Psychological Stress-Induced Pathogenesis of Alopecia Areata: Autoimmune and Apoptotic Pathways

Abstract

Alopecia areata (AA) is an autoimmune dermatological disease with multifactorial etiology and is characterized by reversible hair loss in patches. AA may be closely related to emotional stress and influenced by psychological factors as part of its pathophysiology; however, its etiology remains predominantly unknown. This review aimed to elucidate the association between AA occurrence and the neuropeptide substance P (SP) and corticotropin-releasing hormone (CRH), which are secreted during emotional stress, and have been understood to initiate and advance the etiopathogenesis of AA. Therefore, this review aimed to explain how SP and CRH initiate and contribute to the etiopathogenesis of AA. To assess the etiopathogenesis of AA, we conducted a literature search on PubMed and ClinicalTrials.gov. Overall, several authors described interactions between the hair follicles (HFs) and the stress-associated signaling substances, including SP and CRH, in the etiology of AA; this was attributed to the understanding in that AA can occur without the loss of HFs, similar to that observed in hereditary hair loss with age. Most studies demonstrated that the collapse of “immune privilege” plays a crucial role in the development and exacerbation of the AA; nonetheless, a few studies indicated that substances unrelated to autoimmunity may also cause apoptosis in keratocytes, leading to the development of AA. We investigated both the autoimmune and apoptotic pathways within the etiology of AA and assessed the potential interactions between the key substances of both pathways to evaluate potential therapeutic targets for the treatment of AA. Clinical trials of marketed/unreviewed intervention drugs for AA were also reviewed to determine their corresponding target pathways.

A case of alopecia areata after rabies vaccination: unreported adverse effect?

“…Administration of PVRV via intramuscular injection has been associated with a pronounced T helper type 2 immune induction, leading to a cascade of chemokine and cytokine release, further target hair follicles, resulting in AA [ 5 ]. However, in our case, being attacked by a dog is undoubtedly a stress event, may resulting in disturbance of endocrine, which considered to play a crucial role in AA development [ 6 ]. Given the absence of adjuvants in rabies vaccines and no familial predisposition, vaccination and emotional stress jointly cause immune dysregulation and abnormal neuroendocrine dynamics emerges as the most plausible etiology for AA.…”

The Hormonal Background of Hair Loss in Non-Scarring Alopecias

“…CRF is secreted by the paraventricular nucleus of the hypothalamus under numerous stressors and plays a pivotal role in the regulation of the stress response, as it activates the HPA axis and promotes the synthesis of ACTH by the pituitary gland. ACTH stimulates the adrenal cortex to produce and release glucocorticoids, such as cortisol [ 78 , 79 ]. Receptors for cortisol and CRF are found, among others, in the skin [ 74 ].…”

“…Dysfunctional cutaneous HPA axis might be one of the underlying causes of alopecia areata. Elevated CRH, ACTH, and α-melanocyte-stimulating hormone (α-MSH) levels were observed in HFs and the scalp epidermis of patients with AA [ 79 , 81 ]. Above all, CRH (along with substance P) may initiate AA.…”

“…The autoimmune pathway dominates and is based on the collapse in the immune privilege of HFs. HFs begin to show a higher expression of major histocompatibility (MHC) class antigens and become a target for the immune system [ 76 , 79 , 82 ]. Some studies in vitro suggest a restoration of the immune privilege of HFs in the treatment of AA.…”

Comparative Study between The Efficacy and Safety of Topical Immune Therapy with Diphenylcyclopropenone versus Anthralin in The Treatment of Resistant Alopecia Areata

“…AA may be associated with anxiety and it increases the risks of psychiatric complications [e.g., generalized anxiety, depression, obsessivecompulsive disorders, suicidal thoughts, body dysmorphic condition, post-traumatic stress syndrome and phobic conditions] [4][5][6] .…”