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Aspergillus niger pneumonia with fatal pulmonary oxalosis
JB.Infect Chemother (1999) 5:97–100 Jochimsen et al.: Stetteria hydrogenophila
© Japan Society of Chemotherapy 1999 97
CASE REPORT Yoshihisa Nakagawa · Kazuyoshi Shimazu Momoko Ebihara · Kazuko Nakagawa
Aspergillus niger pneumonia with fatal pulmonary oxalosis
Received: July 23, 1998 / Accepted: December 21, 1998
Abstract Metabolic products of Aspergillus species may play a significant role in the pulmonary destructive process. We describe a patient who died of respiratory failure, in whom postmortem examination revealed aspergilloma and numerous calcium oxalate crystals around the aspergilloma, as well as extensive consolidation areas. An-87-year-old man with a history of pulmonary tuberculosis and asbestos exposure was admitted to our hospital with fever and hemosputum. Chest radiograph on admission showed several small cavities in the right upper lung fields, but did not indicate the presence of a fungus ball. The patient was treated with several antibiotics, but his symptoms, and findings for inflammatory indicators and findings on chest radiographs deteriorated, and he died of respiratory failure 45 days after admission. Postmortem examination of the thoracic cavities showed marked involvement with extensive adhesions, fibrosis, caseation, and necrotic tissue. Aspergillus niger formed a mass in the right upper cavity and a localized invasion surrounding the cavity wall, but no organisms were detected in the left consolidation area. Numerous calcium oxalate crystals were found in the cavity wall, as well as an extensive consolidation area. We consider that oxalic acid produced by Aspergillus was the main cause of the patient’s respiratory failure. Key words Aspergillus niger · Calcium oxalate crystals · Aspergilloma · Respiratory failure · Exotoxin
Y. Nakagawa (*) · K. Shimazu · M. Ebihara Department of Internal Medicine, National Kumamoto South Hospital, 2338 Matsubase, Toyofuku, Shimomashiki, Kumamoto 869-0524, Japan K. Nakagawa First Department of Internal Medicine, Kumamoto University School of Medicine, Kumamoto, Japan
Introduction Semi-invasive pulmonary aspergillosis (SIPA)1 and chronic necrotizing pulmonary aspergillosis (CNPA)2 are locally destructive forms of chronic pulmonary aspergillosis; both have been poorly defined histologically. Transbronchial or percutaneous lung biopsies of the infiltration shadows have shown only necrotic tissue and squamous metaplasia without Aspergillus invasion.2 It is interesting to consider the role of exotoxin produced by Aspergillus in this destructive pulmonary process.3 We describe an 87-year-old man who died of respiratory failure; postmortem examination of the thoracic cavities indicated aspergilloma and numerous calcium oxalate crystals in the cavity wall, as well as an extensive consolidation area.
