Psychoneuroimmune Aspects of Atopic Dermatitis

Pathogenetic events in atopic dermatitisAtopic dermatitis (AD) include the dysregulation of immune pathways and neuroimmune circuits, which are related with clinical AD features, including inflammation, itch, skinSkin xerosis, and barrier dysfunction. Previously, AD was known as “neurodermitis”, a name based on its association with neuropsychological pathways and psychological changes. By the end of twentieth century and beginning of the twenty-first century, new data/discoveries in the fields of immunology and psychoneuroimmunology (PNI) supported that psychological factors/stressStress affect AD manifestations and severity. Psychoneuroimmunologic pathways in AD includes roles of sensory nerves (associated with the itch sensation), which can be activated by various triggers, including exogenous/environmentalEnvironmental or endogenous factors; sensory nerve endings may be excited/sensitized by various factors (cytokines, chemokines, opioids, proteases, lipids, ions, etc.) which may induce various clinical AD characteristics (pruritus, skinSkin inflammation, skinSkin barrier disruption). PNI is a field that focuses on psychological stressPsychological stress and its influence on the body, including disease development and course. The body's stressStress reaction involves a coordinated response of the hypothalamic, pineal, and adrenal structures. AD clinical severity is significantly related to psychological stressPsychological stress, and the hypothalamic–pituitary–adrenal (HPA) axis, which is in accordance with research results confirming HPA axis dysfunction in patients with allergic diseases. Thus, links and communications between the brain and cutaneous structures primarily includes psycho-neuro/endocrine-immuno-cutaneous interactions, involving various neuropeptides, cytokines (primarily interleukins), and immune system messengers. The initial stressStress-induced response can vary by individual in the intensity and duration of the activated neuroimmune and neuroendocrine systems. In chronic stressStress, the initial adaptation/adjustment mechanisms (aimed to cope with the stressStress agent) stimulate the synthesis/secretion of various neuropeptides and neurohormones, which can affect the onset, course, and other aspects of a disease. Psychological stressPsychological stress may stimulate AD manifestations by leading to impaired epidermal barrier function and by favoring immune switching towards a TH2 cell response (both are associated with the AD pathogenic network and disease onset). Research has confirmed that cutaneous keratinocytes express different receptors for neurotransmittersNeurotransmitter and hormonesHormone (adrenergic, glucocorticosteroid, muscarinic, androgenic, estrogenic) and thus keratinocytes actively participate in PNI stressStress-associated skinSkin pathways. So, agents which improve the brain's neural network, stressStress response systems, and skinSkin homeostasisHomeostasis may be effective therapeutic interventions (e.g., stressStress management therapy). Also, to control pruritus in AD, additional targeted therapies for neuroimmune circuits (aside from standard therapy) could be helpful to these patients. These psychological and PNI aspects of AD are also evident in the latest recommendations for AD treatmentTreatment, which include psychosomatic counselling.