Psychological Stress and Chronic Urticaria: A Neuro-immuno-cutaneous Crosstalk. A Systematic Review of the Existing Evidence

Abstract

Purpose: It has been observed that certain patients with chronic spontaneous or idiopathic urticaria (CSU/ CIU) have a personal history of a significant stressor before urticaria onset, while the prevalence of any psychopathology among these patients is significantly higher than in healthy individuals. Research has confirmed that skin is both an immediate stress perceiver and a target of stress responses. These complex interactions between stress, skin, and the nervous system may contribute to the onset of chronic urticaria. This systematic review investigated the association between CSU/CIU and neuroimmune inflammation with or without evidence of co-existing psychological stress from in vivo and ex vivo studies in human beings. Methods: PubMed and Scopus were searched to September 2019 for reports in human beings describing neuroimmune inflammation, stress, and CSU/CIU. A comprehensive search strategy was used that included all the relevant synonyms for the central concept. Findings: A total of 674 potentially relevant articles were identified. Only 13 satisfied the predefined inclusion criteria and were included in the systematic review. Five of these 13 studies evaluated the correlation between CSU/CIU, stress, and neuroimmune-cutaneous factors, while the remaining 8 focused on the association between CSU/CIU and these factors without examining any evidence of stress. Implications: The complex neuro-immunecutaneous model that involves numerous neuropeptides and neurokinins, inflammatory mediators and cells, hypothalamic-pituitary-adrenal axis hormones, and the skin may better explain the underlying pathophysiological mechanisms involved in the onset of urticaria. In addition, the elevated psychological stress level that has been closely related to CSU/CIU could be attributed to the imbalance or irregularity of this neuro-immune-cutaneous circuit. It is still unclear and must be further investigated whether any psychological stress results in or triggers CSU/CIU onset on top of a preexisting neuroimmune dysregulation. Nevertheless, new psycho-phenotypic or neuro-endotypic CSU/CIU subsets should be considered as the era of personalized treatment strategies emerges. A better understanding of CSU/ CIU pathophysiology and consideration of the patient as a whole is vital for identifying targets for new potential treatment options (Clin Ther.

Impact of coronavirus disease 2019 on the mental health of university students in Sichuan Province, China: An online cross‐sectional study

“…In regard to mental health care, an acute public health event can act as a stressor. A stressor refers to a type of environmental stimulus that leads to a specific psychological and physiological response in an individual, which threatens the individual’s important needs and coping ability (Konstantinou & Konstantinou 2020; Li & Hasson 2020). The key characteristics and unknown details of the event itself can increase people’s uncertainty about the causes of the public health event and the means to deal with it; thus, they are prone to experiencing stress manifesting as anxiety, fear, and other emotions (Main et al .…”

The psychosocial burden of urticaria

“…Patients with spontaneous urticaria, compared to those with inducible urticaria, are shown to have significantly higher urticarial activity and a stronger perception of stress 9 . Also, another study showed a significant association between stress levels, systemic inflammation, elevations (IL) -18, and C-reactive protein (CRP) levels, and this relationship was even more pronounced in patients with a more severe clinical representation and other autoimmune diseases 8 . In addition, several studies have shown that abnormalities in the functioning of the hypothalamic-pituitary-adrenal axis (HPA axis) are present in patients suffering from urticaria 8 .…”

“…Both research studies and clinical experience show that various dermatological diseases are psychosomatic, urticaria being one of them. Research suggests that the relation between stress and urticaria is due to complex interrelations of the neurological and immune systems with the skin, involving numerous neuropeptides, neurokinins, inflammatory mediators, and HPA axis cells and hormones 8 . The results of a recently published systematic review clearly show that many patients experience elevated levels of psychological stress before the onset of urticaria and link the onset and worsening of the disease to unpleasant and stressful experiences 8 .…”

“…Research suggests that the relation between stress and urticaria is due to complex interrelations of the neurological and immune systems with the skin, involving numerous neuropeptides, neurokinins, inflammatory mediators, and HPA axis cells and hormones 8 . The results of a recently published systematic review clearly show that many patients experience elevated levels of psychological stress before the onset of urticaria and link the onset and worsening of the disease to unpleasant and stressful experiences 8 . For example, one study investigated the relationship between disease activity and stress levels in patients with spontaneous and inducible urticaria.…”

Perceived stress links income loss and urticaria activity during the coronavirus disease 2019 pandemic

“…Few epidemiologic studies have addressed this question, but a recent review summarized the neuro-immuno-cutaneous crosstalk as a mechanism that links psychological stress and urticaria. 4 The outbreak of COVID-19 uniquely creates a quasi-experiment and provides an opportunity to study this association. We assumed that the income loss could increase urticaria activity through mental stress; hence, we conducted a social media–based investigation in adult Chinese patients between February 27, 2020, and March 11, 2020.…”