Hypersensitivity Pneumonitis

Hypersensitivity pneumonitis (HP, extrinsic allergic alveolitis) is an immune mediated granulomatous interstitial and small airways disease caused by repeated inhalation of organic antigens or reactive chemicals in susceptible individuals.

Antigens: avian proteins (bird fancier lung, feather duvets), thermophilic actinomycetes in mouldy hay (farmer lung), mould in humidifiers, hot tubs (Mycobacterium avium complex), metalworking fluids, isocyanates, mould in damp buildings, bagasse.

Prevalence is 1 to 2 per 100,000; no antigen identified in up to 50%.

Now classified as non fibrotic or fibrotic HP; fibrotic HP has worse outcomes (median survival about 5 to 7 years), resembling IPF.

Mechanisms: type III (immune complex) and type IV (T cell, Th1/Th17) hypersensitivity.

• Acute: 4 to 8 hours after exposure, fever, chills, malaise, cough, dyspnoea, myalgia, resolving in 24 to 48 hours.
• Subacute: progressive cough, dyspnoea, fatigue, weight loss over weeks to months.
• Chronic: insidious dyspnoea, clubbing, crackles, weight loss, with fibrosis; "squeaks" on inspiration.
• Symptoms improve away from exposure.

• Exposure history (home, work, hobbies) with identification of the antigen; specific IgG precipitins (supportive, not diagnostic).
• HRCT: ground glass, poorly defined centrilobular nodules, mosaic attenuation with air trapping on expiratory images (three density sign); fibrotic features with traction bronchiectasis, honeycombing (lower lobe, upper or random distribution).
• Pulmonary function: restrictive or mixed; reduced DLCO.
• Bronchoalveolar lavage: lymphocytosis over 30% (often 50%), CD4/CD8 ratio low; transbronchial cryobiopsy: poorly formed non necrotising granulomas, cellular bronchiolitis, interstitial pneumonia.
• Inhalational challenge uncommon. Multidisciplinary diagnosis.

• Antigen avoidance is the key intervention: remove birds and feather bedding, repair damp, clean humidifiers, change occupation, respirator use when avoidance impossible.
• Prednisolone 0.5 mg/kg (30 to 40 mg) daily for 4 to 8 weeks, tapered over 3 to 6 months, in symptomatic or physiologically impaired non fibrotic disease or severe acute episodes.
• Steroid sparing agents in chronic or relapsing disease: mycophenolate mofetil 1 to 1.5 g twice daily, azathioprine 1 to 2 mg/kg; rituximab in refractory cases.
• Progressive fibrotic HP: nintedanib 150 mg twice daily (INBUILD) to slow FVC decline.
• Pneumocystis prophylaxis and bone protection during therapy.
• Long term oxygen, pulmonary rehabilitation, vaccinations; lung transplantation for end stage.
• Follow up with spirometry, DLCO and HRCT at 3 to 6 months; fibrosis may progress despite avoidance.