Bronchocentric Granulomatosis

Bronchocentric granulomatosis is a histological pattern, not a single disease, in which necrotising granulomatous inflammation is centred on bronchi and bronchioles, destroying the airway wall. It presents as a lung nodule, mass or consolidation, and is rare.

Two clinical groups are recognised. About half of patients are asthmatic, with allergic bronchopulmonary aspergillosis (or another fungal hypersensitivity) as the usual cause, peripheral eosinophilia and a younger age. The rest have no asthma and a cause is found in many: mycobacterial or fungal infection, rheumatoid arthritis, granulomatosis with polyangiitis, inflammatory bowel disease or an inhaled antigen.

Pathophysiology. In the asthmatic form, fungal antigen in the airway provokes a type I and type III hypersensitivity response with eosinophilic and necrotic granulomas replacing the bronchial wall. In the non-asthmatic form, infection or systemic autoimmune disease causes the same pattern, so the histology directs a search for the cause.

Cough, wheeze, fever, malaise, pleuritic pain and mucus plugs or brown sputum in the asthmatic group. In others, the finding is often incidental on imaging, or there are features of the underlying disease (joint disease, sinus disease, haematuria). Examination is often normal.

Haemoptysis, rapidly progressive hypoxaemia or features of vasculitis need urgent assessment.

• Diagnosis requires tissue showing necrotising granulomas centred on bronchioles, from surgical or CT-directed biopsy, with special stains for fungi and mycobacteria.
• Chest radiograph and high resolution CT: a solitary nodule or mass (often with an irregular edge), patchy or lobar consolidation, atelectasis from mucus plugging, central bronchiectasis and high attenuation mucus in the asthmatic group.
• Blood: eosinophil count, total IgE (over 1000 IU/mL supports allergic bronchopulmonary aspergillosis), Aspergillus specific IgE and IgG, skin prick test.
• Exclude infection: sputum and lavage cultures for mycobacteria and fungi, interferon gamma release assay, serum galactomannan, cryptococcal antigen.
• Autoimmune tests: rheumatoid factor, anti-cyclic citrullinated peptide, ANCA, antinuclear antibody.
• Spirometry with bronchodilator reversibility.

Differential diagnosis.

• Lung cancer
• Tuberculosis and other granulomatous infection
• Granulomatosis with polyangiitis
• Eosinophilic granulomatosis with polyangiitis
• Rheumatoid nodules
• Sarcoidosis
• Organising pneumonia

• Treat the cause. Antimicrobial therapy for mycobacterial or fungal infection should be started before steroid in the non-asthmatic group.
• Asthmatic group (allergic bronchopulmonary aspergillosis): prednisolone 0.5 mg/kg daily (30 to 40 mg) for 2 to 4 weeks, then taper over 3 to 6 months, with itraconazole 200 mg twice daily for 16 weeks as a steroid sparing option. Check itraconazole levels (target trough over 0.5 mg/L) and liver function. Add inhaled corticosteroid and a long acting bronchodilator for the asthma.
• Idiopathic non-asthmatic disease: prednisolone 0.5 to 1 mg/kg daily with slow taper, and azathioprine 1 to 2 mg/kg daily (after thiopurine methyltransferase testing) for relapse.
• Systemic vasculitis: rituximab 1 g on days 1 and 15 or cyclophosphamide 600 mg/m2 monthly with steroid, using the regimen for the vasculitis itself.
• Resection of a localised mass is often diagnostic and curative.
• Prophylaxis against Pneumocystis when prednisolone is 20 mg or more daily for over 4 weeks: co-trimoxazole 960 mg three times weekly.

Complications and prognosis. Most respond to steroid and removal of the cause. Relapse is common after steroid withdrawal, and bronchiectasis and fibrosis can follow.

Monitoring. Review at 4 and 12 weeks with symptoms, eosinophils, IgE and chest imaging, then every 3 to 6 months for the first 2 years.

Referral and escalation. Refer to a respiratory physician and a thoracic pathologist for diagnosis, and to rheumatology if systemic disease is found.