Chilblains and Covid-19 (Covid Toes)

NewsBot · Jun 16, 2020

Chilblains in children in the time of Covid‐19: new evidence with serology assay
C Colonna F Spinelli NA Monzani F Ceriotti C Gelmetti
13 June 2020

In a previous report in Pediatric Dermatology, we described chilblains‐like lesions in four pediatric patients. From April 18 to May 10, 2020, 45 children presented to our Pediatric Dermatology department with similar acral lesions. The clinical appearance ranged from red to violaceous macules and dusky, purpuric plaques on the heels, soles and lateral margin of the feet, often accompanied by painful edema, consistent with chilblains.
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NewsBot · Jun 16, 2020

Rash as a presenting complaint in a child with COVID‐19
Anna Klimach Jordan Evans Jennifer Stevens Nikola Creasey
11 June 2020

Cutaneous manifestations are becoming increasingly well‐documented in adults with COVID‐19. There is now also a growing body of literature regarding skin involvement in children, with reports of papulovesicular, petechial and widespread macular and papular lesions, as well as chilblains (pernio). We describe the case of a thirteen‐year‐old boy with confirmed COVID‐19 in the United Kingdom who presented with skin findings localized to the plantar aspects of the feet, axillae and lower limbs. The morphology was predominantly maculopapular but also included petechiae and annular lesions.
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NewsBot · Jun 16, 2020

Cutaneous Manifestations of COVID-19: A Systematic Review
Giulia Daneshgaran et al
Research Square

Background: The COVID-19 pandemic has affected 4.5 million people and killed over 300,000 patients. Although this virus primarily
causes respiratory symptoms, an increasing number of cutaneous manifestations associated with this disease have been reported.
Objective: The aim of this review was to collate and categorize the dermatologic ndings reported in COVID-19 patients and identify
specic lesions that may facilitate diagnosis and prognostication.
Methods: A systematic review of the PubMed database was conducted on May 14
th
, 2020 using the search terms “Covid-19 skin,”
“Covid-19 rash,” “Covid-19 exanthem,” and “Covid-19 chilblains.” Peer-reviewed publications containing original COVID-19 patient cases
and a discussion of the associated cutaneous ndings were included in the analysis.
Results: The literature search identied 115 records, of which 34 publications describing 996 dermatologic patients were included. Case
reports (n=15), case series (n=10) and observational studies (n=7) were the most common publication types. Pseudo-chilblains (PC)
was the most frequent lesion identied (40.4% of cases), appearing in young adults (mean age, MA, 23.2 years) after the onset of
extracutaneous COVID-19 symptoms (55/100 patients). Erythematous maculopapular rashes (EMR) affected 21.3% of patients, most
frequently impacting middle-aged adults (MA 53.2 years) and occurring at the same time as non-cutaneous symptoms (110/187
patients). Vesicular rashes (VR) affected 13.0% of patients, appearing in middle-aged adults (MA 48.3 years) after the onset of other
symptoms (52/84 patients). Urticarial rashes (UR) affected 10.9% of patients, appearing in adults (MA 38.3 years) and occurring at the
same time as non-cutaneous symptoms (46/78 patients). Vascular rashes resembling livedo/purpura/necrosis (LPN) were uncommon
(4% of cases), appearing in elderly patients (MA 77.5 years) and occurring at the same time as non-cutaneous COVID-19 symptoms
(18/29 patients). Erythema multiforme-like eruptions (EME), although infrequent (3.7% of cases), affected mostly children (MA 12.2
years).
Conclusions: VR may suggest an initial diagnosis of COVID-19, PC may be most appropriate for epidemiological uses, and LPN may be
a useful prognostic marker for severe disease. As a potential correlate to disease severity, prognosis, or infectibility, it is critical that all
health care professionals be well-versed in these increasingly common cutaneous manifestations of COVID-19.
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NewsBot · Jun 19, 2020

PodChatLive Episode 81 with Nadia Dembsky on Chilblains and COVID-19 ("COVID-TOES")

NewsBot · Jun 21, 2020

Major cluster of pediatric “ true ” primary chilblains during the COVID‐19 pandemic: a consequence of lifestyle changes due to lockdown
Neri Iria Virdi Annalucia Corsini Ilaria Guglielmo Alba Lazzarotto Tiziana Gabrielli Liliana Misciali Cosimo Patrizi Annalisa Lanari Marcello
13 June 2020

Background
Over the last months, during the COVID‐19 pandemic, a growing number of chilblain‐like lesions was reported mainly in children, rarely in young adults. The relationship with SARS‐CoV‐2 infection was postulated, often without any laboratory, instrumental or clinical confirmation. The disclosure of information about chilblain‐like lesions as a COVID‐19 manifestation in social media has created concern in children’s families and pediatricians

Objectives
to verify whether the chilblain‐like lesions were caused by SARS‐CoV‐2 infection.

Methods
prospective study on a case series including children who presented with acral lesions at the Pediatric Dermatology Outpatient and Pediatric Emergency Unit of the University of Bologna, from April 1 to April 30, 2020. We reported demographical, laboratory and clinical features, history of close contact with COVID‐19 patients, presence of similar skin lesions in other family members, precipitating and risk factors for chilblain onset.

Results
We evaluated 8 patients (5 females, 3 males) aged between 11 and 15 years. We excluded acute or previous SARS‐CoV‐2 infection with RT‐PCR nasopharyngeal swab, serum antibody levels using chemiluminescent immunoassays. Other acute infections causing purpuric lesions at the extremities were negative in all patients. Skin lesion biopsy for histological and immunohistochemical evaluation was made in two cases and was consistent with chilblain.

