Job's not done: BCG-itis as the first manifestation of hyper-IgE syndrome. A case report and review of the literature.

The Bacille Calmette-Guérin (BCG) vaccine is widely used to prevent tuberculosis (TB), especially in newborns and children in high TB prevalence areas. Though generally safe, it can cause adverse reactions like BCG-itis, a localized inflammatory response, and BCG-osis, a systemic infection. This case report details the clinical journey of a male toddler from a non-consanguineous family who presented with regional BCG-itis and later developed a disseminated mycobacterial infection. The patient had a history of recurrent suppurative otitis media and chronic granulomatous inflammation, with mycobacteria identified through biopsy. Despite initial treatments, he exhibited persistent and severe symptoms, including central nervous system abscesses, onychomycosis, and elevated serum Immunoglobulin E levels (13,160 IU/ml). Whole-exome sequencing identified a pathogenic heterozygous missense variant in STAT3 exon 13 (c.1144C > T, p.Arg382Trp), confirming autosomal dominant Hyper-IgE Syndrome. The patient showed improvement with antibiotics and intravenous immunoglobulin, yet struggled with relapses upon dose reduction of antitubercular drugs. The literature review revealed two similar cases, underscoring the importance of genetic and immunological insights in managing adverse vaccine reactions in Hyper-IgE Syndrome. CD4+ Th17 cells and interleukins 17, 21, 22, and 23 are crucial in fighting mycobacteria by activating autophagy in infected monocytes and MAIT cells. Type 2 interferon immunity and superoxide production are key in combating mycobacterial diseases like Mendelian Susceptibility to Mycobacterial Disease and Chronic Granulomatous Disease. Studies show that Asian and Latin American patients are overrepresented in non-tuberculous mycobacterial infections due to mandatory BCG vaccination at birth. It is recommended to contraindicate BCG vaccination in patients with known or suspected immune deficiencies and delay live vaccines until 6 months of age.