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Epidural abscess, vertebral destruction, and paraplegia caused by extending infection from an aspergilloma
Epidural Abscess, Vertebral Destruction, and Paraplegia Caused by Extending Infection from an Aspergilloma
An aspergilloma developed In a lung cyst In a 53.year-old man. Asperglllus lnfectkn then contigwusly spread to the epldural space, causing an abscess, vertebral destructlon, and paraplegla at the level of T4. Chronic alcoholism, liver cirrhosis, and cortkosterold treatment may have been predlsposlng factors In this patient. Although Asperglllus epldural abscess has been described lnfrequently, this complkatkn has not been described In assoclatkn with an aspergllkma. Symptoms, signs, or roentgenosraphk or laboratory flndlngs suggestlve of vertebral or menlngeal pathologic lesions In patients with aspergllkma should alert the physklan to the posslblllty of contiguous spread of Infectlon.
DAVID K. WAGNER, M.D. BASIL VARKEY, M.D. NEELA K. SHETH, M.D. GARY J. DaMERT, M.D. Milwaukee. Wisconsin
Aspergillus is known to cause invasive pneumonia in patients whose immune competence is impaired due to disease or immunosuppressive therapy. Disseminated infection to various organs such as gastrointestinal tract, brain, heart, liver, spleen, kidney, and thyroid may follow [l]. Vertebral and epidural space involvement is very uncommon and was not found in 191 patients described in two series [2,3]. We reviewed the medical literature and found reports of six patients with Aspergillus epkfural abscess [4-g]. Two of these were renal transplant recipients who were immunosuppressed with corticosteroids and azathioprlne [4,5]. In both of them, chest roentgenographic findings were normal and the portal of entry of Aspergillus was undetermined. Another patient, a six-year-old boy, who died from multiple infections and aspergillosis probably had chronic granulomatous disease [S] . In the three remaining patients, there were no serious underlying disease8 and no history of immunosuppressive drug intake. In these patients, chest roentgenographic results were abnormal, other organs were uninvolved, and the location of the epidural abscess suggested the possibility of contiguous extension from a lung focus [7-g]. We report a similar case with an exceptional feature of an aspergilloma in a pre-existing lung cyst. Direct extension of Aspergillus infection from the aspergilloma caused an epidural abscess, vertebral destruction, spinal cord compression, and paraplegia. CASE
Fromthe Departmentsof Medicineand Pathology, WoodVeteransAdministration Medical Center and Medical College of Wisconsin, Milwaukee, Wlsconsln. Requests for rsprlnts should bs M&ssssd to Dr. Basil Vsrkey, Pulmonary Disease Section, Veterans Administration Msdlcsl Center. Wood, Wisconsin 53193. Manuscript accepted May 2, 1984.
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REPORT
In July 1983, a 5byear-old man who habitually used alcohol and tobacco in excess was hospitalizedfor acute alcoholic hepatitis. Hepatic encephakroethy and left lower lobe pneumonia of presumed bacterial origin developed. Of incidental note on chest roentgenography was a large right upper lobe bulla or cyst (Figure 1, top). He was treated with antibiotics (cefoxitln, tobramycin)
and high-dose corticosteroids. His condition improved and the left lower lobe pneumonia cleared. After a month of hospitalization, he was discharged and followed at regular intervals by his private physician. Treatment with corti-
