Asian Cardiovasc Thorac Ann 2001;9:146-149
© 2001 Asia Publishing EXchange Pte Ltd
Pulmonary Mucormycosis
Hong Yoon Joo, MD,
Lee Doo Yun, MD,
Park Young Sik, MD
Department of Thoracic and Cardiovascular Surgery
Ewha Woman's University Dongdaemun Hospital
Seoul, Korea
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For reprint information contact: Lee Doo Yun, MD Tel: 82 2 3497 3380 Fax: 82 2 3461 8282 email: dylee{at}yumc.yonsei.ac.kr Department of Thoracic and Cardiovascular Surgery, Yongdong Severance Hospital, Yonsei University College of Medicine, 146 92 Dogok-dong, Seoul 135-270, Korea.
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Abstract
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A 78-year-old diabetic man presented with consolidation in the middle and lower lobe of the right lung. An endobronchial mucoid mass was found to be obstructing the right middle lobe and right lower lobe bronchi. The patient was treated with intravenous amphotericin B followed by a right pneumonectomy. Histopathology of the resected specimen demonstrated broad nonseptate hyphae branching at right angles, characteristic of mucormycosis.
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Introduction
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Mucormycosis is an acutely fatal disease caused by the ubiquitous saprophytic fungi of the order Mucorales and class Zygomycetes. It occurs mainly in immunocompro-mised patients.1 Approximately 120 cases of isolated pulmonary mucormycosis have been described in the English-language literature. As the numbers of patients undergoing organ transplantation and high-dose cancer chemotherapy increase, immunocompromised patients susceptible to mucormycosis also increase. Pulmonary mucormycosis is the third most common opportunistic fungal infection and the most common fungal infection causing morbidity and mortality in immunocompromised patients.2 The rapid progression of the clinical course and strong propensity for invasion of large vessels and central airways leading to fatal massive hemoptysis, respiratory failure, or fungal sepsis is responsible for the high overall mortality rate of 80%.2 Early recognition and prompt aggressive multimodality therapy of combined medical and surgical treatment is very important to achieve any chance of cure.
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Case Report
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A 78-year-old man was admitted with increasing cough, sputum, and intermittent fevers to 39°C of one month's duration. He had received intravenous antibiotics (first-generation cephalosporin) without notable improvement. He denied any history of diabetes, positive tuberculin reaction, or exposure to active tuberculosis. Chest auscultation revealed fine inspiratory rales over the right lower lobe posteriorly. A room-air arterial blood gas analysis showed a pH of 7.47, PaCO2 of 35.8 mm Hg, and PaO2 of 63.0 mm Hg. Laboratory findings included a white blood cell count of 19.6 x 109/L with 82% segmented neutrophils, hemoglobin 97 g•L–1, hematocrit 29.1%, platelets 324 x 109/L, serum glucose 1.77/3.93 g•L–1 (preprandial/postprandial), and hemoglobin A1C of 12.9%. Glycosuria without pyuria or proteinuria was present on urinalysis and sputum Gram stain revealed no organisms; culture grew normal respiratory flora. An insulin study indicated uncontrolled non-insulin-dependent diabetes mellitus. A consolidation of approximately 8 x 8 cm in the right mid lung and lower lung fields and an inner radiolucent cavitary lesion were noted on chest radiography (Figure 1A
). Computed tomography of the chest demonstrated a consolidated lesion in the right mid lung zone and the medial basal portion of the right lower lung, with an inner portion of low attenuation and a radiopaque lesion in the lumen of the right intermediate bronchus and middle lobe bronchus (Figure 1B). Initially, the patient was treated with intravenous antibiotics (second-generation cephalosporin and aminoglycoside) for presumed pneumonia and his fever quickly subsided. He expectorated approximately 50 mL of bright red nonclotting blood on the second hospital day. Bronchoscopy performed the next day revealed grayish-white mucoid material obstructing beyond the right proximal bronchus intermedius, and purulent secretions but no evidence of active bleeding. The polypoid mucoid material was biopsied and histopathologic examination showed nonseptate fungal hyphae consistent with mucormycosis. Intravenous amphotericin B was promptly initiated at a dosage of 0.5 mg•kg–1 daily. Since the fungal mass obstructed the central airway, causing distal obstructive pneumonitis with the likelihood of recurrent massive hemoptysis, combined surgical therapy was undertaken to reduce the risks of morbidity and mortality. A right-sided pneumonectomy was performed. The resected specimen revealed a 7 x 8-cm mass in the medial segment of the right middle lobe and the medial basal segment of the right lower lobe (Figure 2A). The vascular wall of the right middle lobe artery was heavily invaded by the fungi (Figure 2B) that showed nonseptate right-angled hyphae with diameters of 5 to 10 µm, typical of mucormycosis (Figure 2C). Amphotericin B was administered from the first postoperative day at a dosage of 0.5 mg•kg–1, increasing up to 1.0 mg•kg–1 until the total dose was 420 mg. The postoperative course was uneventful with no recurrence or complication during 5 months of follow-up.
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Figure 1. (A) Chest radiography on admission revealed a consolidation of approximately 8 x 8 cm in the right mid lung and lower lung fields, and an inner radiolucent cavitary lesion. (B) A computed tomographic scan of the chest demonstrated a consolidated lesion in the right mid lung and the medial basal portion of the right lower lung with an inner portion of low attenuation.
