The dermatologic manifestations associated with SARS-CoV-2 are many and varied, with new information virtually daily. Graeme Lipper, MD, a member of the Medscape Dermatology advisory board, discussed what we know and what is still to be learned with Lindy Fox, MD, a professor of dermatology at University of California, San Francisco (UCSF) and a member of the American Academy of Dermatology’s COVID-19 Registry task force.
Graeme M. Lipper, MD
Earlier this spring, before there was any real talk about skin manifestations of COVID, my partner called me in to see an unusual case. His patient was a healthy 20-year-old who had just come back from college and had tender, purple discoloration and swelling on his toes. I shrugged and said “looks like chilblains,” but there was something weird about the case. It seemed more severe, with areas of blistering and erosions, and the discomfort was unusual for run-of-the-mill pernio. This young man had experienced a cough and shortness of breath a few weeks earlier but those symptoms had resolved when we saw him.
That evening, I was on a derm social media site and saw a series of pictures from Italy that blew me away. All of these pictures looked just like this kid’s toes. That’s the first I heard of “COVID toes,” but now they seem to be everywhere. How would you describe this presentation, and how does it differ from typical chilblains?
Lindy P. Fox, MD
I am so proud of dermatologists around the world who have really jumped into action to examine the pathophysiology and immunology behind these findings.
Your experience matches mine. Like you, I first heard about these pernio- or chilblains-like lesions when Europe was experiencing its surge in cases. And while it does indeed look like chilblains, I think the reality is that it is more severe and symptomatic than we would expect. I think your observation is exactly right. There are certainly clinicians who do not believe that this is an association with COVID-19 because the testing is often negative. But to my mind, there are just too many cases at the wrong time of year, all happening concomitantly, and simultaneous with a new virus for me to accept that they are not somehow related.
Dr. Lipper: Some have referred to this as “quarantine toes,” the result of more people at home and walking around barefoot. That doesn’t seem to make a whole lot of sense because it’s happening in both warm and cold climates.
Others have speculated that there is another, unrelated circulating virus causing these pernio cases, but that seems far-fetched.
But the idea of a reporting bias – more patients paying attention to these lesions because they’ve read something in the mass media or seen a report on television and are concerned, and thus present with mild lesions they might otherwise have ignored – may be contributing somewhat. But even that cannot be the sole reason behind the increase.
Dr. Fox: Agree.
Evaluation of the patient with chilblains – then and now
Dr. Lipper: In the past, how did you perform a workup for someone with chilblains?
Dr. Fox: Pre-COVID – and I think we all have divided our world into pre- and post-COVID – the most common thing that I’d be looking for would be a clotting disorder or an autoimmune disease, typically lupus. So I take a good history, review of systems, and look at the skin for signs of lupus or other autoimmune connective tissue diseases. My lab workup is probably limited to an antinuclear antibody (ANA). If the findings are severe and recurrent, I might check for hypercoagulability with an antiphospholipid antibody panel. But that was usually it unless there was something in the history or physical exam that would lead me to look for something less common – for example, cryoglobulins or an underlying hematologic disease that would lead to a predominance of lesions in acral sites.
My approach was the same. In New England, where I practice, I also always look at environmental factors. We would sometimes see chilblains in someone from a warmer climate who came home to the Northeast to ski.
Dr. Lipper: Now, in the post-COVID world, how do you assess these patients? What has changed?
Dr. Fox: That’s a great question. To be frank, our focus now is on not missing a secondary consequence of COVID infection that we might not have picked up before. I’m the first to admit that the workup that we have been doing at UCSF is extremely comprehensive. We may be ordering tests that don’t need to be done. But until we know better what might and might not be affected by COVID, we don’t actually have a sense of whether they’re worth looking for or not.
Right now, my workup includes nasal swab polymerase chain reaction (PCR) for COVID, as well as IgG and IgM serology if available. We have IgG easily available to us. IgM needs approval; at UCSF, it is primarily done in neonates as of now. I also do a workup for autoimmunity and cold-associated disease, which includes an ANA, rheumatoid factor, cryoglobulin, and cold agglutinins.
Because of reported concerns about hypercoagulability in COVID patients, particularly in those who are doing poorly in the hospital, we look for elevations in d-dimers and fibrinogen. We check antiphospholipid antibodies, anticardiolipin antibodies, erythrocyte sedimentation rate, and C-reactive protein. That is probably too much of a workup for the healthy young person, but as of yet, we are just unable to say that those things are universally normal.
There has also been concern that complement may be involved in patients who do poorly and tend to clot a lot. So we are also checking C3, C4, and CH50.
To date, in my patients who have had this workup, I have found one with a positive ANA that was significant (1:320) who also had low complements.
There have been a couple of patients at my institution, not my own patients, who are otherwise fine but have some slight elevation in d-dimers.