Pulmonary Eosinophilia Workup

  • Author: Jussi J Saukkonen, MD; Chief Editor: Zab Mosenifar, MD   more...
 
Updated: Jan 18, 2012
 

Laboratory Studies

  • The workup should start with the history and physical examination. Pertinent history of travel, evidence of collagen vascular disease, status of the immune system, usage of medications, duration of symptoms, and evidence of airway obstruction are essential elements to consider. The final diagnosis always rests with the response to treatment, even with infectious syndromes.
    • Rule out infectious etiologies based on the travel history, regardless of how remote.
    • Initially, examine stool for ova and parasites.
    • Individualize additional studies.
    • Intrinsic eosinophilic syndromes, including chronic eosinophilic pneumonia (CEP), and idiopathic hypereosinophilic syndrome (IHES), become more likely in the differential diagnosis once extrinsic etiologies have been excluded.
  • Blood leukocyte count with differential is necessary.
    • Leukocytosis is common in all of these syndromes. The eosinophil percentage is less sensitive than the absolute eosinophil count (AEC). Normal blood AEC is as high as 250/µL.
    • CBC count and AEC should be monitored to assess the course of illness and response to treatment when appropriate.
    • Bronchoalveolar lavage (BAL) fluid cell count and differential are often valuable diagnostically (see Procedures).
    • Blood and pulmonary eosinophilia are generally present together in persons with Loeffler syndrome, parasitic and fungal infections, CEP, allergic bronchopulmonary aspergillosis (ABPA), Churg-Strauss syndrome (CSS), and IHES.
    • Isolated pulmonary eosinophilia may be observed in persons with AEP, medication-related syndromes, P carinii pneumonia, BOOP, tuberculosis, and eosinophilic granuloma (EG) (Langerhans cell).
  • Microbiologic studies, rarely, may show evidence of infection with Mycobacterium tuberculosis, P carinii, or fungi. Make additional efforts to exclude parasitic or other fungal co-infection.
    • Parasitic infections may be detected by examining stool, urine, and sputum or BAL fluid.
      • Stool specimens sent for ova and parasite evaluation may be unrevealing if intestinal infection is not established. Multiple specimens should be sent and examined by experienced laboratory personnel. Stool or gastric aspirate examination is generally useful for detecting Strongyloides species, Schistosoma species, and C sinensis; is often less useful for detecting Paragonimus, Ancylostoma, Necator, and Ascaris infection; and is usually not helpful for detecting Toxocara, Trichinella, and Echinococcus species and tropical pulmonary eosinophilia (TPE)–associated filariae.
      • Urine examination may be useful in cases of schistosomiasis.
      • Sputum or BAL fluid examination may be useful for detecting Paragonimus, Ascaris, Strongyloides, and, rarely, Schistosoma infections.
    • Fungal infection may be detected by examining respiratory secretions.
      • ABPA is supported by growth of Aspergillus species from respiratory secretions.
      • Coccidioides species may be cultured from respiratory secretions.
  • Immunologic studies, ie, serologic testing, may be useful in persons with ABPA, parasitic infection, and CSS. Serologic testing may obviate the need for invasive testing in the case of parasitic infections. Use a targeted approach to serologic testing, bolstered by clinical information.
    • Total IgE values are often elevated in persons with these syndromes, and this finding has no specific diagnostic value. Some general trends may be noted.
      • Levels of less than 1000 ng/mL are usually observed in association with asthma and low-intensity infections.
      • ABPA and parasitic infections are typically associated with high levels, often greater than 2000 ng/mL.
    • The diagnosis of ABPA is supported by an elevated IgE level, an elevated Aspergillus -specific IgE level, a positive result for Aspergillus precipitins, and an immediate skin hypersensitivity response to Aspergillus.
      • Levels correlate with the activity of ABPA.
      • If levels are within the reference range in a patient with respiratory symptoms, ABPA can usually be excluded.
    • Some parasitic infections may be diagnosed based on serological results. These include TPE-associated filarial infection (eg, B malayi, W bancrofti); echinococcal infection (serology results are positive in 60-90% of cases); and toxocariasis, with best results obtained by enzyme-linked immunosorbent assay (ELISA).
    • A variety of sensitive and specific serologic tests, including complement fixation, ELISA, and immunoblot, have been developed to detect Paragonimus infection.
    • Tests with limited value are available for Strongyloides and Ascaris infections.
  • In CSS, perinuclear antineutrophil cytoplasmic antibody results are positive in at least 60% of cases.
  • In CEP, check antinuclear antibody or rheumatoid factor levels because CEP may be associated with connective tissue diseases.
  • In 2009, Velthove et al report on possible biomarkers (neutrophilia, eosinophilia) for inflammation in obstructive lung disease. Based on the results of their case-control study, they suggested both neutrophil counts and eosinophil counts may be useful biomarkers for exacerbations in obstructive lung disease.[16] Additionally, Hillas et al suggest eosinophil counts are the future direction of focus for a noninvasive method of assessing airway inflammation in clinical practice and not just research settings.[17]
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Imaging Studies

