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Tracheoesophageal fistula and sinusitis from invasive aspergillosis
Tracheoesophageal fistula and sinusitis from invasive aspergillosis BRENDAN C. STACK, JR, MD, MARION B. RIDLEY,MD, JOHN N. GREENE, MD, and DAVID S. HUBBELL,MD, Tampa, Florida
Aspergillus
infections are on the increase as the community of immunocompromised patients continues to grow.1 Increased use of immunosuppressive agents for organ transplantation and autoimmune disorders is partly responsible. The growing number of patients infected with HIV likewise contributes to this population. Chemotherapeutic regimens used in the treatment of hematologic malignancies, solid tumors, and as induction for bone marrow transplantation render a significant number of patients susceptible to opportunistic infections as well. 2-4 Aspergillus, a ubiquitous soil saprophyte, is an airborne fungus that is inhaled routinely.5 It is second only to Candida species as an opportunistic infecting fungus among immunocompromised patients. 6 Aspergillus is one of the leading causes of death from fungal disease in immunocompromised patients. Although the most common site of Aspergillus infection is the lungs,7 Aspergillus infections of the head and neck are also being seen with increased frequency. All head and neck sites can be involved. 7 Common sites of infection in the head and neck include the paranasal sinuses, nose, mandible, larynx, and ear. 4 Consequently, Aspergillus as a cause of certain head and neck problems must always be considered when evaluating an immunocompromised host.7 Head and neck Aspergillus infections must be strongly suspected in those patients in whom pulmonary involvement is already diagnosed. We present the case of an immunocompromised host initially diagnosed with and treated for invasive Aspergillus sinusitis. Later a tracheoesophageal fistula
From the Divisions of Otolaryngology-Head and Neck Surgery (Drs. Stack and Ridley), Infectious Disease (Dr. Greene), and Thoracic Surgery (Dr. Hubbell), H. Lee Moffitt Cancer Center and Research Institute, University of South Florida College of Medicine. Presented at the 88th Annual Clinical Congress of the Southern Medical Association, Orlando, Fla., Nov. 2-5, 1994. Reprint requests: Marion B. Ridley, MD, FACS, Division of Otolaryngology, University of South Florida, 12902 Magnolia Dr., Suite 3057, Tampa, FL 33612. Otolaryngol Head Neck Surg 1997; 116:116-9. Copyright © 1997 by the American Academy of OtolaryngologyHead and Neck Surgery Foundation, Inc 0194-5998/97/$5.00 + 0 23/4/70611
116
(TEF) developed fi'om invasive aspergillosis. This case is the second reported case of a TEF resulting from invasive Aspergillus infection. CASE REPORT
Acute myelogenous leukemia was diagnosed in an 18year-old woman in July 1993. The patient was treated elsewhere with chemotherapy (transretinoic acid) for 14 days. The patient was subsequently admitted to our center for neutropenia, thrombocytopenia, and fever. Workup revealed a right lower lobe pneumonia and Staphylococcus aureus bacteremia. The patient was treated with broad-spectrum intravenous antibiotics (vancomycin, ceftazidime, and tobramycin) and fungal prophylaxis (fluconazole). Ten days after the patient started antibiotics, dysphagia developed. A diagnosis of esophagitis presumed caused by Candida vs. herpes simplex virus was made. Acyclovir was added for antiviral coverage. Two weeks later the patient was noted to have left nasal obstruction. Physical examination revealed a dark, crusting lesion on the left nasal septum. Otolaryngology consultation was obtained, and mild left maxillary and ethmoid sinusitis was noted on CT (Fig. 1). A biopsy specimen of the lesion revealed septated, filamentous hyphae, mad subsequent culture grew Aspergillus. Fluconazole was discontinued, and the patient began receiving amphotericin B and rifampiu. A left medial maxillectomy, transantral ethmoidectomy, partial septectomy, and inferior turbinectomy were performed. On postoperative day 3 a productive cough and choking with liquids developed. A conventional barium swallow revealed "aspiration" and external compression of the esophagus at the level of the right main bronchus. A dynamic video esophagram study demonstrated a normal swallow followed by a cough, at which time tracheal contrast was noted. There was no glottic penetration during the pharyngeal phase of swallowing. Flexible bronchoscopy revealed a left mainstem, black, necrotic lesion on the posterior wall (Fig, 2). The patient then underwent esophagogastroduodenoscopy with biopsy, which revealed a similar lesion on the anterior wall of the esophagus. Biopsy results demonstrated invasive aspergillosis (Fig. 3). A diagnosis of TEF was made. An enteral feeding tube was placed endoscopically, and the patient was medically and nutritionally optimized for surgery. The patient underwent exploration and resection of the necrotizing esophageal aspergilloma approximately 2
OtolaryngologyHead and Neck Surgery Volume 116 Number 1
STACK et af. 117
Fig. 1. CT findings of mild left maxillary sinusitis.
