What treatment options are available for a patient with diffuse cutaneous psoriasis on Stelara (ustekinumab) experiencing a breakthrough rash, with a history of heavy alcohol use and cirrhosis?

Treatment Options for Breakthrough Psoriasis in a Patient with Cirrhosis and Active Alcohol Use

Given the patient's cirrhosis and ongoing heavy alcohol use, methotrexate is absolutely contraindicated, and the best approach is to optimize the current Stelara (ustekinumab) regimen by increasing dosing frequency to every 8 weeks or escalating the dose to 90 mg if the patient weighs ≤100 kg, while adding high-potency topical corticosteroids for breakthrough lesions. 1

Critical Contraindications in This Patient

• Methotrexate is absolutely contraindicated in patients with cirrhosis and active alcoholism due to severe hepatotoxicity risk 1
• Cyclosporine should be avoided as it causes renal impairment and hypertension, and the patient likely has underlying metabolic complications from alcohol use 1
• Acitretin is problematic as up to 16% of patients develop elevated liver function tests, and 25-50% develop triglyceride elevations, both of which are particularly dangerous in alcoholic cirrhosis 1

Optimizing Current Ustekinumab Therapy

For breakthrough disease on standard dosing, the following escalation strategies are evidence-based:

• Increase dosing frequency from every 12 weeks to every 8 weeks for patients with inadequate response 1
• If the patient weighs ≤100 kg and is currently on 45 mg, escalate to 90 mg every 12 weeks 1
• Consider both dose escalation strategies simultaneously (90 mg every 8 weeks) for severe breakthrough 1
• Assess response after 12 weeks of the adjusted regimen, as this is the appropriate timeframe for definitive response evaluation 1

Topical Therapy for Breakthrough Lesions

High-potency topical corticosteroids should be added as combination therapy:

• Clobetasol propionate 0.05% (gel, cream, foam, or spray depending on body location) applied twice daily to breakthrough areas 2, 3
• Treatment duration should be limited to 2 consecutive weeks maximum with no more than 50 g per week to avoid systemic absorption and HPA axis suppression 2
• For scalp involvement, clobetasol shampoo formulation provides better adherence and efficacy 3
• Combination of ustekinumab with topical corticosteroids has demonstrated improved clinical response 1

Alternative Biologic Options if Ustekinumab Optimization Fails

If dose optimization of ustekinumab fails after 12 weeks:

• Switch to a different biologic class rather than adding traditional systemic agents given the hepatic contraindications 1
• TNF inhibitors (adalimumab, etanercept, infliximab) have no known deleterious effects on hepatic function and no relevant drug interactions 1
• IL-17 inhibitors (secukinumab, ixekizumab) are alternatives with no hepatotoxicity concerns 1
• IL-23 inhibitors (guselkumab, tildrakizumab) targeting only IL-23 (not IL-12) may provide superior efficacy 1

Phototherapy Considerations

Narrowband UVB phototherapy can be added to ustekinumab:

• NB-UVB combined with ustekinumab has demonstrated improved clinical response with acceptable safety 1
• Requires 2-3 treatments per week for 20-30 sessions, which may be logistically challenging 1
• Avoid PUVA due to increased risk of hepatotoxicity from oral psoralen and potential drug interactions with alcohol 1
• Home NB-UVB units can improve adherence for maintenance therapy 1

Monitoring Requirements

Given the cirrhosis and active alcohol use, enhanced monitoring is essential:

• Baseline and periodic liver function tests every 3 months while on any systemic therapy 1
• Screen for infections before any biologic dose escalation or switching, particularly tuberculosis and hepatitis B reactivation 1
• Monitor for signs of infection during therapy, as biologics increase infection risk even without traditional immunosuppressants 1
• Assess for hepatitis B with surface antigen, core antibody, and surface antibody; if positive core antibody, prophylactic antiviral therapy may be needed 1, 4

Critical Pitfalls to Avoid

• Never use methotrexate in this patient regardless of psoriasis severity—the hepatotoxicity risk is unacceptable 1
• Avoid systemic corticosteroids as they can precipitate severe psoriasis flares upon discontinuation 5
• Do not combine ustekinumab with cyclosporine given renal and hepatic risks 1
• Do not discontinue ustekinumab prematurely before attempting dose optimization 1
• Counsel the patient that continued alcohol use will limit all treatment options and worsen prognosis 1

Addressing the Alcohol Use

While the patient states unwillingness to quit, this must be addressed:

• Heavy alcohol use independently worsens psoriasis and reduces treatment efficacy 1
• Referral to addiction medicine or hepatology for alcohol cessation support should be strongly encouraged, as this is the single most important intervention for both psoriasis and survival 1
• Document the discussion about alcohol cessation and its impact on treatment outcomes 1