What is the best course of action for a patient with a history of pemphigus, previously treated with immunosuppressants (e.g. azathioprine, mycophenolate mofetil), currently on low-dose steroid, and a history of prostate cancer, now experiencing a flare-up?

Management of Pemphigus Flare in Patient with History of Prostate Cancer

Restart immunosuppressive therapy with rituximab plus short-term prednisolone as the optimal first-line approach for this pemphigus flare, given the patient's history of cancer and previous immunosuppressant exposure. 1

Rationale for Rituximab-Based Therapy

Rituximab combined with prednisolone (0.5-1 mg/kg/day) achieves 89% complete remission rates at 2 years and represents the most effective evidence-based treatment for pemphigus vulgaris flares. 1, 2 This approach is particularly appropriate for your patient because:

• The patient has already failed or required a break from conventional immunosuppressants (azathioprine or mycophenolate mofetil) one year ago, making rituximab the logical next step 3
• The history of prostate cancer (now cured) makes rituximab preferable to long-term high-dose steroids or continuous conventional immunosuppressants, as it offers sustained remission with less cumulative immunosuppression 1, 2
• Clinical improvement typically begins within 6 weeks, with complete healing averaging 15 weeks 1, 2

Specific Treatment Protocol

Initial Phase (Weeks 1-4)

• Administer rituximab 1000 mg intravenously at weeks 1 and 3 (pemphigus protocol, not the older rheumatoid arthritis protocol) 2
• Start prednisolone 0.5-1 mg/kg/day orally, adjusting based on disease severity 3, 2
• If the patient is still on low-dose steroids, increase to the therapeutic range above 3

Steroid Tapering (After Disease Control)

• Begin tapering prednisolone once no new lesions appear and existing lesions heal (typically after 4-8 weeks) 3
• Reduce by 5-10 mg weekly initially, then more slowly below 20 mg daily 3
• Taper over at least 4 weeks minimum 3

Pre-Treatment Screening (Critical)

• Perform hepatitis B screening before rituximab initiation, as reactivation can be fatal 2
• Obtain chest radiograph to evaluate for active or latent tuberculosis 2
• Consider PCP prophylaxis during and following rituximab treatment, particularly given the combination with steroids 2

Alternative Approach if Rituximab is Unavailable or Contraindicated

If rituximab cannot be used immediately, restart conventional immunosuppression with either mycophenolate mofetil (2 g/day) or azathioprine (2-2.5 mg/kg/day) combined with prednisolone 3:

• Mycophenolate mofetil 2 g/day plus prednisolone is preferred if the patient previously used azathioprine 3, 4
• Start prednisolone at 40-60 mg/day for mild-moderate flares or 60-100 mg/day for severe flares 3
• If no response within 5-7 days, increase prednisolone by 50-100% increments 3

However, this conventional approach has lower long-term remission rates (10% sustained remission with mycophenolate mofetil vs. 40% with rituximab at 52 weeks) 1, making it a less optimal choice.

Management of Refractory Disease

If the patient fails to respond adequately to rituximab plus steroids within 6-8 weeks, add immunoadsorption 5, 2:

• Immunoadsorption removes circulating pathogenic antibodies rapidly, providing up to 95% reduction in desmoglein antibodies over 3 consecutive days 5, 6
• This combination addresses both immediate antibody removal (immunoadsorption) and prevention of new antibody formation (rituximab) 5, 7, 6
• The protocol involves daily immunoadsorption initially at 3-week intervals, then 4-week intervals until 90% healing 6

Monitoring and Follow-Up

Short-Term (First 6 Months)

• Assess for clinical improvement within 6 weeks; expect complete healing by 15 weeks on average 1, 2
• Monitor for infections closely, particularly if combining multiple immunosuppressants 2, 6
• Check complete blood count, liver and kidney function regularly 3

Long-Term (Beyond 6 Months)

• Expect potential relapse in 40-65% of patients, typically occurring 13-17 months after rituximab 1, 2
• Mean time to disease control is 11 months, with remission achieved at 58 months on average 2
• Continue surveillance even after apparent remission, as relapses can occur years later 3

Critical Caveats Regarding Cancer History

The history of treated prostate cancer does not contraindicate rituximab or immunosuppressive therapy, but requires consideration:

• Rituximab's targeted B-cell depletion offers a more favorable risk profile than prolonged high-dose steroids or continuous conventional immunosuppressants 1, 8
• Avoid unnecessarily prolonged or high-dose conventional immunosuppression (azathioprine, mycophenolate mofetil) given the theoretical oncogenic risks 3
• Coordinate with the patient's oncologist regarding timing and monitoring, though current evidence does not show increased cancer recurrence with rituximab in this setting 8

What NOT to Do

Do not simply increase the current low-dose steroid without adding definitive immunosuppression - this will likely fail to control the flare and expose the patient to prolonged steroid toxicity 3, 8

Do not restart the same immunosuppressant that was used a year ago without considering rituximab first - the patient has already demonstrated inadequate long-term control with that approach 3, 1

Do not delay treatment waiting for "perfect" conditions - pemphigus flares can progress rapidly and early aggressive treatment improves outcomes 3, 6