Alopecia areata is an autoimmune-like disease that causes sudden and rapid hair loss. Often it causes circular bald patches at random spots on the scalp. The lifetime risk for alopecia areata is ~2%, so you are not alone in this!
Here I’ll explain the triggers of alopecia areata, why the hair falls out, genetic variants that increase susceptibility, and possible treatment options. As always, I’ll include links to relevant recent research studies, so you can dig deeper if you want to.
What causes alopecia areata?
Alopecia areata is an autoimmune-like disorder in which the immune system attacks the hair follicle. It is a complex, polygenic, immune-mediated disease that can affect people at any age. The average age of onset is in the 30s, and it occurs at the same rate in both males and females. It is the most frequent autoimmune disorder worldwide.[ref][ref][ref]
Coin-sized spots of hair loss are commonly how alopecia areata begins. But alopecia areata can cause:[ref]
- widespread hair loss
- patchy hair loss
- loss of eyelashes
- brittle nails
- bald patches in beards
Hair loss is due to the infiltration of white blood cells into the hair follicle, damaging the cells and causing hair loss.
Normally, hair follicles are ‘immune privleged’. This term means that the immune system doesn’t see the hair follicle. It is both an active and passive mechanism protecting the hair follicle from an immune response. The hair follicle cells present signals (HLA class I and class II molecules) that tell the immune system everything is ok. T regulatory cells (Tregs) are also present to keep the immune response at bay.
Immune privilege is a state that protects certain tissues in the body from being challenged by the immune system. For example, tissues in the eye, testes, and placenta have ‘immune privilege’.
Researchers theorized that hair follicles need immune privilege during the pigment activation and hair shaft production phases. The activation of melanocytes for pigmentation can trigger immune cells. Plus, for most mammals, hair maintenance is a survival factor that needs to be protected even when there is a wound. Thus, researchers theorize that the immune system needs to be modulated to keep it from being overly activated in the hair follicles (and likely in the feather follicles in birds).[ref]
In the area of the hair follicles, cells generate immunosuppressants during the period in which hair is actively growing, which is called the anagen phase. The cells produce molecules such as TGF-B1 and MIF, which suppress natural killer cells.[ref]
In alopecia areata, immune privilege goes awry.
- T cells (white blood cells) and natural killer cells infiltrate the hair follicle.
- Mast cells also are activated and give off inflammatory payloads.[ref]
- Inflammatory cytokine levels elevate. Specifically, IL-2, TNF-alpha, IL-12, and IL-17 are higher in alopecia areata patients.[ref][ref]
- Excessive interferon-gamma production, such as during a viral infection, can also upregulate T cells in the hair follicle.[ref]
Triggers of alopecia areata:
Alopecia areata occurs more often in people with depression, anxiety, Hashimoto’s, lupus, vitiligo, psoriasis, RA, and inflammatory bowel diseases. What do all of these conditions have in common? Overactivation of the immune system.
Most people (more than 80%) will spontaneously regrow hair within a year of the onset of alopecia areata. But, like many immune system-related diseases, relapses are common…
There are two pathways that researchers think can lead to hair loss:[ref]
- Autoimmune alopecia areata is induced by autoreactive CD8+ T cells that respond to hair follicle-associated autoantigens. This response is coupled with insufficient T regulatory activity to counteract the autoimmune response.
- Alternatively, some cases may not truly be an autoimmune disorder. Researchers also think that alopecia areata can be triggered by excessive natural killer cells or mast cell activities. It could be coupled with or caused by dysbiosis of the hair follicle microbiome.[ref]
Both can trigger the collapse of the hair follicle immune privilege, leading to infiltration by T cells, a type of white blood cell, and apoptosis of hair follicle cells.
Interferon-gamma: During viral infections, interferon-gamma is elevated dramatically. For example, alopecia areata was triggered in a few individuals by the swine flu.[ref]
Th17 shift: T helper 17 cells are a subset of T cells that produce inflammatory cytokines (IL-17A and IL17F). Th17 cells are implicated in causing several different autoimmune diseases, such as RA, lupus, and psoriasis. Researchers have also found Th17 cells in the affected hair follicles of people with alopecia areata.[ref]
Lifestyle factors: Environmental and dietary factors influence the risk of alopecia areata. These include:[ref]
- Smoking activates Th17 cells and increases IL-17 production.
- Sleep disorders cause a 300% increase in the risk for alopecia areata.
- Obesity causes a 15% increase in the risk of alopecia areata.
- Alcohol at normal consumption levels is actually associated with a lower risk of AA.
Here’s a graphical overview of what is impacting the hair follicle.
Is alopecia areata hereditary?
Alopecia areata has a genetic component. Genetic variants related to elevated immune response and susceptibility to autoimmune diseases increase the relative risk of AA. But genes alone do not cause AA. Instead, it is a combination of environmental triggers and genetic susceptibility.
Covid-19 vaccine and alopecia areata:
Alopecia areata has been reported in conjunction with the SARS-CoV-2 vaccines. Here are some of the case reports published by physicians.
- A case series was written about 9 people with AA following SARS-CoV-2 vaccination. None of the people had previously had AA. On average, the patients were seeking treatment for AA about 2 -8 weeks after their second dose of the vaccine.[ref]
- Another case report was on an 80-year-old who had hair (though with some hair loss) before the vaccine. A week after the Pfizer vaccine, he had hair loss and patchy beard loss. After the second vaccine, he had total hair loss (alopecia areata totalis).[ref]
- A case series showed rapid hair loss in people who had previously had AA. They all had rapid hair loss within a week of vaccination (Pfizer and AstraZeneca).