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Discussion
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This case illustrates an unusual presentation of pulmonary mucormycosis as an endobronchial mass. Given this presentation, a diagnosis of malignancy with post-obstructive pneumonia was initially considered most likely, and the histopathologic diagnosis of mucormycosis from the bronchoscopic biopsy specimen was incidental. Mucormycosis is an important opportunistic infection with a high mortality rate due to its acute fulminant course. The main risk factors include diabetes mellitus (56%) with ketoacidosis, hematologic malignancy (32%), renal insufficiency (13%), and organ transplantation.1 The incidence of mucormycosis in organ transplant recipients was reported to be 1% to 9% and the in-hospital mortality was as high as 27%; neutropenia and renal insufficiency are considered the predictors of death.1,2
Diabetes mellitus is the most common underlying condition in mucormycosis as the fungi grow well in acidic glucose-rich media.1,2 Mucoraceous fungi exist in two physiologic forms, the metabolically inert spo-rangiospore that favors a carbon-rich environment, and the pathogenic hyphal form that is produced in an oxygen-rich environment.3 It was experimentally proven that the host defense mechanism of non-phagocytic killing of Mucor or Rhizopus species by neutrophils is damaged in neutropenic immunocompromised patients, and sporangiospores germinate into hyphal forms causing disease.4 Early diagnosis of mucormycosis is very difficult due to its rarity, nonspecific clinical and radiologic findings, and a sensitivity of less than 50% in micro-biologic assessments.5 Symptoms include fever, cough, chest pain, sputum production, malaise indistinguishable from bacterial pneumonia, and occasional hemoptysis.1,5
Radiologic manifestations include pulmonary infiltrates or consolidation with or without cavity formation, most commonly in the upper lung fields.1,5 The air-crescent sign that is a pathognomonic sign of aspergillosis, is a predictor of massive pulmonary hemorrhage and death from hemoptysis in cases of mucormycosis.5 Even with a strong suspicion, confirmed diagnosis from fungal culture of a surgical or bronchoscopic biopsy specimen is not easily obtained. Mucormycosis and invasive aspergillosis are both opportunistic fungal infections with airborne transmission, characterized by blood vessel invasion causing hemoptysis, pulmonary vascular thrombosis, hemorrhagic infarction, or pseudoaneurysm formation of pulmonary arteries.5,6
Hemoptysis is far more massive and fatal in mucormycosis because the hyphae of Mucor are 10 to 50 µm in diameter, compared to 5 to10 µm for Aspergillus, and they invade larger airways and vessels. The right angulation and lack of septation of Mucor hyphae allow differentiation from Aspergillus that shows septate hyphae with acute angulation and the characteristic fruiting body.6 When pulmonary mucormycosis is suspected, early diagnosis and aggressive treatment by combined medical and surgical therapy are imperative. Associated underlying conditions and predisposing factors should be corrected. Once diagnosed, intravenous administration of ampho-tericin B should be initiated.2,5 When the disease is mild to moderate, a 1-mg test dose should be given on the first day, increasing by 5 mg every day up to 1.0 mg•kg–1; for more severe cases, a 1-mg test dose should be given in the first few hours, increasing by 10 to 15 mg every 12 hours up to 0.7–1.0 mg•kg–1 per day.5 The introduction of a liposomal form of amphotericin B has enabled safe clinical use in patients refractory to amphotericin B deoxycholate or in those with renal impairment or other drug-related toxicity.6
Overall in-hospital mortality was reported to be 80% (65% for isolated pulmonary cases and 96% for disseminated cases) by Tedder and colleagues.5 Mortality from associated medical conditions ranged from 93% for patients with renal failure to 60% for diabetics and transplant recipients.5,7 The 11% mortality in patients treated surgically with or without antifungal agents, was significantly lower than the 68% observed in those treated medically.5,8 Temeck and colleagues8 described 36 immunosuppressed patients undergoing thoracotomy for pulmonary fungal disease and suggested that the most important prognostic survival factor was the patient's underlying disease rather than the recurring fungal infection. Before surgical exploration, the underlying medical status must be optimized; chemotherapy should be withheld, and ideally, steroid dosage should be tapered.8
They also pointed out that resection would provide little benefit in patients with hematologic disorders and dysfunctional neutrophils because they most likely have systemic fungemia at the time of presentation, and multiorgan system failure may be inevitable because of the severity of the underlying cellular and humoral host defense.8 We successfully treated our case of pulmonary mucormycosis by a combination of prompt administration of amphotericin B, control of the underlying diabetes mellitus, and extensive surgical debridement.
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References
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Lehrer RI, Howard DH, Sypherd PS, Edward JE, Segal GP, Winston DJ. Mucormycosis. Ann Intern Med 1980; 93:93–108.
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Diamond RD, Krzesicki R, Epstein B, Jao W. Damage to hyphal forms of fungi by human leukocytes in vitro: a possible host defense mechanism in aspergillosis and mucormycosis. Am J Pathol 1978;91:313–28.[Abstract]
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Tedder M, Spratt JA, Anstadt MP, Hegde SS, Tedder SD, Lowe E. Pulmonary mucormycosis: results of medical and surgical therapy. Ann Thorac Surg 1994;57:1044–50.[Abstract]
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Mackaness GB. Arguments for a new formulation of liposomal amphotericin B: an historical perspective. J Liposome Res 1990;1:503–10.
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Brown RB, Johnson JH, Kessinger JM, Sealy WC. Bronchovascular mucormycosis in the diabetic: an urgent surgical problem. Ann Thorac Surg 1992;53:854–5.[Abstract]
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Temeck BK, Venzon DJ, Moskaluk CA, Pass HI. Thoracotomy for pulmonary mycoses in non-HIVimmunosuppressed patients. Ann Thorac Surg 1994; 58:333–8.[Abstract]
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V. J. Reid, D. L. Solnik, T. Daskalakis, and K. P. Sheka
Management of Bronchovascular Mucormycosis in a Diabetic: A Surgical Success
Ann. Thorac. Surg.,
October 1, 2004;
78(4):
1449 - 1451.
[Abstract]
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Abstract
Introduction