Fig. 2. View of fungal mycetoma through flexible bronchoscope. Note the mycetoma at the site of the fistula in the left mainstem bronchus just distal to the carina.
weeks after the diagnosis of TEE Surgical excision and repair consisted of a right thoracotomy, distal esophagectomy, gastric pull-up with primary anastomosis, pyloromyotomy, fundoplication, and closure of the tracheal defect with two intercostal muscle flaps. The patient's postoperative course was complicated by right lower lobe Xanthomonas maltophilia pneumonia and empyema that resolved with antibiotic therapy. The patient was discharged with an oral diet on postoperative day 17. She has required no subsequent esophageal dilations or sinonasal surgery. The patient is presently at home in remission pursuing her college education 12 months after surgery.
DISCUSSION
Aspergillus is a ubiquitous airborne fungal agent that is frequently found to colonize the paranasal sinuses of patients with chronic sinusitis and may form aspergillomata (fungus balls), which can be seen on x-ray film.3 An atopic reaction within the nose resulting in an allergic rhinosinusitis may also result from Aspergitlus colonization. When Aspergillus is inhaled by an immunocomproraised host, colonization or infection may result.5 Colonization is thought to occur in the nasopharynx,
118 STACKet al.
OtolaryngologyHead and Neck Surgery January 1997
Fig. 3. Biopsy sample of mycetoma showing characteristic branching hyphae. (Periodic acid-Schiff stain; original magnification x40.) (Courtesy of Dr. J, Ackerman.)
which may lead to tracheobronchial aspiration of the organism and subsequent pulmonary involvement.3 Immunocompromised patients noted to have paratracheal or hilar masses on chest radiographs may have pulmonary Aspergillus involvement.5 Infection of the immunocompromised host by Aspergillus when located in the lungs and locally destructive is known as invasive pulmonary aspergillosis. 1 Extrapulmonary involvement with invasive Aspergillus infection is seen with a 10% to 25% incidence. Organs that are most frequently involved include the sinuses, gastrointestinal tract (esophagus), brain, heart, and liver.3,6 Factors that appear to facilitate Aspergillus infection include neutropenia and erosive mucositis. 3 The pathophysiology of invasive AspergiIlus infection includes soft tissue extension, vascular invasion, and infarction.2 This process can result in the transmural necrosis of a viscus (trachea, bronchus, or gastrointestinal tract). Vascular invasion may also result in hemorrhage severe enough to cause death.7 Massive hemoptysis, bronchopleural fistula, and TEF are possible with pulmonary involvement. This aggressive behavior also results in contiguous bone erosion when the paranasal sinuses are involved.7 Diagnosis of Aspergillus infection is based on a heightened level of suspicion in the immunocompromised population. Surveillance nasal cultures in highrisk groups have shown a high correlation with invasive pulmonary aspergillosis. 3 Serologic testing is actively being researched, but no reliable method for diagnostic purposes is available. The gold standard for diagnosis remains histopathologic examination of biopsy speci-