Case report An-87-year-old man who had a history of pulmonary tuberculosis and asbestos exposure was admitted to our hospital with fever and hemosputum. He had no history of immunosuppressive disease or alcohol abuse. His respiration was weak in both infrascapular areas, but there were no rales. A chest radiograph on admission showed several small cavities in the right upper lung fields and severe asbestos pleural plaque in both lung fields (Fig. 1), but did not indicate the presence of fungus ball. Laboratory findings showed marked inflammation; for example, the erythrocyte sedimentation rate and C-reactive protein level were 56 mm/h and 26.4 mg/dl, respectively, but the white blood cell (WBC) count was 5500/mm3. His immunostatus was normal. A sputum sample with Gram staining showed many white blood cells and mixed respiratory flora. A sputum sample with Papanicolaou staining showed no malignant cells. Sputum culture showed only normal respiratory flora. The patient was started on a regimen of intravenous betalactam antibiotics. However his symptoms and findings for
98
Fig. 1. Chest radiograph on admission showed several small cavities in the right upper lung fields, and severe asbestos pleural plaque in both lung fields, but did not indicate the presence of a fungus ball
inflammatory indicators and on chest radiographs showed that his condition had deteriorated, although the antibiotics were changed and antituberculosis agents were administered. Repeated sputum cultures were carried out, but only normal flora were detected. Chest radiographs 1 month after admission showed consolidation shadows around the cavity of the right upper lung fields (Fig. 2). Subsequently, his symptoms and findings for inflammatory indicators rapidly deteriorated, and severe hypoxia occurred. Chest radiographs 40 days after admission showed a new left middle lung field infiltrate (Fig. 3). Chest computed tomogram could not be carried out because of the rapid development of respiratory failure after the appearance of infiltration shadows on the chest radiographs. The patient died of respiratory failure 45 days after admission. Postmortem examination of the thoracic cavities showed marked involvement of the left thoracic cavity with extensive adhesions, fibrosis, caseation, and necrotic tissue. Aspergillus hyphae formed a mass in the right upper cavity and a localized invasion surrounding the cavity wall, but no fungal elements were detected in the left consolidation area. Aspergillus niger was cultured from this cavity but no other bacteria, acid-fast bacilli, or fungi were detected by smear or culture from either thoracic cavity. Numerous calcium oxalate crystals were found around the cavity, as well as extensive necrotic tissue and a consolidation area in the left lung, which were identified by the polarization technique (Fig. 4). Calcium oxalate crystals were not found in the remaining normal lung tissue. A sputum sample with Papanicolaou staining preserved during the patient’s lifetime, was re-examined and revealed scattered calcium ox-
N. Matsuda et al.: EGF receptor and osteoblastic differentiation
Fig. 2. Chest radiograph 1 month after admission showed consolidation shadows around the cavity of the right upper lung fields
Fig. 3. Chest radiograph 40 days after admission showed marked consolidations in the right upper lung fields and left middle and lower lung fields
alate crystals among white blood cells (Fig. 5). In serum preserved during the patient’s lifetime. Aspergillus antigen (Pastorex Aspergillus; Diagnostics Pasteur, France) and Aspergillus antibody (Ouchterlony test) were both positive.
B. Jochimsen et al.: Stetteria hydrogenophila
Fig. 4. Numerous calcium oxalate crystals (arrows) were found in the necrotic tissue and among the mononuclear cell infiltrates. H & E, 3 50
Discussion In recent years, aspergilloma was considered to be a manifestation of chronic destructive infection by Aspergillus, but not a result of colonization by the saprophytic form.4 Hebisawa et al.4 reported that aspergilloma could not be differentiated from CNPA, and that both should be categorized as secondary bronchopulmonary aspergillosis. Yousem5 reported the histological spectrum of ten patients with CNPA; some posed a problem in differential diagnostis with pulmonary aspergilloma5. Caras and Pluss6 reported that the complete differentiation of these two disorders may not be possible histologically, because rare cases of locally invasive Aspergillus fungus ball have been reported, and because the histologic findings of CNPA have not been well described in a large number of patients. Invasive pulmonary aspergillosis has two distinct pathologic patterns. One pattern is acute invasive pulmonary aspergillosis, which is found almost exclusively in immunosuppressed patients. This