Rhabdomyolysis Associated With Primary Human Herpesvirus-6 Infection
The Pediatric Infectious Disease Journal: December 2019 - Volume 38 - Issue 12 - p e341
doi: 10.1097/INF.0000000000002476
Letters to the Editor
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To the Editors:
We read with great interest the article by Fujino et al.1 There had been no other report on human herpesvirus (HHV)-6 infection accompanied by rhabdomyolysis. We recently experienced another case of primary HHV-6 infection exhibiting rhabdomyolysis.
A 1-year-old Japanese girl who presented with high fever for 3 days, mild diarrhea and anorexia was admitted to our hospital. The patient’s medical history and her family history were unremarkable. No medications and no vaccinations were administered in the month before the admission. Blood tests showed marked elevations of creatine kinase (CK) (2967 U/L) and myoglobin (4103 ng/mL). Dark urine was not observed, but her urine tested positive for myoglobin (67 ng/mL). The patient was treated with intravenous hydration and experienced defervescence on the fourth day of illness with the development of a maculopapular rash on her face and trunk. CK reached a peak (4408 U/L) on the fifth day of illness and normalized (35 U/L) on the 19th day of illness. No seizures were observed during the course of illness. The patient did not develop renal failure, and her neurodevelopmental status was normal after hospital discharge.
Given the elevated serum CK, serum myoglobin and urinary myoglobin levels, the patient was diagnosed with rhabdomyolysis. Because exanthem subitum was suspected as a cause of the fever based on the clinical course, serologic tests for HHV-6 and HHV-7 were performed. HHV-6 immunoglobulin M antibody was positive, and HHV-6 immunoglobulin G antibody increased (80–1280) on indirect immunofluorescent assay of paired sera. HHV-7 immunoglobulin M antibody was negative, and HHV-7 immunoglobulin G antibody did not increase (160–160). Other viral antigen tests were all negative. Screening for inborn errors of metabolism by tandem mass spectrometry detected no disorders. Based on these clinical findings, the diagnoses of rhabdomyolysis and primary HHV-6 infection (exanthem subitum) were confirmed.
To date, rhabdomyolysis in children with primary HHV-6 infections has been reported in only 2 cases, including the present case.1 Because both cases involved Japanese patients, the pathogenic mechanism might be attributed to their genetic background. However, because primary HHV-6 infection occurs in 90% of children by 2 years of age, the association is either very rare or requires other factors for manifestation.2 This is in contrast the many case reports of children with influenza virus infection and comorbid rhabdomyolysis.3–5 One possible explanation is that the affinity of HHV-6 to skeletal muscle through direct invasion or myotoxic cytokines may be lower than that of other reported viruses. Another possible explanation is that comorbid rhabdomyolysis may be more likely to be missed in children with HHV-6 when compared with cases associated with other pathogenic viruses, because primary HHV-6 infection usually occurs in infants,2 in whom myalgia and muscle weakness are often mistaken for irritability and lethargy due to febrile illness. However, the true incidence of this association and the muscular virulence of HHV-6 should be elucidated in future research.
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