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Medically reviewed by Dr. Shani Saks, D.O. on Sept. 12, 2023

The pathogenesis of stress-induced alopecia areata involves apoptotic and autoimmune pathways that may interact with one another in the development of the disease, serving as potential therapeutic targets.

Alopecia areata is an autoimmune dermatological condition that leads to reversible hair loss in the form of patches. This condition may be linked to emotional stress, as psychological factors have been associated with its pathogenesis.

A study published in the International Journal of Molecular Sciences evaluated the apoptotic and autoimmune pathways involved in the development of alopecia areata and potential therapy targets in treating this condition. The study’s findings confirm that stress-induced alopecia areata involves autoimmune and apoptotic pathways. The former is associated with the ectopic expression of MHC class I in the hair follicles, whereas the latter pathway is associated with the regulation of messengers promoting apoptosis in the keratinocytes.

Apoptotic Pathway 

Substance P and corticotropin-releasing hormone (CRH) are signaling molecules that initiate the development of alopecia areata. Substance P induces apoptosis by upregulating the p75 neurotrophin receptor and downregulating immunoreactivity to tropomyosin receptor kinase A. Conversely, CRH is associated with the tumor necrosis factor signaling pathway, leading to apoptosis and the development of alopecia areata. While the apoptotic pathway substantially contributes to alopecia areata, this pathway is not the primary etiological factor in developing this autoimmune dermatological condition.

Autoimmune Pathway 

Psychological stress is known to mediate the secretion of CRH and substance P by the sensory nerves in the dermal layer of the skin. Substance P and CRH also mediate the development of neurogenic inflammation in proximity to hair follicles via degranulation of mast cells. This results in the progression of hair follicles into the catagen phase of the hair growth cycle. This forced progression into the catagen stage is also termed the regression stage and indicates the development of alopecia areata and the collapse of immune privilege. Substances associated with apoptotic pathways tend to induce earlier transition of hair follicles into the catagen phase, indicating an interaction between apoptotic and autoimmune pathways.

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Therapeutic Strategies 

The direct treatment method involves drugs that promote the regeneration of immune privilege in hair follicles. These include calcineurin inhibitors, which downregulate the expression of MHC class I. Ultraviolet A-1 phototherapy can elevate α-melanocyte stimulating hormone. Drugs targeting cytokines and Janus kinase/signal transducers and activators of transcription (JAK/STAT) are also indicated for treating alopecia areata.


Ahn, D. H., Kim, H., Lee, B., & Hahm, D. (2023). Psychological Stress-Induced Pathogenesis of alopecia areata: autoimmune and apoptotic pathways. International Journal of Molecular Sciences, 24(14), 11711. https://doi.org/10.3390/ijms241411711