PCR‐assay on skin lesion biopsy for Parvovirus B19, Mycoplasma pneumoniae and SARS‐CoV‐2 was performed in a patient and resulted negative. We identified common precipitating and risk factors: physical (cold and wet extremities, low BMI), cold and wet indoor and outdoor environment, behaviors, habits, lifestyle. We therefore reached a diagnosis of primary chilblains.

Conclusions
During the COVID‐19 pandemic, a “cluster” of primary chilblains developed in predisposed subjects, mainly teenagers, due to to cold exposure in the lockdown period. Laboratory findings support our hypothesis, although it is also possible that an unknown infectious trigger may have contributed to the pathogenesis.
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NewsBot · Jun 24, 2020

Patients with specific skin disorders who are affected by COVID ‐19: what do experiences say about management strategies? : A systematic review
Niloufar Najar Nobar Azadeh Goodarzi
18 June 2020

Background and aim
In patients with dermatologic disorders who are affected by new corona virus, we know little about course (underlying disease and new onset‐infection) and the most proper management strategies include both issues that are what this systematic review targets.

Method
Databases of PubMed, Scopus, Google Scholar, Medscape and CEBD coronavirus dermatology resource of Nottingham University searched completely and initial 237 articles selected to further review and finally nine articles (including 12 patients) entered to this study.

Result
from 12 patients with chronic underlying dermatologic disease treated with systemic therapies, only one patient required ICU admission, the others have been treated for mild‐ moderate symptoms with conventional therapies. The biologic or immunosuppressive/ Immunomodulator agents has been ceased during the course of disease. The course of COVID‐19 its management was as similar as normal populations. Their underlying dermatologic disease was exacerbating from mild to moderate. Their treatment has been continued as before, after the symptoms improved.

Conclusion
Exacerbation of patients underlying dermatologic disease is mild‐ moderate. Discontinuing the treatment in the acute period of COVID and the restart after recovery may prevent severe recurrence in these patients.
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NewsBot · Jun 24, 2020

An internet-based algorithm for diabetic foot infection during the COVID-19 pandemic

NewsBot · Jun 24, 2020

The mystery of the COVID toes – turning evidence-based medicine on its head
Ivan R. Bristow & Alan M. Borthwick
Journal of Foot and Ankle Research volume 13, Article number: 38 (2020)

The recent and rapid emergence of COVID-19 infection has led to a flood of publications describing all aspects of the disease and its presentation. The appearance of chilblain-like lesions, in children and young adults has particularly caught the attention of healthcare professionals with an interest in the foot. With such a novel infection, demand for information is high at a time when evidence is scarce. Consequently, there has been a renaissance in the publication of case studies. This type of research, previously relegated from many mainstream journals, as a low level source of evidence, has permitted the rapid reporting, publication and dissemination of much needed clinical data which can be used as a foundation to inform further research and investigations about a new global infection.
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NewsBot · Jun 25, 2020

SARS‐CoV‐2 endothelial infection causes COVID‐19 chilblains: histopathological, immunohistochemical and ultraestructural study of 7 paediatric cases
I. Colmenero C. Santonja M. Alonso‐Riaño L. Noguera‐Morel A. Hernández‐Martín D. Andina T. Wiesner J.L. Rodríguez‐Peralto L. Requena A. Torrelo
BJD: 20 June 2020

Background
Chilblains ("COVID toes") are being seen with increasing frequency in children and young adults during the COVID‐19 pandemic. Detailed histopathological descriptions of COVID‐19 chilblains have not been reported, and causality of SARS‐CoV‐2 has not been established yet.

Objective
To describe histopathological features of Covid‐19 chilblains and explore the presence of SARS‐CoV‐2 in the tissue.

Methods
We examined skin biopsies from 7 paediatric patients presenting with chilblains during the COVID‐19 pandemic. Immunohistochemistry for SARS‐CoV‐2 was performed in all cases and electron microscopy in one.

Results
Histopathology showed variable degrees of lymphocytic vasculitis ranging from endothelial swelling and endothelialitis to fibrinoid necrosis and thrombosis. Purpura, superficial and deep perivascular lymphocytic inflammation with perieccrine accentuation, oedema, and mild vacuolar interface damage were also seen. SARS‐CoV‐2 immunohistochemistry was positive in endothelial cells and epithelial cells of eccrine glands. Coronavirus particles were found in the cytoplasm of endothelial cells on electron microscopy.

Conclusions
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. Endothelial damage induced by the virus could be the key mechanism in the pathogenesis of COVID‐19 chilblains and perhaps also in a group of patients severely affected by COVID‐19 presenting with features of microangiopathic damage.
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NewsBot · Jun 28, 2020

Understanding the role that ‘COVID toe’ has in recognizing the potential extent of COVID-19 infections: a case study
Alex Noakes & Sophie Majoe
Pathogens and Global Health: 24 Jun 2020

Dermatological manifestations have shown to be associated with COVID-19 infections. The numbers of papers have quadrupled within May 2020 alone. One particular cutaneous manifestation named pseudo chilblains (COVID toe), expressed mostly in otherwise asymptomatic younger patients, has had particular media attention. Public health bodies, on the other hand, have been slow to recognize it as a symptom. This article will be discussing two case studies to demonstrate the lack of public knowledge and of public health guidance associated with this symptom. We will further explore the use of COVID toe in the epidemiology of COVID-19 and its utility as a sign for total cases and contact tracing.
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NewsBot · Jun 28, 2020

Pernio-like skin lesions associated with COVID-19: a case series of 318 patients from 8 countries
Esther E.Freeman et al
Journal of the American Academy of Dermatology; 30 May 2020

Background
Increasing evidence suggests pernio-like lesions are cutaneous manifestations of COVID-19.

