Invasive Aspergillus niger with Fatal Pulmonary Oxalosis in Chronic Obstructive Pulmonary Disease

even in the absence of cardiac function, cardiopulmonary bypass resuscitation is more effective than lAB D in cardiac arrest." The time to cardiopulmonary bypass is extremely important in reducing mortality and morbidity after failed PTCA. S.6 New portable systems currently available allow rapid institution of cardiopulmonary bypass in the catheterization laboratory. Percutaneous methods have been reported to afford prophylactic circulatory support for the high-risk patient undergoing PTCA or for emergency resuscitation following failed PTCA and cardiac arrest.v' Percutaneous cannula insertion in the catheterization laboratory has been demonstrated to be rapid, safe, and relatively simple and can be accomplished during cardiac massage and defibrillation attempts. K.9 Along with the compact size of the portable system and the ease of application of the technique, this helps allow cardiopulmonary bypass support to be readily available in the catheterization laboratory setting. Percutaneous cardiopulmonary bypass may reduce reperfusion injury following acute coronary occlusion, thus limiting myocardial damage. 10 By affording hemodynamic stability and myocardial protection following acute catastrophic coronary occlusion during PTCA, emergent portable cardiopulmonary bypass may be lifesaving and may help improve long-term morbidity. ACKNO\VLEDGMENT: The authors wish to thank Pam Pottorff for her secretarial assistance in preparation of this manuscript.

REFERENCES

2

3 4

5

Brahos G, Baker N, Ewy H, Moore ~ Thomas J, Sanfelippo ~ et aI. Aortocoronary bypass following unsuccessful PTCA: experience in 100 consecutive patients. Ann Thorne Surg 1985; 40:7-10 Shawl F, Domanski M, Hernandez T, Punja S. Emergency percutaneous cardiopulmonary bypass support in cardiogenic shock from acute myocardial infarction. Am J Cardiol 1989; 64: 967-70 Overlie e Emergency use of portable cardiopulmonary bypass. Cathet Cardiovasc Diagn 1990; 20:27-31 Levine R, Gorayeb M, Safar ~ Abramson N, Stezoski ~ Kelsey S. Cardiopulmonary bypass after cardiac arrest and prolonged c1osed-chest CPR in dogs. Ann Emerg Med 1987; 16:29-36 Reul G, Cooley D, Hallman G, Duncan J, Livesay J, Frazier 0, et aI. Coronary artery bypass for unsuccessful percutaneous transluminal coronary angioplasty. J Thorac Cardiovasc Surg 1984; 88:685-94

6 Shawl FA. Percutaneous cardiopulmonary bypass support in high risk interventions. J Invasive Cardioll989; 1:287-93 7 V()~el JHK, Ruiz CE, Jahnke EJ, McFadden RB, Setty R, West C, et aI. Percutaneous (nonsurgical) supported angioplasty in unprotected left main disease and severe left ventricular dysfunction. Clin Cardioll989; 12:297-300 8 Shawl FA, Domanski MJ, Wish MH, David M, Punja S, Hernandez TJ. Emergency cardiopulmonary bypass support in patients with cardiac arrest in the catheterization laboratory. Cathet Cardiovasc Diagn 1990; 19:8-12 9 Shawl FA, Domanski MJ, Wish MH, Davis M. Percutaneous cardiopulmonary bypass support in the catheterization laboratory: technique and complications. Am Heart J 1990; 120:195203

10 Axelrod HI, Murphy MS, Galloway AC, Baumann FG, Laschinger JC, Colvin SB, et aI. Percutaneous cardiopulmonary bypass limits myocardial injury from ischemic fibrillation and reperfusion. Circulation 1988; 78(suppI3):I48-52

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Invasive Aspergillus niger with Fatal Pulmonary Oxalosls In Chronic Obstructive Pulmonary Disease* Erick A l(jmmerling, D.Q;t joseph A. Fedrick, M.D.;* and Michael F. Tenholder, M. D., F.C. C. ~§

The ubiquitous Aspergillus fungus has numerous manifestations when associated with lung disease (primary Aspergillus pneumonia, aspergilloma, allergic bronchopulmonary aspergillosis, and invasive Aspergillus). This fungus also can colonize preexisting lung disease in an indolent manner and then acutely assume a more invasive nature. Although the species Aapergillua niger is infrequendy encountered, the endobronchial visualization of black necrotic debris or a fungus bailor the Bnding of black acidic sputum or pleural 8uid suggests the presence of A niger and the destructive by-product of its fermentation, oxalic acid. (Chat 1992; 101:810-72) AspergiUus niger has been infrequently described as an invasive pathogen in the past.'.... Most cases are seen in patients with severe underlying altered immune defenses.v" The following case describes the occurrence of invasive A niger in a nonimmunosuppressed patient with chronic obstructive lung disease and previous Mycobacterium aviumintracellulare (MAl) pulmonary infection. It demonstrates the severe destructive nature of oxalic acid, an associated by-product of the metabolism of this fungus.

