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Fatal mycotic endocarditis from a primary esophageal aspergilloma
Fatal mycotic endocarditis from a primary esophageal aspergilloma
S Komanduri, K Bruninga, J Losurdo, et al.
CASE REPORTS Fatal mycotic endocarditis from a primary esophageal aspergilloma Srinadh Komanduri, MD, Keith Bruninga, MD, John Losurdo, MD, Syed Zaidi, MD
Aspergillus infection can result in significant morbidity and mortality. Immune impaired individuals and those with pre-existing pulmonary disease are predisposed to this infection. GI involvement is rare, even in the immunocompromised host, and usually occurs as a result of systemic infection. Aspergillus is a fastidious mold that has a predilection for the sinuses and lungs.1 Reported cases of esophageal involvement range from Aspergillus esophagitis to invasion of the mediastinum with development of tracheoesophageal fistulae.1-3 In all but one report, esophageal involvement was predated by severe pulmonary infection.2,4 A unique case is presented of an 18-year-old girl with acute myelogenous leukemia who developed fatal mycotic endocarditis from a primary esophageal aspergilloma as a result of an esophageal-atrial fistula. This case highlights the importance of rapid endoscopic diagnosis in immunosuppressed patients with dysphagia.
Figure 1. Endoscopic view of mid esophagus showing 8-cm friable, ulcerated mass.
CASE REPORT An 18-year-old girl was hospitalized with neutropenia, fever, and intermittent dysphagia for solid food after iniCurrent affiliations: Rush Presbyterian–St. Luke’s Medical Center, Chicago, Illinois. Reprint requests: Srinadh Komanduri, MD, Division of Digestive Diseases, Rush Presbyterian–St. Luke’s Medical Center, 1725 W. Harrison St., Suite 206, Chicago, IL 60612. Copyright © 2002 by the American Society for Gastrointestinal Endoscopy 0016-5107/2002/$35.00 + 0 37/4/128164 doi:10.1067/mge.2002.128164 VOLUME 56, NO. 4, 2002
Figure 2. Photomicrograph showing large numbers of Aspergillus organisms (silver stain, orig. mag. 400). tial consolidation chemotherapy (mitoxantrone, cytarabine, and amifostine) for acute myelogenous leukemia. Examination was significant only for fever (temperature of 104°F). Laboratory tests revealed an absolute neutrophil count of 100. Empiric treatment with broad-spectrum antibiotics (cefepime, vancomycin) and fluconazole GASTROINTESTINAL ENDOSCOPY
577
S Komanduri, K Bruninga, J Losurdo, et al.
Fatal mycotic endocarditis from a primary esophageal aspergilloma
Figure 4. Gross autopsy specimen with perforation at site of aspergilloma.
Figure 3. CT chest demonstrating partially obstructive esophageal mass with submucosal air. were initiated. The dysphagia worsened and fever and neutropenia persisted. Chest radiograph, urine, and blood cultures (aerobic, anaerobic, fungal) were consistently negative. Upper endoscopy disclosed an 8-cm friable, ulcerated mass in the mid esophagus (Fig. 1). Biopsy specimens demonstrated Candida species on staining with hematoxylin and eosin, but the silver stain demonstrated large numbers of Aspergillus organisms (Fig. 2). Chest CT confirmed the presence of an intraluminal esophageal mass with evidence of submucosal air (Fig. 3). Over the next 24 hours the patient experienced generalized seizures, hypotension, and expired after cardiac arrest. An echocardiogram 3 days before clinical decompensation demonstrated no valvular or myocardial abnormalities. Autopsy revealed a fistulous communication between the esophageal mass and the right atrium (Fig. 4). Furthermore, there was evidence of multiple mycotic vegetations within the right atrium and on the mitral valve that were confirmed histopathologically as Aspergillus. Dissection of the brain demonstrated diffuse aspergillosis emboli.
