Andrew H. Zabolotsky, MD, is a second year gastroenterology and hepatology fellow at Thomas Jefferson University Hospital in Philadelphia, Pennsylvania. He received his MD from Rutgers New Jersey Medical School in Newark, NJ and then completed his internship and residency in internal medicine at Thomas Jefferson University Hospital.
A 53-year-old black man with a past medical history of hepatitis C and HIV on antiretroviral therapy presented to the outpatient gastroenterology clinic with a complaint of rectal bleeding. He had noticed bright red blood mixed with his stool for about 1 week prior to his clinic visit, and has associated dyschezia.
Andrew H. Zabolotsky
The patient's medical history was significant for hepatitis C infection, for which he completed a course of Harvoni (ledipasvir/sofosbuvir, Gilead Sciences) and achieved sustained virologic response, as well as HIV infection, for which he was on Intelence (etravirine, Janssen) and Truvada (emtricitabine/tenofovir, Gilead Sciences). He was also on terbinafine for onychomycosis. His infectious disease care provider was contacted, and disclosed that his HIV was under good control and his most recent CD4+ count was over 450. The patient does not smoke cigarettes, but did admit to alcohol consumption on a regular basis, typically in periodic binges. The patient is homosexual, participating in anal intercourse with men.
Two days prior to coming in, he went to the ED with the same complaint where he received an anoscopy. He was told he did not have hemorrhoids or anal fissures. Laboratory studies in the ED disclosed anemia (hemoglobin, 13.2 g/dL), and he was referred to follow up with gastroenterology as an outpatient. He had never had rectal bleeding before. He denied any other associated symptoms, including abdominal pain, nausea or vomiting and has not had any recent weight loss. He had no melena and had not noticed any change in stool caliber. He had never had a colonoscopy.
On exam, the patient's vital signs were stable, and he was afebrile. He did not have any abdominal tenderness and his rectal exam showed no external or internal hemorrhoids and no fissures or skin tags, but he had rectal tenderness on exam with heme-negative, brown stool in the vault. The patient was scheduled for a colonoscopy.
Colonoscopy showed ulceration and friability in the rectum and sigmoid colon that bled on contact and extended up to 25 cm from the anal verge. Proximal to that, the colonic mucosa was normal and it was an otherwise normal colonoscopy. Biopsies were taken of the ulcerated areas. Pathology of the biopsies showed intestinal spirochetosis.
Figure 1. Silver stained colon ulcer biopsy, highlighting the spirochetes docked perpendicularly to the colonic epithelium.
Figure 2. Colonoscopic view of ulceration in the sigmoid colon.
Source: Thomas Jefferson University Hospitals
Intestinal spirochetosis is known as a potentially devastating disease in the world of veterinary medicine, well described in many domesticated and livestock animal species. However, its clinical significance in humans heavily debated. On histology and electron microscopy, the spirochete bacteria are seen adhering to the colorectal epithelium, which is thought to be pathognomonic for the mechanism by which the bacteria cause disease. In veterinary medicine, spirochetosis can cause diarrhea, which is frequently described as “porridge-like,” as well as slowed growth rates and malnutrition.
Despite being documented in Asia, Africa, Indonesia, as well as the Western World, the disease in humans is still not well understood. Studies have shown that disease manifestation does correspond to living in a developing region (32.6% prevalence among Australian aboriginal children vs. 1.2% in non-aboriginal Australian children and adults, in patients with GI symptoms). There is a 1% to 1.5% prevalence in most developed regions.
The most common spirochetes associated with intestinal spirochetosis are Brachyspira aalborgi and pilosicoli. Treponema has also been described in patients with clinically insignificant and significant disease. In symptomatic cases of intestinal spirochetosis, the most common complaints are a chronic, watery diarrhea as well as a vague, crampy abdominal pain for which there is no other discernible etiology. Most cases are incidentally diagnosed on screening colonoscopy. Most cases present with mild to moderate symptoms, but the severity can range from completely asymptomatic to rapidly fatal, as there have been nine cases of invasive disease described in British literature, mostly in critically ill and immunocompromised patients.
The biopsies of infected individuals show villus blunting of the epithelium, mitochondrial swelling and glycocalyx defects. The amount of cell destruction correlates with the severity of symptoms, with patients with more severe symptoms showing a greater degree of microvillus destruction and a higher burden of spirochete attachment. The diarrhea associated with symptomatic intestinal spirochetosis is thought to be related to the decrease in absorptive surface area due to the architectural disruption caused by the spirochetes.
In patients with HIV infection, such as the patient discussed here, a higher degree of epithelial invasion and a more severe loss of microvilli has been seen, compared with HIV negative patients. Interestingly, among men with HIV infection who have sex with men in developed countries, the colonization rate of spirochetes is highest, with a 20.6% to 62.5% colonization rate described. This finding has caused debate on whether intestinal spirochetosis is sexually transmittable. The degree of immunodeficiency has not been found to correlate with disease severity.
Treating intestinal spirochetosis is done with the use of antibiotic therapy. Most commonly, metronidazole 500 mg four times daily for 10 days has been used. Symptomatic improvement has also been reported with the use of macrolides and clindamycin.
The patient’s infectious disease care provider was contacted regarding this diagnosis and she explained that he had had a history of numerous treatment courses for syphilis. She believed that this case of intestinal spirochetosis may very likely be syphilis proctitis and an appointment was made for him to follow up with his infectious disease clinic. The care provider planned on empirically treating the patient with penicillin for the presumed diagnosis of syphilis proctitis, and if he did not respond to treatment, then a trial of metronidazole therapy would be started.
Although uncommon, and even more uncommonly symptomatic, intestinal spirochetosis should be considered on the differential diagnosis for a patient with diarrhea and hematochezia, especially in patients with HIV infection.
Tsinganou E and Gebbers J-O. GMS German Medical Science. 2010;8:doi:10.3205/000090.
Voltaggio L, et al. Adv Anat Pathol. 2014;doi:10.1097/PAP.0000000000000014.