Alopecia areata and subsequent Marie Antoinette syndrome following COVID-19 infection and vaccination: A case report

Introduction

Cutaneous manifestations of COVID-19 (severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)) have been of significant interest to dermatologists worldwide since the start of the pandemic, particularly the association of SARS-CoV-2 infection and hair disorders such as acute telogen effluvium. ¹ Interestingly, androgenetic alopecia and gray hair have been proposed to be independent risk factors for more severe infection with SARS-CoV-2.^2,3 In addition, cases of recurrent alopecia areata after vaccination for SARS-CoV-2 had been documented. ⁴ To our knowledge, what has not yet been reported is the case of Marie Antoinette syndrome, or Canities subita, post-SARS-CoV-2 and/or vaccination, where the scalp hair suddenly turns white. ⁵ In the following report, we describe a case of alopecia areata post-SARS-CoV-2 infection and mRNA-1273 vaccinations, and even more uniquely, with depigmented regrowth.

Case report

In August 2021, a 44-year-old male was referred to our clinic for rapid diffuse hair loss with subsequent depigmented, snow-white regrowth. He endorsed a history of COVID-19 infection and double mRNA-1273 (Moderna) vaccinations. This patient tested positive for SARS-CoV-2 in February 2021, although he claimed to be asymptomatic. He was first vaccinated on 5 May 2021; then 2 weeks later, he developed well-circumscribed patches of hair loss on his scalp without itch or pain. He was prescribed prednisone 50 mg PO daily for 5 days on 25 May 2021, and betamethasone valerate 0.05% lotion, which he discontinued its use after one tube due to significant dermatitis and abscesses. Both treatments were ineffective. His SARS-CoV-2 immunization was boosted on 18 June 2021. One week later, he experienced diffuse hair loss on his scalp, eyelashes, beard hair, and eyebrows. His scalp was also intensely pruritic. Another week later, he experienced facial hair regrowth, followed by scalp hair. He endorsed the initial regrowth of both gray and brown hairs, but they had turned completely white 3 days later. His hair has continued to regrow, albeit thinner, and has remained diffusely white. No further treatment was attempted. He has experienced further new-onset hair loss on his arms and lower legs since. Before May 2021, he endorsed a full head of brown hair, with intermittent gray hair. There is no personal or family history of hair loss, including androgenetic alopecia. He is otherwise healthy. He previously smoked a pack a week for 23 years but has been cigarette-free for 8 months. Blood work ordered by his family physician in between the first and second vaccination, consisting of albumin, ferritin, diabetes mellitus screening, thyroid-stimulating hormone (TSH), prostate specific antigen (PSA), and complete blood count (CBC), was normal, aside from a mildly elevated triglyceride level at 1.80 mmol/L (high end of normal is 1.70 mmol/L).

Physical examination at his visit revealed diffuse white hair over the scalp with no evidence of scalp erythema, perifollicular scale, or circumscribed areas of hair loss. Between the first and second vaccination, he had well-circumscribed patchy hair loss, in keeping with alopecia areata, demonstrated in Figure 1(a).

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Figure 1.

(a) Patchy areas of hair loss showing alopecia areata after mRNA-1273 vaccination. (b) Marie Antoinette syndrome after the regrowth of hair.

Discussion

Unfortunately, as our first visit with our patient was after both the hair loss and regrowth, we were not able to perform trichoscopy or bedside diagnostic tests, to further delineate the nature of his hair loss. However, the well-circumscribed patchy hair loss as shown in Figure 1(a), followed by a diffuse loss with additional affected areas, is a strong indication of alopecia areata. Furthermore, the spontaneous total regrowth, albeit depigmented, suggests a non-cicatricial etiology shown in Figure 1(b). The uncanny timing of our patient’s first-time hair loss following SARS-CoV2 infection and mRNA-1273 vaccination could imply an association with either the SARS-CoV2 infection or mRNA-1273 vaccinations.

Alopecia areata has been proposed to be an immune privilege breakdown in the hair follicle. ⁵ Data suggest that molecular mimicry of the shared hexa- and heptapeptide between the SARS-CoV-2 spike glycoprotein and mammalian proteomes may trigger autoimmune responses following SARS-CoV-2 infection or vaccination. ⁶ This hypothesis could support the first incidence of alopecia areata in our case report, but not the acute loss of our patient’s hair pigment, which is consistent with the Marie Antoinette syndrome. ⁵

A possible mechanism for the loss of pigment is the rapid depletion of melanocyte stem cells from acute stress. ⁷ Inversely, melanocyte destruction was not observed in the hypopigmented regrowth hairs in alopecia areata while the number of melanocytes reduced. Rather, there was a reduced pigment activity, as the keratinocytes were attacked and thus could not accept pigment or induce melanocyte activity. ⁸ These attacks could also cause apoptosis of the follicular keratinocyte. Since the SARS-CoV-2 virus enters human cells via the angiotensin-converting enzyme 2 (ACE2) receptor, which also was highly expressed in keratinocytes and the basal cell layer, ⁹ an autoimmune response on follicular keratinocytes post SARS-CoV-2-infection or vaccination could inhibit the keratinocytes to induce melanocyte activity and accept pigment, leading to depigmented hair. Furthermore, it was also proposed that a melanin-related antigen is involved with alopecia-areata-associated hypopigmentation, as the pigmented hair tends to be preferentially lost over non-pigmented hairs, with hypopigmented hair often being the first to regrow. ⁵

Finally, androgenetic alopecia was shown to be an independent risk factor for SARS-CoV-2 infection.^2,3 To increase cellular uptake of the virus, SARS-CoV-2 was found to hijack the transmembrane protease serine 2 (TMPRSS-2), the only known promoter of which is upregulated by androgens. ¹⁰ While our patient was asymptomatic with SARS-CoV-2, as a male, he could inherently have relatively more circulating androgens compared to female or pre-pubescent male counterparts. Therefore, it could be hypothesized that his initial SARS-CoV2 infection predisposed him to a stronger autoimmune response to both the follicular keratinocytes and/or surrounding melanocytes.

In conclusion, we report a case of alopecia areata and subsequent Marie Antoinette syndrome following SARS-CoV2 infection and mRNA-1273 vaccinations and propose that increased circulating androgens and molecular mimicry could be a viable explanation for the phenomenon. We have also gathered a few mechanisms to explain the sudden loss of pigment, including the preferential attack of a melanin-related antigen and follicular keratinocytes, and stress-induced depletion of melanocytes. However, further research will be needed to investigate the relationship between SARS-CoV-2 infection and/or vaccination with follicular melanocytes and alopecia areata. We have reported this potential vaccine association to Moderna.