key: cord-1050060-eya21wnk
authors: Raccampo, Luca; Sembronio, Salvatore; Tel, Alessandro; Veronica, Cacitti; Robiony, Massimo
title: Oral Lichen Planus arising after BNT162b2 mRNA COVID-19 Vaccine: report of two cases
date: 2022-04-11
journal: Oral Surg Oral Med Oral Pathol Oral Radiol
DOI: 10.1016/j.oooo.2022.04.003
sha: b05ce77d842c47d0663d9640f7d8da52d597998d
doc_id: 1050060
cord_uid: eya21wnk

The ongoing pandemic of Coronavirus disease 2019 (COVID-19) required a firm and prompt effort into the development of an effective vaccine. Reports of adverse reactions are increasing. Lichen planus, and its oral variant, is a condition that has been previously reported associated with vaccines. This is one of the first report of oral lichenplanus(OLP) arising after any COVID-19 vaccine. Here we present two cases of OLP occurred after BNT162b2 mRNA COVID-19 vaccination (Comirnaty, Pfizer, New York, NY, USA; BioNTech, Mainz, Germany).

Lichen planus (LP) is a chronic idiopathic inflammatory condition that involves both the skin and mucous membranes. LP has a reported prevalence of roughly 1%, with a female-to-male ratio of approximately 2:1 1 . Although the mean age of the patients affected by LP is over 40 years, cases have also been reported in pediatric patients 2 . Oral lichen planus (OLP) is typically characterized by relapses and remissions and it is chronic, while the cutaneous lesions are mostly pruritic and self-limiting. OLP clinical presentation is variable. The onset of the disease is insidious, since most of the patients are unaware of the condition. The tongue and the gingiva are the most commonly involved parts of the oral cavity and white reticular patches or ulcerations are the typical oral mucosal presentation. Patients usually complain about burning symptoms and hypersensitivity of the mucosa to hot and spicy food. Even though many etiological theories have been proposed to explain the pathogenesis of LP, it is still considered an idiopathic disease 3, 4 . Growing evidence suggests that a T-cells mediated response is implicated in its pathogenesis, triggered by the exposure of specific antigens on the surface of epithelial basal cells 3, 5 . This T cells cross-reaction mechanism seems to be primed by chronic infections (HBV, HIV), drugs (thiazide diuretics, antimalarial agents, NSAIDs etc), contact allergens and dental restorative materials (amalgam, gold, and nickel). LP has also been linked with vaccines including hepatitis B, influenza, rabies, diphtheria, tetanus, pertussis (DTaP) and measles, mumps and rubella (MMR) [6] [7] [8] [9] [10] [11] . The vaccines against COVID-19 were rapidly developed and approved, therefore their short-and long-term effects, their safety and effectiveness were reported in clinical trials. Taking all of this into account, we present two cases of OLP that occurred after the administration of the BNT162b2 mRNA COVID-19 vaccination in the community setting (Comirnaty, Pfizer, New York, NY, USA;

BioNTech, Mainz, Germany).

Case 1: A 54-year-old woman presented with a bilateral white reticular pattern on oral mucosa with no other reported skin or nail lesions. The lesions were asymptomatic but the entity of clinical manifestations and the sudden appearance led the patient to visit her stomatologist. She received the second dose of the COVID-19 vaccine 10 days before the oral lesions appeared. She did not report history of any previous LP presentation, or dermatologic disease. Medical history did not reveal any disease or drugs taken by the patient. When asked about possible alternative triggers, the patient denied any dental procedures, signs of infection, changes in medication or stressful events in the weeks before. She had received all the compulsory vaccinations and she reported never having experienced any vaccine side effects. She had not been diagnosed with COVID-19.

During clinical examination the lesions presented as lacy, white, raised patches of tissues overlying the oral mucosa. Slightly white lace-like network lines (Wickham striae) were observed on oral mucosae, with well-distributed pigmentation on the whole surface (Fig. 1A) . The patient underwent oral biopsy of the lesions under local anesthesia. In both cases, a topical corticosteroid treatment was prescribed with mouth rinses. At subsequent evaluations both patients showed partial remission of lesions, and were scheduled for periodical 6month follow-up.

Clinical and histological findings, combined with the timing of onset with respect to the vaccination, led us to the diagnosis of OLP, which was likely secondary to COVID-19 vaccination.

In both cases the oral biopsy revealed the presence of the characteristic band-like lymphoid subepithelial infiltrate ( Fig. 2A) . At a higher magnification, the inflammatory infiltration into the basal layer and the basal hydropic degeneration of epidermal basal cells could be seen. As it occurs in the skin lesions biopsy, colloid bodies, also known as Civatte bodies, formed as a result of the degeneration of keratinocytes, were visible in the oral epithelium (Fig. 2B ).