Objective
To describe clinical and pathologic findings of pernio-like lesions in confirmed or suspected COVID-19 cases.

Methods
An international dermatology registry was circulated to healthcare providers worldwide through the American Academy of Dermatology (AAD), International League of Dermatologic Societies (ILDS), and other organizations.

Results
We documented 505 patients with dermatologic manifestations associated with COVID-19, including 318 (63%) with pernio-like lesions. Patients with pernio-like lesions were generally young and healthy, with relatively mild COVID-19. Of 318 cases confirmed or suspected as COVID-19 by providers, twenty-three cases (7%) were laboratory-confirmed COVID-19 positive, and 20 others (6%) were close contacts of confirmed COVID-19 cases. Given current testing criteria, many patients lacked COVID-19 testing access. For 55% of patients, pernio-like lesions were their only symptom. In patients with other COVID-19 symptoms, pernio-like lesions typically appeared after other symptoms. Pernio-like lesions lasted a median of 14 days (IQR 10-21).

Limitations
A case series cannot estimate population level incidence or prevalence. Additionally, there may be confirmation bias in reporting. We cannot exclude an epiphenomenon.

Conclusions
Pernio-like skin changes of the feet and hands, without another explanation, may suggest COVID-19 infection and should prompt confirmatory testing.
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NewsBot · Jun 29, 2020

Recent outbreak of chilblain‐like lesions is not directly related with SARS‐CoV‐2 infection
J. Rouanet E. Lang F. Beltzung B. Evrard C. Henquell I. Joulie M. D’Incan
26 June 2020 https://doi.org/10.1111/jdv.16776

Throughout March and April 2020, dermatologists have observed an outbreak of chilblains despite climatic conditions not conducive to their apparition. These lesions have occurred simultaneously to the COVID‐19 epidemic, suggesting a relationship between their onset and SARS‐CoV‐2 infection. Here we describe a series of 10 patients presenting chilblain‐like lesions in whom we have searched for evidence of SARS‐CoV‐2 infection.
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NewsBot · Jul 2, 2020

COVID‐19 and outbreak of chilblains: are they related?
C. Lesort J. Kanitakis A. Villani E. Ducroux P. Bouschon K. Fattouh B. Bensaid M. Danset D. Jullien
27 June 2020

SARS‐CoV‐2 is a new coronavirus that causes COVID‐19, a disease associated with severe pneumonia.1 Many other clinical manifestations have been associated with the disease (diarrhoea, anosmia, dysgeusia, etc.) and patients can be healthy carriers of the virus.2 Several dermatologic manifestations associated with COVID‐19 have been reported.3 Among them are numerous cases of chilblain‐like lesions (CBLL) in young patients in good general condition, often not tested, or tested negative, for the SARS‐CoV‐2.4,5 In a recent study on 375 Spanish patients with suspected or confirmed COVID‐19, these CBLL accounted for 19% of all cutaneous lesions;3 they were observed in young patients with mild systemic symptoms and seemed to appear late in the course of the disease.
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NewsBot · Jul 2, 2020

Evaluation of Chilblains as a Manifestation of the COVID-19 Pandemic
Anne Herman et al
June 25, 2020
JAMA Dermatology

Key Points

Question Is there an association between chilblains and coronavirus disease 2019 (COVID-19)?

Findings In this case series of 31 patients who had recently developed chilblains, none of the patients tested positive for COVID-19 on nasopharyngeal swabs, nor were blood immunoglobulin (Ig) M or IgG antibodies detected.

Meaning These ischemic, acral cutaneous lesions appeared not to be directly associated with COVID-19.
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Importance During the coronavirus disease 2019 (COVID-19) pandemic, several cases of chilblains have been reported.

Objective To determine if chilblains are associated with COVID-19.

Design, Setting, and Participants This monocentric case series was conducted at the Department of Dermatology at Cliniques universitaires Saint-Luc, a tertiary care hospital in Brussels, Belgium, between April 10 and April 17, 2020. We evaluated a total of 31 referred patients who had recently developed chilblains.

Main Outcomes and Measures Real-time reverse transcriptase–polymerase chain reaction (RT-PCR) was used to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA on nasopharyngeal swabs for all patients and in skin biopsy specimens for 22 patients. Blood samples from all patients were tested for specific anti–SARS-CoV-2 immunoglobulin (Ig) M and IgG antibodies. All patients had extended blood analyses. Histologic (22 patients) and immunofluorescence examinations (15 patients) were performed on the skin biopsy specimens.

Results The 31 patients were generally in good health; most were teenagers or young adults, and 19 were women. Histopathologic analysis of skin biopsy specimens (22 patients) confirmed the diagnosis of chilblains and showed occasional lymphocytic or microthrombotic phenomena. Immunofluorescence analyses showed vasculitis of small-diameter vessels in 7 patients. In all patients, SARS-CoV-2 RNA remained undetected by RT-PCR on nasopharyngeal swabs and in biopsy samples of the skin lesions. The IgM and IgG antibody titers were negative for SARS-CoV-2 in all patients (<1.0 arbitrary unit/mL). No significant abnormalities in blood test results were suggestive of systemic disease. Antinuclear antibody titers were low in 7 patients and higher in 1 patient.

Conclusions and Relevance Chilblains appeared not to be directly associated with COVID-19 in this case series. Lifestyle changes associated with community containment and lockdown measures are a possible explanation for these lesions.
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NewsBot · Jul 2, 2020

Assessment of Acute Acral Lesions in a Case Series of Children and Adolescents During the COVID-19 Pandemic
Juncal Roca-Ginés et al
JAMA Dermatol. Published online June 25, 2020. doi:10.1001/jamadermatol.2020.2340

Key Points

Question What is the association between acute acral lesions and coronavirus disease 2019 (COVID-19) in children and adolescents?

