Chilblain-like acral lesions during the COVID-19 pandemic ("COVID toes"): Histologic, immunofluorescence, and immunohistochemical study of 17 cases

Abstract

Background: During the coronavirus disease 2019 pandemic, several acral chilblain-like lesions were observed in young patients with suspected, but mostly unconfirmed, infection with severe acute respiratory syndrome coronavirus 2. The histopathologic aspect of these lesions is as yet poorly known.

Objective: To investigate the pathologic features of chilblain-like lesions.

Methods: Biopsies were obtained from 17 cases of chilblain-like lesions during the coronavirus disease 2019 pandemic in France and were studied by routine histologic examination, immunohistochemistry, and direct immunofluorescence. The patients had suspected but unconfirmed infection with severe acute respiratory syndrome coronavirus 2 (negative nasopharyngeal polymerase chain reaction and serologic test results).

Results: Chilblain-like lesions showed many features in common with those reported in idiopathic and autoimmune-related chilblains, including epidermal necrotic keratinocytes, dermal edema, perivascular and perieccrine sweat gland lymphocytic (predominantly CD3/CD4⁺) inflammation, and frequent vascular changes (endothelialitis, microthromboses, fibrin deposition, and immunoreactant deposits on vessels).

Conclusions: Chilblain-like lesions show histopathologic features similar to those of idiopathic and autoimmune-related chilblains, with a high rate of vascular changes and direct immunofluorescence positivity. The role of severe acute respiratory syndrome coronavirus 2 in the development of these puzzling lesions remains to be elucidated.

Keywords: COVID-19; SARS-CoV-2; chilblains; dermatopathology; direct immunofluorescence; eosinophils; immunohistochemistry.

Fig 1

Chilblain-like lesion. Scanning magnification shows diffuse upper dermal edema and a dense dermal (perivascular and perieccrine sweat gland) inflammatory infiltrate. (Hematoxylin-eosin-saffron stain; original magnification: ×40.) esg, Eccrine sweat gland.

Fig 2

Chilblain-like lesion. Dense lymphocytic infiltrate around an eccrine sweat gland. Inset: perieccrine clusters of CD303⁺/BDCA-2 plasmacytoid dendritic cells. (Hematoxylin-eosin-saffron stain; original magnification: ×250; inset [immunoperoxidase revealed with diaminobenzidine]; original magnification: ×250.)

Fig 3

Chilblain-like lesion. Dense lymphocytic dermal perivascular infiltrate admixed with occasional eosinophils (arrowheads). Endothelial cell swelling and extravasated red blood cells (asterisks).

Fig 4

Chilblain-like lesion. Eosinophilic thrombi within the lumen of a dermal venule. (Hematoxylin-eosin-saffron stain; original magnification: ×400.)

Fig 5

Chilblain-like lesion. Eosinophilic fibrin deposits on the wall of a dermal venule. Inset shows vascular deposits of immunoglobulin M. (Hematoxylin-eosin-saffron stain; original magnification: ×400; inset [direct immunofluorescence]; original magnification: ×400.)