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costeroids (dexamethasone 2 mg daily for about three months, followed by prednisone 10 mg in tapering doses) was continued until December 7, 1983. He was admitted to the Wood Veterans Administration Medical Center for the first time on December 13, 1983 with complaints of cough productive of yellowish sputum and right-sided pleuritic chest pain of three weeks’ duration. He denied any past exposure to tuberculosis and did not experience any hemoptysis, fever, or chills. On examination, he was found to be oriented, anxious, and tremulous with a temperature of 100.8’F (oral), blood pressure 124/70 mm Hg, and pulse 112 beats per minute. He was not jaundiced but had spider angiomata over his chest. Also noted were poor dentition, marked periodontal disease, enlarged liver (total span of 12 cm), and bronchial breath sounds over the right upper chest posteriorly. Results of neurologic examination were within normal limits. Laboratory tests showed a hemoglobin level of 13.8 g/dl, hematocrit of 42.6 percent, and a total white cell count of 18, 100/mm.3 Differential count showed 82 percent segmented neutrophils, 9 percent band forms, 1 percent metamyelocytes, and 8 percent lymphocytes. Results of urine analysis and blood studies of electrolytes, glucose, urea nitrogen, creatinine, bilirubin, and transaminase were normal. The alkaline phosphatase level was increased (201 Ill/liter) and serum protein electrophoresis showed decreased albumin (2.6 g/dl) and increased gammaglobulin (2.8 g/dl) levels. Chest roentgenography (posteroanterior view) showed a right upper lobe intracavitary density with air around it, adjacent pleural thidcening, and infiltrates (Figure 1, middle). Lateral view and tomography localized it to the posterior segment and confirmed the presence of an intracavitary density that was most likely an aspergilloma (Figure 1, bottom). Sputum smears showed fungal hyphae, and cultures gew oral flora and Aspergillus fumigatus. Three consecutive smears stained with Ziehl-Neelsen stain did not reveal any acid-fast bacilli. Results of a PPD 5 TU skin test were negative as were results of skin tests with mumps and Candida. Results of immuncdiffusion study of serum for precipitating antibodies against A. fumigatus were strongly positive. In addition to the aspergilloma, the patient was presumed to have anaerobic pneumonitis and began to receive intravenous penicillin 1 million units every four hours. He continued to have fever, and was noted to have periods of confusion. A spinal tap was therefore performed on December 27, 1983, and the spinal fluid revealed a protein level of 620 mg/dl, glucose level of 26 mg/dl (serum 99 mg/dl), a polymorphonuclear leukocyte count of 356/mm3, and a lymphocyte count of 80/mm3. No organisms were seen on Gram stain, Ziehl-Neelsen stain, and India ink preparation. Contrast-enhanced computed tomographic scanning of the head showed normal findings. Treatment with penicillin was discontinued and administration of high-dose ampicillin and chloramphenicol was begun for presumed partially treated bacterial meningitis. A spinal tap was repeated three days later; the fluid showed no organisms and similar findings as on the previous examination. Results of cultues of the spinal fluid were negative. Over the next 12 days, the patient remained febrile and periodically disoriented. He complained of upper mid-back pain, and bone scanning showed diffuse
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Figure 1. Top, roentgenographic view of right upper lung shows a large bulla or cyst (arrowheads indicate the wall). Middle, chest roentgenogram shows a right upper lung cavity with an intracavitary density, pericavitary pleural thickening, and infiltrates. Bottom, tomogram delineates an intracavitary density with air around it, highly suggestive of an aspergilloma.
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were noted on microscopy. The lung parenchyma outside the bulla did not show invasion by Asperglllus, and other organs of the body, including the brain, were not infected. The liver showed micronodular cirrhosis. COMMENTS
Figure 2. Computed tomogram of the thorax shows a cavitary lung density posteriorly, an intracavitary mass, a paravetiebral soft tissue mass, and mottling and decreased attenuation of the vertebral body.
