case_images: PMC11416167_01
case_images: Autopsy findings of fulminant systemic C. perfringens infection in a healthy patient. (a) The skin and soft tissue of the upper extremities showed swelling with gas and subcutaneous hemorrhage. (b) There was abscess formation with multiple air spaces in the right lobe of the icteric liver. Scale bar, 2 cm. (c) Hematoxylin and eosin (HE) section of the liver tissue showed coagulative necrosis of the hepatocytes with numerous bacterial colonies (arrows). Inset, magnified view of the bacterial colony (Gram-positive rods) with Gram staining. (d) HE section of the bone marrow from the lumber spine showed coagulative necrosis of the marrow tissue with massive bacterial colonies (arrows) and multiple bubbles (asterisk). (e) Both lungs displayed congestive edema (HE staining). (f) Hemophagocytic activities of the macrophages (arrows) were significantly increased in the bone marrow (HE staining). Inset, magnified view of CD68-positive hemophagocytic macrophages.
case_images: CRIPA2024-9213132.001.jpg
case_images: PMC11416167_01_CRIPA2024-9213132.001.jpg
case_images: fig1
case_images: His trunk and extremities were swollen with wide-spreading subcutaneous hemorrhage (Figure 1(a)). Abscess formation with necrosis and air spaces was observed in the right lobe of the liver (1300 g) (Figure 1(b)). Numerous Gram-positive bacilli were seen under the microscope (Figure 1(c)), and C. perfringens was identified in culture from the antemortem blood sample. Many rods were also found in the vertebral marrow (Figure 1(d)), indicating a systemic distribution of the pathogens. Consistent with the status of systemic inflammatory response syndrome (SIRS), there were congestive pulmonary edema (left 780 g and right 1100 g), centrilobular necrosis of the liver with reactive hepatitis, acute splenitis (185 g), shock kidney (tubular degenerative necrosis) (left 240 g and right 210 g), and hemophagocytosis in each organ of the patient (Figures 1(e) and 1(f)).
case_images: A diverse role of C. perfringens toxins in the pathogenesis of fulminant infection in a healthy patient. (a) HE section of ileum (left panel) and ascending colon (right panel) showed multiple bubbles in the intestinal walls (arrows). Immunostaining of tight junction-related molecule claudin 4 showed massive loss of its reactivity in the ileal epithelium of the present case (b), in comparison with positive control (autopsied ileal samples from non-Welch infection patient) (c). Note that some intact glands preserved the immunopositivity of claudin 4 as an internal control in the present case (arrows) (b). Immunostaining protocol was according to the previous reports. Left panels, stained with 3,3'-diaminobenzidine (DAB) (brown, claudin 4); right panels, Alexa Fluor 555-stained immunofluorescence (red, claudin 4; blue, 4',6-diamidino-2-phenylindole (DAPI)). (d) A diverse role of C. perfringens toxins in the pathogenesis of fulminant infection of the present case. (1) alpha-toxin could induce intravascular hemolytic attack, and (2) CPE could destruct claudin 4 of tight junctions and facilitate systemic dissemination of the bacilli even in this immunocompetent host. CPE, C. perfringens enterotoxin; SIRS, systemic inflammatory response syndrome. Solid arrows indicate deterministic causality; dotted arrows indicate presumptive causality.
case_images: CRIPA2024-9213132.002.jpg
case_images: PMC11416167_01_CRIPA2024-9213132.002.jpg
case_images: fig2
case_images: Of interest, mild pneumatosis cystoides intestinalis-like air spaces were observed in the small and large intestines (Figures 2(a)), and immunostaining of claudin 4 (clone EPRR17575, Abcam, Cambridge, UK) showed massive loss of its reactivity in the mucosal epithelium of his lower gastrointestinal tract (positive control: autopsied intestinal samples from non-Welch infection patient) (Figures 2(b) and 2(c)), suggesting destruction of enterocytes' tight junctions and involvement of peculiar toxins to the pathogenesis of the fulminant infection in this immunocompetent host (Figure 2(d)).