A 32-year-old woman with systemic lupus erythematosus (SLE) is started on mycophenolate mofetil (MMF) for lupus nephritis. After 6 weeks of therapy, she develops severe diarrhea and abdominal pain. Which investigation is most appropriate to assess for a potential serious adverse effect of MMF?

Explanation

## Clinical Context Mycophenolate mofetil is a selective inosine monophosphate dehydrogenase (IMPDH) inhibitor used in autoimmune diseases and transplant rejection. Gastrointestinal toxicity is a well-known dose-limiting adverse effect. ## Why Stool Culture and C. difficile Toxin Assay? **Key Point:** MMF causes severe gastrointestinal toxicity, most commonly manifesting as diarrhea. The differential diagnosis of diarrhea in an immunosuppressed patient on MMF must exclude infectious causes, particularly *Clostridioides difficile* infection, which is more common in immunocompromised individuals. **High-Yield:** MMF-induced diarrhea is: - Dose-dependent (often reversible with dose reduction) - Can progress to severe colitis - Must be differentiated from *C. difficile* colitis, which requires specific antimicrobial therapy **Clinical Pearl:** The combination of immunosuppression (MMF) + diarrhea creates a high-risk scenario for *C. difficile* superinfection. Stool studies (culture and toxin assay) are the gold standard to exclude this treatable infectious cause before attributing symptoms purely to MMF toxicity. ## Why Other Options Are Incorrect | Investigation | Limitation | |---|---| | **Serum MPA level** | Useful for dose optimization in steady state, not for acute GI toxicity assessment | | **Colonoscopy with biopsy** | Invasive; reserved for severe cases or when diagnosis remains unclear after stool studies | | **Abdominal ultrasound** | Non-specific imaging; does not identify infectious etiology | ## Management Algorithm ```mermaid flowchart TD A[MMF-induced diarrhea]:::outcome --> B{Stool studies done?}:::decision B -->|No| C[Stool culture + C. difficile toxin]:::action C --> D{Positive for C. difficile?}:::decision D -->|Yes| E[Start metronidazole or vancomycin]:::action D -->|No| F[Reduce MMF dose or switch agent]:::action B -->|Yes, negative| G[Colonoscopy if severe/persistent]:::action ```