.l1

CASE REpORT

A 64-year-old white man with a long history of severe chronic obstructive pulmonary disease (forced vital capacity, 3.14 L; FEV 1, 1.22 L; FEV1%, 39 percent) was admitted with a one-week history of fever, cough, hemoptysis, and left pleuritic chest pain. He had a 100 pack-year history of tobacco use, and he had worked in the spinning room of a cotton mill for 20 years. He had been given a diagnosis of MAl 6brocavitary disease of the right upper lobe and had completed an 18-month course of daily therapy with isoniazid (300 mg), rifampin (600 mg), ethambutol (1,000 mg), and pyrazinamide (2,000 mg) six months prior to this admission. The patient had no other previous illnesses or exposures to chemicals, toxins, animals, or industrial vapors. He denied weight loss, diabetes mellitus, alcohol abuse, or previous prednisone therapy. His blood pressure was 13G'78 mm Hg, his pulse rate was 96 beats per minute; his respiratory rate was 32 breaths per minute; and his oral temperature was 37 .2°C. He was a well-developed man in moderate respiratory distress. There were diJJuse, bilateral expiratory wheezes; increased bronchial breath sounds in both upper lobes; and a pleuritic rub heard over the left upper posterior chest wall. The hemoglobin level was 12.1 Wdl, and the total leukocyte count was 13,OOOIcu mm. The total protein value was 8.0 Wdl, with an albumin level of 4.0 Wdl. Immunoelectrophoresis demonstrated polyclonal gammopathy. Testing for human immunodeficiency virus was negative. A chest roentgenogram revealed bilateral upper lobe *From the Medical College of Georgia and VA Medical Center, Augusta. tFellow in Pulmonary Medicine. *Resident, Pathology Service. §Associate Professor of Medicine, Medical College of Georgia, and Chief, Pulmonary Disease Section, VA Medical Center. This work was supported by the Research Service of the Veterans Affairs Medical Center, Augusta, Ga. InvasIYe A. niger with Fatal Pulmonary 0xaI0sis (Kimmerling, Fedrick, Tenholder)

in the cavity, as well as the chest wall, and were id,'ntified by polarization techniques. Both lungs showed emphysema. anthracosis, and multiple granulomas with caseation necrosis. Postmortem culture grew A nig,,,., but no other residual acid-fast bacilli. bacteria. or fungi were detected by smear or culture . DISCUSSION

FIGURE 1. Postero-anterior chest roentgenogram shows bilateral upper lobe cavitation with a new infiltrate in the left cavity.

scarring and cavity formation with a new lingular infiltrate (Fig 1). A sputum Gram stain showed many white blood cells and mixed respiratory flora. The patient was started on a regimen ofintravenous cefuroxime, 1.5 ~ every 8 h. Approximately 24 h after admission, the patient's respiratory status deteriorated, and he was intubated. Due to the onset of acute respiratory failure, increasing leukocytosis (16,SOO/cu mm), increasin~ temperature (38.9°C), and absence of an isolatable organism. emergent bronchoscopy was performed . No endobronchial pathologic changes were seen, but smears were positive for Candida, Aspergillus, and a single acid-fast bacillus. Cultures grew only Pseudomonas maltophilia, sensitive to ceftazidime and gentamicin, and therapy was switched to these drugs, The patients condition continued to deteriorate, with increased leukocytosis (24,OOOIcu mm) and hypoxia . The chest x-ray 6lm showed progression of the 6brocavitary process in the left upper lobe. A second 6beroptic bronchoscopy was performed . After removal of multiple specimens of a black, friable , gritty material by transbnmchial biopsy, close inspection of the apieoposterior segmental bronchus demonstrated that this bronchus actually opened into a large cavity. There was direct visualization of an eccentrically located black, glistening mass in the cavity. Transbronchial biopsy specimens revealed necrotic tissue, calcium oxalate crystals, Aspergillus hyphae, and Candida. Culture of the transbronchial biopsies grew A niger and Candida albicans . All previously ohtained blood cultures were negative for bacterial, fungal, or acid-fast organisms. Despite intravenous amphotericin B therapy and bronchoseopically guided intracavitary instillation of 50 mg of amphotericin B, the patient died on the eighth hospital day. Postmortem examination of the thoracic cavities was remarkable for involvement of the left thoracic cavity with extensive adhesions, fibrosis, caseation, and necrotic tissue. The left chest wall also was invaded by a mat of white mycelia with numerous areas of confluent black fruiting bodies. A lactophenol cotton hlue stain revealed masses of dichotomously branching hyphae with well-formed septa consistent with A niger (Flg 2). Calcium oxalate crystals were found

