Can a patient on Plaquenil (hydroxychloroquine) have a negative colonoscopy and biopsy despite gastrointestinal symptoms?

Negative Colonoscopy and Biopsy in Patients on Plaquenil

Yes, a patient on Plaquenil (hydroxychloroquine) can have a negative colonoscopy and biopsy despite having gastrointestinal symptoms. This is because Plaquenil does not typically cause endoscopically visible or histologically detectable changes in the colon that would be evident on routine colonoscopy and biopsy.

Why Colonoscopy Can Be Negative Despite Symptoms

Limitations of Colonoscopy

• Colonoscopy may miss pathology in up to 5.9% of cases, even when colorectal cancer is present 1
• Common reasons for false-negative colonoscopy results include:
  • Incomplete colonoscopy (failure to reach the cecum)
  • Poor bowel preparation
  • Misinterpretation of findings
  • Inadequate biopsy sampling
  • Systems failures in follow-up

Small Bowel Disease Not Visible on Colonoscopy

• Colonoscopy can only visualize the colon and terminal ileum
• In patients with suspected Crohn's disease with negative ileocolonoscopy, capsule endoscopy is recommended to assess the small bowel 2
• Up to 8% of patients may have imaging findings of small bowel inflammation despite negative ileoscopy and biopsy 3

Diagnostic Approach When Colonoscopy is Negative

Additional Endoscopic Evaluations

• Capsule endoscopy should be considered when:
  • Clinical features suggest Crohn's disease but ileocolonoscopy and imaging studies are negative 2
  • Symptoms persist despite negative colonoscopy 2
  • Small bowel involvement is suspected 2

Imaging Studies

• MR enterography is the preferred imaging modality to assess small bowel disease 2
• Small bowel ultrasonography may also be useful 2
• CT enterography should be limited due to radiation exposure concerns 2

Laboratory Testing

• CRP should be assessed as a marker of inflammation in all symptomatic patients 2
• Fecal calprotectin is a useful marker of intestinal inflammation 2
• Complete blood count, electrolytes, liver function tests, iron studies, vitamin B12, folate, thyroid function tests, and celiac disease serology should be included in initial workup 4

Specific Considerations for Patients on Plaquenil

Medication-Induced Colitis

• NSAIDs like diclofenac can cause colitis that may be missed on initial evaluation 5
• While Plaquenil is not commonly associated with colitis, medication-induced causes should be considered when other etiologies are ruled out

Diagnostic Yield of Terminal Ileum Biopsies

• Biopsy of endoscopically normal terminal ileum has low diagnostic yield 6
• Terminal ileum biopsies are most valuable in patients with:
  • Known or suspected Crohn's disease
  • Abnormal imaging studies of the terminal ileum
  • Endoscopic evidence of "ileitis," ulcers, or erosions 6

Management Approach

1. Review medication history thoroughly, including Plaquenil and any other medications that might cause GI symptoms
2. Consider additional testing if symptoms persist:
   • Capsule endoscopy to evaluate small bowel
   • Cross-sectional imaging (preferably MR enterography)
   • Stool studies for infectious causes
   • Inflammatory markers (CRP, fecal calprotectin)
3. Evaluate for other causes of GI symptoms:
   • Microscopic colitis (requires biopsies from both right and left colon)
   • Bile acid malabsorption
   • Small intestinal bacterial overgrowth
   • Celiac disease

Conclusion

A negative colonoscopy and biopsy in a patient on Plaquenil does not rule out significant gastrointestinal pathology. Further evaluation with capsule endoscopy, cross-sectional imaging, and laboratory testing may be necessary to identify the cause of persistent symptoms, particularly when small bowel disease is suspected.