Drug reactionImmune checkpoint inhibitorICD-10 L27.0 (drug-induced)
Cutaneous immune-related adverse events
Cutaneous irAEs; ICI-induced dermatitis; checkpoint-inhibitor skin toxicity
Cutaneous immune-related adverse events are the commonest toxicity of immune checkpoint inhibitor (ICI) therapy — anti-CTLA-4 (ipilimumab), anti-PD-1 (pembrolizumab, nivolumab, cemiplimab), anti-PD-L1 (avelumab, atezolizumab, durvalumab) and anti-LAG-3 (relatlimab) — affecting 30–50% of patients on monotherapy and 60–70% on combination. Five major phenotypes — maculopapular / eczematoid, lichenoid, psoriasiform, bullous pemphigoid-like, and rare but severe SJS / TEN. Most cases respond to topical / oral steroids and rarely require ICI discontinuation; severe reactions need urgent dermatology / oncology MDT input. Patchy vitiligo specifically is associated with improved melanoma outcomes — see irAE-induced vitiligo.
CurrentLast reviewed 15 May 2026
Epidemiology and timing
- Cutaneous irAEs affect 30–50% of patients on anti-PD-1 / anti-PD-L1 monotherapy and 60–70% on combination ipilimumab + nivolumab.
- Most appear within the first 6–8 weeks of treatment, but onset can range from days to over a year.
- Pruritus alone (without rash) affects an additional 20–30%.
- Cutaneous irAEs are generally lower-grade than gastrointestinal, endocrine or pulmonary irAEs and more responsive to topical therapy.
Five major phenotypes
- Maculopapular / eczematoid — commonest pattern; symmetric pruritic erythematous macules and papules on the trunk and extremities. Often called "maculopapular rash" in trial reports.
- Lichenoid — violaceous flat-topped papules, sometimes with Wickham striae; histologically interface dermatitis. Slower to settle than the eczematoid pattern.
- Psoriasiform — well-defined erythematous plaques with silvery scale, often re-emergence in patients with prior psoriasis; nail dystrophy can occur.
- Bullous pemphigoid-like — pruritic urticarial plaques evolving to tense bullae; positive BP180 / BP230 serology in many cases. Anti-PD-1 most often implicated.
- SJS / TEN — rare (< 1%) but severe; mucosal involvement, epidermal detachment; mortality risk. Urgent burns / dermatology / oncology input.
- Other reported patterns — granulomatous / sarcoid-like reactions, lupus-like, eosinophilic fasciitis, alopecia areata, oral lichenoid mucositis.
CTCAE grading
- Grade 1 — < 10% BSA; topical intervention only; ICI continues.
- Grade 2 — 10–30% BSA, oral / topical steroids; ICI held or continued depending on response.
- Grade 3 — > 30% BSA or significant impact on ADLs; oral / IV steroids; ICI held until improvement to G ≤ 1.
- Grade 4 — life-threatening (SJS / TEN); permanent ICI discontinuation; admission, IV methylprednisolone, supportive care in a burns / specialist setting.
- Always follow the institution's organ-specific algorithm — see oncology / dermatology shared protocol.
Management
- Grade 1–2 — emollients, topical potent / superpotent steroids (clobetasol propionate), oral antihistamines for pruritus. Most cases continue ICI.
- Grade 2 refractory or Grade 3 — oral prednisolone 0.5–1 mg/kg/day, tapered over 4–6 weeks. Hold ICI until G ≤ 1.
- Lichenoid — often needs longer steroid taper and dermatology input; PUVA / narrowband UVB in selected refractory cases.
- Bullous pemphigoid-like — oral steroids, doxycycline, dapsone, dupilumab; refractory disease may need omalizumab or rituximab; consider ICI discontinuation.
- SJS / TEN — permanent ICI discontinuation; admit to burns / specialist unit for supportive care; ciclosporin is favoured; systemic corticosteroids (e.g. IV methylprednisolone) and IVIg are adjuncts of uncertain benefit, used per local protocol.
- Rechallenge after irAE — generally safe for Grade 1–2 dermatitis after recovery; multidisciplinary discussion for Grade 3+ events.
Practice points
- A pruritic rash on ICI is irAE until proven otherwise — but exclude infection (bacterial, fungal, viral), drug eruption from concurrent medication, and intercurrent dermatosis flare.
- Baseline skin examination before starting ICI helps distinguish pre-existing dermatoses (psoriasis, eczema) from new-onset toxicity.
- Maintain a high index of suspicion for paraneoplastic or systemic irAE — endocrine, GI, hepatic, pulmonary, neurological — which can co-occur with skin disease.
- Patient counselling — most cutaneous irAE settles with topical treatment; do not stop ICI without specialist advice.
References
- Sibaud V. Dermatologic reactions to immune checkpoint inhibitors — skin toxicities and immunotherapy. Am J Clin Dermatol; 2018.
- Schneider BJ et al. Management of immune-related adverse events in patients treated with ICI therapy — ASCO Clinical Practice Guideline Update. J Clin Oncol; 2021.
- Haanen J et al. Management of toxicities from immunotherapy — ESMO Clinical Practice Guideline. Ann Oncol; 2022.
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