uptake in T4. A spinal tap was again performed and revealed a protein level of 1,800 mg/dl, glucose level of 18 mg/dl, polymorphonuclear leukocyte count of 1 02/mm3, and lymphocyte count of 10/mm3. No organisms were seen, and counterimmunoelectrophoresis for Streptococcus pneumoniae, Neisseria meningitidis, and Hemophilus influenzae and latex agglutination test for Cryptococcus showed negative findings. The patient was transferred to the intensive care unit. The following day, paraplegia developed at the level of Tq. Computed tomographic scanning of the thorax showed right
lung infiltrates, an intracavitarydensity, a paravertebral mass, and mottling of the T4 vertebral body (Figure 2). Myelography confirmed complete blockage of the dye at T4. The patient was taken to the operating room on January 18, 1984. A necrotic T3-T4 disk was removed and the adjacent epidural abscess was drained. Tissue sections on microscopy revealed hyphae of Aspergillus, and the drainage from the abscess on culture grew A. fumigatus as a single isolate. The patient began to receive intravenous amphotericin B, totaling 696 mg over the next 20 days. His clinical condition deteriorated and he died of renal and respiratory failure on February 9, 1984. His family consented to a postmortem examination. At autopsy, both lungs showed bullous emphysematous changes, particularly in the upper lobes. There was a large bulla in the right upper lobe that communicated with a bronchus and contained a ball of brown friable material (Figure 3). The posteromedial wall of this bulla was adherent to the right lateral surface of T3 and T4 by fibrocollagenous tissue forming an illdefined mass. Necrotic and purulent material extended into the paravertebral soft tissue, eroded the vertebral and intervertebral disk, and extended along the spinal meninges from the level of T2 to T5. Microscopically, the wall of the right upper lobe bulla showed granulation tissue, and some parts of the wall were lined with stratified squamous epithelium. The friable mass inside the bulla showed dichotomously branching Aspergillus hyphae and conidiophores in a necrotic matrix (Figure 3, inset). Aspergillus extended into the vertebra and paravertebral area, and infiltrated the myelin sheath and spinal cord (Figure 4). No other organisms
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Aspergillus epidural abscess was diagnosed in our patient only after paraplegia developed, although he had abnormal spinal fluid findings three weeks earlier followed by back pain and abnormalities on scanning of Tq. In reviewing the three comparable cases in the literature, a diagnostic delay of several months is noted in two patients who had localized symptoms and signs of upper back pain with radiation to arms and decreased pain and touch along the distribution of T1 dermatome [7,8]. The protein level was mildly elevated (80 mg/dl) in spinal fluid in one patient, and vertebral destruction was confirmed in two patients. Paraplegia developed at levels of T2 to T4 in all three patients. These patients had roentgenographic evidence of localized lung disease (mass, shadow, fibrotic changes) in the upper lobes. Although an aspergilloma was not roentgenographically diagnosed, such a possibility needs to be considered, since chest roentgenographic results that were persistently abnormal were noted in two patients, and resected lung tissue showed “confluent granulomas containing mycelia” in one patient [S] and a mass containing A. fumigatus in another [7]. The common features of these four cases (including our case) of Aspergillus epidural abscess with localized upper lobe disease underscore the importance of recognizing that symptoms, signs, and abnormal roentgenographic findings localized to the upper back and abnormal spinal fluid findings may be present because of extension of Aspergillus infection from the lung to the epidural space and vertebra. Aspergillomas form by colonization and proliferation of Aspergillus in pre-existing pulmonary cavities. Tuberculosis heads the list of a variety of conditions, including lung cysts, that predispose to aspergillomas [ 10,111. Aspergillomas may also follow invasive pulmonary aspergillosis, chronic necrotizing pulmonary aspergillosis [ 111, and allergic bronchopulmonary aspergillosis [ 121. In these settings, Aspergillus initiates a necrotic process by invasion, blood vessel involvement, or immunologic reactions in the host. Our patient did not have neoplastic disease, lung parenchymal invasion with Aspergillus, or asthma. An aspergilloma developed in a pre-existing lung cyst. Therefore, the logical questions that arise are how commonly do aspergillomas cause localized extension of Aspergillus infection and why did it happen in our patient. In three separate long-term studies of aspergillomas involving a total of 69 patients, there were no cases of local or disseminated spread of infection [ 13-151. In
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Figure 3. Photograph shows aspergilloma in the right upper lobe bulk Inset: photomicrograph shows hyphae and conidiophores of Aspergiilus fumigatus (Gmwri methenamine silver stain: original magnification X 400, reduced by 35 percent).
Figure 4. Photomicrograph shows an exudative infiltrate invotving the myelin sheath and underlying neural tissue (hematoxylin-eosin stain; original magnification X 50, reduced by 35 percent). Inset: photomicrograph corresponds to the area shown by the arrow, showing mycelial ehments of Aspergilius @ading the spinal cord (Gomori methenamine silver stain; original rmgMicaticn X 400, reduced by 35 percent).
variance with this observation, a recent British study reported invasive aspergillosis in five of 23 patients with aspergilloma [ 161. In one patient, diagnosis of a preexisting aspergllloma was not established. In two patients who died, postmortem examination confirmed the diagnosis, and In three who survived after antifungal treatment, the diagnosis of invasive pulmonary aspergillosis was by “progressive pulmonary shadowing” observed on chest roentgenography. It is noteworthy that two patients had debilitating diseases (ulcerative colitis, chronic empyema) and two others were receiving corticosteroid treatment.
