Original article
Mechanisms of allergic and immune diseases
Association among stress, hypocortisolism, systemic inflammation, and disease severity in chronic urticaria

https://doi.org/10.1016/j.anai.2016.01.016Get rights and content

Abstract

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.

Introduction

Chronic urticaria (CU) is a disease characterized by short-lived but recurrent wheals, itching, and erythema lasting for more than 6 weeks. CU poses problems with respect to high prevalence, reduced quality of life, lack of long-term efficacy, and expense of current treatments for severe intractable symptoms. The pathogenesis of CU is poorly understood, but autoimmunity is considered one of the major underlying causes (30%–50%) of this disease, although other theories exist.1 There have been many reports suggesting that stress factors may be implicated in the pathogenesis.2 It has also been reported in previous studies that patients with CU experience secondary insomnia due to stress and itching caused by the disease before their disease onset, which may disturb the circadian rhythm of cortisol secretion and further precipitate CU.3 There are also reports of successful treatment of urticaria with selective serotonin reuptake inhibitors (SSRIs)4 and the whole-person treatment approach.2

In general, during acute stress, both the adrenocortical and medullary systems are activated, leading to increased release of cortisol and catecholamines. On the contrary, chronic stress causes hypothalamic-pituitary-adrenocortical (HPA) axis fatigue, resulting in reduced cortisol secretion and leading to increased secretion of inflammatory cytokines, such as interleukin (IL)-6 and IL-18, which are typically counterregulated by cortisol.5 Hence, we conducted this study to explore the association of disease and stress severity with markers of systemic inflammation and cortisol levels in patients with CU.

Section snippets

Methods

This cross-sectional study was performed in 45 patients with CU attending the Department of Dermatology, Jawaharlal Institute of Postgraduate Medical Education and Research, and 45 age- and sex-matched healthy controls conforming to the inclusion and exclusion criteria after obtaining written informed consent from the study participants. Ethical clearance was obtained from the Institute Ethics Committee (Human Studies), and written informed consent was obtained from all study participants

Results

In this cross-sectional study, the serum levels of cortisol, hs-CRP, and IL-18 and the PSLE and DHUS-R scores for stress were compared for 45 patients with CU and 45 age- and sex-matched controls. Baseline characteristics were comparable between cases and controls (Table 1). Of 45 patients with CU, 33 (73.3%) tested APST positive and 12 (26.7%) APST negative (Table 2). The median UAS of CU patients in our study was 5.0 (IQR, 4.0–6.0), and the median duration of the symptoms was 12.0 (IQR,

Discussion

Previous studies have proposed a role for psychological stress in CU[3], [12], [13] in a 2-way interaction, wherein CU heightens psychological distress and chronic stress may be a trigger of CU.12 There is evidence of the occurrence of stressful life events as precursors to the onset of CU. In a previous case-control study by Yang et al3 on patients with CU and the association between chronic idiopathic urticaria and stress from major life events, the investigators observed that patients with

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    Disclosures: Authors have nothing to disclose.

    Funding Source: This study was supported by intramural funds from the Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India.

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