COVID 19-associated chilblain-like acral lesions among children and adolescents: an Italian retrospective, multicenter study.

BACKGROUND: Since the COVID-19 pandemic started, great interest has been given to this disease, especially to its possible clinical presentations. Besides classical respiratory symptoms, dermatological manifestations occur quite often among infected and non-infected patients, particularly in children. A prominent IFN-I response, that is generally higher in children compared to adults, may not only cause chilblain lesions, but it could also prevent infection and viral replication, thus justifying the negative swab results, as well as the absence of relevant systemic symptoms in positive cases. Indeed, reports have emerged describing chilblain-like acral lesions in children and adolescents with either proven or suspected infection. METHODS: Patients aged from 1 to 18 years old were enrolled in this study from 23 Italian dermatological units and were observed for an overall period of 6 months. Clinical pictures were collected along with data on the location and duration of skin lesions, their association with concomitant local and systemic symptoms, presence of nail and/or mucosal involvement, as well as histological, laboratory and imaging findings. RESULTS: One hundred thirty-seven patients were included, of whom 56.9% were females. Mean age was 11.97±3.66 years. The most commonly affected sites were the feet (77 patients, 56.2%). Lesions (48.5%) featured cyanosis, chilblains, blisters, ecchymosis, bullae, erythema, edema, and papules. Concomitant skin manifestations included maculo-papular rashes (30%), unspecified rashes (25%), vesicular rashes (20%), erythema multiforme (10%), urticaria (10%) and erythema with desquamation (5%). Forty-one patients (29.9%) reported pruritus as the main symptom associated with chilblains, and 56 out of 137 patients also reported systemic symptoms such as respiratory symptoms (33.9%), fever (28%), intestinal (27%), headache (5.5%), asthenia (3.5%), and joint pain (2%). Associated comorbid conditions were observed in 9 patients presenting with skin lesions. Nasopharyngeal swabs turned out positive in 11 patients (8%), whereas the remainder were either negative (101, 73%) or unspecified (25, 18%). CONCLUSIONS: COVID-19 has been credited as the etiology of the recent increase in acro-ischemic lesions. The present study provides a description of pediatric cutaneous manifestations deemed to be potentially associated with COVID-19, revealing a possible association between acral cyanosis and nasopharyngeal swab positivity in children and teenagers. The identification and characterization of newly recognized patterns of skin involvement may aid physicians in diagnosing cases of asymptomatic or pauci-symptomatic COVID patients.

Chilblain-like lesions onset during SARS-CoV-2 infection in a COVID-19-vaccinated adolescent: case report and review of literature.

BACKGROUND: COVID toes or chilblain-like skin lesions have been widely reported during COVID-19 pandemic. Most cases were described in patients with negative microbiological tests for SARS-CoV-2, therefore the possible relationship with SARS-CoV-2 infection, as well as with the nowadays broadly available mRNA-based vaccination, has not been fully elucidated.  CASE PRESENTATION: We here describe the case of a 14-year-old male who developed chilblain-like skin eruptions during SARS-CoV-2 infection despite two mRNA-based vaccine doses and review the clinical and epidemiological characteristics of chilblain-like lesions as a cutaneous presentation of COVID-19 in children. CONCLUSIONS: Most children and adolescent with COVID toes have a mild or asymptomatic SARS-CoV-2 infection. Our report aims to highlight the possible onset of these skin lesions in vaccinated children, if infection has occurred, and the potential use of systemic corticosteroids as a first line treatment. Additional evidence is required to better understand SARS-CoV-2 infection and cutaneous manifestations in children and determine the relationship between chilblain-like lesions and COVID-19 vaccination.

Chilblains in immune-mediated inflammatory diseases: a review.

Chilblains were first described over a hundred years ago as cutaneous inflammatory lesions, typically on the digits, occurring on cold exposure. Chilblains can be primary, or secondary to a number of conditions such as infections, including COVID-19, and immune-mediated inflammatory disorders (IMIDs) with SLE being the commonest. Chilblain lupus erythematosus (CHLE) was first described in 1888 as cold-induced erythematous lesions before the terms 'chilblains' or 'perniosis' were coined. Diagnostic criteria exist for both chilblains and CHLE. Histopathologically, CHLE lesions show interface dermatitis with perivascular lymphocytic infiltrate. Immunofluorescence demonstrates linear deposits of immunoglobulins and complement in the dermo-epidermal junction. This narrative review focuses on chilblains secondary to immune-mediated inflammatory disorders, primarily the epidemiology, pathogenesis and treatment of CHLE.

