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Previous Volume 349:507-508 July 31, 2003 Number 5 Next

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To the Editor: We report the case of a patient with severe acute respiratory syndrome (SARS) who died of aspergillosis after prolonged treatment with corticosteroids. The patient was a 39-year-old male physician based at the intensive-care unit of a small hospital in Guangzhou, China; he had no concurrent medical illness. Many patients with SARS were admitted to the hospital where he worked during the eight weeks before April 4, 2003, when he presented with a sore throat and a low-grade fever (37.3°C). Five days later, he had a high fever (38.5°C) and a low leukocyte count (3.4 x10⁹ per liter; 63.6 percent neutrophils and 26.2 percent lymphocytes), and he was admitted to the hospital with suspected SARS.

The patient was treated with twice-daily methylprednisolone (80 mg in the morning and 40 mg in the evening) for two days; the dose was decreased to 20 mg twice daily as the fever subsided, on April 12. The fever recurred on April 14, and chest radiography showed an infiltrate in the left lower lobe; the leukocyte count was 13.5x10⁹ per liter (94.0 percent neutrophils and 6.0 percent lymphocytes). Methylprednisolone was given again (20 mg in the morning and 80 mg in the evening), and the patient was transferred to a larger hospital on April 15. Intravenous methylprednisolone therapy (80 mg twice daily) was then administered. The patient's clinical condition improved; he had no fever and could walk without dyspnea. The infiltrate in the left lung diminished in density, and the dose of methylprednisolone was reduced to 40 mg twice daily on April 19.

On April 29, the patient was again dyspneic, and radiographs showed a left basilar infiltrate. Bone marrow aspiration revealed suppression of all three cell lineages. On May 4, the patient was transferred to a university teaching hospital. Methylprednisolone (240 mg twice daily) was given, but the next day the oxygen saturation fell to 60 percent, and endotracheal intubation was performed to allow mechanical ventilation. The patient showed signs that were consistent with the presence of tentorial herniation; his pupils were fixed and dilated. Computed tomographic examination of the cranium showed diffuse cerebral edema with localized hemorrhage. Enzyme-linked immunosorbent assay and indirect immunofluorescence established the presence of specific antibodies against a SARS-associated virus in the serum. The fungal culture of sputum obtained on April 14 was negative; the bacterial cultures of sputum obtained on May 2 and May 4 were negative as well. Despite massive supportive care, the patient died on May 7.

Autopsy showed SARS-associated pathologic changes,^1,2 including consolidation, hemorrhage, and edema of the lungs; proliferation and desquamation of alveolar epithelial cells; exudation of monocytes, lymphocytes, and plasma cells in alveoli; and formation of hyaline membranes. In addition, there were multiple lung abscesses containing aspergillus (Figure 1). There was also cerebral edema, diffuse cerebral hemorrhage, aspergillus meningitis, and multiple brain abscesses containing aspergillus. Multiple abscesses containing aspergillus were also found in the heart, liver, kidney, spleen, stomach, pancreas, and adrenal glands.

View larger version (70K): [in this window] [in a new window]   Figure 1. Specimens of the Lung. Panel A shows the cut surface of a lung. The pathological specimen in Panel B shows extensive hyaline membranes, desquamated epithelial cells, and exuded monocytes in alveoli (hematoxylin and eosin, x100). Aspergillus mycelia were observed on microscopical examination of the abscess and were isolated by culture as well.

 
In this patient, it is likely that SARS infection induced mild immunosuppression³ and that immune function was further suppressed by high-dose corticosteroid treatment. At this time, it has not been established whether corticosteroid treatment has an effect on SARS-associated mortality,⁴ although it may decrease clinical morbidity.⁵ We speculate that use of corticosteroids over the course of many weeks led to the serious secondary aspergillus infection that contributed to the death of this patient. We urge caution and restraint in the use of corticosteroids in the treatment of SARS.

Huijun Wang, M.D.
Yanqing Ding, M.D.
Xin Li, M.D.
Lei Yang, M.D.
Wenli Zhang, M.D.
Wei Kang, M.D.
First Military Medical University
Guangzhou 510515, People's Republic of China
hjwang{at}fimmu.com

References

1. Ding Y, Wang H, Shen H, et al. The clinical pathology of severe acute respiratory syndrome (SARS): a report from China. J Pathol (in press). 
2. Nicholls JM, Poon LM, Lee KC, et al. Lung pathology of fatal severe acute respiratory syndrome. Lancet 2003;361:1773-1778. [CrossRef][ISI][Medline]
3. Panesar NS. Lymphopenia in SARS. Lancet 2003;361:1985-1985. [Medline]
4. Oba Y. The use of corticosteroids in SARS. N Engl J Med 2003;348:2034-2035. [Free Full Text]
5. Lee N, Hui D, Wu A, et al. A major outbreak of severe acute respiratory syndrome in Hong Kong. N Engl J Med 2003;348:1986-1994. [Free Full Text]

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