What is the management approach for a patient with a pathology report showing chronic active colitis, increased crypt apoptosis, and a slight increase of eosinophils in lamina propria, suggestive of mycophenolate (Cellcept) injury?

From the Guidelines

The patient with a pathology report showing chronic active colitis, increased crypt apoptosis, and a slight increase of eosinophils in lamina propria, suggestive of mycophenolate (Cellcept) injury, should immediately discontinue mycophenolate and start corticosteroids (initial dose of 1-2 mg/kg/d prednisone or equivalent) until symptoms improve. The management approach for this patient involves discontinuation of the offending medication and initiation of supportive care to manage symptoms. According to the guidelines for managing immune-related adverse events 1, the patient's symptoms should be graded, and in this case, since the report suggests chronic active colitis, it is likely a grade 3 adverse event, which requires hospitalization if there is dehydration or electrolyte imbalance.

• The patient should stop taking mycophenolate and consult with their transplant physician or specialist to determine an appropriate alternative immunosuppressant.
• Administer corticosteroids (initial dose of 1-2 mg/kg/d prednisone or equivalent) until symptoms improve to grade 1, and then start taper over 4-6 weeks, as recommended for grade 3 colitis 1.
• Consider early introduction of infliximab or vedolizumab in addition to steroids if there are high-risk endoscopic features on initial endoscopy examination or inadequate response to steroids (persistent symptoms after 3 days) 1.
• Supportive care with anti-diarrheal medications like loperamide may help manage symptoms while the drug is cleared from the system. The pathologic findings of increased crypt apoptosis with eosinophilic infiltration are characteristic of mycophenolate toxicity, which occurs because the drug inhibits purine synthesis and affects rapidly dividing cells in the intestinal mucosa, as seen in this patient's pathology report. This medication-induced colitis must be distinguished from infection, inflammatory bowel disease, and graft-versus-host disease, as the management approaches differ significantly.

From the FDA Drug Label

5.5 Gastrointestinal Complications Gastrointestinal bleeding requiring hospitalization, ulceration and perforations were observed in clinical trials. Physicians should be aware of these serious adverse effects particularly when administering mycophenolate mofetil to patients with a gastrointestinal disease.

The management approach for a patient with a pathology report showing chronic active colitis, increased crypt apoptosis, and a slight increase of eosinophils in lamina propria, suggestive of mycophenolate (Cellcept) injury, is to discontinue or reduce the dose of mycophenolate mofetil. This is because mycophenolate mofetil can cause gastrointestinal complications, including bleeding, ulceration, and perforations, particularly in patients with pre-existing gastrointestinal disease.

• Monitor the patient closely for signs of gastrointestinal complications, such as bleeding or perforation.
• Consider alternative treatments that do not involve the use of mycophenolate mofetil.
• Manage the patient's symptoms and prevent further complications.

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From the Research

Pathology Report Findings

• The pathology report reveals chronic active colitis with increased crypt apoptosis and a slight increase of eosinophils in lamina propria.
• These findings, along with the clinical history, raise suspicion for mycophenolate (Cellcept) injury 3.

Management Approach

• The management of mycophenolate-induced colitis is primarily clinical, and diagnosis can be challenging due to non-specific colonoscopic and histopathologic changes 3.
• Reducing the dose of mycophenolate may lead to cessation of symptoms, as seen in a case report where a patient's diarrhea stopped after the MMF dose was reduced 3.
• In cases of immune checkpoint inhibitor-induced colitis, mycophenolate mofetil alongside high-dose corticosteroids may be used to manage the condition and reduce corticosteroid exposure 4.
• For ulcerative colitis, treatment options include aminosalicylates, corticosteroids, immune modulators, and anti-tumor necrosis factor (TNF) agents, with the goal of inducing and maintaining remission 5.

Treatment Options

• Mycophenolate mofetil may be an alternative treatment for patients with contraindications to azathioprine, although it may be less effective and have a higher risk of adverse events 6.
• Eosinophilic colitis, which may be related to the increased eosinophils in lamina propria, lacks codified guidelines for diagnosis and treatment, and management is often based on case reports and small case series 7.
• Infliximab may be used to treat colitis flares that occur during corticosteroid weaning in patients with immune checkpoint inhibitor-induced colitis 4.