Lymphomatoid drug reaction developed after BNT162b2 (Comirnaty) COVID‐19 vaccine manifesting as pityriasis lichenoides et varioliformis acuta‐like eruption

Abstract

Editor The current global healthcare response to the COVID-19 pandemic is focused on a widespread vaccination campaign, which started with the authorization of Pfizer/BioNTech and Moderna mRNA COVID-19 vaccines in December 2020. Local injection site reactions have been described during the clinical trials of both the abovementioned mRNA vaccines; skin rashes were additionally reported in the trial of Moderna. Despite this, cutaneous adverse reactions to the vaccines and their timing remain to date poorly characterized.1, 2 A 31-year-old Caucasian woman presented with an acute generalized rash arising 10 days after the first dose of BNT162b2 (Comirnaty, Pfizer/BioNTech), which was mildly itchy and associated with fatigue. No reactions at the site of injection and no systemic symptoms, such as fever, were reported. The patient denied taking any medication prior to the eruption. Past and recent medical history was uneventful. Skin examination showed erythematous-pinkish papular lesions partially covered by sero-hematic crusts, involving the trunk, the arms, legs and the face (Fig. 1). The mucous membranes were apparently spared. Bilateral inguinal lymphadenopathy was appreciated at physical examination. The evaluation of serum inflammatory markers, liver and renal function tests, vasculitis-specific antibodies and other markers of autoimmunity was unremarkable. Blood tests for viral and bacterial infections were also negative. The diagnostic workup was completed by skin histologic and immunohistochemical studies: the histopathologic findings were hyperkeratosis producing scaling and crusting. There was reactive epidermal hyperplasia, diffuse spongiosis with foci of mixed, lympho-monocytic infiltrates, as well as the presence of Langerhans cells and granulocytes. The superficial and medium dermis were also involved with a dense, polymorphic inflammatory infiltrate, consisting of small, medium and blastoid elements, as well as few eosinophils. Newly formed capillaries demonstrated parietal oedema and epithelioid features in absence of vasculitis (Fig. 2). Immunohistochemistry was positive for pan-T antigens CD3 (90%), CD5 (80%) and CD7, CD4/CD8 ratio was 2:1. Sparse cells expressed CD30+ (3%), 20% expressed Ki67. Clinical features were suggestive of pityriasis lichenoides et varioliformis acuta (PLEVA); the histopathologic examination could be suspicious for drug-induced pityriasis rosea (PR) but our findings of marked inflammatory reaction with pleomorphic elements and some CD30+ activated cells, that are not described in PR,6 led us to a diagnosis of lymphomatoid drug reaction. The patient started methylprednisolone 16 mg po daily, tapered over three weeks, achieving the complete control of the cutaneous manifestations and leaving hyperpigmented lesions with associated scaling on the trunk and limbs. The patient underwent the second vaccination injection under low dose of systemic corticosteroids and antihistamines, without any significant reactions resulting. All skin sequelae eventually cleared over 2 months. Currently, a classification of COVID-19 vaccine cutaneous reactions is lacking, and their clinical presentation is poorly characterized. The only data available consist in 414 cases reported in the international registry of cutaneous manifestations of SARS-CoV-2 (www.aad.org/covidregistry). According to the registry data, cutaneous reactions were generally mild and self-limited and 43% of patients with skin findings after the first dose showed recurrence after the second dose with no severe sequelae, supporting the tolerability of these vaccines, and reassuring against withdrawal of the second dose in case of previous reactions.3 Data consisted in 71 reports following Pfizer vaccination. The most frequently observed events were urticaria, local injection site reactions and morbilliform rashes. Less common reports were PR-like reactions (four in total).3 The lymphomatoid drug reaction (LDR) observed in our case is a skin manifestation, which, similarly to lymph node modifications, is characterized by strong immunoblastic activation and may be triggered by the antigenic challenge of the vaccine.4, 5. To our knowledge, there are no antecedent reports of LDR following Pfizer vaccine; also, the histological and immunohistochemical characterization of cutaneous adverse events to COVID-19 vaccinations is still scarce.7 Clinical aspects of PLEVA, a rare cutaneous inflammatory disorder that may potentially present with severe systemic symptoms,8 have been previously described in isolated cases after measles-mumps-rubella vaccine9 and are firstly reported following COVID-19 vaccination in our case. The patient in this manuscript has given written informed consent to publication of their case details. The authors have no competing interests to disclose. None. The data that support the findings of this study are available from the corresponding author, TG, upon reasonable request.

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