Medicine – Extrinsic Allergic Alveolitis (Hypersensitivity Pneumonitis)

Extrinsic allergic alveolitis (EAA), now more commonly called hypersensitivity pneumonitis (HP), is an immune-mediated inflammatory disease of the lung caused by repeated inhalation of certain environmental antigens. These antigens are usually derived from organic dusts, fungi, bacteria such as thermophilic actinomycetes, or animal proteins.

Unlike asthma, the main inflammatory process occurs in the alveoli and pulmonary interstitium rather than primarily in the bronchi, which explains why breathlessness and cough are prominent while wheezing is usually absent.

1. Pathogenesis

EAA develops when a susceptible individual repeatedly inhales an antigen capable of producing an abnormal immune response within the distal airways and alveoli.

Traditionally, the disease has been described as involving a combination of type III immune-complex hypersensitivity and type IV delayed T-cell-mediated hypersensitivity.

Repeated inflammation produces lymphocytic alveolitis and interstitial inflammation. If exposure continues, chronic inflammation may eventually result in permanent pulmonary fibrosis.

2. Immunological Mechanism

Patients exposed to the responsible antigen may develop circulating IgG antibodies, sometimes called precipitating antibodies or precipitins.

These antibodies indicate sensitisation to the antigen but do not necessarily prove that it is causing the patient’s lung disease. Cellular immunity, particularly involving T lymphocytes, is also central to the development of hypersensitivity pneumonitis.

Important Types of Extrinsic Allergic Alveolitis

3. Farmer’s Lung

Farmer’s lung is a classic form of hypersensitivity pneumonitis caused by exposure to microorganisms growing in mouldy hay and other agricultural material.

Traditional organisms associated with farmer’s lung include the thermophilic actinomycetes Saccharopolyspora rectivirgula (formerly Micropolyspora faeni) and Thermoactinomyces species.

Farmers may inhale large quantities of these antigens while handling damp or mouldy hay, particularly in poorly ventilated environments.

4. Bird-Fancier’s Lung

Bird-fancier’s lung occurs following repeated exposure to avian proteins from birds such as pigeons, budgerigars, parrots, and poultry.

Antigens are present in bird droppings, feathers, and feather bloom, and may become airborne as fine particles that are inhaled deeply into the lungs.

Repeated exposure can produce either episodic acute disease or a more insidious chronic form.

5. Malt Worker’s Lung

Malt worker’s lung is an occupational form of hypersensitivity pneumonitis associated with exposure to fungal antigens during the production and handling of malt.

A classic causative organism is Aspergillus clavatus, which may contaminate barley and malt and release airborne fungal spores.

Clinical Features

6. Acute Disease

In acute hypersensitivity pneumonitis, symptoms characteristically develop several hours after significant antigen exposure, traditionally around 4–9 hours later.

Patients may experience fever, chills or flu-like symptoms, dry cough, chest tightness, malaise, and shortness of breath. Fine inspiratory crackles may be heard on examination.

Absence of Wheeze

Wheezing is usually absent, which can help distinguish EAA from allergic asthma.

In asthma, the predominant problem is reversible bronchial obstruction. In EAA, inflammation predominantly involves the alveoli, small airways, and interstitial tissues.

Resolution After Exposure

A mild acute episode may improve considerably within approximately 24–48 hours after removal from the causative antigen.

However, symptoms can recur each time the individual is re-exposed. Repeated episodes should therefore prompt careful investigation of occupational, domestic, and recreational exposures.

7. Chronic Hypersensitivity Pneumonitis

Repeated or continuous antigen exposure can produce chronic hypersensitivity pneumonitis.

Patients may develop gradually progressive exertional dyspnoea, persistent cough, fatigue, exercise limitation, and weight loss rather than obvious attacks occurring after exposure.

Longstanding inflammation can lead to irreversible pulmonary fibrosis, architectural distortion, traction bronchiectasis, and eventually chronic respiratory impairment.

Diagnosis

8. Chest Imaging

The chest radiograph may be normal, particularly in mild or early disease.

When abnormal, it may demonstrate diffuse or patchy hazy infiltrates and small nodular opacities.

High-resolution CT (HRCT) is considerably more sensitive and may demonstrate ground-glass opacities, centrilobular nodules, mosaic attenuation, air trapping, and—in chronic fibrotic disease—features of pulmonary fibrosis.

9. Pulmonary Function Tests

Pulmonary function testing commonly demonstrates a restrictive ventilatory defect, particularly when significant interstitial disease is present.

