Hypersensitivity pneumonitis (extrinsic allergic alveolitis)

Overview

Hypersensitivity pneumonitis (HP) / extrinsic allergic alveolitis (EAA) - inflammatory interstitial lung disease caused by immune response to inhaled organic antigens in a sensitised individual. Genuinely reversible if antigen removed early.

Presentation

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Classic vignette: patient whose breathlessness improves on weekends/holidays - always ask about occupational and hobby exposures (pigeons, farming, damp environments).
Acute vs chronic HP
FeatureAcute HPChronic HP
OnsetSymptoms 4-8 h after exposureInsidious, months to years
Key symptomsDyspnoea, fever, chills, dry cough, myalgiaProgressive exertional dyspnoea, weight loss, fatigue
ExaminationOften normal between episodesBilateral fine inspiratory crackles, digital clubbing (late)
ReversibilityFull recovery if antigen removedFibrosis largely irreversible

Investigations

•Chest X-ray - bilateral diffuse infiltrates, upper/mid-zone predominance; normal CXR does not exclude HP
•HRCT thorax - ground-glass opacification, centrilobular nodules, mosaic attenuation (acute); honeycombing and traction bronchiectasis (chronic/fibrotic)
•Pulmonary function tests - restrictive pattern (reduced FEV1, FVC, preserved FEV1:FVC ratio) + reduced TLCO/DLCO
•Serum precipitins (antigen-specific IgG) - confirms sensitisation; positive in most exposed individuals but does NOT confirm disease
•Bronchoalveolar lavage (BAL) - hallmark: raised lymphocytes (lymphocytosis); inverted CD4:CD8 ratio (predominantly CD8+)
•Surgical lung biopsy (gold standard) - non-caseating granulomata with lymphocytic alveolitis; reserved for diagnostically uncertain cases
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Positive precipitins = sensitisation only, not disease. Negative precipitins do NOT exclude HP - history and HRCT carry significant diagnostic weight.

Differential diagnosis

Key differentials
ConditionDistinguishing features
SarcoidosisGranulomatous disease but CD4:CD8 ratio elevated (not inverted); bilateral hilar lymphadenopathy; multi-system involvement
IPFNo identifiable allergen, no BAL lymphocytosis, no reversibility; chronic HP can mimic radiologically
Community-acquired pneumoniaAcute HP with fever mimics infection; key: temporal link to antigen exposure, no productive cough
PsittacosisChlamydia psittaci from birds; true pneumonia with relative bradycardia and splenomegaly; treat with doxycycline

Management

🥇 First-line

•antigen removal - identify and eliminate causative agent; complete avoidance gives best prognosis; may require occupational change or environmental modification
•supplemental oxygen - for hypoxaemia in acute episodes; target SpO2 94-98%

🥈 Second-line

•oral prednisolone - if symptoms persist despite antigen removal; tapering course; accelerates resolution in acute disease

🥉 Third-line

•immunosuppressants - azathioprine or cyclophosphamide if inadequate corticosteroid response; under specialist guidance
•End-stage: lung transplantation assessment for progressive fibrotic disease

Pathophysiology and causes

•Type III (immune complex/IgG precipitins) + Type IV (T-cell granulomatous) hypersensitivity - dual mechanism
•Result: lymphocytic alveolitis with non-caseating granulomata → if persistent, irreversible fibrosis
Named condition
Antigen source
Farmer's lung
Thermophilic actinomycetes (mouldy hay)
Bird-fancier's lung
Avian proteins (pigeons, budgerigars)
Malt worker's lung
Aspergillus clavatus (mouldy malt)
Mushroom worker's lung
Thermophilic actinomycetes (compost)
Hot tub lung
Mycobacterium avium complex (contaminated water)

Prognosis and complications

•Acute HP - excellent prognosis with full recovery if antigen removed promptly
•Chronic fibrotic HP - substantially worse; may be indistinguishable from IPF; continued antigen exposure is the strongest predictor of poor outcome
•Complications: irreversible pulmonary fibrosis, type 1 respiratory failure, pulmonary hypertension, cor pulmonale