Fatal HHV-6 pediatric myocarditis following immunosuppression

A case report published by a group at the University of Minnesota details two cases of fatal myocarditis associated with HHV-6 in two immunosuppressed children. Both these patients were treated with steroids, but neither received antiviral treatment in spite of HHV-6 viremia, fever, and rash. Diagnosis of HHV-6 myocarditis was made after an autopsy evaluation.

In the first case, a 13-year-old boy with pre-B cell acute lymphoblastic leukemia underwent a double umbilical cord blood transplant and was discharged from the hospital on day +22. Due to fever and generalized erythroderma with maculopapular features over 75% of the body, he was readmitted to the hospital on day +25. He was treated with intravenous methylprednisone for Grade II acute GVHD. At this time, PCR of the blood was positive for HHV-6 with 7,600 copies/mL. By day +34, this number increased to 146,200 copies/mL of blood. On day +35, he developed acute respiratory decompensation. On day +36, he died. Autopsy revealed mild interstitial lymphocytic infiltrate without evidence of fibrosis or viral inclusions. PCR from the left ventricle and left lung upper pulmonary lobe was positive for HHV-6. Viral myocarditis was ruled as the cause of death upon finding HHV-6 in the cardiac tissue.

In the second case, a 2-year-old girl was diagnosed with Evans syndrome after her white blood cell count decreased from 2,400 cells/uL to 400 cells/uL, hemoglobin decreased from 9.9 g/dL to 7.9 g/dL, and platelets decreased from 7,000/uL to 0/uL over the course of 1 day. She was started on prednisone 2 mg/kg per day twice a day. On day 6, she presented with decreased urine output, change in mental status, and hypotension. She could not be resuscitated after going into shock, and died. PCR of the blood was positive for HHV-6 at 64,600 copies/mL. Autopsy revealed acute lymphocytic myocarditis consistent with viral infection in both ventricles. Immunofluorescence showed HHV-6 in the cardiac tissue.

Although endomyocardial biopsy is currently the primary method for diagnosing myocarditis, it demonstrates a low sensitivity, so most centers rely on viremia when trying to guess the cause of myocarditis. Unfortunately, HHV-6 is not including in standard testing at many transplant centers, so the diagnosis often comes too late. Also both children received steroids which exacerbate HHV-6 infection disproportionately compared to other herpesviruses (Ishida 2014, Inazawa 2015).

These cases illustrate the importance of initiating early treatment of HHV-6 and myocarditis in immunocompromised patients, as it could decrease both morbidity and mortality.

For more details, read the full paper.