Pemphigus vulgaris after COVID-19 infection and vaccination.

To the Editor: Pemphigus Vulgaris (PV) is a rare autoimmune skin blistering disorder; there have been previous reports of COVID-19 triggering autoimmune responses, including PV. However, there remains limited discussion on the incidences of PV after COVID-19 infection and vaccination. We present a review of PV onset after COVID-19 infection and vaccination and its implications for shared clinical decision making between patients and clinicians.

Literature searches were conducted on PubMed and Google Scholar ranging from 2019 to December 2021. Five articles were selected on the basis of subject relevance; cases of PV flares were excluded. To date (February 2022), there have been 3 cases of PV after COVID-19 vaccination and 1 case of PV after COVID-19 infection (Table I ).1, 2, 3, 4

Table I

Reported cases of pemphigus vulgaris after COVID-19 infection and vaccination

Patient profile	After infection or vaccination?	COVID-19 vaccine type	Onset (days after vaccine administration/infection)	Location of lesions	Treatment	Clinical outcome
60-year–old man	Vaccination	Moderna mRNA-1273, second dose	7 d	Mouth	Rituximab (2 doses spaced 2 wk apart)	Remission within 14 d after the second rituximab dose, failed prednisone/Bactrim/fluconazole/vitamin D3 therapy
40-year–old woman	Vaccination	mRNA BNT162b2 (Pfizer), first and second doses	5 days after the first dose, 3 d after the second dose	Mouth (first and second doses), trunk and back (second dose only)	Oral prednisone and azathioprine	Remission without reported relapse (unspecified timeline)
38-year–old woman	Vaccination	AZD1222 (AstraZeneca), first dose	7 d	Mouth	Topical steroid (fluocinolone acetonide 0.05%)	Remission within 7 d
43-year–old man	Infection	None	40 d	Chest, abdomen, back, upper limbs, and lower limbs	Oral prednisone and subcutaneous methotrexate	Remission after 15 d

It is hypothesized that the Moderna mRNA-1273 vaccine upregulates T cell–dependent production of interleukin (IL) 17, interferon γ, and tumor necrosis factor ɑ cytokines to mediate PV. Meanwhile, the mRNA BNT162b2 (Pfizer) vaccine indirectly upregulates the production of IL-4, IL-17, and IL-21 cytokines that have been implicated in autoimmune disorders, including PV. Finally, the double-stranded DNA inside the AZD1222 (AstraZeneca) adenovirus vector vaccine activates toll-like receptor 9, which subsequently upregulates the production of type I interferons that may induce PV-related autoimmunity. However, reports have disputed these hypotheses that vaccine developers have added stabilizing adjuvants and removed interferon-stabilizing double-stranded messenger RNA from the final preparations to reduce the risk of stimulating autoimmune reactions. For PV onset after COVID-19 infection, it is hypothesized that the development of PV after COVID-19 infection could be triggered by molecular mimicry, bystander activation, epitope spreading, or a combination of these 3 autoimmune phenomena.

PV has been reported very rarely after COVID-19 infection and vaccination. The benefits of COVID-19 vaccines significantly outweigh the risks, particularly for the patient population with PV because of their heightened risk of COVID-19 infection and severe complications, such as long-term health impairments and death. We recommend that health care providers discuss the risks and benefits of receiving the COVID-19 vaccine with sensitivity and transparency and remain vigilant against the rare but severe risk of postvaccination PV onset.

Conflicts of interest

None disclosed.