Fungus Ball in a Nontuberculosis, Nonneutropenic Patient

by Bernard M. Karnath, MD; Michael C. Boyars, MD; Chester S. Chua, MDGuest Editors Gregory W. Rouan, MDColumn Editor

ABSTRACT Aspergillus is a ubiquitous, filamentous fungus found in soil and organic debris. Pulmonary aspergillosis generally is linked to the immunocompromised patient, whereas an aspergilloma or fungus ball is more likely to occur in a patient with a history of cavitary tuberculosis. In this clinical vignette, we report the case of a nonneutropenic, nontuberculosis patient with an aspergilloma. Historically, the standard of care in patients with an aspergilloma has been surgical resection; however, in this case we report the use of intracavitary amphotericin B infusion as an alternative.

A 41-year-old man presented with a 2-week history of cough that produced yellow-green phlegm, fever of up to 101F, 15-lb weight loss, and a 2-day history of hemoptysis. Social history was significant for alcohol and tobacco abuse. Though the patient reported drinking a 12-pack of beer per day and smoking 2 packs of cigarettes per day with marijuana use, he denied any history of tuberculosis (TB). Physical examination revealed a current temperature 101F, blood pressure of 103/84 mm Hg, heart rate of 105 beats per minute, and respirations of 20 breaths per minute. His HIV serology and purified protein derivative were negative, and the patients white blood cell count was 10 000 cells per mm3. A chest x-ray (Figure 1) showed emphysema and a cavitary lesion in the left apex; a computed tomography (CT) scan of his chest, shown in Figure 2, revealed a left apical cavity with crescent sign consistent with a fungus ball. Aspiration of the cavity revealed Aspergillus organisms, and acid-fast bacillus stains were negative. The patient started a dosage of amphotericin B lavages (50 mg per 10 mL in D5W) through a 7-Fr pigtail catheter for a 14-day period.

soil and organic debris; however, only a few species of Aspergillus are pathogenic to humans.1 The spectrum of pulmonary disease in humans ranges from aspergilloma, invasive pulmonary aspergillosis, and allergic bronchopulmonary aspergillosis. Generally, aspergillomas occur in patients with preexisting pulmonary cavities, such as those with a history of TB. Epidemiologic shifts, however, have led to a decreased number of TB-associated aspergillomas. A study conducted from 1974 to 1991 in France reported a 57% association of aspergillomas with TB, whereas a follow-up study in subsequent years (1992-1997) reported a 17% association with TB.2,3 Another study from France showed an 82% incidence of TB-associated aspergillomas from 1977 to 1987 compared with 60% from 1987 to 1997.4 The epidemiology of TB-associated pulmonary aspergilloma differs in various parts of the world. Cavitary TB is the most common cause of aspergilloma in East Asia, where TB precedes aspergillomas in 80% of cases.5 Invasive pulmonary aspergillosis, on the other hand, generally occurs in immunocompromised patients with neutropenia being the most important risk factor. The risk of invasive pulmonary aspergillosis increases with the duration of neutropenia. Invasive pulmonary aspergillosis is the most common cause of hemoptysis in the neutropenic

Figure1. Chest X-ray Showing Apical Cavitary Lesion

EPIDEMIOLOGY Aspergillus is a ubiquitous, filamentous fungus found in

Dr Karnath is Associate Professor of Medicine, Department of Internal Medicine, Division of General Medicine; Dr Boyars is Professor, Department of Internal Medicine, Division of Pulmonary Medicine; and Dr Chua is Resident, Department of Medicine, The University of Texas Medical Branch, Galveston, Texas. Dr Rouan is Richard W. and Sue Vilter Professor of Clinical Medicine and Associate Chairman of Education, Department of Internal Medicine, School of Medicine, University of Cincinnati, Cincinnati, Ohio.

Johns Hopkins Advanced Studies in Medicine

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CLINICAL VIGNETTE

Figure 2. Computed Tomography Scan of Filled Cavitary Lesion With Crescent Sign Consistent With a Mycetoma