Findings In this case series of 20 patients aged 1 to 18 years with new-onset acral inflammatory lesions, all lacked systemic manifestations of COVID-19. Both reverse transcriptase–polymerase chain reaction and serologic test results were negative for severe acute respiratory syndrome coronavirus 2.

Meaning An association between acral skin disease and COVID-19 has yet to be proved.
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Importance A novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has recently been identified as the cause of a pandemic called coronavirus disease 2019 (COVID-19). In this context, some associated skin diseases have been described. Cutaneous lesions referred to as acute acro-ischemia have been reported as a possible sign of COVID-19 in adolescents and children.

Objective To evaluate the pathogenesis of these newly described acute acral lesions.

Design, Setting, and Participants This prospective case series was conducted at La Fe University Hospital, a tertiary referral hospital in Valencia, Spain, between April 9 and April 15, 2020. Among 32 referred patients, 20 children and adolescents with new-onset inflammatory lesions did not have a diagnosis.

Exposures Patients were not exposed to any drug or other intervention.

Main Outcomes and Measures We performed reverse transcriptase–polymerase chain reaction for SARS-CoV-2 and a range of blood tests for possible origins of the lesions. Skin biopsies were performed in 6 patients.

Results Of the 20 patients enrolled, 7 were female and 13 were male, with an age range of 1 to 18 years. Clinical findings fit into the following patterns: acral erythema (6 patients), dactylitis (4 patients), purpuric maculopapules (7 patients), and a mixed pattern (3 patients). None of the patients had remarkable hematologic or serologic abnormalities, including negative antibodies to SARS-CoV-2. Biopsies performed in 6 patients showed histologic findings characteristic of perniosis.

Conclusions and Relevance The clinical, histologic, and laboratory test results were compatible with a diagnosis of perniosis, and no evidence was found to support the implication of SARS-CoV-2 infection.
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NewsBot · Jul 3, 2020

This clinical "trial" was just registered:
COVID-19 and Chilblains (ECCES)

Brief Summary:
Chilblains (inflammatory lesion of the feet or hands) have been reported with an unusual frequency during the confinement period, most commonly in children, teenagers and young adults. The aim of the ECCES study is to find out whether these manifestations of chilblains can be linked to the SARS-CoV-2 coronavirus.

For this, an epidemiologic study will compare two types of family (or more precisely people who were confined together in March-April-May):

"case family" in which at least one of the members had chilblains
"comparator family" in which none of the members had chilblains Environment (home lockdown) of the two types of family will be analyzed. Each member of the "family" will be suggested doing a serological test.
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NewsBot · Jul 6, 2020

Chilblain‐like lesions during COVID‐19 pandemic: a serological study on a case series
L. Rizzoli L. Collini M. Magnano S. Termine R. Barcelli S.D. Infusino P. Bauer G. Rech C. R. Girardelli R. Balestri
01 July 2020

The outbreak of chilblain‐like lesions (CLL) coincidentally to the COVID‐19 pandemic is a topic of great concern. SARS‐CoV‐2 has been hypothesized as the etiologic agent of CLL, on the basis of the temporal correlation between the “burst” of skin manifestations and the viral pandemic. However, the relationship between CLL and COVID‐19 remains unclear, since authors failed to confirm the SARS‐CoV‐2 infection in these patients using a real‐time reverse transcription polymerase chain reaction (rt‐PCR) test from nasopharyngeal swabs, which seldom resulted positive. Indeed, the most recent articles on the prevalence of the SARS‐CoV‐2 infection in CLL reported a positive swab test in only about a fifth of these patients.
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NewsBot · Jul 6, 2020

Clinical and Histopathological Features and Potential
Pathological Mechanisms of Skin Lesions in
COVID-19: Review of the Literature
Gürkan Kaya et al
Dermatopathology 2020, 7, 3–16;: 30 June 2020

In recent weeks, several reports have emerged of skin lesions with different clinical
presentations in COVID-19 cases. All dermatologists should be aware of these cutaneous lesions,
which may be early clinical symptoms of infection. We reviewed the literature on cutaneous
manifestations in the PubMed database from December 2019 and June 2020. From the cases described
as case reports or series in 57 recent articles, it appears that skin lesions (i) are highly varied,
(ii) may not be related to the severity of the condition and (iii) resolve spontaneously in a few days.
The frequency of these lesions in COVID-19 patients varies between 1.8% and 20.4%. The major clinical
forms described were maculopapular eruptions, acral areas of erythema with vesicles or pustules
(pseudochilblain), urticarial lesions, other vesicular eruptions and livedo or necrosis. The lesions
were mainly localized in the trunk and extremities. The majority of patients were male, aged between
4.5 and 89 years. A minority of the patients were children presenting with acral, chilblain-like lesions,
papulo-vesicular eruptions or Kawasaki disease-like pediatric inflammatory multisystem syndrome.
The mean duration of the lesions was a few days, but some lasting as little as 20 min and others as
long as four weeks have been reported. The mean latency time in the majority of cases was between 1
and 14 days; however, in some patients, lesions appeared 2 to 5 days before the onset of COVID-19
symptoms. The histopathological features of these lesions also vary, corresponding to the diversity
of clinical manifestations. These features underline the nature of epidermal and dermal vascular
lesions—and in severe cases, microvascular injury and thrombosis—associated with COVID-19,
and provide important clues to their pathological mechanisms.
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NewsBot · Jul 6, 2020

Dermoscopy Features of COVID-19-related Chilblains in Children and Adolescents
Lourdes Navarro et al
J Eur Acad Dermatol Venereol. 2020 Jul 2.

