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Vol. 99. Issue 5.
Pages 758-762 (1 September 2024)
Visits
2023
Vol. 99. Issue 5.
Pages 758-762 (1 September 2024)
Letter - Clinical
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Severe aggravation and possible triggering of pemphigus vulgaris following COVID-19 vaccination: report of two cases
Visits
2023
Kinuko Irie
Corresponding author
kinuko07@fmu.ac.jp

Corresponding author.
, Toshiyuki Yamamoto
Department of Dermatology, Fukushima Medical University, Fukushima, Japan
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Table 1. Reported cases of pemphigus vulgaris triggered by, or exacerbated following, COVID-19 vaccination.
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Dear Editor,

Pemphigus vulgaris (PV) is a severe autoimmune blistering dermatosis. Genetic, malignant, and drug-induced PV triggers have been reported. Here we report two cases of patients who had severe aggravation or exacerbation of PV after COVID-19 vaccination.

Case 1: A 60-year-old man with a two months history of painful erosion on the oral mucosa, which was treated by an otolaryngologist and an internist, received the second dose of the COVID-19 vaccine (Comirnaty®). One week later, erythema and erosions appeared at the vaccination site on his left arm. Subsequently, he developed erythema and erosions on his trunk and was referred to our department one month after the vaccination. Clinical examination showed the presence of post-bullous erosions, especially on the trunk, scalp, and left arm (Fig. 1A). He also had multiple erosions on the buccal mucosa (Fig. 1B). A skin biopsy showed acantholysis within the lower epidermal layers, and the presence of dense lymphocytic and eosinophilic dermal infiltrates (Fig. 2A). Direct immunofluorescence (DIF) revealed intercellular deposition of IgG and C3 in the epidermal cells (Fig. 2B). Serum levels of anti-Desmoglein (Dsg)-1 antibodies (120 U/mL, normal < 3 U/mL) and anti-Dsg-3 antibodies (262 U/mL, normal < 3 U/mL) were elevated. Oral prednisolone (50 mg/day (1 mg/kg/day)) was started; however, the response was poor and thus methylprednisolone pulse (1000 mg/day for consecutive three days), plasma exchange, and methotrexate (6 mg/week) were added. After obtaining remission, he received third and fourth dose of the COVID-19 vaccination without recurrence.

Figure 1.

(A) Crusted plaque and erythema at the vaccination site on the left upper arm. (B) Erosions of the oral mucosa.

(0.29MB).
Figure 2.

(A) Histopathological findings showing acantholysis within the lower epidermal layers, and the presence of dense lymphocytic and eosinophilic dermal infiltrates (×40). (B) Direct immunofluorescence revealed intercellular deposition of IgG in the epidermal cells (×40).

(0.99MB).

Case 2: A 69-year-old woman received the third dose of the COVID-19 vaccine (Spikevax®), and at about the same time, she experienced a scald injury on her right arm. Subsequently, she developed erosions on her extremities and trunk, which gradually increased in number, and was referred to our department three months after the vaccination. Clinical examination showed extensive erythema, flaccid blisters and post-bullous erosions on the trunk (Fig. 3). She also had multiple erosions on the oral mucosa. A skin biopsy from her abdomen revealed acantholysis within the lower epidermal layers, and the presence of dense lymphocytic and neutrophilic dermal infiltrates (Fig. 4A). DIF revealed intercellular deposition of IgG (Fig. 4B) and C3 in the lower epidermal cells. Serum levels of anti-Dsg-3 antibodies were high (8360 U/mL, normal < 3 U/mL), whereas those of anti-Dsg-1 antibodies were normal. Treatment with oral prednisolone (45 mg/day [1 mg/kg/day]), methylprednisolone pulse therapy (1000 mg/day for consecutive three days), and azathioprine (100 mg/day) resulted in complete epithelialization of erosions after 5 weeks of treatment.

Figure 3.

Extensive erythema, flaccid blisters and post-bullous erosions on the trunk.

(0.36MB).
Figure 4.

(A) Histopathological findings showing acantholysis within the lower epidermal layers, and the presence of dense lymphocytic and neutrophilic dermal infiltrates (×40). (B) Direct immunofluorescence revealed intercellular deposition of IgG in the lower epidermal cells (×40).

(0.92MB).