DISCUSSION Fungal esophageal infections are a significant cause of morbidity and mortality in immunocompromised patients. Specifically, the loss of functioning granulocytes predisposes these patients to fungal infection.2 The most common pathogen is Candida species, followed by Aspergillus and Histoplasma.2 In patients with human immunodeficiency virus infection, consensus opinion is that the presence of oral thrush and symptoms of dysphagia/odynophagia indicates that an empiric trial of orally administered antifungal agents is cost-effective.3 However, persistence of symptoms or development of abdominal pain, nausea, or vomiting warrants urgent investigation with upper endoscopy. In this situation, the possibility of co-infection with a virus (herpes simplex virus, cytomegalovirus) or a second 578
GASTROINTESTINAL ENDOSCOPY
fungal form is a distinct possibility, the most lifethreatening co-infection being Aspergillus.5 Aspergillus species are ubiquitous, rapidly growing molds, most commonly A fumigatus and A flavus. Aspergillus is differentiated from Candida by its distinct morphology (septate hyphae, dichotomously branched at angles of 45°).5 They are best visualized when silver stains are used and may be missed in specimens stained with hematoxylin and eosin.5 In patients who are immunocompromised, Aspergillus infection behaves aggressively, infecting the sinuses, lungs, and adjacent organs without regard for tissue planes.2 The incubation period ranges from 36 hours to 3 months.5 In patients who are neutropenic, invasive Aspergillosis is virtually never manifested before the twelfth day of profound neutropenia.6 Aspergillus may cause esophagitis directly with resultant symptoms of dysphagia/odynophagia. In addition, mucosal candidiasis and weight loss may be present. Aspergillus should always be considered in patients with suspected Candidal infection who do not respond to first-line antifungal therapy. Endoscopic biopsies or brushings are essential for diagnosis. The mortality rate for invasive aspergillosis is nearly 100%.5 There are no data on the efficacy of treatment for Aspergillus esophagitis. Data pertaining to systemic infection indicate that treatment is successful in 20% to 40% of cases, depending on the underlying immunocompromised status of the patient.7 By extrapolation from these data, the treatment for Aspergillus esophagitis is intravenously administered Amphotericin B. Primary esophageal aspergillosis is extremely rare, even in the setting of severely impaired immunity. Nevertheless, the aggressive nature of this fungus warrants consideration in the differential diagnosis of dysphagia in the immunosuppressed patient, even in the absence of evidence of pulmonary involvement. Urgent endoscopy with biopsies should be performed to expedite diagnosis and prevent severe life-threatening complications from this potentially treatable disease.4 VOLUME 56, NO. 4, 2002
Multiple lymphomatous polyposis of the GI tract
REFERENCES 1. Gerson SI, Talbot GH, Hurwitz S, Strom BL, Lusk EJ, Cassiletti PA. Prolonged granulocytopenia: the major risk factor for invasive pulmonary aspergillosis in patients with acute leukemia. Ann Int Med 1984;100:345-51. 2. Baehr PH, McDonald GB. Esophageal infections: risk factors, presentation, diagnosis, and treatment. Gastroenterology 1994;106:509-32. 3. Wilcox M. Esophageal disease in the acquired immunodeficiency syndrome: etiology, diagnosis, and management. Am J Med 1992;92:412-9.
VOLUME 56, NO. 4, 2002
M Vignote, M Chicano, F Rodriguez, et al.
4. Choi JH, Yoo JH, Chung IJ, Kim DW, Kim DJ. Esophageal aspergillosis after bone marrow transplantation. Bone Marrow Transplant 1997;19:293-4. 5. Denning DW. Invasive aspergillosis. Clin Infect Dis 1998;26: 781-805. 6. Wheeler R, Peacock JE, Cruz JM, Richter JE. Esophagitis in the immunocompromised host: role of esophagoscopy in diagnosis. Rev Infect Dis 1987;9:88-96. 7. Denning DW. Aspergillus species. Mandell: principles and practice of infectious diseases. 5th ed. London: Churchill Livingston; 2000. p. 2674-82.