Chilblains are skin condition frequently seen by physicians worldwide during the COVID-19 outbreak. We attended 22 children and adolescents with chilblains during the outbreak peak of COVID-19 in Madrid. The clinicopathologic and laboratory features of these patients have been reported. We describe herein the dermoscopic findings. Approval from the institutional Ethics Committee and Board was obtained. Standard informed consents were obtained for recording images in all patients.
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NewsBot · Jul 6, 2020

Cutaneous chilblains-like lesions (CCLL) versus COVID-19 toes during the pandemic. Confocal findings and proposal for new acronym, CCLL – is there a diagnostic window?
Joanna Ludzik et al
F1000Research 2020, 9:668

The COVID-19 outbreak caused by the novel coronavirus, SARS-CoV-2, typically presents with symptoms including fever, cough, headache, myalgia, asthenia, anosmia, diarrhea, and sometimes pneumonia, which can be fatal. Recently, new dermatologic findings have been described in association with the disease that can potentially be a distinguishing feature of infection. One such feature resembles chilblains and this case report represents a unique presentation of this feature.
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NewsBot · Jul 8, 2020

Concurrent chilblains and retinal vasculitis in a child with COVID‐19
Lucía Quintana‐Castanedo Marta Feito‐Rodríguez Celia Fernández‐Alcalde María Granados‐Fernández Dolores Montero‐Vega Ander Mayor‐Ibarguren Raúl de Lucas‐Laguna
02 July 2020

Reports on COVID‐19 in children are limited. Despite new data emerging, and understanding of the disease improves rapidly, there are as yet several features and complications related to the disease that remain unknown. Herein, we report the first case of a child with chilblains and retinal vasculitis related to COVID‐19.
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NewsBot · Jul 11, 2020

Coronavirus (COVID-19) Infection–Induced Chilblains
A Brisk Perieccrine Inflammatory Response
Wargo, Jeffrey J. MD; Weir, Nathan M. MD, PhD; Shamma, H. Nicholas MD
The American Journal of Dermatopathology: June 30, 2020

The varying cutaneous and pathological manifestations of coronavirus 2 (SARS-CoV-2 or COVID-19) may have prognostic implications. Acral ischemic findings present with a hypercoagulable state in critically ill COVID-19 patients. Pathologically confirmed varicella-like exanthem and perniosis COVID-19 cases have correlated with paucisymptomatic and asymptomatic patients in previous reports. We present the second case of biopsy-proven COVID-19 infection–induced chilblains (pernio) in a paucisymptomatic patient with a brisk perieccrine lymphocytic response. Based on an antecedent pathological study, we know coronavirus particles have been seen in the eccrine gland associated with a brisk peri-inflammatory response. The prominent perieccrine inflammation is helpful in the diagnosis of COVID-19 infections. Currently, nonischemic pathological findings correlate with a good prognosis based on the paucisymptomatic or asymptomatic nature of their disease courses. Patients presenting with suspected COVID-19 infection–induced chilblains who are paucisymptomatic or asymptomatic should be isolated and immediately tested with polymerase chain reaction (PCR) testing (as there is a delay in diagnosis based on the poor sensitivity of the current rapid test). We continue to stress the importance of early diagnosis and quarantining to prevent spread to the older and immunocompromised patients.
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NewsBot · Jul 12, 2020

Chilblains in Children in the Setting of COVID-19 Pandemic
David Andina et al
Pediatr Dermatol. 2020 May;37(3):406-411

Background: Different skin manifestations of COVID-19 are being reported. Acral lesions on the hands and feet, closely resembling chilblains, have been recognized during the peak incidence of the COVID-19 pandemic.

Material and methods: A retrospective review of 22 children and adolescents with chilblain-like lesions seen over a short period of time in the Emergency Department of a children's hospital during the peak incidence of COVID-19 in Madrid, Spain.

Results: All patients had lesions clinically consistent with chilblains of the toes or feet, with three also having lesions of the fingers. Pruritus and mild pain were the only skin symptoms elicited, and only 10 had mild respiratory and/or GI symptoms. None had fever. Coagulation tests, hemogram, serum chemistry, and lupus anticoagulant were normal in all patients tested. One out of 16 tested cases had elevated D-dimer results, but without systemic symptoms or other laboratory anomalies. SARS-CoV-2 PCR tested in 19 cases was positive in just one case. Skin biopsies obtained in six patients were consistent with chilblains. On follow-up, all cases showed spontaneous marked improvement or complete healing.

Conclusion: Acute chilblains were observed during COVID-19 pandemic in children and teenagers. It is a mildly symptomatic condition with an excellent prognosis, usually requiring no therapy. Etiopathogenesis remains unknown.
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NewsBot · Jul 14, 2020

Most chilblains observed during the COVID‐19 outbreak occur in patients who are negative for COVID‐19 on PCR and serology testing
L. Le Cleach L. Dousset H. Assier S. Fourati S. Barbarot C. Boulard C. Bourseau Quetier L. Cambon C. Cazanave A. Colin E. Kostrzewa C. Lesort A. Levy Roy F. Lombart … See all BJD: 06 July 2020

Introduction
Acral lesions, mainly chilblains, are the most frequently reported cutaneous lesions associated with COVID‐19. In more than 80% of tested patients, nasopharyngeal swabs were negative on RT‐PCR for SARS‐CoV‐2 when performed, and serology was generally not performed.

Materials and Methods
A national survey was launched on March 30, 2020 by the French society of dermatology asking physicians to report cases of skin manifestations in patients with suspected or confirmed COVID‐19 by using a standardized questionnaire. We report the results for acral manifestations.