Aspergillus species are ubiquitous organisms, which are spread by aerosolization of the spores. The most common species involved in human lung diseases an' Aspergillus fumigatus, Aspergillus fiavus, and A niger; in decreasing frequency of occurrence .' The most common predisposing factor to the formation of an aspergilloma is the presence of a preexisting lung cavity. Aspergillornas have been identified in cavities associated with a wide array of lung diseases, including tuberculosis, histoplasmosis, sarcoidosis, bronchial cysts, asbestosis, ankylosing spondylitis, bronchiectasis, and malignant diseases.' In this case, we feel that bronchiectatic changes from a preexisting MAl infection predisposed the patient to this pattern of infection. Mycetomas have been found within several weeks after acute necrotizing lung infections. Metzger and colleagues" described a diabetic man with a right upper 4 X 5-cm cavity with sputum growth of Serratia marcescens, Klebsiella pneumoniae, lToteus mirabilis; and A niger. Thoracentesis revealed black turbid fluid with a pH less than 5.9. Lactophenol cotton blue preparations of both fluid and sputum showed septate hyphae. The patient survived with surgical resection and a prolonged course of intravenous amphotericin B. Some aspergillomas follow a very benign course and either remain stable, increase in size, or spontaneously resolve without treatment.' Many cause hemoptysis and are

FIGURE

2. A lactophenol cotton blue mount taken from matt-rial

growing on the left chest wall demonstrates A niger. The black

staining fruiting bodies from which this species received its name are apparent (original magnification x 4(0). CHEST I 101 13 I MARCH. 1992

871

treated by surgical removal, bronchial artery embolization, or intracavitary instillation of antifungal drugs. Under unusual circumstances, however, the behavior of an aspergillorna may change from a chronic, benign lesion into an invasive, life-threatening infection, as in our patient. Two distinct pathologic patterns of invasion exist. The most dramatic is the rapidly developing acute invasive pulmonary aspergillosis, which is found almost exclusively in immunosuppressed and myelosuppressed patients," Cases like ours, without a predisposing immune compromise, are infrequently reported.?" In vitro testing has verified the critical role of phagocytic cells in host defense against Aspergillus, but some role for lymphocyte-directed, cellmediated immunity has also been proposed.' Both our case and that of Metzger et al3 demonstrate that acute invasive pulmonary aspergillosis can occur simultaneously with acute bacterial pneumonia with fever, nonproductive cough, pleuritic chest pain, and a pleural friction rub. The most common initial radiographic pattern in this situation is patchy bronchopneumonia at multiple peripheral sites. As the infectious process progresses, cavitation is seen in the areas of infiltration. A more indolent form of invasive aspergillosis, called chronic necrotizing pulmonary aspergillosis or semi-invasive pulmonary aspergillosis, has also been described. 8,9 This infection most commonly occurs in mildly immunocompromised hosts (eg, patients with diabetes mellitus and patients receiving low-dose corticosteroids) and progresses slowly over several months. The radiographic hallmark of this type of infection is the development of slowly evolving infiltrates with cavitary formation. These hosts, in contrast to those with the acute form, have a productive cough with positive sputum cultures for Aspergillus. It is interesting to consider the role of oxalic acid in this destructive and invasive process. The association of oxalic acid as a fermentation product of Aspergillus sp (most notably A niger) was 6rst reported in 1891 by Wehmer. 10 Nime and Hutchins!' describe not only the local destructive nature of calcium oxalate but also the systemic complications of acute widespread oxalosis. Kurrien and co-workers 12 reported an A niger fungus ball in a patient who died of massive hemoptysis. Oxalic acid was incriminated in the blood vessel destruction by identifying oxalate crystals by polarization. The appearance of black sputum with an acidic pH in pleural fluid, sputum, or cavitary washings should suggest the presence of A niger infection and/or invasion. We have described a patient with emphysema and a subsequent secondary infection with MAl. This resulted in formation of numerous caseating granulomas throughout the lung parenchyma with fibrotic cavitary lesions in both upper lobes. These lesions became secondarily colonized with Aspergillus, which existed in a chronic necrotizing state for several months. With the Aspergillus growth, the metabolic by-product oxalic acid may have caused further tissue destruction, which extended into the chest wall. This final insult from this invasive A niger infection led to respiratory failure and death in a patient whose pulmonary reserve was already severely compromised. REFERENCES 1 Young RC, Bennett JE, Vogel CL, Carbone P~ DeVita Yr. Aspergillosis: the spectrum of the disease in 98 patients. 872

