Reaction patterns may aid in diagnosis of COVID-19 vaccine-related cutaneous side effects

A registry-based study has recently shown diverse COVID-19 vaccine-associated dermatologic reactions, including papulovesicular, pityriasis rosea-like, and papulosquamous eruptions classified as vaccine-related eruption of papules and plaques (V-REPP).

“We propose defining a subset of V-REPP, as well as 12 other patterns, following COVID-19 vaccination,” the researchers said.

Using an international registry, all reports of dermatologic reactions associated with COVID-19 vaccination were evaluated. Available histopathology reports were then categorized by reaction patterns. A total of 803 vaccine reactions were reported, of which 58 (7 percent) had biopsy reports available for review.

Among histopathologic reaction patterns observed, the most common was spongiotic dermatitis. This pattern clinically ranged from robust papules with overlying crust, to pityriasis rosea-like eruptions, to pink papules with fine scale. This spectrum was dubbed V-REPP by the researchers. [J Am Acad Dermatol 2022;86:113-121]

Other clinical patterns were as follows: bullous pemphigoid-like (n=12), dermal hypersensitivity (n=4), herpes zoster (n=4), lichen planus-like (n=4), pernio (n=3), urticarial (n=2), neutrophilic dermatosis (n=2), leukocytoclastic vasculitis (n=2), morbilliform (n=2), delayed large local reactions (n=2), erythromelalgia (n=1), and others (n=5).

“The histopathologic spectrum of V-REPP all showed some degree of spongiosis, ranging from significant spongiosis with intraepidermal vesicle formation (robust V-REPP), to pityriasis rosea-like changes (moderate V-REPP), to minimal spongiosis (mild V-REPP),” the researchers said.

In a reported case of pityriasis rosea-like eruption following a second dose of the Pfizer vaccine, spongiosis with interface changes also appeared. [J Eur Acad Dermatol Venereol 2021;35:e546-e548]

Likewise, pityriasis rosea-like eruptions had been previously reported following vaccination for polio, smallpox, influenza, tuberculosis, tetanus, papillomaviruses, pneumococcus, diphtheria, hepatitis B, and yellow fever. [J Eur Acad Dermatol Venereol 2016;30:544-545]

“The mechanism of V-REPP after COVID-19 vaccination is unknown, but the delayed occurrence of these reactions suggests two potential mechanisms: (1) delayed hypersensitivity response to vaccination; or (2) T-cell-mediated skin reaction due to molecular mimicry with a viral epitope,” the researchers said.

Moreover, infection with SARS-CoV-2 correlated with pityriasis rosea-like eruptions. Histopathology of pityriasis rosea-like eruptions following infection was also reported to exhibit spongiosis and a superficial perivascular lymphocytic infiltrate. [J Am Acad Dermatol 2020;83:1118-1129; Br J Dermatol 2021;184:1194-1195]

“However, robust V-REPP, in which papulovesicles may be observed due to exuberant spongiosis, appear to be different from other vesicular eruptions caused by true SARS-CoV-2 infection,” the researchers noted.

The current study was limited by a minority of registry entries represented by cases in which histopathology was available. In addition, analysis of registry data could not measure incidence.

“We hope these data will aid physicians and other providers in the diagnosis of dermatologic conditions associated with the COVID-19 vaccine, which will likely be encountered more frequently as vaccine distribution expands globally,” the researchers said.