
==== Front
Cureus
Cureus
2168-8184
Cureus
2168-8184
Cureus Palo Alto (CA)

10.7759/cureus.66303
Pediatrics
Dermatology
Infantile Bullous Pemphigoid: Vaccination and SARS-CoV-2 Infection as Triggers
Muacevic Alexander
Adler John R
Moens Héloise 1
Delcambre Louise N 2
De Greef Axel 1
Leboutte Marie-Emeline 3
Baeck Marie 1
1 Dermatology, Cliniques Universitaires Saint-Luc, Brussels, BEL
2 Pediatrics, Cliniques Universitaires Saint-Luc, Brussels, BEL
3 Pediatrics, Jolimont Hospital, La Louvière, BEL
Marie Baeck marie.baeck@saintluc.uclouvain.be
6 8 2024
8 2024
16 8 e663035 8 2024
Copyright © 2024, Moens et al.
2024
Moens et al.
https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License CC-BY 4.0., which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
This article is available from https://www.cureus.com/articles/278069-infantile-bullous-pemphigoid-vaccination-and-sars-cov-2-infection-as-triggers
Bullous pemphigoid (BP) is an acquired auto-immune blistering disease, which is uncommon during childhood. Infantile BP usually has a good prognosis with rare recurrence and the suspected triggers are vaccines or viruses. We report the case of a three-month-old infant girl who presented with BP a week after a SARS-CoV-2 infection and three weeks after the first doses of polio, tetanus, diphtheria, pertussis, Haemophilus influenzae type-b, hepatitis, and pneumococcus vaccinations. Both triggers (infection and vaccination) could be implicated as a slight recurrence was observed after the second doses of vaccines. Rapid clinical resolution was obtained with topical corticosteroids.

pediatric rare diseases
auto-immune blistering disease
vaccine
sars cov-2
infantile bullous pemphigoid
==== Body
pmcIntroduction

Bullous pemphigoid (BP) is a rare disease among children. However, it is the second most common acquired immunobullous disease after linear IgA dermatosis in this life age, with which it shares clinical features. For these reasons, diagnosis is challenging and requires a skin biopsy to be confirmed [1,2]. Scientific evidence is still lacking regarding triggers or treatment management. We report here the case of an infant who presented BP a few days after a documented COVID-19 infection with a slight recurrence after vaccination. The patient responded well to topical treatment.

Case presentation

A three-month-old girl was admitted for an acral bullous eruption, rapidly spreading to the face, chest, and arms. Three days before the rash, the infant presented with fever and a positive nasal PCR swab for SARS-CoV-2. There was no relevant family history and the infant was otherwise healthy.

Paracetamol was administered for the fever and no other medication was recorded. Immunization was started 24 days before the eruption with the first doses of polio, tetanus, diphtheria, pertussis, Haemophilus influenzae type-b, hepatitis, and pneumococcus vaccines. Physical exam revealed vesicles and blisters with erythema and edema on the hands and feet (Figures 1A, 1B). On the trunk and limbs, erythematous macules with an annular appearance were observed (Figures 1C, 1D). The mucosa was not involved. Nikolsky's sign was negative.

Figure 1 Clinical aspect

Tense blisters, erythematous plaques, and erosions on the palms and soles of the feet observed at the start of the eruption (A, B) then extension on the face (C). Circled-like lesions on the arms and the trunk (D).

Laboratory findings showed moderate eosinophilia (1.090/nL, normal value 0.04-0.58/nL), with no other significant abnormalities. Microbiological analyses were negative. Histopathological examination of a skin biopsy showed an inflammatory dermal infiltrate with numerous eosinophilic polymorphonuclear cells with margination along the dermo-epidermal junction. Direct immunofluorescence revealed IgG antibodies and C3 linear deposits along the dermo-epidermal junction (Figures 2A, 2B). Enzyme-linked immunosorbent assay (ELISA) testing with recombinant BP180 was positive (228.33 U /ml), while it was negative for the recombinant BP230. Based on the clinical features, and histopathological and immunologic findings, the diagnosis of BP was made.

Figure 2 Immunohistochemistry

Direct immunofluorescence (DIF) examination of a perilesional skin biopsy. IgG antibodies (A) and C3 linear deposits (B) detected along the dermo-epidermal junction.

Treatment with topical corticosteroids (mometasone furoate 0,1% - in a thin layer on the lesions once a day) was initiated and led to complete resolution of the lesions within two weeks. Treatment was stopped after a few days of complete resolution. Despite delaying the second dose of vaccines by 10 days, a slight recurrence of the lesions was observed. However, topical corticosteroids, at the same dosage, once again allowed for a rapid improvement. There was no recurrence of the lesions at the third vaccination.

Discussion

BP is rare during infancy, with two peaks of incidence: in the first year of life and around eight years old [1]. It is the second most common acquired immunobullous disease in children after linear IgA dermatosis [2]. The bullous lesions and the annular erythematous involvement on the limbs and trunk led us to consider IgA dermatosis as the primary differential diagnosis, although the initial acral involvement could have suggested BP. However, an eosinophilic rather than a neutrophilic infiltrate, along with linear deposits of IgG and C3 complements, confirmed the diagnosis of BP. This emphasizes the importance of skin biopsy in the differential diagnosis of bullous lesions in children. Positive autoantibodies against BP180 antigen and negative anti-BP230 are common in the infantile form of BP as in the present case [3,4].