mens demonstrating tissue or vascular invasion by septate, acute-angle, branched hyphae. Evaluation of patients with or at risk for aspergillosis should include serial physical examination and radiologic studies of vulnerable sites when indicated (lungs and sinuses). The otolaryngologist should consider frequent nasal endoscopic evaluation and paranasal sinus CT, as warranted, of patients with pulmonary aspergiUosis. Likewise, when primary head and neck Aspergilius infection is identified, other sites (lungs) should be examined for additional fungal disease. Chest x-ray findings of paratracheal opacity, tracheal narrowing, pneumomediastinum, or diffuse parenchymal infiltrates in an immunocompromised patient should alert the physician to possible pulmonary aspergillosis and warrant CT examination of the chest and bronchoscopy with biopsy when possible. 5 Persistent dysphagia or clinical signs of aspiration should alert the clinician to possible laryngopharyngeal dysfunction or tracheoesophageal communication. These symptoms warrant further investigation, including dynamic contrast swallowing studies and endoscopy. Treatment of Aspergillus infections in the immunocompromised population includes correction of the immunodeficiency (if possible), high-dose intravenous amphotericin B, resection of the necrotic tissue, and reconstruction of any involved structures when feasible (esophagus, trachea, vessels, etc.). New approaches for future treatment of invasive aspergillosis include liposomal amphotericin B (not approved by the Food and
OtolaryngologyHead and Neck Surgery
STACK et al. 119
Volume 116 Number 1
Drug Administration), itraconazole, and early aggressive surgical resection.
CONCLUSION Invasive aspergillosis is being seen with increasing frequency as the population of immunocompromised patients continues to grow. This is the second case report of TEF resulting from invasive Aspergillus infection in an immunocompromised host. As our patient demonstrates, a high level of suspicion must be maintained for Aspergillus infections among immunocompromised hosts. Otolaryngologists must be cognizant that paranasal sinus involvement with aspergillosis is only second in incidence to pulmonary involvement. Head and neck symptoms associated with Aspergi/lus infection may be multiple and vague but rapidly progressive. Early recognition and intervention may be lifesaving in this infection, which frequently portends a fatal outcome.
REFERENCES 1. Treger TR, Visscher DW, Bartlett MS, Smith JW. Diagnosisof pulmonaryinfectioncaused by aspergillus:usefulnessof respiratory cultures. J Infect Dis I985;152:572-6. 2. Albelda SM, Gefter WB, Epstein DM, Miller WT. Bronchopleural fistula complicating invasive pulmonary aspergillosis. Am Rev Respir Dis 1982;126:163-5. 3. Hebert PA, BayerAS. Fungal pneumonia(part 4): invasivepup monary aspergillosis.Chest 1981;80:220-5. 4. Berlinger NT, Freeman TJ. Acute airway obstruction due to necrotizing tracheobronchial aspergillosis in immunocomprorrfised patients: a new clinicalentity.Ann Otol Rbinol Laryngol 1989;98:718-20. 5. VailCM, Chiles C. Invasivepulmonaryaspergillosis:radiologic evidence of tracheal invoIvement.Radiology 1987;t 65:745-6. 6. Obrecht WF, Richter JE, Olympio GA, Gelfand DW. Tracheoesophageal fistula: a serious complicationof infectious esophagitis. Gastroenterology1984;87:1174-9. 7. Schubert MM, Peterson DE, Myers JD, Hackman R, Thomas ED. Head and neck aspergillosis in patients undergoingbone marrow transplantation.Cancer 1986;57:1092-6.
Postgraduate Course in Head and Neck Anatomy A 4-day course titled "The Alton D. Brashear Postgraduate Course in Head and Neck Anatomy" will be held March 10-13, 1997, at the Medical College of "Virginia,Departmentof Anatomy. Credit: 44 credit hours in Category 1 of the Physician's RecognitionAward of the American Medical Associationand the Academy of GeneralDentistry. For further information, contact Dr. Hugo R. Seibel, Department of Anatomy, RO. Box 980709, Medical College of Virginia,Richmond,VA 23298-0709.