Conflicting impressions are gained from clinical reports on whether or not corticosteroids enhance the possibility of invasive aspergillosis in nonimmunocompromised hosts, Corticosteroids, when used in patients with aspergillomas who had sarcoidosis or asthmatic symptoms, did not result in invasive aspergillosis [ 15,17-l 91. However, Lake and associates [ 201 described an asthmatic patient, with no other underlying disease, in whom invasive and disseminated aspergillosis developed following a brief course of cot-ticosteroids. Corticosteroids have been considered a factor in the development of aspergillosis in patients with
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cancer [2,3] and renal transplant recipients [21]. Experimental studies in animals implicate corticosteroids as a predisposing factor in aspergillosis [22-241. One mechanism by which cot-ticosteroids potentiate Aspergillus infection is by decreasing intracellular killing of spores by macrophages [24], allowing intracellular germination [23]. Invasive and disseminated aspergillosis has been described very infrequently (less than 20 cases in the literature) in presumably immunocompetent hosts [20,25]. It has also been described in association with chronic alcoholism and liver disease (subacute hepatic necrosis, viral hepatitis, eclampsia, cirrhosis) [26,27]. In our patient, chronic alcoholism, liver cirrhosis, and prolonged corticosteroid treatment are possible factors
that predisposed to extension of Aspergillus infection. Antibiotic treatment is an unlikely predisposing factor because of the short duration of treatment and the lack of evidence favoring such a predisposing role for antibiotics [3,28]. ADDENDUM
After this manuscript was accepted for publication, Polatty and associates [29] described a patient with advanced sarcoidosis (treated with corticosteroids), lung cysts, and bilateral aspergillomas in whom spinal cord compression developed from an Aspergillus epidural abscess without signs of disseminated disease. The patient later died of azotemia and poor pulmonary reserve. Permission for autopsy was not granted.
REFERENCES
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Herbert PA, Bayer AS: Fungal pneumonia. Invasive pulmonary aspergillosis. Chest 1981; 80: 220-225. Meyer RD. Young LS, Armstrong D, Yu B: Aspergillosis complicating neoplastic disease. Am J Med 1973; 54: 8-15. Young RC, Bennett JE, Vogel CL, Carbone P, DeVita VT: Aspergillosis. The spectrum of the disease in 98 patients. Medicine (Baltimore) 1970; 49: 147-173. lngwer I, McLeish KR, Tight RR, White AC: Aspergillus fumig&us epidural abscess in a renal transplant recipient. Arch Intern Med 1978; 138: 153-154. Byrd BF, Weiner MH, McGee ZA: Aspergillus spinal epidural abscess. JAMA 1982; 248: 3138-3139. Redmond A, Carre IJ, Biggart JD, MacKenzie DWR: Aspergillosis (Aspergillus nidulans) involving bone. J Pathol Bacteriol 1985; 89: 391-395. Seres JL, Dno H, Benner EJ: Aspergillosis presenting as spinal cord compression. J Neurosurg 1972; 38: 221-224. Dietz R, Huber G, Thetter 0, Volkmer I: Aspergillosis of the lung with osteoclasis and paraplegia. Neuroradiology 1982; 23: 219-221. Chee YC, Poh SC: Aspergillus epidural abscess in a patient with obstructive airway disease. Postgrad Med J 1983; 59: 43-45. Glimp RA, Bayer AS: Pulmonary aspergilloma. Diagnostic and therapeutic cosiderations. Arch Intern Med 1983; 143: 303-308. Binder RE, Faling LJ, Pugatch RD, Mahasaen C, Snider GL: Chronic necrotizing pulmonary aspergillosis: a discrete clinical entity. Medicine (Baltimore) 1982; 81: 109-124. Anderson CJ, Craig S, Bardana EJ: Allergic bronchopulmonary aspergillosis and bilateral fungus balls terminating in disseminated aspergillosis. J Allergy Clin lmmunol 1980; 85: 83-88. Varkey B, Rose HD: Pulmonary aspergilloma: a rational approach to treatment. Am J Med 1978; 81: 828-831. Faulkner SL, Vernon R, Brown PP, Fisher RD, Bender HW: Hemoptysis and pulmonary aspergilloma. Operative versus nonoperative treatment. Ann Thorac Surg 1978; 25: 389-392. Kaplan JK, Johns CJ: Mycetomas in pulmonary sarcoidosis. Non-surgical management. Johns Hopkins Med J 1979;
