Fibrosing Mediastinitis

Fibrosing mediastinitis (sclerosing mediastinitis) is a rare condition in which dense fibrous tissue proliferates in the mediastinum and compresses or invades the airways, great vessels, oesophagus and pulmonary arteries and veins. It is a chronic, progressive process.

The commonest cause in the Americas is histoplasmosis (Histoplasma capsulatum), and in many other regions tuberculosis is a leading cause. Other causes are sarcoidosis, IgG4-related disease, prior radiotherapy, silicosis, other fungal infections (Aspergillus, Blastomyces, Coccidioides), Behçet disease, drugs (methysergide), and idiopathic disease. It affects young to middle aged adults, and children and adolescents in endemic regions.

Pathophysiology. In histoplasmosis, an exaggerated immune response to leaked fungal antigen from caseous mediastinal lymph nodes drives fibroblast activation and collagen deposition, and not active infection. In IgG4-related disease, plasma cells and storiform fibrosis cause a similar picture. Fibrosis may be focal (a single calcified subcarinal or paratracheal mass, commonly in histoplasmosis) or diffuse (infiltrating the mediastinum, common in IgG4 disease and sarcoidosis).

Many are asymptomatic. Others have cough, dyspnoea, wheeze, haemoptysis, chest pain and recurrent pneumonia from airway or pulmonary vessel narrowing. Superior vena cava obstruction (facial swelling, venous distension, headache), pulmonary hypertension from pulmonary artery obstruction, pulmonary vein obstruction (mimicking mitral stenosis with pulmonary oedema), dysphagia and chylothorax can occur. Pleural effusion and constitutional symptoms are variable.

Massive haemoptysis, severe airway compromise, tense superior vena cava syndrome or right heart failure needs urgent assessment.

• Contrast CT (or MRI): infiltrating soft tissue mass in the mediastinum with calcification (common in granulomatous causes), obliterating mediastinal fat planes and narrowing the vessels, airways or oesophagus. Lack of calcification suggests an IgG4 or malignant process.
• CT pulmonary angiography or venography, and ventilation perfusion scanning for pulmonary vascular obstruction, with echocardiography and, where needed, right heart catheterisation.
• Bronchoscopy for airway narrowing and to exclude endobronchial disease.
• Microbiological and serological tests: Histoplasma urine and serum antigen and antibody (complement fixation, immunodiffusion), tuberculosis tests, other fungal serology, angiotensin converting enzyme, serum IgG4 and IgG subclasses, ANCA, antinuclear antibody and inflammatory markers.
• Biopsy if the cause is uncertain or malignancy is suspected: endobronchial ultrasound directed transbronchial needle aspiration, mediastinoscopy or surgical biopsy, with caution because of vascular risk. Histology shows dense collagen with few cells, and special stains for fungi.
• Lung function with flow volume loops, and perfusion imaging.

Differential diagnosis.

• Mediastinal lymphoma, thymoma or other tumour
• Lung cancer with nodal metastasis
• Sarcoidosis
• Tuberculous lymphadenitis
• Mediastinal granuloma (without fibrosis)
• Vasculitis or aortitis
• Pulmonary vein stenosis from other causes

• No therapy is fully effective, and treatment is directed at the cause and the complication.
• Histoplasma related, progressive disease: itraconazole 200 mg twice daily for 12 months (after a loading dose of 200 mg three times daily for 3 days), with itraconazole level monitoring (trough over 1 mg/L) and liver function, though benefit is not proven because the process is largely fibrotic.
• Tuberculous disease: antituberculosis therapy (rifampicin 10 mg/kg, maximum 600 mg, isoniazid 5 mg/kg, maximum 300 mg, pyrazinamide 25 mg/kg and ethambutol 15 mg/kg daily for 2 months, then rifampicin and isoniazid for 4 months), with prednisolone 0.5 mg/kg when inflammation is prominent.
• IgG4-related and sarcoid disease: prednisolone 0.5 to 0.6 mg/kg daily (30 to 40 mg) for 4 to 8 weeks, then taper over 3 to 6 months, with rituximab 1 g on days 1 and 15 or azathioprine 1 to 2 mg/kg as steroid sparing therapy.
• Endovascular and airway intervention for symptoms: stent for superior vena cava obstruction (self-expanding stent after balloon angioplasty, with anticoagulation), pulmonary artery or pulmonary vein angioplasty and stenting (recurrence of stenosis is frequent), and airway stenting or dilatation for bronchial stenosis.
• Surgical bypass or resection in selected patients, and lung resection for destroyed lung with recurrent infection or haemoptysis. Operative mortality is high.
• Management of haemoptysis: tranexamic acid 500 mg to 1 g orally three times daily, and bronchial artery embolisation.
• Right heart failure and pulmonary hypertension: diuretics, oxygen when PaO2 is 7.3 kPa or less, and anticoagulation for thrombosis.

Complications and prognosis. Slowly progressive in many, and stable in others. Mortality is higher with bilateral pulmonary artery or vein involvement, with survival often 5 to 10 years or more after diagnosis.

Monitoring. CT every 6 to 12 months, echocardiography yearly, spirometry, and follow up of stents with Doppler or angiography at 3 to 6 months.

Referral and escalation. Refer to a centre with interventional radiology, thoracic surgery and pulmonary hypertension expertise.