Steven-Johnson Syndrome/Toxic Epidermal Necrolysis is Associated with PD-1/PD-L1 Inhibitors Usage: A Case Series

Riqu Cao1, Tianhong Xu1

  • 1Department of Dermatology, Hangzhou Third People's Hospital, Hangzhou, Zhejiang, China.

Insights

Immune-related adverse events, including severe skin reactions like Steven-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), can occur with programmed cell death-1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors. This study highlights SJS/TEN cases in Chinese cancer patients treated with these immunotherapy drugs.

Area of Science:

  • Oncology
  • Dermatology
  • Immunology

Background:

  • Increasing use of PD-1/PD-L1 inhibitors in China for various cancers.
  • Observed immune-related adverse events (irAEs), particularly severe skin reactions.
  • Steven-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) as a critical irAE associated with these therapies.

Purpose of the Study:

  • To investigate and characterize cases of SJS/TEN following PD-1/PD-L1 inhibitor use in China.
  • To summarize clinical features and management strategies for SJS/TEN in this patient population.
  • To raise awareness of SJS/TEN as a potential, under-recognized adverse event of PD-1/PD-L1 inhibitors.

Main Methods:

  • Retrospective review of inpatient medical records at Hangzhou Third People's Hospital (2012-2024).
  • Analysis of SJS/TEN onset, PD-1/PD-L1 inhibitor types, severity scores, laboratory findings, and treatments.
  • Inclusion of 12 patients diagnosed with SJS/TEN after PD-1/PD-L1 inhibitor treatment.

Main Results:

  • Identified 12 SJS/TEN cases associated with PD-1/PD-L1 inhibitors (sintilimab, tislelizumab, toripalimab, keytruda, cadonilimab).
  • Onset of SJS/TEN ranged from 11 days to nine months post-initial inhibitor dose.
  • Half of the patients received concurrent chemotherapy; most cases required multiple therapies.

Conclusions:

  • PD-1/PD-L1 inhibitors represent a potential cause of SJS/TEN in cancer patients.
  • Characterization of SJS/TEN features provides insights for clinical management.
  • Optimizing clinical safety through prompt recognition and effective management of these severe irAEs is crucial.

Related Concept Videos

Toxic Reactions: Overview01:26

Toxic Reactions: Overview

When toxic substances penetrate the human body, they disseminate to various tissues, undergoing metabolic changes. This process yields reactive metabolites that may covalently bind with specific target molecules, resulting in toxicity.
Toxicity falls into two primary categories: local and systemic.
Local toxicity appears at the exposure site, such as protein denaturation caused by caustic substances.
In contrast, systemic toxicity requires the toxic agent's absorption and distribution,...
Drug Toxicity: Risk factors01:24

Drug Toxicity: Risk factors

Adverse Drug Reactions (ADRs) are potential complications that arise during pharmacotherapy, influenced by multiple risk factors. Age plays a significant role; both neonates and the elderly are at heightened risk due to their respective immature and diminished metabolic and elimination processes. Gender also impacts ADRs, with females experiencing a 1.5 to 1.7-fold greater risk than males, which may be linked to pharmacokinetic, pharmacodynamic, and hormonal differences. Notably, neonates, the...
Drug Toxicity: Dose-Dependent Reactions01:24

Drug Toxicity: Dose-Dependent Reactions

Drug toxicities can be stratified into pharmacological, pathological, or genotoxic based on their mechanisms. The incidence and severity of these toxicities generally increase with the drug's concentration in the body and exposure time.Pharmacological toxicity is evident when the therapeutic effects of drugs overshoot into adverse reactions in a predictable, dose-dependent manner. Central nervous system (CNS) depression from barbiturates is a classic example, with effects escalating from...
Drug Toxicity: Allergic Reactions01:30

Drug Toxicity: Allergic Reactions

Drug-related allergies are immune-mediated responses triggered by the administration of pharmacological agents. These hypersensitivity reactions are classified based on the immune mechanisms involved. The four primary types—Type I, II, III, and IV—are mediated by different immunological pathways and exhibit distinct clinical manifestations.Type I Hypersensitivity/ IgE-Mediated Reactions: Immunoglobulin E (IgE) immediately mediates Type I hypersensitivity reactions. Upon initial exposure to a...
Hypersensitivity Reactions: Cytolytic Reactions01:01

Hypersensitivity Reactions: Cytolytic Reactions

Type II hypersensitivity involves IgG and IgM antibodies targeting cell surface antigens, leading to cell destruction. This can occur through complement activation, antibody-dependent cell-mediated cytotoxicity (ADCC), or acting as opsonins for phagocytosis. When excessive, these reactions cause significant tissue damage.Drug-induced hemolytic anemia is a common example, where drugs like penicillin or cephalosporins bind to red blood cells, forming drug-protein complexes. These complexes...
Drug toxicity: Idiosyncratic Reactions01:16

Drug toxicity: Idiosyncratic Reactions

Idiosyncratic drug reactions represent abnormal chemical responses that vary significantly among individuals, ranging from extreme sensitivity to low doses to insensitivity to high doses. These reactions often occur due to the drug's covalent binding with serum proteins, forming a foreign hapten that triggers an immunotoxicological response. The variability in drug reactions has a strong pharmacogenetic foundation, with genetic differences crucial in how individuals metabolize drugs. For...