Aspergillus
infections are on the increase as the community of immunocompromised patients continues to grow.1 Increased use of immunosuppressive agents for organ transplantation and autoimmune disorders is partly responsible. The growing number of patients infected with HIV likewise contributes to this population. Chemotherapeutic regimens used in the treatment of hematologic malignancies, solid tumors, and as induction for bone marrow transplantation render a significant number of patients susceptible to opportunistic infections as well. 2-4 Aspergillus, a ubiquitous soil saprophyte, is an airborne fungus that is inhaled routinely.5 It is second only to Candida species as an opportunistic infecting fungus among immunocompromised patients. 6 Aspergillus is one of the leading causes of death from fungal disease in immunocompromised patients. Although the most common site of Aspergillus infection is the lungs,7 Aspergillus infections of the head and neck are also being seen with increased frequency. All head and neck sites can be involved. 7 Common sites of infection in the head and neck include the paranasal sinuses, nose, mandible, larynx, and ear. 4 Consequently, Aspergillus as a cause of certain head and neck problems must always be considered when evaluating an immunocompromised host.7 Head and neck Aspergillus infections must be strongly suspected in those patients in whom pulmonary involvement is already diagnosed. We present the case of an immunocompromised host initially diagnosed with and treated for invasive Aspergillus sinusitis. Later a tracheoesophageal fistula
From the Divisions of Otolaryngology-Head and Neck Surgery (Drs. Stack and Ridley), Infectious Disease (Dr. Greene), and Thoracic Surgery (Dr. Hubbell), H. Lee Moffitt Cancer Center and Research Institute, University of South Florida College of Medicine. Presented at the 88th Annual Clinical Congress of the Southern Medical Association, Orlando, Fla., Nov. 2-5, 1994. Reprint requests: Marion B. Ridley, MD, FACS, Division of Otolaryngology, University of South Florida, 12902 Magnolia Dr., Suite 3057, Tampa, FL 33612. Otolaryngol Head Neck Surg 1997; 116:116-9. Copyright © 1997 by the American Academy of OtolaryngologyHead and Neck Surgery Foundation, Inc 0194-5998/97/$5.00 + 0 23/4/70611
116
(TEF) developed fi'om invasive aspergillosis. This case is the second reported case of a TEF resulting from invasive Aspergillus infection. CASE REPORT
Acute myelogenous leukemia was diagnosed in an 18year-old woman in July 1993. The patient was treated elsewhere with chemotherapy (transretinoic acid) for 14 days. The patient was subsequently admitted to our center for neutropenia, thrombocytopenia, and fever. Workup revealed a right lower lobe pneumonia and Staphylococcus aureus bacteremia. The patient was treated with broad-spectrum intravenous antibiotics (vancomycin, ceftazidime, and tobramycin) and fungal prophylaxis (fluconazole). Ten days after the patient started antibiotics, dysphagia developed. A diagnosis of esophagitis presumed caused by Candida vs. herpes simplex virus was made. Acyclovir was added for antiviral coverage. Two weeks later the patient was noted to have left nasal obstruction. Physical examination revealed a dark, crusting lesion on the left nasal septum. Otolaryngology consultation was obtained, and mild left maxillary and ethmoid sinusitis was noted on CT (Fig. 1). A biopsy specimen of the lesion revealed septated, filamentous hyphae, mad subsequent culture grew Aspergillus. Fluconazole was discontinued, and the patient began receiving amphotericin B and rifampiu. A left medial maxillectomy, transantral ethmoidectomy, partial septectomy, and inferior turbinectomy were performed. On postoperative day 3 a productive cough and choking with liquids developed. A conventional barium swallow revealed "aspiration" and external compression of the esophagus at the level of the right main bronchus. A dynamic video esophagram study demonstrated a normal swallow followed by a cough, at which time tracheal contrast was noted. There was no glottic penetration during the pharyngeal phase of swallowing. Flexible bronchoscopy revealed a left mainstem, black, necrotic lesion on the posterior wall (Fig, 2). The patient then underwent esophagogastroduodenoscopy with biopsy, which revealed a similar lesion on the anterior wall of the esophagus. Biopsy results demonstrated invasive aspergillosis (Fig. 3). A diagnosis of TEF was made. An enteral feeding tube was placed endoscopically, and the patient was medically and nutritionally optimized for surgery. The patient underwent exploration and resection of the necrotizing esophageal aspergilloma approximately 2
OtolaryngologyHead and Neck Surgery Volume 116 Number 1
STACK et af. 117
Fig. 1. CT findings of mild left maxillary sinusitis.
