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PA25.5 | Occupational & Interstitial Lung Disease — SDL Guide (Part 3)

Hypersensitivity Pneumonitis

A four-panel medical diagram explaining hypersensitivity pneumonitis, its antigen sources, immune mechanism, lung morphology, and distinction from sarcoidosis.

Hypersensitivity Pneumonitis: Antigens, Mechanism, and Morphology

Panel A: Repeated inhalation of organic antigens, alveoli, interstitium, Type III immune complex hypersensitivity, Type IV cell-mediated hypersensitivity, activated T cells, macrophages, granuloma formation. Panel B: Farmer’s lung with Saccharopolyspora rectivirgula from mouldy hay, bird-fancier’s lung with avian proteins from serum/droppings, bagassosis with Thermoactinomyces sacchari from mouldy sugarcane. Panel C: Bronchiole, alveoli, lymphocytic and plasma-cell interstitial infiltrate, poorly formed non-caseating granulomas, bronchiolocentric distribution, absence of fibrin or necrosis in acute phase, chronic interstitial fibrosis. Panel D: Hypersensitivity pneumonitis granulomas that are poorly formed and bronchiolocentric compared with sarcoidosis granulomas that are well formed and perilymphatic.

Hypersensitivity pneumonitis (HP), also called extrinsic allergic alveolitis, is an immunologically mediated ILD caused by repeated inhalation of organic antigens — in contrast to the mineral dust diseases above.

Mechanism: Combined Type III (immune complex) + Type IV (cell-mediated, granulomatous) hypersensitivity.

Classic examples:

SyndromeAntigenSource
Farmer's lungSaccharopolyspora rectivirgula (thermophilic actinomycete)Mouldy hay
Bird-fancier's lungAvian proteins (serum, droppings)Pigeons, parrots
BagassosisThermoactinomyces sacchariMouldy sugarcane

Morphology: Diffuse lymphocytic and plasma-cell interstitial infiltrate; poorly formed non-caseating granulomas (bronchiolocentric); no fibrin or necrosis in acute phase. Chronic HP → interstitial fibrosis.

Key distinction from sarcoidosis: HP granulomas are poorly-formed and bronchiolocentric; sarcoidosis granulomas are well-formed and perilymphatic. HP has a clear antigen exposure history; sarcoidosis does not.

Outcome: Removal from antigen exposure → resolution in acute/subacute HP. Chronic continued exposure → irreversible fibrosis.

Idiopathic Pulmonary Fibrosis (UIP Pattern)

Diagram of idiopathic pulmonary fibrosis showing basal sub-pleural lung fibrosis, UIP histology with honeycombing and fibroblastic foci, pathogenesis, and HRCT correlation.

Idiopathic Pulmonary Fibrosis: UIP Pattern

Panel A: Paired lungs with bilateral sub-pleural basal fibrosis, lower-lobe predominance, honeycomb cysts, normal upper lung parenchyma, pleural surface.. Panel B: UIP histology showing normal lung adjacent to dense fibrosis and honeycombing, emphasizing spatial and temporal heterogeneity.. Panel C: High-power fibroblastic focus with proliferating fibroblasts in myxoid stroma at the advancing edge of collagen fibrosis.. Panel D: Pathogenesis flowchart from repeated alveolar epithelial injury to persistent fibroblast activation and fibrosis, paired with HRCT reticular opacities and honeycombing..

Idiopathic pulmonary fibrosis (IPF) is the most common and most lethal idiopathic ILD. It has no known exogenous cause.

Histological pattern: Usual Interstitial Pneumonia (UIP)
• Spatial and temporal heterogeneity — areas of normal lung adjacent to fibrosis and honeycombing (temporal heterogeneity)
• Fibroblastic foci — the hallmark: clusters of actively proliferating fibroblasts in a myxoid stroma at the advancing edge of fibrosis
• Sub-pleural, basal predominance
• Honeycombing (cystic spaces lined by bronchiolar epithelium) in advanced disease

High-resolution CT (HRCT): Bilateral, sub-pleural, basal-predominant reticular opacities ± honeycombing — the UIP pattern on imaging.

