Salivary cortisol and perceived psychological stress in patients with chronic contact hand dermatitis.

Like other skin diseases, chronic contact hand dermatitis (CHD) (which includes allergic and irritant contact dermatitis) might be influenced by psychological stress (PS). Stress-induced physiological responses, regulated by the hypothalamic–pituitary–adrenal (HPA) axis, can result in increased cortisol secretion, negatively affecting immune functioning.1 Thus, the aim of this study was to explore PS and its effect on quality of life and disease severity in CHD patients with objective and subjective measuring tools/biomarkers. This exploratory multidisciplinary cross-sectional study involved 59 patients with CHD that had a chronic course (defined as lasting >3 months or as having ≥2 exacerbations in 1 year)2 and 19 healthy controls (HCs) (Supporting Information). Inclusion and exclusion criteria are mentioned in the supplement file (Table S1). We assessed subjective intensity of PS severity with the Perceived Stress Scale (PSS).3 Cortisol levels of saliva samples taken between 6 and 8 a.m. were analysed as objective biomarkers of stress using the ‘Cortisol Saliva ELISA kit’ (Euroimmun®, Lübeck, Germany) according to the manufacturer's instructions (Supporting Information).4, 5 Additionally, all the CHD patients filled in the Dermatological Quality of Life Index (DLQI) questionnaire6 and self-assessed the Hand Eczema Extent Score (HEES).7 Values were compared between the two subject groups with the Mann–Whitney U test. Effect size was estimated using r = Z/√N. A small effect size was r = 0.14–0.36, moderate was r = 0.36–0.50, and >0.5 was considered large. The correlations between morning salivary cortisol levels, PSS, DLQI and HEES were evaluated by Spearman's correlation, given that the data had a normal distribution. For positive correlations, linear regression analysis was used additionally. The majority of participants were female (73%). The median age was 38 with an interquartile range of 28.2–53 years and an average age of 40.2 years old. There was no statistically significant difference in sex distribution and age between the CHD patients and HCs. Sensitizations to nickel sulphate (40.7%) and cobalt (30.5%) were most common, with 35.7% being positive to more than one allergen. All of the patients had positivity to at least one contact allergen, but not all of these sensitizations were relevant for their CHD. CHD patients had significantly lower morning salivary cortisol level and higher PSS scores than HCs (p ≤ 0.001), with a somewhat bigger effect size for PSS (r = 0.425 vs. r = −0.392) (Table 1). Additionally, 13.6% of CHD patients had morning salivary cortisol concentrations that were considered low (<5.72 nmol/L) while all the HCs had salivary cortisol concentrations that were considered average as defined by the manufacturer of the ELISA kit. Significant correlations between DLQI and HEES scores (r = 0.399, p = 0.002) and between DLQI and PSS scores (r = 0.492, p < 0.001) were found in the CHD patients (Table 2). This association is moderate, linear and positive. According to multiple linear regression analysis, only higher HEES and PSS were significant predictors of higher DLQI scores (more impaired quality of life), controlling for age, sex, duration of disease and morning salivary cortisol (Table 3). To our knowledge, this is the first study that examines intensity and biomarkers of PS in patients with CHD. In earlier research, it was observed that atopic dermatitis (AD) patients had lower morning salivary cortisol values than HCs, especially in those with severe AD, and a negative correlation between acute stress-associated increased salivary cortisol levels and AD severity was found.5, 8, 9 Similarly, lower morning salivary cortisol levels were found in our CHD patients compared to HCs. It is likely that our CHD patients were exposed to chronic PS. The low morning cortisol levels could be related to chronic PS which increases total daily cortisol levels, but in turn causes HPA axis imbalance and disruption of the physiological circadian rhythm. To counteract chronically elevated cortisol levels, the HPA axis lowers the morning levels and acute increases in cortisol concentrations.10 Simultaneously, chronically elevated cortisol values shift the immune balance towards the intensification of lymphocyte T helper cells and cytotoxic T lymphocytes responses, consequently affecting inflammatory dermatoses like CHD.10 In accordance with the low morning salivary cortisol levels, patients with CHD had a significantly higher PS intensity (PSS) than HCs. Notably, we did not find the expected correlation between a higher PS intensity and lower salivary cortisol levels or a higher disease severity (HEES). However, a significant positive correlation between the DLQI and the PSS score as well as the HEES score was observed suggesting a relationship between a low health-related quality of life and both a high PS intensity and a severe disease. It is possible that emotional factors and chronic PS exposure can often worsen itching and scratching and further impair a patient's quality of life. More severe disease was associated with lower quality of life which was expected. One study limitation is the small sample size. Also, patients may potentially had multiple diagnoses (e.g., atopic dermatitis, irritant contact dermatitis, allergic contact dermatitis). The question remains if these findings may pivot future approach to CHD patients in multidisciplinary way (e.g., including emotional and psychological approach/involvement in treatment). As the PS intensity is high and associated with a low health-related quality of life and may also affect inflammatory processes, CHD patients may benefit from multidisciplinary treatments, including emotional and psychological support. Nives Pondeljak: Conceptualization; investigation; writing – original draft; methodology; writing – review and editing; formal analysis. Lucija Tomić: Writing – review and editing. Elvira Lazić Mosler: Writing – review and editing. Mirna Šitum: Writing – review and editing. Dalibor Karlović: Writing – review and editing. Liborija Lugović-Mihić: Supervision; resources; project administration; visualization; validation; methodology; writing – review and editing; conceptualization. The authors declare no conflicts of interest. Data S1. Supporting Information Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. 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