Cutaneous Manifestations of SARS-CoV-2 Infection

Thy Huynh; Xavier Sanchez-Flores; Judy Yau; Jennifer T. Huang

Disclosures

Am J Clin Dermatol. 2022;23(3):277-286. 

In This Article

Chilblain-like/Pernio-like Lesions

Clinical Presentation

CBLL/pernio-like lesions (commonly known as 'Covid toes'), are considered to be the most common cutaneous manifestations associated with SARS-CoV-2 infection. CBLL is clinically identical to idiopathic lupus erythematosus and other autoimmune-related chilblains. Chilblains is a superficial inflammatory vascular response on acral surfaces and occurs after exposure to cold. CBLL is characterized by dusky erythematous to edematous papules, nodules, plaques or, less frequently, bullae formation (Table 1). These lesions are found on the dorsum of the toes, lateral aspects of the feet and soles, and, less commonly, fingers, and may also be seen with localized digital swelling (Figure 1a, b).

Figure 1.

a Dusky erythematous and edematous plaques involving the left second, third, and fourth toes. b Dusky erythematous and edematous plaques on the left toes

Pathogenesis

SARS-CoV-2-related CBLL can be explained by tissue damage caused by immune complex depositions in blood vessels, peripheral thrombotic microangiopathy caused by elevated type-1 interferon (IFN-1) signaling, and/or secondary ischemia due to vascular damage.[9,10]

Histopathology

The histopathologic findings of CBLL show a superficial and deep perivascular lymphocytic infiltrate of predominantly CD3+/CD4+ T cells with perieccrine extension, intramural lymphocytes with endothelium thickening (lymphocytic vasculitis), interface dermatitis, epidermal keratinocyte necrosis/apoptosis, papillary edema, epidermal microthrombosis, endothelialitis, and fibrin deposition in blood vessel walls.[11,12] Evidence of SARS-CoV-2 was shown by electron microscopy, which showed halo-like, round membrane-bound structures with electro-lucent centers surrounded by small spikes within the cytoplasm of endothelial cells. In addition, tubuloreticular inclusions within endothelial cells were present.[12] Direct immunofluorescence is usually negative.[13]

Prognosis/Treatment

In a large international registry-based case series, Freeman et al. reported 318 patients identified with CBLL with laboratory testing confirming that 23 (7%) patients were positive through mostly polymerase chain reaction (PCR) and/or antibody testing.[14] Feito-Rodriguez et al. reported 37 patients with CBLL where 8.1% of all patients had SARS-CoV-2-positive nasopharyngeal PCR results and 8.1% of all patients had positive SARS-CoV-2 serology results—but there was no evidence of SARS-CoV-2 on electron microscopy or PCR testing of skin samples.[15] These two studies indicate that CBLL may be a late manifestation of SARS-CoV-2 infection. However, Stavert et al. performed antibody testing on 24 patients with CBLL on an average of 24 days post-onset of SARS-CoV-2 symptoms, finding that 24 (100%) and 22 (91.7%) patients tested negative for SARS-CoV-2 IgG and IgM, respectively.[16] These contradicting studies show that it is unclear when CBLL appear during the clinical course of COVID-19 infection.

If CBLL presents with other SARS-CoV-2 symptoms, it indicates an overall good prognosis, as these lesions typically occur in mild SARS-CoV-2 cases.[14,17] In a case series study, Strom et al. reported that no CBLL was seen in a group of 15 hospitalized and critically ill patients with SARS-CoV-2 infection.[18] CBLL are self-limiting, lasting from 10 to 14 days and occasionally for a few months.[13]

Avoiding cold temperatures and wearing protective and warm clothing, gloves, and socks will help improve CBLL. Pharmacologic treatments can also help CBLL; these include topical corticosteroids, topical and oral vasodilatory agents such as nitric oxide paste, oral calcium channel blockers, pentoxifylline, sildenafil or aspirin.

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