The exact etiology and the triggering factors of infantile BP are not yet known. Research supports the involvement of genetic and environmental factors such as viral infection or immunization [5]. There are several reports related to vaccine administration [6]. The mean time between vaccination and BP was 7.5 days (range: 5 hours to 3 weeks) [7]. In the case of vaccine-induced dermatosis, the hyperinflammation state produced seemed to be initiated by molecular mimicry and immune cross-reaction [8]. However, the causality link is difficult to prove. In most cases, vaccination was pursued with only a few relapses. The first potential trigger in the case herein reported was the proven SARS-CoV-2 infection a few days before the first lesion. In fact, some viruses may induce a nonspecific immune activation and via similarities between viral peptides and self-peptides of skin membrane, leading to an immune response against self-antigens [9]. These autoantibodies react against epidermic basal membrane antigens (BP-180 or BP-230, a component of hemidesmosomes) and cause tissue damage. Potential triggering by COVID-19 has already been reported [10].

Infantile BP has generally a good prognosis and resolves rapidly after treatment. Topical or systemic corticosteroids remain the first-line treatment. If necessary, immunosuppressive agents can be added such as dapsone, mycophenolate mofetil or cyclosporine. Other treatments such as sulfapyridine, erythromycin ethulsuccinat, intra-venous immunoglobulins, rituximab, and omalizumab have been proposed in refractory BP [1,3,11].

Conclusions

BP is a rare disease among children but should be considered in the case of childhood bullous eruption with predominant acral involvement. This case report is original in that two triggering factors are potentially involved or even associated. To our knowledge, few cases have been reported following infection with SARS-CoV-2. Monotherapy with topical corticosteroids was effective, even after relapse, thus avoiding potential side effects of oral steroids. Further studies are needed to improve treatment guidelines and better assess the triggers of this disease.

The two first authors, Dr. Moens and Dr Delcambre, contributed equally to this work. We thank Dr. Mariana Andrade, M.D., who provided editorial assistance. We thank Dr. Heijmans, M.D., and Dr. Sanchez, M.D., for their clinical resources.

Disclosures

Author Contributions

Human subjects: Consent was obtained or waived by all participants in this study.

Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following:

Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work.

Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work.

Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.

Concept and design:  Héloise Moens, Louise N. Delcambre, Marie Baeck

Acquisition, analysis, or interpretation of data:  Héloise Moens, Louise N. Delcambre, Axel De Greef, Marie-Emeline Leboutte, Marie Baeck

Drafting of the manuscript:  Héloise Moens, Louise N. Delcambre, Marie Baeck

Critical review of the manuscript for important intellectual content:  Héloise Moens, Louise N. Delcambre, Axel De Greef, Marie-Emeline Leboutte, Marie Baeck

Supervision:  Marie Baeck
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References

1 Bullous pemphigoid in infancy: clinical and epidemiologic characteristics J Am Acad Dermatol Waisbourd-Zinman O Ben-Amitai D Cohen AD 41 48 58 2008 17945382
2 A case report of bullous pemphigoid in infancy J Am Acad Dermatol Howell S Enginli A Strowd L Ahn C 0 85 2021
3 Bullous pemphigoid in infants: characteristics, diagnosis and treatment Orphanet J Rare Dis Schwieger-Briel A Moellmann C Mattulat B 185 9 2014 25491396
4 Pemphigoide bulleuse de l’enfant Annales de Dermatologie et de Vénérologie Saad S Ghariani Fetoui N Mani O 0 3 2023
5 Bullous pemphigoid: etiology, pathogenesis, and inducing factors: facts and controversies Clin Dermatol Lo Schiavo A Ruocco E Brancaccio G Caccavale S Ruocco V Wolf R 391 399 31 2013 23806156
6 The pathogenesis of bullous skin diseases J Transl Autoimmun Yang M Wu H Zhao M Chang C Lu Q 100014 2 2019 32743502
7 Bullous pemphigoid in infant post vaccination: myth or reality? Int J Immunopathol Pharmacol Neri I Greco A Bassi A 295 299 29 2016 26684642
8 Plaque psoriasis exacerbation and COVID-19 vaccination: assessing the characteristics of the flare and the exposome parameters Vaccines (Basel) Karampinis E Papadopoulou MM Chaidaki K 178 12 2024 38400161
9 Autoimmune disease and molecular mimicry: an hypothesis Trends Biochem Sci Baum H Butler P Davies H Sternberg MJE Burroughs AK 140 144 18 1993 8493726
10 Case report: infantile bullous pemphigoid: triggering by COVID-19 is speculative Front Med (Lausanne) Rosińska-Więckowicz A Jałowska M Bowszyc-Dmochowska M Dmochowski M 760823 8 2021 34881262
11 Infantile bullous pemphigoid treated using intravenous immunoglobulin: case report and review of the literature Pediatr Dermatol Tekin B Yücelten AD 723 726 32 2015 26119800
