Pernio‐like skin lesions after the second dose of Pfizer‐BioNTech COVID‐19 vaccine

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Dear Editor,

We present the case of a 60‐year‐old patient who reported the onset of pernio‐like lesions on both hands, approximately 14 days after the administration of the second dose of the Pfizer‐BioNTech vaccine. Local and systemic symptoms such as pain at the injection site, asthenia and headache of mild‐to‐moderate severity also appeared following the administration of the first and second doses and resolved within 2 days. Physical examination showed erythematous‐violaceous patches and swelling on the fingers, accompanied by itching and burning sensation (Fig. 1). The occasional appearance of livedo reticularis‐like manifestations on the lower limbs was also referred.

Figure 1.

Pernio‐like lesions on the fingers of right hand after the second dose of Pfizer‐BioNTech vaccine.

Laboratory tests (complete blood count, antinuclear antibodies, antiphospholipid antibodies, C‐reactive protein, erythrocyte sedimentation rate, serum protein electrophoresis and serum cryoglobulins) were normal, excluding the presence of concomitant systemic diseases.

Given the association between the new onset of pernio‐like manifestations and COVID‐19 infection, ¹ a polymerase chain reaction test for COVID‐19 was performed with a negative result.

Pernio or chilblains is an inflammatory condition, frequently affecting women, characterized by erythema and swelling that commonly occur in response to cold on acral regions.

Pernio lesions are generally idiopathic and, in some cases, secondary to other diseases such as systemic lupus erythematosus. Skin biopsy is generally not performed as this clinical condition is not characterized by specific histopathology. In fact, in the reported case no skin biopsy was performed and the diagnosis was clinical. Raynaud's phenomenon, cryoglobulinemia, acrocyanosis and cold panniculitis should be considered in the differential diagnosis. ²

Management of pernio skin lesions consists of avoiding exposure to cold and the use of corticosteroids and vasodilatory agents such as nifedipine. ³

During the COVID‐19 pandemic, an increase in the occurrence of pernio‐like acral lesions was highlighted, ⁴ and therefore, a correlation between COVID‐19 infection and this cutaneous eruption has been hypothesized. ⁵

A large international registry‐based case series of 318 patients with pernio‐like lesions and confirmed or suspected COVID‐19 infection showed that skin manifestations were only on the feet in 84% of patients and only on the hands in 5.1% of patients. ⁶

The pathogenetic mechanisms that have been proposed to explain the association between COVID‐19 and pernio‐like eruptions suggest an increase in vasospasm, and pro‐inflammatory and prothrombotic activity of the angiotensin II pathway, triggered by cellular infection; furthermore, a massive release of type I interferon could be involved. ³

In the reported case, the pernio‐like manifestations occurred 2 weeks after the administration of the second dose of the Pfizer‐BioNTech vaccine. The patient had never experienced chilblain‐like eruptions before; therefore, it cannot be excluded that these manifestations were related to the vaccine.

Pfizer‐BioNTech vaccine, administered intramuscularly in two injections 21 days apart, is a nucleoside‐modified RNA encoding the SARS‐CoV‐2 spike protein, which stimulates the production of SARS‐CoV‐2 neutralizing antibodies and an immune response mediated by antigen‐specific Th1‐type CD4⁺ T cells and CD8⁺ T cells. ⁷ , ⁸ , ⁹ The main cutaneous reactions reported in patients who received the mRNA COVID‐19 vaccines were reactions at the injection site, urticaria and morbilliform eruption; more rarely have been observed cosmetic filler reactions, zoster and herpes simplex flares, pityriasis rosea‐like reactions and pernio eruptions. ¹⁰

At the present, only a few cases of pernio‐like skin lesions induced by mRNA COVID‐19 vaccines have been reported and, in particular, five cases have been observed after the Pfizer‐BioNTech vaccine. ¹⁰ This case, together with those already reported in the literature, raises the question of whether the vaccine‐elicited immune response could be involved in the development of pernio‐like manifestations, as it has been described following COVID‐19 infection.

It is important for the dermatologist to recognize such clinical findings in order to provide a proper diagnosis and therapeutic management.