Bloody Diarrhea without a Clear Cause
Clinical Vignette
A 36-year-old man with relapsing-remitting multiple sclerosis and psoriasis presents with intermittent constipation alternating with diarrhea and rectal bleeding for 10 days.
Two months prior to presentation, he was treated with a 14-day course of amoxicillin–clavulanate for presumed bacterial sinusitis. He denies sick contacts, consumption of undercooked food, or known inflammatory bowel disease.
He was born in Guatemala and currently lives in the United States. He reports recent travel to Puerto Rico within the past three months. He is sexually active with both men and women and takes daily HIV pre-exposure prophylaxis with tenofovir alafenamide/emtricitabine (TAF/FTC). He has no history of HIV infection.
On presentation, he is afebrile with a heart rate of 102 beats per minute and a blood pressure of 124/67 mm Hg. Rectal examination does not reveal gross blood. Stool testing for common bacterial pathogens, Clostridioides difficile toxin/antigen, and fecal inflammatory markers is unrevealing. HIV testing is negative.
Because symptoms persist, a colonoscopy is performed. The colonic mucosa appears grossly normal throughout. Random biopsies are obtained to evaluate for microscopic colitis. Histopathology reveals a basophilic “blue fringe” along the surface epithelium on hematoxylin and eosin staining, and a Warthin–Starry silver stain highlights spirochetes lining the colonic surface.


H&E stain (left) demonstrates a basophilic “blue fringe” of spirochetes along the colonic epithelium. Silver stain (right) highlights spirochetes lining the mucosal surface.
Source: https://www.sciencedirect.com/science/article/pii/S2949918625001536
What is the most likely diagnosis?
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Rationale
Intestinal spirochetosis is defined by colonization of the colonic epithelium by Brachyspira species (classically B. aalborgi and B. pilosicoli). Patients may be asymptomatic or present with nonspecific gastrointestinal symptoms such as diarrhea, abdominal pain, bloating, and occasionally rectal bleeding. It is described more frequently in immunocompromised individuals, but it can also occur in immunocompetent patients.
The key diagnostic challenge is that colonoscopy often looks normal or shows only subtle, nonspecific mucosal changes. Diagnosis relies on biopsy: the organisms form a dense band on the epithelial surface, creating the classic basophilic “blue fringe” on H&E. Silver stains (e.g., Warthin–Starry) or immunostaining for spirochetes highlight the organisms and confirm the diagnosis.
Treatment is most commonly metronidazole, with macrolides as alternatives. Symptomatic response can be excellent, but relapse has been reported—sometimes months after treatment—so clinical follow-up is important, and repeat evaluation may be needed if symptoms recur.
Which treatment is most commonly recommended for symptomatic intestinal spirochetosis?
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Teaching points
Intestinal spirochetosis is often an incidental histologic diagnosis; symptoms, when present, can mimic IBS.
Colonoscopy may be grossly normal—biopsy is required, and pathologists must consider special stains.
Classic pathology: basophilic “blue fringe” on H&E; organisms highlighted by Warthin–Starry or spirochete immunostain.
Metronidazole is commonly effective, but relapse can occur; symptom recurrence should prompt reassessment.
References
Bipneet Singh, Jack Visser, Sakshi Bai, Jahnavi Ethakota, Palak Grover, Gurleen Kaur, Syed-Mohammed Jafri, Intestinal spirochetosis, Medical Reports, Volume 13, 2025, 100308, ISSN 2949-9186, https://doi.org/10.1016/j.hmedic.2025.100308. (https://www.sciencedirect.com/science/article/pii/S2949918625001536)