A 37-year-old Japanese man presented to our hospital with a nonproductive cough of two weeks in duration. He did not have fever or dyspnea. He had a history of right hemiparesis, intellectual disability with pica, and symptomatic epilepsy caused by intracerebral hemorrhage, which occurred at two years of age. He had never smoked or consumed alcoholic beverages.
His initial vital signs were as follows: blood pressure, 105/55 mm Hg; pulse rate, 70 beats/minute; respiratory rate, 18 breaths/min; SpO2, 93% in room air; body temperature, 36.5 C. There was no lymphadenopathy. Auscultation revealed no chest rales. A cardiovascular examination was normal, and no murmurs, rubs, or gallops were detected. Abdominal and neurological examinations were unremarkable, and the patient had no rash or petechiae. A chest radiograph revealed bilateral diffuse infiltration (Figure 1). Chest computed tomography (CT) revealed bilateral airspace consolidation and ground-glass opacity (Figure 2).
The patient's laboratory test values were as follows: hemoglobin, 14.9 g/dl; white blood cell count, 8,850/mm3 with a left shift; platelets, 329,000/mm3; serum aspartate aminotransferase 29 U/L (normal, 0-35 U/l); serum alanine aminotransferase, 31 U/L (normal, 0-35 U/l); serum lactate dehydrogenase, 425 U/L (normal, 119-229 U/l); serum total protein, 5.3 g/dl (normal, 6.5-8 g/dl); serum albumin, 2.1 g/dl (normal, 4-5 g/dl); serum C-reactive protein, 9.18 mg/dl (normal, < 0.2 mg/dl); serum KL-6, 2940 U/ml (normal, < 500 U/ml); serum surfactant protein D, 173.0 ng/ml (normal, < 109.9 ng/mL); and serum surfactant protein A, 115.0 ng/ml (normal, < 43.8 ng/mL). The patient's serum was negative for rheumatoid factor and antinuclear antibodies. The serum levels of immunoglobulin M, G, and A were within the normal ranges. An electrocardiogram revealed normal findings. An examination of the patient's sputum showed no predominant pathogen and no acid-fast organisms were observed on staining. Two sets of blood cultures were prepared at the time of admission; however, they did not yield any organisms.
The patient underwent a fiberoptic bronchoscopic examination that revealed a normal endobronchial system, and combined bronchoalveolar lavage (BAL)/transbronchial biopsy (TBLB) was performed. BAL fluid (BALF) was obtained from the right middle lobe. The results of the BALF analysis were as follows: histiocytes, 87%; neutrophils, 6%; lymphocytes, 4%; and eosinophils, 3%. Routine cultures of bronchial the washings were negative. The TBLB sample from the right upper lobe revealed alveolar septal thickening due to chronic inflammation, as well as collagen-type fibrosis.
After these examinations, the patient was diagnosed with acute interstitial pneumonia, and intravenous levofloxacin (500 mg) was administered once daily with corticosteroid pulse therapy (methylprednisolone [1000 mg] for three days) followed by prednisolone (1 mg/kg/day). On the 5th day after the initiation of therapy, his respiratory condition worsened and noninvasive positive pressure ventilation was started. His interstitial pneumonia was thought to be getting worse, and cyclophosphamide (500 mg/body) was administered intravenously. On the same day, an additional examination revealed the elevation of the serum (1-3) beta-D glucan (BG) level (104.3 pg/ml; normal, <6.0 pg/ml). He was therefore suspected to have fungal infection or PCP, and voriconazole (200 mg, every 12 hours) and sulfamethoxazole trimethoprim (1600 mg and 320 mg, respectively, every 8 hours) were started. An additional HIV antibody test was negative and the serum protein electrophoresis revealed normal findings. Despite the additional antifungal therapy, his respiratory status gradually worsened, and intravenous corticosteroid pulse therapy (methylprednisolone [1000 mg] for three days) and cyclophosphamide therapy (500 mg/body) were each administered a second time, on the 8th and 11th days, respectively, without improvement. The patient died due to respiratory failure on the 12th day.
A postmortem pathological examination of the lung tissue demonstrated that the alveolar spaces were filled with foamy amorphous material composed of abundant numbers of cystic forms of Pneumocystis jirovecii and cellular debris, as well as an inflammatory reaction with hyaline membranes (Figure 3). Retrospectively, Grocott's methenamine silver (GMS) staining of the BALF and TBLB samples obtained on the day of admission revealed a small amount of the cystic form of Pneumocystis jirovecii (Figure 4). It was therefore thought that PCP had been present on the day of his admission.