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Should patients with new onset of chilblains get tested for COVID-19?


Evelyn Lewin


1/09/2020 3:31:43 PM

Dermatologists say at the very least, these patients require a thorough history taking for COVID-19 symptoms and potential contacts.

Toes with chilblains
Doctors have seen a ‘noted increase’ in perniosis this winter.

‘I have seen a noted increase in perniosis this winter, and so have my colleagues. But whether perniosis is an early sign of COVID-19 I think is very controversial.’
 
That is Melbourne-based dermatologist Dr Jack Green.
 
He is talking to newsGP about the increased incidence of perniosis, commonly known as chilblains, seen this year.
 
Patients are now presenting to health professionals to ask whether that condition alone warrants testing for COVID-19 as it may be ‘COVID toe’, a vasculitic phenomenon documented in some COVID positive patients who have no other symptoms of the infection.
 
‘There’s a lot of controversy about this “COVID toe” business,’ Dr Green said.
 
‘The question is, what do you do if someone has perniosis for the first time?’
 
Dr Green says he does not believe that perniosis as a stand-alone symptom in the absence of other COVID-19 symptoms automatically warrants testing for SARS-CoV-2.
 
‘I would have thought that you need to base whether you do a COVID test on the standard features that have been identified in government regulations, whether you’ve got respiratory signs or fever [or other recognised symptoms of COVID-19],’ he said.
 
‘I think you’ve got to keep to those rules.’
 
However, Dr Green says if it is a first-time presentation of perniosis in a patient where there is no other likely explanation, then any possible risk factors for COVID-19 need to be taken into account in deciding whether a test for the virus may be warranted.
 
‘Certainly you have to take each person on their own situation,’ he said.
 
In a newly released position statement seen by newsGP, The Australasian College of Dermatologists (ACD) echoes Dr Green’s sentiments.
 
According to the ACD, the presence of typical perniosis without any history of potential COVID-19 symptoms or contact does not necessitate COVID-19 investigation.
 
However, with patients presenting with perniosis for the first time in the setting of a COVID-19 outbreak, the ACD says ‘there is a dilemma for clinicians’.
 
‘The presence of pernio should prompt a thorough history to be taken about other COVID-19 symptoms and potential COVID-19 contacts,’ the statement said.
 
‘This would involve a detailed assessment of other pertinent symptoms in the individual as well as close contacts including fevers, dry cough, lethargy, and aches and pains.
 
‘An assessment of possible COVID-19 contact in the preceding weeks to even months ought to be sought.’

Dr-Jack-Green-Article.jpg
Dermatologist Dr Jack Green believes there are other reasons why there may be a higher incidence of perniosis this year.

If there is no clinical suspicion of COVID-19, the statement says it is then not necessary to arrange PCR testing with just a perniosis presentation.
 
However, the ACD says it would be ‘reasonable’ with more atypical and widespread presentations to consider testing, even though it would likely be negative, even in those with known COVID association.
 
Associate Professor Hassan Vally is an epidemiologist with a special interest in infectious diseases at La Trobe University.
 
He told newsGP he agrees the question of whether to send patients with new onset of perniosis-like lesions alone for testing for COVID-19 is not straightforward.
 
‘That’s a really difficult question because where do you draw the line at what you use as a signal to actually test?’ Associate Professor Vally said.
 
‘I would probably say it depends on the context. If you’re in a place where there are cases [of COVID-19] running rampant, then that’s an environment when people should be testing more and you might as well assume everything is a potential sign of COVID and test.
 
‘If you’re in an environment where they’ve pretty much eliminated COVID, then it would seem pretty unlikely and low yield activity to be testing every time someone has those sorts of symptoms.’
 
Dr Green believes there are other reasons why there may be a higher incidence of perniosis this year.
 
Firstly, he says the incidence varies yearly, so it may just be that this is a particularly ‘bad’ year for the condition.
 
Secondly, more people are working from home, and their homes may be at a colder ambient temperature than their usual office.
 
Dr Green and his colleagues are referring to that phenomenon as ‘quarantine toe’.
 
The ACD position statement says the more sedentary lifestyle associated with public measures to control the outbreak may also contribute to this phenomenon.
 
Associate Professor Vally agrees with this theory.
 
‘All aspects of society have changed and people’s behaviours have changed, so if there is anything going on [with COVID toe], and that’s not clear, then it could be a secondary thing with people doing things differently, exercising less, and all that,’ he said.
 
Dr Green says another reason there may have been an increased incidence of perniosis may relate to people being worried about the condition.
 
‘Maybe more people are presenting with perniosis for assessment because there is concern out there [about COVID toe] and it’s bringing people to their doctors,’ he said.
 
When did ‘COVID toe’ first emerge as an issue?
The first reports of an association between a vasculitic chilblain-like phenomenon and COVID-19 is said to have occurred in early March in Italy, when a 13-year-old boy developed lesions in the context of fever, myalgia and headache.
 
Testing for COVID-19 was not possible in this case, but family members had respiratory symptoms and an association was suspected.
 
Similar reports were then circulated on an Italian paediatric dermatology forum.
 
In the second week of April, the American Academy of Dermatology, the Pediatric Dermatology Research Alliance, and the Spanish General Council of Podiatrists announced registries that would facilitate the study of chilblain-like lesions and COVID-19.

Associate-Professor-Hassan-Vally-article.jpg
Associate Professor Hassan Vally said the increased incidence of perniosis may relate to people being more worried about the condition.
 
