Hypersensitivity Pneumonitis and Pulmonary Infiltrates with Eosinophilia¶
Chapter 299 | Part 7: Disorders of the Respiratory System
KEY CLINICAL POINTS¶
- Hypersensitivity pneumonitis (HP) is an immune-mediated lung disease triggered by inhalation of antigens (e.g., fungal, bacterial, bird droppings), leading to inflammation of alveoli and small airways.
- Pulmonary infiltrates with eosinophilia encompass a group of disorders characterized by eosinophilic infiltration of lung tissue, often associated with allergic reactions, infections, or autoimmune processes.
- Diagnosis of HP relies on exposure history, imaging (HRCT), serum precipitins, and exclusion of other conditions like IPF or sarcoidosis.
- Acute HP typically resolves with antigen avoidance, while chronic HP may require corticosteroids or antifibrotic agents like nintedanib.
- Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic vasculitis with eosinophilia, asthma, and multi-organ involvement, treated with corticosteroids and immunosuppressants.
1. DEFINITION & OVERVIEW¶
Hypersensitivity pneumonitis (HP) is an inflammatory lung disease caused by repeated inhalation of antigens (e.g., fungal, bacterial, bird droppings) leading to immune-mediated alveolar and airway inflammation. Pulmonary infiltrates with eosinophilia refer to conditions with eosinophilic infiltration of lung tissue, often associated with allergic, infectious, or autoimmune mechanisms.
Table 299-1 Examples of Hypersensitivity Pneumonitis¶
| DISEASE | ANTIGEN | SOURCE |
|---|---|---|
| Farmer’s lung | Thermophilic actinomycetes (e.g., Saccharopolyspora rectivirgula); fungus | Grain, moldy hay, silage |
| Bagassosis | Thermophilic actinomycetes | Sugarcane |
| Cheese washer’s lung | Penicillium casei; Aspergillus clavatus | Cheese |
| Coffee worker’s lung | Coffee bean dust | Coffee beans |
| Malt worker’s lung | Aspergillus species | Barley |
| Miller’s lung | Sitophilus granarius (wheat weevil) | Wheat flour |
| Mushroom worker’s lung | Thermophilic actinomycetes; mushroom spores | Mushrooms |
| DISEASE | ANTIGEN | SOURCE |
|---|---|---|
| Potato riddler’s lung | Thermophilic actinomycetes; Aspergillus species | Moldy hay around potatoes |
| Tobacco grower’s lung | Aspergillus species | Tobacco |
| Wine maker’s lung | Botrytis cinerea | Grapes |
| Bird fancier’s lung | Proteins derived by parakeets, pigeons, budgerigars; bird feathers, serum proteins | Bird droppings |
| Duck fever | Duck feathers, serum proteins | Ducks |
| Fish meal worker’s lung | Fish meal dust | Fish meal |
| Furrier’s lung | Dust from animal furs | Animal furs |
| Laboratory worker’s lung | Rat urine, serum, fur | Laboratory rats |
| Poultry worker’s lung | Chicken serum proteins | Chickens |
| Turkey handling disease | Turkey serum proteins | Turkeys |
| Chemical worker’s lung | Isocyanates | Polyurethane foam, varnish, lacquer |
| Detergent worker’s lung | Bacillus subtilis enzymes | Detergent |
| Hot tub lung | Cladosporium species; Mycobacterium avium complex | Contaminated water, mold on ceiling |
| Humidifier fever (and air conditioner lung) | Several microorganisms (e.g., Aureobasidium pullulans, Candida albicans, thermophilic actinomycetes, Mycobacterium species, Klebsiella oxytoca, Naegleria gruberi) | Humidifiers and air conditioners (contaminated water) |
| Machine operator’s lung | Pseudomonas species; Mycobacteria species | Metal working fluid |
| Sauna taker’s lung | Aureobasidium species; other antigens | Sauna water |
| Suberosis | Penicillium glabrum; Chrysonilia sitophila | Cork dust |
| Summer-type pneumonitis | Trichosporon cutaneum | House dust mites, bird droppings |
| Woodworker’s lung | Alternaria species; Bacillus subtilis | Oak, cedar, pine, mahogany dusts |
1.1 INTRODUCTION AND DEFINITION¶
HP, also termed extrinsic allergic alveolitis, is a pulmonary disease triggered by inhalation of antigens leading to immune-mediated inflammation. Pulmonary infiltrates with eosinophilia are characterized by increased eosinophils in lung tissue, sputum, or BAL fluid, often associated with systemic symptoms.
