Age: 1.0
Sex: M
Vaccine: VARCEL
Symptoms: Immunology test abnormal, Laboratory test abnormal, Lumbar puncture abnormal, Lymphocyte count, Magnetic resonance imaging head abnormal
Clinical narrative: rash/ skin lesions (the patient had 25 vesicles)/ presented to hospital with headache and fever/ disseminated varicella; Bone marrow transplant; Menningitis; The patient with Pre B cell acute lymphocytic leukemia was administered VARIVAX; This spontaneous report was received from a pharmacist and refers to a currently 14-year-old male patient with precursor B cell acute lymphocytic leukemia, graft versus host disease and allergy to chlorhexidine and metoclopramide. Concomitant therapies included sirolimus, calcium (unspecified), omega-3 marine triglycerides (reported as "fish oil"), budesonide, sulfamethoxazole (+) trimethoprim (BACTRIM), lisinopril (manufacturer unknown), vitamin D (unspecified), multivitamins, mecobalamin (MARINOL), tacrolimus and triamcinolone.   On an unknown date, the patient was vaccinated with a dose of varicella virus vaccine live (oka/merck) (VARIVAX) (lot number, expiration date, exact dose, vaccination schedule, anatomical location, and route of administration were not reported), for routine vaccination as a child (prophylaxis).   In February 2015, the patient had a cord blood stem cell transplant. On 18-DEC-2015, the patient developed rash. He was hospitalized and treated with acyclovir intravenously since 24-DEC-2015. The reporter didn't know if the vaccine strain reactivated after the transplant. Lab tests including varicella zoster virus (VZV) polymerase chain reaction (PCR), VZV in cerebrospinal fluid (CSF) and VZV in plasma were performed and the results were unavailable.   The outcome of rash was reported as recovering. The outcome of cord blood stem cell transplant and bone marrow transplant was unknown. The relatedness between the events and varicella virus vaccine live (oka/merck) (VARIVAX) was not provided.  The reporter considered the events rash and bone marrow transplant as life threatening and also considered the event rash to be medically significant as acyclovir was given to prevent serious criteria.  Follow-up information was received from the pharmacist on 21-JAN-2016.  The pharmacist reported that on 18-DEC-2015, the patient developed rash on an unspecified location that lasted for an unspecified duration, after bone marrow transplant. On an unspecified date, he subsequently developed meningitis for an unspecified duration.  The reporter considered meningitis as life threatening. Upon internal review the event of meningitis was determined to be medically significant. The event of rash was not considered as medically significant since the treatment with acyclovir was not cardiopulmonary resuscitation (CPR), oxygen or some other life saving measure.  Follow-up information was received from the same reporter who was a physician (previously reported as pharmacist) on 22-JAN-2016. The patient's vaccination history included all routine vaccinations as a child. The patient never had chicken pox.  On an unknown date, the sample from the skin lesion (the patient had 25 vesicles) was not stored properly and no specimen was available. On an unknown date, PCR results on CCF were 14 million, serum had 8700 (units not provided) and skin lesion just showed positive. On 13-DEC-2015, the patient presented to hospital with headache and fever. The reporter at that time thought tumor was cause. On 24-DEC-2015, the reporter was called to consult on the patient and the patient's mother told them at that time that patient had the vesicles for at least a week and half. On an unknown date, the patient was diagnosed with disseminated varicella by the reporter. The outcome of the events was reported as recovered on an unknown date.   Follow-up information was received on 28-JAN-2016. The patient was enrolled in the Program to identify if VZV is present and if it is present, to identify if it is associated with the wild-type (WT) VZV strain or with the OKA/ Merck vaccine strain.  The result of the PCR analysis revealed that the CSF specimen obtained on 14-JAN-2016 contained VZV vaccine strain. The plasma sample was also positive for VZV DNA with very low copy numbers which were not enough for genotyping.  Follow-up information was received on 19-MAY-2016.  Upon internal review, the events of bone marrow transplant, disseminated varicella zoster vaccine virus infection and cord blood transplant therapy were medically significant. Therefore, serious criteria and narrative were updated. The patient was lost to follow-up.   This is an amended report. Upon review, the PCR results were incorrect in the narrative. Per the questionnaire, follow up dated 28-JAN-2016, the plasma sample was positive for VZV DNA, but not positive for vaccine strain.  Therefore, the sentence "The plasma sample was also positive (vaccine strain) for VZV DNA with very low copy numbers which were not enough for genotyping" was changed to "The plasma sample was also positive for VZV DNA with very low copy numbers which were not enough for genotyping".  