Erosive acute colitis associated with intestinal spirochetosis

Although usually believed to be harmless, intestinal spirochetosis may active erosive colitis associated with intestinal spirochetosis that may mimic idiopathic chronic inflammatory bowel disease. Case presentation. A 49-year-old homosexual male patient sought medical assistance due to asthenia, rectal bleeding, tenesmus, and diarrhea for one month. He had been using corticosteroids for nine months to treat sciatic nerve pain. Colonoscopy showed rectum and distal sigmoid with diffuse erythema with many surface erosions. Rectal biopsy showed inflammatory changes including chronic changes such as architectural distortion and basal plasmacytosis, and active inflammation including crypt microabscesses. In all large bowel sample, dense colonization of intestinal spirochetosis was observed. Patient also had a positive PCR testing for Chlamydia trachomatis. The patient was treated with metronidazole for 14 days, ciprofloxacin for 14 days and azithromycin (single dose). Symptoms improved and the patient is asymptomatic after two months of follow-up. In some high-risk groups, intestinal spirochetosis may cause colonic manifestations with overlapping features with intestinal bowel diseases. Awareness of this association is importance since proper antibiotic therapy against Brachyspira (metronidazole) is highly effective. Coinfection with other sexually transmitted infections is common and proper treatment is required.


Background
Intestinal spirochetosis is characterized by the presence of spirochetes (spirally shaped microorganisms) on the luminal surface of the large bowel mucosa. In western countries, its prevalence in biopsies is 2-16% and is significantly higher in homosexual men and HIV infected patients (up to 50%). Associations with diverticular disease, intestinal bowel disease, hyperplastic and adenomatous polyps have been described. Most common organisms implicated in intestinal spirochetosis are Brachyspira aalborgi and Brachyspira pilosicoli and are not genetically related to Treponema pallidum. The colonization of luminal border of the colonic mucosa is usually not associated with endoscopic abnormalities or inflammatory changes at microscopy (occasional cryptitis may be seen) (Odze and Goldblum, 2014). The organisms stain with Warthin-Starry, silver impregnation, Alcian blue (pH 2.5) and PAS stains, however, some of are subjected to technical quality variations and significant background staining. Specific anti-Brachyspira immunohistochemistry, polymerase chain reaction and in situ hybridization have been developed but are not widely available. A useful supplementary diagnostic tool is the cross reactivity between anti-Treponema using in immunohistochemistry and the microorganisms that cause intestinal spirochetes (Tanahashi et al. 2008;Graham et al. 2018).

Case presentation
A 49-year-old homosexual male patient sought medical assistance due to asthenia, rectal bleeding, tenesmus, and diarrhea for one month. He had been using corticosteroids (oral and intramuscular) and gabapentin for nine months to treat sciatic nerve pain. He had a prior history of syphilis treatment three years before. Colonoscopy showed rectum and distal sigmoid with diffuse erythema (moderate to severe) with many surface erosions (Fig. 1). Colonic segments and terminal ileum were normal.
Rectal biopsy showed inflammatory changes including basal plasmacytosis, and active inflammation including crypt microabscesses (Fig. 2). In all large bowel samples (cecum, ascendant, transverse, sigmoid and rectum), a dense basophilic surface of spirally shaped organisms was observed. These organisms stained strongly positive for PAS stain and anti-Treponema antibody by immunohistochemistry (Fig. 3).
Serology was negative for CMV, HIV, herpes virus. Serology for syphilis (low VDRL titers) were consistent with past infection. PCR for Chlamydia trachomatis was positive in an anal sample (cobas® 4800 CT/NG Test, Roche). The patient was treated with metronidazole for 14 days, ciprofloxacin for 14 days and azithromycin (single dose). Symptoms improved and the patient is asymptomatic after two months of follow-up.

Discussion
Although usually believed to be harmless, intestinal spirochetosis has been associated in a case control study with watery diarrhea, change in bowel habits (Alsaigh and Fogt 2002). Most infections are asymptomatic (Tanahashi et al. 2008). Some recent reports highlight the potential association between intestinal spirochetes and active colitis and mucosal erosions. Agrawal and colleagues reported a 45year-old HIV-positive men with clinical history of one month of constipation, abdominal pain, and intermittent rectal bleeding. Colonoscopy showed aphthous ulcers in rectosigmoid and cecum. The patient had history of syphilis, chlamydia infection and contact with dogs. Symptoms completely resolved after treatment with metronidazole 500 mg 4 times a day for 10 days (Agrawal et al. 2019). Other recent publication reports a 38year-old man with recent diagnosis of HIV infection. He had clinical history of fatigue, palpitations, and dyspnea for six months. He had severe anemia and tachycardic. After episodes of rectal bleeding, colonoscopy was performed and revealed fissure, severe colitis with pseudopolyposis, deep ulcerations, erythema, and friability from the anal verge to 17 cm. Magnetic resonance imaging showed perirectal lymphadenopathy and perianal fissures. Treatment was started with steroids due to presumed Crohn's disease. No history or testing for chlamydia was reported. After the pathology report of intestinal spirochetosis involving proximal to sigmoid colon, the patient was treated with metronidazole 500 mg 3 times daily for 10 days and antiretroviral therapy. Symptoms improved within 4 days and resolved in two weeks (Vipani and Yang 2019).
In the patient presented herein, it is not possible to exclude that the main etiologic factor for the mucosal damage was chlamydial infection, or a synergic association of both infections. Chlamydia trachomatis (serovars D-K) is usually a cause of mild proctitis associated with pruritus, mucoid discharge, and perianal pain. Two thirds of all infections are asymptomatic (Hamlyn and Taylor 2006). Serotypes L1, L2, and L3 causes lymphogranuloma venereum which may be associated with severe proctitis, rectal ulcerations, purulent or sanguineous anal discharge (Hamlyn and Taylor 2006). Patients may also present with perirectal abscesses, anal fissures, fistula formation and chronic diarrheathus simulating Crohn's disease (Assi et al. 2014). The patient had no significant lymphadenopathy at time of presentation. The PCR test comprises the L1, L2 and L3 serotypes. The successful treatment, however, was not the recommended regimen for lymphogranuloma venereum (21 days of doxycycline, azithromycin, and erythromycin). There is no serologic testing established and starboarded for lymphogranuloma venereum (Center of Disease Control and Prevention, USA, 2021). In the present case, we did not observe increased intramucosal eosinophils (in lamina propria or intraepithelial) in any biopsy samples. Some recent studies highlighted these findings as commonly associated with intestinal spirochetosis (Walker et al. 2015;Ogata et al. 2021).

Conclusion
In some high-risk groups, notably homosexual men and HIV positive patients, intestinal spirochetosis may cause colonic manifestations with overlapping features with intestinal bowel diseases. Awareness of this association is importance since proper antibiotic therapy against Brachyspira (metronidazole) is highly effective. Coinfection with other sexually transmitted infections is common and proper treatment is required.
Abbreviations HE: Hematoxylin and eosin stain