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145: 157-181. Rafferty P, Biggs BA, Crompton GK, Grant IWB: What happens to patients wlth pulmonary aspergilloma? Analysis of 23 cases. Thorax 1983; 38: 579-583. Israel HL, D&row A: Sarcoldosis and aspergilloma. Am J Med 1989; 47: 243-250. Davies D, Somner AR: Pulmonary aspergillornas treated with corticosteroids. Thorax 1972; 27: 158-182. McCarthy DS, Pepys J: Pulmonary aspergilloma. Clinical immunology. Clin Allergy 1973; 3: 57-70. Lake KB, Browne PM, VanDyke JJ, Ayers L: Fatal disseminated aspergillosis in an asthmatic patient treated with corticosteroids. Chest 1983; 83: 138-139. Burton JR, Zachery JB, Bessin R, et al: Aspergillosis in four renal transplant recipients: diagnosis and effective treatment with amphotericin B. Ann Intern Med 1972; 77: 383-388. Sidransky HJ, Epstein SM, Verney E, Horowitz C: Experimental visceral aspergillosis. Am J Pathol 1972; 89: 55-70. Turner KJ. Had&raw R. Paoadimitriou J, Wetherall JD, Pernott J: Experimental aspergiilosis in rats infected via intraperitoneal and subcutaneous routes. Immunology 1975; 29: 55-88. Merkow LP, Epstein SM, Sidransky H, Verney E, Pardo M: The pathogenesis of experimental pulmonary aspergillosis: an ultrastructural study of alveolar macrophages after phagocytosis of A. flavus spores in vivo. Am J Pathol 1971; 82: 57-84. D’Silva HD, Burke JF, Cho SY: Disseminated aspergillosis in a presumably immunocomponent host. JAMA 1982; 248: 1495-1497. Varkey B: Liver disease and aspergillosis. JAMA 1983; 24: 2020. Walsh TJ, Hamilton SR: Disseminated aspergillosis complicating hepatic failure. Arch Intern Med 1983; 143: 1189-1191. Siiansky H, Friedman L: The effect of cortisone and antibiotic agents on experimental pulmonary aspergillosis. Am J Pathol 1959; 35: 189-179. Polatty RC, Cooper KR, Kerkering TM: Spinal cord compression due to an aspergilloma. South Med J 1984; 77: 845-848.
An aspergilloma developed In a lung cyst In a 53.year-old man. Asperglllus lnfectkn then contigwusly spread to the epldural space, causing an abscess, vertebral destructlon, and paraplegla at the level of T4. Chronic alcoholism, liver cirrhosis, and cortkosterold treatment may have been predlsposlng factors In this patient. Although Asperglllus epldural abscess has been described lnfrequently, this complkatkn has not been described In assoclatkn with an aspergllkma. Symptoms, signs, or roentgenosraphk or laboratory flndlngs suggestlve of vertebral or menlngeal pathologic lesions In patients with aspergllkma should alert the physklan to the posslblllty of contiguous spread of Infectlon.
DAVID K. WAGNER, M.D. BASIL VARKEY, M.D. NEELA K. SHETH, M.D. GARY J. DaMERT, M.D. Milwaukee. Wisconsin
Aspergillus is known to cause invasive pneumonia in patients whose immune competence is impaired due to disease or immunosuppressive therapy. Disseminated infection to various organs such as gastrointestinal tract, brain, heart, liver, spleen, kidney, and thyroid may follow [l]. Vertebral and epidural space involvement is very uncommon and was not found in 191 patients described in two series [2,3]. We reviewed the medical literature and found reports of six patients with Aspergillus epkfural abscess [4-g]. Two of these were renal transplant recipients who were immunosuppressed with corticosteroids and azathioprlne [4,5]. In both of them, chest roentgenographic findings were normal and the portal of entry of Aspergillus was undetermined. Another patient, a six-year-old boy, who died from multiple infections and aspergillosis probably had chronic granulomatous disease [S] . In the three remaining patients, there were no serious underlying disease8 and no history of immunosuppressive drug intake. In these patients, chest roentgenographic results were abnormal, other organs were uninvolved, and the location of the epidural abscess suggested the possibility of contiguous extension from a lung focus [7-g]. We report a similar case with an exceptional feature of an aspergilloma in a pre-existing lung cyst. Direct extension of Aspergillus infection from the aspergilloma caused an epidural abscess, vertebral destruction, spinal cord compression, and paraplegia. CASE
Fromthe Departmentsof Medicineand Pathology, WoodVeteransAdministration Medical Center and Medical College of Wisconsin, Milwaukee, Wlsconsln. Requests for rsprlnts should bs M&ssssd to Dr. Basil Vsrkey, Pulmonary Disease Section, Veterans Administration Msdlcsl Center. Wood, Wisconsin 53193. Manuscript accepted May 2, 1984.
