Pathophysiology of Alopecia Areata in the Pediatric Patient

March 2025 in “ Pediatric Dermatology ”

Madeline H. Fitzhugh, Jes B. Hansen, Ali Jabbari, Kristen G. Berrebi

alopecia areata autoimmune condition HLA haplotypes chromosome 6 immune privilege hair follicle bulb anagen phase IFN-γ JAK-STAT pathway MHC class I MHC class II NKG2D+ CD8 T cells pro-inflammatory cytokines IL-2 IL-15 hair loss immune system genetic factors inflammation

TLDR Alopecia areata in children is caused by the immune system attacking hair follicles due to genetic factors.

Alopecia areata (AA) is an autoimmune condition causing non-scarring hair loss, influenced by genetic susceptibility and possibly environmental factors. Genome-wide association studies link AA to HLA haplotypes on chromosome 6 and other gene variants, suggesting a genetic component supported by familial and twin studies. The pathogenesis involves the collapse of immune privilege at the hair follicle bulb during the anagen phase, with upregulation of IFN-γ activating the JAK-STAT pathway. This leads to increased MHC class I and II expression, making the hair follicle vulnerable to attack by NKG2D<sup>+</sup> CD8 T cells. The interaction of pro-inflammatory cytokines like IFN-γ, IL-2, and IL-15, and their JAK-STAT signaling, plays a crucial role in the persistence of AA.

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research Inhibition of T-Cell Activity in Alopecia Areata: Recent Developments and New Directions

4 citations , November 2023 in “Frontiers in immunology”

New treatments targeting T-cell pathways are needed for better alopecia areata management.

research AIRE Deficiency Leads to the Development of Alopecia Areata-Like Lesions in Mice

2 citations , October 2022 in “The journal of investigative dermatology/Journal of investigative dermatology”

AIRE deficiency causes hair loss similar to alopecia areata in mice.

research An Overview of JAK/STAT Pathways and JAK Inhibition in Alopecia Areata

40 citations , August 2022 in “Frontiers in immunology”

Blocking JAK/STAT pathways can help treat hair loss from alopecia areata.

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56 citations , January 2021 in “Clinical and Experimental Medicine”

The document concludes that while there are various treatments for Alopecia Areata, there is no cure, and individualized treatment plans are essential due to varying effectiveness.

research Hair Follicle Immune Privilege and Its Collapse in Alopecia Areata

134 citations , July 2020 in “Experimental dermatology”

Hair follicles are normally protected from the immune system, but when this protection fails, it can cause hair loss in alopecia areata.

research A Transcriptomic Map of Murine and Human Alopecia Areata

26 citations , May 2020 in “JCI Insight”

Alopecia areata involves specific immune cells, offering potential treatment targets.

research Serum Level of Interleukin-15 in Active Alopecia Areata Patients and Its Relation to Age, Sex, and Disease Severity

14 citations , January 2020 in “Advances in Dermatology and Allergology”

Higher interleukin-15 levels are linked to more severe alopecia areata, but not to age or gender.

Alopecia Areata: A Multifactorial Autoimmune Condition

research Recombinant Human Hepatitis B Vaccine Initiating Alopecia Areata: Testing the Hypothesis Using the C3H/HeJ Mouse Model

23 citations , January 2009 in “Veterinary Dermatology”

The hepatitis B vaccine did not cause hair loss in the tested mice.

research Role of the Autoimmune Regulator (AIRE) Gene in Alopecia Areata: Strong Association of a Potentially Functional AIRE Polymorphism With Alopecia Universalis

86 citations , December 2002 in “Tissue Antigens”

A specific gene change is linked to severe hair loss.

research Hair Loss After Routine Immunizations

87 citations , October 1997 in “JAMA”

Some vaccines might rarely cause hair loss, more research is needed.

Pathophysiology of Alopecia Areata in the Pediatric Patient

Research cited in this study

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research Hair Follicle Immune Privilege and Its Collapse in Alopecia Areata

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research Imbalance of T-Helper 17 and Regulatory T Cells in Patients with Alopecia Areata

research Plasmacytoid Dendritic Cells in Alopecia Areata: Missing Link?

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research Type 1 Interferon Signature in the Scalp Lesions of Alopecia Areata

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research Probing the Effects of Stress Mediators on the Human Hair Follicle

research Human Leukocyte Antigen Class II Alleles Are Associated with Risk of Alopecia Areata

research Role of the Autoimmune Regulator (AIRE) Gene in Alopecia Areata: Strong Association of a Potentially Functional AIRE Polymorphism With Alopecia Universalis

research Hair Loss After Routine Immunizations