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

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 chronic spontaneous or idiopathic urticaria (CSU/CIU) and neuroimmune inflammation with or without evidence of co-existing psychological stress from in vivo and ex vivo studies in human beings.

The team studied 13 studies that fit the predefined inclusion criteria. Five of these 13 studies evaluated the correlation between CSU/CIU, stress, and neuro-immune-cutaneous factors, while the remaining 8 focused on the association between CSU/CIU and these factors without examining any evidence of stress.

The complex neuro-immune-cutaneous 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. 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.