Severe multifocal form of buruli ulcer after streptomycin and rifampin treatment: comments on possible dissemination mechanisms

Abstract

Buruli ulcer (BU), a disease caused by Mycobacterium ulcerans, leads to the destruction of skin and sometimes bone. Here, we report a case of severe multifocal BU with osteomyelitis in a 6-year-old human immunodeficiency virus (HIV)-negative boy. Such disseminated forms are poorly documented and generally occur in patients with HIV co-infection. The advent of antibiotic treatment with streptomycin (S) and rifampin (R) raised hope that these multifocal BU cases could be reduced. The present case raises two relevant points about multifocal BU: the mechanism of dissemination that leads to the development of multiple foci and the difficulties of treatment of multifocal forms of BU. Biochemical (hypoproteinemia), hematological (anemia), clinical (traditional treatment), and genetic factors are discussed as possible risk factors for dissemination.

Figure 1.

Patient DR at admission (May 18, 2007), with bifocal lesions on (A, B) the right foot and (C, D) the left hand. This figure appears in color at www.ajtmh.org.

Figure 2.

Histopathologic appearance of lesions at admission. Type of specimen: skin (epidermis, dermis, hypodermis). Lesions: psoriasiform hyperplasia of the skin (A); coagulative necrosis (B, >>) of the hypodermis with calcification foci (C, +) and inflammatory infiltration of mild to moderate intensity (neutrophils, lymphocytes) (D, ***). Images of vasculitis (D, = >). Diagnosis: consistent with BU. Hematoxylin and eosin staining (HE). This figure appears in color at www.ajtmh.org.

Figure 3.

Histopathologic appearance of lesions after 4 weeks of S+R therapy (June 2007). Ziehl-Neelsen (ZN) staining showing coagulative necrosis, steatonecrosis, many clusters of bacilli in the interlobular wall (A) and few clusters of bacilli in the coagulative necrosis area (B). Magnifications: A and B: ZN ×100. This figure appears in color at www.ajtmh.org.

Figure 4.

Patient DR dissemination steps after the beginning of S+R therapy: July 2007 (W10): (A) first dissemination with swelling of the left elbow and (B) right hand; August 2007 (W12): (C) second dissemination with swelling of the left foot and (D) a plaque with a small ulcer on the right elbow; December 2007 (M7) and January 2008 (M8): (E) fourth and fifth disseminations with swelling of the right wrist and (F) the right foot; March 2008 (M10): (G) sixth dissemination with ulcer on the right knee; January 2009 (M20): (H) seventh dissemination with swelling on the lateral aspect of the right leg. This figure appears in color at www.ajtmh.org.