Fibrosing mediastinitis secondary to zygomycosis in a twenty-two-month-old child

Abstract

We report the case of a 22-month-old immunocompetent male child with fibrosing mediastinitis secondary to zygomycosis, an unusual presentation of a rare fungal infection. This patient was successfully treated with amphotericin B and itraconazole for 20 weeks. Stenting of the superior vena cava was helpful in relieving the patient’s superior vena cava syndrome. Case report. A 22-month-old Caucasian boy presented to a community hospital with wheezing and facial swelling. Parents reported a 6-week history of fever, cough and weight loss. Chest radiograph revealed a right pleural effusion, a right perihilar mass and an enlarged cardiac silhouette. A chest chest axial tomography (CT) showed an ill-defined right perihilar mass (∼4 by 4 cm) compressing the superior vena cava, right pulmonary artery and the right main stem bronchus, as well as a large right pleural effusion and a pericardial effusion. He was hospitalized with a diagnosis of superior vena cava (SVC) syndrome and presumed mediastinal infection or malignancy. Broad spectrum antibiotics were given empirically during the first week of admission. His past medical history was significant for reactive airways disease at age 4 to 5 months. He had a history of chronic exposure to wet sheet rock and wood in his South Central Texas house. He had no prior surgical history and no history of travel outside the continental United States. Admission vital signs revealed moderate hypertension, tachycardia, fever, normal arterial oxygen saturation and tachypnea. Physical examination revealed facial edema and bilateral upper extremity swelling. Heart auscultation revealed tachycardia but was otherwise normal. Right lung auscultation revealed markedly decreased breath sounds with intermittent wheezes. The white blood cell count was 26.3 × 103 cells/mm3, with 48% segmented neutrophils, 6% immature neutrophils and3% eosinophils. Serum lactate dehydrogenase was 203 units/liter, erythrocyte sedimentation rate 108 mm/h, serum IgG 1151 mg/dl and IgM 85 mg/dl. The CD4 count was depressed at presentation to 195 cells/mm3 and remained low until the SVC syndrome was relieved. There was subsequent recovery to 765 cells/mm3 after the patient’s chylothorax resolved. Further evaluation of the patient’s immunologic function, including serum complement and complete immunoglobulin values, revealed no immunodeficiency. An echocardiogram demonstrated a large pericardial effusion without cardiac tamponade. Pericardiocentesis yielded a serous fluid with marked eosinophilia but no microorganisms. Right thoracentesis revealed a chylothorax without evidence of microorganisms. Gastric aspirates for acid-fast bacilli, a purified protein derivative test and anergy panel were negative. Bone marrow biopsy and lumbar puncture yielded no malignant cells or evidence of bacterial or fungal infection. A right thoracotomy was performed to obtain biopsies of the perihilar mass and lymph nodes. The lymph nodes were firm and enlarged, and the mass was gray, wooden-like and fibrotic. Initial microscopic examination of the hilar mass revealed a dense, fibrosing process with no malignant cells. The diagnosis of fibrosing mediastinitis was made. Empiric amphotericin B monotherapy was initiated for a possible underlying fungal etiology. Further pathologic review of the perihilar mass specimen revealed a fibrosing process with a single focus of hemorrhage and inflammation. Broad, ribbon-like, aseptate hyphal elements were seen on multiple sections of the biopsy (Fig. 1). The histopathologic appearance of the organism was most consistent with an organism of the Zygomycetes class of fungi.Fig. 1: Fibrosing process surrounding a pauciseptate hyphae consistent with Zygomycetes.Itraconazole was empirically added 3 weeks after presentation because of the patient’s failure to improve. A single blood culture obtained at that time grew Actinomyces; no Actinomyces was ever grown from another source. Given that the presumed diagnosis of Zygomycetes infection was based on histopathology alone and that Actinomyces was a potential cause of the mediastinal mass, it was treated until 4 months after presentation. Four weeks after presentation magnetic resonance imaging revealed a 6- by 6-cm mass completely surrounding the aorta and superior vena cava. The right pulmonary artery and the right upper/middle lobe bronchi were severely compressed with a large amount of postobstructive lung consolidation. Five weeks after admission a percutaneous stent was placed into the patient’s superior vena cava; this intervention allowed resolution of the patient’s SVC syndrome, pericardial effusion and chylothorax. After 12 weeks of inpatient treatment, he was discharged home to receive amphotericin B and itraconazole. Itraconazole was later discontinued as his condition continued to improve. Four months after presentation a chest CT revealed a substantial decrease in the size of the mediastinal mass with no bronchial or vascular compression. Amphotericin B was continued for 3 additional weeks. Serial CT scans since then have revealed a progressively smaller mediastinal mass. One year after presentation the patient was a robust 2-year-old with no chronic cardiorespiratory symptoms. Discussion. We present a case of fibrosing mediastinitis secondary to zygomycosis in an immunocompetent 20-month-old with SVC syndrome and chylothorax. Therapy with antifungal medications for 5 months and stenting of the SVC resulted in a substantial decrease in the size of the fibrosing mass and resolution of symptoms. A MEDLINE literature search from 1960 to 2001 revealed rare reports of zygomycosis as a cause of fibrosing mediastinitis in children. Marwaha et al. 1 report a case of an immunocompetent 8-year-old girl in India who presented with SVC syndrome, respiratory distress and chylothorax; she was diagnosed with Zygomycetes infection by biopsy specimen. The patient died despite several weeks of antifungal treatment. Eckert et al. 2 reported a 15-month-old immunocompetent child in North America with fibrosing mediastinitis secondary to Entomophthora infection. Like the case we report, this case involved a young immunocompetent child living in North America with no history of travel to tropical areas. This patient was successfully treated with amphotericin B for 2.5 months and was well at follow-up 17 months later. In contrast to our case this patient had invasion of multiple mediastinal structures by the fibrosing mass. Fibrosing mediastinitis typically has a dismal prognosis with a mean survival in one case series of 5.9 years. 3 Antifungal treatment does not alter the course of disease in cases associated with Histoplasma infection because the fibrosis is thought to be a delayed immunologic response to past Histoplasma infection as opposed to acute complication of existing infection. 4 Surgical debulking and airway reconstruction have been associated with a high morbidity and significant mortality; thoracotomy for diagnostic purposes is often needed, as it was in the case we present. 3 Treatment of fibrosing mediastinitis usually consists of immunosuppression or attempts at treating the underlying disease process. One author reported no objective improvement in the disease process after treatment with corticosteroids. 5 Steroids were stopped in our case because pathologic review of the surgical specimens revealed a causative agent, Zygomycetes, throughout the fibrosis. Our patient’s symptoms were consistent with zygomycosis with widespread mediastinal involvement. 6 Because of the chylothorax he was given parenteral nutrition until stenting of the superior vena cava ameliorated his chylothorax and allowed him to take enteral nutrition. Successful percutaneous stenting of the pulmonary arteries and the SVC in adults with fibrosing mediastinitis has been reported. 7 The significance of the Actinomyces grown from blood culture in our patient is unknown. We think that the fungus was the true cause of the patient’s mediastinal mass because it was found on multiple sections of the mass biopsy and because Actinomyces was not grown from culture of the mediastinal mass.