Pathogenesis: Current model — repeated alveolar epithelial injury (from micro-aspirations, smoking, viral infections?) → abnormal epithelial-mesenchymal signalling → fibroblast activation that fails to switch off. NOT primarily inflammatory (anti-inflammatory drugs ineffective).

Prognosis: Median survival 2–3 years from diagnosis. Anti-fibrotic agents (pirfenidone, nintedanib) slow progression but do not reverse fibrosis.

Sarcoidosis

A four-panel educational diagram shows pulmonary sarcoidosis with bilateral hilar lymphadenopathy, non-caseating granulomas, giant-cell inclusions, and chest radiology stages I to IV.

Sarcoidosis: Granulomas, Inclusions, and Lung Staging

Panel A: Lungs, bilateral hilar lymphadenopathy, perilymphatic nodules, bronchovascular bundles, subpleural distribution, skin involvement, eye involvement, peripheral lymph nodes, increased serum ACE note, fibrosis to cor pulmonale note.. Panel B: Well-formed non-caseating granuloma, epithelioid macrophages, Langhans-type multinucleate giant cell, foreign-body-type giant cell, surrounding lymphocytes, outer rim of fibrosis, no central caseous necrosis, crossed-out TB caseation comparison inset.. Panel C: Schaumann body as calcified concentric laminar inclusion, Asteroid body as stellate inclusion, multinucleate giant cells.. Panel D: Stage I bilateral hilar lymphadenopathy alone, Stage II bilateral hilar lymphadenopathy with pulmonary infiltrates, Stage III pulmonary infiltrates without hilar lymphadenopathy, Stage IV pulmonary fibrosis..

Sarcoidosis is a systemic granulomatous disease of unknown aetiology affecting lungs (90%), lymph nodes, skin, eyes, and other organs.

Key pathological feature: non-caseating granulomas
• Well-formed, discrete aggregates of epithelioid macrophages (activated) with multinucleate giant cells (Langhans and foreign-body type)
• No central necrosis (caseation) — distinguishes from TB
• Surrounded by lymphocytes; outer rim of fibrosis in older lesions
• Perilymphatic distribution (along bronchovascular bundles and sub-pleural)

Inclusions in giant cells:
• Schaumann bodies (calcified concentric laminar structures)
• Asteroid bodies (stellate inclusions)

Clinical-radiological stages (lungs):
• Stage I: Bilateral hilar lymphadenopathy (BHL) alone
• Stage II: BHL + pulmonary infiltrates
• Stage III: Pulmonary infiltrates, no BHL
• Stage IV: Pulmonary fibrosis

Serology: ↑ Serum ACE (angiotensin-converting enzyme) — not specific but useful for monitoring.

Outcome: Most patients (60–70%) remit spontaneously. ~20% develop chronic disease. End-stage fibrosis → cor pulmonale.

SELF-CHECK

A 35-year-old pigeon-keeper presents with progressive breathlessness, low-grade fever, and bilateral interstitial opacities. Lung biopsy shows poorly-formed bronchiolocentric granulomas with lymphocytic infiltrate and no caseation. Which diagnosis fits best?

A. Sarcoidosis

B. Miliary tuberculosis

C. Hypersensitivity pneumonitis (bird-fancier's lung)

D. Idiopathic pulmonary fibrosis

Reveal Answer

Answer: C. Hypersensitivity pneumonitis (bird-fancier's lung)

Bird-fancier's lung (hypersensitivity pneumonitis from avian proteins) produces poorly-formed, bronchiolocentric granulomas — in contrast to sarcoidosis (well-formed, perilymphatic) and TB (caseating). The pigeon-keeping history, the organic antigen exposure, and the bronchiolocentric pattern clinch the diagnosis. IPF shows fibroblastic foci and honeycombing, not granulomas. Miliary TB has numerous caseating granulomas.