Gas transfer may also be impaired, with a reduced DLCO/TLCO. Some patients, particularly those with prominent small-airway involvement, can demonstrate obstructive or mixed abnormalities.

10. Serum Precipitins

Measurement of serum antigen-specific IgG antibodies, traditionally called serum precipitins, can help demonstrate previous exposure and sensitisation to a suspected antigen.

However, a positive result does not prove active hypersensitivity pneumonitis, because healthy exposed individuals may also develop these antibodies. Similarly, a negative test does not completely exclude the disease.

11. Eosinophilia

Peripheral blood eosinophilia is not a typical feature of EAA.

This is useful when distinguishing hypersensitivity pneumonitis from disorders characterised by prominent eosinophilic inflammation, such as eosinophilic pneumonia or eosinophilic granulomatosis with polyangiitis.

12. Bronchoalveolar Lavage

Bronchoalveolar lavage (BAL) commonly demonstrates an increased proportion of lymphocytes, reflecting the lymphocyte-predominant inflammatory response occurring within the lungs.

Older descriptions emphasise a normal or reduced CD4:CD8 ratio. Although this may occur, the CD4:CD8 ratio is variable and is not sufficiently reliable to diagnose or exclude hypersensitivity pneumonitis.

Treatment

13. Avoidance of the Precipitating Antigen

The most important aspect of treatment is identifying and avoiding the responsible antigen.

This may involve modifying working practices, improving ventilation, using appropriate respiratory protection, removing contaminated material, or—in some cases—completely avoiding the occupational or environmental exposure.

Early antigen avoidance can prevent recurrent attacks and reduce the risk of progression to irreversible fibrosis.

14. Corticosteroids

Systemic corticosteroids may be used in patients with significant acute or subacute disease to reduce pulmonary inflammation and accelerate symptomatic improvement.

Steroids do not replace antigen avoidance, which remains the cornerstone of management. Treatment of chronic fibrotic hypersensitivity pneumonitis is more complex because established fibrosis may be irreversible.

Key Clinical Pattern

Think of extrinsic allergic alveolitis/hypersensitivity pneumonitis when a patient develops fever, dry cough and breathlessness several hours after exposure to an organic antigen, particularly when there is no prominent wheeze.

Classic associations include mouldy hay → farmer’s lung, bird proteins → bird-fancier’s lung, and Aspergillus clavatus → malt worker’s lung.

Diagnosis is supported by the exposure history, HRCT findings, restrictive physiology, antigen-specific IgG and BAL lymphocytosis. The most important treatment is avoidance of the causative antigen, with corticosteroids used when clinically appropriate.

1. Pathogenesis EAA develops when a susceptible individual repeatedly inhales an antigen capable of producing an abnormal immune response within the distal airways and alveoli. Traditionally, the disease has been described as involving a combination of type III immune-complex hypersensitivity and type IV delayed T-cell-mediated hypersensitivity. Repeated inflammation produces lymphocytic alveolitis and interstitial inflammation. If exposure continues, chronic inflammation may eventually result in permanent pulmonary fibrosis. 

2. Immunological Mechanism Patients exposed to the responsible antigen may develop circulating IgG antibodies, sometimes called precipitating antibodies or precipitins. These antibodies indicate sensitisation to the antigen but do not necessarily prove that it is causing the patient’s lung disease. Cellular immunity, particularly involving T lymphocytes, is also central to the development of hypersensitivity pneumonitis. 

Important Types of Extrinsic Allergic Alveolitis 3. Farmer’s Lung Farmer’s lung is a classic form of hypersensitivity pneumonitis caused by exposure to microorganisms growing in mouldy hay and other agricultural material. Traditional organisms associated with farmer’s lung include the thermophilic actinomycetes Saccharopolyspora rectivirgula (formerly Micropolyspora faeni) and Thermoactinomyces species. Farmers may inhale large quantities of these antigens while handling damp or mouldy hay, particularly in poorly ventilated environments. 

4. Bird-Fancier’s Lung Bird-fancier’s lung occurs following repeated exposure to avian proteins from birds such as pigeons, budgerigars, parrots, and poultry. Antigens are present in bird droppings, feathers, and feather bloom, and may become airborne as fine particles that are inhaled deeply into the lungs. Repeated exposure can produce either episodic acute disease or a more insidious chronic form. 

5. Malt Worker’s Lung Malt worker’s lung is an occupational form of hypersensitivity pneumonitis associated with exposure to fungal antigens during the production and handling of malt. A classic causative organism is Aspergillus clavatus, which may contaminate barley and malt and release airborne fungal spores. 

