneumonia (AEP) symptoms progress over several days. Chronic eosinophilic pneumonia (CEP) symptoms progress over weeks, months, or even years. - Acute eosinophilic pneumonia
- Fever of acute onset (often high) usually lasts less than 5 days.
- Symptoms include myalgias and pleuritic chest pain.
- Most subjects in a recently reported series of deployed soldiers with AEP were smokers.
- Hypoxemic respiratory failure, which can mimic acute respiratory distress syndrome (ARDS) and acute infectious pneumonia, often requires mechanical ventilation.
- Chronic eosinophilic pneumonia
- Fever slowly increases over weeks, months, or even years.
- Patients experience cough, weight loss, night sweats, and dyspnea.
- Sixty percent of patients have a history of allergic rhinitis and asthma.
- Ninety percent of patients are nonsmokers.
- Asthma may precede CEP by several years.
- Rarely, EP is the initial manifestation of rheumatoid arthritis.
Physical: - Patients with AEP are acutely ill, febrile, tachypneic, and tachycardic.
- Patients with CEP are chronically ill, with low-grade fever and weight loss.
- Lung examination findings
- Bilateral basilar crepitations without wheezing occur in AEP.
- End-expiratory wheezing or basilar crackles occur in 60% of CEP cases.
Causes: - Primary EPs are idiopathic and are not related to drugs, medications, or systemic diseases such as vasculitis. Cigarette smoking has been reported to trigger AEP with respiratory failure.
- Elevated macrophage-derived chemokine levels and thymus-regulated and activation-regulated chemokine levels were detected in bronchoalveolar lavage fluid obtained from patients with EP.
- Elevated serum parainfluenza virus 3 (PIV-3) antibody titer levels were reported in a case of chronic EP.
- Secondary EPs are induced by parasites (eg, Ascaris lumbricoides, Strongyloides stercoralis) or by medications (eg, amiodarone, nitrofurantoin).
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DIFFERENTIALS
| Section 4 of 10 |
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Acute Respiratory Distress Syndrome
Ascariasis
Aspergillosis
Asthma
Churg-Strauss Syndrome
Eosinophilia
Eosinophilic Granuloma (Histiocytosis X)
Filariasis
Hypereosinophilic Syndrome
Pneumonia, Bacterial
Pneumonia, Fungal
Pulmonary Eosinophilia
Sarcoidosis
Tuberculosis
Wegener Granulomatosis
Other Problems to be Considered:
Acute bronchopulmonary mycosis (ABPM)
Allergic bronchopulmonary aspergillosis (ABPA)
Bronchocentric granulomatosis
Drug-induced EP
Löffler syndrome
Parasite-induced EP
Periarteritis nodosa |
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Patient Education
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Click here for patient education.
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Lab Studies:
- A CBC count may show increased eosinophils and/or thrombocytosis; however, the absence of peripheral eosinophilia does not exclude a diagnosis of eosinophilic pneumonia (EP).
- Analyze stool for ova and parasites.
- The serum immunoglobulin G (IgG) level is elevated in two thirds of patients.
- The erythrocyte sedimentation rate (ESR) is elevated.
- Examine sputum for eosinophils.
- Perform serologies for parasites if the index of clinical suspicion is high.
- Tryptase levels may be elevated in bronchoalveolar lavage fluid of patients with CEP.
- The dissociation between normal KL-6 (Krebs yon den Lundgen-6) levels and elevated SP-A (surfactant protein-A and SP-D (surfactant protein-D) levels in the serum and bronchoalveolar lavage fluid may help confirm a diagnosis of AEP.
- Macrophage-derived chemokine (MDC) and thymus and activation-regulated chemokine (TARC) have been detected in bronchoalveolar lavage fluid obtained from patients with idiopathic eosinophilic pneumonia (Manabe, 2005).
Imaging Studies:
- Patients with AEP exhibit bilateral, diffuse, peripheral infiltrates and pleural effusion. Early stages may show Kerley B lines. Late stages may show mixed interstitial and alveolar infiltrates.
