Age: 1.0
Sex: M
Vaccine: VARCEL
Symptoms: CSF protein normal, CSF red blood cell count, Cerebral infarction, Cytomegalovirus test negative, Dermatitis atopic
Clinical narrative: This spontaneous report was received from a physician concerning an approximately 3 year old male patient. At the time of this report patient was 6 years old. The patient had a normal vaccination history. On an unknown date, when the patient was 12 months old (approximately on an unknown date in 2008), the patient was vaccinated with the first dose of VARIVAX (lot number, expiry date, dose and route unspecified). No concomitant medications were reported. The child had no adverse reactions immediately postvaccination after VARIVAX or other childhood vaccines. On an unknown date, beginning at age 3, the patient began to experience recurrent skin infections, including herpes simplex at age 3 (unknown date in 2010), another herpes simplex infection at age 4(unknown date in 2011), and herpes zoster at age 5(unknown date in 2012). These were each confirmed via diagnostic testing. The child was treated each time with unspecified antiviral therapy and recovered from each episode. In addition to those 3 skin episodes, he also developed atopic dermatitis, eczema, asthma, eosinophilia, pneumonia and pneumatocele on an unknown date. The patient subsequently had an immunological workup and was found to have a rare disorder called DOCK8 immunodeficiency syndrome which was confirmed via genetic testing (date of diagnosis was unknown). It was reported that DOCK8 disoder results in severe immunodeficiency. In addition to severe eczema, staphylococcal skin abscesses and pneumonia, patients with this syndrome may also develop cutaneous viral infections with human papilloma virus (HPV), molluscum contagiosum,herpes simplex virus (HSV), and varicella zoster virus (VZV). He indicated that most children with this immunodeficiency do not live past the age of 10 years old. On an unknown date, the physician consulted the patient due to his having neurologic symptoms and being hospitalized (date unspecified). The patient was subsequently diagnosed with VZV vasculopathy. His cerebrospinal fluid (CSF) contained a high level of VZV antibodies. Polymerase chain reaction (PCR) analysis of the CSF revealed it was positive for Oka vaccine strain VZV. The child did not have any skin lesion. A magnetic resonance imaging (MRI) of the brain revealed multiple cerebral infarctions and large cerebral arteries. The patient was treated with unspecified antiviral therapy, and within 1 week, he was completely better. He had no neurologic sequelae and a repeat brain MRI was significantly improved. The patient discharged from the hospital (date unspecified). At the time of reporting, he continued to be very well and fully recovered. The relatedness for the events was unknown for VARIVAX. Follow up information has been received from the authors of a letter to the editor as stated above. The patient's medical history included food allergies often with anaphylaxis, biopsy-confirmed eosinophilic esophagitis and recurrent upper respiratory tract infections. During flares of respiratory or skin disease, he was treated with oral corticosteroids intermittently for 3 to 5 days, a few times annually. On an unspecified date, a magnetic resonance imaging with axial diffusion-weighted images revealed multiple areas of acute infarction in areas supplied by both anterior cerebral arteries, a branch of the anterior cerebral artery, the right posterior cerebral artery, and the left middle cerebral artery, a complete blood cell count revealed a total eosinophil count of 2160/micro-L, but no other abnormalities. It was reported that the patient was treated with acetylsalicylic acid and intravenous methylprednisolone followed by oral prednisolone, 2 mg/kg for 3 days after which prednisolone was maintained at 1 mg/kg daily. On an unknown date (reported as on presentation 1 month later), he had developed paresthesias of his hands. Neurologic examination showed only mild weakness in the hands. Computed tomography angiogram revealed diffuse vasculopathy. Subsequent 3-dimensional time-of-flight magnetic resonance angiographic imaging of the circle of Willis revealed vascular narrowing and poststenotic dilatation. Postcontrast T1W black blood arterial wall imaging illustrated avid enhancement and thickening of the distal supraclinoid internal carotid arterial walls bilaterally. Cerebrospinal fluid (CSF) was obtained. While awaiting results of testing for viral CNS infections, the patient was treated with acyclovir, 30 mg/kg intravenous daily, and maintained on oral prednisolone, 2 mg/kg daily. The CSF at the time of diagnosis of vasculopathy contained 21 mononuclear cells and no red blood cells; protein was 39 mg/dL, and glucose was 72 mg/dL. Quantitative PCR amplified 7116 copies of VZV DNA/mL in the CSF. The CSF also contained anti-VZV IgG antibodies, but no antibodies to herpes simplex virus (HSV)-1 or HSV-2, enterovirus, cytomegalovirus,or EBV were detected and the respective PCR analyses were similarly negative. The serum to CSF ratio of anti-VZV IgG antibody was markedly decreased (ratio 2.3) compared with albumin (ratio 149). Two weeks after treatment with acyclovir, the neurologic examination was completely normal, the CSF was acellular, and PCR was negative for VZV DNA. Analysis of VZV DNA in the CSF revealed that the VZV genotype was vaccine strain, demonstrating, for the first time, that VZVreactivation after vaccination in childhood can result in VZV vasculopathy. The authors considered the causality between viral vasculitis and VARIVAX to be related.