What systemic agent is suitable for treating psoriasis in a patient with a history of transitional cell carcinoma (TCC) of the bladder, a urostomy in situ, solitary kidney, and impaired renal function?

Systemic Treatment for Psoriasis in a Patient with Solitary Kidney, Urostomy, and Renal Impairment

In this complex clinical scenario with raised creatinine, a solitary kidney, and history of bladder TCC, biologic therapy—specifically a TNF-α inhibitor—is the most appropriate systemic agent for psoriasis treatment, as biologics have no known deleterious effects on renal function and avoid the nephrotoxic risks of traditional systemic agents. 1

Why Traditional Systemic Agents Are Contraindicated

Cyclosporine: Absolutely Contraindicated

• Cyclosporine is explicitly contraindicated in patients with abnormal renal function 1
• The drug causes dose-dependent nephrotoxicity with glomerulosclerosis, and patients with pre-existing renal impairment are at highest risk 2, 3
• Even low-dose cyclosporine (average 3 mg/kg/day) causes significant GFR decline—in one study, GFR fell from 117 to 97 ml/min after just 9 weeks of treatment 3
• Long-term use (5-10 years) produces persistent creatinine elevations >30% in nearly half of patients, with some showing >50% increases 2
• Additionally, cyclosporine is contraindicated in patients with previous or concomitant malignancy, which applies to this patient's bladder TCC history 1

Methotrexate: Contraindicated Due to Renal Impairment

• Methotrexate is contraindicated in individuals with renal impairment because the drug is renally excreted and accumulates in renal dysfunction, leading to severe bone marrow suppression 1
• The guidelines explicitly list "renal impairment" as a contraindication to methotrexate therapy 1
• Drug interactions causing bone marrow suppression are a major concern, and this risk is amplified in renal dysfunction 1

Acitretin: Possible but Suboptimal

• Acitretin is not immunosuppressive and has no direct nephrotoxic effects 1
• However, acitretin requires baseline and ongoing monitoring of liver function and lipids 1
• The drug has limited efficacy as monotherapy—expert opinion suggests doses exceeding 25 mg/day are often needed for significant improvement, with dose-dependent mucocutaneous side effects 1
• Response time is relatively slow at 6 weeks, compared to biologics 1

Why Biologic Therapy Is the Optimal Choice

TNF-α Inhibitors: No Renal Toxicity

• Biologic therapies offer significant advantages in patients with complex medical histories because there are no known drug interactions with TNF-α antagonists and they have no known deleterious effect on renal function 1
• TNF-α inhibitors (etanercept, adalimumab, infliximab) are appropriate first-line biologic therapy 1, 4, 5
• These agents are considered to have fewer significant safety issues compared with traditional systemic agents 1

Specific Biologic Options

Infliximab:

• Dosed at 5 mg/kg intravenously at weeks 0,2, and 6, then every 8 weeks 1
• Weight-based dosing may be advantageous in certain patients 1
• Demonstrates rapid and often complete disease clearance 4, 6

Adalimumab or Etanercept:

• Fixed-dose subcutaneous options that don't require dose adjustment for renal function 1
• No known renal effects or drug interactions 1

Apremilast (Alternative Non-Biologic Option):

• Apremilast is FDA-approved for moderate to severe plaque psoriasis in adults who are candidates for systemic therapy 7
• Importantly, no dose adjustment is required for renal impairment based on the FDA label 7
• The drug is not immunosuppressive and has no significant drug interactions with methotrexate or other commonly used medications 7
• Achieved PASI-75 in 28.8-33.1% of patients at 16 weeks 7

Critical Pretreatment Considerations

Infection Screening Before Biologics

• Screen for active or latent tuberculosis (tuberculin skin test or interferon-gamma release assay) 1
• Screen for hepatitis B and fungal infections due to increased infection risk with TNF-α inhibitors 6
• All TNF-α antagonists carry warnings about granulomatous infections including tuberculosis, histoplasmosis, and coccidiomycosis 1

Malignancy History Considerations

• The patient's history of bladder TCC requires careful consideration 1
• While older guidelines listed "previous or concomitant malignancy" as a contraindication to cyclosporine, biologics have been used in patients with remote cancer histories 1
• The time interval since TCC treatment and current cancer-free status should be documented 8

Monitoring Requirements for Biologic Therapy

• No routine renal function monitoring is required specifically for biologic therapy (unlike cyclosporine or methotrexate) 1
• However, baseline and periodic monitoring of complete blood count is recommended 1
• Monitor for signs of infection given immunosuppressive effects 1

Common Pitfalls to Avoid

• Never use PUVA photochemotherapy in this patient—it is contraindicated in patients with previous cutaneous malignancy or those who have received ionizing radiation 1
• Never prescribe systemic corticosteroids for psoriasis—they precipitate erythrodermic or generalized pustular psoriasis upon discontinuation, potentially causing fatal deterioration 4, 5, 6
• Do not attempt to use cyclosporine even at reduced doses—the contraindication is absolute in abnormal renal function 1
• Avoid the temptation to use methotrexate at reduced doses—renal impairment remains an absolute contraindication due to drug accumulation and toxicity risk 1