Severe Facial Herpes Vegetans and Viremia in NFKB2-Deficient Common Variable Immunodeficiency

Abstract

With the accessibility of next-generation sequencing modalities, an increasing number of primary immunodeficiency disorders (PIDDs) such as common variable immunodeficiency (CVID) have gained improved understanding of molecular pathogenesis and disease phenotype with the identification of a genetic etiology. We report a patient with early-onset CVID due to an autosomal dominant loss-of-function mutation in NFKB2 who developed a severe herpes vegetans cutaneous infection as well as concurrent herpes simplex virus viremia. The case highlights features of CVID, unique aspects of NF-κB2 deficiency including susceptibility to herpesvirus infections, the detection of neutralizing anticytokine antibodies, and the complexity of medical management of patients with a PIDD that can be aided by a known genetic diagnosis.

Rubella virus chronic inflammatory disease and other unusual viral phenotypes in inborn errors of immunity

“…This complication has also been documented in various IEIs. 270,276 In immunodeficient patients with rapidly growing cutaneous masses, herpes simplex vegetans should be included in the differential diagnoses.…”

“…Acyclovir or related agents have been useful in patients with IEI 277 . Foscarnet was used successfully in a patient with NFKB2 deficiency 270 . Subcutaneous pegylated interferon‐α 2b has been used in recalcitrant cases, starting at a dose of 0.6 μg/kg/week, followed by 1 μg/kg/week 277 …”

“…277 Foscarnet was used successfully in a patient with NFKB2 deficiency. 270 Subcutaneous pegylated interferon-α 2b has been used in recalcitrant cases, starting at a dose of 0.6 μg/kg/week, followed by 1 μg/kg/week. which conceptually aligns with HIV pathogenesis.…”

Autoimmunity as a continuum in primary immunodeficiency

“…Beyond antibodies to IFNa, IFNv and IL-12 in patients with partial RAG deficiency [14,36] and APECED [37], Rosenberg et al [38] reported neutralizing anti-IFNa antibodies among patients with IPEX in two large cohorts from Seattle Children's Hospital and San Rafaelle Hospital (Milan, Italy). Anti-IFNv antibodies were recently described in a patient with NFkB2 deficiency after herpes virus infection [39]. In addition, novel autoantibodies against lung-specific bactericidal/permeabilityincreasing fold-containing protein B1 (BPIFB1) and the potassium channel regulator protein (KCNFG), have been linked to onset of autoimmune pneumonitis in disorders of central T-cell tolerance (APECED, RAG deficiency, and thymoma) [39].…”

“…Anti-IFNv antibodies were recently described in a patient with NFkB2 deficiency after herpes virus infection [39]. In addition, novel autoantibodies against lung-specific bactericidal/permeabilityincreasing fold-containing protein B1 (BPIFB1) and the potassium channel regulator protein (KCNFG), have been linked to onset of autoimmune pneumonitis in disorders of central T-cell tolerance (APECED, RAG deficiency, and thymoma) [39]. It is intriguing that presence of anticytokine antibodies are also proposed as markers of prognosis in APECED, as they noted negative correlation of anti-IFNa antibodies and the incidence of T1DM [40,41].…”