Association of interleukin-6 and tumor necrosis factor-α with mortality in hospitalized patients with cancer

J Am Acad Dermatol. 2021 Feb;84(2):273-282. doi: 10.1016/j.jaad.2020.03.010. Epub 2020 Mar 12.

Abstract

Background: Severe cutaneous adverse reactions (SCARs) are associated with high morbidity and mortality in patients with cancer. Early identification and treatment of SCARs may improve outcomes.

Objective: To identify biomarkers to predict outcomes in hospitalized patients with cancer who developed SCARs.

Methods: Retrospective review of 144 hospitalized patients with cancer with a morbilliform rash, recorded testing for serum cytokines (interleukin [IL]-6, IL-10, and tumor necrosis factor [TNF]-α) or elafin, and a dermatology consultation. Rashes were categorized as simple morbilliform rash without systemic involvement or complex morbilliform rash with systemic involvement.

Results: Fifty-four of 144 (37.5%) patients died during follow-up. Elevated levels of IL-6, IL-10, and TNF-α were associated with decreased survival. Overall survivals in patients with elevated levels of IL-6, IL-10, and TNF-α were 53.7%, 56.6%, 53.6%, respectively, compared with 85.7%, 82.5% and 83.6%, respectively, in those with lower levels. Patients with increased levels of both IL-6 and TNF-α had a nearly 6-fold increase in mortality (hazard ratio, 5.82) compared with patients with lower levels.

Limitations: Retrospective design, limited sample size, and high-risk population.

Conclusions: Hospitalized patients with cancer with rash and elevated IL-6 and TNF-α were nearly 6 times more likely to die over the course of follow-up. These biomarkers may serve as prognostic biomarkers and therapeutic targets for this high-risk population.

Keywords: biomarker; cytokine; drug rash; drug reaction; drug reaction with eosinophilia and systemic symptoms; drug-induced hypersensitivity syndrome; graft-versus-host disease; interleukin-6 (IL-6); mortality; severe cutaneous adverse reaction; survival; tumor necrosis factor alpha (TNF-α).

MeSH terms

  • Antineoplastic Agents / adverse effects*
  • Biomarkers, Tumor / blood*
  • Biomarkers, Tumor / immunology
  • Drug Eruptions / blood
  • Drug Eruptions / diagnosis*
  • Drug Eruptions / immunology
  • Drug Eruptions / mortality
  • Female
  • Follow-Up Studies
  • Hospital Mortality
  • Humans
  • Interleukin-10 / blood
  • Interleukin-10 / immunology
  • Interleukin-6 / blood*
  • Interleukin-6 / immunology
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neoplasms / blood
  • Neoplasms / drug therapy
  • Neoplasms / immunology
  • Neoplasms / mortality*
  • Prognosis
  • Retrospective Studies
  • Risk Assessment / methods
  • Severity of Illness Index
  • Tumor Necrosis Factor-alpha / blood*
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • IL10 protein, human
  • IL6 protein, human
  • Interleukin-6
  • TNF protein, human
  • Tumor Necrosis Factor-alpha
  • Interleukin-10