518
March 1985
The Amsrkan
Journal of Mklns
REPORT
In July 1983, a 5byear-old man who habitually used alcohol and tobacco in excess was hospitalizedfor acute alcoholic hepatitis. Hepatic encephakroethy and left lower lobe pneumonia of presumed bacterial origin developed. Of incidental note on chest roentgenography was a large right upper lobe bulla or cyst (Figure 1, top). He was treated with antibiotics (cefoxitln, tobramycin)
and high-dose corticosteroids. His condition improved and the left lower lobe pneumonia cleared. After a month of hospitalization, he was discharged and followed at regular intervals by his private physician. Treatment with corti-
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costeroids (dexamethasone 2 mg daily for about three months, followed by prednisone 10 mg in tapering doses) was continued until December 7, 1983. He was admitted to the Wood Veterans Administration Medical Center for the first time on December 13, 1983 with complaints of cough productive of yellowish sputum and right-sided pleuritic chest pain of three weeks’ duration. He denied any past exposure to tuberculosis and did not experience any hemoptysis, fever, or chills. On examination, he was found to be oriented, anxious, and tremulous with a temperature of 100.8’F (oral), blood pressure 124/70 mm Hg, and pulse 112 beats per minute. He was not jaundiced but had spider angiomata over his chest. Also noted were poor dentition, marked periodontal disease, enlarged liver (total span of 12 cm), and bronchial breath sounds over the right upper chest posteriorly. Results of neurologic examination were within normal limits. Laboratory tests showed a hemoglobin level of 13.8 g/dl, hematocrit of 42.6 percent, and a total white cell count of 18, 100/mm.3 Differential count showed 82 percent segmented neutrophils, 9 percent band forms, 1 percent metamyelocytes, and 8 percent lymphocytes. Results of urine analysis and blood studies of electrolytes, glucose, urea nitrogen, creatinine, bilirubin, and transaminase were normal. The alkaline phosphatase level was increased (201 Ill/liter) and serum protein electrophoresis showed decreased albumin (2.6 g/dl) and increased gammaglobulin (2.8 g/dl) levels. Chest roentgenography (posteroanterior view) showed a right upper lobe intracavitary density with air around it, adjacent pleural thidcening, and infiltrates (Figure 1, middle). Lateral view and tomography localized it to the posterior segment and confirmed the presence of an intracavitary density that was most likely an aspergilloma (Figure 1, bottom). Sputum smears showed fungal hyphae, and cultures gew oral flora and Aspergillus fumigatus. Three consecutive smears stained with Ziehl-Neelsen stain did not reveal any acid-fast bacilli. Results of a PPD 5 TU skin test were negative as were results of skin tests with mumps and Candida. Results of immuncdiffusion study of serum for precipitating antibodies against A. fumigatus were strongly positive. In addition to the aspergilloma, the patient was presumed to have anaerobic pneumonitis and began to receive intravenous penicillin 1 million units every four hours. He continued to have fever, and was noted to have periods of confusion. A spinal tap was therefore performed on December 27, 1983, and the spinal fluid revealed a protein level of 620 mg/dl, glucose level of 26 mg/dl (serum 99 mg/dl), a polymorphonuclear leukocyte count of 356/mm3, and a lymphocyte count of 80/mm3. No organisms were seen on Gram stain, Ziehl-Neelsen stain, and India ink preparation. Contrast-enhanced computed tomographic scanning of the head showed normal findings. Treatment with penicillin was discontinued and administration of high-dose ampicillin and chloramphenicol was begun for presumed partially treated bacterial meningitis. A spinal tap was repeated three days later; the fluid showed no organisms and similar findings as on the previous examination. Results of cultues of the spinal fluid were negative. Over the next 12 days, the patient remained febrile and periodically disoriented. He complained of upper mid-back pain, and bone scanning showed diffuse
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Figure 1. Top, roentgenographic view of right upper lung shows a large bulla or cyst (arrowheads indicate the wall). Middle, chest roentgenogram shows a right upper lung cavity with an intracavitary density, pericavitary pleural thickening, and infiltrates. Bottom, tomogram delineates an intracavitary density with air around it, highly suggestive of an aspergilloma.