1.2 CLINICAL PRESENTATION¶
HP presents with acute, subacute, or chronic forms. Acute HP features sudden onset of fever, cough, and dyspnea. Chronic HP may present with progressive dyspnea, fatigue, and clubbing. Pulmonary infiltrates with eosinophilia may present with cough, fever, and respiratory symptoms, often with systemic manifestations.
2. EPIDEMIOLOGY¶
HP incidence and prevalence vary by geography, occupation, and environment. Risk factors include occupational exposure (e.g., farmers, bird owners, industrial workers), avocations (e.g., hot tub use), and environmental factors. Smokers have a decreased risk of developing HP. Chronic HP may progress to fibrosis with honeycombing, resembling IPF.
2.1 INCIDENCE AND PREVALENCE¶
HP incidence and prevalence vary globally based on occupational, environmental, and geographic factors. Chronic HP may progress to fibrosis with honeycombing, similar to IPF.
2.2 RISK FACTORS¶
Occupational exposure (farmers, bird owners, industrial workers), avocations (hot tub use), and environmental factors (e.g., mold, dust) increase risk. Smoking is associated with decreased HP risk.
3. ETIOLOGY & PATHOPHYSIOLOGY¶
HP is caused by inhalation of antigens (fungal, bacterial, bird-derived, chemical) leading to immune-mediated inflammation. Pathophysiology involves dysregulated T1 and T17 immune responses, with roles for both adaptive and innate immunity. Chronic HP may involve fibrocyte-driven fibrosis.
3.1 MECHANISMS¶
Inhalation of antigens triggers immune responses, leading to alveolar and airway inflammation. Toll-like receptors (TLRs) and MyD88 signaling mediate neutrophil recruitment. Genetic factors (e.g., MUC5B polymorphism) may contribute to chronic HP.
3.2 PATHOGENESIS¶
Dysregulated T1 and T17 responses, with adaptive immunity (IgG antibodies) and innate immunity (TLRs) involved. Chronic HP may involve fibrocyte-driven fibrosis, similar to IPF.
4. CLINICAL FEATURES¶
HP presents with acute, subacute, or chronic symptoms. Pulmonary infiltrates with eosinophilia may include cough, fever, dyspnea, and systemic symptoms. Chronic HP may present with progressive dyspnea, fatigue, weight loss, and clubbing.
4.1 SYMPTOMS¶
Acute HP: fever, cough, dyspnea. Chronic HP: progressive dyspnea, fatigue, weight loss, clubbing. Pulmonary infiltrates with eosinophilia: cough, fever, respiratory symptoms, systemic manifestations.
4.2 COMPLICATIONS¶
Chronic HP may progress to fibrosis with honeycombing (similar to IPF). EGPA may involve multi-organ vasculitis, leading to cardiac, GI, and renal complications.
5. DIFFERENTIAL DIAGNOSIS¶
Differentiate HP from infections (e.g., TB, fungal), sarcoidosis, IPF, and other eosinophilic syndromes. EGPA must be distinguished from other pulmonary eosinophilic disorders by multi-organ involvement and vasculitis.
5.1 OTHER CONDITIONS¶
IPF, sarcoidosis, allergic bronchopulmonary aspergillosis (ABPA), and eosinophilic granulomatosis with polyangiitis (EGPA) must be differentiated by imaging, serology, and clinical features.
6. INVESTIGATIONS & DIAGNOSIS¶
Diagnosis of HP requires exposure history, imaging (HRCT), serum precipitins, and exclusion of other conditions. Pulmonary infiltrates with eosinophilia are diagnosed using imaging, BAL, and serologic tests.