Follow-up information of this literature article has been received from the authors of a published literature article, titled as stated below, referring to a 14-year-old boy who underwent a cord blood transplant 10 months earlier for relapsed acute lymphoblastic leukemia (previously reported as adverse event). The patient's past medical history was remarkable for delayed immune reconstitution posttransplant, with low CD4 and CD8 T-cell counts and a normal CD19 B-cell count but a low total IgG count. He had ongoing grade IIa skin and gut graft-versus-host disease, managed with budesonide, sirolimus, and topical tacrolimus.  He had received 2 doses of varicella virus vaccine live (oka/merck) (manufacturer unknown) (exact dose, vaccination schedule, route of administration, anatomical location of injection, lot # and expiration date unknown) at 1 and 10 years of age (contraindicated product administered), and pretransplant, he was seropositive for varicella-zoster virus (VZV) and received acyclovir prophylaxis through day 100 posttransplant.  The patient presented with a 6-day history of abdominal rash, 5-day history of headache, and a fever. Examination revealed a 3-mm vesicular lesion on an erythematous base with central umbilication on his left upper abdomen and 10 to 20 similar vesicular lesions on his right wrist and bilateral chest and back in a nondermatomal distribution. He had a white blood cell count (WBC) count of 6100/microlitre, an absolute neutrophil count of 3080/microlitre, an absolute lymphocyte count of 1641/microlitre, and a C-reactive protein level of 1.5 mg/dL (normal: no more than 0.8 mg/dL). Head computed tomography scan appeared normal, but lumbar puncture opening pressure was elevated at 43 cm of water. Cerebrospinal fluid (CSF) was Gram-stain negative for organisms, with glucose level of 65 mg/dL, protein level of 164 mg/dL, red blood cell count of 1/cubic millimetre, and WBC count of 81/cubic millimetre with 1% neutrophils. Polymerase chain reaction (PCR) detected VZV in the CSF (14 000 000 copies per milliliter), serum (8700 copies per milliliter), and from a scraping of a vesicular skin lesion. Virus from CSF was genotyped as vOka.  Intravenous (IV) acyclovir was started at a dose of 20 mg/kg every (q) 8 hours; fevers and new lesions continued for 3 additional days. The patient gradually improved; however, on day 12 of acyclovir, he developed a new fever, perioral numbness, slurred speech and aphasia, and right upper extremity numbness. A brain magnetic resonance imaging (MRI) demonstrated T2 prolongation in the left nucleus accumbens, anterior inferior hypothalamus, and anteroinferior putamen consistent with VZV encephalitis. The neurology service felt that his symptoms were most consistent with neurologic dysfunction secondary to acute viral infection. VZV PCR results of the CSF on day 13 of acyclovir remained positive (4500 copies per milliliter). He recovered within hours but experienced a similar episode, although without fever, 4 days later, which also quickly resolved. CSF obtained on day 20 of acyclovir remained positive for VZV (800 copies per milliliter). IV acyclovir was continued to complete 27 days of therapy. One week after completing IV acyclovir, the patient experienced a third episode of aphasia and numbness, beginning in the right hand, progressing up the arm, and extending to the face; the episode resolved within 2 hours and was not associated with fever. Acyclovir was restarted. A brain MRI demonstrated improvement in the previously noted lesions consistent with evolving VZV meningoencephalitis. CSF VZV PCR result was negative, and acyclovir was stopped after 24 hours. Because of concern for seizure, an electroencephalogram (EEG) was obtained and demonstrated intermittent slowing and excessive b activity consistent with encephalopathy. He had no further episodes. An immune workup post meningitis identified adequate T-cell function but reduced mature memory and switched memory B cells. His serum VZV IgG became negative 18 months after his meningitis, and he continued acyclovir prophylaxis indefinitely.  The authors considered meningitis to be related to varicella virus vaccine live (Oka/Merck) (manufacturer unknown).  Upon internal review, meningitis was determined to be medically significant.  A copy of the published article is attached as further documentation of the patient's experience.  This is one of two reports derived from the same literature (cross-referenced with US-009507513-1912USA003361).  Literature Report:   It has been determined that case # <US-009507513-1912USA005082> is a duplicate of case # <US-009507513-1601USA007707>. Therefore, case # <US-009507513-1912USA005082> is being deleted from our files and the cases are consolidated into case # <US-009507513-1601USA007707>.; Sender's Comments:  US-009507513-1912USA003361: