COVID-19 patients may develop skin rashes and discoloration, studies find

Authors: By Jacqueline Howard, CNN | Posted – Aug. 5, 2020 at 2:36 p.m.

CNN — 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 and 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.”

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Coronavirus: are mouth lesions another Covid-19 symptom?

A research team in Spain has published a study that finds some coronavirus sufferers with a skin rash also have enanthems, or mouth lesions.

Authors: AS English Update: 22 July 2020 15:28 EDT

Lesions inside the mouth may be an indicator that a person has contracted the coronavirus, according to a study carried out in Spain.

Six of 21 Covid-19 patients with skin rash also had mouth lesions

Researchers at the Ramón y Cajal University Hospital in Madrid say their findings show that around a third of Covid-19 sufferers found to have a skin rash also turn out to have rash-like oral-cavity lesions, known as enanthems.

Of 21 patients with Covid-19 and skin rash, 6 patients (29%) had enanthem,” researchers said in a paper published in the medical journal JAMA Dermatology last Thursday. “The age range of these patients was between 40 and 69 years, and 4 of the 6 (66%) were women.”

This work describes preliminary observations and is limited by the small number of cases and the absence of a control group,” they cautioned.

Rash among less common Covid-19 symptoms listed by WHO

According to the World Health Organization (WHO), the most common symptoms of the coronavirus are a fever, a dry cough and tiredness, while the virus’ less common indicators include “a rash on skin, or discolouration of fingers or toes”.

Last week, however, a study carried out at King’s College London in the UK called for rashes – known as exanthems when they occur on the outside of the body – to be included as the fourth key symptom of Covid-19.

The research, which is yet to be peer-reviewed, found that 21% of people who had a skin rash and were suffering from Covid-19 reported that this was their only symptom of the disease.

In its findings in JAMA Dermatology, meanwhile, the team at the Ramón y Cajal University Hospital noted that a recent study on patients in Italy had also underlined the apparently regular occurrence of rashes among Covid-19 patients.

Enanthems could help determine if skin rash linked to Covid-19

However, the Madrid study points out that establishing for certain that a skin rash has been brought about by the coronavirus – rather than another cause – is not straightforward. With this in mind, it says, the process of identifying a clear link could be helped by finding out whether or not a patient also has enanthems.

“Whether these manifestations [skin rashes] are directly related to Covid-19 remains unclear, since both viral infections and adverse drug reactions are frequent causes of exanthems,” the Spanish researchers explain. “An important clue to distinguish between both entities is the presence of enanthem […].”

Mouths not often checked for safety reasons

They also note, though, that an obstacle towards this is that the insides of mouths are often not checked by medical staff: “Owing to safety concerns, many patients with suspected or confirmed Covid-19 do not have their oral cavity examined.”

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COVID-19: Cutaneous manifestations and issues related to dermatologic care

Authors: Steven R Feldman, MD, PhD, Esther E Freeman, MD, PhD Literature review current through: Jul 2021. | This topic last updated: Apr 06, 2021.

INTRODUCTION

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), raises many critical issues in dermatology and dermatologic care. Addressing these issues is necessary, yet also challenging, because there are few direct data on which to base recommendations [1].

This topic will discuss issues related to dermatologic care during the COVID-19 pandemic. Other relevant aspects of SARS-CoV-2 infection and patient management are discussed in detail separately.

●(See “COVID-19: Epidemiology, virology, and prevention”.)

●(See “COVID-19: Clinical features”.)

●(See “COVID-19: Diagnosis”.)

●(See “COVID-19: Infection control for persons with SARS-CoV-2 infection”.)

●(See “COVID-19: Outpatient evaluation and management of acute illness in adults”.)

●(See “COVID-19: Hypercoagulability”.)

●(See “COVID-19: Multisystem inflammatory syndrome in children (MIS-C) clinical features, evaluation, and diagnosis”.)

●(See “COVID-19: Management in hospitalized adults”.)

●(See “COVID-19: Questions and answers”.)

●(See “COVID-19: Cancer screening, diagnosis, post-treatment surveillance in uninfected patients during the pandemic, and issues related to COVID-19 vaccination in cancer patients”.)

●(See “COVID-19: Care of adult patients with systemic rheumatic disease”.)

CUTANEOUS MANIFESTATIONS OF COVID-19

Case series from around the world have identified a range of potential dermatologic manifestations of coronavirus disease 2019 (COVID-19) [2-5]. The frequency (ranging from 0.2 to 20.4 percent of cases) and timing of cutaneous manifestations of COVID-19 are difficult to ascertain [6-8]. Also unclear is the association of certain skin manifestations with the illness severity [9]. Moreover, it cannot be excluded that in some patients the observed skin findings may represent cutaneous reactions to the numerous treatments used for COVID-19 [9,10].