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were noted on microscopy. The lung parenchyma outside the bulla did not show invasion by Asperglllus, and other organs of the body, including the brain, were not infected. The liver showed micronodular cirrhosis. COMMENTS
Figure 2. Computed tomogram of the thorax shows a cavitary lung density posteriorly, an intracavitary mass, a paravetiebral soft tissue mass, and mottling and decreased attenuation of the vertebral body.
uptake in T4. A spinal tap was again performed and revealed a protein level of 1,800 mg/dl, glucose level of 18 mg/dl, polymorphonuclear leukocyte count of 1 02/mm3, and lymphocyte count of 10/mm3. No organisms were seen, and counterimmunoelectrophoresis for Streptococcus pneumoniae, Neisseria meningitidis, and Hemophilus influenzae and latex agglutination test for Cryptococcus showed negative findings. The patient was transferred to the intensive care unit. The following day, paraplegia developed at the level of Tq. Computed tomographic scanning of the thorax showed right
lung infiltrates, an intracavitarydensity, a paravertebral mass, and mottling of the T4 vertebral body (Figure 2). Myelography confirmed complete blockage of the dye at T4. The patient was taken to the operating room on January 18, 1984. A necrotic T3-T4 disk was removed and the adjacent epidural abscess was drained. Tissue sections on microscopy revealed hyphae of Aspergillus, and the drainage from the abscess on culture grew A. fumigatus as a single isolate. The patient began to receive intravenous amphotericin B, totaling 696 mg over the next 20 days. His clinical condition deteriorated and he died of renal and respiratory failure on February 9, 1984. His family consented to a postmortem examination. At autopsy, both lungs showed bullous emphysematous changes, particularly in the upper lobes. There was a large bulla in the right upper lobe that communicated with a bronchus and contained a ball of brown friable material (Figure 3). The posteromedial wall of this bulla was adherent to the right lateral surface of T3 and T4 by fibrocollagenous tissue forming an illdefined mass. Necrotic and purulent material extended into the paravertebral soft tissue, eroded the vertebral and intervertebral disk, and extended along the spinal meninges from the level of T2 to T5. Microscopically, the wall of the right upper lobe bulla showed granulation tissue, and some parts of the wall were lined with stratified squamous epithelium. The friable mass inside the bulla showed dichotomously branching Aspergillus hyphae and conidiophores in a necrotic matrix (Figure 3, inset). Aspergillus extended into the vertebra and paravertebral area, and infiltrated the myelin sheath and spinal cord (Figure 4). No other organisms
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Aspergillus epidural abscess was diagnosed in our patient only after paraplegia developed, although he had abnormal spinal fluid findings three weeks earlier followed by back pain and abnormalities on scanning of Tq. In reviewing the three comparable cases in the literature, a diagnostic delay of several months is noted in two patients who had localized symptoms and signs of upper back pain with radiation to arms and decreased pain and touch along the distribution of T1 dermatome [7,8]. The protein level was mildly elevated (80 mg/dl) in spinal fluid in one patient, and vertebral destruction was confirmed in two patients. Paraplegia developed at levels of T2 to T4 in all three patients. These patients had roentgenographic evidence of localized lung disease (mass, shadow, fibrotic changes) in the upper lobes. Although an aspergilloma was not roentgenographically diagnosed, such a possibility needs to be considered, since chest roentgenographic results that were persistently abnormal were noted in two patients, and resected lung tissue showed “confluent granulomas containing mycelia” in one patient [S] and a mass containing A. fumigatus in another [7]. The common features of these four cases (including our case) of Aspergillus epidural abscess with localized upper lobe disease underscore the importance of recognizing that symptoms, signs, and abnormal roentgenographic findings localized to the upper back and abnormal spinal fluid findings may be present because of extension of Aspergillus infection from the lung to the epidural space and vertebra. Aspergillomas form by colonization and proliferation