Clinical and Genetic Characteristics of BCG Disease in Chinese Children: a Retrospective Study

Summarize the characteristics of a large cohort of BCG disease and compare differences in clinical characteristics and outcomes among different genotypes and between primary immunodeficiency disease (PID) and patients without identified genetic etiology.

We collected information on patients with BCG disease in our center from January 2015 to December 2020 and divided them into four groups: chronic granulomatous disease (CGD), Mendelian susceptibility to mycobacterial disease (MSMD), severe combined immunodeficiency disease (SCID), and gene negative group.

A total of 134 patients were reviewed, and most of them had PID. A total of 111 (82.8%) patients had 18 different types of pathogenic gene mutations, most of whom (91.0%) were classified with CGD, MSMD, and SCID. CYBB was the most common gene mutation (52/111). BCG disease behaves differently in individuals with different PIDs. Significant differences in sex (P < 0.001), age at diagnosis (P = 0.013), frequency of recurrent fever (P = 0.007), and vaccination-homolateral axillary lymph node enlargement (P = 0.039) and infection severity (P = 0.006) were noted among the four groups. The CGD group had the highest rate of males and the oldest age at diagnosis. The MSMD group had the highest probability of disseminated infection (48.3%). The course of anti-tuberculosis treatment and the survival time between patients with PID and without identified genetic etiology were similar.

Greater than 80% of BCG patients have PID; accordingly, gene sequencing should be performed in patients with BCG disease for early diagnosis. BCG disease behaves differently in patients with different types of PID. Patients without identified genetic etiology had similar outcomes to PID patients, which hints that they may have pathogenic gene mutations that need to be discovered.