Association among stress, hypocortisolism, systemic inflammation, and disease severity in chronic urticaria

Ann Allergy Asthma Immunol. 2016 Apr;116(4):344-348.e1. doi: 10.1016/j.anai.2016.01.016. Epub 2016 Feb 20.


Background: Chronic urticaria (CU) is an immune-mediated disease characterized by wheals for at least 6 weeks. The role of stress and the correlation of stress, hypocortisolism, and inflammatory markers are not well understood.

Objectives: To estimate C-reactive protein (CRP), interleukin (IL)-18, and cortisol levels in patients with CU and to explore their association with disease severity and stress.

Methods: Forty-five patients with CU and 45 age- and sex-matched healthy controls were recruited for this cross-sectional study. Disease severity was assessed by the urticaria activity score (UAS) and stress by Presumptive Stressful Life Events (PSLE) and Daily Hassles and Uplifts Scale-Revised (DHUS-R) scoring. IL-18 and high-sensitivity CRP (hs-CRP) were estimated using enzyme-linked immunosorbent assay kits and cortisol levels by chemiluminescence.

Results: We observed significant systemic inflammation (increased hs-CRP and IL-18 levels) and stress scores, whereas there was a lowering of basal cortisol levels in patients with CU compared with controls. This finding was more pronounced with increasing disease severity and autoimmune disease, except for stress scores, which did not vary between patients with positive and negative autologous plasma skin test results. We further observed that patients with CU with hypocortisolism had higher levels of hs-CRP and IL-18 and higher PSLE and DHUS-R scores compared with those without hypocortisolism. The hs-CRP level, IL-18 level, PSLE score, DHUS-R score, and duration of the symptoms are significantly positively correlated with UAS, whereas the cortisol level is significantly negatively correlated with UAS. Cortisol has a significant negative correlation with PSLE score, DHUS-R score, and the duration of the disease.

Conclusion: CU is associated with systemic inflammation and stress, along with a significant lower basal cortisol, especially with severe disease and autoimmune urticaria. Thus, chronic stress may precipitate the vicious cycle in the pathogenesis of CU.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Autoantibodies / blood
  • C-Reactive Protein / metabolism
  • Chronic Disease
  • Cross-Sectional Studies
  • Disease Progression
  • Female
  • Humans
  • Hydrocortisone / blood*
  • Inflammation Mediators / blood
  • Interleukin-18 / blood
  • Male
  • Skin / immunology*
  • Stress, Physiological / immunology
  • Urticaria / diagnosis*


  • Autoantibodies
  • Inflammation Mediators
  • Interleukin-18
  • C-Reactive Protein
  • Hydrocortisone