New onset or exacerbation of PV triggered by vaccinations or viral infections have been reported.1–9 There have been reported cases of PV induction or exacerbation following vaccination against influenza, rabies, hepatitis B, tetanus and diphtheria.1 In addition, cases of induction or exacerbation of autoimmune bullous diseases, psoriasis, lichen planus, dermatomyositis, and SLE, following COVID-19 vaccination have recently been reported.10 Activation of innate immunity due to the vaccine is thought to be the cause of exacerbation or development of skin symptoms. BNT162b2 injection induces activation of T-cells and B-cells, and after injection, CD4+ and CD8+ T-cells increase with production of IFN-γ and IL-2.2 It has been suggested that COVID-19 vaccination contributes to the production of cytokines like IL-4, IL-17, and IL-21 that play important roles in autoimmune bullous diseases such as PV.3 Vaccinations also activate B-cells, leading to increased antibody production.4 The reported cases1–9 of PV that developed de novo or deteriorated following COVID-19 vaccination are summarized in Table 1. PV developed a median of 7 (range 1–30) days each after the first, second, and third vaccinations. In contrast, the median time for cases of exacerbations was 3 days (range 3‒14), which is a significantly shorter period of time than the onset cases. However, there are two cases who were able to receive additional vaccinations after undergoing enhanced treatment for PV without flare-up of the disease. One of our cases also allowed for additional COVID-19 vaccinations without worsening the disease. The COVID-19 vaccine can certainly exacerbate PV in very rare cases, but even if exacerbation occurs, the vaccine can be safely administered in PV patients whose disease is well-controlled. Since vaccination is a necessary procedure to prevent aggravation of COVID-19 in immunosuppressed patients, the rare cases of progression of PV should not discourage the vaccination of patients with PV.

Table 1.

Reported cases of pemphigus vulgaris triggered by, or exacerbated following, COVID-19 vaccination.

Nº  Author  Age (years)  Sex  Vaccine  Location of bullous lesion  Dose  New onset/Flare  Time-to-onset (days)  Dsg1/Dsg3  Treatment  Booster vaccination 
1Singh et al.144MChAdOx1 nCov-19Oral mucosa trunk, face, neck, extremities2ndNew7NA/+OC/IVC/  No
IVIg/AZP/ 
Thongprasom et al.1  38  AZD1222  Oral mucosa  1st  New  NA  TC  No 
Koutlas et al.1  60  mRNA-1273  Oral mucosa  2nd  New  -/-  OC/RTX  No 
Knechtl et al.1  89  BNT162b2  Oral mucosa, trunk, back, left arm  2nd  New  30  +/+  OC/RTX  No 
Damiani et al.1  40  mRNA-1273  Back, upper limbs  1st  Flare  NA  OC increased/MMF  Received after treatment for PV/No change in PV condition. 
Damiani et al.1  80  BNT162b2  Back  1st  Flare  NA  OC  Received after treatment for PV/No change in PV condition. 
Solimani et al.2  40  BNT162b2  Oral mucosa, trunk, back  1st/2nd  New/Flare  5/3  +/+  OC/AZP  Received before treatment for PV/PV lesions worsened. 
Shakoei et al.3  28  BBIBP-CorV  N/A  1st  Flare  14  NA  OC/RTX  No 
Shakoei et al.3  30  BBIBP-CorV  Oral mucosa  1st  New  16  NA  OC/RTX  No 
10  Corrá et al.4  61  BNT162b2  Face, trunk  3rd  New  +/+  OC  No 
11  Corrá et al.4  73  BNT162b2  Oral mucosa  3rd  New  30  NA/+  OC/RTX  No 
12  Corrá et al.4  63  ChAdOx1 nCov-19  Oral mucosa, face, trunk  1st/2nd  New/Flare  28/4  +/+  OC/RTX  Received before treatment for PV/PV lesions worsened. 
13  Calabria et al.5  60  BNT162b2  Oral mucosa, oropharynx mucosa  2nd  New  -/+  OC/RTX   
14  Akoglu5  69  ChAdOx1 nCov-19  Oral mucosa, head, limbs  1st  New  +/+  MTX  No 
15  Agharbi et al.6  72  BNT162b2  Oral mucosa, trunk, head, neck, extremities  2nd  New  +/+  OC/AZP  No 
16  Hali et al.7  58  BNT162b2  Oral and genital mucosa, trunk, face, neck, extremities  1st  New  30  NA  OC  Scheduled intake. 
17  Norimatsu et al.8  86  BNT162b2  left arm, face, lumbus  2nd  New  +/+  OC/IVC  No 
18  Saffarian et al.9  76  BBIBP-CorV  Oral and genital mucosa, trunk, head  2nd  New  30  -/-  OC/RTX  No 
19  Our case 1  60  BNT162b2 (1st, 2ndOral mucosa, scalp, trunk, left arm  2nd  Flare  +/+  OC/IVC/PE/MTX  Received after treatment for PV/No change in PV condition. 
20  Our case 2  69  BNT162b2 (1st, 2nd), mRNA-1273 (3rdOral mucosa, trunk, back  3rd  New or Flare  NA  -/+  OC/IVC/AZP  No 

