Rare Case of Homozygous Ifnar1 Deficiency in a Samoan Child with Disseminated Varicella after Vaccination

ABSTRACT

Introduction: Autosomal recessive interferon alpha/beta receptor 1 (IFNAR1) deficiency increases susceptibility to live-attenuated vaccines and wild-type viruses. Currently 16 cases, half with Polynesian ancestry have been reported since the discovery in 2019. Most cases present with severe MMR or yellow fever vaccine-related disease. Some cases report severe SARS-CoV-2, herpes simplex, and enterovirus. Varicella vaccine-related disease has been hypothesized but not previously reported. Case Description A pediatric Samoan girl with congenital cardiac anomaly, otherwise healthy until receiving Varicella and MMR vaccines at 12 months. Two weeks later with presumed incomplete Kawasaki Disease with 10-day fever, red lips, and maculopapular rash, given IVIG and infliximab;also, positive SARS-CoV-2 PCR and IgG that admission. Developed diffuse vesicular rash 3 weeks after vaccination requiring re-admission for disseminated varicella. At 14 months, admitted again for acute respiratory failure with viral pericarditis, positive for rhinovirus/enterovirus on respiratory viral panel and varicella serum PCR. Samoan parents are first-degree cousins and her stillborn sister had significant homozygosity on genetic evaluation. Normal lymphocyte subsets, normal mitogen proliferation, absent antigen proliferation in vitro, and normal NK function. Intact humoral immunity. Primary immunodeficiency disease panel identified homozygous pathogenic variant in IFNAR1. Future live viral vaccines contraindicated. Managed with acyclovir with return to baseline. Discussion(s) This case demonstrates a novel finding of homozygous IFNAR1 deficiency predisposing to disseminated varicella after vaccination. TNF inhibition may have also contributed. IFNAR1 deficiency should be considered in patients with severe varicella or other severe viral illnesses, especially after live-attenuated viral vaccines in those of Polynesian ancestry. Copyright © 2022