ABSTRACT
BACKGROUND: The abundance of publications of COVID-19-induced chilblains has resulted in a confusing situation. METHODS: This is a prospective single-institution study from 15 March to 13 May 2020. Thirty-two patients received PCR nasopharyngeal swabs. Of these, 28 patients had a thoracic CT-scan, 31 patients had blood and urine examinations, 24 patients had skin biopsies including immunohistochemical and direct immunofluorescence studies, and four patients had electron microscopy. RESULTS: COVID-19-induced chilblains are clinically and histopathologically identical to chilblains from other causes. Although intravascular thrombi are sometimes observed, no patient had a systemic coagulopathy or severe clinical course. The exhaustive clinical, radiological, and laboratory work-up in this study ruled-out other primary and secondary causes. Electron microscopy revealed rare, probable viral particles whose core and spikes measured from 120 to 133 nm within endothelium and eccrine glands in two cases. CONCLUSION: This study provides further clinicopathologic evidence of COVID-19-related chilblains. Negative PCR and antibody tests do not rule-out infection. Chilblains represent a good prognosis, occurring later in the disease course. No systemic coagulopathy was identified in any patient. Patients presenting with acral lesions should be isolated, and chilblains should be distinguished from thrombotic lesions (livedo racemosa, retiform purpura, or ischemic acral necrosis).
Subject(s)
COVID-19/complications , COVID-19/diagnosis , Chilblains/etiology , Chilblains/pathology , Toes/pathology , Adolescent , Adult , Aged , Biopsy/methods , COVID-19/metabolism , COVID-19/virology , Chilblains/diagnosis , Chilblains/virology , Child , Diagnosis, Differential , Eccrine Glands/pathology , Eccrine Glands/ultrastructure , Eccrine Glands/virology , Endothelium/pathology , Endothelium/ultrastructure , Endothelium/virology , Female , Humans , Livedo Reticularis/pathology , Male , Microscopy, Electron/methods , Middle Aged , Prognosis , Prospective Studies , Purpura/pathology , SARS-CoV-2/genetics , Skin/pathology , Toes/virology , Young AdultABSTRACT
BACKGROUND: Prior studies have shown the presence of immunohistochemical staining for the SARS-CoV-2 spike protein (SP) in endothelial cells and eccrine epithelium of acral perniosis classified as "COVID toes." Yet, other studies have been unable to detect SARS-CoV-2 RNA in skin biopsies of "COVID toes" by reverse-transcriptase polymerase chain reaction testing. OBJECTIVE: In order to address these apparently conflicting findings, we compared detection of SARS-CoV-2 SP, through RNA in situ hybridization (ISH) vs immunohistochemistry (IHC), in skin biopsies of acral perniotic lesions presenting during the COVID-19 pandemic. RESULTS: Three of six cases showed positive immunohistochemical labeling of endothelial cells, with one of three cases with sufficient depth also having labeling of eccrine glands, using an anti-SP SARS-CoV-2 antibody. These three cases positive with IHC were negative for SP by RNA ISH. CONCLUSION: While the gold standard for detection of SARS-CoV-2 in tissue sections has yet to be determined, the detection of SARS-CoV-2 SP alone without spike RNA suggests that cleaved SP may be present in cutaneous endothelial cells and eccrine epithelium, providing a potential pathogenetic mechanism of COVID-19 endotheliitis.