Age: 0.9
Sex: M
Vaccine: VARCEL
Symptoms: Herpes zoster, Injection site infection, Irritability, Neuroblastoma, Pyrexia
Clinical narrative: It was reported that an apparently healthy male patient was vaccinated in his right thigh with a dose of varicella virus vaccine live just prior to his one year well child examination. Subsequently, at that visit an abdominal mass was noted and a CT scan revealed a large retroperitoneal mass obstructing the left renal collecting system. Biopsy revealed a neuroblastoma. Chemotherapy was begun five days later (5 days post vaccine). The patient  was hospitalized. Anti-tumor therapy was complicated by a non-functioning left kidney, hypertension, and multiple episodes of fever and neutropenia. Three months later he developed herpes zoster at the vaccination site. Acyclovir treatment, while chemotherapy cycles continued, produced improvement in the skin lesion, but these never resolved completely. ACV at several different doses was continued. Four months after the onset of HZ, his lesions increased in number and are aof involvement. The lesions developed a verrucous appearance and spread over his right anterior and lateral thigh and buttock. Continuing anti-tumor therapy included infusion of autologous stems collected more than a month after completing the second and third cycle of induction chemotherapy. He continued to  receive ACV for one month after stem cell infusion without any change in his rash. He then developed fever and multiple erythematous papules involving his scalp, face, and trunk. An LP was performed because of irritability. VZV PCR of both serum and cerebrospinal fluid were positive. Foscarnet was started and the lesions improved. ACV was discontinued. Over the next three months Foscamet therapy was frequently altered because of variation in creatinine clearance. Worsening HZ lesions, disseminated lesions, fever, and irritability recrudesced when the Foscarnet dose was decreased or the dosing interval increased. Four months after transplantation additional therapy included an infusion of autologous frozen stem cells and VZV immune globulin. Within 10 days his ras was improved, and he was discharged on Foscarnet. Gradual healing occurred with continuing IV Foscarnet therapy at home for three months. Weight gain and resumption of development milestones were observed, and have continued off of therapy for 75 days. During the healing phase the lymphocyte responses to pokeweed mitogen and VZV antigen were present, but responses to Candida and tetanus antigens have remained negative. The skin biopsy showed verrucous appearing sking with intraepidermal vesicles and necrosis. Electron microscopy showed intranuclear particles consistent with herpes viruses. VZV was not isolated from a swab of the chronic HZ lesions or from a subsequent skin biopsy, but the VZV polymerase gene was detected by pCR perfomred on DNA extracted from the biopsy. Further PCR analysis of this DNA indicated the presence of the Oka vaccine VZV strain. The VZV DNA amplified from cerebrospinal fluid was also identified as Oka vaccine strain. The VZV thymidine kinase gene was amplified by PCR from the DNA extracted from the skin and its nucleotide sequence compared to the tk gene identical in sequence with the exception at VZV genome position 65074 of a substitution of a T in the amplified specimen DNA for the C in the Oka vaccine. This substitution introduces a TAG stop codon in place of a CAG glutamine codon in the tk coding sequence at amino acid position number 90 in the 341 amino acid tk protein. The effect of this mutation was determined in vitro by comparing the tk activity induced by sequences from the Oka vaccine strain and the amplified specimen DNA, using sequences encoding beta-glactosidase as a negative control. This was accomplished by in vitro translation of plasmids containing these sequences. The presence of tk was detected by phosphorylation of radiolabeled thymidine and binding of the resulting thymidine monophosphate to a filter: non-phosphorylated thymidine substrate is washed through the filter. In this experiment, a small amount of filter-associated residual radioactivity was observed with the beta glaltosidase negative control, while protein translated from the tk gene of the Oka vaccine strain was associated with robust tk activity. Protein translated from the tk gene of the VZV DNA extracted from the skin biopsy showed very low tk activity indistinguishable from that of the negative control. Similar results were obtained using both ATF and CTF as phosphate donors. Thus, the stop condon mutation completely abrograted tk activity as determined by this assay. The author indicated that this case demonstrates that the Oka vaccine strain VZV is capable of causing severe HZ and systematic disease in immunocompromised patients after reactivation from latency. Additional information has been requested.