pattern is a result of Aspergillus invasion of the lung parenchyma and hemorrhage. A more chronic pattern is seen in CNPA; the infiltration shadows show only necrotic tissue and squamous metaplasia without Aspergillus invasion. Although the biological behavior of this clinical syndrome has been recognized by pulmonary specialists, its histopathology and causative factors have been poorly described. It is interesting to consider the role of exotoxin produced by Aspergillus in this destructive pulmonary process. The association of oxalic acid as a fermentation product of Aspergillus spp. (most notably A. niger) has been reported. Kurrien et al.7 reported an A. niger fungus ball in a patient who died of massive hemoptysis. Oxalic acid was implicated in the tissue destruction, including blood vessels. Kimmerling et al.3 first reported an invasive A. niger pneumonia with numerous oxalic acid crystal
99
Fig. 5. Calcium oxalate crystals were also recognized on sputum cytology. Papanicolaou, 3 200
deposits in the lung, and the oxalic acid produced by Aspergillus was implicated as the main cause of respiratory failure.3 Yoshida8 reported tissue injury by calcium oxalate crystals in rat lung with experimental A. niger infection. This report suggested that the crystals in the bronchial epithelium may expand and destroy the cells around them. In our patient, the consolidation around the right upper cavity and the extensive consolidation of the left lung fields on the chest radiographs revealed no fungal elements and numerous calcium oxalate crystals at the postmortem examination. Calcium oxalate crystals were not found in normal lung tissue. We consider that the intra-cavitary aspergilloma of the right lung may have led to the discharge of metabolic products of A. niger, including the oxalate crystals, out of the cavity, and thence into the left lung, and that these metabolic products caused the lung injury. The pathological diagnosis in our patient could not distinguish CNPA from active aspergilloma. Some CNPA reported to date may have involved invasive aspergilloma, but this distinction has little significance in regard to treatment. It is interesting that, on careful observation, the calcium oxalate crystals were recognized in the sputum. Niki et al.9 reported calcium oxalate crystals on sputum cytology and transbronchial lung biopsy in A. niger pneumonia, and they considered that the crystals in the sputum, in combination with serological assays, were useful for the early diagnosis of the Aspergillus pneumonia. It is well known that serum Aspergillus antigen (Pastorex Aspergillus; Diagnostics Pasteur, France) and beta-Dglucan are useful tools for the diagnosis of tissue invasive Aspergillus infection. In recent years, the clinical usefulness of the polymerase chain reaction for the detection of DNA for Aspergillus spp. in serum was also reported.10 However, we did not suspect Aspergillus pneumonia in our patient. If the calcium oxalate crystals had been recognized on sputum cytology in the patient’s lifetime, we may have been able to resolve the patients condition.
100
References 1. Gefter WB, Weingrad TR, Epstein DM, Ochs RH, Miller WT. “Semi-invasive” pulmonary aspergillosis. Radiology 1981;140: 313–21. 2. Binder RE, Faling LJ, Pugatch RD, Mahansen C, Snider GL. Chronic necrotizing pulmonary aspergillosis: A discrete clinical entity. Medicine 1982;61:109–23. 3. Kimmerling EA, Fedric JA, Tenholder MF. Invasive Aspergillus niger with fatal pulmonary oxalosis in chronic obstructive pulmonary disease. Chest 1992;101:870–2. 4. Hebisawa A, Kurashima A, Nagai H, Komatsu H, Yoneda R, Saiki S. Pathology of bronchopulmonary aspergillosis (in Japanese). Kekkaku 1997;72:109–18. 5. Yousem SA. The histological spectrum of chronic necrotizing forms of pulmonary aspergillosis. Hum Pathol 1997;28:650– 6.
N. Matsuda et al.: EGF receptor and osteoblastic differentiation 6. Caras WE, Pluss JL. Chronic necrotizing pulmonary aspergillosis: pathologic outcome after itraconazole therapy. Mayo Clin Proc 1996;71:25–30. 7. Kurrien F, Green GH, Rowles SL. Localized deposition of calcium oxalate around a pulmonary Aspergillus niger fungus ball. Am J Clin Pathol 1975;64:556–63. 8. Yoshida K . The correlation between tissue injury and calcium oxalate crystal production in rat’s lung with experimental Aspergillus niger infection (in Japanese). J J A Infect Dis 1998;72:621– 30. 9. Niki Y, Hashiguti K, Tamada S, Yoshida K, Sugimura S, Nakajima M, et al. A case of Aspergillus niger pneumonia cured with an early diagnosis (in Japanese). J J A Infect Dis 1994;68:788– 91. 10. Yamakami Y, Hashimoto A, Tokimatsu I, Nasu M. Detection of DNA specific for Aspergillus species in serum of patients with invasive aspergillosis by polymerase chain reaction. J Clin Microbiol 1996;34:2464–8.
