UCSF team sees link to pediatric swelling
The children began showing up in early April with unusual bruiselike swellings on their feet that so baffled Dr. Kelly Cordoro, a pediatric dermatologist at UCSF, that she decided to launch an investigation.
As many as 15 children from San Francisco and the Peninsula were coming into UCSF’s Benioff Children’s Hospital every week with the reddishpurple lesions known as acral perniosis, a condition that is also known as “frost nip” and is normally associated with cold, damp weather.
“The number of patients is extraordinary,” said Cordoro, who has seen dozens of children with the condition. Normally, “I may see three kids with pernio in a season, total.”
The otherwise healthy patients seen by Cordoro and her colleagues had only one thing in common — they all had an adult relative who had recently exhibited cold or flulike symptoms. Cordoro’s study, which will be published in the upcoming issue of the journal Pediatric Dermatology, suggests that the cluster is an immune response to COVID19.
“Some of them had mild cold symptoms in the few weeks prior to the lesions, but all had exposure to an adult who had significant viral symptoms that could be attributed to a presentation of mild COVID,” Cordoro said. “It’s certainly related to the pandemic in some way.”
The problem is, none of the young patients tested positive for or had antibodies to the disease, and most of the adult relatives were never tested.
Although there is no definitive link to the coronavirus, Cordoro cannot find any other explanation for the cluster. It was not unusually cold in the Bay Area at the time, so there was no meteorological reason for the number of cases to spike suddenly.
And there is plenty of circumstantial evidence that exposure to the coronavirus can cause inflammation after the fact.
Infectious disease specialists believe that overly robust immune responses might be responsible for an inflammatory reaction similar to Kawasaki disease, which has recently been detected in children exposed to the coronavirus. That ailment, known as pediatric multisystem inflammatory syndrome, can cause rashes, fevers and heart inflammation more than a month after exposure to the virus, even if the person exposed never showed symptoms, researchers said.
Strange clusters of patients with perniosislike lesions have also been reported around the world, with at least 80 cases in Chicago, New York, Boston and other places on the East Coast. The condition has also been found in Europe. It has, in fact, been referred to as “COVID toes” since the first cases were reported on an online pediatric dermatology forum in Italy.
“There are many anecdotal reports of acral perniosis associated with SARSCoV2 — so many reports that there is likely an association,” said John Swartzberg, an infectious disease expert and clinical professor emeritus at the UC BerkeleyUCSF Joint Medical Program. “The mechanism is not understood. Clearly, physicians should be, and likely are, aware of this association as this will help lead them to the diagnosis of COVID19.”
The local study is the most comprehensive look at the phenomenon in children. It focuses on six otherwise healthy adolescent siblings in two families who were among 30 patients with similar symptoms evaluated during a single week in April.
Five males and one female patient, ranging in age from 12 to 17, all came to the children’s hospital within a 48hour period, the study says.
Cordoro said the lesions on their feet, and sometimes on their hands, were unusual in that they often had a netlike pattern of discoloration called Livedo reticularis, which is linked to swollen blood vessels and is not typical of frost nip.
She said the perniosis symptoms are more common in adolescents, but she has also seen the lesions on adults up to age 40, infants, toddlers and young children.
“These skin changes are very frightening, because they could indicate autoimmune diseases, blood clotting disorders, problems with the blood,” she said, “but none of them have any of that.”
In fact, everyone she has looked at was healthy in every other way.
The hypothesis is that the discoloration is skin inflammation that is somehow triggered as people recover from mild cases of COVID19 that were successfully controlled by their immune system.
“It may be that the antiviral immune system generates a chemical that protects these kids from a severe COVID infection but is in the process flipping this inflammatory switch,” Cordoro said.
The only other possibility, she said, is that they developed the condition by walking around on cold floors barefoot while sheltering in place, a problematic theory given that there haven’t been similar increases in cold places like Minnesota.
Cordoro and her colleagues are collaborating with specialists around the country in an attempt to figure out the geographic distribution of patients to determine how many people are affected and whether climatic conditions have anything to do with it. The Pediatric Dermatology Research Alliance has set up a registry of cases.
One obstacle, she said, is the troubling fact that most antibody test kits are unreliable. She is working with UCSF scientists in an attempt to optimize testing and availability.
“We’re right in the middle of the mystery right now, and we’re working very hard to figure it out,” she said. “There are more chapters to be written, and I do think the answer to this will eventually unfold.”