Idiopathic Fibrosing Mediastinitis

Questions posed and edited by Candace McIntosh and Lucille Enix
Reponses by James Loyd, M.D.


What are the symptoms of Idiopathic FM?

Possibly chronic cough, night sweats, fever, fluid accumulation in the lungs and pericardial sac, shortness of breath, chest pain would be included.

Idiopathic FM can have any or all of the symptoms listed above. Other symptoms may include swelling of face, neck and arms from compression of the superior vena cava. Some patients with this form of FM may also have fibrosis in remote locations, including the neck, the thyroid gland, or behind the abdomen (retroperitoneum), which may cause symptoms related to disease in those sites.

What causes the cough and shortness of breath experienced by many Idiopathic FM sufferers?

Cough and shortness of breath occur with many lung diseases, so they are nonspecific symptoms. In Idiopathic FM cough may be related to the direct compression on the airways, or to fluid accumulation in the lung caused by compression of vessels.

Is the circulatory system affected and, if so, in what ways?

The circulatory system can be affected by direct compression of the pulmonary arteries (which carry blood to the lungs) or the pulmonary veins (which carry blood from the lungs). Compression of the superior vena cava may cause swelling of face or arms, and enlargement of the veins on the chest.

How is the disease diagnosed? Five of the people whom we have contacted were originally diagnosed as having a lymphoma.

The diagnosis of Idiopathic proliferative FM may be first suspected by a CT scan. A CT scan usually shows excessive proliferation of abnormal tissue in the mediastinum (the space between the lungs), but the abnormal tissue does not have calcification, which usually is present in the form of FM which occurs late after Histoplasmosis infection. Such proliferation of mediastinal tissue without calcification is also common for lymphoma, which occurs more commonly than FM, so lymphoma is often the initial provisional diagnosis. When a biopsy of the proliferative tissue in the mediastinum reveals only fibrosis, with no evidence of infection, lymphoma or other disorder, then a diagnosis of idiopathic FM may be established.

What are the causative agents? Viruses, exposure to radiation and environmental hazards, time spent in wooded and forested area. Others?

There are no proven causes of Idiopathic FM. Some medications which were used in the past, such as methysergide or cafergot for migraine headaches, and some of the earliest beta blockers were associated with abnormal fibrosis.

Does the immune system become impaired? Do you consider Idiopathic Fibrosing Mediastinitis an autoimmune disease?

There are no reports of studies of the immune system in Idiopathic FM. Impairment of the immune system is usually manifested as excessive infections. In general, patients with idiopathic FM do not have more infections than other individuals, so their immune systems do not appear to be impaired. It does seem reasonable to consider idiopathic FM among the autoimmune diseases, in part because it does seem to respond to prednisone or other immunosuppressive treatment, at least in part.

What is HLA-A2 antigen?

HLA are Human Leukocyte Antigens, which are on the surface of nearly every human cell and are important in immune recognition and other functions. These are the antigens tested by laboratories to determine the cross compatibility of transplanted organs, including bone marrow and kidney. There are hundreds of combinations of different HLA antigens, and some specific antigens may be associated with increased risk of specific diseases. Association of HLA-A2 with FM was described in a population of patients who had the post Histoplasmosis form. There are to few patients with the Idiopathic form to study whether there is an HLA association.

What medications can arrest the spread of fibrosis and improve breathing?

Because there are so few patients with Idiopathic FM, reliable information about response to treatment is scarce. The only treatment data is from reports about short term treatment of individual patients. Some reports describe responses of individual patients to prednisone or tamoxifen, but we need better information about the magnitude of response, its duration, and for what percent of patients.

Are there complications from the drugs, such as tamoxifen, imuran, and the inflammatory drugs Prednisone and indocin, used to treat the disease?

All drugs have complications in some patients. Allergic or toxic reactions may occur to any drug in an individual patient. Prednisone has many possible side effects, some of which include altered mood, high blood pressure, high blood sugar, cataracts, thin skin with easy bruising, swollen cheeks, increased appetite and weight gain, difficulty sleeping and others. Imuran (azathioprine) may cause hepatitis (inflamed liver), pancreatitis, low white blood cell count. Both prednisone and imuran may increase the risk of infection.

Are drug treatments ongoing or finite? And, is it known whether the various drug treatments can cause the fibrosis to go into remission, or just arrest the fibrosis?

There are no longitudinal reports that provide answers to these important questions. Idiopathic FM seems to be a persistent disease in most patients, even with treatment, but it varies greatly between different patients. It may go into long term remission in some.

What causes the fibrosis to become inflamed, thus making it necessary for those with Idiopathic FM to take anti-inflammatory drugs? What anti-inflammatory drugs do you use with patients? Prednisone? Indocin? Others?

Inflammation and fibrosis are related processes that occur together in many different disease processes, and it seems that either one can lead to the other. In Idiopathic FM we do not really know which comes first. In Idiopathic FM, prednisone or similar medications seem to help some patients, so they are reasonable to try in most patients.