- Patients with CEP exhibit dense, bilateral, peripheral infiltrates, often described as the negative image of pulmonary edema, in the outer two thirds of the lung fields. The bilateral, diffuse, peripheral infiltrates are considered virtually diagnostic of CEP but occur in only 25% of patients. Unilateral pulmonary infiltrates and, rarely, consolidation, cavitation, and atelectasis are present. CEP can mimic pulmonary tuberculosis (PTB).
- Though never reported, AEP is expected to mimic ARDS.
- Peripheral airspace disease may be visualized in CEP, even with abnormal chest radiographic findings. Mediastinal adenopathy is observed in 50% of cases.
- Experimental imaging studies
- Other imaging studies, such as gallium scan or technetium-99 glucoheptonate scan, are experimental.
- Experimental imaging studies might show abnormalities but are nonspecific.
Procedures:
- Fiberoptic flexible bronchoscopy and bronchoalveolar lavage
- In AEP, the percentage (average, 40%) of eosinophils in bronchoalveolar lavage is strikingly high, in contrast to an eosinophilic count that falls within the reference range on peripheral smear.
- In CEP, a high percentage (usually >25%) of eosinophils is a frequent finding and may be the first clue to the diagnosis.
- In both AEP and CEP, biopsy procedures include endobronchial biopsy (EBB), transbronchial biopsy (TBB), video-assisted thoracoscopic surgery (VATS), and open lung biopsy (OLB).
- In both AEP and CEP, either TBB or EBB is performed. Rarely, VATS or OLB may be needed.
Histologic Findings: Eosinophils with edema in alveolar spaces and bronchioles are observed. Additional cells are nonspecific and can include monocytes, histiocytes, and polymorphonuclear leukocytes or neutrophils (PMN).
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TREATMENT
| Section 6 of 10 |
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Medical Care: - The mainstay of acute eosinophilic pneumonia (AEP) treatment consists of systemic steroids (eg, prednisone, methylprednisolone) along with supportive care, which may include mechanical ventilation.
- The mainstay of chronic eosinophilic pneumonia (CEP) treatment consists of systemic steroids, with dramatic response occurring within 2 days. CEP rarely resolves spontaneously.
Consultations: - Infectious diseases specialist
Diet: - Special diets have not been evaluated and are not known to affect the course of the disease.
Activity: - Activity restrictions are not necessary as long as the patient is not hypoxic.
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MEDICATION
| Section 7 of 10 |
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Glucocorticosteroids are the mainstay of treatment and facilitate resolution of eosinophilic pneumonia (EP).
Drug Category: Glucocorticoids -- Have anti-inflammatory properties and cause profound and varied metabolic effects. In addition, these agents modify the body's immune response to diverse stimuli. Drug Name
| Prednisone (Deltasone, Meticorten, Orasone) -- Immunosuppressant for treatment of autoimmune disorders. Can decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. |
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| Adult Dose | CEP
Initial: 0.5-3 mg/kg/d PO
Maintenance: 5-20 mg PO qd/qod
AEP
Maintenance: 1-3 mg/kg after conversion from IV methylprednisolone with tapering over 2-4 wk to discontinuation |
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| Pediatric Dose | Not established; 1 mg/kg/d PO suggested |
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| Contraindications | Documented hypersensitivity; viral infection; peptic ulcer disease; hepatic dysfunction; connective tissue infections; fungal or tubercular skin infections |
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| Interactions | Coadministration with estrogens may decrease clearance; when used with digoxin, digitalis toxicity secondary to hypokalemia can increase; phenobarbital, phenytoin, and rifampin can increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor patient for hypokalemia with coadministration of diuretics |
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| Pregnancy |
B - Usually safe but benefits must outweigh the risks.
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| Precautions | Abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur with glucocorticoid use |
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Drug Name
| Methylprednisolone (Solu-Medrol, Depo-Medrol) -- Decreases inflammation by suppressing migration of PMNs and reversing increased capillary permeability. |
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| Adult Dose | 80-125 mg IV q6h for AEP, used with later conversion to prednisone and rapid taper (see prednisone) |
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| Pediatric Dose | 80-125 mg IV q6h for AEP, suggested |
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| Contraindications | Documented hypersensitivity; viral, fungal, or tubercular skin infections |
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| Interactions | Coadministration with digoxin can increase digitalis toxicity secondary to hypokalemia; estrogens can increase levels; phenobarbital, phenytoin, and rifampin can decrease levels (adjust dose); monitor patients for hypokalemia when taking medication concurrently with diuretics |
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| Pregnancy |
C - Safety for use during pregnancy has not been established.
