Faculty of Veterinary Medicine, Clinic of Small Animal Medicine, Centre for Clinical Veterinary Medicine, LMU Munich, Munich, Germany
Acute hemorrhagic diarrhea (AHD) is a common complaint in dog population presented to primary care veterinarians. The term “hemorrhagic gastroenteritis” (HGE) was established in 1970 and defines a syndrome characterized by acute-onset vomiting, anorexia and lethargy, progressing to hematemesis and severe hemorrhagic diarrhea. Recently, the term HGE was replaced by “acute hemorrhagic diarrhea syndrome” (AHDS). A significant increase in PCV is considered characteristic for this disorder, and in many cases no underlying causes for this disorder could be identified.
A recently published study demonstrated acute intestinal mucosal necrosis (10/10) and intestinal neutrophilic infiltration (10/10) as a characteristic histopathologic finding in duodenal biopsies taken intra vitam from 10 dogs with AHDS. A striking feature observed in the histologic sections of the intestinal biopsies of most dogs with AHDS was a dense layer of large rod-shaped bacteria adherent to necrotic villous tips. These bacteria were identified as Clostridium perfringens by immunohistochemical staining and culture.
A primary pathogenic role of C. perfringens in dogs with AHDS was suspected and supported by the fact that no other explanation for the necrosis of the superficial intestinal epithelium could be identified. Also, the presence of bacteria was closely associated with epithelial lesions. Influence of C. perfringens enterotoxin (CPE) could potentially explain the extensive fluid loss and intestinal necrotic lesions characteristically observed in dogs with AHDS, and was suggested as being responsible for diarrhea. However, the prevalence of CPE in the feces of dogs with AHDS is only 24% and therefore it does not play a significant role in dogs with AHDS.
Recently, a novel toxin in C. perfringens type A strains has been isolated from a dog with fatal hemorrhagic enteritis. It was speculated that this pore-forming toxin (netF), related to the leukocidin/hemolysin superfamily, has been responsible for the necrotic enterocolitis in this dog. In order to confirm this hypothesis, C. perfrigens strains isolated from the duodenum of the six dogs with acute hemorrhagic diarrhea and of the two dogs in which endoscopy was performed for unrelated disease, were genotyped. Additionally, PCR was performed for the pore forming toxins netE and netF. In all dogs, clostridial strains were categorized as C. perfringens type A. However, only the clostridial strains of dogs with AHDS and not those of the two control dogs encoded for pore forming toxins. A second study with the aim to determine the prevalence of C. perfringens encoding netE and netF in feces of dogs with AHDS has been performed recently. Fecal samples of 54 dogs with AHDS, 54 dogs with canine parvovirus (CPV) infection and 66 healthy dogs were tested by real-time PCR for netE and netF genes. A significant differences in the prevalence of the pore-forming toxins netE and netF have been found between the three groups (dogs with AHDS: 26/54 (48.1%); dogs with CPV-infection: 0/54 (0%); healthy dogs; 8/66 (12.1%). Results from that study suggested that overgrowth of C. perfringens type A strains encoding for netE and netF is not a general sequel of acute hemorrhagic diarrhea, since these genes were not detected in dogs with CPV infection. A primary pathogenic role of these toxins in AHDS is likely, however, it is not known if additional clostridial toxins are also involved in the disease process. Therefore, additional studies are needed in order to identify the inciting cause for the overgrowth and increased toxin production of C. perfringens in dogs with AHDS.
Although bacterial toxins are involved in the pathogenesis of AHDS and necrosis of the intestinal mucosal surfaces, antimicrobial administration as a routine treatment in dogs with AHDS is not needed. In a prospective placebo-controlled treatment study, it has been confirmed that in dogs with aseptic AHDS, antibiotics do not change outcome or recovery time. However, close patient monitoring is essential since ruling out an enteral infection with pathogenic bacteria is challenging, and bacterial translocation is a potentially life-threatening complication in dogs with AHDS.
The following parameters should be used as an indication for antibiotic treatment in dogs with AHDS:
- Rectal temperature >39.5°C
- Tachycardia after rehydration and pain management >120/min
- WBC <4 or >25 x 109/l
- Band neutrophils >1.5 x 109/l
Besides these criteria, evaluation of the clinical course and response to fluid therapy is important in detecting low numbers of patients that require antibiotic treatment. With adequate fluid therapy (crystalloids; fluid amount depending on dehydration, maintenance demands, and ongoing losses) a rapid improvement of clinical signs can typically be observed during the first 48 hours without antibiotic treatment. Dogs that do not adequately respond to fluid therapy after 4 hours (i.e., alert mental status, heart and respiratory rate dropping into normal range, adequate production of urine) should be categorized as “complicated AHDS” patients. That should prompt the clinician to look for other underlying causes (e.g., acute pancreatitis, viral enteritis). In patients with suspected bacterial infection with an enteropathogen or bacterial translocation from the intestinal tract resulting in sepsis, bacterial cultures from blood, aspirated material from enlarged abdominal lymph nodes, bile or even feces might help to isolate the responsible pathogen and to select an appropriate antibiotic. Until sensitivity testing is available, suspect septic patients should be treated with intravenously administered antibiotics effective primarily against gram-negative and anaerobic bacteria (e.g., fluoroquinolones and metronidazole).
In summary, several studies demonstrated an apparent association between C. perfringens and the occurrence of acute hemorrhagic diarrhea. There is strong supportive evidence regarding clostridial toxins as a cause for the intestinal epithelial necrosis in dogs with AHDS. Most dogs with acute hemorrhagic diarrhea are significantly dehydrated and show a rapid clinical improvement with adequate fluid therapy. Septic events are uncommon, and prognosis is good even in patients without antibiotic treatment. Close patient monitoring is essential to identify dogs requiring antibiotic treatment.