Results
We collected 311 cases of acral manifestations (58.5% females, median age 25.7 years [range 18‐39]). The most frequent clinical presentation (65%) was typical chilblains. In total, 93 cases (30%) showed clinical suspicion of COVID‐19, 67 (22%) had only less specific infectious symptoms, and 151 (49%) had no clinical signs preceding or during the course of acral lesions. Histology of skin biopsies was consistent with chilblains (n= 26/29). Twelve patients showed significant immunological abnormalities. Ten patients were positive among the 150 (48%) who were tested (RT‐PCR and/or serology). Seven of 121 RT‐PCR–tested patients were positive and 5 of 75 serology‐tested patients were positive (IgG) among them RT‐PCR and serology were both positive for two patients. Seven of 121 RT‐PCR–tested patients were positive for SARS‐CoV‐2 (6%), and 5 of 75 serology‐tested patients had IgG anti‐ SARS‐CoV‐2 (7 %). Tested and untested patients or those with and without confirmed COVID‐19 did not differ in age, sex, history or acral‐lesion clinical characteristics.

Conclusion
The results of this survey do not rule out that SARS‐CoV‐2 could be directly responsible for some cases of chilblains but found no evidence of SARS‐CoV‐2 infection in large majority of patients with acral lesions during the COVID‐19 lockdown period in France.
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NewsBot · Jul 17, 2020

Are chilblains a skin expression of COVID-19 microangiopathy?
Marie Baeck et al
J Thromb Haemost. 2020 Jul 13

The unexpected outbreak of chilblains during the current coronavirus disease 2019 (COVID-19) pandemic has been causally linked to severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) infection (1). The pathophysiology of these chilblains observed in otherwise healthy patients is widely discussed.
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NewsBot · Jul 17, 2020

RE: SARS-CoV-2-related chilblains in a 16 year old female
Catharine L. Dewar, Rheumatologist, (Rheumatology, Lions Gate Hospital, North Vancouver, BC: Retired in 2020)
13 July 2020
I read this article (1) with interest but it raised a few concerns. In females in this age group, the association between anorexia nervosa and pernio or chilblains has been noted for several

decades (2,3). This case report makes no mention of the patient's body habitus or BMI, in fact there is no description of a physical examination which is seminal in ruling out autoimmune disorders such a lupus, or malignancy. The laboratory investigations are thorough, but a normal chest radiograph and CT scan of the abdomen would have added weight to the final diagnosis of covid-19 related chilblains. The dermal pathology of pernio or chilblains is non-specific (4) and therefore a skin biopsy is not recommended (4). There is no description of the patient's smoking history, including e-cigarette usage ('vaping') as nicotine will exacerbate the vasospasm seen in pernio or chilblains (4). During the current pandemic, clinicians are adopting a 'hands-off' or telehealth approach to reviewing patients, including history taking. However, there are individuals for which an office visit and physical examination is very important. I fear this may be one of those cases; the positive covid-19 antibody serology may be incidental and unrelated to her skin condition.
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This was in response this article: https://www.cmaj.ca/content/cmaj/192/28/E804.full.pdf

NewsBot · Jul 24, 2020

COVID-19-associated vasculitis and vasculopathy
Richard C. Becker
Journal of Thrombosis and Thrombolysis (2020)

The COVID-19 pandemic now totaling 13,000,000 cases and over 571,000 deaths has continued to teach the medical, scientific and lay communities about viral infectious disease in the modern era. Among the many lessons learned for the medical community is the potential for transmissibility and host infectivity of the SARS–CoV-2 virus. Moreover, it has become clear that the virus can affect any organ including the circulatory system, directly via either tissue tropism or indirectly stemming from inflammatory responses in the form of innate immunity, leukocyte debris such as cell-free DNA and histones and RNA viral particles. The following review considers COVID-19-associated vasculitis and vasculopathy as a defining feature of a virus-induced systemic disease with acute, subacute and potential chronic health implications.
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NewsBot · Jul 24, 2020

Novel outbreak of acral lesions in times of COVID-19: A description of 74 cases from a tertiary university hospital in Spain

NewsBot · Jul 28, 2020

The differing pathophysiologies that underlie COVID‐19 associated perniosis and thrombotic retiform purpura: a case series
C. Magro J.J. Mulvey J. Laurence S. Sanders N. Crowson M. Grossman J. Harp G. Nuovo
22 July 2020

Background
There are two distinctive acral manifestations of COVID‐19 embodying disparate clinical phenotypes: one is perniosis occurring in mildly symptomatic patients, typically children; the second is the thrombotic retiform purpura of critically ill COVID19 adults.

Materials and Methods
We compare light‐microscopic, phenotypic, cytokine, and SARS‐CoV‐2 protein and RNA profiles in COVID‐19‐associated perniosis of mildly symptomatic or asymptomatic patients with the thrombotic retiform purpura of critical patients with COVID‐19.

Results
The COVID‐19‐associated perniosis exhibited vasocentric and eccrinotropic T‐cell and monocyte‐derived CD11c, CD14, and CD123+ dendritic cell infiltrates. Both COVID associated and idiopathic perniosis showed striking expression of the type I interferon‐inducible myxovirus resistance protein‐A (MXA), an established marker for type I interferon signaling in tissue. SARS‐CoV‐2 RNA, IL‐ 6 and caspase 3 were minimally expressed and confined to mononuclear inflammatory cells. The biopsies from livedo/retiform purpura showed pauci‐inflammatory vascular thrombosis without any MXA decoration. Blood vessels exhibited extensive complement deposition with endothelial cell localization of SARS‐CoV‐2 protein, IL6, and caspase 3; SARS CoV‐2 RNA was not seen.

