The tropical necrotizing skin disease Buruli ulcer (BU) caused by Mycobacterium ulcerans is associated with extensive tissue destruction and local immunosuppression caused by the macrolide exotoxin mycolactone. Chemotherapy with a combination of rifampicin and streptomycin for 8 weeks is the currently recommended treatment for all types of BU lesions, including both ulcerative and non-ulcerative stages (plaques, nodules and edema). Our histopathological analysis of twelve BU plaque lesions revealed extensive destruction of sub-cutaneous tissue. This frequently led to ulceration during antibiotic treatment. This should not be mistaken as a failure of the antimycobacterial chemotherapy, since we found no evidence for the persistence of active infection foci. Large necrotic areas were found to persist even after completion of antibiotic treatment. These may disturb wound healing and the role of wound debridement should therefore be formally tested in a clinical trial setting

A Chauty

Ange Dodji Dossou

CE Attinger

CL Gordon

D Schütte

DP O'Brien

FS Sarfo

G Broughton

Gerd Pluschke

Ghislain Emmanuel Sopoh

HS Thangaraj

K Asiedu

K Kibadi

Luc Valère Brun

Marie-Thérèse Ruf

MC Robson

NJ Trengove

Pamela L. C. Small

PDR Johnson

PG Bowler

Roch Christian Johnson

RS Cornell

S Etuaful

S Rondini

TS van der Werf

WA Nienhuis

Yves Thierry Barogui

PLoS Neglected Tropical Diseases

English

PubMed

BACKGROUND: Buruli 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 FINDINGS: Included 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/SIGNIFICANCE: Our 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

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Histopathological changes and clinical responses of Buruli ulcer plaque lesions during chemotherapy: a role for surgical removal of necrotic tissue?

 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.Included 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.Our 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

Ruf Marie-Thérèse

Sopoh Ghislain Emmanuel

Brun Luc Valère

Dossou Ange Dodji

Barogui Yves Thierry

Johnson Roch Christian

Pluschke Gerd

Public Library of Science (PLOS)

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

BACKGROUND: Buruli 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 FINDINGS: Included 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/SIGNIFICANCE: Our 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 stay

Ruf, M. T.

Sopoh, G. E.

Brun, L. V.

Dossou, A. D.

Barogui, Y. T.

Johnson, R. C.

Pluschke, G.

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Histopathological changes and clinical responses of Buruli ulcer plaque lesions during chemotherapy : a role for surgical removal of necrotic tissue?

Crossref

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

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