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As Covid-19 started to spread across the United States earlier this year, dermatology offices began to see suspicious signs on some patients' skin: Red or purple toes, itchy hives, mottled bumps on fingers, a lacy red rash that spread across legs and arms.
But were those truly associated with the novel coronavirus? After all, many other factors could be at play.
"Many viral infections can trigger a skin rash, so when you catalog these case reports, you have to have other data. Was the patient on a medication a week before the rash began? Are there other possible causes?" asked Dr. Art Papier, an associate professor of dermatology at the University of Rochester Medical Center in New York.
"This is the challenge that Covid-19 brings up. With these different types of presentations and different rashes, is it hives because the patient just has hives or hives related to Covid-19?"
Case reports began to be released in medical journals. The latest, published Wednesday in the journal JAMA Dermatology, describes the experiences of four patients with severe Covid-19 who were admitted to hospitals in New York City in March and April.
The patients, ages 40 to 80, had discoloration of their skin as well as lesions called retiform purpura, according to the research report.
Biopsies were performed for each patient and they showed that the patients had a type of vasculopathy, meaning that their blood vessels were affected.
The researchers -- from NewYork-Presbyterian/Weill Cornell Medical College -- wrote in their report that the skin discoloration could represent partial occlusion or blockage of blood vessels, and the retiform purpura could represent full blockage.
Such rashes and discoloration of the skin can be a "clinical clue" to there being possible blood clotting in the body, the study said. Since early on in the pandemic, doctors have noticed that severe Covid-19 could cause abnormal blood clotting in patients.
The report comes with some limitations, including that the researchers were not able to confirm the precise timing of when rashes and other issues with the skin first appeared for each patient. Also, more research is needed to determine whether similar findings would emerge among a larger group of Covid-19 patients.
Yet overall, the researchers wrote in their report that physicians caring for Covid-19 patients should be aware of skin discoloration and rashes as "potential manifestations" of abnormal underlying blood clotting.
Many Viral Infections Can Affect the Skin
Doctors and researchers from around the world also have reported about other types of skin rashes among Covid-19 patients.
Covid-19 often triggers significant inflammation in its victims, in some cases producing the so-called cytokine storm that appears to be causing the worst damage in advanced patients.
The skin is particularly sensitive to inflammation, said board-certified dermatologist Dr. Seemal Desai, a spokesperson for the American Academy of Dermatology.
"The cytokines that are cranking up the immune engine of the car is what then triggers a variety of these immune molecules to go into the skin and wreak havoc on the skin," said Desai, a dermatologist in Plano, Texas.
In July, researchers from King's College London in the United Kingdom called for skin rashes and "Covid fingers and toes" to be considered as a key symptom of Covid-19, even arguing that they can occur in the absence of any other symptoms.
Key coronavirus symptoms that are widely accepted include fever, cough, and shortness of breath, but a range of other signs have been suggested. The loss of smell and taste, another outlier, was recently included on the list of most common symptoms by the US Centers for Disease Control and Prevention.
The Kings College researchers used data from the Covid-19 Symptom Study app, which is submitted by around 336,000 people in the UK. They found that 8.8% of people who tested positive for coronavirus reported a skin rash as a symptom, compared with 5.4% of people who tested negative.
The KLC team then set up a separate online survey, gathering information from nearly 12,000 people with skin rashes and suspected or confirmed Covid-19. The researchers found that 17% of respondents who tested positive for the coronavirus reported a rash as the first symptom of the disease. For 21% of people who reported a rash and had confirmed Covid-19, the rash was their only symptom.
The researchers reported their findings in a pre-print study posted to the online server medRXiv.org. The findings have not been published yet in a peer-reviewed journal.
"Many viral infections can affect the skin, so it's not surprising that we are seeing these rashes in Covid-19," Dr. Veronique Bataille, consultant dermatologist at St Thomas' Hospital and King's College London, who was involved in the pre-print study, said in a press release in July.
"However, it is important that people know that in some cases, a rash may be the first or only symptom of the disease," Bataille said. "So if you notice a new rash, you should take it seriously by self-isolating and getting tested as soon as possible."
Measles-Like Rashes & Rashes Inside the Mouth
Preliminary research has suggested that skin rashes and lesions inside the mouth might be a symptom of coronavirus infection -- but researchers say more study is needed.
In May, scientists around the world did a literature review and found patients were also presenting with red, itchy welts, and with a red or pinkish rash that looked a lot like measles.
"It's a reaction that we typically call morbilliform which means measles, which presents in kind of pink spots, lots of little pink spots all over the skin," said Papier, the dermatologist at the University of Rochester Medical Center.
Another study published in JAMA Dermatology in July, found that among 21 patients in Spain who were confirmed to have Covid-19 and skin rash, six of those patients or 29% had enanthem, or lesions or rash in the mouth.
The mean amount of time between the onset of Covid-19 symptoms and developing enanthem was about 12 days among the patients, according to researchers from the Hospital Universitario Ramon y Cajal in Madrid.
"This work describes preliminary observations and is limited by the small number of cases and the absence of a control group," the researchers wrote, adding that their findings still suggest enanthem to be a possible Covid-19 symptom and not a reaction to medications, for instance.
"Despite the increasing reports of skin rashes in patients with COVID-19, establishing an etiological diagnosis is challenging," the researchers wrote. "However, the presence of enanthem is a strong clue that suggests a viral etiology rather than a drug reaction."