Conclusion
The COVID‐19‐associated perniosis represents an exaggerated immune reaction to a virus with significant type‐I interferon signaling important to SARS‐CoV‐2 eradication and has implications in regards to a more generalized highly‐inflammatory response. We hypothesize that in the thrombotic retiform purpura of critically ill patients with COVID‐19, the vascular thrombosis in the skin and other organ systems is associated with a minimal interferon response allowing excessive viral replication with release of viral proteins that localize to extrapulmonary endothelium and trigger extensive complement activation.
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NewsBot · Jul 28, 2020

Cutaneous manifestations associated with COVID19 in children: A Systematic Review
Seema Shah et al
Research Square

Background: Cutaneous manifestation of COVID 19 in children has not yet been reviewed systematically
and hence this review gives a future direction to the clinicians to be vigilant for skin presentations during
such pandemic.
Methodology: The review was done as per the guidelines of PRISMA and literature search was done on
PubMed database using keywords as COVID-19, children and skin in different combinations. Articles
published in English with cases of age 1 month to 18 years were eligible. The outcome included varied
aspects of cutaneous and COVID-19 infection. The review protocol was not registered.
Results: Of 51 publications identied, 13 studies containing 149 children met the eligibility criteria. Acrally
located erythematous maculopapular lesion was the most common nding in 138 children. Erythema
multiforme, varicella like exanthem and Kawasaki disease like presentations were reported in the rest of
the cases. The duration of the skin lesion was 1-2 weeks in 43%. Skin biopsy done in 18 cases revealed
supercial & deep perivascular and peri-eccrine lymphocytic inltrate & lymphocytic vasculitis. RT-PCR
was positive in 13.8% cases. Serological markers for HSV, parvovirus B19 analyzed across various
studies, were found negative, except for mycoplasma pneumoniae in 2 of 20 cases tested.
Discussion: Clinicopathologic analysis established chilblains like lesion in 43% cases with no conrmed
etiology like cold exposure, autoimmune dysfunction, drug reaction, or viral infection. The usual cephalocaudal spread of a viral exanthem was also missing. However, a low number of discussed cases was a
limitation of the study.
Conclusion: In the absence of any conrmed etiology for such cutaneous manifestations, the possibility
of COVID-19 should be explored and evaluated thoroughly during such pandemic.
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NewsBot · Jul 29, 2020

Whatever happened to COVID toes?

NewsBot · Jul 29, 2020

Pernio-like skin lesions associated with COVID-19: A case series of 318 patients from 8 countries
Esther E Freeman et al
J Am Acad Dermatol. 2020 Aug;83(2):486-492

Background: Increasing evidence suggests pernio-like lesions are cutaneous manifestations of coronavirus infectious disease 2019 (COVID-19).

Objective: To describe clinical and pathologic findings of pernio-like lesions in patients with confirmed or suspected COVID-19.

Methods: An international dermatology registry was circulated to health care providers worldwide through the American Academy of Dermatology, International League of Dermatologic Societies, and other organizations.

Results: We documented 505 patients with dermatologic manifestations associated with COVID-19, including 318 (63%) with pernio-like lesions. Patients with pernio-like lesions were generally young and healthy, with relatively mild COVID-19. Of 318 patients with confirmed or suspected COVID-19 by providers, 23 (7%) were laboratory-confirmed COVID-19 positive, and 20 others (6%) were close contacts of patients with confirmed COVID-19. Given current testing criteria, many patients lacked COVID-19 testing access. For 55% of patients, pernio-like lesions were their only symptom. In patients with other COVID-19 symptoms, pernio-like lesions typically appeared after other symptoms. Pernio-like lesions lasted a median of 14 days (interquartile range, 10-21 days).

Limitations: A case series cannot estimate population-level incidence or prevalence. In addition, there may be confirmation bias in reporting. We cannot exclude an epiphenomenon.

Conclusions: Pernio-like skin changes of the feet and hands, without another explanation, may suggest COVID-19 infection and should prompt confirmatory testing.
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NewsBot · Aug 9, 2020

NEWS RELEASE 7-AUG-2020
COVID-19 - The virus and the vasculature

In severe cases of COVID-19, the infection can lead to obstruction of the blood vessels in the lung, heart and kidneys. Ludwig-Maximilians-Universitaet (LMU) in Munich researchers have now shown that activated immune cells and blood platelets play a major role in these pathologies.

The novel coronavirus SARS-CoV-2 infects the respiratory tract and in severe cases, the infection can result in lung failure, which necessitates the use of mechanical ventilation. In addition, these patients develop further complications, such as pulmonary embolisms or thromboses (clots) in their veins. Whether or not virus-associated respiratory failure is functionally related to the systemic increase in the incidence of intravascular clot formation has remained unclear. However, a new study led by LMU clinicians Leo Nicolai and Konstantin Stark, which appears in the journal Circulation, has identified a link between virus-induced changes in the blood vessels of the lung and the increased thrombotic risk. Upon post-mortem examination of the lungs of COVID-19 patients who had died of the disease, Nicolai and colleagues found many microclots within the finest branches of the pulmonary vasculature. Similar observations were made in the heart and the kidney.

These clots were primarily made up of platelets and activated immune cells, in particular neutrophils. Detailed analysis of the thrombi suggested that an activating interaction between platelets and neutrophils is responsible for promoting intravascular coagulation. Neutrophils belong to the innate immune system and their principal task is to fight invading pathogens. Their involvement in abnormal clotting has led to the designation of this process as immunothrombosis. In COVID-19 patients, the stimulation of clot formation eventually compromises the supply of blood to nearby tissues. This in turn ultimately leads to respiratory failure, while the tendency to trigger clotting becomes systemic.

