A 71-year-old patient with autoimmune hepatitis in remission (normal liver function tests) who was switched from azathioprine to mycophenolate mofetil has now developed invasive squamous cell carcinoma of the skin; what management steps should be taken?

Management of AIH Patient with Invasive Squamous Cell Carcinoma on Mycophenolate Mofetil

You should discontinue mycophenolate mofetil and transition to low-dose prednisolone monotherapy (5-10 mg/day) to maintain AIH remission while minimizing cancer risk, and ensure aggressive dermatologic management of the squamous cell carcinoma.

Immediate Actions

1. Discontinue Mycophenolate Mofetil

The most recent 2025 BSG guidelines explicitly address this scenario: "Current or recent cancer, resulting in reluctance to use azathioprine or mycophenolate" is a specific indication for steroid monotherapy 1. This recommendation prioritizes patient safety over theoretical concerns about AIH control, particularly since your patient already has normal liver function tests indicating disease remission.

2. Transition to Prednisolone Monotherapy

• Start or continue prednisolone at 5-10 mg/day 1, 2
• This maintains AIH remission while substantially reducing cancer-promoting immunosuppression
• The 2025 guidelines note that small doses of prednisolone can be useful "in patients in whom there is reluctance to use azathioprine (for example, cancer)" 1

Rationale: Cancer Risk with Immunosuppression

Evidence Hierarchy

The cancer risk data strongly favor stopping mycophenolate:

Non-melanoma skin cancer (NMSC) risk increases:

• 2.95-fold (range 1.57-28.0) in AIH patients on long-term immunosuppression 1
• Risk is "probably related partly to immunosuppressive therapy" 1

Critical distinction between agents:

• A 2017 meta-analysis of transplant patients showed mycophenolate had lower cancer rates than azathioprine 1
• However, both agents increase skin cancer risk compared to steroids alone
• Prednisolone alone showed no association with cancer risk in a national AIH registry 1

Dose-dependent effects:

• Higher mycophenolate doses (1818 mg/day vs 1038 mg/day) doubled SCC risk (RRadj 2.22) 3
• Risk was particularly elevated in patients immunosuppressed >5 years (RRadj 11.05) 3

Ongoing Management Strategy

Monitor AIH Status Closely

• Check ALT, AST, IgG every 4-6 weeks initially after transition
• If biochemical relapse occurs (rising transaminases):
  • Temporarily increase prednisolone to 20-30 mg/day 2
  • Re-taper once remission re-achieved
  • Consider alternative agents only if prednisolone fails or causes intolerable side effects

Dermatologic Management

Ensure aggressive treatment of the invasive SCC:

• Surgical excision with 4-6 mm margins for standard-risk tumors 4
• Mohs surgery if high-risk features or cosmetically/functionally sensitive location 4
• Radiation therapy if surgery contraindicated 4

Ongoing surveillance:

• The 2025 guidelines acknowledge that "benefits of routine screening are not established" but recommend patients "minimize exposure to sunlight and be vigilant for newly developing skin lesions" 1
• Given invasive SCC history, dermatology follow-up every 3-6 months is prudent

Important Caveats

If Cirrhosis is Present

The guidelines note greater caution about stopping immunosuppression in cirrhotic patients, though "risk of AIH relapse is not increased, but its consequences might be more serious" 1. Your patient's normal LFTs suggest well-controlled disease, but if cirrhosis exists:

• Consider maintaining very low-dose prednisolone (5 mg/day) indefinitely
• Monitor more frequently for decompensation

If AIH Relapses on Prednisolone Alone

The evidence on continuing immunosuppression with active cancer is "inconclusive" 1:

• CESAME study (IBD patients): IST did not increase new/recurrent cancer 1
• Transplant data: stopping tacrolimus after cancer diagnosis showed no improved outcome 1
• However, "theoretical concerns about IST impairing immune response to cancer" remain 1

If relapse occurs despite prednisolone optimization:

1. Ensure SCC is completely excised and no evidence of metastasis
2. Discuss risks/benefits with patient and oncology
3. Consider budesonide (if no cirrhosis) as it has lower systemic immunosuppression 1
4. Only restart mycophenolate if absolutely necessary for AIH control and cancer is definitively treated

Age Considerations

At 71 years old, this patient faces:

• Higher baseline cancer risk (age is independent risk factor) 5
• Potentially greater steroid side effects (osteoporosis, diabetes, cataracts)
• Need for FRAX score/DEXA scan if not done recently 1
• Annual eye examinations if on steroids >12 months and age >60 1

What NOT to Do

Do not continue mycophenolate - The 2025 guidelines explicitly list "current or recent cancer" as a reason to avoid this agent 1

Do not restart azathioprine - Azathioprine carries even higher skin cancer risk than mycophenolate, with switching from azathioprine to MMF showing reduced SCC incidence in transplant recipients 5. The 2011 guidelines note azathioprine is associated with "increased risk of non-melanoma skin cancer" 2

Do not use high-dose steroids long-term - Keep prednisolone ≤10 mg/day for maintenance to minimize dose-dependent adverse effects 1