Clinical Scenario:
A 7-month-old infant is brought with persistent fever, poor feeding and failure to gain weight. He received BCG vaccination shortly after birth, but the vaccination site has remained ulcerated with persistent discharge. Over the past 2 months, he has developed enlarged axillary and cervical lymph nodes, and examination reveals hepatosplenomegaly.
He has also had two episodes of pneumonia requiring hospitalization. There is no known contact with tuberculosis.
Which of the following is the most likely diagnosis?
A. Disseminated tuberculosis
B. Disseminated BCG infection
C. Chronic granulomatous disease
D. Kawasaki disease
E. Severe bacterial sepsis
Correct answer & Explanation:
Explanation
Correct answer: B. Disseminated BCG infection
BCG is a live attenuated strain of Mycobacterium bovis. In most healthy infants, vaccination causes a small local reaction followed by healing. Persistent ulceration at the BCG site together with systemic symptoms, generalized lymphadenopathy and hepatosplenomegaly should raise strong suspicion of disseminated BCG disease.
Disseminated BCG infection is particularly important because it may be the first clinical manifestation of an underlying primary immunodeficiency. Defects affecting cell-mediated immunity and the IL-12/IFN-γ pathway are well-recognized associations. Severe combined immunodeficiency (SCID) is another important underlying disorder.
The recurrent pneumonia in this infant further supports the possibility of an underlying immunodeficiency.
Why not disseminated tuberculosis? Both BCG and M. tuberculosis can cause disseminated mycobacterial disease, but the history of recent BCG vaccination followed by a persistent BCG-site lesion and regional lymphadenopathy progressing to systemic disease strongly favors disseminated BCG infection.
Why not chronic granulomatous disease? CGD predisposes to recurrent infections, including mycobacterial infections, but disseminated BCG disease is particularly associated with defects in T-cell/IFN-γ–IL-12 immunity.
Reference:
World Health Organization. BCG vaccines: WHO position paper / Global Advisory Committee on Vaccine Safety.
Bustamante J, Boisson-Dupuis S, Abel L, Casanova JL. Mendelian susceptibility to mycobacterial disease: genetic, immunological, and clinical features. Immunological Reviews. 2014;264:145–160.