The American Academy of Dermatology’s COVID-19 Registry, a collaboration between the American Academy of Dermatology and the International League of Dermatologic Societies, is attempting to collate cases and better define the cutaneous manifestations of COVID-19 [11] (see ‘Registries’ below). Among 171 laboratory-confirmed COVID-19 patients with cutaneous manifestations from the registry, the most commonly reported were morbilliform rash (22 percent), pernio-like acral lesions (18 percent), urticaria (16 percent), macular erythema (13 percent), vesicular eruption (11 percent), papulosquamous eruption (9.9 percent), and retiform purpura (6.4 percent) [12]. Fever and cough were reported in approximately 60 percent of cases:

Exanthematous (morbilliform) rash – In several case series, a morbilliform rash predominantly involving the trunk has been reported as the most common cutaneous manifestation of COVID-19 [2,3,7,12-14]. The rash has been noted either at the disease onset or, more frequently, after hospital discharge or recovery [7].

Pernio (chilblain)-like acral lesions – Pernio (chilblain)-like lesions of acral surfaces (“COVID toes”) present as erythematous-violaceous or purpuric macules on fingers, elbows, toes, and the lateral aspect of the feet, with or without accompanying edema and pruritus (picture 1A-B). They have been described across the age spectrum in patients with confirmed or suspected COVID-19, in the absence of cold exposure or underlying conditions associated with pernio [2-4,12,15-22].

Resolution may occur in two to eight weeks. A prolonged course of more than 60 days has been reported in some patients with pernio (“long haulers”) [23].

The development of pernio-like lesions in COVID-19 may be associated with a relatively mild COVID-19 disease course [2,4,24]. In the American Academy of Dermatology/International League of Dermatologic Societies registry study, 55 percent of patients overall were otherwise asymptomatic. Ninety-eight percent of patients in the study were treated in the outpatient setting alone; this finding held true when restricted to laboratory-confirmed cases only, with 78 percent remaining in the outpatient setting [4].

Our understanding of the pathogenesis of these lesions is still under evolution, though it appears to be a primarily inflammatory process with histopathologic and direct immunofluorescence findings similar to those seen in idiopathic and autoimmune-related pernio [3,18,20,25-28]. (See “Pernio (chilblains)”.)

A French study demonstrated increased in vitro production of interferon-alpha from stimulated peripheral blood T cells in patients with pernio compared with patients with polymerase chain reaction (PCR)-positive, moderate to severe COVID-19 [29]. The histologic and biologic patterns of these patients with pernio were similar to a type I interferonopathy, suggesting that a robust, innate immune response may lead to rapid control of the virus in these patients and could, at least in part, explain the relatively mild disease course and low level of antibody production.

Pernio-like lesions may represent a postviral or delayed-onset process, with 80 out of 318 cases in the American Academy of Dermatology/International League of Dermatologic Societies registry developing lesions after the onset of other COVID-19 symptoms [4]. This finding is similar to data from Spain, where 42 out of 71 patients developed lesions after other symptoms [2].

There are several case reports and case series of patients with pernio-like lesions testing positive for immunoglobulin M (IgM), immunoglobulin G (IgG), or immunoglobulin A (IgA) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and negative for PCR, possibly indicating a later stage in the disease process [4,24,30]. However, pernio-like lesions can, in some cases, appear while patients are still PCR positive for the virus, which has potential implications for infectivity and viral spread [4,22]:

•In a French, prospective study, 40 consecutive patients with chilblain-like lesions (median age 22 years, range 12 to 67) were tested for SARS-CoV-2 RNA with reverse transcription (RT)-PCR and SARS-CoV-2-specific IgA, IgM, and IgG antibodies with enzyme-linked immunosorbent assays (ELISAs) [24]. None of these patients were PCR positive at the time of dermatologic consultation; 12 (30 percent) had positive serology for antibodies, of whom seven had only IgA. Twenty-five patients (63 percent) were asymptomatic, and the remaining had only mild symptoms.

•In another French series of 311 patients (median age 26 years) with acral manifestations seen between March and May 2020, 150 (49 with symptoms suspicious for COVID-19) underwent nasopharyngeal swab RT-PCR and/or serology for SARS-CoV-2 [31]. Five of 75 patients were positive for SARS-CoV-2 serology, and 7 of 121 patients were positive for SARS-CoV-2 RT-PCR. Overall, 10 of 170 patients (7 percent) had confirmed COVID-19.

