Sex: F
Vaccine: VARCEL
Symptoms: CSF white blood cell count increased, Disseminated varicella zoster vaccine virus infection, Erythema, Fatigue, Flow cytometry
Clinical narrative: This literature marketed report has been received from an other health professional referring to a 14 year old female patient. The patient's concurrent conditions included iron deficiency anemia. The patient's medical history was "previously healthy". The patient denied exposure to, or infection with, primary varicella. Concomitant medications were not provided. On unknown dates, in her 18 months and 12 years age, the patient was vaccinated with the first and second dose of varicella virus vaccine live (oka/merck) (manufacturer unknown) (dose, frequency, route, site of administration, lot # and expiration date unknown) for prophylaxis, respectively. On an unknown date, the patient had confirmed immunity with a positive varicella-zoster virus (VZV) immunoglobulin G (IgG) titer. On an unknown date (reported as "on day 3 of illness"), the patient noticed a pruritic rash on her trunk and presented to an emergency department. The rash was noted to be vesicular and in a left truncal dermatomal distribution, not crossing midline. She was prescribed an unknown dose of valacyclovir for presumed herpes zoster and discharged home. However, she was unable to tolerate any oral doses of valacyclovir at home due to nausea and she presented again the following day to the same emergency department for evaluation. A review of systems was positive for nausea, weakness, and myalgias, but negative for neck stiffness, fever, chills, vision change, numbness, as well as any respiratory, gastrointestinal, or genitourinary symptoms. A brain magnetic resonance imaging was performed and showed no abnormalities. Lumbar puncture (LP) was attempted but was unsuccessful due to patient discomfort. She was given intravenous (IV) fluids, ketorolac 15 mg IV, metoclopramide 10 mg IV, and morphine 2 mg IV, and subsequently transferred to the another hospital for children for further evaluation. Initial examination at the hospital revealed a tired, but nontoxic-appearing adolescent with vital signs appropriate for her age. Notably, she was afebrile. She had multiple intact vesicles on an erythematous base with areas of confluence in a T5 dermatomal distribution, from just below her left breast wrapping around to her back. There were no signs of bacterial superinfection with no purulent drainage. Her neurologic exam was overall unremarkable including a fundoscopic exam revealing a sharp disc on the left (right was unable to be visualized), intact cranial nerves 2 to 12, no nystagmus, normal tone and strength, and intact finger-to nose testing. Initial laboratory studies revealed peripheral white blood cell (WBC) count of 6.53 K/µL (72.8% neutrophils, 13.5% lymphocytes, 12.9% monocytes, and hemoglobin of 9.6 g/dL with MCV 77.9 (unit not provided). Inflammatory markers were normal with erythrocyte sedimentation rate 17 mm/h and C-reactive protein 0.3 mg/L. Pediatric neurology was consulted due to concern for possible idiopathic intracranial hypertension given worsening headache in the morning and in a supine position. Pediatric infectious disease was also consulted for diagnostic guidance. Iron studies were obtained for her anemia. The results of these studies were consistent with iron deficiency as ferritin and iron levels were low, 8 and 24 µg/dL, respectively. She was started empirically on IV acyclovir, 10 mg/kg every 8 hours. LP was obtained with the patient lying flat under sedation with an opening pressure of 37 cm H2O. Cerebrospinal fluid (CSF) was sent for VZV polymerase chain reaction (PCR), herpes simplex virus (HSV) PCR, and cell count. CSF cell count was notable for elevated WBC count at 568 cells/µL, with 92% lymphocytes and 8% monocytes in tube 1. CSF VZV PCR returned positive, while CSF HSV PCR was negative. A CSF sample was subsequently sent for genotyping, which confirmed vaccine-strain Clade 2 VZV genotype. Human immunodeficiency virus (HIV) antibody, VZV IgG, and B and T cells flow cytometry were also sent to assess for coinfection and signs of immunodeficiency. VZV IgG was positive and HIV antibody was negative. The results of flow cytometry showed that the absolute number of T cells, B cells, and NK cells were within normal range. The patient was continued on parenteral acyclovir for a total of 7 days. Her rash completely crusted over by day 10 of illness and her headache resolved on day 11 of illness. She was sent home to complete an additional 14 days of oral valacyclovir 1,000 mg, three times a day. On the day of discharge, she reported complete resolution of her central nervous system (CNS) symptoms and had no new skin lesions. Unfortunately, she did not return for her scheduled follow-up visits in the outpatient pediatric infectious disease clinic, and her family was unable to be reached via telephone. The reporter reported that the patient developed a severe vesicular rash along a single dermatome and meningitis without focal neurologic deficits ("herpes zoster complicated by meningitis" / "zoster infection secondary to reactivation of vaccine-strain VZV") (herpes zoster meningitis). The reporter considered that this case added to a growing number of case reports describing immunocompetent children with CNS disease secondary to VZV reactivation. The reporter commented that, in this case, there might have been an inappropriately decreased suspicion for disseminated VZV infection on initial presentation, as headache and rash were the only initial complaints. There was no fever, and she was a fully vaccinated, immunocompetent adolescent. Thus, there was a delay in diagnosis and treatment. The reporter stated that while the patient was lost to follow-up, her near-complete resolution of symptoms at the time of discharge argued that she would likely have a favorable outcome and full recovery. The reporter considered the events to be related to varicella virus vaccine live (Oka/Merck) (manufacturer unknown). Upon internal review, "herpes zoster complicated by meningitis" / "zoster infection secondary to reactivation of vaccine-strain VZV" and disseminated varicella zoster vaccine virus infection were determined to be medically significant.