GASTROINTESTINAL ENDOSCOPY
579
S Komanduri, K Bruninga, J Losurdo, et al.
CASE REPORTS Fatal mycotic endocarditis from a primary esophageal aspergilloma Srinadh Komanduri, MD, Keith Bruninga, MD, John Losurdo, MD, Syed Zaidi, MD
Aspergillus infection can result in significant morbidity and mortality. Immune impaired individuals and those with pre-existing pulmonary disease are predisposed to this infection. GI involvement is rare, even in the immunocompromised host, and usually occurs as a result of systemic infection. Aspergillus is a fastidious mold that has a predilection for the sinuses and lungs.1 Reported cases of esophageal involvement range from Aspergillus esophagitis to invasion of the mediastinum with development of tracheoesophageal fistulae.1-3 In all but one report, esophageal involvement was predated by severe pulmonary infection.2,4 A unique case is presented of an 18-year-old girl with acute myelogenous leukemia who developed fatal mycotic endocarditis from a primary esophageal aspergilloma as a result of an esophageal-atrial fistula. This case highlights the importance of rapid endoscopic diagnosis in immunosuppressed patients with dysphagia.
Figure 1. Endoscopic view of mid esophagus showing 8-cm friable, ulcerated mass.
CASE REPORT An 18-year-old girl was hospitalized with neutropenia, fever, and intermittent dysphagia for solid food after iniCurrent affiliations: Rush Presbyterian–St. Luke’s Medical Center, Chicago, Illinois. Reprint requests: Srinadh Komanduri, MD, Division of Digestive Diseases, Rush Presbyterian–St. Luke’s Medical Center, 1725 W. Harrison St., Suite 206, Chicago, IL 60612. Copyright © 2002 by the American Society for Gastrointestinal Endoscopy 0016-5107/2002/$35.00 + 0 37/4/128164 doi:10.1067/mge.2002.128164 VOLUME 56, NO. 4, 2002
Figure 2. Photomicrograph showing large numbers of Aspergillus organisms (silver stain, orig. mag. 400). tial consolidation chemotherapy (mitoxantrone, cytarabine, and amifostine) for acute myelogenous leukemia. Examination was significant only for fever (temperature of 104°F). Laboratory tests revealed an absolute neutrophil count of 100. Empiric treatment with broad-spectrum antibiotics (cefepime, vancomycin) and fluconazole GASTROINTESTINAL ENDOSCOPY
577
S Komanduri, K Bruninga, J Losurdo, et al.
Fatal mycotic endocarditis from a primary esophageal aspergilloma
Figure 4. Gross autopsy specimen with perforation at site of aspergilloma.
Figure 3. CT chest demonstrating partially obstructive esophageal mass with submucosal air. were initiated. The dysphagia worsened and fever and neutropenia persisted. Chest radiograph, urine, and blood cultures (aerobic, anaerobic, fungal) were consistently negative. Upper endoscopy disclosed an 8-cm friable, ulcerated mass in the mid esophagus (Fig. 1). Biopsy specimens demonstrated Candida species on staining with hematoxylin and eosin, but the silver stain demonstrated large numbers of Aspergillus organisms (Fig. 2). Chest CT confirmed the presence of an intraluminal esophageal mass with evidence of submucosal air (Fig. 3). Over the next 24 hours the patient experienced generalized seizures, hypotension, and expired after cardiac arrest. An echocardiogram 3 days before clinical decompensation demonstrated no valvular or myocardial abnormalities. Autopsy revealed a fistulous communication between the esophageal mass and the right atrium (Fig. 4). Furthermore, there was evidence of multiple mycotic vegetations within the right atrium and on the mitral valve that were confirmed histopathologically as Aspergillus. Dissection of the brain demonstrated diffuse aspergillosis emboli.
