Hypersensitivity Pneumonitis (HP) / Extrinsic Allergic Alveolitis (EAA)
Hypersensitivity pneumonitis (HP) is an immune-mediated interstitial lung disease (ILD) caused by repeated inhalation of a sensitizing antigen in susceptible individuals, leading to inflammation of:
- Alveoli
- Terminal bronchioles
- Interstitium
Unlike asthma, HP primarily affects the alveolar-interstitial compartment rather than the conducting airways.
HP may progress from reversible inflammation to irreversible pulmonary fibrosis if antigen exposure continues.
Classification:
Older classification:
- Acute HP
- Subacute HP
- Chronic HP
Current classification (ATS/JRS/ALAT):
- Non-fibrotic HP
- Fibrotic HP
This classification better predicts prognosis.
Epidemiology
- Can occur at any age
- Usually adults 40–70 years
Common occupations:
- Farmers
- Bird breeders
- Poultry workers
- Mushroom workers
- Cheese workers
- Woodworkers
- HVAC workers
- Textile workers
Pathogenesis
HP is primarily a combination of:
Type III Hypersensitivity—Immune complex mediated
and
Type IV Hypersensitivity—T-cell mediated delayed hypersensitivity
Persistent exposure causes:
- Fibroblast activation
- Collagen deposition
- Architectural distortion
- Honeycombing
Common Antigens
|
Type of Hypersensitivity Pneumonitis |
Exposure Source |
Causative Antigen/Organism/Agent |
|
Bird-Related HP (Bird Fancier’s Lung) |
Pigeons, Parrots, Budgerigars, Poultry |
Feathers, Serum proteins, Droppings |
|
Farmer’s Lung |
Moldy hay |
Thermophilic actinomycetes (Saccharopolyspora rectivirgula, Thermoactinomyces vulgaris) |
|
Humidifier Lung |
Contaminated humidifiers, Air conditioners |
Bacteria, Fungi |
|
Hot Tub Lung |
Hot tubs, aerosolized water exposure |
Mycobacterium avium complex (MAC) |
|
Mushroom Worker’s Lung |
Mushroom compost |
Organic fungal antigens from compost |
|
Bagassosis |
Sugarcane bagasse |
Thermophilic microorganisms in bagasse dust |
|
Malt Worker’s Lung |
Moldy barley |
Mold/fungal antigens |
|
Wood Worker’s Lung |
Mold-contaminated wood |
Mold/fungal antigens |
|
Chemical-Induced HP |
Industrial/occupational chemical exposure |
Isocyanates, Polyurethane paints, Epoxy resins |
Clinical Forms
|
Acute HP |
Subacute HP |
Chronic/Fibrotic HP |
|
Occurs: 4–12 hours after heavy antigen exposure |
Occurs due to: Repeated low-level antigen exposure |
Occurs after: Years of ongoing exposure |
|
Symptoms: Fever, Chills, Malaise, Dry cough, Dyspnea, Chest tightness, Headache, Myalgia |
Symptoms: Progressive dyspnea, Chronic cough, Fatigue, Weight loss |
Symptoms: Progressive exertional dyspnea, Dry cough, Weight loss, Fatigue |
|
Often resembles an influenza-like illness |
Duration: Weeks to months |
Progressive and often irreversible disease |
|
Physical findings: Tachypnea, Tachycardia, Bibasal crackles |
Physical findings may be minimal or nonspecific |
Signs: Digital clubbing, Inspiratory crackles, Pulmonary hypertension, Respiratory failure |
|
Symptoms typically improve within 24–72 hours after cessation of exposure |
Symptoms persist with continued exposure |
Associated with pulmonary fibrosis and chronic respiratory impairment |
Symptom Pattern
Symptoms improve:
- Weekends
- Vacations
- Away from workplace
Strong clue for HP.
Physical Examination
- Fine inspiratory crackles—Most common finding.
- Wheeze—Less common than asthma.
- Clubbing—Suggests fibrosis.
- Cyanosis—Advanced disease.
Differential Diagnosis
|
Disease |
Distinguishing Feature |
|
Asthma |
Airway disease, eosinophilia |
|
COPD |
Smoking history |
|
Sarcoidosis |
Well-formed granulomas, hilar nodes |
|
Viral pneumonia |
Infectious syndrome |
|
Organizing pneumonia |
Different CT pattern |
|
IPF |
UIP pattern without air trapping |
|
Connective tissue disease ILD |
Autoimmune features |
Diagnostic Approach (ATS/JRS/ALAT)
Diagnosis is based on integration of:
1. Exposure Identification(Most important step)
2. HRCT Findings(Typical pattern)
3. BAL Lymphocytosis(Supportive evidence)
4. Lung Biopsy(When diagnosis remains uncertain)
Combination of all four may establish diagnosis without surgical biopsy.
