Apoptosis in Buruli ulcer: A clinicopathological study of 45 cases

Aims: To investigate the presence and pathogenetic role of apoptosis in Buruli ulcer (BU), a highly destructive skin disease caused by Mycobacterium ulcerans. Methods and results: Forty-five skin biopsies obtained from 30 Beninese patients affected by BU, in different clinical and therapeutic periods, were analysed for the main histopathological features (inflammatory infiltration, necrosis, sclerosis, oedema, granulomas and nerve damage). Immunofluorescent detection of antigens (anti-Bax, anti-caspases-3 and -8), together with deoxyuridine, 5′-triphosphate (dUTP) nick end labelling (TUNEL) assay, were also performed. A significant decrease in inflammatory infiltration (P=0.0001) was detected between the beginning and end of antibiotic treatment. Neutrophils predominated in the first phase, while lymphocytes and plasma cells were increased at the end of the therapy. An inverse correlation between tissue necrosis and sclerosis was observed (P=0.001). In 11 cases, inflammatory and regressive changes involved the nerve bundles with axonal degeneration and disruption of nerve fibres. TUNEL assay detected apoptotic bodies within nerve bundles, and these decreased from beginning to end of therapy. Bax, caspase-3 and -8 were down-regulated over the course of antibiotic therapy. Conclusions: In BU, apoptosis plays a role in promoting and sustaining the destructive changes and is implicated in the neural pathology that is associated with clinically detected anaesthesia.