Evolution of incidence of chilblain-like lesions in children during the first year of COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic has brought innumerable reports of chilblains. The relation between pernio-like acral eruptions and COVID-19 has not been fully elucidated because most reported cases have occurred in patients with negative microbiological tests for SARS-CoV-2. METHODS: A retrospective study of 49 cases of chilblains seen during the first year of the pandemic in a children's hospital in Madrid, Spain. The incidence of these skin lesions was correlated with the number of COVID-19 admissions and environmental temperatures. Patients were separated into two groups depending on the day of onset (strict lockdown period vs. outside the lockdown period). RESULTS: Most chilblains cases presented during the first and third waves of the pandemic, paralleling the number of COVID-19 admissions. The first wave coincided with a strict lockdown, and the third wave coincided with the lowest ambient seasonal temperatures of the year. Systemic symptoms preceding chilblains were more frequent in the first wave (45.8% vs. 8.0%, p = .002), as was the co-occurrence with erythema multiforme-like lesions (16.7% vs. 0%, p = .033). Laboratory test and skin biopsies were performed more frequently in the first wave (75.0% vs. 12.0%, p < .001; and 25.0% vs. 0%, p = .007; respectively). Five patients developed recurrent cutaneous symptoms. CONCLUSIONS: An increased incidence of chilblains coincided not only with the two major waves of the pandemic, but also with the strict lockdown period in the first wave and low seasonal temperatures during the third wave. Both increased sedentary behaviors and cold environmental temperatures may have played an additive role in the development of COVID-19-related chilblains.

Chilblain or perniosis-like skin lesions in children during the COVID-19 pandemic: A systematic review of articles.

COVID toes or chilblain-like skin lesions represent a widespread and specific skin presentation mostly in the feet that may be attributed to COVID-19 infection. They may last for several months. We conducted this study to investigate chilblain-like lesions in children during the COVID-19 pandemic, any predisposition, location, clinical course, and prognosis. We searched Google Scholar, Scopus, and Medline (PubMed) databases using the following keywords: "Coronavirus" OR "COVID-19" AND "Chilblains" OR "Pernio" OR "Perniosis" OR "Children" OR "Cutaneous" OR "skin." The inclusion criteria were: (a) Studies that described the specific vascular skin lesion. (b) Studies that included patients aged >1 month till 18 years. (c) Case reports, case series, retrospective or prospective cohort studies, case-control studies. A total of 28 articles were included. The total number of children with chiblain-like lesions (CLL) was 433. The mean age of children presenting CLL during the COVID-19 pandemic was estimated as 12.58 ± 2.15. Of note, 53.6% of them were male. The nasopharyngeal SARS-CoV-2 RT-PCR test and anti-SARS-CoV-2 antibodies were mostly negative for the virus. In conclusion, it is crucial to be familiar with various presentations of COVID-19 infection and their clinical significance to approach the earliest diagnosis, immediate treatment, estimate the prognosis, and finally isolate the patients to prevent spreading. Chilblain-like lesions as a possible cutaneous presentation of COVID-19 in children may last several months with the indolent course.

Prognosis of rash and chilblain-like lesions among outpatients with COVID-19: a large cohort study.

In a large regional observational cohort study of adult (≥ 18 years), outpatients with COVID-19, prevalence, characteristics, and outcome of patients with rash and/or chilblain-like lesions (CLL), compared with population without cutaneous features, were studied. In total, 28,957 outpatients were included; the prevalence of rash and CCL were 9.5% and 3.7%, respectively. Presence of rash was significantly associated with presence of asthenia, shivers or myalgia, respiratory and gastro-intestinal symptoms, and anosmia/ageusia. The presence of CCL was associated with chest pain, chest oppression, nausea/vomiting, and anosmia/ageusia. Patients with CCL were significantly less prone to an unfavourable outcome (hospitalization or death).

A clinicopathological description of COVID-19-induced chilblains (COVID-toes) correlated with a published literature review.

BACKGROUND: The abundance of publications of COVID-19-induced chilblains has resulted in a confusing situation. METHODS: This is a prospective single-institution study from 15 March to 13 May 2020. Thirty-two patients received PCR nasopharyngeal swabs. Of these, 28 patients had a thoracic CT-scan, 31 patients had blood and urine examinations, 24 patients had skin biopsies including immunohistochemical and direct immunofluorescence studies, and four patients had electron microscopy. RESULTS: COVID-19-induced chilblains are clinically and histopathologically identical to chilblains from other causes. Although intravascular thrombi are sometimes observed, no patient had a systemic coagulopathy or severe clinical course. The exhaustive clinical, radiological, and laboratory work-up in this study ruled-out other primary and secondary causes. Electron microscopy revealed rare, probable viral particles whose core and spikes measured from 120 to 133 nm within endothelium and eccrine glands in two cases. CONCLUSION: This study provides further clinicopathologic evidence of COVID-19-related chilblains. Negative PCR and antibody tests do not rule-out infection. Chilblains represent a good prognosis, occurring later in the disease course. No systemic coagulopathy was identified in any patient. Patients presenting with acral lesions should be isolated, and chilblains should be distinguished from thrombotic lesions (livedo racemosa, retiform purpura, or ischemic acral necrosis).

"COVID Toes" in Three Siblings.

