Pemphigus vulgaris after COVID-19 infection and vaccination

Abstract

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.1De Medeiros V.L.S. Monteiro-Neto A.U. França D.D.T. Castelo Branco R. de Miranda Coelho É.O. Takano D.M. Pemphigus vulgaris after COVID-19: a case of induced autoimmunity.SN Compr Clin Med. 2021; 3: 1768-1772https://doi.org/10.1007/s42399-021-00971-8Crossref PubMed Google Scholar 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).1De Medeiros V.L.S. Monteiro-Neto A.U. França D.D.T. Castelo Branco R. de Miranda Coelho É.O. Takano D.M. Pemphigus vulgaris after COVID-19: a case of induced autoimmunity.SN Compr Clin Med. 2021; 3: 1768-1772https://doi.org/10.1007/s42399-021-00971-8Crossref PubMed Google Scholar, 2Koutlas IG, Camara R, Argyris PP, Davis MDP, Miller DD. Development of pemphigus vulgaris after the second dose of the mRNA-1273 SARS-Cov-2 vaccine. Oral Dis. Published online 26 November 2021:odi.14089. https://doi.org/10.1111/odi.14089Google Scholar, 3Solimani F. Mansour Y. Didona D. Dilling A. Ghoreschi K. Meier K. Development of severe pemphigus vulgaris following SARS-CoV-2 vaccination with BNT162b2.J Eur Acad Dermatol Venereol. 2021; 35: e649-e651https://doi.org/10.1111/jdv.17480Crossref PubMed Scopus (25) Google Scholar, 4Thongprasom K, Pengpis N, Phattarataratip E, Samaranayake L. Oral pemphigus after COVID-19 vaccination. Oral Dis. Published online 28 September 2021:odi.14034. https://doi.org/10.1111/odi.14034Google ScholarTable IReported cases of pemphigus vulgaris after COVID-19 infection and vaccinationPatient profileAfter infection or vaccination?COVID-19 vaccine typeOnset (days after vaccine administration/infection)Location of lesionsTreatmentClinical outcome60-year–old manVaccinationModerna mRNA-1273, second dose7 dMouthRituximab (2 doses spaced 2 wk apart)Remission within 14 d after the second rituximab dose, failed prednisone/Bactrim/fluconazole/vitamin D3 therapy40-year–old womanVaccinationmRNA BNT162b2 (Pfizer), first and second doses5 days after the first dose, 3 d after the second doseMouth (first and second doses), trunk and back (second dose only)Oral prednisone and azathioprineRemission without reported relapse (unspecified timeline)38-year–old womanVaccinationAZD1222 (AstraZeneca), first dose7 dMouthTopical steroid (fluocinolone acetonide 0.05%)Remission within 7 d43-year–old manInfectionNone40 dChest, abdomen, back, upper limbs, and lower limbsOral prednisone and subcutaneous methotrexateRemission after 15 d Open table in a new tab 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.2Koutlas IG, Camara R, Argyris PP, Davis MDP, Miller DD. Development of pemphigus vulgaris after the second dose of the mRNA-1273 SARS-Cov-2 vaccine. Oral Dis. Published online 26 November 2021:odi.14089. https://doi.org/10.1111/odi.14089Google Scholar 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.3Solimani F. Mansour Y. Didona D. Dilling A. Ghoreschi K. Meier K. Development of severe pemphigus vulgaris following SARS-CoV-2 vaccination with BNT162b2.J Eur Acad Dermatol Venereol. 2021; 35: e649-e651https://doi.org/10.1111/jdv.17480Crossref PubMed Scopus (25) Google Scholar 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.5Wack S. Patton T. Ferris L.K. COVID-19 vaccine safety and efficacy in patients with immune-mediated inflammatory disease: review of available evidence.J Am Acad Dermatol. 2021; 85: 1274-1284https://doi.org/10.1016/j.jaad.2021.07.054Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar 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.5Wack S. Patton T. Ferris L.K. COVID-19 vaccine safety and efficacy in patients with immune-mediated inflammatory disease: review of available evidence.J Am Acad Dermatol. 2021; 85: 1274-1284https://doi.org/10.1016/j.jaad.2021.07.054Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar 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.1De Medeiros V.L.S. Monteiro-Neto A.U. França D.D.T. Castelo Branco R. de Miranda Coelho É.O. Takano D.M. Pemphigus vulgaris after COVID-19: a case of induced autoimmunity.SN Compr Clin Med. 2021; 3: 1768-1772https://doi.org/10.1007/s42399-021-00971-8Crossref PubMed Google Scholar 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.5Wack S. Patton T. Ferris L.K. COVID-19 vaccine safety and efficacy in patients with immune-mediated inflammatory disease: review of available evidence.J Am Acad Dermatol. 2021; 85: 1274-1284https://doi.org/10.1016/j.jaad.2021.07.054Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar 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. None disclosed.