Fatal Massive Hemoptysis in a Patient on Low-Dose Oral Prednisone: Chronic Necrotizing Pulmonary Aspergillosis Case Reports Fatal Massive Hemoptysis in a Patient on Low-Dose Oral Prednisone: Chronic Necrotizing Pulmonary Aspergillosis Bobbak Vahid MD and Paul E Marik MD We report a case of chronic necrotizing aspergillosis in a 74-year-old man with chronic lung disease, who was on low-dose oral prednisone. The patient was treated with various antibiotics but had no improvement. Samples obtained via bronchoscopy grew Aspergillus, and the patient was started on lipid formulation amphotericin B. Three days after admission the patient developed fatal massive hemoptysis, presumably secondary to acquired systemic-to-pulmonary vascular communication. This is an unusual presentation of a rare manifestation of pulmonary aspergillosis. A high index of suspicion is needed to diagnose this condition in susceptible patients. Key words: chronic necrotizing aspergillosis, hemoptysis, pulmonary mycosis. [Respir Care 2007;52(1):56 –58. © 2007 Daedalus En- terprises] Introduction Chronic necrotizing pulmonary aspergillosis was first described in 1981 by Gefter et al,1 who described 5 pa- tients with locally invasive pulmonary aspergillosis. Gefter et al used the term “semi-invasive pulmonary aspergillo- sis” to differentiate this clinical entity from colonization of the respiratory tract and frank pulmonary invasive aspergil- losis.1 In 1982, Binder et al2 cited 22 cases in the literature that were consistent with the diagnosis of chronic necro- tizing pulmonary aspergillosis, and coined the term “chronic necrotizing aspergillosis.” Terms that were used to de- scribe cases of chronic necrotizing pulmonary aspergillo- sis before 1982 were “primary pulmonary aspergillosis,” “pulmonary aspergillosis with cavitation,” and “symptom- atic pulmonary aspergilloma.”2 Massive hemoptysis is a rare and potentially fatal com- plication of chronic necrotizing pulmonary aspergillosis. We describe a case of chronic necrotizing pulmonary as- pergillosis that was misdiagnosed as bacterial pneumonia for several months and led to massive hemoptysis, with a fatal consequence. Case Summary A 74-year-old African American man was admitted to the hospital for dyspnea, weight loss, and chronic cough. A chest radiograph and chest computed tomogram (Fig. 1) showed bilateral pulmonary consolidations. Review of a chest radiograph from 2 months before this presentation revealed progression of infiltrates in the left upper and left lower lobes. No cavitary lesions were seen. The patient had been treated with several courses of various antibiotics (azithromycin, levafloxicin, and doxycycline) during the several months before this presentation, but his fever, cough, and dyspnea progressed. His medical history was notable for chronic obstructive pulmonary disease (COPD), hypertension, diabetes mellitus, and gastroesophageal re- flux disease. The COPD was diagnosed 5 years before this presentation. The patient reported frequent hospital admis- sions for COPD exacerbations. His last spirometry showed severe airway obstruction (forced expiratory volume in the first second 0.83 L). The patient was a smoker for 50 years. He also reported a tuberculosis exposure in the past, but his recent skin tuberculin test was nonreactive. He also had a substantial asbestos exposure when he worked at a Navy shipyard. His medications on presentation to us in- cluded metformin, lisinopril, aspirin, oral prednisone (10 mg/d for about 2 years, for COPD), and an as-needed bronchodilator. Bobbak Vahid MD and Paul E Marik MD are affiliated with the Depart- ment of Pulmonary and Critical Care Medicine, Thomas Jefferson Uni- versity, Philadelphia, Pennsylvania. The authors report no conflicts of interest related to the content of this paper. Correspondence: Bobbak Vahid MD, Department of Pulmonary and Crit- ical Care Medicine, Thomas Jefferson University, 834 Walnut Street, Suite 610, Philadelphia PA 19107. E-mail: bobbak.vahid@mail.tju.edu. 56 RESPIRATORY CARE • JANUARY 2007 VOL 52 NO 1 Physical examination on admission showed a tempera- ture of 38.0°C, blood pressure of 146/82 mm Hg, heart rate of 96 beats/min, respiratory rate of 20 breaths/min, and oxygen saturation of 87% on room air. He was in mild respiratory distress. Chest examination revealed bilateral crackles. The heart and abdominal examination was unre- markable. There was no peripheral edema or clubbing. Laboratory findings were: white-blood-cell count 8.5 � 103/�L, hemoglobin 8.6 g/L, and creatinine of 1.2 mg/dL. Bronchoalveolar lavage fluid collected during bron- choscopy