Rhabdomyolysis associated with probable SARS.

To the Editor:

Severe acute respiratory syndrome (SARS) is an emerging disease that was first recognized in November 2002 (1). Previous studies have pointed out that patients with probable SARS may have abnormal laboratory examination results, including elevated creatine kinase levels 2, 3, 4. We report 3 patients with probable SARS who developed rhabdomyolysis.

The first patient was a 38-year-old woman who suffered from probable SARS during a nosocomial outbreak in Taiwan (5). She developed fever and chills on April 20, 2003. Her chest radiograph showed bilateral pneumonic patches. Because SARS was suspected, she was admitted to our hospital on April 28. She was intubated and given midazolam and succinylcholine for respiratory failure. Fever of up to 39°C was noted on the same day. Repeat blood, urine, and sputum cultures did not yield any pathogens. Vero cells from a throat swab yielded a coronavirus. SARS-associated coronavirus infection was confirmed by detection of coronavirus ribonucleic acid by real-time reverse transcription polymerase chain reaction tests from sputum. Serum creatine kinase level increased from 21 to 13,834 U/L from May 2 to 3, while serum creatinine level increased to 3.27 mg/dL. By May 6, serum creatine kinase level had increased to a peak value of 339,750 U/L, even after hydration and alkalization, while serum myoglobin level had increased to 167 ng/mL (normal, <70 ng/mL). Rhabdomyolysis was diagnosed clinically. Acute renal failure developed on May 4 and the patient went into a deep coma. She died 3 weeks later due to secondary bacterial infection despite mechanical ventilatory support, hemodialysis, and antibiotic treatment. A skeletal muscle biopsy specimen showed necrotic muscle fibers, basophilic change of sarcoplasm, enlarged vesicular nuclei, and centrally located nuclei.

The second patient was a 52-year-old-man who suffered from probable SARS during a nosocomial outbreak at the same hospital (5). He started to have fever and chills since April 21, with myalgia and headache. A dry cough developed since April 24 and a chest radiograph revealed a pneumonia patch over the right lower lung field. Acute respiratory distress syndrome and hypotension developed on April 26. Initial microbiologic workup that included blood, urine, and sputum cultures was negative, except for Vero cells from a throat swab, sputum, and stool that were positive for coronavirus. Indirect fluorescent antibody to SARS-associated coronavirus was also positive. Serum creatine kinase level increased from 378 to 7659 U/L from April 24 to 30, and renal failure developed. Serum myoglobin level on May 7 was 989 ng/mL. The patient died on May 15 because of multiple organ failure. No autopsy was performed.

The third patient was a 42-year-old woman who suffered from SARS since May 10. The diagnosis was based on fever, pneumonia, and a history of caring for a SARS patient. All of the microbiological studies for pathogens in community-acquired pneumonia were negative, except for detection of antibody to SARS coronavirus by indirect fluorescent antibody assay. SARS-associated coronavirus from the sputum was also detected by real-time reverse transcription polymerase chain reaction. Respiratory failure developed on May 21. Serum creatine kinase level increased from 364 to 9050 U/L from June 2 to 4. Serum myoglobin level was also elevated at 2136 ng/mL on June 6. A muscle biopsy specimen showed degeneration of muscle fibers with vacuolization of sarcoplasm and empty sarcolemmal tubes. After aggressive hydration and urine alkalization, the creatine kinase level decreased to within normal range, and the patient was taken off treatment successfully.

Rhabdomyolysis has been associated with many infectious diseases, including viral infections such as influenza (6). In the 3 patients with probable SARS who developed rhabdomyolysis during their disease course, succinylcholine-related malignant hyperthermia might have been another possible etiology in the first patient (7), whereas no other predisposing factors of rhabdomyolysis, such as toxins, drugs, electrolytes, or infectious agents, were found in the other 2 patients. Serum creatine kinase cardiac isoenzymes were less than 5% of the creatine kinase level in all 3 patients.

Elevated serum creatine kinase levels of up to 3000 U/L have been noted in previous patients with SARS. However, an extremely high serum level with positive serum myoglobin, which leads to acute renal failure, has not been reported 2, 3, 4. We conclude that rhabdomyolysis-associated renal failure may be another unusual but severe presentation of SARS. Patients with SARS should have their creatine kinase levels monitored carefully, even if initial levels are only slightly elevated.