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

Studysummary This study found that alopecia areata is linked to genetic factors, specifically HLA haplotypes on chromosome 6, and involves immune privilege collapse at hair follicles which is mediated by the JAK-STAT pathway and pro-inflammatory cytokines like IFN-γ.

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Research cited in this study

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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”

In this narrative review, researchers outlined the role of T cells in the autoimmune pathogenesis of alopecia areata and highlighted ongoing research into therapeutic pathways, beyond current JAK inhibitors, aimed at developing new treatments for the disease.

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”

This study found that Aire‒/‒ mice spontaneously developed persistent AA-like lesions, highlighting a potential role for AIRE in hair follicle biology and pathogenesis of alopecia areata.

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

40 citations , August 2022 in “Frontiers in immunology”

This review discusses the potential of JAK inhibitors as a promising treatment strategy for alopecia areata, highlighting their mechanism and recent FDA approval based on clinical trial efficacy.

research Effect of PTPN22, FAS/FASL, IL2RA, and CTLA4 Genetic Polymorphisms on Alopecia Areata Risk: Systematic Review and Meta-Analysis

10 citations , November 2021 in “PLoS ONE”

This study suggests that the T allele of the SNP rs2476601 in the PTPN22 gene may increase the risk of alopecia areata, although further studies are necessary to validate this finding across different populations.

research Alopecia Areata: A Review on Diagnosis, Immunological Etiopathogenesis, and Treatment Options

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

This review highlights the challenges in treating alopecia areata, noting that current therapies often lead to relapse and have uncertain long-term effectiveness; it also points to potential future treatments such as JAK-STAT inhibitors and PRP.

research Hair Follicle Immune Privilege and Its Collapse in Alopecia Areata

134 citations , July 2020 in “Experimental dermatology”

This review discusses immune privilege in anagen hair follicles and its collapse in alopecia areata, emphasizing the importance of restoring this function for effective management and disease relapse prevention.

research A Transcriptomic Map of Murine and Human Alopecia Areata

26 citations , May 2020 in “JCI Insight”

In this study, single-cell sequencing revealed clonal expansions of CD4+ and CD8+ T cells in murine and human alopecia areata, supporting the development of predictive models for human disease.

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”

This study found that elevated serum levels of IL-15 in active alopecia areata patients are correlated with disease severity, suggesting it plays a role in disease pathogenesis.

research Alopecia Areata: A Multifactorial Autoimmune Condition

148 citations , December 2018 in “Journal of autoimmunity”

This review discusses genetic and environmental factors contributing to autoimmunity in alopecia areata and reports no new clinical findings, emphasizing the need for further study on its aetiology and pathophysiology.

research What Is Behind the 'Swarm of Bees' in Alopecia Areata

7 citations , November 2018 in “British Journal of Dermatology”

Alopecia areata is caused by immune system issues, and JAK inhibitors might help treat it.

research Immune-Related Alopecia (Areata and Universalis) in Cancer Patients Receiving Immune Checkpoint Inhibitors

87 citations , December 2016 in “British journal of dermatology/British journal of dermatology, Supplement”

This study describes and characterizes four cases of alopecia areata induced by immune checkpoint inhibitor therapy in cancer patients, highlighting the importance of recognizing and managing these hair-related adverse events.

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

62 citations , June 2015 in “The Journal of Dermatology”

This study found that patients with alopecia areata had higher levels of Th17 cells and lower levels of regulatory T cells compared to healthy controls, suggesting an immune imbalance in these patients.

research Plasmacytoid Dendritic Cells in Alopecia Areata: Missing Link?

45 citations , December 2014 in “Journal of the European Academy of Dermatology and Venereology”

This study found that plasmacytoid dendritic cells are central to the pathogenesis of alopecia areata, suggesting they may help differentiate it from trichotillomania and androgenetic alopecia.

research Alopecia Areata Is Driven by Cytotoxic T Lymphocytes and Is Reversed by JAK Inhibition

701 citations , August 2014 in “Nature medicine”

This study found that JAK inhibitors promote hair regrowth in both mice and human alopecia areata cases by blocking key immune pathways involved in disease development.

research Genome-Wide Association Study in Alopecia Areata Implicates Both Innate and Adaptive Immunity

717 citations , June 2010 in “Nature”

This study identified key genetic regions associated with alopecia areata, highlighting both acquired and innate immune involvement, with a novel link to the upregulation of ULBP ligands in autoimmune disease.

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

52 citations , March 2010 in “British Journal of Dermatology”

This study demonstrated the expression of type 1 interferon-related proteins in inflammatory lesions of alopecia areata, showing a distinct distribution pattern compared to cicatricial alopecia.

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”

This study found that recombinant hepatitis B vaccine may increase the risk of alopecia areata onset in older predisposed mice but larger trials suggest this effect might lie within normal variation.

research Maintenance of Hair Follicle Immune Privilege Is Linked to Prevention of NK Cell Attack

253 citations , December 2007 in “Journal of Investigative Dermatology”

This study suggests that human hair follicles may actively suppress natural killer cells, which contrasts with the observed defects in NK cell regulation in alopecia areata.

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

159 citations , November 2007 in “American Journal of Pathology”

In this study, researchers found that substance P triggered premature catagen development and immune changes in human scalp hair follicles, providing a possible biological link between stress and hair loss conditions like telogen effluvium and alopecia areata.

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

36 citations , July 2007 in “Journal of Investigative Dermatology”

This study observed a strong negative association between the HLA-DQB1*0201 allele and the alopecia totalis/alopecia universalis phenotype in Caucasian individuals, indicating a potential protective role.

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”

In this study, researchers found that the AIRE G961C variant is a significant risk factor for severe alopecia areata and early-onset cases, particularly in patients with alopecia universalis.

research Hair Loss After Routine Immunizations

87 citations , October 1997 in “JAMA”

This case series suggests a possible, though likely very rare, association between vaccinations and hair loss, calling for further research in more defined populations.