Laboratory Findings
|
Investigation |
Finding |
Clinical Significance |
|
CBC |
Leukocytosis during acute attacks |
Reflects acute inflammatory response; nonspecific |
|
ESR/CRP |
Elevated |
Indicates systemic inflammation; nonspecific |
|
Serum Precipitating Antibodies (IgG) |
Positive against causative antigens such as avian proteins and thermophilic actinomycetes |
Supports exposure and sensitization; positive test alone does not establish disease |
|
Bronchoalveolar Lavage (BAL) |
One of the most useful supportive tests |
Helps support diagnosis when interpreted with exposure history and HRCT findings |
|
BAL Lymphocytosis |
Usually ≥30–40%; often >50% |
Characteristic finding of HP; strongly supportive of diagnosis |
|
BAL CD4/CD8 Ratio |
Usually decreased |
Supportive but not diagnostic; considerable variability exists among patients |
Imaging
Chest X-ray(May be normal)
Possible findings:
- Diffuse reticulonodular opacities
- Ground-glass infiltrates
High-Resolution CT (HRCT)-Investigation of Choice
Non-Fibrotic HP
- Classic findings:Ground-Glass Opacities (Diffuse or patchy)
- Centrilobular Nodules-Poorly defined
- Mosaic Attenuation-Due to air trapping
- Three-Density Pattern (Most Specific Sign)
Formerly called:”Headcheese sign”
Represents coexistence of:
- Normal lung
- Ground-glass opacity
- Air trapping
Expiratory CT-Demonstrates:Air trapping,Highly supportive of HP.
Fibrotic HP HRCT Findings
- Reticulation
- Traction Bronchiectasis
- Architectural Distortion
- Honeycombing
May resemble:
- Idiopathic Pulmonary Fibrosis
- Other fibrotic ILDs
Features favoring HP:
- Air trapping
- Mosaic attenuation
- Centrilobular nodules
- Upper/mid-lung predominance
Histopathology
Classic Triad:
1. Cellular Bronchiolitis
2. Chronic Interstitial Inflammation(Lymphocyte predominant)
3. Poorly Formed Noncaseating Granulomas(Characteristic finding)
Additional Findings
- Giant cells
- Cholesterol clefts
- Organizing pneumonia
Pulmonary Function Tests (PFTs)
Typical Pattern-Restrictive defect
|
Parameter |
Finding |
|
FVC |
↓ |
|
TLC |
↓ |
|
DLCO |
↓↓↓ |
|
FEV1/FVC |
Normal or ↑ |
Advanced Disease
May show:Mixed restrictive-obstructive pattern.
Management
1. Antigen Avoidance (Most Important Treatment)
Cornerstone of management.
Examples:
- Remove birds
- Change occupation
- Improve ventilation
- Remove mold
- Clean humidifiers
Early avoidance may completely reverse disease.
2. Corticosteroids
Used for:
- Symptomatic disease
- Significant physiologic impairment
- Acute severe HP
Prednisone
Typical regimen:0.5–1 mg/kg/day
Usually:40–60 mg/day For 2–4 weeks
Then gradual taper over: 3–6 months
Benefits:
- Faster symptom improvement
- Faster radiologic improvement
Does not reliably prevent fibrosis if exposure continues.
3. Immunosuppressive Agents
Used in chronic progressive disease.
Examples:
- Azathioprine
- Mycophenolate mofetil
Evidence less robust than in CTD-ILD.
4. Antifibrotic Therapy
For progressive fibrotic HP.
Nintedanib(Shown to slow FVC decline in progressive fibrosing ILD)
Pirfenidone(May be considered in selected cases)
Supportive Care
- Oxygen therapy
- Pulmonary rehabilitation
- Vaccination
- Smoking cessation
- Nutrition optimization
Lung Transplantation
Consider in:
- End-stage fibrotic HP
- Progressive respiratory failure
- Severe pulmonary hypertension
Complications
Respiratory
- Progressive pulmonary fibrosis
- Chronic respiratory failure
- Acute exacerbations
Cardiovascular
- Pulmonary hypertension
- Cor pulmonale
Functional
- Exercise limitation
- Reduced quality of life