Are chemotherapy and radiation ever used and, if so, under what circumstances? Have these treatments been used successfully? If so, is the treatment ongoing or finite?

In the modern era, radiation is rarely used for any condition other than cancer. In the very few patients with FM that received radiation therapy, it was usually because they were thought to have cancer at the time. Radiation therapy does have significant risk of injury to other organs and has not been studied for treatment of FM. Azathioprine(Imuran) has been reported to help some patients with retroperitoneal fibrosis, which is a similar condition.

Do the diagnostic procedures themselves complicate the treatment or aggravate the disease or its symptoms?

Diagnostic procedures do have risks from the anesthesia or from a surgical complication, but there is no evidence that anesthesia or surgery per se aggravate the disease. I know one patient who had extensive tissue of Idiopathic FM which surrounded the windpipe and a surgeon tried to remove it all surgically. The surgical removal was associated with rapid regrowth of new fibrotic tissue back to its former extent within just a few months of its removal.

Are Serevent and Flovent inhalers helpful to patients?

Serevent is a long acting bronchodilator and Flovent is a corticosteroid. These inhalers are generally used for asthma and wheezing. In selected patients with idiopathic FM which causes wheezing and cough, these medications may be helpful.

How is the patient most effectively followed by a physician? CT scans, MRI? Others?

Each of the imaging modalities used clinically has unique advantages and disadvantages. CT scan is the best modality to show calcification, to help distinguish the post Histoplasmosis form of FM which usually has calcification, from the Idiopathic proliferative form of FM which is usually not calcified. MRI scanning has some advantages for imaging the blood vessels, and has the additional advantage of not requiring radiographic contrast. Nuclear Medicine perfusion scanning is the best method for demonstrating the overall distribution of blood flow to the lungs.

Is it important for a patient to know her/his occluded/compression areas in the chest?

In my experience, most patients want to know which structures are affected by the disease, perhaps to better understand the cause of their symptoms. It could be important for patients to know which structures are occluded in selected circumstances, such as if they needed a central vein catheter for some other problem.

In what ways do the progress and treatment of Idiopathic FM differ from the progress and treatment of Histo-related FM?

There are so few reports of patients with Idiopathic FM that the course of the disease is not well known, but some patients seem to respond to prednisone or tamoxifen.

My experience with Histo-related FM suggests that it is uncommon for it to progress further after patients develop symptoms and the diagnosis is made. Obviously it must have progressed at an earlier time to have caused the obstruction of vessels or airways, but the time course is unknown. It is not even known whether the progression is continuous or intermittent, since most of it occurs before symptoms begin. Histo-related FM is rarely if ever affected by medications, but mechanical approaches, such as intralumenal stents may be helpful for selected patients in either form of FM.

Have you had a patient with Idiopathic FM whose fibrosis shrank or disappeared after treatment? If so, what treatment did you use and why do you think the fibrosis receded?

I have not seen any patient whose FM disappeared after treatment. I have seen a few patients with Idiopathic FM who had some decrease in the amount of abnormal tissue, associated with improvement in symptoms, after treatment with prednisone or tamoxifen or both.

Thyroid deficiency seems to be a common characteristic among many FM patients. Is there a relationship between thyroid deficiency and Idiopathic FM?

Thyroid disease is common in the general population, so it would be expected to also be common in patients with FM. I do not know of any series that examined an association of FM and thyroid disease.

What is the prognosis?

There are no studies of FM that followed patients over long periods of time, so the prognosis is not known. Patients who have both lungs affected by any form of FM appear to have a worse prognosis than those with only one lung affected.

Have any of your patients died from Histo-related or Idiopathic FM and, if so, how did the disease precipitate their deaths?

In my experience the post Histo-related form of FM appears to be far more common, perhaps 10 times as common as diffuse proliferative Idiopathic FM. I have seen about 100 patients with post Histo FM during the past 20 years, and about 10 patients with the Idiopathic diffuse form in the past 8 years. Patients in whom FM affects both lungs are at the greatest risk, and approximately 10-20% of patients with the post Histo form have both lungs affected. I know several patients (eleven) who died from FM affecting both lungs, usually because of respiratory failure or heart failure. Because the Idiopathic form is far less common, there is far less information about the risk of death from it. I have seen some patients in whom this disease caused serious obstruction, so it has the potential to be life threatening, but I do not know any patient who died as a direct result of Idiopathic FM.

James E. Loyd, M.D.



Rudy W. Jacobson Professor of Medicine

Researcher

Vanderbilt University Medical Center
Nashville, TN

Dr. Loyd is currently regarded as this country's leading authority on Fibrosing Mediastinitis and Idiopathic FM. If you are interested in participating in a study of these diseases, recently instigated by Dr. Loyd, you can reach him at Jim.Loyd@Vanderbilt.edu

More about Dr. Loyd


Published with permission from Dr. James Loyd, Candace McIntosh and Lucille Enix who created this work originally published on the Fibrosing Mediastinitis website created by Nita Rice.