•In the American Academy of Dermatology/International League of Dermatologic Societies registry study, of 318 cases from eight countries, 14 of these cases were PCR positive.

•In an Italian study that screened 22 patients presenting with pernio-like lesions, 6 (26 percent) were PCR positive for SARS-CoV-2 [22].

Although the finding of PCR positivity is not universal and not all observed cases of pernio during the COVID-19 epidemic are necessarily related to COVID-19, it may be prudent that patients presenting with new-onset, pernio-like lesions that have no other clear cause be tested for SARS-CoV-2 PCR within seven days of the onset of pernio lesions [32-35]. For patients who have had these lesions for >4 weeks, IgM and IgG antibody testing may be appropriate, following local guidelines and depending on the quality of available tests, acknowledging that many of these patients may only make transient antibody responses or IgA responses that are not currently being tested in commercial laboratories. Work-up of other causes of pernio is discussed in greater detail separately [2,4,24]. (See “Pernio (chilblains)”.)

There are no treatment guidelines for COVID-19-associated, pernio-like lesions of the feet or hands. However, high-potency topical corticosteroids may be helpful if the lesions are causing discomfort.

Some patients have been noted to have “long COVID”/long-hauler COVID toes [23]. Additionally, some patients have been found to have recurrent pernio after initial SARS-CoV-2 infection, which may be triggered by cold [36].

For More Information: https://www.uptodate.com/contents/covid-19-cutaneous-manifestations-and-issues-related-to-dermatologic-care#!

Toxic Epidermal Necrolysis Post COVID-19 Vaccination – First Reported Case

Authors: Mohamad BakirHanan AlmeshalRifah AlturkiSulaiman ObaidAreej Almazroo


Published: August 16, 2021

Abstract

Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a spectrum of acute, delayed-type hypersensitivity reactions that affect the skin and the mucous membranes. Medications are the culprit cause of these disorders in addition to infections and in very rare instances vaccinations. We report a case of TEN in a 49-year-old woman with no previous medical history. The disorder developed one week after receiving the first dose of COVID-19 vaccine with no other identifiable causes. The patient received two doses of tumor necrosis factor-alpha inhibitor (etanercept) and she stopped developing new lesions after two days of the initial dose; complete healing was observed after 22 days and no side effects were observed in our patient. This case demonstrates an extremely rare complication to the COVID-19 vaccine. The benefits of receiving the COVID-19 outweigh the potential risk. 

Introduction

Toxic epidermal necrolysis (TEN) is a rare immune-mediated, life-threatening skin reaction characterized by blistering and extensive epidermal detachment of more than 30% of body surface area. The incidence is estimated to be 0.4 to 1.9 cases per million population per year worldwide and an estimated mortality rate of 25% to 35% [1, 2]. Medication is usually the cause of TEN (e.g., certain antibiotics and antiepileptics) [3]. Vaccination-induced Stevens-Johnson syndrome (SJS)/TEN is rare, with less than twenty reported cases in the published literature, with the measles vaccine being reported to cause both SJS and TEN, varicella, smallpox, anthrax, tetanus, and influenza vaccines were reported to cause SJS alone, and MMR (measles, mumps, rubella), hantavirus and meningococcal B vaccines were reported to cause TEN [4, 5, 6]. The patient usually develops a fever and other flu-like symptoms one to three weeks after being exposed to medication followed by painful erythematous to purpuric skin lesions that tend to coalescence. Next erosions and vesiculobullous lesions and epidermal detachment over wide body surface area develop. Mucous membranes are also involved, and the patient develops oral ulcers, vaginal ulcers, and possible acute conjunctivitis [7]. In this paper, we report a case of TEN following the administration of the Pfizer COVID-19 vaccine (Pfizer, Inc., New York, USA).

For More Information: https://www.cureus.com/articles/68051-toxic-epidermal-necrolysis-post-covid-19-vaccination—first-reported-case

Pathological findings in organs and tissues of patients with COVID-19: A systematic review

Authors: Sasha Peiris 1 2Hector Mesa 3Agnes Aysola 4Juan Manivel 5Joao Toledo 1 2Marcio Borges-Sa 6Sylvain Aldighieri 1 2Ludovic Reveiz 2 7

Abstract

Background: Coronavirus disease (COVID-19) is the pandemic caused by SARS-CoV-2 that has caused more than 2.2 million deaths worldwide. We summarize the reported pathologic findings on biopsy and autopsy in patients with severe/fatal COVID-19 and documented the presence and/or effect of SARS-CoV-2 in all organs.

