Clinicopathologic correlations of COVID-19-related cutaneous manifestations with special emphasis on histopathologic patterns

Abstract

Skin is one of target organs affected by the novel coronavirus SARS-CoV-2, and in response to the current COVID-19 pandemic, a fast body of literature has emerged on related cutaneous manifestations. Current perspective is that the skin is not only a bystander of the general cytokines storm with thrombophilic multiorgan injury, but it is directly affected by the epithelial tropism of the virus, as confirmed by the detection of SARS-CoV-2 in endothelial cells and epithelial cells of epidermis and eccrine glands. In contrast with the abundance of epidemiologic and clinical reports, histopathologic characterization of skin manifestations is limited. Without an adequate clinicopathologic correlation, nosology of clinically similar conditions is confusing, and effective association with COVID-19 remains presumptive. Several patients with different types of skin lesions, including the most specific acral chilblains-like lesions, showed negative results at SARS-CoV-2 nasopharyngeal and serologic sampling. The aim of this review is to provide an overview of what has currently been reported worldwide, with a particular emphasis on microscopic patterns of the skin manifestations in patients exposed to or affected by COVID-19. Substantial breakthroughs may occur in the near future from more skin biopsies, improvement of immunohistochemistry studies, RNA detection of SARS-CoV-2 strain by real-time polymerase chain reaction-based assay, and electron microscopic studies.

Fig. 1

(A) Chilblain-like lesions of the dorsal aspect of the toes (COVID-19 toe) having dusky erythematous edematous macules or plaques with a purpuric hue. (B) Superficial and deep perivascular lymphocytic infiltrate with perieccrine accentuation (hematoxylin & eosin [HE], 40 ×). (C) Perieccrine extension of the lymphocytic infiltrate (HE, 200 ×). (D) The dermal infiltrate tightly cuffs the vessels walls (“lymphocytic vasculitis”) with endothelium thickening without true thrombosis (HE, 200 ×).

Fig. 2

(A) Acro-ischemic/livedoid/necrotic lesions of the toe with dry gangrene. (B) Epidermal necrosis and thrombotic vasculopathy, involving the superficial vessels (hematoxylin & eosin [HE], 200 ×). (C) Thrombotic vasculopathy with most of the superficial small vessels filled with hyaline thrombi and pauci perivascular inflammatory infiltrate. No signs of leukocytoclastic vasculitis are seen (HE, 200 ×).

Fig. 3

(A) Varicella-like/vesicular eruption with small, scattered vesicles, and erythematous papules of the trunk involvement. (B, C) Slightly atrophic epidermis, vacuolar degeneration of the basal layer, and multinucleate, hyperchromatic keratinocytes with dyskeratotic (apoptotic) cells associated with minimal to absent inflammatory infiltrate in early lesions (hematoxylin & eosin [HE], 200 ×). (D) Later findings include intra-epidermal unilocular vesicles, exocytosis, reticular degeneration of the epidermis, acantholytic cells, and scattered dyskeratotic keratinocytes similar to herpetic lesions (HE, 200 ×).

Fig. 4

(A) Maculopapular eruption of the trunk in a COVID-19 symptomatic man. (B) Parakeratosis, slight spongiosis, and vacuolar degeneration of basal cell layer, and perivascular and interstitial infiltrate made by lymphocytes, histiocytes, and some neutrophils with red blood cell extravasation (hematoxylin & eosin, 200 ×).

Fig. 5

(A) Figurate urticarial eruption of the extremities in a COVID-19 symptomatic woman. (B) Normal epidermis and a superficial perivascular infiltrate with eosinophils and some neutrophils with slight edema (hematoxylin & eosin, 100 ×).

Fig. 6

(A) Petechial/purpuric eruption in a 59-year-old symptomatic COVID-19 man. (B) Histopathologic findings showing a typical leukocytoclastic vasculitis of small vessels with red blood cell extravasation (hematoxylin & eosin, 200 ×).