grew Aspergillus fumigatus. The bronchoalveo- lar lavage fluid bacterial, viral, and mycobacterial cultures were negative. Chronic necrotizing pulmonary aspergillo- sis was suspected, and the patient was started on lipid formulation amphotericin B. Three days after presentation, the patient developed massive hemoptysis and died sec- ondary to respiratory failure. The lungs at autopsy showed patchy pulmonary parenchymal invasion of fungal ele- ments, with involvement of the bronchial wall, consistent with chronic necrotizing pulmonary aspergillosis (Fig. 2). There was no vascular invasion. Although there was pleu- ral thickening and chronic inflammation, we found no As- pergillus invasion of the pleura, nor disseminated aspergil- losis in other organs. The massive hemoptysis was thought to be secondary to acquired systemic-to-pulmonary vas- cular communications seen in chronic inflammatory and infectious diseases of the lung. Discussion Chronic necrotizing pulmonary aspergillosis is defined as an indolent but destructive inflammatory lung infection by invasive Aspergillus species (usually A. fumigatus), and is characterized by local invasion of lung tissue by fungal elements, but absence of vascular invasion. Although chronic necrotizing aspergillosis is progressive over sev- eral months, there is no dissemination to other organs.3,4 Chronic necrotizing pulmonary aspergillosis is usually seen in middle-age and elderly patients. Symptoms are nonspecific and include fever, cough, hemoptysis, and weight loss of 1– 6 months duration.4 Most patients with chronic necrotizing pulmonary aspergillosis have either underlying chronic lung diseases or systemic diseases that predispose them to the disease. In one study, 9% of pa- tients had no reported risk factors and 37% of patients had multiple risk factors. The pulmonary risk factors include COPD, interstitial lung disease, previous mycobacterial infections, asthma, cystic fibrosis, previous lung resection, sarcoidosis, and pneumoconiosis.3– 8 The systemic risk factors are diabetes mellitus, low-dose corticosteroids, rheu- matoid arthritis, ankylosing spondylitis, and malnutri- tion.1,3,4 Other rare clinical manifestations are pneumotho- rax,9 immune reconstitution syndrome in patients infected with human immunodeficiency virus who are on antiret- roviral therapy,6 pulmonary infiltrates following crypto- coccal infection,10 and Pancoast syndrome.11 Radiographic findings include an infiltrative process in the upper lobes or superior segment of the lower lobes, and cavitary le- sions, with adjacent pleural thickening. A mycetoma (fun- gus ball) can be seen in about 50% of patients with cav- itary lesions. Histologic examination of the lung parenchyma shows necrotizing granulomas, invasion and destruction of lung tissue by mycetoma, or primary bron- chiolar infection.3,4 Fig. 1. Chest computed tomogram showing bilateral infiltrates. Fig. 2. Fungal elements, showing the 45° branching that is con- sistent with Aspergillus species (�200 silver stain). CHRONIC NECROTIZING PULMONARY ASPERGILLOSIS RESPIRATORY CARE • JANUARY 2007 VOL 52 NO 1 57 Diagnosing chronic necrotizing pulmonary aspergillosis can be challenging. Diagnosis may be helped by histologic evidence of tissue invasion by fungus, clinical and radio- graphic features consistent with the diagnosis, and isola- tion of Aspergillus from sputum or bronchoscopic samples after exclusion of other conditions. Delayed diagnosis is common and can contribute to morbidity and mortality. In one study, the average delay in diagnosis ranged from 3 months to 7 months. Treatment options include antifun- gal therapy with amphotericin B, itraconazole, or voricon- azole. Although voriconazole is equal or superior to am- photericin B for invasive aspergillosis, there are few data on chronic necrotizing aspergillosis. Surgical resection is limited to a small subset of patients with local infection, adequate pulmonary reserve, and acceptable surgical risk.3,4 Chronic necrotizing pulmonary aspergillosis should be included in the differential diagnosis of pulmonary infil- trates in a patient with pulmonary or systemic risk factors and fever, cough, dyspnea, and weight loss. Massive he- moptysis is a potentially fatal complication of chronic ne- crotizing pulmonary aspergillosis. REFERENCES 1. Gefter WB, Weingrad TR, Epstein DM, Ochs RH, Miller WT. “Semi- invasive” pulmonary aspergillosis: a new look at the spectrum of Aspergillus infections of the lung. Radiology 1981;140(2):313–321. 2. Binder RE, Faling LJ, Pugatch RD, Mahasaen C, Snider GL. 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