Answer to March 2021 Photo Quiz

Answer: Disseminated varicella-zoster virus. The patient was prescribed oral valaciclovir when the lesions first appeared, and after 7 days of treatment, most of lesions resolved. PCR of swabs from the lesions was positive for varicella-zoster virus (VZV) DNA. Stains and culture for bacteria, fungi, and acid-fast bacilli were negative. The patient confirmed that he had had clinical chickenpox as a child.

The initial differential diagnosis was wide, given the patient’s prolonged immunosuppression and concomitant cutaneous graft-versus-host disease (GvHD). Ecthyma gangrenosum secondary to systemic Pseudomonas infection was considered, but this typically presents with far fewer lesions, which increase in size and ulcerate (1). Disseminated fungal infection was also considered, especially following previous fungal complications. Atypical VZV infection was considered more likely, based on the number and distribution of the lesions as well as the presence of crusting around some of the lesions. The color of the lesions was attributed to intralesional hemorrhage in the setting of profound thrombocytopenia (platelet count, 35 × 10⁹/liter). VZV infection commonly spares the palms and soles and involves the oral cavity, particularly the hard palate (2). Histopathological examination of a biopsy sample may identify the pathognomonic “three M’s” (multinucleation, nuclear molding, and margination of chromatin) of herpetic infection, as seen in our patient (3). However, these findings are seen in infections due to herpes simplex viruses I and II as well as VZV, and therefore PCR (or specific immunohistochemical staining) is required for a species-level diagnosis. Commercial multiplex PCR assays (e.g., the Quidel Solana platform) can test for all three viruses at once.

Long-term aciclovir reduces the incidence of VZV infection in the year following allogeneic stem cell transplantation (4). However, the incidence of VZV infection rises once aciclovir is discontinued (5). In case series conducted before the era of prolonged aciclovir prophylaxis, the incidence of VZV infection posttransplant ranged from 16.6 to 41%, depending on the intensity and duration of follow-up (6, 7). Although the majority of cases occur within 1 year, the timing of onset varied substantially within cohorts; one case series reported a median interval between transplantation and infection of 227 days but a range from 45 days to 3.7 years (6). Around one in five cases of posttransplant VZV are disseminated (6, 7), and a history of chickenpox does not appear to affect the odds of developing localized zoster compared with generalized varicella (7). GvHD has been identified as an independent risk factor for VZV infection (5, 7).

Our patient was not prescribed aciclovir prophylaxis, as he was receiving full-dose foscarnet for CMV reactivation; foscarnet retains activity against herpesviruses 1 to 3 as well as CMV. However, when foscarnet-resistant CMV was identified, the patient was switched to maribavir through a compassionate early-access scheme. Maribavir targets the UL97 protein of CMV, and therefore, prophylaxis against other herpesviruses (with aciclovir or valaciclovir) should continue during therapy with maribavir, until successful immune reconstitution.

See https://doi.org/10.1128/JCM.00118-20 in this issue for photo quiz case presentation.