What to do if Losartan (angiotensin II receptor antagonist) enteropathy is suspected?

Management of Losartan-Induced Enteropathy

When losartan-induced enteropathy is suspected, the most important intervention is immediate discontinuation of the medication and switching to an alternative antihypertensive agent that is not an angiotensin II receptor blocker (ARB). 1

Diagnostic Approach

Clinical Presentation

• Chronic diarrhea (often severe)
• Significant weight loss
• Malabsorption symptoms
• Dehydration
• Possible abdominal pain and bloating

Initial Evaluation

1. Review medication history thoroughly

   • Focus on duration of losartan use (symptoms typically appear after months to years of use)
   • Check for dose-dependent relationship 2

2. Rule out celiac disease

   • Obtain complete celiac serology panel:
     • Anti-tissue transglutaminase (tTG)
     • Deamidated gliadin peptide (DGP) antibodies
     • Endomysial antibody (EMA)
     • Total IgA levels 1

3. Endoscopic evaluation with biopsies

   • Upper endoscopy with duodenal biopsies
   • Look for villous atrophy and inflammation
   • Consider colonic biopsies to check for microscopic colitis 3, 4

4. Histopathological examination

   • Have biopsies reviewed by an experienced GI pathologist
   • Typical findings include:
     • Villous atrophy (similar to celiac disease)
     • Variable degrees of mucosal inflammation
     • Possible subepithelial collagen deposition
     • Increased intraepithelial lymphocytes 1, 4

Management Algorithm

Step 1: Discontinue Losartan

• Immediately stop losartan 1, 3, 4
• Switch to an alternative antihypertensive that is not an ARB
• Consider ACE inhibitors, calcium channel blockers, or beta-blockers

Step 2: Supportive Care

• Manage dehydration with IV fluids if severe
• Monitor electrolytes and renal function
• Provide nutritional support if significant weight loss or malnutrition is present
• Consider temporary parenteral nutrition in severe cases 5

Step 3: Follow-up and Monitoring

• Assess clinical response after discontinuation
  • Symptoms typically improve within days to weeks
  • Complete resolution may take longer in severe cases 4, 6
• Monitor weight gain and symptom improvement
• Consider follow-up endoscopy with biopsies to document histological recovery (typically 3-6 months after discontinuation) 1

Step 4: For Persistent Symptoms

• If symptoms persist despite losartan discontinuation:
  • Consider short course of budesonide (open-capsule preferred) 1
  • Evaluate for other potential causes of symptoms:
    • Small intestinal bacterial overgrowth
    • Microscopic colitis
    • Pancreatic insufficiency
    • Lactose or fructose intolerance 1

Important Considerations

Differential Diagnosis

• Other medication-induced enteropathies (mycophenolate, methotrexate, azathioprine) 1
• Celiac disease
• Autoimmune enteropathy
• Common variable immunodeficiency
• Tropical sprue (if relevant travel history)
• HIV enteropathy 1

Potential Complications

• Severe dehydration
• Electrolyte abnormalities
• Acute kidney injury
• Possible hepatic involvement (rare) 2
• Significant malnutrition

Prevention

• Consider this diagnosis in any patient on losartan with unexplained chronic diarrhea
• Early recognition can prevent severe complications
• For patients requiring antihypertensive therapy with history of ARB-induced enteropathy, avoid all drugs in this class 6

Key Pitfalls to Avoid

1. Misdiagnosing as celiac disease - ARB enteropathy can mimic celiac disease histologically but does not respond to gluten-free diet 4
2. Delayed diagnosis - Symptoms may develop after years of medication use, making the connection difficult to recognize 5
3. Incomplete medication review - Always thoroughly review all medications in cases of unexplained enteropathy 1
4. Failure to discontinue the medication - The most critical intervention is stopping the offending drug 3, 4
5. Missing other ARB-induced enteropathies - While olmesartan is most commonly reported, other ARBs including losartan can cause similar symptoms 6, 5