What is fibrosing mediastinitis? 

Fibrosing Mediastinitis (FM) is a rare disease where there is a progressive invasive fibrous tissue proliferating inside the mediastinum (large compartment within the thoracic chest in the space between the lungs, consisting of the heart, blood vessels, trachea, oesophagus, lymph nodes and nerves).¹ FM affects important organs that are crucial for survival, and due to the progressive nature of the disease, it can become fatal if it affects the lungs.²

Subtypes

There are two forms of FM:

• Post-Histoplasma fibrosing mediastinitis (PHFM): caused by an abnormal prolonged immune response to the fungus Histoplasma Capsulatum and by tuberculosis infection^1,2
• Idiopathic fibrosing mediastinitis (IFM): is idiopathically associated with IgG4 disease²  

 Both subtypes of FM are rare and are asymptomatic until the condition has progressed to cause severe complications such as restricting blood flow in the airway. 

Epidemiology

FM is a rare disease, and most cases are caused by a histoplasmosis infection, a lung infection caused by the fungus Histoplasma Capsulatum. H. Capsulatum is a fungus that is present in the soil near river valleys and is endemic in the US states of Mississippi and Ohio. The fungus is also found in Central and South America, Europe, Africa, Asia and Oceania. H. Capsulatum can also be found in soils where there is high frequency of bird droppings (as it acts as a fertiliser), bat droppings and caves where bats live, and in chicken houses.² 

FM affects individuals who are between 13 and 65 years old, and there is a higher prevalence of fibrosing mediastinitis in young people assigned female at birth.¹ Most patients are originally infected with H. Capsulatum when they are young children, but symptoms begin to show when they are in their 30s or 40s.² Only 1% of individuals exposed to the fungus develop a histoplasmosis infection, which can lead to PHFM.² It is estimated that there are less than 1000 cases of PHFM in the United States. PHFM cases have only been observed in individuals who live in histoplasmosis-endemic hotspots. IFM is even rarer and affects fewer individuals.²

Pathophysiology

FM is characterised by fibrosis and chronic inflammation of the soft tissue within the mediastinum.³

Mechanisms of fibrosis

Fibrosis is a term used to describe the thickening or scarring of tissues when the connective tissues replace normal wound healing caused by abnormal chronic inflammation.⁴ Instead of replacing damaged tissues that would have finished wound healing, there is an irregular accumulation of Extracellular matrix (ECM), which causes the formation of a fibrotic scar.⁴ Fibrosis therefore occurs where there is an excess of collagen within the ECM, which leads to the formation of fibrotic scars which can cause tissues to become thick and stiff. Fibrotic tissue formation can affect the physiology of how the organs work and can cause severe complications. 

In FM, an individual will develop an abnormal immune response to H. Capsulatum, which causes inflammation and in turn, will cause fibrosis to occur. It is thought that the spores of H. Capsulatum can survive in the lymph nodes and are responsible for the continued immune response and therefore responsible for the chronic inflammation which scars the vessels in the airway causing fibrosing mediastinitis to develop.²

The areas affected in FM:

• Trachea
• Bronchi
• Lymph nodes
• Oesophagus 
• Superior vena cava
• In severe cases, fibrosing mediastinitis can also spread to both lungs

Symptoms and clinical presentations

Patients with FM are asymptomatic for years before showing symptoms such as:

• Shortness of breath
• Fatigue
• Blood when coughing 
• Chronic chest pain
• Lung infections
• Difficulty in swallowing
• Swelling in the arms and face

Patients with IFM can also experience the following symptoms:

• Fever
• Chills and sweating
• Chest pains
• Coughing
• Shortness of breath
• Fibrosis in other sites of the body, outside the mediastinum²

Radiographic findings

A chest radiograph can show:

• The mediastinum area widening
• The lymph nodes become enlarged
• The trachea and bronchi become narrower
• The nodes within the mediastinum have become calcified¹

CECT scans can also show:

• The severity of the scarring
• Which organs are scarred
• How much the vascular structure is affected¹

Differential diagnosis

The symptoms of FM can also be observed in and mistaken for the following medical conditions:

• Superior vena cava syndrome: occurs when the blood flow through the superior vena cava is obstructed, restricting blood flow
• Mediastinal granuloma: This is also caused by histoplasmosis, where the mediastinal lymph nodes become enlarged due to an immune response
• Sarcoidosis: granulomas (swollen tissues) develop in the organs such as the lungs, lymph nodes and skin
• Acute or subacute adenitis: inflammation within lymph nodes caused by an infection²