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| Precautions | Hyperglycemia, edema, osteonecrosis, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, growth suppression, myopathy, and infections are possible complications of glucocorticoid use |
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Drug Category: Tyrosine Kinase Inhibitors -- These agents inhibit tyrosine kinase, which in turn inhibits activation of intracellular pathways that can promote deregulated cell proliferation.Drug Name
| Imatinib (Gleevec) -- Has recently proven effective in the treatment of myeloproliferative variant of hypereosinophilic syndrome. However, this drug still has to be considered experimental. |
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| Adult Dose | 400-600 mg PO qd; up to 400 mg bid |
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| Pediatric Dose | Not established |
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| Contraindications | Documented hypersensitivity; liver disease |
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| Interactions | CYP3A4 inhibitors (ketoconazole increases distribution of imatinib); CYP3A4 substrates (simvastin increases maximum concentration of imatinib by a 2-3.5-fold factor); CYP3A4 inducers (phenytoin decreases AUC by approximately one fifth of typical AUC); likely to increase blood levels of drugs that are substrates of CYP2C9, CYP2D6, and CYP3A4/5 |
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| Pregnancy |
D - Unsafe in pregnancy
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| Precautions | Dose must be reduced or interrupted if edema or anemia occur, transaminases or bilirubin become elevated, or grade 3-4 neutropenia or thrombocytopenia develop; pediatric patient commonly experience musculoskeletal pain; monitor CBC weekly for 4 weeks, then every other wk for 4 wk, then periodically; monitor liver function tests at baseline and then qmo |
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FOLLOW-UP
| Section 8 of 10 |
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Further Inpatient Care:
- Seventy percent of patients with chronic eosinophilic pneumonia (CEP) have radiographic improvement within 1 week. After clinical improvement, patients can be discharged.
Further Outpatient Care:
- After the initial 6 months, monthly revisits are recommended to try to taper steroids to a maintenance dose of 10 mg/d.
- In cases of relapse, patients may need to restart prednisone at 1 mg/kg/d.
- The CEP relapse rate is greater than 10% if prednisone is withdrawn within the first 6 months.
- CEP relapses usually respond within 2 days of restarting prednisone.
- The CEP relapse rate is less than 5% at a dose of 20 mg/d of prednisone.
- Although some patients may require steroids for years, attempt to wean patients off steroids after the first 6 months of treatment.
In/Out Patient Meds:
- Inhaled steroids do not currently have a defined role in treating EPs.
- In acute eosinophilic pneumonia (AEP), 80-125 mg of methylprednisolone IV q6h tapered over 2-4 weeks is recommended.
- The relapse rate in AEP is low after a brief course of treatment.
Complications:
- AEP complications can be life threatening.
- According to reports, only 2 patients have been placed on mechanical ventilation.
Prognosis:
- Without treatment, AEP may be life threatening, although no mortality is reported in either AEP or CEP.
- In CEP, later progression to asthma is debatable, and less than 5% of cases progress to pulmonary fibrosis.
Patient Education:
- Instruct patients not to discontinue prednisone without the physician's knowledge.
- Instruct patients to seek medical attention if symptoms recur.
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MISCELLANEOUS
| Section 9 of 10 |
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Medical/Legal Pitfalls:
- PTB can be missed, although patients have been treated for PTB first and later had chronic eosinophilic pneumonia (CEP) diagnosed.
- Early administration of steroids lessens acute eosinophilic pneumonia (AEP) morbidity.
Special Concerns:
- To avoid fetal hypoxemia, do not discontinue prednisone during pregnancy.
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BIBLIOGRAPHY
| Section 10 of 10 |
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Eosinophilic Pneumonia excerpt |
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