Makindo Medical Notes

HHV-6 encephalitis is a critical complication after stem cell transplants with hyponatraemia, cognitive decline, seizures, and memory loss. Get CSF and PCR. MRI and EEG can also help identify early brain abnormalities. MRI shows medial temporal lobes, particularly the amygdala and hippocampus hyperintensities in these regions are visualized on T2, FLAIR and DWI sequences. Treat with antiviral therapy with drugs like foscarnet or ganciclovir. Prompt diagnosis and intervention is essential to prevent irreversible neurological damage

Overview

• HHV-6 is the collective name for the double-stranded DNA viruses HHV-6A and HHV-6B
• HHV-6A is part of the Herpesviridae family, which also includes viruses like HSV and CMV.
• HHV-6B is commonly associated with roseola in children
• HHV-6A is less well understood and more often associated with immunocompromised individuals.
• It is a DNA virus, containing double-stranded DNA and primarily infects T-lymphocytes.

Transmission

• HHV-6 is a ubiquitous virus found worldwide
• HHV-6A: transmitted close contact/via saliva. Exact routes of transmission are not fully understood.
• Infection is often asymptomatic, particularly in immunocompetent individuals.
• Reactivation of latent virus in immunocompromised individuals is more common and can lead to various complications.

Pathogenesis

• HHV-6A primarily infects CD4+ T cells, epithelial cells, glial cells, and macrophages. HHV-6A can remain latent in monocytes, macrophages, tissues, reactivating when the immune system is weakened. HHV-6A can disrupt immune responses, contributing to chronic inflammation and potentially leading to autoimmune diseases or neurological disorders.
• HHV-6B is the causative agent in exanthema subitum (also known as roseola infantum), a childhood disease characterized by high fever and a mild skin rash, and accounts for up to 10 to 17% of acute febrile Emergency department visits in children up to 36 months of age.

Clinical Manifestations

• HHV-6A infection is less frequently associated with specific clinical symptoms compared to HHV-6B.
• However, reactivation of HHV-6A is linked to the following conditions:
  • Neurological Diseases: Some studies suggest a link between HHV-6A and neurological conditions such as multiple sclerosis (MS), encephalitis, and cognitive dysfunctions. May have SIADH
  • Chronic Fatigue Syndrome (CFS): Reactivation of HHV-6A has been proposed as a possible contributing factor to CFS, though this remains an area of ongoing research.
  • Immune Suppression: HHV-6A can contribute to immunosuppression, particularly in individuals with compromised immune systems (e.g., transplant recipients).
  • HIV Co-infection: HHV-6A may exacerbate the progression of HIV by directly infecting and depleting CD4+ T cells.
• Many cases of HHV-6A infection remain asymptomatic or cause only mild flu-like symptoms in healthy individuals.

Diagnosis

• Diagnosis of HHV-6A infection can be challenging due to the similarity of its symptoms with other conditions and the fact that it often remains latent.
• Polymerase Chain Reaction (PCR): The most common method for detecting HHV-6A, used to amplify and detect viral DNA in blood or tissue samples.
• Serology: antibodies against HHV-6A, distinguishing between HHV-6A and HHV-6B can be difficult.
• Viral Culture: requires a high level of viral presence to be effective.
• Tissue Biopsy: biopsy of affected tissues (e.g. brain tissue in encephalitis cases) may be performed to detect the presence of HHV-6A.
• MRI: medial temporal lobes, particularly the amygdala and hippocampus hyperintensities in these regions are visualized on T2, FLAIR and DWI sequences

Primary HHV-6 infection can cause acute encephalopathy in a child

Treatment

• Most HHV-6 infections are asymptomatic, transient, and do not require antiviral treatment. Universally, HHV-6 primary infection is benign with spontaneous resolution in 5 to 7 days. The most common complication of roseola infantum is febrile seizures. Additional complications are often due to HHV-6 neurotrophic effects
• For severe infection due to HHV-6A Ganciclovir, Foscarnet, and Cidofovir may be used, especially in immunocompromised individuals or those with severe reactivation symptoms. Supportive care is often necessary for managing symptoms and secondary infections associated with HHV-6A reactivation. For neurological manifestations, treatment may involve managing symptoms like seizures, inflammation, or other complications caused by the virus.

Complications: Reactivation of HHV-6A with severe complications in immunocompromised individuals:

• Encephalitis: Inflammation of the brain, often seen in transplant patients or those with compromised immune systems.
• Multiple Sclerosis (MS): While not conclusively proven, HHV-6A reactivation has been proposed as a potential trigger or exacerbating factor in MS.
• Chronic Fatigue Syndrome: HHV-6A has been suggested as a possible contributor to CFS, though this remains a hypothesis under investigation.

Prevention

• There is currently no vaccine for HHV-6A.
• Prevention strategies focus on reducing exposure in immunocompromised individuals and managing conditions that may trigger viral reactivation (e.g., organ transplants, HIV infection).
• Immunocompromised patients should be regularly monitored for signs of HHV-6A reactivation, especially after organ transplantation or during treatments that suppress the immune system.

Conclusion

• HHV-6A remains less understood compared to its counterpart, HHV-6B, but emerging research points to its role in neurological diseases, chronic fatigue syndrome, and immune system modulation.
• Further research is needed to fully understand the pathogenesis, transmission, and effective treatment strategies for HHV-6A.
• For now, antiviral therapy and supportive care are the primary methods for managing reactivation in vulnerable populations.