A 64-year-old woman was referred to our hospital for bronchial asthma with atypical pneumonia unresolved by antibiotic treatment. She had no history of being diagnosed as asthma but had suffered from intermittent sensation of chest constriction by exposure to cold air.
She had taken steroid for her joint arthritis without consulting a doctor for several years. She has never smoked and had no history of tuberculosis, diabetes mellitus or other cardiovascular disease. About 20 days before admission, the patient suffered from fever, cough, sputum and dyspnea. She visited another hospital and was treated with antibiotics and steroids. Despite treatment, there was no clinical improvement of her symptoms. She was referred to our hospital for further evaluation.
On admission, her body temperature was 37.2 C, pulse rate was 110/min, respiration rate was 24/min and blood pressure was 160/100 mmHg. Physical examination revealed bilateral diffuse inspiratory crackle without wheezing. Laboratory tests were performed: white blood cell count was 48,220/muL (neutrophils were 98%, monocytes 1% and lymphocytes 1%), hemoglobin 11.2 g/dL, hematocrit 32.1% and platelet count 394,000/muL on complete blood cell counts. Arterial blood gas analysis findings were pH 7.497, PaCO2 42.5 mmHg, PaO2 63.4 mmHg, bicarbonate 32.6 mmol/L and oxygen saturation 93.3% on oxygen 3 L/min via nasal prong. Sodium was 126 mEq/L, potassium 2.7 mEq/L, chloride 98 mEq/L, urea nitrogen 13.9 mg/dL, creatinine 1.24 mg/dL, cholesterol 168 mg/dL, total protein 5.1 mg/dL, albumin 2.6 mg/dL, AST 22 IU/L, ALT 22 IU/L and total bilirubin was 0.82 mg/dL on blood chemistry. Chest radiography and high-resolution computed tomography (HRCT) showed multifocal variable-sized consolidation with reticulonodular opacities (Figure 1) and cavitary lesion in both upper lobes and right lower lobe. There were also multiple small nodular densities and ground glass attenuation around the consolidation (Figure 2A, B).
Microscopic examination of sputum showed no acid-fast bacilli. Other laboratory findings, including IgG, IgM, IgA, IgE PRIST, C3, C4, CH50, rheumatoid factor (RF), antinuclear antibody (ANA), anti-neutrophil cytoplasmic antibody (ANCA), antistreptolysin-O (ASO), VDRL and cold cryoglobulin, were all negative.
Despite empiric broad-spectrum antibiotics and steroid treatment, dyspnea progressively aggravated. Open lung biopsy was done on the tenth hospital day. Histopathologic findings of the biopsy specimen showed large areas of necrotizing pneumonia with an infarct-like appearance (Figure 3A). There were some scattered fungal hyphae within the lung parenchyma (Figure 3B). The bronchi and bronchioles often showed dilated lumen which were filled with mucus, numerous necrotic debris, inflammatory cells and branching septated hyphae characteristic of aspergillus. Some terminal bronchioles were found to be destroyed and were replaced by granulomatous inflammation (Figure 4). The bronchocentric granulomatous reaction extended into the adjacent lung parenchyma to a degree. Gomori-Methenamine-Silver (GMS) staining revealed many fungal hyphae consistent with aspergillus species. There was no evidence of angioinvasion by aspergillus or aspergillous emboli. With an impression of invasive aspergillus infection with BCG-like elements, 15 mg of amphotericin-B once day was administered intravenously and the dose was increased up to 30 mg daily. Steroids was tapered progressively. There were some improvement in her clinical symptoms. However despite vigorous antifungal treatment, sudden respiratory arrest occurred due to acute tracheobronchial tree obstruction with bronchial casts on the thirty-fourth hospital day. Histopathologic examination of the casts revealed fibrinoid necrotic tissue containing neutrophils, a few metaplastic squamous cell nests and variably fragmented fungal hyphae (Figure 5).