Age: 1.25
Sex: F
Vaccine: VARCEL
Symptoms: Febrile neutropenia, Haemoglobin decreased, Herpes simplex test negative, Herpes zoster reactivation, Immunodeficiency
Clinical narrative: Disseminated varicella zoster vaccine virus infection; Literature Report:  This literature marketed report has been received from the authors of a published literature article, entitled as stated above and refers to a 16-year-old female patient. The patient's concurrent conditions, concomitant therapies and patient drug reactions or allergies were not provided. Medical history included Hodgkin's disease nodular sclerosis stage IV. There was no history of a post-vaccine rash after Varicella-zoster virus (VZV) immunization. Thus, she completed her primary vaccinations without complication (immunsation).  On an unknown date in 2008 (also reported as at 15 months), the patient was vaccinated with the first dose of varicella virus vaccine live (Oka/Merck) (VARIVAX) injection, administered for prophylaxis and on an unknown date in 2012 (also reported as at 66 months), received the second dose (strengths, specific dosages, routes of administration, anatomical sites of application, lot numbers and expiration dates were not provided).   On an unknown date (reported as the day prior to admission (Day - 1), the patient was seen in the outpatient oncology setting and reported a two-day history of vesicular rash on her left upper leg with blisters. On examination, there were several clusters of vesicular lesions which were blanchable and in different stages of eruption along the L2/3 dermatomes unilaterally. She was swabbed for Varicella-zoster virus (VZV) and herpes simplex virus (HSV). Subsequently, she was hospitalized after her polymerase chain reaction (PCR) tests were positive for Varicella-zoster virus (VZV) and negative herpes simplex virus (HSV). On admission to the hospital for Varicella-zoster virus (VZV) infection (Day 0), the patient was placed in a negative pressure room with modified airborne precautions, precautions used for vaccine preventable diseases and/or conditions transmitted by the airborne route, requiring patient placement in an airborne isolation room but no requirement of respiratory protection for immune healthcare workers. The patient was non-toxic in appearance, with stable vital signs, and oriented in time, place and person, with a Glasgow Coma Scale score of 15. A review of systems was positive for dyspnea possibly due to anemia, headaches due to migraines, and nausea/vomiting from chemotherapy. Physical examination was significant for crops of vesicular lesions across the left upper leg, with 3 isolated vesicles seen on the abdomen, right ante¬rior wrist, and neck respectively. All lesions were tender to palpation. There were no signs or symp¬toms of meningitis, encephalitis, cellulitis, or myositis. There was no mucosal involvement to suggest a systemic hypersensitivity reaction. Lab results showed pancyto¬penia (hemoglobin 7.9 [11.914.8 g/dL], leukocytes 0.5 [3.810.4 × 109/L], absolute neutrophil count [ANC] 0.19 [2.007.40 × 109/L], platelets 132 [158362 × 109/L]). Liver and renal function tests were within the normal range without evidence of transaminitis (aspartate ami¬notransferase 18 [843 U/L], alanine aminotransferase 29 [745 U/L]) or acute kidney injury (blood urea nitrogen 19 (unit not provided), creatinine 0.51 (unit not provided)). Chest X-ray showed no focal findings concerning for pneumonia, pleural effusion, or pneu¬mothorax. Due to normal mentation, investigations to evaluate encephalitis were not obtained. In addition, skin cultures for bacteria were not obtained. IV vancomycin was added due to concern for vesicular lesions in the setting of febrile neutropenia. The patient's overall presentation was consistent with disseminated herpes zoster, involving multiple dermatomes, without evidence of respiratory, hepatic, or neurological complications. A lesion swab was sent to the Department of Health and a bi-allelic TaqMan PCR test used to differentiate between the two forms of VZV.  The assay detects three single nucleotide polymorphisms (SNPs) found in ORF62 of the vaccine-strain for differentiation, therefore, the  specimen was reported as positive for the vaccine-strain. The reactivation represented vaccine virus strain from previous immunization . Over the next 5 days of hospitalization, the disseminated rash progressively worsened involving new vesicular lesions in the following areas: abdomen, right anterior wrist, right chin/cheek, scalp, lower back, buttocks, left anteromedial and lateral thigh, left knee and lower leg. In addition, the patient developed both intractable migraines and emesis, requiring multimodal medication management. This change in her neurological status, considering the progressively worsening rash, raised concern for encephalitis. However, on Day 6 of hospitalization, an effective antiemetic and abortive migraine relief regimen were achieved. In addition, no new vesicular lesions were noted for the first time, which coincided on the day when an absolute neutrophil count (ANC) count recovery was achieved. The patient was discharged on Day 8. At discharge, there were no new lesions and all existing lesions had scabbed over. Final diagnosis was disseminated herpes zoster due to reactivation of vaccine-strain (Oka) varicella in an immunocompromised host (Disseminated varicella zoster vaccine virus infection). She had achieved absolute neutrophil count (ANC) recovery, afebrile status, negative blood cultures and reassuring lab results. She was transitioned to valacyclovir to treat the active Varicella-zoster virus (VZV) infection for a total of 10 days. Subsequently, she was started on twice daily valacyclovir 500 mg suppression treatment indefinitely until immune reconstitution. She adhered to this regimen for 11 weeks until cessation by the outpatient Hematology and Oncology team. In the outpatient setting, she remains well without any long-term sequelae of herpes zoster e.g. post-herpetic neuralgia (recovered).  Upon internal review, the event Disseminated varicella zoster vaccine virus infection was determined to be medically significant.   The authors of the article considered the event to be related to suspect therapy.   A copy of the published article is attached as further documentation of the patient's experience.  Lot # is being requested and will be submitted if received.