Fig. 2. View of fungal mycetoma through flexible bronchoscope. Note the mycetoma at the site of the fistula in the left mainstem bronchus just distal to the carina.
weeks after the diagnosis of TEE Surgical excision and repair consisted of a right thoracotomy, distal esophagectomy, gastric pull-up with primary anastomosis, pyloromyotomy, fundoplication, and closure of the tracheal defect with two intercostal muscle flaps. The patient's postoperative course was complicated by right lower lobe Xanthomonas maltophilia pneumonia and empyema that resolved with antibiotic therapy. The patient was discharged with an oral diet on postoperative day 17. She has required no subsequent esophageal dilations or sinonasal surgery. The patient is presently at home in remission pursuing her college education 12 months after surgery.
DISCUSSION
Aspergillus is a ubiquitous airborne fungal agent that is frequently found to colonize the paranasal sinuses of patients with chronic sinusitis and may form aspergillomata (fungus balls), which can be seen on x-ray film.3 An atopic reaction within the nose resulting in an allergic rhinosinusitis may also result from Aspergitlus colonization. When Aspergillus is inhaled by an immunocomproraised host, colonization or infection may result.5 Colonization is thought to occur in the nasopharynx,
118 STACKet al.
OtolaryngologyHead and Neck Surgery January 1997
Fig. 3. Biopsy sample of mycetoma showing characteristic branching hyphae. (Periodic acid-Schiff stain; original magnification x40.) (Courtesy of Dr. J, Ackerman.)
which may lead to tracheobronchial aspiration of the organism and subsequent pulmonary involvement.3 Immunocompromised patients noted to have paratracheal or hilar masses on chest radiographs may have pulmonary Aspergillus involvement.5 Infection of the immunocompromised host by Aspergillus when located in the lungs and locally destructive is known as invasive pulmonary aspergillosis. 1 Extrapulmonary involvement with invasive Aspergillus infection is seen with a 10% to 25% incidence. Organs that are most frequently involved include the sinuses, gastrointestinal tract (esophagus), brain, heart, and liver.3,6 Factors that appear to facilitate Aspergillus infection include neutropenia and erosive mucositis. 3 The pathophysiology of invasive AspergiIlus infection includes soft tissue extension, vascular invasion, and infarction.2 This process can result in the transmural necrosis of a viscus (trachea, bronchus, or gastrointestinal tract). Vascular invasion may also result in hemorrhage severe enough to cause death.7 Massive hemoptysis, bronchopleural fistula, and TEF are possible with pulmonary involvement. This aggressive behavior also results in contiguous bone erosion when the paranasal sinuses are involved.7 Diagnosis of Aspergillus infection is based on a heightened level of suspicion in the immunocompromised population. Surveillance nasal cultures in highrisk groups have shown a high correlation with invasive pulmonary aspergillosis. 3 Serologic testing is actively being researched, but no reliable method for diagnostic purposes is available. The gold standard for diagnosis remains histopathologic examination of biopsy speci-