Major complications

FM is a progressive disease where there is a build-up of fibrous tissues within the mediastinum.² The build-up of scarring is slow, with 1 mm growing every year, and symptoms don't appear until the disease has progressed and has caused major complications.² 

The major complications associated with fibrosing mediastinitis include:³

Superior vena cava syndrome (SVC syndrome)

As mentioned above, SVC syndrome is caused by a partial or complete obstruction of blood flowing through the superior vena cava. The blockage is caused by the build-up of fibrous connective tissues within the walls of the superior vena cava, and the blockage will prevent blood flow to the body, impacting the physiology of the body. 

Thrombosis

Thrombosis occurs when there are blood clots which block the blood vessels. Blood clots are caused by the excess fibrous tissues which block blood vessels, and the blood clots can become dangerous and lead to conditions like heart attack or strokes. 

Pulmonary hypertension

Pulmonary hypertension is when there is high blood pressure within blood vessels in the lungs. This condition is a severe complication as hypertension can damage the right side of the heart, which thickens and stiffens the walls of pulmonary arteries, which then restricts blood flow. This forces the heart to work harder to pump blood around the body, which can lead to heart failure. 

Oesophageal compression

Oesophageal compression is a condition that is caused by pressure acting on the oesophagus. In the context of fibrosing mediastinitis, the pressure is caused by fibrotic tissues acting and compressing the oesophagus. This causes patients to struggle to swallow and experience pain when swallowing.

Airway stenosis

Airway stenosis occurs when the airway becomes narrowed. This causes patients to cough, struggle with breathing and have a shortness of breath.

Pleural effusions

Pleural effusion is a medical condition where there is fluid build-up in the space between the chest wall and the lungs, and this causes patients to experience a shortness of breath, coughing and chest pain.

Tracheobronchial obstruction

Tracheobronchial obstruction is a life-threatening condition where the trachea and bronchial become narrow and the upper airways become blocked. This makes it harder for the patient to breathe and immediate medical attention is needed.

Comorbidities

Patients with FM can also have other medical conditions, whether already diagnosed or underlying conditions. These can include:

• Recurrent pneumonia: Pneumonia is an infection that causes air sacs in the lungs to become inflamed and fill with fluid. Recurrent pulmonary infection and pneumonia are common conditions associated with fibrosing mediastinitis²
• Chronic infection of tuberculosis is a bacterial infection that infects the lungs, and tuberculosis is able to cause fibrosing mediastinitis like H. Capsulatum¹
• Autoimmune diseases such as sarcoidosis
• Hypertension
• Chronic obstructive pulmonary disease (COPD)

Diagnosis

FM is diagnosed using imaging scans that can show abnormal changes in the mediastinum.² Imaging scans such as chest CT scan, X-ray, CECT and MRI are used to view the chest and determine changes to the mediastinum.² Laboratory diagnosis is sometimes used when the imaging is not definite and techniques such as histoplasma serologies where antibodies against the pathogen are detected or a biopsy of the mediastinum tissues.² 

Diagnosing FM is difficult and may take several years as some symptoms overlap with other medical conditions and are not specific enough, or the scans don't show the diagnosis.² This, unfortunately, means that patients are mistakenly diagnosed with other medical conditions. 

Management and prognosis

There is no cure or known effective medical treatment for FM, and treatment is focused on treating symptoms and complications of FM.² The disease is slow progressing, and there are three treatments available:³

• Antifungal or corticosteroid treatment: to treat histoplasmosis, which causes FM 
• Surgery: to remove the scarred tissue in the mediastinum
• Treating complications and symptoms of fibrosing mediastinum 

The prognosis of FM depends on the subtype and which organs are involved in the mediastinum. In 80% of patients, one lung is affected, and as long as the condition is detected and treated, the other lung can be saved, and life expectancy is normal.² 

Conclusion

FM is a rare disease where there is a progressive invasive fibrous tissue proliferating inside the mediastinum. FM is characterised by fibrosis and chronic inflammation of the soft tissue within the mediastinum. Complications of FM can be vascular, affecting blood vessels like superior vena cava syndrome, thrombosis and pulmonary hypertension, or respiratory conditions like tracheobronchial obstruction, pleural effusion and airway stenosis.