Using multidimensional flow cytometry assays, the LMU researchers showed that in COVID-19 patients who had suffered lung failure and required mechanical ventilation, the numbers of activated neutrophils and platelets in the circulation were greatly enhanced. Since the two cell types reciprocally activate each other, these interactions lead to the formation of obstructive blood clots in the lung. In addition, activated neutrophils extrude mesh-like complexes made up of DNA and cytoplasmatic proteins, which are known as neutrophil extracellular traps (NETs). These normally serve to trap and destroy bacterial and viral pathogens, but they also play a significant role in immunothrombosis by stabilizing thrombi. While this process is initially localized in the lung exacerbating respiratory failure and result in a systemic thrombogenic state. "These findings contribute to a better understanding of the pathophysiology that underlie disease progression in COVID-19," says Konstantin Stark. "The study also identifies immunothrombosis as a promising target for the prevention and treatment of lung failure and thrombotic complications that arise in cases of COVID-19."

NewsBot · Aug 17, 2020

‘Pretty conclusive’ link between ‘COVID toe’ and virus indicates infection far more widespread in children as Tories plough on with return to school

NewsBot · Aug 18, 2020

Aussie docs report uptick in chilblains, or are they COVID-toe?

NewsBot · Aug 19, 2020

Chilblains and COVID‐19: why SARS‐CoV‐2 endothelial infection is questioned
M. Baeck D. Hoton L. Marot A. Herman
15 August 2020 https://doi.org/10.1111/bjd.19489

Recently, Colmenero et al (1) demonstrated, by immunohistochemistry, the presence of SARS‐CoV‐2 in endothelial cells of skin biopsy specimens of chilblains in seven patients. These results raise some questions:

The presence of the virus at cutaneous and vascular levels in otherwise asymptomatic patients with negative RT‐PCR is unexpected. Vascular damage by direct viral effect is expected to be a sign of severity. It is also surprising that only feet are affected.
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NewsBot · Aug 19, 2020

Negative tests for SARS‐CoV‐2 infection do not rule out its responsibility for chilblains
G. Battesti V. Descamps
13 August 2020 https://doi.org/10.1111/bjd.19483

We read with great interest the report of Le Cleach et al discussing chilblains as a manifestation of COVID‐19 pandemic. They reported 311 patients with acral lesions occurring during the COVID‐19 lockdown in France. The most frequent clinical presentation of these acral lesions was typical chilblains. Among the 150 patients with RT‐PCR testing and/or serology, only 10 had confirmed COVID‐19. They concluded that there is no evidence of SARS‐CoV‐2 infection in the large majority of patients with acral lesions. They hypothesized that the situation could be due to the media stating that chilblains were caused by SARS‐CoV‐2 infection and leading to a higher rate of consultation or the lockdown leading to more inactivity and long periods at home barefoot on a cold floor1.
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NewsBot · Aug 22, 2020

Response to “No evidence of SARS‐CoV‐2 infection by PCR or serology in children with pseudochilblain”
S. Recalcati S. Tonolo F. Luzzaro F. Fantini
16 August 2020

We read with interest the article by Caselli D et al., reporting a case series of 38 children with chilblain‐like lesions (CLL). Testing for SARS‐CoV‐2, including PCR, rapid test serology and ELISA method for IgA and IgG antibodies yielded negative results in all cases. They concluded that their data do not allow them to support the relationship of CLL with SARS‐CoV‐2 infection. So far, data in the literature studying CLL documented a very low percentage of laboratory confirmed SARS‐CoV‐2. However, Colmenero and colleagues were able to detect SARS‐CoV‐2 in endothelial cells of cutaneous chilblain lesions by immunohistochemistry methods in 7 pediatric patients with negative nasopharyngeal swabs.
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NewsBot · Aug 25, 2020

Chilblains in COVID-19 Infection
Vinuta Mohan and Robert Lind
Cureus. 2020 Jul; 12(7): e9245.

COVID-19 has quickly become a worldwide pandemic and is well-known for its pulmonary complications. Dermatologic manifestations such as chilblain-like lesions have been recently described, but it is unclear if they are truly secondary to the infection or not. Here we describe a young patient who developed chilblain-like eruptions on his toes, likely secondary to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We discuss the literature that supports the hypothesis that these are in fact secondary to the infection, as well as provide insight into the pathology of these lesions.
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NewsBot · Aug 25, 2020

Similarities in Cutaneous Histopathological Patterns between COVID-19-positive and COVID-19 High-risk Patients with Skin Dermatosis
Raffaele Gianotti, Antonella Coggi, Francesca Boggio, Giovanni Fellegara
Acta Derm Venereol. 2020 Aug 12

Only recently histopathological studies of patients with dermatosis and concomitant SARS-Cov-2 viral infection were published. Seven months into the COVID-19 pandemic, more skin biopsies of COVID-19 positive patients are taking place. We examined the histological features of 30 skin biopsies from two groups of patients: Ten specimens of patients tested positive for COVID-19 with an active systemic infection and associated dermatosis. Twenty specimens were from patients not considered COVID-positive (due to PCR swab negativity or not tested at all) with cutaneous lesions either showing viral infection symptoms (fever, cough, ageusia and severe immunocompromised condition due to HIV infection and malignancies), or presented a high risk of being infected (such as cohabitation with COVID-19 positive parents and siblings with simultaneous chilblains). This study analyses the histological and immunohistochemical (SARS-CoV-2 2019-nCoV nucleocapsid antibody) characteristics of the two groups and identifies 4 histopathological patterns. The histopathological features of the two groups present similar features that may help to identify an ongoing COVID-19 infection even in asymptomatic carriers with dermatosis.
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Chilblains and Covid-19 (Covid Toes)

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