Dermatologists reported an outbreak of pernio (red to purple swollen painful toes) during the COVID-19 pandemic. Most subjects lacked positive CoV-19 polymerase chain reaction (PCR) or antibodies or a preceding illness. The dermatologists termed the illness "COVID toes." Pernio usually affects adults versus "COVID toes" usually children. Pernio is preceded by a clear history of exposure to wet and cold. Patients with "COVID toes" lack this history. Also, it is not unusual for multiple family members to have "COVID toes." Our case report describes "COVID toes" in an 18-year-old with no preceding illness, a negative SARS-CoV-19 PCR, and an initially negative SARS-CoV-19 antibody, and also his 2 siblings also developed "COVID toes." In our index case, repeat SARS-CoV-19 antibodies were positive. Seroconversion has rarely been reported in patients with "COVID toes." Why most "COVID toes" patients lack a clinical history of COVID-19 and are SARS-CoV-19 PCR and antibody negative is a mystery.

Perniosis in the COVID-19 era.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) and the most common symptoms include fever, dry cough, dyspnea, fatigue, anorexia, ageusia, and anosmia. Cutaneous manifestations are less common and we share our experience with an otherwise healthy and asymptomatic young man. The patient presented with painless acrocynosis of the left toes which progressed to desquamation by day 16 of disease onset. Disease progression is documented via multiple photographs that portray progression of disease and subsequent resolution over approximately six weeks. Symptomatic treatment included non-steroidal anti-inflammatory medications, leg elevation, and warm compresses.

Bilateral Chilblain-like Lesions of the Toes Characterized by Microvascular Remodeling in Adolescents During the COVID-19 Pandemic.

Importance: Chilblain-like lesions have been one of the most frequently described cutaneous manifestations during the COVID-19 pandemic. Their etiopathogenesis, including the role of SARS-CoV-2, remains elusive. Objective: To examine the association of chilblain-like lesions with SARS-CoV-2 infection. Design, Setting, and Participants: This prospective case series enrolled 17 adolescents who presented with chilblain-like lesions from April 1 to June 30, 2020, at a tertiary referral academic hospital in Italy. Main Outcomes and Measures: Macroscopic (clinical and dermoscopic) and microscopic (histopathologic) analysis contributed to a thorough understanding of the lesions. Nasopharyngeal swab, serologic testing, and in situ hybridization of the skin biopsy specimens were performed to test for SARS-CoV-2 infection. Laboratory tests explored signs of systemic inflammation or thrombophilia. Structural changes in peripheral microcirculation were investigated by capillaroscopy. Results: Of the 17 adolescents (9 [52.9%] male; median [interquartile range] age, 13.2 [12.5-14.3] years) enrolled during the first wave of the COVID-19 pandemic, 16 (94.1%) had bilaterally localized distal erythematous or cyanotic lesions. A triad of red dots (16 [100%]), white rosettes (11 [68.8%]), and white streaks (10 [62.5%]) characterized the dermoscopic picture. Histologic analysis revealed a remodeling of the dermal blood vessels with a lobular arrangement, wall thickening, and a mild perivascular lymphocytic infiltrate. SARS-CoV-2 infection was excluded by molecular and serologic testing. In situ hybridization did not highlight the viral genome in the lesions. Conclusions and Relevance: This study delineated the clinical, histologic, and laboratory features of chilblain-like lesions that emerged during the COVID-19 pandemic, and its findings do not support their association with SARS-CoV-2 infection. The lesions occurred in otherwise healthy adolescents, had a long but benign course to self-resolution, and were characterized by a microvascular remodeling with perivascular lymphocytic infiltrate but no other signs of vasculitis. These results suggest that chilblain-like lesions do not imply a concomitant SARS-CoV-2 infection. Ongoing studies will help clarify the etiopathogenic mechanisms.

Cutaneous Manifestations of COVID-19 in the Inpatient Setting.

Cutaneous findings have increasingly been reported in patients with coronavirus disease 2019 (COVID-19). This review discusses associated skin findings in patients with COVID-19 in the inpatient setting, ranging from vasculopathy-related lesions associated with high hospitalization rate and poor prognosis to inflammatory vesicular and urticarial eruptions that are rarely associated with prolonged hospitalization. We also discuss other reported COVID-19 cutaneous manifestations such as Sweet's syndrome, purpuric eruptions, and Multisystem Inflammatory Syndrome in Children. Although the relationship between dermatologic changes and COVID-19 disease progression is not fully elucidated, familiarity with cutaneous manifestations is valuable for physicians caring for patients hospitalized with COVID-19 and may help improve disease recognition and care.

COVID-19 Toes and Other Skin Lesions During the Pandemic: Emerging Entities?

There is accumulating evidence to indicate an association between coronavirus infectious disease 2019 (COVID-19) and clusters of incident cutaneous eruptions. Of these, chilblains-like perniosis have received widespread medical and media attention. These typically affect the toes, and have been called "COVID-toes." Other acral lesions such as large bullae have also been reported. However, a definitive causal relationship with the severe acute respiratory syndrome coronavirus 2 has not yet been definitively proven, nor has a pathogenic mechanism been established. These episodes are self-limiting, but we need to know whether long-term sequelae exist.