TREATMENT Systemic antifungal therapy is ineffective in patients with an aspergilloma. Historically, the standard of care in patients with an aspergilloma has been surgical resection, with hemoptysis as the most common indication for surgery.10 Observation is suggested in the asymptomatic patient.1 Surgical resection is not without risk; perioperative mortality rates have been reported at 8% and higher.2 The use of intracavitary infusion of amphotericin B was considered a novel therapy 25 to 35 years ago.11,12 With the use of CT guidance, intracavitary therapy has been shown to be an effective, definitive treatment that resolves the most dangerous and alarming symptom, pulmonary hemorrhage.13 CT-guided intracavitary therapy is a good alternative for those patients for whom surgery is contraindicated.13 The use of intracavitary amphotericin B previously was reported by Hargis et al.11 Other novel therapies include thoracoscopic resection via videothoracoscopy.14
References
1. Soubani AO, Chandrasekar PH. The clinical spectrum of pulmonary aspergillosis. Chest. 2002;121:1988-1999. 2. Massard G, Roeslin N, Wihlm JM, Dumont P, Witz JP, Morand G. Pleuropulmonary aspergilloma: clinical spectrum and results of surgical treatment. Ann Thorac Surg. 1992;54:1159-1164. 3. Chatzimichalis A, Massard G, Kessler R, et al. Bronchopulmonary aspergilloma: a reappraisal. Ann Thorac Surg. 1998;65:927-929. 4. Regnard JF, Icard P, Nicolosi M, et al. Aspergilloma: a series of 89 surgical cases. Ann Thorac Surg. 2000;69:898-903. 5. Chen JC, Chang YL, Luh SP, Lee JM, Lee YC. Surgical treatment for pulmonary aspergilloma: a 28 year experience. Thorax. 1997;52:810-813. 6. Brown E, Freedman S, Arbeit R, Come S. Invasive pulmonary aspergillosis in an apparently nonimmunocompromised host. Am J Med. 1980;69:624-627. 7. Karam GH, Griffin FM Jr. Invasive pulmonary aspergillosis in nonimmunocompromised, nonneutropenic hosts. Rev Infect Dis. 1986;8:357-363. 8. Lee SH, Lee BJ, Jung do Y, et al. Clinical manifestations and treatment outcomes of pulmonary aspergilloma. Korean J Intern Med. 2004;19:38-42. 9. Kawamura S, Maesaki S, Tomono K, Tashiro T, Kohno S. Clinical evaluation of 61 patients with pulmonary aspergilloma. Intern Med. 2000;39:209-212. 10. Park CK, Jheon S. Results of surgical treatment for pulmonary aspergilloma. Eur J Cardiothorac Surg. 2002;21:918-923. 11. Hargis JL, Bone RC, Stewart J, Rector N, Hiller FC. Intracavitary amphotericin B in the treatment of symptomatic pulmonary aspergillomas. Am J Med. 1980;68:389-394. 12. Krakowka P, Traczyk K, Walczak J, et al. Local treatment of aspergilloma of the lung with a paste containing nystatin or amphotericin B. Tubercle. 1970;51:184-191. 13. Giron J, Poey C, Fajadet P, et al. CT-guided percutaneous treatment of inoperable pulmonary aspergillomas: a study of 40 cases. Eur J Radiol. 1998;28:235-242. 14. Nakajima J, Takamoto S, Tanaka M, Takeuchi E, Murakawa T. Thoracoscopic resection of the pulmonary aspergilloma: report of 2 cases. Chest. 2000;118:1490-1492.

patient. Prolonged corticosteroid therapy also is a major risk factor. Other high-risk patients include organ transplant recipients, patients with AIDS, individuals with hematologic malignancies, and patients with chronic obstructive pulmonary disease who take corticosteroids for prolonged periods. Invasive pulmonary aspergillosis can occur in apparently nonimmunocompromised patients.6,7

DIAGNOSIS To the authors knowledge, this is the first reported case of a fungus ball (mycetoma) in a nonneutropenic, nonimmunocompromised, non-TB patient. A Medline search using the keywords fungus ball, aspergilloma, mycetoma, and marijuana failed to reveal any previous case reports in this type of a patient. There have been several reported cases of pulmonary aspergillosis, but not aspergilloma, in patients with no obvious risk factors.7 The apparent link in this case appears to be the use of marijuana, again unreported in the literature. It could be argued that this patient also may be considered somewhat immunocompromised due to his alcohol use. Aspergilloma should be suspected in a patient presenting with hemoptysis. However, it is not a first-line consideration. Hemoptysis is the most common manifestation of an aspergilloma.8 Chest x-ray is helpful in that, according to one series, a chest x-ray showed a fungus ball in two thirds of cases9; in most instances, a follow-up CT scan reveals a moveable fungus ball. Sputum sampling, bronchoalveolar lavage, and serum immunoglobulin G Aspergillus antibodies also are helpful in establishing a diagnosis.

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