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- Presentation
Diagnosis and Treatment of Dermatologic Immune-Related Adverse Events
Description
The speaker reviewed diagnosis and treatment of dermatologic immune-related adverse events from checkpoint inhibitors, emphasizing that management should be guided by morphology rather than vague labels like “maculopapular” rash. She described a Delphi-based framework that sorts eruptions into specific morphologic categories or prompts basic workup when morphology is unclear, aiming to improve diagnostic certainty and severity grading. For lichenoid eruptions, she noted that checkpoint-inhibitor lichen planus can look variable on exam and is often associated with mucositis; treatment may include higher-dose acitretin, with occasional use of tocilizumab for severe refractory cases. She also discussed psoriasis, eczema, and pruritus, highlighting topical therapy as first-line, biologics such as anti-TNF agents, IL-23 inhibitors, dupilumab, and omalizumab for more severe disease, while generally avoiding IL-17 inhibitors because of concern for inflammatory bowel disease. For bullous pemphigoid, she noted delayed onset, eosinophilia, and atypical eczematous or urticarial presentations, recommending topicals for mild cases and steroid-sparing systemic options like methotrexate, dupilumab, or omalizumab for more severe disease. She strongly advised minimizing systemic prednisone, especially early after checkpoint initiation, and always coordinating systemic treatment with oncology because of trial eligibility and cancer-control implications. The talk also distinguished two patterns of severe erosive mucocutaneous reactions: true SJS/TEN, which is more fulminant and should be treated aggressively, and a more delayed, often drug-triggered entity the speaker called PERM, which may allow future checkpoint rechallenge in selected patients. For true SJS/TEN, she described a shift toward early JAK inhibitor use, especially upadacitinib, based on emerging mechanistic data. Overall, the key takeaways were to diagnose by morphology, avoid prolonged steroids when possible, involve oncology early, and aim for improvement to a tolerable grade rather than complete clearance so patients can continue life-extending cancer therapy.
View moreConclusions
- Dermatologic immune-related adverse events should be treated based on morphology rather than a one-size-fits-all rash label.
- Specific clinical patterns can usually be mapped to core diagnoses that guide more targeted and less empiric therapy.
- Systemic corticosteroids are often overused early in checkpoint inhibitor treatment and should be avoided or tapered quickly when possible, especially in the first two months.
- For immune checkpoint inhibitor lichenoid eruptions, acitretin is often useful and complete skin clearance is usually unrealistic, so treatment goals should emphasize tolerability.
- ICI-associated lichenoid disease may have Th2-skewed biology, making dupilumab a plausible and often effective option, though it can occasionally worsen lichenoid disease.
- Pre-existing psoriasis is usually not a contraindication to checkpoint inhibitor therapy, and most flares can be managed without stopping cancer treatment.
- For ICI psoriasis, topicals and acitretin are first-line for mild disease, while biologics such as anti-TNF or IL-23/IL-12-23 agents may be needed for severe disease.
- ICI-associated eczema often responds very well to dupilumab, including dose escalation when standard dosing is insufficient.
- In ICI bullous pemphigoid, prednisone, doxycycline/nicotinamide, and other broadly immunosuppressive strategies are less favored, while methotrexate and biologics such as dupilumab or omalizumab are preferred in more severe cases.
- Dupilumab appears to be a reasonably safe and effective option for selected D-irAEs and does not appear to worsen survival in available observational data.
- SJS/TEN-like eruptions during checkpoint inhibitor therapy may actually represent a distinct entity with delayed onset, a more benign course, and a frequent second trigger, rather than classic SJS/TEN.
- This distinct SJS-like entity was renamed progressive ICI-related mucocutaneous eruption, or PIRME, to reflect the possibility of later checkpoint inhibitor rechallenge in selected patients.
- Classic ICI-associated SJS/TEN behaves differently from PIRME, with rapid onset, more severe disease, and poor prognosis, so it should still prompt permanent ICI discontinuation.
- True SJS/TEN from checkpoint inhibitors may benefit from early JAK inhibition, reflecting emerging evidence that JAK1 is implicated in TEN pathogenesis.
- Across D-irAEs, the therapeutic goal should be symptom control and treatment continuity rather than complete skin clearance, since most patients do not fully return to baseline.
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