The Critical Role of Pathology in the Investigation of Bioterrorism-Related Cutaneous Anthrax

Abstract

Cutaneous anthrax is a rare zoonotic disease in the United States. The clinical diagnosis traditionally has been established by conventional microbiological methods, such as culture and gram staining. However, these methods often yield negative results when patients have received antibiotics. During the bioterrorism event of 2001, we applied two novel immunohistochemical assays that can detect Bacillus anthracis antigens in skin biopsy samples even after prolonged antibiotic treatment. These assays provided a highly sensitive and specific method for the diagnosis of cutaneous anthrax, and were critical in the early and rapid diagnosis of 8 of 11 cases of cutaneous anthrax during the outbreak investigation. Skin biopsies were obtained from 10 of these 11 cases, and histopathological findings included various degrees of ulceration, hemorrhage, edema, coagulative necrosis, perivascular inflammation, and vasculitis. Serology was also an important investigation tool, but the results required several weeks because of the need to test paired serum specimens. Other tests, including culture, special stains, and polymerase chain reaction assay, were less valuable in the diagnosis and epidemiological investigation of these cutaneous anthrax cases. This report underscores the critical role of pathology in investigating potential bioterrorism events and in guiding epidemiological studies, Anthrax captured worldwide attention and aroused serious public health concerns following the intentional release of the etiological agent Bacillus anthracis in the United States postal system during Fall 2001, 1,2 resulting in 11 cases of inhalational anthrax and 11 cases of cutaneous anthrax. [3][4][5][6][7] In its conventional form, cutaneous anthrax accounts for 95% of all naturally occurring B. anthracis infections in the United States. 8 -11 Patients often have a history of occupational contact with animals or animal products contaminated with B. anthracis spores. 12-14 These pathogenic spores are introduced through a cutaneous cut or abrasion, with the most common areas of exposure are the head, neck, and extremities, although any area can be involved. Bacteremia and toxemia following cutaneous infection can occur with a fatality rate of 20% to 25% among untreated cases. [15][16][17] Cutaneous anthrax is characterized by the formation of a black eschar surrounded by prominent edema and vesicles, which may resemble many other skin lesions, such as the brown recluse spider bite, 18 -21 ulceroglandular tularemia, 22,23 plague, 24,25 ecthyma gangrenosum, 26,27 various spotted fever group rickettsial infections, 28 -31 and scrub typhus. 32,33 The clinical diagnosis of cutaneous anthrax is traditionally established by microbiological methods (eg, demonstrating gram-positive, capsulated bacilli on the smear of the lesion or isolating B. anthracis in culture). 34,35 However, gram stain and culture for B. anthracis can be unrevealing for patients who receive antibiotic therapy before specimens are obtained. 36,37 Historically, skin biopsies ...

Acquired coagulant factor VIII deficiency induced byBacillus anthracislethal toxin in mice

“…53,54 The drug rFVIII may enable enhancing coagulation in patients with anthrax who exhibit severe hemorrhage and coagulopathy, as described in clinical settings. [9][10][11][12]31 To develop an effective treatment against anthrax, combining other anti-anthrax agents with a coagulation intervention strategy may be a feasible approach. Figure 6.…”

“…6 However, the reason both clinical and animal studies have revealed that hemorrhagic disorder is one of the major manifestations of LT-treated or B. anthracis-infected hosts remains unclear. [7][8][9][10][11][12][13] Recent studies have shown that LT might contribute to hemorrhage by inducing thrombocytopenia and megakaryocytic suppression. [14][15][16] The mechanism underlying coagulation suppression, however, remains undetermined.…”

Anthrax Lethal Toxin Enhances IκB Kinase Activation and Differentially Regulates Pro-inflammatory Genes in Human Endothelium

“…In addition, we showed that LT enhances vascular cell adhesion molecule-1 (VCAM-1) expression and monocyte adhesion on the surface of tumor necrosis factor-␣ (TNF)-activated primary human endothelial cells, suggesting a possible link between LT and the vasculitis associated with anthrax (9,22,23). The enhanced expression of VCAM-1 was found to be transcriptionally driven by the cooperative activation of the VCAM1-regulating transcription factors, interferon regulatory factor-1 (IRF-1), and NF-B (24).…”

Histopathological effects of anthrax lethal factor on rat liver

“…Interestingly, others have claimed the pathologic damage after exposure to the LT occurs independently from any change in expression of cytokines (see Moayeri et al, 2003). Guarner et al (2003) suggested that the toxic effects of LT might be caused by hemorrhage, pleural effusion, and vasculitis. Vascular dysfunction is an important component in the pathogenesis of anthrax, although the underlying cause of this dysfunction is not yet known (Cui et al, 2004;Fritz et al, 1995;Shieh et al, 2003).…”