© Japan Society of Chemotherapy 1999 97
CASE REPORT Yoshihisa Nakagawa · Kazuyoshi Shimazu Momoko Ebihara · Kazuko Nakagawa
Aspergillus niger pneumonia with fatal pulmonary oxalosis
Received: July 23, 1998 / Accepted: December 21, 1998
Abstract Metabolic products of Aspergillus species may play a significant role in the pulmonary destructive process. We describe a patient who died of respiratory failure, in whom postmortem examination revealed aspergilloma and numerous calcium oxalate crystals around the aspergilloma, as well as extensive consolidation areas. An-87-year-old man with a history of pulmonary tuberculosis and asbestos exposure was admitted to our hospital with fever and hemosputum. Chest radiograph on admission showed several small cavities in the right upper lung fields, but did not indicate the presence of a fungus ball. The patient was treated with several antibiotics, but his symptoms, and findings for inflammatory indicators and findings on chest radiographs deteriorated, and he died of respiratory failure 45 days after admission. Postmortem examination of the thoracic cavities showed marked involvement with extensive adhesions, fibrosis, caseation, and necrotic tissue. Aspergillus niger formed a mass in the right upper cavity and a localized invasion surrounding the cavity wall, but no organisms were detected in the left consolidation area. Numerous calcium oxalate crystals were found in the cavity wall, as well as an extensive consolidation area. We consider that oxalic acid produced by Aspergillus was the main cause of the patient’s respiratory failure. Key words Aspergillus niger · Calcium oxalate crystals · Aspergilloma · Respiratory failure · Exotoxin
Y. Nakagawa (*) · K. Shimazu · M. Ebihara Department of Internal Medicine, National Kumamoto South Hospital, 2338 Matsubase, Toyofuku, Shimomashiki, Kumamoto 869-0524, Japan K. Nakagawa First Department of Internal Medicine, Kumamoto University School of Medicine, Kumamoto, Japan
Introduction Semi-invasive pulmonary aspergillosis (SIPA)1 and chronic necrotizing pulmonary aspergillosis (CNPA)2 are locally destructive forms of chronic pulmonary aspergillosis; both have been poorly defined histologically. Transbronchial or percutaneous lung biopsies of the infiltration shadows have shown only necrotic tissue and squamous metaplasia without Aspergillus invasion.2 It is interesting to consider the role of exotoxin produced by Aspergillus in this destructive pulmonary process.3 We describe an 87-year-old man who died of respiratory failure; postmortem examination of the thoracic cavities indicated aspergilloma and numerous calcium oxalate crystals in the cavity wall, as well as an extensive consolidation area.
Case report An-87-year-old man who had a history of pulmonary tuberculosis and asbestos exposure was admitted to our hospital with fever and hemosputum. He had no history of immunosuppressive disease or alcohol abuse. His respiration was weak in both infrascapular areas, but there were no rales. A chest radiograph on admission showed several small cavities in the right upper lung fields and severe asbestos pleural plaque in both lung fields (Fig. 1), but did not indicate the presence of fungus ball. Laboratory findings showed marked inflammation; for example, the erythrocyte sedimentation rate and C-reactive protein level were 56 mm/h and 26.4 mg/dl, respectively, but the white blood cell (WBC) count was 5500/mm3. His immunostatus was normal. A sputum sample with Gram staining showed many white blood cells and mixed respiratory flora. A sputum sample with Papanicolaou staining showed no malignant cells. Sputum culture showed only normal respiratory flora. The patient was started on a regimen of intravenous betalactam antibiotics. However his symptoms and findings for
98
Fig. 1. Chest radiograph on admission showed several small cavities in the right upper lung fields, and severe asbestos pleural plaque in both lung fields, but did not indicate the presence of a fungus ball
