Berylliosis

Overview

•Rare occupational lung disease caused by inhaled beryllium (dust/fumes) - used in aerospace, nuclear, and dental industries

•Two forms: acute beryllium disease (toxic chemical pneumonitis - heavy short-term exposure) and chronic beryllium disease (CBD) (granulomatous, immune-mediated - far more clinically significant)

•Pathophysiology of CBD: type IV (delayed-type) hypersensitivity - beryllium acts as a hapten → CD4+ T-cell sensitisation → macrophage activation → non-caseating granuloma formation → progressive fibrosis

•HLA-DP beta-1 glutamate-69 allele confers genetic susceptibility

•Prescribed occupational disease in the UK - industrial injuries benefit may apply

Presentation

Acute vs chronic beryllium disease
FeatureAcute beryllium diseaseChronic beryllium disease (CBD)
OnsetAcute, after heavy exposureInsidious, often years after first exposure
MechanismDirect toxic pneumonitisType IV hypersensitivity / immune-mediated
SymptomsAcute dyspnoea, cough, fever, malaise, chest pain; conjunctivitis, rhinitis, skin rashProgressive exertional dyspnoea, dry cough, fatigue, weight loss, night sweats
SignsFeatures of acute pneumonitisFinger clubbing, fine bibasal crackles, lymphadenopathy
PrognosisGood - most recover fully if exposure terminatedProgressive; spontaneous remission rare

Feature	Acute beryllium disease	Chronic beryllium disease (CBD)
Onset	Acute, after heavy exposure	Insidious, often years after first exposure
Mechanism	Direct toxic pneumonitis	Type IV hypersensitivity / immune-mediated
Symptoms	Acute dyspnoea, cough, fever, malaise, chest pain; conjunctivitis, rhinitis, skin rash	Progressive exertional dyspnoea, dry cough, fatigue, weight loss, night sweats
Signs	Features of acute pneumonitis	Finger clubbing, fine bibasal crackles, lymphadenopathy
Prognosis	Good - most recover fully if exposure terminated	Progressive; spontaneous remission rare

⚠️
CBD is clinically, radiologically, and histologically indistinguishable from sarcoidosis. Always take a detailed occupational history in any patient with apparent sarcoidosis - the distinction has major medicolegal and compensation implications.

Investigations

•Beryllium lymphocyte proliferation test (BeLPT) - the specific diagnostic test; measures proliferation of blood or BAL lymphocytes in response to beryllium antigen; positive result confirms beryllium sensitisation

•Chest X-ray - reticulonodular shadowing, hilar lymphadenopathy, or normal early in disease

•Pulmonary function tests - restrictive pattern (reduced FVC, normal/elevated FEV1/FVC ratio) with reduced TLCO

•Serum ACE - typically normal or mildly elevated in CBD (contrast: often markedly raised in active sarcoidosis) - useful in differential diagnosis

•HRCT chest (gold standard imaging) - perilymphatic nodules, ground-glass opacification, honeycombing in advanced disease

•BAL with BeLPT - CD4+ lymphocytosis + positive BeLPT on BAL fluid highly specific for CBD

•Lung biopsy - non-caseating granulomas (identical to sarcoidosis); diagnosis requires granulomas + positive BeLPT

🎯
Histology alone cannot distinguish CBD from sarcoidosis - the BeLPT is the key differentiator. Positive BeLPT + beryllium exposure + non-caseating granulomas = CBD.

Differential Diagnosis

•Sarcoidosis - histologically identical; differentiate by occupational history, BeLPT negative, serum ACE more markedly raised

•Hypersensitivity pneumonitis - organic antigen exposure; serum precipitins positive; lymphocytic alveolitis (not granulomas) on biopsy

•Silicosis - different occupational exposure; upper-lobe nodules on HRCT

•TB - caseating granulomas; positive Mantoux/IGRA; microbiological confirmation

Management

🥇 First-line

•permanent removal from beryllium exposure - most important initial step for all forms

•First-line (CBD): prednisolone orally (typically 40 mg/day, tapering) - suppresses granulomatous inflammation; indicated in symptomatic CBD with physiological impairment or progressive disease

•Second-line (steroid-sparing): methotrexate or azathioprine - for unacceptable corticosteroid side effects or steroid-refractory disease

🥉 Third-line

•lung transplantation - end-stage fibrotic disease with severe respiratory failure

•Acute beryllium disease: supportive care + corticosteroids; majority recover fully if heavy exposure terminated promptly

Prevention

•COSHH Regulations 2002 - employers must minimise exposure below the workplace exposure limit (WEL)

•Engineering controls preferred (enclosed systems, local exhaust ventilation) over PPE

•Regular BeLPT surveillance of exposed workers - sensitised workers relocated to non-beryllium roles even before symptoms emerge

Complications

•Progressive pulmonary fibrosis → restrictive respiratory failure (type I)

•Pulmonary hypertension → cor pulmonale

•Increased lung cancer risk - beryllium is a Group 1 human carcinogen (IARC), independent of smoking

•Long-term corticosteroid complications - osteoporosis, diabetes, hypertension, adrenal suppression