How stress affects the skin: from designs to mechanisms

Short abstract

Linked Article: Schmidt et al. Br J Dermatol 2021; 185:130–138.

The reciprocal relationship between stress and skin diseases is well known, showing that for example many chronic skin diseases induce moderate‐to‐severe stress responses,¹, ² such as subjective levels of psychological distress and a physiological stress response of altered hypothalamic–pituitary–adrenal (HPA) axis activity, that in turn might trigger a worsened disease course or progression.³ Although there is considerable evidence showing that stress is a common psychological consequence of skin conditions,¹ there is much less ‘hardcore’ evidence from prospective studies about the possible causal effects of stress on the origin or course of a skin disease.⁴ There are at least three ways through which stress can affect the skin that all ask for different designs.

• (i)Stress as a causal factor for the origin of the disease: examples are psychiatric diagnoses of factitious disorders (e.g. dermatitis artefacta) or compulsive disorders (e.g. trichotillomania), without a specific dermatological cause. These cases are usually studied in a clinical context, showing for example that successful treatments can cure these conditions.⁵
• (ii)Stress as a trigger for the worsening of a (chronic) skin disease. Examples are prospective diary studies showing that a worsening of chronic skin diseases, such as psoriasis or eczema, is temporally preceded by a phase of more stress, that for example induces maladaptive behaviour,⁶, ⁷ such as higher scratching response or less adherence, or an altered HPA axis response.³ The number of prospective studies in this area is relatively low,⁴ but increasingly confirms the large number of cross‐sectional studies that suggest a relationship between stress and the course of skin diseases,³, ⁸ at least during periods of high stress.⁶, ⁷ Furthermore, experimental research showing that stress induction is related to increased itch severity in nonclinical populations underlines the potential relevance of experimentally examining stress‐related disease processes in patients with skin conditions.⁹
• (iii)Stress as a trigger for the onset of the skin disease: examples are many retrospective reports of patients with chronic skin conditions that report life events or other stressors in the period before the first onset of the condition, notwithstanding all the limitations of retrospective data.⁴ In contrast, large prospective and epidemiological studies, as presented by Schmidt et al.¹⁰ in this issue, are usually missing to demonstrate these possible causal relationships.

In the article by Schmidt et al.,¹⁰ the authors present an example for stress as a trigger for the onset of a skin disease with a unique dataset of 77 310 Danish citizens, showing a relationship between higher perceived stress responses and the onset of herpes zoster (HZ). The study is characterized by several advantages in comparison with the existing literature, including its large, population‐based sample, prospectively collected data and dose–response analyses. Although these types of studies are important to advance knowledge about the role of stress in the onset of skin conditions, the reported relationships are still descriptive and cannot explain the underlying mechanisms or really prove the causal effects of stress on HZ.

As a next step, it is crucial to disentangle the mechanisms underlying exactly how stress might affect these inflammatory processes. For example, future studies might focus on experimental (treatment) designs in patients with HZ and healthy participants to demonstrate, for example, specific psychoneuroimmunological [such as interleukin (IL)‐6 or IL‐8 responses, altered cortisol levels] as well as behavioural (e.g. scratch responses, low adherence, lifestyle factors) pathways to explain the specific mechanisms underlying the relationship between stress and disease processes in HZ and other skin diseases.

Author Contribution

Andrea W.M. Evers: Conceptualization (lead); Writing‐original draft (lead); Writing‐review & editing (equal). Sylvia van beugen: Conceptualization (supporting); Writing‐original draft (supporting); Writing‐review & editing (equal).