Correlation of granuloma structure with clinical outcome defines two types of idiopathic disseminated BCG infection.

Bacillus Calmette Guérin (BCG) is an attenuated strain of Mycobacterium bovis that is currently used as a live vaccine for human tuberculosis. Disseminated BCG infection may rarely occur following vaccination of children. In half of the cases, regarded as idiopathic, no well-defined immunodeficiency condition can account for the infection. However, the high rates of parental consanguinity and familial forms and the associated opportunistic infections with Salmonella suggest that these idiopathic BCG infections result from one or several new type(s) of inherited immune disorder(s). As an approach to the description and understanding of this newly described condition, the associated lesions were examined. Samples from 14 patients collected from a French national retrospective study were analysed. Pathological data from 22 cases reported in the world literature were also reviewed. Two types of granuloma were found. The first type (type I, tuberculoid) consisted of well-circumscribed and well-differentiated granulomas, with epithelioid and multinucleated giant cells containing very few acid-fast rods, surrounded by lymphocytes and fibrosis and occasionally with central caseous necrosis. The second type (type II, lepromatous-like) consisted of ill-defined and poorly differentiated granulomas, with few if any giant cells and lymphocytes but widespread macrophages loaded with acid-fast bacilli. Most children displayed a single type of granuloma. One half displayed type 1 lesions and the other half displayed type II lesions. There was a strong correlation between the type of granuloma and the clinical outcome. Tuberculoid lesions were associated with survival, whilst lepromatous-like lesions correlated with death. Correlation of granuloma structure with clinical outcome defines two types of idiopathic disseminated BCG infection. The phenotypic heterogeneity of the course of BCG infection reflects distinct pathogenic mechanisms and probably results from a genotypic heterogeneity of the underlying inherited immune disorder.