Alopecia Areata Genotype Report
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CTLA4 gene: regulates Tregs cells
Check your genetic data for rs1024161 (23andMe v4, v5; AncestryDNA):
- C/C: typical risk
- C/T: slightly increased risk of alopecia areata
- T/T: increased risk of alopecia areata[ref]
Members: Your genotype for rs1024161 is —.
Check your genetic data for rs231775 49A/G (23andMe v4, v5; AncestryDNA):
- A/A: typical risk of autoimmune conditions
- A/G: increased risk of autoimmune conditions, decrease CTLA4 expression[ref]
- G/G: increased risk of autoimmune conditions, decrease CTLA4 expression[ref][ref][ref][ref]; increased risk of alopecia areata[ref][ref]
Members: Your genotype for rs231775 is —.
PTPN22 gene: encoding the protein tyrosine phosphatase, non-receptor type 2, which is an immune system modulator linked to many autoimmune diseases
Check your genetic data for rs2476601 R620W (23andMe v4; AncestryDNA):
- G/G: typical
- A/G: increased risk of autoimmune diseases, and 3-fold increased risk of alopecia areata
- A/A: increased risk of autoimmune diseases including: vitiligo[ref], Graves’ disease, type 1 diabetes[ref], Meniere’s disease[ref], juvenile arthritis[ref], psoriasis[ref] endometriosis[ref]; 4-fold increased risk of alopecia areata[ref]
Members: Your genotype for rs2476601 is —.
HLA-DRB1*0401: serotype linked to autoimmune diseases including RA and alopecia areata
Check your genetic data for rs660895 (tag for HLA-DRB1*0401) (23andMe v4; v5; AncestryDNA):
- G/G: high risk of RA (~6-fold)[ref][ref], increased risk of alopecia areata[ref]
- A/G: increased risk of RA, increased risk of alopecia areata
- A/A: typical risk
Members: Your genotype for rs660895 is —.
Check your genetic data for rs763780 G7488A (23andMe V5 only):
- T/T: typical
- C/T: typical risk
- C/C: increased risk of AA[ref], increased risk of rheumatoid arthritis; Hasimoto’s.[ref][ref][ref]
Members: Your genotype for rs763780 is —.
IL17RA gene: encodes the receptor for IL-17
Check your genetic data for rs879577 (23andMe v4, v5):
- C/C: typical
- C/T: decreased risk of AA
- T/T: decreased risk of AA[ref]
Members: Your genotype for rs879577 is —.
IL-18 gene: encodes interleukin 18
Check your genetic data for rs1946518 (23andMe v4, v5; AncestryDNA):
- T/T: lower risk of AA
- G/T: typical risk of AA
- G/G: typical risk of AA[ref]
Members: Your genotype for rs1946518 is —.
IL-2 gene: involved in controlling the survival and proliferation of Treg cells
Check your genetic data for rs7682241 (23andMe v5; AncestryDNA):
- G/G: typical risk
- G/T: slightly increased risk of alopecia areata
- T/T: increased risk of alopecia areata[ref]
Members: Your genotype for rs7682241 is —.
IL-2RA gene: receptor for IL-2 (also important in proliferation of T reg cells)
Check your genetic data for rs3118470 (23andMe v4; AncestryDNA):
- C/C: typical risk
- C/T: slightly increased risk of alopecia areata
- T/T: increased risk of alopecia areata[ref]
Members: Your genotype for rs3118470 is —.
MIF gene: encodes the migration inhibitory factor, which prevents excessive interferon-gamma
Check your genetic data for rs755622 (23andMe v4):
- C/C: typical
- C/G: decreased risk of AA
- G/G: decreased risk of AA[ref]
Members: Your genotype for rs755622 is —.
TNF gene: encodes the TNF-alpha pro-inflammatory cytokine
Check your genetic data for rs1800629 -308A/G (23andMe v4, v5; AncestryDNA):
- A/A: Higher TNF-alpha levels. Increased risk of: alopecia areata[ref], ulcerative colitis, septic shock, Hashimoto’s thyroiditis, skin infections, periodontitis, heart disease[ref][ref][ref][ref][ref][ref][ref]
- A/G: somewhat higher TNF-alpha levels – see above
- G/G: typical, better response to high protein/low carb diet
Members: Your genotype for rs1800629 is —.
Lifehacks: Natural ways to target alopecia areata
The first place to start is to go to your doctor or a dermatologist.
Conventional Prescription Treatments:
Common courses of treatment prescribed by a doctor include cortisone injections, minoxidil, and immunosuppressive drugs such as methotrexate or cyclosporine. A topical contact-sensitizing drug, diphencyprone, is also available by prescription. Additionally, research into using JAK inhibitors is currently going on.[ref]
Diphencyprone is an allergic contact sensitizer, which causes low-grade chronic dermatitis. It likely causes the T cells to divert from the hair follicle to the epidermal cells on the scalp.[ref]
Photochemotherapy is also being investigated. The trial used targeted UVA (ultraviolet light) after the topical application of 8-methoxypsoralen.[ref]
Natural supplements for Alopecia Areata:
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