Case data
The patient, a 67-year-old female, presents with severe abdominal pain and progressive worsening of non-bloody diarrhoea a few months ago, with fecal incontinence and nocturnal symptoms. The patient lost about 20 pounds and his physical condition decreased.
The patient has a history of collagenous colitis and was diagnosed with watery diarrhoea in another hospital 9 months ago without associated abdominal pain, fecal incontinence, or weight loss, and laboratory tests including haemoglobin, albumin, and CRP were normal. Colonoscopy is also normal, but shows histologic features of collagenous colitis. The patient started taking alosetron approximately 5 months prior to this visit. Other medications include amlodipine, which is used to treat high blood pressure, and hydrochlorothiazide. Notably, the patient was not taking selective serotonin reuptake inhibitors, nonsteroidal anti-inflammatory drugs, or proton pump inhibitors.
患者此次就诊，实验室检查显示血红蛋白9.6 g/dL（11.6-15.0 g/dL），钾3.2 mmol/L（3.6-5.2 mmol/dL），肌酐1.16 mg/dL（0.59-1.04 mg/dL），CRP 230 mg/L（<8.0 mg/L），白蛋白2.4 g/dL（3.5-5.0 g/dL）。 乳糜泻血清学试验呈阴性。 胃肠道病原体检测呈阴性。 CT小肠成像显示小肠未见异常增厚或增强，但存在经直肠远端横结肠的弥漫性肠壁增厚和黏膜增厚（图A）。
Figure A
Colonoscopy revealed significant hyperemia, erythema, and deep perforated ulcers in multiple parts of the colon (Figure B).
Figure B
Biopsy revealed the following results (panel C): negative cytomegalovirus staining with the exception of amyloid, histoplasmosis, and mycobacterial special staining.
Figure C
How should it be diagnosed?
Analytical diagnosis
Diagnosis: ischemic colitis secondary to alosetron.
The differential diagnosis of colitis other than inflammatory bowel disease (IBD) is broad, including various infections, drug-induced colitis, ischemia, diverticular disease-associated segmental colitis, isolated rectal ulcer syndrome, and vasculitis. Depending on the patient's exposure history and immunity, the class of infection to be identified may include bacteria (Salmonella, Shigella, Campylobacter, and Clostridium difficile), viruses (cytomegalovirus), fungi (histoplasmosis), and mycobacteria (Mycobacterium tuberculosis). A detailed sexual history should be obtained in patients with isolated proctitis, as syphilis, Neisseria gonorrhoeae, and Chlamydia trachomatis (lymphogranuloma venereum) may mimic ulcerative proctitis. Radiation proctitis, shunt colitis, and graft-versus-host disease are also included in the differential diagnosis in patient populations with a history of relevance. To make an accurate diagnosis, a thorough examination of the patient's symptoms, risk factors, medications, endoscopic features, and histologic findings is required.
In this case, the diagnosis of drug-induced colitis secondary to alosetron is based on the presence of severe colitis, no evidence of chronic IBD, and exclusion of a variety of other underlying causes, including common and atypical infections. This case highlights the need for clinicians to explore alternative diagnostic approaches when patients with microscopic colitis have significant systemic disease features, such as anemia, markedly elevated inflammatory markers, weight loss, hypoalbuminemia, and decreased function (Figure D). These objective findings cannot be caused or explained by microscopic colitis, and other pathological factors need to be excluded.
Figure D
Summary of the case
- Ischemic colitis secondary to alosetron is a rare but serious adverse event.
- Alosetron is a selective 5-HT3 antagonist originally approved by the FDA in 2000 for the treatment of women with diarrheal irritable bowel syndrome (IBS-D); Voluntary withdrawal due to serious adverse events (severe complications of ischemic colitis and constipation).
- In 2002, the FDA approved the reintroduction of alosetron, restricting its use to women with severe IBS-D at an initial dose of 0.5 mg twice daily under a risk management program. If constipation occurs, the patient must stop taking the drug until symptoms have resolved, and the drug can be restarted at 0.5 mg per day; However, if constipation recurs at lower doses, alosetron should be discontinued. If symptoms are not controlled after 4 weeks, the dose can be increased to 1 mg twice daily. If symptoms persist after another 4 weeks, alosetron should be discontinued.
- In a systematic review and network meta-analysis of patients with IBS-D, alosetron has been shown to be superior to placebo in terms of FDA-recommended endpoints, including IBS overall score, abdominal pain, and stool consistency response.
Patient clinical outcomes
After discontinuation of alosetron, patients reported significant improvement in diarrhea and relief of abdominal pain and fecal incontinence within a week. Follow-up colonoscopy about 8 weeks after discontinuation of the drug showed almost complete resolution of colonic inflammation (Figure E).
Figure E
Follow-up colonoscopy after about 12 months shows a normal appearance from the cecum to splenic flexure, with residual scarring of the descending colon, sigmoid colon, and rectum. Biopsy findings consistent with collagenous colitis but no other histologic abnormalities.
Bibliography:
1. Voth E, Johnson A. A Curious Case of Colitis. Gastroenterology. 2024 Apr 25:S0016-5085(24)00491-8. doi: 10.1053/j.gastro.2024.04.026.
2. Lembo A, Sultan S, Chang L, et al. AGA Clinical Practice Guideline on the Pharmacological Management of Irritable Bowel Syndrome With Diarrhea[J]. Gastroenterology, 2022, 163(1): 137-151.
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