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Cutaneous adverse effects of anti-PD-1 and anti-PD-L1 therapy
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Cutaneous adverse effects of anti-PD-1 and anti-PD-L1 therapy

Contributors: Michael J. Woodbury, Susan Burgin MD
Other Resources UpToDate PubMed

Synopsis

Novel monoclonal antibodies directed against the immune checkpoint inhibitor protein programmed cell death-1 (PD-1), including nivolumab and pembrolizumab, and PD ligand 1 (PD-L1) inhibitor therapy are effective in the treatment of advanced non-small cell and small cell lung cancer, melanoma, head and neck squamous cell carcinoma, lymphomas, and other advanced solid organ cancers. Anti-PD-L1 antibodies including atezolizumab and durvalumab have shown efficacy in treating urothelial cancers and avelumab in treating metastatic Merkel cell carcinoma.

During therapy with PD-1 and PD-L1 inhibitors, a unique set of adverse effects may develop called immune-related adverse events (irAEs). Pneumonitis, colitis, hepatitis, and immune-related endocrinopathies may be seen. Cutaneous irAEs are estimated to occur in up to around one-half of patients receiving PD-1 / PD-L1 inhibitors, with variable time to onset after initiation of anti-PD-1 / PD-L1 therapy.

The most common cutaneous irAEs include lichenoid reactions, eczema, and vitiligo, with each occurring in 15%-17% of patients taking PD-1 inhibitors in 1 large study. The lichenoid reaction appears within days to months and sometimes after a year of therapy initiation, eczema appears within weeks up to around a year, and vitiligo appears within days to approximately 9 months. "Maculopapular rash" (exanthematous eruption) is also reported in up to 20% of patients, occurring within 3-6 weeks of drug onset.

Isolated pruritus, psoriasis (new onset or exacerbation of preexisting psoriasis; time to onset 2-22 weeks), and bullous pemphigoid (time to onset 3-84 weeks) have been associated. Granulomatous reactions (induced by PD-1 inhibitors), Stevens-Johnson syndrome (SJS) / toxic epidermal necrolysis (TEN), and lupus erythematosus are rarer. A few cases each of alopecia areata, eosinophilic fasciitis, and leukocytoclastic vasculitis have also been reported. Two cases of dermatomyositis that resolved after drug discontinuation have been documented.

Cutaneous irAEs are given grades as follows:
  • Grade 1: Rash covers < 10% body surface area (BSA)
  • Grade 2: Rash covers 10%-30% BSA or limits self-care activities, or it is a mild rash covering > 30% BSA
  • Grade 3: Rash covers > 30% BSA with moderate or severe symptoms, or it limits self-care activities
  • Grade 4: Life-threatening rash, requires urgent intervention
Related topics: anti-TNF-alpha-induced eruptions, immune-related adverse effects

Codes

ICD10CM:
L27.0 – Generalized skin eruption due to drugs and medicaments taken internally

SNOMEDCT:
28926001 – Eruption caused by drug

Look For

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Diagnostic Pearls

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Differential Diagnosis & Pitfalls

Lichenoid reactions: Eczema: Vitiligo: Maculopapular / exanthematous eruption: Bullous pemphigoid: Granulomatous reactions: SJS/TEN:

Best Tests

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Management Pearls

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Therapy

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Drug Reaction Data

Below is a list of drugs with literature evidence indicating an adverse association with this diagnosis. The list is continually updated through ongoing research and new medication approvals. Click on Citations to sort by number of citations or click on Medication to sort the medications alphabetically.

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References

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Last Reviewed:01/27/2021
Last Updated:02/05/2021
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Cutaneous adverse effects of anti-PD-1 and anti-PD-L1 therapy
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Cutaneous adverse effects of anti-PD-1 and anti-PD-L1 therapy
Copyright © 2021 VisualDx®. All rights reserved.