• Increase of <4 stools/day over baseline
• Mild increase in ostomy output compared with baseline

• Increase of 4–6 stools/day over baseline
• Moderate increase of output in ostomy compared with baseline

• Increase of ≥7 stools/day over baseline; incontinence
• Hospitalization indicated
• Severe increase in ostomy output compared with baseline
• Limiting self-care ADLs

• Life-threatening (e.g., perforation, bleeding, ischemic necrosis, toxic megacolon)
• Urgent intervention required

• Asymptomatic; clinical or diagnostic observation only; intervention not indicated

• Abdominal pain; blood or mucus in stool

• Severe abdominal pain; change in bowel habits; medical intervention indicated; peritoneal signs

• Life-threatening (e.g., hemodynamic collapse); urgent intervention indicated

• May continue immunotherapy

Diet modifications (very important):

• Institute bland diet; decrease fiber, uncooked fruits/vegetables, red meats, fats, dairy, oil, caffeine, alcohol, sugar

• Send stool sample for C difficile testing, culture, and ova and parasite
• Immunotherapy to be withheld until Grade ≤1 or patient’s baseline (ipilimumab, pembrolizumab, nivolumab)
• Provide anti-diarrheals: Imodium^® (loperamide) or Lomotil^® (diphenoxylate/atropine)
• If upper or lower GI symptoms persist >5–7 days
  • Oral steroids* to be started (prednisone 0.5 mg–1 mg/kg/day or equivalent)
  • After control of symptoms, a ≥4-week steroid* taper will be initiated
• Immunotherapy to be discontinued if Grade 2 symptoms persist ≥6 weeks (ipilimumab) or ≥12 weeks (pembrolizumab, nivolumab), or for inability to reduce steroid dose to ≤7.5 mg (ipilimumab) or ≤10 mg prednisone or equivalent (pembrolizumab, nivolumab) within 12 weeks

Diet modification:

• Institute bland diet low in fiber, residue, and fat (BRAT [Bananas, Rice, Applesauce, Toast] diet)
• Decrease fiber, uncooked fruit and vegetables, red meats, fats, dairy, oil, caffeine, alcohol, sugar
• Avoid laxatives or stool softeners
• Advance diet slowly as steroids are tapered,* reduced to low doses and assess for loose or liquid stool for several days or longer
• Steroids* to be tapered slowly over at least 4 weeks

(Moderate) persistent or relapsed symptoms with steroid* taper

• Consider gastroenterology consult for possible intervention (flex sig/colonoscopy/endoscopy)
• IV steroids* to be started at 1 mg/kg/day
• Immunotherapy to be held until ≤Grade 1
• Control symptoms, then ≥4-week steroid* taper
• Recurrent diarrhea is more likely when treatment is restarted

• Onset:
  • Continued diet modification, anti-diarrheals, and steroid titration
• Immunotherapy:
  • Grade 3: Pembrolizumab or nivolumab to be withheld when used as single agent; ipilimumab to be discontinued as single agent and nivolumab when given with ipilimumab
  • Grade 4: Ipilimumab and/or PD-1 inhibitor to be discontinued
• Dosage of steroids* to be increased:
  • Steroids* 1-2 mg/kg/day prednisone or equivalent: methylprednisolone (Solu-Medrol^®) 1 g IV (daily divided) doses
• Hospitalization
• GI consultation
• Assess for peritoneal signs, perforation (NPO & abdominal x-ray, surgical consult prn)
• Use caution with analgesics (opioids) and anti-diarrheal medications

Steroid* refractory: (if not responsive within 72 hours to high-dose IV steroid* infusion)

• Infliximab (Remicade^®) 5 mg/kg infusion may be considered
• May require ≥1 infusion to manage symptoms (may re-administer at week 2 & week 6)
• Avoid with bowel perforation or sepsis
• PPD (tuberculin) testing not required in this setting
• Infliximab infusion delay may have life-threatening consequences

Diet modification:

• Very strict with acute symptoms: clear liquids; very bland, low fiber and low residue (BRAT) diet
• Advance diet slowly as steroids* reduced to low doses
• Steroids* to be tapered slowly over at least 4 weeks
• Supportive medications for symptomatic management:
  • Loperamide: 2 capsules at the onset & 1 with each diarrhea stool thereafter, with a maximum of 6 per day
  • Diphenoxylate/atropine 1-4 tablets per day
  • Simethicone when necessary