  • Chest radiography of extrinsic syndromes
    • Loeffler syndrome: Fleeting interstitial infiltrates may be evident.
    • AEP: Interstitial infiltrates progress to alveolar-filling infiltrates. Small pleural effusions and Kerley B lines may be present.
    • Parasitic infections: These typically manifest as interstitial or indistinct nodular densities, usually in the middle and/or basilar lung fields. Infiltrates may be migratory. Chest x-ray films may yield normal findings in many individuals.
    • TPE: Fibrosis may be evident in persons with chronic disease.
    • Echinococcus infection: This manifests as large, smooth-edged, masslike densities, with or without calcification.
    • Chronic schistosomiasis: Patients with chronic schistosomiasis may have hilar enlargement and right ventricular enlargement as a consequence of pulmonary hypertension.
    • ABPA: Fleeting infiltrates, atelectasis, pneumonitis, and bronchiectasis may be evident.
  • Chest radiography of intrinsic syndromes
    • CEP: Peripheral alveolar infiltrates may be migratory, and they have the classic appearance of the photographic negative of pulmonary edema in one fourth of cases.
    • IHES: Interstitial infiltrates, pleural effusions, pulmonary edema, pulmonary infarct, and fibrosis may be present.
    • CSS: Interstitial infiltrates, alveolar infiltrates, and nodular opacities may be present. Cavitary, small, patchy irregularities are not usually present.
    • EG: Reticulonodular infiltrates, increased lung volumes, cystic changes, coalescing nodules, and pneumothorax may be seen.
  • Chest CT scan: CT scan of the chest helps define the extent and distribution of the disease; helps distinguish between predominantly interstitial or alveolar infiltrates; helps detect lymphadenopathy, fibrosis, and bronchiectasis; may be helpful in distinguishing between malignancy and other etiologies; and may be needed if biopsy is contemplated. High-resolution CT scan is preferred to enhance the evaluation of the pulmonary parenchyma.
    • ABPA: Fleeting infiltrates, atelectasis, pneumonitis, and bronchiectasis may be evident. High attenuation mucoid impaction is associated with higher IgE levels, eosinophilia, Aspergillus -specific titers, and a greater probability of relapse.[18]
    • Parasitic diseases: CT scan images provide finer detail of nodules and interstitial infiltrates. In schistosomiasis and echinococcal diseases, additional cysts may be seen in the liver.
    • AEP: Ground-glass infiltrates are commonly seen, but dense consolidation, nodules, and septal thickening may also be revealed.
    • CEP: Alveolar ground-glass infiltrates in a peripheral distribution are highly characteristic of CEP.
    • IHES: Nodules and effusions may be seen.
    • CSS: In addition to abnormalities seen on plain radiographs, irregular pulmonary arteries may be seen.
    • BOOP: Peripheral triangular-shaped infiltrates are classic, but alveolar filling may be evident.
    • EG: Cystic changes, nodules, and fibrosis are seen.
    • Idiopathic pulmonary fibrosis: Interstitial infiltrates, a ground-glass alveolar pattern, nodules, and fibrosis are seen.
  • Positron-emission tomography (PET) scanning: Patients with pulmonary eosinophilia have been reported to have F-18 fluorodeoxyglucose (FDG)–avid uptake on positron emission scans.[19]
  • Echocardiography
    • Establishing an estimation of right ventricular, left ventricular, and valvular function is indicated in individuals with certain intrinsic syndromes (eg, CSS, IHES) or in individuals with sustained high-level eosinophilia in which cardiac complications are relatively common.
    • Establishing an estimation of pulmonary systolic pressure and right ventricle function is indicated in persons with chronic schistosomiasis because pulmonary hypertension is common.
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Other Tests

  • Pulmonary function testing
    • This testing may be useful in the initial evaluation to help narrow the differential diagnosis. It is helpful as an initial test to distinguish between obstructive and restrictive diseases.
    • An obstructive pattern may be seen in persons with asthma, ABPA, bronchocentric granulomatosis, EG, BOOP, CSS, and, occasionally, IHES.
    • A restrictive pattern may be seen in persons with TPE, intrinsic eosinophilic syndromes, and interstitial lung diseases.
    • This type of testing helps assesses the severity of airway obstruction or parenchymal restriction.
  • Ventilation/perfusion scanning
    • This scan may be useful in some patients with IHES in the appropriate clinical setting who have a propensity to develop pulmonary emboli.
    • Schistosomiasis and other parasitic diseases may result in matched and unmatched defects.
  • Skin testing
    • Prick testing and intradermal testing can be performed for an immediate hypersensitivity response to Aspergillus infection.
    • Avoid skin testing if the patient has significant wheezing.
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Procedures

