Meningoencephalitis Caused by Varicella-Zoster Virus Reactivation in a Child With Dominant Partial Interferon-Gamma Receptor-1 Deficiency

Abstract

We describe a previously symptom-free 13-year-old boy with dominant partial interferon-γ receptor-1 deficiency and unusual varicella-zoster virus reactivation. This case supports the unsettled notion that some interferon-γ R-deficient patients are at enhanced risk for viral disease.

Anti–IFN-γ autoantibodies in adults with disseminated nontuberculous mycobacterial infections are associated with HLA-DRB1*16:02 and HLA-DQB1*05:02 and the reactivation of latent varicella-zoster virus infection

“…Consistent with our hypothesis, Roesler et al also reported a dominant partial IFN-␥ receptor-1 deficiency in a child with meningoencephalitis that was caused by VZV reactivation. 45 Browne et al found that a considerable proportion of patients suffering from dNTM infections with or without opportunistic infections also suffered from severe VZV infections. 34 Anti-IFN-␥ autoantibodies were detected in 88% of the patients in that study, similar to the findings in our cohort.…”

Mendelian susceptibility to mycobacterial disease: Genetic, immunological, and clinical features of inborn errors of IFN-γ immunity

“…Other mutations in the immediate vicinity of 818del4 may also underlie AD IFN-γR1 deficiency (818delT, 794delT, E278X, 811del4, 774del4 and 805delT) [46, 120, 121, 125–130] (Figure 1). In total, 43 families containing 68 patients have been described, including four asymptomatic patients for the case-definition MSMD phenotype [41, 42, 46, 49, 86, 99, 120–123, 125–137]. Large amounts of IFN-γR1 protein are detected on the cell surface, due to the accumulation of truncated IFN-γR1 receptors lacking the recycling domain [120].…”

“…Generally, patients are susceptible to BCG or EM ( M. abcessus , M. avium complex, M. asiaticum , M. bohemicum , M. chelonei , M. gordonae , M. kansasii , M. scrofulaceum ) (Figure 4). In 72% of patients, the infection affects the bone and some patients even develop osteomyelitis with no other organ involvement [41, 42, 46, 49, 86, 99, 120–123, 125–137]. Two patients with mycobacterial osteomyelitis were initially incorrectly diagnosed as having Langerhans cell histiocytosis and received chemotherapy [138].…”

“…The other associated pathogens detected are Cocciodiodes spp. [42], Histoplasma capsulatum [41] and VZV [49]. Two patients suffered from tuberculosis, one due to M. tuberculosis [126, 127] the other to M. bovis , corresponding to the only infection of this second patient [46] (Figure 4).…”

“…Other severe infections have been reported more rarely, typically in single patients, and include infections caused by various intramacrophagic bacteria (listeriosis, nocardiosis, klebsiellosis) [26, 37–39], fungi (candidiasis, histoplasmosis, paracoccidioidomycosis, coccidioidomycosis) [31–36, 40–43] and parasites (leishmaniasis, toxoplasmosis) [44, 45]. Viral infections have also been reported, including diseases caused by cytomegalovirus (CMV), human herpes virus 8 (HHV8), parainfluenza virus type 3 (PRV-3), respiratory syncitial virus (RSV) and varicella zoster virus (VZV) [46–49]. Six cases of malignancies, namely B-cell lymphoma, esophageal carcinoma, cutaneous squamous cell carcinoma, Kaposi sarcoma, liver cancer and pineal germinoma have also been reported [27, 50–54].…”