Histopathological Changes and Clinical Responses of Buruli Ulcer Plaque Lesions during Chemotherapy: A Role for Surgical Removal of Necrotic Tissue?

Abstract

BackgroundBuruli ulcer (BU) caused by Mycobacterium ulcerans is a necrotizing skin disease usually starting with a subcutaneous nodule or plaque, which may ulcerate and progress, if untreated, over months and years. During the currently recommended antibiotic treatment with rifampicin/streptomycin plaque lesions tend to ulcerate, often associated with retarded wound healing and prolonged hospital stays.Methodology/Principal FindingsIncluded in this study were twelve laboratory reconfirmed, HIV negative BU patients presenting with plaque lesions at the CDTUB in Allada, Benin. Punch biopsies for histopathological and immunohistochemical analysis were taken before start of treatment and after four to five weeks of treatment. Where excision or wound debridement was clinically indicated, the removed tissue was also analyzed. Based on clinical judgment, nine of the twelve patients enrolled in this study received limited surgical excision seven to 39 days after completion of chemotherapy, followed by skin grafting. Lesions of three patients healed without further intervention. Before treatment, plaque lesions were characterized by a destroyed subcutis with extensive necrosis without major signs of infiltration. After completion of antibiotic treatment partial infiltration of the affected tissue was observed, but large necrotic areas remained unchanged.Conclusion/SignificanceOur histopathological analyses show that ulceration of plaque lesions during antibiotic treatment do not represent a failure to respond to antimycobacterial treatment. Based on our results we suggest formal testing in a controlled clinical trial setting whether limited surgical excision of necrotic tissue favours wound healing and can reduce the duration of hospital stays.

Mapping biopsy for Buruli ulcer self‐medicated with occlusive dressing

“…Then, the histopathological findings change into significant infiltrates of inflammatory cells including granuloma formation. 13 Retrospectively, the lesion was relatively localized almost within the visual inspection, and the preoperative mapping biopsy revealed not only massive necrosis but also granuloma formation, which suggested that host immune defense had already worked as described above, contrary to our expectation based on the fact that the lesion was treated improperly with occlusive dressing. We cannot find any obvious evidences which suggest that the lesion of this case became exacerbated due to occlusive dressing.…”

“…Local immunosuppression dissolves when the burden of mycobacterial toxin is reduced due to the success of the antibiotic treatment. Then, the histopathological findings change into significant infiltrates of inflammatory cells including granuloma formation …”

Nontuberculous Mycobacteria

“…Additional features, more typical for an untreated BU lesion, include fat cell ghosts and minimal perivascular infiltration. 58,59 Management Although spontaneous healing of BU can be seen in up to one-third of cases, this can take months and lead to deep scarring, contractions, and disfiguring scars (Fig. 2).…”

Geographic Distribution, Age Pattern and Sites of Lesions in a Cohort of Buruli Ulcer Patients from the Mapé Basin of Cameroon

“…In 2004, the WHO introduced the use of the combination of streptomycin and rifampicin given daily for 8 weeks as treatment [14]. However, surgery and wound management remain critical aspects of BU care [15], [16].…”