NA, Noavailable; DSG1, Antibody anti-Desmoglein 1; DSG3, Antibody anti-Desmoglein 3; TC, Topical Corticosteroids; OC, Oral Corticosteroids; IVC, Intravenous Corticosteroids; RTX, Rituximab; MTX, Methotrexate; AZP, Azathioprine; MMF, Mycophenolate Mofetil; IVIg, Intravenous high-dose Immunoglobulin therapy; PE, Plasma Exchange; PV, Pemphigus Vulgaris.

Financial support

None declared.

Authors’ contributions

Kinuko Irie: Critical literature review; Data collection, analysis and interpretation; preparation and writing of the manuscript; statistical analysis; study conception and planning; approval of the final version of the manuscript.

Toshiyuki Yamamoto: Study conception and planning; manuscript critical review; approval of the final version of the manuscript.

Conflicts of interest

None declared.

References
[1]
A. Singh, S.J. Bharadwaj, A.G. Chirayath, S. Ganguly.
Development of severe pemphigus vulgaris following ChAdOx1 nCoV-19 vaccination and review of literature.
J Cosmet Dermatol., 21 (2022), pp. 2311-2314
[2]
F. Solimani, Y. Mansour, D. Didona, A. Dilling, K. Ghoreschi, K. Meier.
Development of severe pemphigus vulgaris following SARS-CoV-2 vaccination with BNT162b2.
J Eur Acad Dermatol Venereol., 35 (2021), pp. e649-e651
[3]
S. Shakoei, Y. Kalantari, M. Nasimi, N. Tootoonchi, M.S. Ansari, Z. Razavi, et al.
Cutaneous manifestations following COVID-19 vaccination: a report of 25 cases.
Dermatol Ther., 35 (2022),
[4]
A. Corrá, F. Barei, G. Genovese, M. Zussino, C.B. Spigariolo, E.B. Mariotti, et al.
Five cases of new-onset pemphigus following vaccinations against coronavirus disease.
J Dermatol., 50 (2023), pp. 229-233
[5]
E. Calabria, F. Canfora, M. Mascolo, S. Varricchio, M.D. Mignogna, D. Adamo.
Autoimmune mucocutaneous blistering diseases after SARS-Cov-2 vaccination: a case report of Pemphigus Vulgaris and a literature review.
Pathol Res Pract., 232 (2022),
[6]
F.Z. Agharbi, G. Basri, S. Chiheb.
Pemphigus vulgaris following second dose of mRNA-(Pfizer-BioNTech) COVID-19 vaccine.
Dermatol Ther., 35 (2022),
[7]
F. Hali Sr, L. Araqi Jr, F. Marnissi, A. Meftah, S. Chiheb.
Autoimmune Bullous Dermatosis following COVID-19 vaccination: a series of five cases.
Cureus., 14 (2022),
[8]
Y. Norimatsu, A. Yoshizaki, T. Yamada, Y. Akiyama, S. Toyama, S. Sato.
Pemphigus vulgaris with advanced hypopharyngeal and gastric cancer following SARS-CoV-2 vaccination.
J Dermatol., 50 (2023), pp. e74-e75
[9]
Z. Saffarian, R. Samii, A. Ghanadan, H. Vahidnezhad.
De novo severe pemphigus vulgaris following SARS-CoV-2 vaccination with BBIBP-CorV.
Dermatol Ther., 35 (2022),
[10]
F. Seirafianpour, H. Pourriyahi, M. Gholizadeh Mesgarha, A. Pour Mohammad, Z. Shaka, A. Goodarzi.
A systematic review on mucocutaneous presentations after COVID-19 vaccination and expert recommendations about vaccination of important immune-mediated dermatologic disorders.
Dermatol Ther., 35 (2022),

Study conducted at the Fukushima Medical University, Fukushima, Japan.

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