Why were systemic corticosteroids (corticosteroids), such as prednisone, suggested for an adult patient with a history of cancer and pre-existing psoriasis, experiencing a psoriasis flare after treatment with nivolumab (programmed death receptor (PD) inhibitor)?

Management of Psoriasis Flare Post-Nivolumab with Systemic Corticosteroids

Direct Answer

Systemic corticosteroids were suggested for this psoriasis flare because the immediate benefit of controlling severe immune-mediated inflammation from checkpoint inhibitor therapy outweighs the theoretical risk of post-steroid psoriasis rebound, particularly when the flare threatens quality of life or requires immunotherapy discontinuation. 1, 2

Rationale for Systemic Corticosteroid Use

Primary Justification

• The NCCN guidelines explicitly state that immunosuppressive therapy (including corticosteroids) started after onset of immune-related adverse events does not appear to decrease ICI efficacy based on retrospective data from 576 patients receiving nivolumab for melanoma. 1

• In the pooled analysis, overall response rate was not significantly different between patients who required corticosteroids for managing irAEs and those who did not, supporting their use without compromising cancer outcomes. 1

• Multicenter data from 76 patients with pre-existing psoriasis receiving ICIs showed that 21% required systemic therapy for psoriasis flares, yet only 7% needed immunotherapy discontinuation, demonstrating that aggressive management preserves cancer treatment continuity. 2

Addressing the Steroid-Psoriasis Paradox

• While traditional dermatology teaching warns that systemic corticosteroids can precipitate psoriasis flares upon withdrawal, the literature search for EULAR psoriatic arthritis guidelines found few data beyond case reports supporting this assertion in actual clinical practice. 1

• Registry data reveal systemic steroids are widely used in psoriatic arthritis (up to 30% of patients in German databases), usually at low doses (≤7.5 mg/day), indicating real-world acceptance despite theoretical concerns. 1

• The EULAR task force concluded that systemic glucocorticoids are a therapeutic option in psoriatic disease when used with caution, acknowledging the possibility of skin flare but not considering it an absolute contraindication. 1

Clinical Context for This Patient

• Nivolumab-induced psoriasis flares occur in 57% of patients with pre-existing psoriasis, typically after a median of 44 days of ICI treatment, making this a common and expected complication requiring proactive management. 2

• Among patients experiencing psoriasis flares on ICIs, 53% were managed with topical therapy alone, but 21% required systemic therapy, indicating that approximately one in five patients will need escalation beyond topical treatments. 2

• Progression-free survival was significantly longer in patients who experienced psoriasis flares versus those without (39 vs 8.7 months, p=0.049), suggesting that the inflammatory response may correlate with better cancer outcomes and should not prompt premature ICI discontinuation. 2

Treatment Algorithm for Nivolumab-Induced Psoriasis Flare

Step 1: Initial Assessment

• Evaluate body surface area involvement, presence of pustules, systemic symptoms (fever, malaise), and impact on quality of life to determine flare severity. 3
• Rule out other immune-related adverse events affecting other organ systems, as psoriasis flare may be accompanied by concurrent irAEs. 1, 4

Step 2: Topical Management (First-Line)

• For mild to moderate flares (<10% body surface area, no systemic symptoms), initiate high-potency topical corticosteroids with close monitoring. 2
• This approach successfully manages 53% of psoriasis flares in ICI-treated patients without requiring systemic therapy. 2

Step 3: Systemic Corticosteroid Initiation (Second-Line)

• For moderate to severe flares (>10% body surface area, significant quality of life impact, or failure of topical therapy after 2-4 weeks), initiate prednisone 0.5-1 mg/kg/day. 1
• Continue nivolumab during corticosteroid treatment unless the flare is life-threatening or requires doses >1 mg/kg/day prednisone equivalent. 1, 2

Step 4: Monitoring and Steroid Taper

• Once clinical improvement is achieved (typically 1-2 weeks), taper prednisone by 5-10 mg weekly to minimize rebound risk. 1
• Monitor blood glucose, consider PPI prophylaxis if on NSAIDs/anticoagulants, and provide calcium/vitamin D supplementation during steroid therapy. 1

Step 5: Steroid-Sparing Alternatives

• If systemic therapy is needed beyond 4 weeks or steroid taper fails, consider transitioning to methotrexate, acitretin, or biologics (secukinumab, ustekinumab) rather than prolonged corticosteroids. 1, 5, 6
• Biologics targeting IL-17 or IL-23 are safe in cancer patients and do not compromise ICI efficacy based on available case series. 6

Critical Pitfalls to Avoid

Absolute Contraindications

• Do NOT use systemic corticosteroids as primary therapy for generalized pustular psoriasis or erythrodermic psoriasis, as they can precipitate life-threatening complications and severe rebound. 1, 3
• In these severe presentations, use infliximab 5 mg/kg IV, cyclosporine 2.5-5 mg/kg/day, or acitretin instead of corticosteroids. 3

Coordination with Oncology

• Any systemic immunosuppressive treatment must be undertaken in partnership with medical oncology to avoid conflicts in therapeutic intent and ensure cancer treatment is not compromised. 1
• Document the psoriasis flare severity, treatment response, and any ICI dose modifications to guide future management decisions. 1, 4

When to Discontinue Nivolumab

• Permanently discontinue nivolumab only if the psoriasis flare is refractory to systemic steroids AND biologics, or if it progresses to erythroderma/pustular transformation despite aggressive management. 7, 5
• Temporary holds (1-2 doses) are reasonable for severe flares requiring high-dose steroids (>1 mg/kg/day), but permanent discontinuation should be a last resort given the survival benefit of continued ICI therapy. 2

Evidence Quality Assessment

The recommendation for systemic corticosteroids in this context is supported by high-quality guideline evidence from NCCN 1 and EULAR 1, augmented by the largest multicenter retrospective study of ICIs in psoriasis patients (n=76) 2. The convergence of oncology guidelines permitting immunosuppression for irAEs and rheumatology guidelines accepting cautious steroid use in psoriatic disease provides strong justification for this approach, particularly when the alternative is discontinuing life-saving cancer therapy.