  • Fiberoptic bronchoscopy with BAL
    • BAL is often necessary to obtain adequate specimens to help rule out infection, particularly in the instance of CEP and other intrinsic syndromes.
    • BAL fluid leukocyte and differential cell counts may provide the presenting or only sign of eosinophilic pulmonary syndrome. Normally, few eosinophils are obtained from BAL fluid. The presence of more than 20% suggests Loeffler syndrome, AEP, CEP, or IHES.
    • Pulmonary eosinophilia alone may be present in persons with AEP, medication-related syndromes, P carinii pneumonia, BOOP, tuberculosis, and EG (Langerhans cell).
    • BAL examination may be useful for detecting Paragonimus, Ascaris, Strongyloides, and, rarely, Schistosoma infections.
    • BAL fluid cytology findings may be useful for excluding malignancy.
    • BAL cytology findings may also be useful for detecting EG, for which immunohistochemical staining for the S-100 antigen or electron microscopy (demonstrating the pentilaminar Birbeck granule) can be diagnostic.
  • Transbronchial biopsy
    • Transbronchial biopsy may be performed to help determine if an invasive fungal infection is present.
    • The size of the tissue specimens obtained is generally insufficient to reliably provide the histopathologic information for the syndromes discussed.
  • Transthoracic needle aspiration/biopsy
    • This may occasionally may be used to help distinguish infection from malignancy when the results of other, less-invasive studies have been unrevealing.
    • Dirofilariasis, which is difficult to diagnose with noninvasive methods, has been diagnosed based on findings from this method.
    • Avoid aspiration of echinococcal cysts because of the risk posed by dissemination, resulting in a massive hypersensitivity reaction.
  • Open lung biopsy
    • Open lung biopsy is rarely necessary, but it is usually performed if CSS, interstitial lung disease, or malignancy is suggested.
    • For AEP and CEP, BAL is usually performed. Once infection is excluded, the rapid response to therapy contributes to a clinical diagnosis.
  • Other biopsies
    • Liver biopsy is performed for chronic schistosomiasis with cor pulmonale. It rarely is performed for TPE (which is usually confirmed based on serology findings) and toxocariasis.
    • Lymph node biopsy is occasionally used in cases of TPE.
    • Skin biopsy is performed for trichinosis, and it is occasionally performed for toxocariasis or when skin manifestations of other diseases are prominent.
    • Rectal biopsy is occasionally pursued in persons with schistosomiasis.
    • Muscle biopsy findings may indicate trichinosis.
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Histologic Findings

  • Parasitic diseases: Findings include increased histiocytes, eosinophilic and lymphocytic infiltration of airspaces, eosinophilic abscesses, granulomas, and areas of fibrosis.
  • ABPA: Findings include eosinophilic, lymphocytic, plasmacytic, and monocytic infiltration around bronchi; granulomas; fibrosis; microabscesses; and bronchiectasis.
  • AEP: Findings include eosinophilic infiltration of airspaces and airway walls and edema, but not vasculitis.
  • CEP: Findings include eosinophilic and lymphocytic accumulation in alveoli, eosinophilic abscess formation, bronchiolitis, and fibrosis. Granulomas are not seen. Occasionally, mild vasculitis is seen.
  • CSS: Eosinophilic necrotizing vasculitis of small vessels and granulomas are common.
  • IHES: Findings include eosinophilic infiltration of interstitium and airways and intravascular thrombi.
  • EG: Findings include Langerhans cell proliferation and granulomas, lymphocytic and monocytic infiltration, desquamative interstitial pneumonitis, granulomatous vasculitis, lymphoid follicles, S-100 antigen staining of Langerhans cells, and, with electron microscopy, the Birbeck (X-body) within cytoplasm of Langerhans cells.
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Contributor Information and Disclosures
Author

Jussi J Saukkonen, MD  Associate Professor, Department of Internal Medicine, Division of Pulmonary/Critical Care Medicine, Boston University School of Medicine, Boston Medical Center

Jussi J Saukkonen, MD is a member of the following medical societies: American Thoracic Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Gregory Tino, MD  Director of Pulmonary Outpatient Practices, Associate Professor, Department of Medicine, Division of Pulmonary, Allergy, and Critical Care, University of Pennsylvania Medical Center and Hospital

Gregory Tino, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and American Thoracic Society

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Timothy D Rice, MD  Associate Professor, Departments of Internal Medicine and Pediatrics and Adolescent Medicine, St Louis University School of Medicine

Timothy D Rice, MD is a member of the following medical societies: American Academy of Pediatrics and American College of Physicians

Disclosure: Nothing to disclose.

Chief Editor

Zab Mosenifar, MD  Director, Division of Pulmonary and Critical Care Medicine, Director, Women's Guild Pulmonary Disease Institute, Professor and Executive Vice Chair, Department of Medicine, Cedars Sinai Medical Center, University of California, Los Angeles, David Geffen School of Medicine

Zab Mosenifar, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Federation for Medical Research, and American Thoracic Society

Disclosure: Nothing to disclose.

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