Table 5. Clinical, Endoscopic Finding, and Histology of Anti-CD20 (Rituximab, RTX)-Associated Colitis.
| Case | Clinical | Imaging study | Colonoscopy | Lab | Biopsy finding | Histology on colectomy | IHC | Final diagnosis | Reference |
|---|---|---|---|---|---|---|---|---|---|
| 1 | Severe abdominal pain and diarrhea | N/A | Diffuse severe colitis on sigmoidoscopy | N/D | N/A | Diffuse colitis with pneumatosis in colectomy specimen | N/D | Fulminant colitis | [63] |
| 2 | 2-week history of fever, cough, shortness of breath, and watery diarrhea. On the sixth day of admission the patient developed severe bloody diarrhea (6 - 7 bowel movements/day) | A CT scan revealed diffuse thickening of the entire colon with pericolic stranding adjacent to cecum and ascending colon. | Flexible sigmoidoscopy revealed severe confluent inflammation extending from the anorectal junction to the proximal limit of viewing at 30 cm | CBC neutrophils was 4.9 × 109/L; Stool specimens were negative for Salmonella, Shigella, Campylobacter, parasites, and Clostridium difficile toxin A and B | Biopsies from the rectal and colonic mucosa revealed almost complete dropout of tubules and almost complete loss of surface epithelium without any pseudomembranes. The few residual crypts showed marked depletion of mucin and extensive apoptosis. Immunohistochemistry for CMV was negative. | Total colectomy 2 weeks after the initial onset of bloody diarrhea because of failure to respond to hydrocortisone therapy. Histology of colectomy showed diffuse pancolitis and terminal ileitis. | Lack of CD20+ cells; Normal number to a moderate increase of CD3+ cells; Moderate excess of enlarged macrophages | Severe apoptotic enterocolopathy/RTX-induced immunodysregulatory ileocolitis | [68] |
| 3 | N/A | N/A | N/A | N/A | N/A | Fulminant colitis | N/A | Fulminant colitis | [69] |
| 4 | Developed bloody diarrhea up to 20 stools per day | N/D | Sigmoidoscopy revealed colitis | N/D | Colonic biopsy taken 67days after initiation of RTX: inflammation, irregular crypts, and crypt abscesses | N/D | Biopsy taken 67 days after initiation of RTX: absence of CD20+ cells | Ulcerative colitis | [67] |
| 5 | Developed crampy abdominal pain, bloody diarrhea with 20 stools per day, weight loss, intermittent fevers | Abdominal ultrasound revealed severe pancolitis with wall thickening up to 6 mm. | Severe pancolitis with deep ulcers | Blood, urine, stool cultures negative. Clostridium difficile assays negative. Torovirus detected in the stool by electron microscopy. | Cryptitis with mixed inflammation in the lamina propria. No granulomata were identified. | N/D | Biopsy: absence of CD20+ cells | Severe ulcerative colitis | [66] |
| 6 | Profuse watery diarrhea | N/A | Erythematous mucosa (colitis) | N/A | Important infiltrates composed of mainly CD8+ T lymphocytes | N/D | Biopsy: primarily CD8+ T lymphocytes | Ulcerative colitis developed after initial episode of acute appendicitis | [70] |
| 7 | Bloody diarrhea developed 7 weeks after completion of biweekly at a dose of 1 g/2 weeks | N/D | Moderately severe pancolitis | N/D | Biopsy at 13 weeks: Goblet cell depletion, active and chronic inflammation with crypt abscess | N/D | Biopsy at 13 weeks: absence of CD20+ cell in the colonic biopsies | Ulcerative colitis | [64] |
| 8 | Crohn’s disease | [62] | |||||||
| Two episodes of fever and diarrhea | N/D | Non-specific transverse colon ulcer, normal ileum (at the first episode) | Clostridium difficile was positive for the first episode. | No viral inclusions, granulomas, or changes of chronicity | Treated with metronidazole but had ongoing exacerbations of abdominal pain and diarrhea. | N/D | |||
| A few month later, patient presented with abdominal pain, rectal bleeding | PET-CT revealed FDG-avid disease in her ileum when the patient had abdominal pain. | Ulcer at ileocolic anastomosis and an ulcer at the hepatic flexure and left colon | Fecal calprotectin 5,403 mg/kg | Patchy active inflammation with ulceration and multiple small granuloma, some with multinucleated giant cells | Patient underwent resection 3 month later because of the development of inflammatory mass in the right colon despite budesonide therapy. | N/D | |||
| 9 | Crohn’s disease | [62] | |||||||
| 5-week history of diarrhea, abdominal pain, fevers, and 8 kg of weight loss | Distal ileal wall thickening | Ileal inflammation, linear ulceration, but normal colonic mucosa | Anemia (Hb at 116 g/L); ESR of 74 mm/h; CRP of 87 mg/L; Fecal calprotectin of 3,226 mg/kg | N/A | N/D | N/D | |||
| Re-presented 3 weeks later with recurrent fevers and worsening abdominal pain despite budesonide therapy | PET-CT revealed transmural update and thickening in the mid to distal small bowel. | Ileal inflammation, linear ulceration for at least 15 cm very easy contact bleeding, but normal colonic mucosa | N/D | Active ileitis with ulceration; Focal active colitis with ulceration and a single poorly formed granuloma | N/D | N/D | |||
CMV: cytomegalovirus; CRP: C-reactive protein; ESR: erythrocyte sedimentation rate; FGD: fluorodeoxyglucose; Hb: hemoglobin; N/A: information not available; N/D: not done; PET-CT: positron emission tomography/computed tomography; RA: rheumatoid arthritis; RTX: rituximab; SLE: systemic lupus erythematosus.