Methods and findings: A systematic search of the PubMed, Embase, MedRxiv, Lilacs and Epistemonikos databases from January to August 2020 for all case reports and case series that reported histopathologic findings of COVID-19 infection at autopsy or tissue biopsy was performed. 603 COVID-19 cases from 75 of 451 screened studies met inclusion criteria. The most common pathologic findings were lungs: diffuse alveolar damage (DAD) (92%) and superimposed acute bronchopneumonia (27%); liver: hepatitis (21%), heart: myocarditis (11.4%). Vasculitis was common only in skin biopsies (25%). Microthrombi were described in the placenta (57.9%), lung (38%), kidney (20%), Central Nervous System (CNS) (18%), and gastrointestinal (GI) tract (2%). Injury of endothelial cells was common in the lung (18%) and heart (4%). Hemodynamic changes such as necrosis due to hypoxia/hypoperfusion, edema and congestion were common in kidney (53%), liver (48%), CNS (31%) and GI tract (18%). SARS-CoV-2 viral particles were demonstrated within organ-specific cells in the trachea, lung, liver, large intestine, kidney, CNS either by electron microscopy, immunofluorescence, or immunohistochemistry. Additional tissues were positive by Polymerase Chain Reaction (PCR) tests only. The included studies were from numerous countries, some were not peer reviewed, and some studies were performed by subspecialists, resulting in variable and inconsistent reporting or over statement of the reported findings.

Conclusions: The main pathologic findings of severe/fatal COVID-19 infection are DAD, changes related to coagulopathy and/or hemodynamic compromise. In addition, according to the observed organ damage myocarditis may be associated with sequelae.

For More Information: https://pubmed.ncbi.nlm.nih.gov/33909679/

Pathological findings in organs and tissues of patients with COVID-19: A systematic review

  1. Authors: Sasha Peiris, Hector Mesa, Agnes Aysola, Juan Manivel, Joao Toledo, Marcio Borges-Sa, Sylvain Aldighieri, Ludovic Reveiz

Abstract

Background

Coronavirus disease (COVID-19) is the pandemic caused by SARS-CoV-2 that has caused more than 2.2 million deaths worldwide. We summarize the reported pathologic findings on biopsy and autopsy in patients with severe/fatal COVID-19 and documented the presence and/or effect of SARS-CoV-2 in all organs.

Methods and findings

A systematic search of the PubMed, Embase, MedRxiv, Lilacs and Epistemonikos databases from January to August 2020 for all case reports and case series that reported histopathologic findings of COVID-19 infection at autopsy or tissue biopsy was performed. 603 COVID-19 cases from 75 of 451 screened studies met inclusion criteria. The most common pathologic findings were lungs: diffuse alveolar damage (DAD) (92%) and superimposed acute bronchopneumonia (27%); liver: hepatitis (21%), heart: myocarditis (11.4%). Vasculitis was common only in skin biopsies (25%). Microthrombi were described in the placenta (57.9%), lung (38%), kidney (20%), Central Nervous System (CNS) (18%), and gastrointestinal (GI) tract (2%). Injury of endothelial cells was common in the lung (18%) and heart (4%). Hemodynamic changes such as necrosis due to hypoxia/hypoperfusion, edema and congestion were common in kidney (53%), liver (48%), CNS (31%) and GI tract (18%). SARS-CoV-2 viral particles were demonstrated within organ-specific cells in the trachea, lung, liver, large intestine, kidney, CNS either by electron microscopy, immunofluorescence, or immunohistochemistry. Additional tissues were positive by Polymerase Chain Reaction (PCR) tests only. The included studies were from numerous countries, some were not peer reviewed, and some studies were performed by subspecialists, resulting in variable and inconsistent reporting or over statement of the reported findings.

Conclusions

The main pathologic findings of severe/fatal COVID-19 infection are DAD, changes related to coagulopathy and/or hemodynamic compromise. In addition, according to the observed organ damage myocarditis may be associated with sequelae.

For More Information: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250708

An itchy erythematous papular skin rash as a possible early sign of COVID-19: a case report

Authors: Alice SerafiniPeter Konstantin KurotschkaMariabeatrice Bertolani & Silvia Riccomi 

Background

Several recent studies suggest the possibility of a skin rash being a clinical presentation of coronavirus disease 2019 (COVID-19). The purpose of this case report is to bring attention to skin manifestations in the early stage of COVID-19 in order to support frontline physicians in their crucial activity of case identification.

For More Information: https://jmedicalcasereports.biomedcentral.com/articles/10.1186/s13256-020-02538-y