Dermatology MCQ - Viral Infections - Reactivation of HHV-6

A 65-year-old man with acute myeloid leukemia (AML) undergoing induction chemotherapy develops a diffuse, pruritic, maculopapular rash on his trunk and extremities. He has no fever or mucosal involvement. His medications include cytarabine and idarubicin. A skin biopsy shows a superficial perivascular lymphocytic infiltrate with eosinophils. Which of the following is the most likely underlying cause of this eruption?

A) Drug reaction to cytarabine
B) Graft-versus-host disease (GVHD)
C) Reactivation of human herpesvirus 6 (HHV-6)
D) Leukemia cutis
E) Bacterial sepsis

Correct Answer: C) Reactivation of human herpesvirus 6 (HHV-6)

Explanation

This scenario describes a classic presentation of HHV-6 reactivation in an immunocompromised host, which can mimic drug reactions or other eruptions.

Key Features of HHV-6 Reactivation in Immunocompromised Patients:

• Timing: Often occurs 2-4 weeks after chemotherapy or hematopoietic stem cell transplantation (HSCT).

• Rash Description: A pruritic, maculopapular rash that is often widespread but spares mucous membranes. It can resemble a drug eruption.

• Histopathology: Biopsy typically shows a superficial perivascular lymphocytic infiltrate with eosinophils, which is non-specific but consistent with viral exanthem or drug reaction.

• Systemic Symptoms: May include fever, bone marrow suppression (e.g., delayed engraftment in HSCT), or encephalitis.

Why HHV-6 Reactivation is Likely:

• Chemotherapy (especially for AML) causes profound immunosuppression, allowing latent HHV-6 (and HHV-7) to reactivate.

• HHV-6 reactivation is common in AML patients receiving cytarabine-based regimens.

• The rash is often misdiagnosed as a drug reaction, but HHV-6 PCR in blood or skin can confirm reactivation.

Why Not the Other Options?

• (A) Drug reaction to cytarabine: Cytarabine can cause rash, but HHV-6 reactivation is a common mimic in this setting. The presence of eosinophils is non-specific and seen in both.

• (B) Graft-versus-host disease (GVHD): GVHD typically occurs post-HSCT (not mentioned here) and often involves mucosal sites (e.g., oral ulcers, diarrhea).

• (D) Leukemia cutis: Presents as firm, violaceous nodules or plaques, not a diffuse maculopapular rash. Biopsy would show leukemic cells in the dermis.

• (E) Bacterial sepsis: Sepsis-related rashes (e.g., meningococcemia) are often purpuric or petechial, not pruritic and maculopapular.

Management:

• Confirm with HHV-6 PCR in blood or skin.

• Treatment: Supportive care (antihistamines for pruritus). In severe cases (e.g., encephalitis), antivirals (e.g., ganciclovir, foscarnet) may be used, though evidence is limited.

• Differentiate from drug reaction: If HHV-6 is confirmed, avoid unnecessary drug discontinuation.

Prognosis:
Self-limiting in most cases, but can contribute to delayed engraftment or organ dysfunction in HSCT recipients.

Note: HHV-7 reactivation can cause similar findings but is less common than HHV-6.