mens demonstrating tissue or vascular invasion by septate, acute-angle, branched hyphae. Evaluation of patients with or at risk for aspergillosis should include serial physical examination and radiologic studies of vulnerable sites when indicated (lungs and sinuses). The otolaryngologist should consider frequent nasal endoscopic evaluation and paranasal sinus CT, as warranted, of patients with pulmonary aspergiUosis. Likewise, when primary head and neck Aspergilius infection is identified, other sites (lungs) should be examined for additional fungal disease. Chest x-ray findings of paratracheal opacity, tracheal narrowing, pneumomediastinum, or diffuse parenchymal infiltrates in an immunocompromised patient should alert the physician to possible pulmonary aspergillosis and warrant CT examination of the chest and bronchoscopy with biopsy when possible. 5 Persistent dysphagia or clinical signs of aspiration should alert the clinician to possible laryngopharyngeal dysfunction or tracheoesophageal communication. These symptoms warrant further investigation, including dynamic contrast swallowing studies and endoscopy. Treatment of Aspergillus infections in the immunocompromised population includes correction of the immunodeficiency (if possible), high-dose intravenous amphotericin B, resection of the necrotic tissue, and reconstruction of any involved structures when feasible (esophagus, trachea, vessels, etc.). New approaches for future treatment of invasive aspergillosis include liposomal amphotericin B (not approved by the Food and
OtolaryngologyHead and Neck Surgery
STACK et al. 119
Volume 116 Number 1
Drug Administration), itraconazole, and early aggressive surgical resection.
CONCLUSION Invasive aspergillosis is being seen with increasing frequency as the population of immunocompromised patients continues to grow. This is the second case report of TEF resulting from invasive Aspergillus infection in an immunocompromised host. As our patient demonstrates, a high level of suspicion must be maintained for Aspergillus infections among immunocompromised hosts. Otolaryngologists must be cognizant that paranasal sinus involvement with aspergillosis is only second in incidence to pulmonary involvement. Head and neck symptoms associated with Aspergi/lus infection may be multiple and vague but rapidly progressive. Early recognition and intervention may be lifesaving in this infection, which frequently portends a fatal outcome.
REFERENCES 1. Treger TR, Visscher DW, Bartlett MS, Smith JW. Diagnosisof pulmonaryinfectioncaused by aspergillus:usefulnessof respiratory cultures. J Infect Dis I985;152:572-6. 2. Albelda SM, Gefter WB, Epstein DM, Miller WT. Bronchopleural fistula complicating invasive pulmonary aspergillosis. Am Rev Respir Dis 1982;126:163-5. 3. Hebert PA, BayerAS. Fungal pneumonia(part 4): invasivepup monary aspergillosis.Chest 1981;80:220-5. 4. Berlinger NT, Freeman TJ. Acute airway obstruction due to necrotizing tracheobronchial aspergillosis in immunocomprorrfised patients: a new clinicalentity.Ann Otol Rbinol Laryngol 1989;98:718-20. 5. VailCM, Chiles C. Invasivepulmonaryaspergillosis:radiologic evidence of tracheal invoIvement.Radiology 1987;t 65:745-6. 6. Obrecht WF, Richter JE, Olympio GA, Gelfand DW. Tracheoesophageal fistula: a serious complicationof infectious esophagitis. Gastroenterology1984;87:1174-9. 7. Schubert MM, Peterson DE, Myers JD, Hackman R, Thomas ED. Head and neck aspergillosis in patients undergoingbone marrow transplantation.Cancer 1986;57:1092-6.
Postgraduate Course in Head and Neck Anatomy A 4-day course titled "The Alton D. Brashear Postgraduate Course in Head and Neck Anatomy" will be held March 10-13, 1997, at the Medical College of "Virginia,Departmentof Anatomy. Credit: 44 credit hours in Category 1 of the Physician's RecognitionAward of the American Medical Associationand the Academy of GeneralDentistry. For further information, contact Dr. Hugo R. Seibel, Department of Anatomy, RO. Box 980709, Medical College of Virginia,Richmond,VA 23298-0709.