DISCUSSION Fungal esophageal infections are a significant cause of morbidity and mortality in immunocompromised patients. Specifically, the loss of functioning granulocytes predisposes these patients to fungal infection.2 The most common pathogen is Candida species, followed by Aspergillus and Histoplasma.2 In patients with human immunodeficiency virus infection, consensus opinion is that the presence of oral thrush and symptoms of dysphagia/odynophagia indicates that an empiric trial of orally administered antifungal agents is cost-effective.3 However, persistence of symptoms or development of abdominal pain, nausea, or vomiting warrants urgent investigation with upper endoscopy. In this situation, the possibility of co-infection with a virus (herpes simplex virus, cytomegalovirus) or a second 578
GASTROINTESTINAL ENDOSCOPY
fungal form is a distinct possibility, the most lifethreatening co-infection being Aspergillus.5 Aspergillus species are ubiquitous, rapidly growing molds, most commonly A fumigatus and A flavus. Aspergillus is differentiated from Candida by its distinct morphology (septate hyphae, dichotomously branched at angles of 45°).5 They are best visualized when silver stains are used and may be missed in specimens stained with hematoxylin and eosin.5 In patients who are immunocompromised, Aspergillus infection behaves aggressively, infecting the sinuses, lungs, and adjacent organs without regard for tissue planes.2 The incubation period ranges from 36 hours to 3 months.5 In patients who are neutropenic, invasive Aspergillosis is virtually never manifested before the twelfth day of profound neutropenia.6 Aspergillus may cause esophagitis directly with resultant symptoms of dysphagia/odynophagia. In addition, mucosal candidiasis and weight loss may be present. Aspergillus should always be considered in patients with suspected Candidal infection who do not respond to first-line antifungal therapy. Endoscopic biopsies or brushings are essential for diagnosis. The mortality rate for invasive aspergillosis is nearly 100%.5 There are no data on the efficacy of treatment for Aspergillus esophagitis. Data pertaining to systemic infection indicate that treatment is successful in 20% to 40% of cases, depending on the underlying immunocompromised status of the patient.7 By extrapolation from these data, the treatment for Aspergillus esophagitis is intravenously administered Amphotericin B. Primary esophageal aspergillosis is extremely rare, even in the setting of severely impaired immunity. Nevertheless, the aggressive nature of this fungus warrants consideration in the differential diagnosis of dysphagia in the immunosuppressed patient, even in the absence of evidence of pulmonary involvement. Urgent endoscopy with biopsies should be performed to expedite diagnosis and prevent severe life-threatening complications from this potentially treatable disease.4 VOLUME 56, NO. 4, 2002
Multiple lymphomatous polyposis of the GI tract
REFERENCES 1. Gerson SI, Talbot GH, Hurwitz S, Strom BL, Lusk EJ, Cassiletti PA. Prolonged granulocytopenia: the major risk factor for invasive pulmonary aspergillosis in patients with acute leukemia. Ann Int Med 1984;100:345-51. 2. Baehr PH, McDonald GB. Esophageal infections: risk factors, presentation, diagnosis, and treatment. Gastroenterology 1994;106:509-32. 3. Wilcox M. Esophageal disease in the acquired immunodeficiency syndrome: etiology, diagnosis, and management. Am J Med 1992;92:412-9.
VOLUME 56, NO. 4, 2002
M Vignote, M Chicano, F Rodriguez, et al.
4. Choi JH, Yoo JH, Chung IJ, Kim DW, Kim DJ. Esophageal aspergillosis after bone marrow transplantation. Bone Marrow Transplant 1997;19:293-4. 5. Denning DW. Invasive aspergillosis. Clin Infect Dis 1998;26: 781-805. 6. Wheeler R, Peacock JE, Cruz JM, Richter JE. Esophagitis in the immunocompromised host: role of esophagoscopy in diagnosis. Rev Infect Dis 1987;9:88-96. 7. Denning DW. Aspergillus species. Mandell: principles and practice of infectious diseases. 5th ed. London: Churchill Livingston; 2000. p. 2674-82.
GASTROINTESTINAL ENDOSCOPY
579