inflammatory indicators and on chest radiographs showed that his condition had deteriorated, although the antibiotics were changed and antituberculosis agents were administered. Repeated sputum cultures were carried out, but only normal flora were detected. Chest radiographs 1 month after admission showed consolidation shadows around the cavity of the right upper lung fields (Fig. 2). Subsequently, his symptoms and findings for inflammatory indicators rapidly deteriorated, and severe hypoxia occurred. Chest radiographs 40 days after admission showed a new left middle lung field infiltrate (Fig. 3). Chest computed tomogram could not be carried out because of the rapid development of respiratory failure after the appearance of infiltration shadows on the chest radiographs. The patient died of respiratory failure 45 days after admission. Postmortem examination of the thoracic cavities showed marked involvement of the left thoracic cavity with extensive adhesions, fibrosis, caseation, and necrotic tissue. Aspergillus hyphae formed a mass in the right upper cavity and a localized invasion surrounding the cavity wall, but no fungal elements were detected in the left consolidation area. Aspergillus niger was cultured from this cavity but no other bacteria, acid-fast bacilli, or fungi were detected by smear or culture from either thoracic cavity. Numerous calcium oxalate crystals were found around the cavity, as well as extensive necrotic tissue and a consolidation area in the left lung, which were identified by the polarization technique (Fig. 4). Calcium oxalate crystals were not found in the remaining normal lung tissue. A sputum sample with Papanicolaou staining preserved during the patient’s lifetime, was re-examined and revealed scattered calcium ox-
N. Matsuda et al.: EGF receptor and osteoblastic differentiation
Fig. 2. Chest radiograph 1 month after admission showed consolidation shadows around the cavity of the right upper lung fields
Fig. 3. Chest radiograph 40 days after admission showed marked consolidations in the right upper lung fields and left middle and lower lung fields
alate crystals among white blood cells (Fig. 5). In serum preserved during the patient’s lifetime. Aspergillus antigen (Pastorex Aspergillus; Diagnostics Pasteur, France) and Aspergillus antibody (Ouchterlony test) were both positive.
B. Jochimsen et al.: Stetteria hydrogenophila
Fig. 4. Numerous calcium oxalate crystals (arrows) were found in the necrotic tissue and among the mononuclear cell infiltrates. H & E, 3 50
Discussion In recent years, aspergilloma was considered to be a manifestation of chronic destructive infection by Aspergillus, but not a result of colonization by the saprophytic form.4 Hebisawa et al.4 reported that aspergilloma could not be differentiated from CNPA, and that both should be categorized as secondary bronchopulmonary aspergillosis. Yousem5 reported the histological spectrum of ten patients with CNPA; some posed a problem in differential diagnostis with pulmonary aspergilloma5. Caras and Pluss6 reported that the complete differentiation of these two disorders may not be possible histologically, because rare cases of locally invasive Aspergillus fungus ball have been reported, and because the histologic findings of CNPA have not been well described in a large number of patients. Invasive pulmonary aspergillosis has two distinct pathologic patterns. One pattern is acute invasive pulmonary aspergillosis, which is found almost exclusively in immunosuppressed patients. This pattern is a result of Aspergillus invasion of the lung parenchyma and hemorrhage. A more chronic pattern is seen in CNPA; the infiltration shadows show only necrotic tissue and squamous metaplasia without Aspergillus invasion. Although the biological behavior of this clinical syndrome has been recognized by pulmonary specialists, its histopathology and causative factors have been poorly described. It is interesting to consider the role of exotoxin produced by Aspergillus in this destructive pulmonary process. The association of oxalic acid as a fermentation product of Aspergillus spp. (most notably A. niger) has been reported. Kurrien et al.7 reported an A. niger fungus ball in a patient who died of massive hemoptysis. Oxalic acid was implicated in the tissue destruction, including blood vessels. Kimmerling et al.3 first reported an invasive A. niger pneumonia with numerous oxalic acid crystal