Dermatologists around the world then reported a ‘dramatically increased’ frequency of chilblain-like diagnoses, not infrequently in members of the same family, amidst the pandemic.
 
‘The increased incidence, coupled with the temporal association with viral symptoms, has led to the colloquialisation “COVID toes”,’ the authors of the paper, Going viral: A brief history of chilblain-like skin lesions (“COVID toes”) amidst the COVID-19 pandemic, wrote.
 
Those authors noted chilblain-like lesions appeared to have a predilection for younger patients who are often minimally or asymptomatic and do not require hospitalisation.
 
Lesions were noted to appear late in the evolution of COVID-19 symptoms, often during convalescence.
 
Evidence of infection, however, was not consistently or regularly found when evaluated by PCR for SARS-CoV-2.
 
Should patients with perniosis-like lesions be tested for SARS-CoV-2 via skin biopsy?
The findings in the most recent study published in The Lancet point to the presence of SARS-CoV-2 on skin biopsy, but not via traditional means of testing for the virus, such as nasopharyngeal swab or serology.
 
This may indicate that in patients with perniosis-like lesions, other tests may be needed to look for the presence of the virus.
 
That’s what Dr Zoe Hyde, an epidemiologist at the University of Western Australia, believes.
 
She took to Twitter on 15 August to explore this phenomenon.
 
‘The “COVID Toes” mystery deepens again,’ she tweeted.
 
‘It looks like they are caused by SARS-CoV-2 after all, but people have been looking with the wrong test.’
 
But Dr Green does not believe performing skin biopsies on suspected COVID-19 cases is a practical way to test for SARS-CoV-2.
 
‘Electron microscopy is expensive,’ he said, adding that it can be difficult to access.
 
Associate Professor Vally also does not think such cases merit skin biopsy testing, saying the research so far has not necessarily proven causation between perniosis-like lesions and COVID-19.
 
‘Someone noticing something doesn’t mean that one causes the other,’ he said.
 
‘Correlation does not mean causation.’
 
Research 
The Lancet Infectious Diseases, published on 18 May

  • Three children with chilblain-like lesions who were diagnosed with SARS-CoV-2
  • Two were asymptomatic
  • Findings prompted the authors to conclude that during the pandemic, children and adolescents with chilblain-like lesions who are otherwise asymptomatic should undergo SARS-CoV-2 testing, which could help early detection of silent carriers
The Journal of American Academy of Dermatology, published on 30 May
  • A case series of 318 patients with perniosis-like lesions from eight different countries
  • Only 23 (7%) of 318 patients with confirmed or suspected COVID-19 received laboratory confirmation of being COVID-19 positive, but the authors say many patients lacked testing due to the criteria testing at the time
  • For 55% of patients, perniosis-like lesions were their only symptom
  • The authors concluded such changes, in the absence of another explanation, may suggest COVID-19: ‘We propose that pernio-like lesions be added to the testing criteria for COVID-19 and prompt consideration of testing for both PCR and immunoglobulin (Ig) M and IgG antibodies’
 British Journal of Dermatology, published on 20 June
  • A case series examined skin biopsies taken from seven paediatric patients presenting with chilblains during the COVID-19 pandemic
  • All the children were found to be SARS CoV-2 negative by reverse transcriptase–polymerase chain reaction (RT-PCR), but monoclonal antibodies of biopsies were positive for all seven children
  • Immunohistochemistry for SARS‐CoV‐2 was performed in all cases and electron microscopy in one, with the researchers finding SARS‐CoV‐2 immunohistochemistry was positive in endothelial cells and epithelial cells of eccrine glands and coronavirus particles in the cytoplasm of endothelial cells on electron microscopy
  • ‘Although the clinical and histopathological features were similar to other forms of chilblains, the presence of viral particles in the endothelium and the histological evidence of vascular damage support a causal relation of the lesions with SARS‐CoV‐2,’ the authors wrote
 The Lancet, published on 13 August
  • A case report of the presentation of an 81-year-old febrile woman who had a generalised macular eruption with partial vasculitis-like patterns, with palmoplantar accentuation
  • The woman tested negative for SARS-CoV-2 on nasopharyngeal swab for SARS-CoV-2 and subsequent serology tests against anti-SARS-CoV-2 were negative
  • However, PCR testing of her skin via biopsy detected SARS-CoV-2 at low copy numbers
  • ‘This case is important because it highlights the shortcomings of currently available testing methods for SARS-CoV-2 infection,’ the authors wrote. ‘Swab samples that are taken incorrectly are known drivers of the relatively large number of false negative tests for SARS-CoV-2 ... this case emphasises the use of SARS-CoV-2 PCR testing of skin biopsy samples as an additional diagnostic tool.’
JAMA Dermatology published on 25 June
  • This brief report explored the potential link between chilblains as a manifestation of COVID-19
  • In a case series of 31 patients who had recently developed chilblains in Belgium, none of the patients tested positive for COVID-19 on nasopharyngeal swabs, nor were blood IgM or IgG antibodies detected
  • Skin biopsy was also taken in 22 patients and SARS-CoV-2 RNA remained undetected by RT-PCR in biopsy samples of the skin lesions
  • ‘Chilblains appeared not to be directly associated with COVID-19 in this case series,’ the authors wrote. ‘Lifestyle changes associated with community containment and lockdown measures are a possible explanation for these lesions.’
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