Immune related cutaneous toxicity - Immune Checkpoint Inhibitor Therapy- Toxicity Management

Publication: 02/06/2021  
Next review: 02/06/2024  
Clinical Guideline
ID: 7030 
Approved By: Trust Clinical Guidelines Group 
Copyright© Leeds Teaching Hospitals NHS Trust 2021  


This Clinical Guideline is intended for use by healthcare professionals within Leeds unless otherwise stated.
For healthcare professionals in other trusts, please ensure that you consult relevant local and national guidance.

Immune Checkpoint Inhibitor Therapy-Toxicity Management

Immune related cutaneous toxicity

Summary of Guideline

Patients receiving treatment with ICPIs are at risk of developing skin toxicities during their treatment. This is one of the most common presentations of an immune-related adverse event and can be seen very early in the disease course, often in the first 1 or 2 cycles of treatment.
Cutaneous toxicities can present as either a visible skin rash/change or as itching which can be quite disruptive to quality of life. The presentations can vary from an urticarial or macular-papular rash to areas of bullous skin changes or pustulosis and the management can therefore vary with this. It is always important to ensure other causes are ruled out e.g. other drug causes of rash, environmental changes etc and a skin biopsy can be helpful in further determining the underlying cause.
Management of low grade toxicity would include topical emollients and low potency steroids with treatment escalating with grade and severity of symptoms. .

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This guideline has been put together to guide clinicians when reviewing patients presenting with new skin changes or symptoms whilst undergoing treatment with ICPI therapies for malignant disease. Skin toxicities can present very early in the treatment course and can have a range of different presentations, the most common of which are pruritus, rash and vitiligo (mainly in patients on immune therapies for melanoma). As for most ICPIs the risk of developing a cutaneous toxicity increases if patients are treated with combination therapies rather than single agent.
The European society for medical oncology (ESMO) guidelines suggest that there are four distinct histopathological subtypes:

  1. Inflammatory skin disorders
  2. Immunobullous skin disorders
  3. Keratinocyte alteration
  4. Immune-mediated alteration to melanocytes.

Time frame of presentation
Below are 2 graphs demonstrating the expected time frame of development of toxicities from immunotherapy (taken from ESMO guidelines- see reference). Cutaneous toxicities are often one of the first to manifest. It is also unusual for cutaneous toxicity to develop late and therefore after 3 months, it is unlikely that skin disorders will occur.





Generalised symmetrical red macules (flat patches) and papules (< 5mm lumps).

Erythema Multiforme


Target lesions - sharp margin, regular round shape and three concentric colour zones: the centre is dusky or dark red with a blister or crust; the next ring is a paler pink and is raised due to oedema; the outermost ring is bright red. May be an early sign of SJS/TEN (see below).


Fluid filled blisters >1cm. May be a sign of drug-induced bullous pemphigoid (may require oral tetracycline) or SJS/TEN (see below).

Lichenoid/SLE-like eruption

Extensive slightly scaly purple papules and plaques distributed symmetrically over the trunk and limbs. May have a photosensitive distribution.

Drug reaction with eosinophilia and systemic symptoms (DRESS)

Characterised by high fever, eosinophilia, lymphadenopathy and inflammation of one or more internal organs. The skin eruption can be varied but is most often a morbilliform eruption. Typically presents within 2-6 weeks of starting drug. Treat as at per Grade 3-4

Stevens-Johnson syndrome (SJS) / Toxic Epidermal Necrolysis (TEN)

Tender/painful red skin rash with epidermal detachment (surface layer of skin peels away). Look for target lesions (see above) and mucosal membrane involvement (conjunctiva, oral and genital). Always Grade 3 or 4.
Nikolsky sign - extension of a blister to adjacent un-blistered skin when pressure is put on the top of the blister.
BAD guidelines on management

Acute Generalised Exanthemous Pustulosis (AGEP)

Rapid appearance of areas of red skin studded with small sterile pustules.

Figure 1: Rash subtypes

Figure 3. Rash subtypes

Figure 4. Body surface area calculator Figure 5. Common toxicity criteria for adverse events grading


Record: 7030

Immune checkpoint inhibitor therapies (ICPIs: anti-CTLA4, anti-PD-1, anti-PD-L1 therapies) have been in routine use in the management of cancers for almost a decade. It is well recognised that patients receiving this class of systemic anti-cancer therapies are at risk of multiple and wide-ranging toxicities from these treatments owing to immune activation against self-antigens outside of the therapeutic indication of the drug(s).Immune-related cutaneous toxicity is well documented as one of the most common and earliest toxicities from ICPI. This document aims to provide clinicians with an initial plan for investigation and management of patients who present with new skin rashes and disorders whilst undergoing treatment with these drugs.

Clinical condition:

Immune-related cutaneous toxicity; immunotherapy toxicity; pembrolizumab, nivolumab, atezolizumab, durvalumab, avelumab, ipilimumab

Target patient group: Those patients currently undergoing or recently completing treatment with immune checkpoint inhibitors.
Target professional group(s): Pharmacists
Primary Care Doctors
Secondary Care Doctors
Primary Care Nurses
Secondary Care Nurses
Adapted from:

Evidence base

  1. Curry, JL, Tetzlaff MT, Nagarajan P et al. Diverse types of dermatological toxicities from immune checkpoint blockade therapy. J cutan path (2017); 44(2): 158-176.
  2. ESMO clinical guidelines committee. Management of toxicities from immunotherapy: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Annals of oncology (2017); 28 (suppl 4) i1 19-i1 42.

Approved By

Trust Clinical Guidelines Group

Document history

LHP version 1.0

Related information

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