Pernio dominates
The registry – a collaboration between the AAD and the International League of Dermatological Societies – was launched in April 2020. Any medical professional can enter case information. From April to October, 1,030 total cases and 331 laboratory-confirmed or suspected COVID-19 cases with dermatological manifestations were entered from 41 countries.
Most of the cases were just recorded at a single time point, which is an acknowledged limitation of the study.
Dr. Freeman and colleagues reached out to registry participants in June and August to get updates on COVID lab test results and sign and symptom duration. Overall, 234 total and 96 lab-confirmed COVID infections had more lengthy data about sign and symptom duration.
Pernio lasted a median of 15 days in patients with suspected disease and 12 days for those with lab-confirmed COVID, compared with a median of 7 days for morbilliform eruptions, 4 days for urticarial eruptions, and 20 days for papulosquamous eruptions – all in patients with lab-confirmed disease.
Of the 103 cases of pernio, 7 had symptoms lasting more than 60 days. Only two of those seven patients had lab-confirmed COVID. Initially, the one patient tested negative with nasopharyngeal PCR, and serum IgM and IgG. Six weeks after pernio onset, the patient – still experiencing fatigue and pernio – seroconverted to anti–SARS-CoV-2 IgM positivity.
The other long-haul patient, after a negative PCR, tested positive for SARS-CoV-2 serum IgG 1 month after pernio onset.
Robust immune response?
Dr. Freeman said these patients might have a very high interferon response initially to the virus, which makes for a mild to nonexistent disease, but could create inflammation elsewhere. “I almost view the toes as an innocent bystander of a robust immune response to SARS-CoV-2.”
Although he has not seen extended pernio or other skin manifestations in his patients, Dr. Fernandez said the interferon hypothesis is “fair,” and “the best that’s out there.” Dr. Fernandez is currently studying cutaneous manifestations of COVID-19 as a principal investigator of a trial sponsored by the Clinical and Translational Science Collaborative of Cleveland.
Dr. Christine Ko
Dr. Ko said in an interview that she has not observed long-haul skin issues in her patients, but Yale colleagues have.
In a study, she and Yale colleagues published in September, SARS-CoV-2 spike protein was detected in perniotic lesions, but not nuclear protein or viral RNA. The test they used – immunohistochemistry – can be nonspecific, which muddied results.
She does not think there is replicating virus in the skin or the lesions. Instead, said Dr. Ko, “either there is viral spike protein that has somehow become disassociated from actively replicating virus that somehow got deposited in endothelial cells,” or the staining “was spurious,” or some other protein is cross-reacting. “And the people who are unlucky enough to have that protein in their endothelial cells can manifest this COVID-toe, COVID-finger phenomenon.”
To her, it’s an unsolved mystery. “The weird thing is, we’ve never before had this much perniosis,” Dr. Ko said.
Dr. Fernandez is not convinced yet, noting that, in Cleveland, more pernio cases were observed in March and April than in the summer. “If it is a manifestation of the infection then you also need the right environment, the cold weather for this manifestation to present,” he said. “Or, it really isn’t a direct manifestation of COVID-19 but may be more related to other factors,” such as lifestyle changes related to limitations implemented to help mitigate the spread of the disease.
“To me the jury is still out whether or not the perniotic lesions really can tell us something about a patient’s exposure and infection with SARS-CoV-2,” he said.
Dr. Freeman reported receiving a grant from the International League of Dermatological Societies and nonfinancial support from the AAD for the study. Dr. Ko reported no conflicts. Dr. Fernadnez had no disclosures.