Complete resolution of fibrosing mediastinitis with corticosteroid therapy.

To the Editor: Fibrosing mediastinitis, also known as sclerosing mediastinitis or mediastinal fibrosis, is characterized by an excessive fibrotic reaction in the mediastinum, which can produce compromise of the trachea, great vessels and other mediastinal structures. (1) There is no effective medical therapy known for this disease. We present a case of fibrosing mediastinitis, which resolved completely with corticosteroids.

A 42-year-old African-American male patient presented with hoarseness of voice and pleuritic chest pain for several months. He was seen by an ENT surgeon in Boston and underwent a CT chest scan along with a direct laryngoscopy. He was found to have a chest mass which was believed to be causing his voice hoarseness, resulting from left vocal cord paralysis. Subsequently the patient came to see us for management. A repeat CT of his chest revealed a superior mediastinal soft tissue mass enveloping the aortic arch and its branches, extending down to the trachea. A bronchoscopy was performed with a transtracheal needle aspiration, and subsequently, a mediastinoscopy was attempted but did not yield enough tissue for diagnosis. The patient underwent a median sternotomy with biopsy of the mediastinal mass. Biopsies of the aortic wall and pericardium were also taken, both of which revealed dense fibrosis with a lymphoplasmacytic infiltrate. Acid-fast bacillus and fungal stains were negative. At this point, our differential diagnosis included nodular sclerosing Hodgkin disease, multiple myeloma or a reactive process.

C3, C4 and CRP levels were found to be normal. CH50 and C2 levels were marginally elevated. Antihistoplasma antibodies, anticytomegalovirus immunoglobulin (IgM), anti-Toxoplasma gondii IgM and anticryptococcal antibodies were negative. However, anticytomegalovirus IgG was elevated at 6.3 (negative < 0.9), and Epstein-Barr virus DNA polymerase chain reaction was negative. The pathology slides were sent to a pulmonary pathologist, who confirmed the diagnosis as fibrosing mediastinitis.

Based on anecdotal case reports, the patient was started on 40 mg of oral prednisone taken daily, which was tapered after 6 weeks to 30 mg and eventually to 10 mg. The patient reported gradual but complete resolution of symptoms on prednisone over a period of 10 months. A repeat CT of his chest done 1 year after steroid initiation revealed complete resolution of the fibrosing mediastinitis.

The vast majority of cases of fibrosing mediastinitis are thought to be sequelae of histoplasmosis. The mechanism is proposed to be leakage of fungal antigens from lymph nodes into the mediastinum, leading to a hypersensitivity reaction and exuberant fibrotic response. (1) The signs and symptoms of fibrosing mediastinitis depend on the structures involved. Tracheobronchial narrowing can result in postobstructive pneumonia or atelectasis. Broncholithiasis can result from bronchial erosion by calcific lymph nodes. Hemoptysis can occur secondary to bronchial invasion, postobstructive pneumonia, pulmonary venous hypertension or obstruction of pulmonary arteries leading to anastomoses between bronchial and pulmonary arteries. SVC syndrome, constrictive pericarditis, dysphagia, odynophagia, and tracheoesophageal fistula might also result.

The average time from initial symptoms to diagnosis is 5 years for women and 2.2 years for men. Imaging studies are required to evaluate the extent of the disease. If serologic studies are negative and the patient presents with atypical features, a biopsy is advisable. Biopsy also helps to rule out a neoplasm. Mediastinoscopy is the procedure of choice.

There is no effective medical treatment known for fibrosing mediastinitis. Steroids have not been found to be beneficial except perhaps in the autoimmune form. (2,3) There is also a case report of fibrosing mediastinitis and sclerosing cervicitis responding to treatment with steroids and tamoxifen. (4) Antifungal therapy is generally ineffective although there are case reports suggesting potential benefit. (5) Surgery has been performed to relieve vascular and airway obstruction with variable success.

So far, there have been no medical treatment options available for patients with fibrosing mediastinitis. However, as in our case, steroids might be a possible option, especially in patients who are not good surgical candidates and may result in dramatic results.

Acknowledgments: We want to express our gratitude to Dr. L.D. Gorden, Department of Pathology, University of Tennessee Health Science Center, for his help in reviewing the pathology slides.

Chitra La, MD

Darryl Weiman, MD

Mahmoud Eltorky, MD, PhD

Muthiah Pugazhenthi, MD

University of Tennessee Health

Science Center

Memphis, TN

References

1. Goodwin RA, Nickell JA, Des Prez RM. Mediastinal fibrosis complicating healed primaryhistoplasmosis and tuberculosis. Medicine-(Baltimore) 1972;51:227.

2. Minami S, Asai M, Iwahori K, et al. A case of fibrosing mediastinitis manifesting recurrent laryngeal nerve palsy. Nihon Kokyuki Gakkai Zasshi 2002;40:583-587.

3. Cordasco EM Jr, Ahmad M, Mehta A, et al. The effects of steroid therapy on pulmonary hypertension secondary to fibrosing mediastinitis. Cleve Clin J Med 1990;57:647-652.

4. Savelli BA, Parshley M, Morganroth ML. et al. Successful treatment of sclerosing cervicitis and fibrosing mediastinitis with tamoxifen. Chest 1997;111:1137-1140.

5. Urschel HC, Razzud MA, Netto GJ, et al. Sclerosing mediastinitis: improved management with histoplasmosis titer ketoconazole. Ann Thorac Surg 1990;50:215. Letters to the Editor