of Aspergillus in pre-existing pulmonary cavities. Tuberculosis heads the list of a variety of conditions, including lung cysts, that predispose to aspergillomas [ 10,111. Aspergillomas may also follow invasive pulmonary aspergillosis, chronic necrotizing pulmonary aspergillosis [ 111, and allergic bronchopulmonary aspergillosis [ 121. In these settings, Aspergillus initiates a necrotic process by invasion, blood vessel involvement, or immunologic reactions in the host. Our patient did not have neoplastic disease, lung parenchymal invasion with Aspergillus, or asthma. An aspergilloma developed in a pre-existing lung cyst. Therefore, the logical questions that arise are how commonly do aspergillomas cause localized extension of Aspergillus infection and why did it happen in our patient. In three separate long-term studies of aspergillomas involving a total of 69 patients, there were no cases of local or disseminated spread of infection [ 13-151. In
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Figure 3. Photograph shows aspergilloma in the right upper lobe bulk Inset: photomicrograph shows hyphae and conidiophores of Aspergiilus fumigatus (Gmwri methenamine silver stain: original magnification X 400, reduced by 35 percent).
Figure 4. Photomicrograph shows an exudative infiltrate invotving the myelin sheath and underlying neural tissue (hematoxylin-eosin stain; original magnification X 50, reduced by 35 percent). Inset: photomicrograph corresponds to the area shown by the arrow, showing mycelial ehments of Aspergilius @ading the spinal cord (Gomori methenamine silver stain; original rmgMicaticn X 400, reduced by 35 percent).
variance with this observation, a recent British study reported invasive aspergillosis in five of 23 patients with aspergilloma [ 161. In one patient, diagnosis of a preexisting aspergllloma was not established. In two patients who died, postmortem examination confirmed the diagnosis, and In three who survived after antifungal treatment, the diagnosis of invasive pulmonary aspergillosis was by “progressive pulmonary shadowing” observed on chest roentgenography. It is noteworthy that two patients had debilitating diseases (ulcerative colitis, chronic empyema) and two others were receiving corticosteroid treatment.
Conflicting impressions are gained from clinical reports on whether or not corticosteroids enhance the possibility of invasive aspergillosis in nonimmunocompromised hosts, Corticosteroids, when used in patients with aspergillomas who had sarcoidosis or asthmatic symptoms, did not result in invasive aspergillosis [ 15,17-l 91. However, Lake and associates [ 201 described an asthmatic patient, with no other underlying disease, in whom invasive and disseminated aspergillosis developed following a brief course of cot-ticosteroids. Corticosteroids have been considered a factor in the development of aspergillosis in patients with
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cancer [2,3] and renal transplant recipients [21]. Experimental studies in animals implicate corticosteroids as a predisposing factor in aspergillosis [22-241. One mechanism by which cot-ticosteroids potentiate Aspergillus infection is by decreasing intracellular killing of spores by macrophages [24], allowing intracellular germination [23]. Invasive and disseminated aspergillosis has been described very infrequently (less than 20 cases in the literature) in presumably immunocompetent hosts [20,25]. It has also been described in association with chronic alcoholism and liver disease (subacute hepatic necrosis, viral hepatitis, eclampsia, cirrhosis) [26,27]. In our patient, chronic alcoholism, liver cirrhosis, and prolonged corticosteroid treatment are possible factors
that predisposed to extension of Aspergillus infection. Antibiotic treatment is an unlikely predisposing factor because of the short duration of treatment and the lack of evidence favoring such a predisposing role for antibiotics [3,28]. ADDENDUM
After this manuscript was accepted for publication, Polatty and associates [29] described a patient with advanced sarcoidosis (treated with corticosteroids), lung cysts, and bilateral aspergillomas in whom spinal cord compression developed from an Aspergillus epidural abscess without signs of disseminated disease. The patient later died of azotemia and poor pulmonary reserve. Permission for autopsy was not granted.
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