99
Fig. 5. Calcium oxalate crystals were also recognized on sputum cytology. Papanicolaou, 3 200
deposits in the lung, and the oxalic acid produced by Aspergillus was implicated as the main cause of respiratory failure.3 Yoshida8 reported tissue injury by calcium oxalate crystals in rat lung with experimental A. niger infection. This report suggested that the crystals in the bronchial epithelium may expand and destroy the cells around them. In our patient, the consolidation around the right upper cavity and the extensive consolidation of the left lung fields on the chest radiographs revealed no fungal elements and numerous calcium oxalate crystals at the postmortem examination. Calcium oxalate crystals were not found in normal lung tissue. We consider that the intra-cavitary aspergilloma of the right lung may have led to the discharge of metabolic products of A. niger, including the oxalate crystals, out of the cavity, and thence into the left lung, and that these metabolic products caused the lung injury. The pathological diagnosis in our patient could not distinguish CNPA from active aspergilloma. Some CNPA reported to date may have involved invasive aspergilloma, but this distinction has little significance in regard to treatment. It is interesting that, on careful observation, the calcium oxalate crystals were recognized in the sputum. Niki et al.9 reported calcium oxalate crystals on sputum cytology and transbronchial lung biopsy in A. niger pneumonia, and they considered that the crystals in the sputum, in combination with serological assays, were useful for the early diagnosis of the Aspergillus pneumonia. It is well known that serum Aspergillus antigen (Pastorex Aspergillus; Diagnostics Pasteur, France) and beta-Dglucan are useful tools for the diagnosis of tissue invasive Aspergillus infection. In recent years, the clinical usefulness of the polymerase chain reaction for the detection of DNA for Aspergillus spp. in serum was also reported.10 However, we did not suspect Aspergillus pneumonia in our patient. If the calcium oxalate crystals had been recognized on sputum cytology in the patient’s lifetime, we may have been able to resolve the patients condition.
100
References 1. Gefter WB, Weingrad TR, Epstein DM, Ochs RH, Miller WT. “Semi-invasive” pulmonary aspergillosis. Radiology 1981;140: 313–21. 2. Binder RE, Faling LJ, Pugatch RD, Mahansen C, Snider GL. Chronic necrotizing pulmonary aspergillosis: A discrete clinical entity. Medicine 1982;61:109–23. 3. Kimmerling EA, Fedric JA, Tenholder MF. Invasive Aspergillus niger with fatal pulmonary oxalosis in chronic obstructive pulmonary disease. Chest 1992;101:870–2. 4. Hebisawa A, Kurashima A, Nagai H, Komatsu H, Yoneda R, Saiki S. Pathology of bronchopulmonary aspergillosis (in Japanese). Kekkaku 1997;72:109–18. 5. Yousem SA. The histological spectrum of chronic necrotizing forms of pulmonary aspergillosis. Hum Pathol 1997;28:650– 6.
N. Matsuda et al.: EGF receptor and osteoblastic differentiation 6. Caras WE, Pluss JL. Chronic necrotizing pulmonary aspergillosis: pathologic outcome after itraconazole therapy. Mayo Clin Proc 1996;71:25–30. 7. Kurrien F, Green GH, Rowles SL. Localized deposition of calcium oxalate around a pulmonary Aspergillus niger fungus ball. Am J Clin Pathol 1975;64:556–63. 8. Yoshida K . The correlation between tissue injury and calcium oxalate crystal production in rat’s lung with experimental Aspergillus niger infection (in Japanese). J J A Infect Dis 1998;72:621– 30. 9. Niki Y, Hashiguti K, Tamada S, Yoshida K, Sugimura S, Nakajima M, et al. A case of Aspergillus niger pneumonia cured with an early diagnosis (in Japanese). J J A Infect Dis 1994;68:788– 91. 10. Yamakami Y, Hashimoto A, Tokimatsu I, Nasu M. Detection of DNA specific for Aspergillus species in serum of patients with invasive aspergillosis by polymerase chain reaction. J Clin Microbiol 1996;34:2464–8.