Table 299-2 Pulmonary Infiltrates with Eosinophilia¶
| Primary Pulmonary Eosinophilic Disorders | Pulmonary Disorders of Known Cause | Systemic Diseases |
|---|---|---|
| Acute eosinophilic pneumonia | Asthma and eosinophilic bronchitis | Postradiation pneumonitis |
| Chronic eosinophilic pneumonia | Allergic bronchopulmonary aspergillosis | Rheumatoid arthritis |
| Eosinophilic granulomatosis with polyangiitis (EGPA) | Bronchocentric granulomatosis | Sarcoidosis |
| Hypereosinophilic syndrome | Drug/toxin reaction | Sjögren’s syndrome |
| Cryptogenic organizing pneumonia | Infection (Table 299-4) | Lung cancer |
| Hypersensitivity pneumonitis | Nonparasitic infection | Leukemia |
| Idiopathic pulmonary fibrosis | Parasitic/helminthic disease | Lymphoma |
| Pulmonary Langerhans cell granulomatosis | Nonparasitic infection | Malignant Neoplasms |
Table 299-3 Diagnostic Criteria of Acute Eosinophilic Pneumonia¶
| Criteria |
|---|
| Acute febrile illness with respiratory manifestations <1 month |
| Hypoxemic respiratory failure |
| Diffuse pulmonary infiltrates on chest x-ray |
| Bronchoalveolar lavage eosinophilia >25% |
| Absence of parasitic, fungal, or other infection |
| Absence of drugs known to cause pulmonary eosinophilia |
| Quick clinical response to corticosteroids |
| Failure to relapse after discontinuation of corticosteroids |
6.1 LABORATORY TESTS¶
Serum precipitins, elevated IgE, and BAL eosinophilia (>25%) are key. ESR, CRP, and inflammatory markers may be elevated.
6.2 IMAGING¶
HRCT shows ground-glass opacities, centrilobular nodules, and honeycombing in advanced cases. Chest x-ray may show transient infiltrates or fibrotic changes.
6.3 DIAGNOSTIC CRITERIA¶
Acute eosinophilic pneumonia: <1 month duration, hypoxemia, diffuse infiltrates, BAL eosinophilia >25%. EGPA: asthma, peripheral eosinophilia, vasculitis, multi-organ involvement.
7. MANAGEMENT & TREATMENT¶
Antigen avoidance is the mainstay of treatment for HP. Corticosteroids are used for severe nonfibrotic HP, while antifibrotic agents (nintedanib, pirfenidone) may be used for fibrotic HP. EGPA is treated with corticosteroids, immunosuppressants, and targeted therapies (e.g., imatinib, mepolizumab).
7.1 PHARMACOLOGIC TREATMENT¶
Corticosteroids (prednisone 0.5–1 mg/kg/day) for nonfibrotic HP. Antifibrotic agents (nintedanib, pirfenidone) for fibrotic HP. Anti-IL-5 therapies (mepolizumab, benralizumab) for EGPA.
7.2 NON-PHARMACOLOGIC¶
Avoidance of antigen exposure (e.g., removing birds, improving ventilation). Personal protective equipment (respirators) may be used.
7.3 SURGICAL¶
Lung transplantation may be considered for advanced fibrotic HP or EGPA with progressive lung fibrosis.
8. PROGNOSIS & COMPLICATIONS¶
Acute HP has a favorable prognosis with antigen avoidance. Chronic HP may progress to fibrosis with poor outcomes. EGPA has a variable prognosis, with mortality due to vasculitis, cardiac, or GI complications.
8.1 OUTCOME¶
Nonfibrotic HP resolves with antigen avoidance. Fibrotic HP may progress to honeycombing (IPF-like), with poor prognosis. EGPA mortality is ~50% within 3 months without treatment.
8.2 COMPLICATIONS¶
Cardiac involvement (myocarditis, restrictive cardiomyopathy), GI bleeding, renal failure, and cerebral hemorrhage are common complications of EGPA.
9. SPECIAL CONSIDERATIONS¶
HP in elderly patients with asthma has higher mortality. Smoking reduces HP risk. EGPA in asthma patients may require corticosteroid tapering to prevent relapse. Pregnancy and pediatric considerations are minimal unless exposure is present.
9.1 ASTHMA-COPD OVERLAP¶
Asthma-COPD overlap (ACO) is a syndrome with features of both asthma and COPD. Corticosteroids and anticholinergics may improve outcomes.
9.2 PREGNANCY AND PEDIATRICS¶
Minimal impact unless exposure to antigens is present. Antigen avoidance is critical in children.
10. KEY POINTS & CLINICAL PEARLS¶
- Antigen avoidance is the cornerstone of HP management. 2. Corticosteroids are effective for nonfibrotic HP, while antifibrotics may be used for fibrotic HP. 3. EGPA requires corticosteroids and immunosuppressants. 4. HRCT and BAL are critical for diagnosing HP and eosinophilic syndromes. 5. Differentiate HP from IPF and sarcoidosis using imaging and serology.