Biological Sex and IgE Sensitization Influence Severity of Depression and Cortisol Levels in Atopic Dermatitis

Abstract

Background: Depression is a common comorbid condition with atopic dermatitis (AD), particularly during the active disease cycle. Controversial results regarding the contribution of biological sex, immunoglobulin E (IgE) sensitization, and cortisol on AD severity and comorbid depression justify further investigation. Objective and Methods: To explore the influence of sex and IgE sensitization on biochemical and psychological parameters, and severity of AD, a case-control study of 105 volunteers (56 AD, 49 healthy controls (HC); 50 males, 55 females) was conducted over 10 weeks, starting at dermatological symptom onset. Disease severity, serum IgE, cortisol and testosterone levels, and depression scores were assessed at study baseline and after 10 weeks of conventional treatment. Results: Dermatological severity differed among AD males by IgE sensitization and was elevated in males with extrinsic atopic dermatitis (EAD). Hamilton Depression Rating Scale (HAMD) scores were elevated in all patients at study baseline and improved with symptom reduction to HC levels, except female EAD. Severity of depression and dermatitis were correlated in EAD males at baseline and at week 10. Serum cortisol was elevated in male EAD at baseline, in contrast to males with intrinsic atopic dermatitis (IAD) at week 10. In addition, cortisol levels were found negatively correlated with SCORAD and HAMD scores in EAD males at week 10. Conclusion: Pathophysiological features of AD and depression are likely related to different inflammation-based effects and appear to be biological sex-dependent. Cortisol levels depend on biological sex and IgE sensitization in AD and increase in males with EAD at exacerbation and IAD males at resolution. Biological sex-related disease triggers, IgE sensitization, and cortisol levels are important for the understanding of the mechanisms underlying AD and comorbid depression.

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“…Moreover, dysfunction of the neuroendocrine-immune system was observed in the presence of skin diseases as previously described. Studies have shown that some changes in the metabolism and balance of glucocorticoids and sex hormones may be susceptible factors of immune-mediated diseases ( Kasperska-Zajac et al, 2007 ; Vinnik et al, 2020 ). It has been shown that glucocorticoids, such as cortisol and cortisone, and sex steroids, such as DHEA and testosterone, have multiple immunomodulatory effects ( Bereshchenko et al, 2018 ).…”

A systematic review on shared biological mechanisms of depression and anxiety in comorbidity with psoriasis, atopic dermatitis, and hidradenitis suppurativa

“…However, the authors reported that in AD patients with depressive symptoms and state anxiety, natural killer (NK) activity was reduced along with plasma IL-4 levels. Vinnik et al [ 56 ], on the other hand, identified the increased plasma levels of IgE and cortisol as common pathogenetic mechanisms. The overall risk of bias for this study was high, due to a high score on confounding and information bias.…”

“…However, to what extent such mechanisms contribute clarifying the comorbidity presence remains unclear [ 55 ]. Vinnik et al [ 56 ], in addition, indicated the increased plasma levels of IgE and cortisol. Interestingly, the authors hypothesized that particularly in AD male patients, the major active neurosteroid DHEA appeared significant as a regulator of IgE synthesis and eosinophil proliferation, besides the increased cortisol levels and the activated HPA axis response caused by the IgE-mediated degranulation of mast cells.…”

Sex, Allergic Diseases and Omalizumab

“…In addition, the activity of hormones in atopic dermatitis (AD) has been demonstrated [ 52 ], with a different dermatological manifestation based on IgE sensitization only in male patients [ 53 ].…”