A 29-year-old woman presented with fever and productive cough at our hospital. She had undergone thymectomy for thymoma 9 years ago and had comorbid myasthenia gravis, pure red cell aplasia, and autoimmune hepatitis. She was prescribed immunosuppressants including cyclosporine (200 mg/d) and prednisolone (5 mg/d). Radiotherapy was initiated for a recurrent thymoma lesion 2 weeks before her admission delivered to a total dose of 54 Gy in 27 fractions (Fig. 1). Her bone marrow was an area spared from radiation therapy.
Pneumococcal pneumonia episode in the previous months were remarkable in her medical history. Her chest examination revealed bilateral coarse crackles and rhonchi. Laboratory examination revealed leukocytosis with a left shift and elevated C-reactive protein. Hypogammaglobulinemia, fungal antigens, and Mycobacterium tuberculosis infection were unremarkable on the interferon-gamma release assay and anti-HIV antibodies. Chest computed tomography (CT) revealed infiltrations and a granular shadow in the bilateral lobes (Fig. 2A). She was diagnosed with broncho-pneumonia and hospitalized.
After admission, a 14-d course of piperacillin-tazobactam was initiated for broncho-pneumonia, and her symptoms and laboratory findings improved. However, after switching from piperacillin-tazobactam to an oral antimicrobial (levofloxacin), pneumonia reexercabted (Fig. 2B).
Therefore, piperacillin-tazobactam treatment was resumed and pneumonia was under control again; however, drug fever and granulocytopenia caused by piperacillin-tazobactam was observed and hence cefepime was administered as an alternative. However, severe drug eruptions were observed 4 d after switching to cefepime, and drug eruption exacerbated even after a switch to meropenem. Therefore, antimicrobial treatment was discontinued. Antimicrobial therapy with cefepime, piperacillin-tazobactam, and meropenem were administered for 21 d. Drug eruption improved with no treatment after discontinuation of antimicrobial therapy. Immunodeficiency was suspected as the cause of recurrent lower respiratory tract infections because peripheral CD4-positive cells were reduced to 284 mu/L, and lymphocytopenia (<1,000/muL) occurred after radiation therapy for recurrent thymoma. Hypogammaglobulinemia was not observed; nonetheless, immunoglobulin was administered at 5,000 mg once daily for three consecutive days for severe infection. Furthermore, cyclosporine was gradually tapered to 100 mg/d after admission to control pneumonia. After discontinuation of antimicrobial therapy, fever recurred and the oxygen demand increased, and CT revealed new consolidation in her lower lobe of the left lung (Fig. 2C).
For the third treatment cycle for pneumonia, a combination of vancomycin and doripenem, plus immunoglobulin, was initiated, because methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas fluorescens were detected in sputum cultures after hospitalization. Despite intensive treatment, no improvement in the oxygen demand and fever was observed. Since the patient had pneumonia refractory to broad-spectrum antimicrobial agents, pneumonia caused by agents other than bacterial was suspected as the cause of the respiratory failure and pneumonia findings on chest CT. Simultaneously, candidiasis was noted in the oral cavity (Fig. 3), and the decline in CD4-positive cells suggested T-cell immunodeficiency.
Furthermore, based on elevated serum beta-D glucan levels and a positive PCR test for Pneumocystis jirovecii in sputum samples, P. jirovecii pneumonia was diagnosed as a cause of respiratory failure. Along with antimicrobial treatment, sulfamethoxazole (3,600 mg/d) and trimethoprim (720 mg/d) were initiated, and prednisolone was administered at 80 mg/d. Respiratory failure improved rapidly, and the infiltrative shadow on chest X-ray was obliterated. Prednisolone was tapered to a maintenance dose over 2 weeks, and anti-biotherapy and sulfamethoxazole/trimethoprim were administered for 3 weeks each and completed. During hospitalization, the peripheral lymphocyte count was elevated to almost 2,000/muL, and she was discharged on hospitalization day 99 without pneumonia recurrence after treatment for P. jirovecii pneumonia. Her clinical course after admission is described in Fig. 4. During her hospitalization, her gammaglobulin levels remained within the normal range, while her peripheral lymphocyte counts tended to slowly increase.
Chest computed tomographic images on the third onset of pneumonia. . Consolidation of the right upper lobe improved, and a novel extensive infiltrative shadow was observed from the upper region to the basilar region of the left lower lobe.