What are dermatologic irAEs?
Immune-related skin toxicities usually manifest as a rash (often maculopapular) and pruritis, and, if left untreated, the rash can become ulcerative and demonstrate bullous dermatitis, with potentially life-threatening consequences.
Pruritic maculopapular rash involving the trunk. Reproduced by permission from Springer Nature: Springer. J Clin Dermatol; 19: 345. Sibaud V. © 2018. All rights reserved. doi: 10.1007/s40257-017-0336-3
Incidence and onset of dermatologic toxicities in patients receiving immunotherapy
Dermatologic irAEs are the most common irAEs, with 50% of patients treated with the anti-CTLA4 ICI ipilimumab experiencing rash and/or pruritus and approximately 30–40% of those treated with the anti-PD-1 ICIs nivolumab or pembrolizumab having skin complications [2]. Vitiligo is another frequent immune-related skin toxicity, although this can occur more frequently in patients being treated for melanoma; it was reported in 25% of melanoma cases treated with pembrolizumab in one study [3]. Interestingly, in this setting, vitiligo appears to be an indicator of good prognosis [3]. Rashes are typically mild to moderate in severity, but if left untreated and unrecognized, they can become severe and life-threatening [1]. A clinical trial comparing pembrolizumab with chemotherapy reported severe (grade 3/4) skin reactions in 3.9% of patients in the pembrolizumab arm [4].
Of all the irAEs, dermatologic toxicity often presents the earliest, with an average onset of 3.6 weeks after commencement of treatment [5].
Symptoms and management of dermatologic toxicities
Patient assessment
At clinical review patients should be assessed for the following:
- Check of vital signs
- Blood assay to include full blood count and a serum chemistry panel including liver function tests (LFTs) and C-reactive protein tests
- Calculation of body surface area (BSA) using the rule of nines chart
- Advice to patient on skin regime as per algorithm
- Photograph of skin lesion or rash as soon as possible
- Referral to a dermatologist as soon as possible – severe rashes must be discussed with a dermatologist urgently. For a moderate rash, the patient should be seen as soon as possible by the dermatology team.
Rashes should be graded using Common Terminology Criteria for Adverse Events (CTCAE) v5.0:
| Grade 1 | Grade 2 | Grade 3 | Grade 4 |
| Macules/papules covering <10% BSA with or without symptoms (eg, pruritus, burning, tightness) | Macules/papules covering 10-30% BSA with or without symptoms (eg pruritus, burning, tightness); limiting instrumental activities of daily life (ADL); rash covering >30% BSA with or without mild symptoms | Macules/papules covering >30% BSA with moderate or severe symptoms; limiting self-care ADL | Papulopustular rash associated with life-threatening superinfection; Stevens-Johnson syndrome, TEN and bullous dermatitis covering >30% of BSA and requiring intensive care unit admission |
Patients should be warned of irAEs and advised to contact the care team, as timely communication between patients and HCPs is essential in the early recognition and management of irAEs.
Management algorithm
An algorithm for managing immune-related skin toxicities has been published by the Clatterbridge Cancer Centre NHS foundation Trust. This has been utilized and adapted by other cancer centers, are user-friendly, and offer safe, concise, and standardized management of dermatologic irAEs.