UW plans to study ‘COVID toes’
Strange ailment baffles scientists and doctors
In April, the toes of one of Molly Knigge’s teenagers turned red, and when the teen looked up the symptom on the internet, it seemed to match frostbite.
April may be chilly in Wisconsin, but the diagnosis made no sense. The whole family had been staying at home in response to the COVID-19 pandemic. After several weeks, the teenager’s toes became itchy and painful, and the family consulted their pediatrician.
“The doctor stated, ‘We believe it could be COVID toes,’ ” Knigge said. “We’ve not been given any alternate diagnosis.”
The youth had no other symptoms of COVID-19, and a test found no antibodies for the disease. Nor has anyone else in the family experienced COVID-19 symptoms.
The Knigges were left with a mystery shared by hundreds of patients around the world.
Although it has been linked by scientists to the COVID-19 pandemic, the toe condition has not been proved to be caused by the new coronavirus. Adding to the medical riddle is the fact that COVID toes is virtually identical to a rare ailment known as chilblains or pernio.
“Typically, a dermatologist sees one or two of these cases in the middle of the winter,” said Lisa Arkin, an assistant professor of dermatology and pediatrics at the University of Wisconsin School of Medicine and Public Health. “In Madison, we’ve seen about 40 patients in four and a half weeks. So there is something driving this.”
In all of 2018 and 2019, UW Health recorded just 12 patients with inflamed toes.
Last week, Arkin launched a study of Wisconsin patients with COVID toes, which will involve input from immunologists, rheumatologists, geneticists and virologists. Doctors around
the world are also investigating these patients.
What they find suspicious is that hundreds of cases of a rare condition have suddenly been reported across the USA, Italy, Spain, France and other nations in the middle of a pandemic.
“This is the most contagious infection in a century. Why are we seeing this explosion of purple toes in people who don’t have COVID-19?” Arkin said.
‘We were all seeing these cases’
At Stanford Health Care in the San Francisco Bay area, doctors noticed a sharp increase in an illness resembling chilblains after COVID-19 arrived.
“We see in California a handful of chilblains cases a year,” said Albert Chiou, a dermatologist at Stanford Health Care who is studying the condition.
“But there was a period recently when everybody was sending emails around because we were all seeing these cases at the same time.”
Chiou said he has a list of 25 patients with the condition, including a couple of small clusters that included two members of the same family. Only one of the 25 patients tested positive for antibodies to COVID-19, Chiou said.
Ronald Sweren, an assistant professor of dermatology at Johns Hopkins Medicine, said he saw three patients with COVID toes in the same week, “enough to suggest to my colleagues that we should collect cases . ... Early reports from Italy and France suggested this was most common in children who were often asymptomatic.”
Sweren said patients with COVID toes may be carriers of the disease – information of great value to doctors.
In one of the largest studies, a group of researchers examined 318 patients with the toe condition in eight countries and found that about 45% had other COVID-19 symptoms.
Just 7% were confirmed to have had the disease.
Two died, according to the study published in the Journal of the American Academy of Dermatology.
The small number testing positive for COVID-19 – a consistent finding in studies of the toe condition – could reflect the lack of broad testing for the disease. Or it could indicate that patients with the inflamed toes experienced extremely mild COVID-19, so mild that their bodies may not have made antibodies to fight off the virus.
The study concluded by warning that patients with the condition “may still be infectious and pose a public health risk, as at least four patients in the report developed skin lesions prior to (being confirmed as COVID-19 positive), and 14 developed the lesions while still positive.”
“I think people are alarmed if they see discoloration in the toes.” Sandhya Deverapalli Director of chemotherapy and transplant dermatology at Tufts Medical Center in Boston The result of staying at home?
At Stanford Health Care, Chiou said scientists suggested the toe condition may not have been caused by COVID-19 but might indicate that the shelter-athome orders resulted in people walking around their homes barefoot, which can lead to chilblains.
There may be other reasons why people get COVID toes yet test negative for antibodies to the disease.
The tests look for specific antibodies that act against a protein in the virus called “the spike.” It’s possible that people with the toe condition have immune systems that are not attacking the spike protein but something else in the virus.
“Or it could be that they have such a mild infection that these folks develop antibodies much later,” Chiou said.
There is another possibility Chiou finds more troubling. It could be that people who have a mild exposure to the virus are able to fight it off without any detectable immune response.
That could mean that some who catch the virus will have immune systems that do not remember fighting it off. Immune system memory is central to the idea that if you catch a virus once, you have immunity if it returns.
If the red and purple inflamed toes are indeed caused by the new coronavirus, doctors want to understand the process.
In chilblains, discoloration results from the inflammation of small blood vessels in the toes or fingers. This may occur when blood vessels that have been cold suddenly warm up.
People with chilblains develop higher levels of a protein called type 1 interferon. The same protein helps kill off infections, including COVID-19.
It appears that many of the COVID-19 patients who suffer severe disease have very low levels of type 1 interferon.
Investigating the inflamed red toes may not only help scientists better understand COVID-19 but may also help doctors reassure patients who discover they have the condition.
“I think people are alarmed if they see discoloration in the toes,” said Sandhya Deverapalli, director of chemotherapy and transplant dermatology at Tufts Medical Center in Boston.
Deverapalli has seen two patients with COVID toes, one of whom was a woman in her mid-50s who had been staying indoors. “She tested positive for COVID-19 the same day she saw me,” Deverapalli said. “She was feeling very fatigued. It took her around two to three weeks, but she’s much improved.”