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CORRESPONDENCE Table of Contents  
Ahead of print publication
New-onset bullous pemphigoid triggered by AstraZeneca COVID-19 vaccine


 Department of Dermatology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan

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Date of Submission05-Jun-2022
Date of Decision10-Jul-2022
Date of Acceptance30-Jul-2022
Date of Web Publication06-Oct-2022
 


How to cite this URL:
Chao YC, Liu KL. New-onset bullous pemphigoid triggered by AstraZeneca COVID-19 vaccine. Dermatol Sin [Epub ahead of print] [cited 2022 Nov 28]. Available from: https://www.dermsinica.org/preprintarticle.asp?id=358000




Dear Editor,

Bullous pemphigoid is a relatively common autoimmune blistering disease, and mostly affects the elderly. However, the new-onset of bullous pemphigoid triggered by the COVID-19 vaccine is extremely rare. Herein, we would like to report a case of severe bullous pemphigoid triggered by the ChAdOx1 nCoV-19 (Oxford-AstraZeneca) vaccine.

A 49-year-old healthy female denied any systemic disease or family history of skin disorders before. She suffered from generalized itchy erythematous rash the day after the first dose of AstraZeneca vaccination. The itchy plaques spontaneously regressed in a week. Two months later, she developed progressive pruritic annular confluent urticarial plaques 3 days after the second administration of the AstraZeneca vaccine [Figure 1]a. Tense vesicles and bullae with clear yellowish fluid were noted on the neck, trunk, and limbs 5 days after the second vaccination [Figure 1]b, [Figure 1]c, [Figure 1]d. The initial laboratory data showed leukocytosis, eosinophilia, and mildly elevated C-reactive protein level. There were no fever, upper respiratory symptoms, oral ulcers, arthralgia, and myalgia noticed, and no new medication or Chinese herbal medicine was prescribed recently either.
Figure 1: (a) Progressive pruritic annular confluent urticarial plaques appeared on the trunk 3 days after the second dose of ChAdOx1 nCoV-19 (Oxford-AstraZeneca) vaccine, (b-d) Tense vesicles and bullae were noted on the neck, trunk and limbs 5 days after the second vaccination.

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The clinical impression was bullous pemphigoid. Histopathology of the biopsy showed a sub-epidermal blister [Figure 2]a and a perivascular infiltrate of eosinophils and lymphocytes in the dermis [Figure 2]b. Direct immunofluorescence test showed linear deposition of IgG [Figure 2]c and C3 [Figure 2]d at the dermal-epidermal junction. Indirect immunofluorescence assay revealed negative anti-intercellular substance antibody, but positive anti-basement membrane zone antibody with titer 1:40. Other infectious factors that might induce bullous pemphigoid were excluded, with negative results for parasites, mycoplasma, varicella zoster virus and herpes simplex virus 1 and 2. Without a history of any new medication prescribed recently, the new-onset bullous pemphigoid triggered by the AstraZeneca COVID-19 vaccine was highly suspected. Intravenous methylprednisolone 80 mg/day and topical diflucortolone ointment twice a day were prescribed, and the erythematous urticaria-like plaques had subsided. Azathioprine 50 mg/day was also prescribed in conjunction with methylprednisolone. Gradual tapering of corticosteroid dosage was initiated as symptoms improved.
Figure 2: (a) Histopathology revealed the subepidermal blister (H and E, ×100), (b) A perivascular infiltrate of eosinophils and lymphocytes was noted in the superficial dermis (H and E, ×400), (c and d) Direct immunofluorescence test showed a linear deposition of IgG (c) and C3 (d) discernible at split dermal-epidermal junction.

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Bullous pemphigoid usually affects individuals over 60 years of age, but it occurs much younger in our case. The accurate mechanisms for the induction of bullous pemphigoid after vaccinations are not fully understood. It has been reported that bullous pemphigoid might be induced by vaccinations against influenza, rabies, hepatitis B, or rotavirus. It is less likely vaccine itself would cause bullous pemphigoid, since there are no similarities between the vaccine structure and autoantigens BP180 and BP230.[1] It is hypothesized that vaccinations altering or enhancing the immune response through the humoral pathway in patients with genetic predispositions, and destructing the basement membrane zone inappropriately.

New-onset bullous pemphigoid triggered by either the first or second dose of SARS-CoV-2 vaccines have been reported recently; nevertheless, most cases were triggered by the mRNA COVID-19 vaccines with onset time from 1 day to 11 weeks.[2],[3],[4] Only one case report mentioned that bullous pemphigoid was induced by the adenovirus-vector AstraZeneca COVID-19 vaccine.[5] Systemic corticosteroids, topical corticosteroids, doxycycline, methotrexate, nicotinamide, and even dapsone have been prescribed in some patients with good responses.[2],[4]

In general, vaccine-related BP has a relatively benign course if appropriate treatments were given compared to the classic BP. For vaccine-related BP, bullae decreased or disappeared in 3 weeks (median time) with felicitous treatments.[2] At 3 months, most patients can achieve complete remission, whereas some patients had an only partial response or stable disease.[4] In conclusion, the mechanisms of vaccine-induced bullous pemphigoid remain unknown, and further investigative researches are needed to elucidate their relationship.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that her name and initials will not be published and due efforts will be made to conceal her identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Pérez-López I, Moyano-Bueno D, Ruiz-Villaverde R. Bullous pemphigoid and COVID-19 vaccine. Med Clin (Engl Ed) 2021;157:e333-4.  Back to cited text no. 1
    
2.
Tomayko MM, Damsky W, Fathy R, McMahon DE, Turner N, Valentin MN, et al. Subepidermal blistering eruptions, including bullous pemphigoid, following COVID-19 vaccination. J Allergy Clin Immunol 2021;148:750-1.  Back to cited text no. 2
    
3.
Larson V, Seidenberg R, Caplan A, Brinster NK, Meehan SA, Kim RH. Clinical and histopathological spectrum of delayed adverse cutaneous reactions following COVID-19 vaccination. J Cutan Pathol 2022;49:34-41.  Back to cited text no. 3
    
4.
Maronese CA, Caproni M, Moltrasio C, Genovese G, Vezzoli P, Sena P, et al. Bullous pemphigoid associated with COVID-19 vaccines: An Italian multicentre study. Front Med (Lausanne) 2022;9:841506.  Back to cited text no. 4
    
5.
Agharbi FZ, Eljazouly M, Basri G, Faik M, Benkirane A, Albouzidi A, et al. Bullous pemphigoid induced by the AstraZeneca COVID-19 vaccine. Ann Dermatol Venereol 2022;149:56-7.  Back to cited text no. 5
    

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Correspondence Address:
Kwei-Lan Liu,
Department of Dermatology, Kaohsiung Chang Gung Memorial Hospital, No. 123, Dapi Rd., Niaosong Dist., Kaohsiung City
Taiwan
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1027-8117.358000



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