Tracheobronchial Amyloidosis

Tracheobronchial amyloidosis is the localised deposition of amyloid in the submucosa of the trachea and bronchi. The amyloid is nearly always of light chain type, produced by local clonal plasma cells, and it is not linked to systemic disease in most cases.

It presents between 50 and 60 years, in both sexes, with a slowly progressive course. It is often misdiagnosed as asthma or chronic bronchitis for years. Forms are diffuse (the commonest), nodular and mixed.

Pathophysiology. Local plasma cells secrete monoclonal light chains that aggregate into beta sheet fibrils and deposit in the submucosa and around glands. Thickening of the airway wall, with calcification or ossification in some, narrows the lumen and stiffens it.

Cough, dyspnoea, wheeze not responsive to bronchodilator, stridor, hoarseness, haemoptysis (from fragile mucosa), and recurrent pneumonia and atelectasis distal to the narrowing. Examination may show stridor or focal wheeze.

Stridor at rest, haemoptysis over 100 mL or acute airway obstruction needs urgent airway care.

• Flexible bronchoscopy: waxy, yellow white submucosal plaques or nodules with stenosis, with biopsy being safe in most though bleeding is possible.
• Histology: Congo red staining with apple green birefringence under polarised light, with typing of the amyloid by immunohistochemistry or mass spectrometry to confirm light chain type.
• CT chest: diffuse circumferential tracheal and bronchial wall thickening, often with calcification, involving the posterior membrane (which is spared in relapsing polychondritis), with nodules, atelectasis and air trapping.
• Exclude systemic amyloidosis: serum free light chains, serum and urine protein electrophoresis with immunofixation, urinary protein, troponin and natriuretic peptide, echocardiography, and a bone marrow examination when a monoclonal protein is found.
• Spirometry with flow volume loop for upper airway obstruction.

Differential diagnosis.

• Relapsing polychondritis
• Granulomatosis with polyangiitis
• Tracheobronchopathia osteochondroplastica
• Sarcoidosis
• Tracheal tumour
• Tuberculosis
• Asthma

• Asymptomatic or minimal disease is observed.
• Symptomatic narrowing: bronchoscopic debulking by cold forceps, laser, argon plasma coagulation or cryotherapy, repeated as needed, and silicone stenting in selected cases (stents can increase granulation).
• External beam radiotherapy to the airway, about 20 Gy in fractions, shows reduced progression and symptoms in reported series, and is used for diffuse disease.
• Surgical resection with reconstruction for focal, severe stenosis of the trachea.
• Systemic AL amyloidosis, if found: treatment with a haematology team, usually daratumumab with cyclophosphamide, bortezomib and dexamethasone (bortezomib 1.3 mg/m2 and cyclophosphamide 300 mg/m2 weekly, with dexamethasone 20 to 40 mg weekly), with dosing set by haematology and organ function.
• Treat infections beyond the narrowing with antibiotics for 7 to 10 days, for example amoxicillin-clavulanate 625 mg three times daily.
• Avoid unnecessary intubation, and warn the anaesthetist, since airway trauma may cause bleeding.

Complications and prognosis. Airway obstruction, haemorrhage, recurrent pneumonia and respiratory failure. Localised disease has a good outlook with repeated bronchoscopic therapy, whereas recurrence is common.

Monitoring. Bronchoscopy or CT every 6 to 12 months initially, then every 1 to 3 years, with free light chains and cardiac assessment yearly to detect progression to systemic disease.

Referral and escalation. Refer to an interventional pulmonologist and a haematologist. Refer urgently for stridor.