The coronavirus disease 2019 (COVID-19) outbreak represents the most challenging pandemic of the century, and the study of a vaccine against SARS-CoV-2 has drawn global attention in order to stop the spread of the pandemic. The unusual rapidity in the development of various type of vaccines strengthened the hesitancy to vaccination and raised several doubts regarding both short-and especially long-term side effects. According to the Centers for Disease Control and Prevention (CDC) the most common side effects are local, such as pain, redness and swelling on the site where the vaccine is injected, or systemic as tiredness, headache, muscle pains, nausea, chills and fever. In order to determine whether possible short term side effects are directly related to vaccination, first a temporal criterion should be satisfied, together with the nonexistence of other concurrent triggering factors 12 . In both our cases the oral lesions appeared just a few days after the injection, suggesting a possible correlation. As reported by Rotim et al. 13 OLP and oral lichenoid reaction (OLR) are similar entities both clinically and histopathologically. While the cause of OLP is supposed to be an autoinflammatory response to an unknown antigen, several factors are commonly attributed to OLR such as drugs, dental restorative materials and dental plaque.

Despite their clinical and histological similarities the two entities differ in treatment. The elimination of the causative agent represents the only possibility for the LR remission, while OLP benefits from topical corticosteroid therapy. That is the reason why a detailed anamnesis is important, as well as a periodical follow-up helps the differential diagnosis among them. In both our cases the lichenoid reaction hypothesis is plausible, although the patient did not report any pre-existing triggering factors and lesions showed only partial remission after corticosteroid topical treatment, therefore we lean for OLP hypothesis.

Although cutaneous or mucosal reactions represent a fairly rare event, the onset of oral and skin lesions is confirmed by the first studies conducted on healthcare workers in various countries 14, 15 . In many cases the clinical appearance of OLP is mild and even the stomatologist could miss the diagnosis in initial stages, therefore it's always difficult to establish whether this condition was preexistent or a new onset. In both cases reported we can not rule out a prior subclinical form of OLP, however, the lesions became evident two weeks after the vaccine suggesting an enhanced immune response independent of whether the condition was preexistent or not.

LP is an immune-mediated inflammatory condition whose progression depends on a T-cell dominated antigen-specific system. This persistent activation of CD8 autocytotoxic T lymphocytes against epidermal and mucosal cells, may provoke apoptosis of basal layer cells and stimulate the production of various cytokines (eg, IFN-γ, IL-5) to increase expression of class II MHC (major histocompatibility complex) molecules and antigen presentation to CD4 T cells 20, 21 . The mechanisms involved in its pathogenesis remain partially unknown, even though several theories have been proposed. It is believed that proinflammatory cytokines play a key role, also stimulating the production of reactive oxygen species leading to apoptosis of the basal layer cells 22 . Moreover Yang et al. investigated the potential involvement on the OLP pathogenesis of T cell-derived exosomes that cause an elevation of the production macrophage inflammatory protein-1α/β, which in turn may guide the trafficking of CD8+ T cells after binding with CCR1/5 in OLP, contributing to the development of OLP 23 . Although it is considered, as mentioned just before, a T cell-mediated idiopathic inflammatory disease that has been often associated with drugs and even vaccines, especially HBV and influenza vaccination, the specific component responsible for the onset of LP is still unknown 10 . It is likely that the cytokine production secondary to the Th1 response that triggers the vaccination may play a fundamental role on the LP outbreak in these patients, even if the exact pathogenic mechanism still remains unclear.

Every clinician engaged in oral care should be aware of this possible complication following COVID-19 vaccination. OLP might represent an adverse event considering the magnitude of the worldwide vaccination campaign that is ongoing. It is, however, a very rare side effect which should not discourage people to get vaccinated against COVID-19. 

Oral lichen planus in childhood

Diagnosis of oral lichen planus: a position paper of the American Academy of Oral and Maxillofacial Pathology. Oral Surg Oral Med Oral Pathol Oral Radiol

Oral lichen planus: a literature review and update

The pathogenesis of oral lichen planus

The pathogenesis of oral lichen planus

Lichen planus and lichenoid drug eruption after vaccination

Lichen planus occurring after influenza vaccination: report of three cases and review of the literature

Lichen planus as a side effect of HBV vaccination

Lichen planus following tetanus-diphtheriaacellular pertussis vaccination: A case report and review of the literature

Lichen planus eruption following annual influenza vaccination. JAAD Case Rep

WHO. Adverse Events Following Immunization (AEFI): Causality Assessment

ORAL LICHEN PLANUS AND ORAL LICHENOID REACTION--AN UPDATE

Side Effects of mRNA-Based and Viral Vector-Based COVID-19 Vaccines among German Healthcare Workers

Vaccine Side Effects among Healthcare Workers in the Czech Republic

Lichen planus arising after COVID-19 vaccination

New-onset cutaneous lichen planus triggered by COVID-19 vaccination

Oral lichen planus following mRNA COVID-19 vaccination

Development of oral lichen planus after COVID-19 vaccination -a rare case report

Oral lichen planus following the administration of vector-based COVID-19 vaccine (Ad26.COV2.S). Oral Dis

Oral lichen planus: an update on its pathogenesis

Interferon-γ activated T-cell IRGM-autophagy axis in oral lichen planus

Oxidative Stress in Cutaneous Lichen Planus-A Narrative Review

T cell-derived exosomes induced macrophage inflammatory protein-1α/β drive the trafficking of CD8+ T cells in oral lichen planus