Introduction

Fibrosing mediastinitis (FM) is a rare disease affecting the mediastinum, which is the space in the middle of the chest between the lungs and the hilar regions (where the lungs' bronchi, blood vessels, and nerves enter and exit). This disease usually causes excessive thickening or scar tissue build-up within these areas.¹ FM usually affects people between 13 and 65, with a higher occurrence in young females.²

It is important to learn how to effectively manage FM, as it can cause significant health problems and even be fatal. This is because excessive fibrosis or scarring can narrow or block vital structures essential for breathing and circulation, such as the arteries and veins in the lungs, the main vein to the heart, the airways, and the oesophagus, potentially leading to life-threatening complications.³ Since FM is a rare disease with limited information and experience, it's important for patients and their caregivers to be well-educated about FM.⁴ This can encourage them to play an active role in treatment decisions and equip them to manage and follow treatment plans effectively, leading to better outcomes.^4,5 

In this article, you will learn about the causes of FM, its potential complications, and effective management strategies.

What causes fibrosing mediastinitis?

The exact cause of FM is not known,³ but it is believed to be caused by either:

• A response to past infections: FM is considered a rare excessive immune response to remote infections, such as histoplasmosis and tuberculosis (TB)^3,6,7
• Idiopathic reactions (unknown reasons): FM can also occur due to unknown reasons; it may be related to autoimmune diseases, prior radiation therapy, severe viral infections, or trauma. It can also appear with other fibroinflammatory conditions affecting areas outside the chest, such as the kidneys, liver, thyroid, or eyes³

Who is more likely to get affected by FM?

FM can potentially affect anyone, as there is currently no evidence suggesting that it's associated with a specific gender or race. In North America, FM is most often associated with histoplasmosis caused by the fungus Histoplasma capsulatum (H. capsulatum). This fungus is the most common parasitic fungus in the United States, especially in the Mississippi and Ohio River valleys. It can also occasionally cause disease in Central and South America, and some species are also found in Europe, Asia, Africa, and Australia. However, it is much less common in these areas. H. capsulatum thrives in soil, especially when contaminated by bird and bat droppings, and becomes airborne when the soil is disturbed. It’s not known why some people’s immune systems overreact, but it might be due to fungal particles left in the chest lymph nodes, causing severe scarring.³

What is life like for people living with fibrosing mediastinitis?

Patients with FM usually don't notice any symptoms until enough scar tissue builds up to restrict the flow of air or blood in airways or vessels like the superior vena cava or pulmonary arteries. Scarring usually progresses slowly (about 1 millimetre per year), but in some cases, it can occasionally grow faster. For example, people exposed to H. capsulatum in childhood may not experience symptoms until their twenties or thirties. Despite the slow progression, symptoms can suddenly appear once the scarring severely limits blood or airflow.³

Common symptoms to watch for

Histoplasmosis or TB-related FM³

• Superior vena cava syndrome: Swelling in the face and arms
• Airway and pulmonary obstruction: Shortness of breath (dyspnea), chronic cough (with or without blood), and fluid around the lungs
• Difficulty swallowing (dysphagia)
• Chronic chest (pleuritic) pain
• Recurrent pulmonary infections or pneumonias
• Fatigue or loss of stamina

  Idiopathic FM³

• Fever
• Chills
• Sweats
• Shortness of breath
• Cough
• Chest pain
• If there’s fibrosis or inflammation in areas, it can also cause symptoms there.

The diagnosis of FM can be very challenging. According to Tobias Peikert, M.D., a critical care specialist and pulmonologist at Mayo Clinic in Rochester, Minnesota, FM can be very difficult due to the lack of a definitive test. Tissue biopsies are often complicated and risky. In cases associated with histoplasmosis, FM typically presents as a calcified right-sided mediastinal mass. The clinical symptoms depend on the specific structures or organs the condition affects.

How is FM treated?

There are no proven or standard medical treatments for FM. In some cases, patients with idiopathic FM have become better naturally, but this is not the case for FM related to histoplasmosis. As such, management focuses on addressing complications and improving the quality of life for those affected. Some medications, such as prednisone, Tamoxifen, non-steroidal anti-inflammatory drugs (NSAIDs) (like indomethacin), and immunosuppressants (such as azathioprine), have been used in individual cases of idiopathic FM. However, there isn't enough data to confirm the effectiveness of these treatments, as most reports are based on individual cases. Hence, it’s unclear whether the positive outcomes were due to the treatments themselves.³

Some common approaches used to deal with the complications caused by FM include:³

• Fluid retention: Diuretic therapy manages fluid buildup related to vascular obstructions
• Infections: Antibiotics are prescribed for complications like pneumonia
• Exercise: Regular physical activity is encouraged to maintain heart and muscle function, as tolerated by the patient

In more severe cases of FM, additional interventions may be needed to manage complications effectively. These interventions could include:³

• Mechanical interventions: Vascular or airway stenting may be needed when FM causes significant narrowing of blood vessels or airways 
• Surgical resection of scar tissue: This might be considered in rare instances and performed at specialised centres

Moreover, patients with FM may cough up blood due to increased blood pressure in the pulmonary circulation or rupture of fragile arterial collateral vessels, which can lead to significant bleeding. Hemoptysis, or coughing up blood, may require angiography (an x-ray to check blood vessels), embolisation (to stop blood flow to a particular part in the body) or inhaled tranexamic acid to manage bleeding.

Are there new treatments or options for FM?

Research suggests targeting B lymphocytes (a type of immune cell) might help manage FM. A small study of three patients with FM showed some improvement in scans after treatment with rituximab, a drug that depletes B lymphocytes.⁸ However, more research is needed to confirm these findings since no large-scale clinical trials have been conducted yet.

The Cleveland Clinic has also launched a program to understand and manage FM better. 

There are also some additional programs for rare diseases patients and their caregivers can look into, such as:

• MedicAlert assistance program: This program offers protection for rare disease patients in emergencies
• Rare disease educational support program: This program helps patients and caregivers with tools and resources to manage their rare conditions effectively
• Rare caregiver respite program: This is a unique support initiative for caregivers of individuals with rare disorders, providing them with much-needed assistance and relief

Can FM affect life expectancy?

FM can impact life expectancy, depending on its cause and how much it affects the organs in the mediastinal area. For example, if FM affects only one lung, it might gradually lose function (a process sometimes known as "autoamputation"). Despite this, many people with unilateral FM can have normal lives. They might experience symptoms such as chest pain, fluid around the lung (pleural effusion), and recurrent cases of pneumonia, but they generally don’t have a significant impact on overall life expectancy. 

In cases where FM is idiopathic, patients often have an average life expectancy. However, when FM results from histoplasmosis, it can affect both lungs in about 20% of patients, which can be more serious. Early interventions, such as vascular stenting, can help alleviate symptoms and improve survival rates. Stenting is also helpful for both unilateral and bilateral cases, as it can help relieve chest pain and fluid buildup.³

Summary

FM is a rare disease that causes excessive scarring in the middle part of the chest (mediastinum), which could eventually affect vital structures like airways, blood vessels, and nerves. This condition can happen due to past infections, such as histoplasmosis, TB, or other unknown reasons. Symptoms, such as shortness of breath, coughing, and chest pain, may not appear until air or blood flow in affected airways or vessels has occurred. There are no standard treatments for FM. Treatments can range from medications to alleviate symptoms, lifestyle adjustments to maintain overall health, and stenting to keep airways and blood vessels open to surgery. Patients should stay informed about new treatments and resources, as ongoing research could lead to more effective management options.  Being up to date and discussing potential new treatments with healthcare providers can help improve outcomes.