Clinical Features 6. Acute Disease In acute hypersensitivity pneumonitis, symptoms characteristically develop several hours after significant antigen exposure, traditionally around 4–9 hours later. Patients may experience fever, chills or flu-like symptoms, dry cough, chest tightness, malaise, and shortness of breath. Fine inspiratory crackles may be heard on examination. 

Absence of Wheeze Wheezing is usually absent, which can help distinguish EAA from allergic asthma. In asthma, the predominant problem is reversible bronchial obstruction. In EAA, inflammation predominantly involves the alveoli, small airways, and interstitial tissues. 

Resolution After Exposure A mild acute episode may improve considerably within approximately 24–48 hours after removal from the causative antigen. However, symptoms can recur each time the individual is re-exposed. Repeated episodes should therefore prompt careful investigation of occupational, domestic, and recreational exposures. 

7. Chronic Hypersensitivity Pneumonitis Repeated or continuous antigen exposure can produce chronic hypersensitivity pneumonitis. Patients may develop gradually progressive exertional dyspnoea, persistent cough, fatigue, exercise limitation, and weight loss rather than obvious attacks occurring after exposure. Longstanding inflammation can lead to irreversible pulmonary fibrosis, architectural distortion, traction bronchiectasis, and eventually chronic respiratory impairment. 

Diagnosis 8. Chest Imaging The chest radiograph may be normal, particularly in mild or early disease. When abnormal, it may demonstrate diffuse or patchy hazy infiltrates and small nodular opacities. High-resolution CT (HRCT) is considerably more sensitive and may demonstrate ground-glass opacities, centrilobular nodules, mosaic attenuation, air trapping, and—in chronic fibrotic disease—features of pulmonary fibrosis. 

9. Pulmonary Function Tests Pulmonary function testing commonly demonstrates a restrictive ventilatory defect, particularly when significant interstitial disease is present. Gas transfer may also be impaired, with a reduced DLCO/TLCO. Some patients, particularly those with prominent small-airway involvement, can demonstrate obstructive or mixed abnormalities. 

10. Serum Precipitins Measurement of serum antigen-specific IgG antibodies, traditionally called serum precipitins, can help demonstrate previous exposure and sensitisation to a suspected antigen. However, a positive result does not prove active hypersensitivity pneumonitis, because healthy exposed individuals may also develop these antibodies. Similarly, a negative test does not completely exclude the disease. 

11. Eosinophilia Peripheral blood eosinophilia is not a typical feature of EAA. This is useful when distinguishing hypersensitivity pneumonitis from disorders characterised by prominent eosinophilic inflammation, such as eosinophilic pneumonia or eosinophilic granulomatosis with polyangiitis. 

12. Bronchoalveolar Lavage Bronchoalveolar lavage (BAL) commonly demonstrates an increased proportion of lymphocytes, reflecting the lymphocyte-predominant inflammatory response occurring within the lungs. Older descriptions emphasise a normal or reduced CD4:CD8 ratio. Although this may occur, the CD4:CD8 ratio is variable and is not sufficiently reliable to diagnose or exclude hypersensitivity pneumonitis. 

Treatment 13. Avoidance of the Precipitating Antigen The most important aspect of treatment is identifying and avoiding the responsible antigen. This may involve modifying working practices, improving ventilation, using appropriate respiratory protection, removing contaminated material, or—in some cases—completely avoiding the occupational or environmental exposure. Early antigen avoidance can prevent recurrent attacks and reduce the risk of progression to irreversible fibrosis. 

14. Corticosteroids Systemic corticosteroids may be used in patients with significant acute or subacute disease to reduce pulmonary inflammation and accelerate symptomatic improvement. Steroids do not replace antigen avoidance, which remains the cornerstone of management. Treatment of chronic fibrotic hypersensitivity pneumonitis is more complex because established fibrosis may be irreversible. 

Key Clinical Pattern Think of extrinsic allergic alveolitis/hypersensitivity pneumonitis when a patient develops fever, dry cough and breathlessness several hours after exposure to an organic antigen, particularly when there is no prominent wheeze. Classic associations include mouldy hay → farmer’s lung, bird proteins → bird-fancier’s lung, and Aspergillus clavatus → malt worker’s lung. Diagnosis is supported by the exposure history, HRCT findings, restrictive physiology, antigen-specific IgG and BAL lymphocytosis. The most important treatment is avoidance of the causative antigen, with corticosteroids used when clinically appropriate.