Medicine 1970; 49:147-73 2 Bode FR, Pare J~ Fraser RG. Pulmonary diseases in the compromised host. Medicine 1974; 53:255-93 3 Metzger JB, Garagusi VF, Kerwin DM. Pulmonary oxalosis caused by Aspergillus niger: 1984; 129:501-02 4 Pennington JE. Aspergillus lung disease. Med Clin North Am 1980; 64:475-90 5 Williams OM, Krick JA, Remington JS. Pulmonary infection in the compromised host. Ann Rev Respir Dis 1976; 114:359-94 6 Cooper JAD, Weinbaum DL, Aldrich TK, Mandell CL. Invasive aspergillosis of the lung and pericardium in a nonimmunocompromised 33 year old man. Am J Med 1981; 71:903-07 7 Brown E, Freedman S, Arbeit R, Come S. Invasive pulmonary aspergillosis in an apparently non-immunocompromised host. Am J Med 1980; 69:624-28 8 Gefter WB, Weingrad TR, Epstein DM, Ochs RH, Miller WT. "Semi-invasive" pulmonary aspergillosis. Radiology 1981; 140: 313-21 9 Binder RE, Faling LJ, Pugatch RD, Mahasaen C, Snider GL. Chronic necrotizing pulmonary aspergillosis: a discrete clinical entity. Medicine 1982; 61:109-24 10 Raper KB, Fennell DI. The genus Aspergillus. Baltimore: Williams & Wilkins, 1965 11 Nime FA, Hutchins GM. Oxalosis caused by Aspergillus infection. Johns Hopkins Med J 1973; 133:183-94 12 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

Acute Myocarditis in Fulminant Systemic Sclerosis· Barry S. Clemson, M.D.; Wayne R. Miller, M.D.; Luck~ M.D.; and john A. Fenss, M.D.

Jerry C.

Myositis and myocarditis have been reported in progressive systemic sclerosis, and these patients have had favorable therapeutic responses to intravenous pulse methylprednisolone. Thus far, premortem biopsy documentation of myocarditis and myocardial fibrosis has not been reported in such patients. We report the case of a patient with subacute congestive heart failure six months after she developed Raynaud's phenomenon. Clinical examination was typical of scleroderma but there was no proximal muscle weakness. She had elevated creatine kinase and MB-creatine kinase and laboratory evidence of hypothyroidism. Echocardiogram demonstrated four-chamber dilatation and severe left ventricular dysfunction. Cardiac catheterization revealed normal epicardial coronary arteries and severely decreased cardiac index. A skin biopsy specimen of the forearm was consistent with diffuse systemic sclerosis, and an endomyocardial biopsy specimen demonstrated mild fibrosis and lymphocytic infiltrate. Her heart failure initially improved with digoxin, furosemide, and enaIaprii. She also received L-thyroxine and intravenous methylprednisolone. The heart failure progressed over the next six weeks and she died. Patients with scleroderma and new-onset heart failure (Chest 1992; 101:872-74) may have acute myocarditis. *From the Department of Medicine, Divisions of Cardiology and Rheumatology, The Milton S. Hershey Medical Center, The Pennsylvania State University, Hershey, Pa. Reprint requests: Dr. Clemson, Hershey Medical Center, Division of Cardiology, Box 850~ Hershey~ lb 17033 Acute Myocarditis (Clemson at 81)