Chilblain-like lesions and COVID-19 infection: A prospective observational study at Spain's ground zero

Feito-Rodríguez, M.; Mayor-Ibarguren, Ander; Cámara-Hijón, Carmen; Montero-Vega, Dolores; Servera-Negre, Guillermo; Ruiz‐Bravo, Elena; Nozal, Pilar; Rodríguez‐Peralto, José Luis; Enguita, Ana B.; Bravo‐Gallego, Luz Yadira; Granados-Fernández, Marí; Fernández-Alcalde, Celia; Fernández-Heredero, A.; Alonso-Riaño, Marina; Jiménez‐Yuste, Víctor; Nuño-González, Almudena; Lucas-Laguna, R. de; López‐Granados, Eduardo; Pinto, Pedro Herranz

doi:10.1016/j.jaad.2020.09.086

Cited by 9 publications

(11 citation statements)

References 5 publications

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“…In the meta‐analysis pooling prevalence estimates for any positive COVID‐19 diagnostic test in patients with CLL, four studies were excluded: two for not specifying the number of patients with CLL who were diagnosed with COVID‐19 (by PCR and/or serology), 12,35 and two for not performing either test or not specifying how many tests were done 19,23 . The pooled prevalence of patients with CLL who were diagnosed with a SARS‐CoV‐2 infection by PCR and/or serology was 15.2% (95% CI, 10.4–20.7%; Fig.…”

Section: Resultsmentioning

confidence: 99%

“…This would contribute to the clearance of the virus prior to production of immunoglobulins, leading to failed serological detection 41–43 . The up‐regulation of the IFN‐1 pathway would cause severe microangiopathy and trigger the generation of CLL in patients with a genetic predisposition 35,44 . However, the absence of cutaneous or extra‐cutaneous symptoms in other interferonopathies raises unanswered questions around this hypothesis 41 …”

Section: Discussionmentioning

confidence: 99%

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Are the chilblain‐like lesions observed during the COVID‐19 pandemic due to severe acute respiratory syndrome coronavirus 2? Systematic review and meta‐analysis

Sánchez-García

Hernández-Quiles

de-Miguel-Balsa

et al. 2021

Acad Dermatol Venereol

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The expansion of the COVID‐19 pandemic has been accompanied by numerous reports of chilblain‐like lesions (CLL) in different countries; however, the pathogenesis of these lesions is still unclear. This systematic review and meta‐analysis aimed to assess the prevalence of COVID‐19 (diagnosed using PCR and/or serology) in patients with CLL. We undertook a literature search in PubMed, Embase, and Scopus (to 15 March 2021), including studies that reported on the number of patients with CLL with positive PCR and/or serology for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) or with a clinical suspicion of COVID‐19. Regardless of data heterogeneity, a random‐effects model was used to pool prevalence estimates. The meta‐analysis included 63 original studies, involving 2919 cases of CLL. A subgroup of these patients underwent diagnostic tests for COVID‐19 (PCR: n = 1154, 39.5%; serology: n = 943, 32.3%). The pooled prevalence of COVID‐19 in the overall sample and in the subgroup who were tested for COVID‐19 was, respectively: (i) positive PCR: 2.6% [95% confidence interval (CI) 1.9% to 3.4%] and 5.5% (95% CI, 3.7–7.7%); (ii) positive serology for SARS‐CoV‐2: 7.2% (95% CI, 4.7–10.2%) and 11.8% (95% CI, 7.9–16.3%); and (iii) positive PCR and/or serology, 15.2% (95% CI, 10.4–20.7%) and 7.5% (95% CI, 5.1–10.3%). Altogether, a small proportion of diagnostic tests for SARS‐CoV‐2, both PCR and serologies, show positive results in patients with CLL.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Are the chilblain‐like lesions observed during the COVID‐19 pandemic due to severe acute respiratory syndrome coronavirus 2? Systematic review and meta‐analysis

Sánchez-García

Hernández-Quiles

de-Miguel-Balsa

et al. 2021

Acad Dermatol Venereol

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“…As widely reported in the literature, 5,6,13‐15 our sample involved young patients, all from the geographic area of Bergamo; many of them reported non‐specific flulike symptomatology for an average of 30 days before the onset of skin manifestations and/or a positive history of close contact with suspected or confirmed cases of COVID‐19 14 days prior to symptoms onset. These epidemiological observations led us to suspect that the systemic symptoms, when present, could be considered indicative of mild COVID‐19, and that the skin manifestations could represent a late expression of the same condition.…”

Section: Discussionmentioning

confidence: 99%

“…Laboratory assessments for COVID‐19 were not possible for most of our cases; only 3 patients were tested for SARS‐CoV‐2 RT‐PCR on nasopharyngeal swabs, with only one positive, and none for SARS‐CoV‐2 serum antibody detection. Even in the literature, there is a limited number of cases with ChLL tested, with positive serologic results ranging from 8.1% 6 to 30% 16,18 and with positive nasopharyngeal swabs in lower percentages 19,20 …”

Section: Discussionmentioning

confidence: 99%

“…The possible cutaneous manifestations of SARS‐CoV‐2 infection are varied and are still being characterized 1‐4 . Chilblain‐like lesions (ChLL) were increasingly reported worldwide during the first peak of the COVID‐19 pandemic; they generally affected children and young adults, paucisymptomatic or asymptomatic, many of whom tested negative for both SARS‐CoV‐2 by PCR on nasopharyngeal swab and anti‐SARS‐CoV‐2 antibodies on blood samples 5,6 . Despite the large number of reports of ChLL, a definitive causal link with SARS‐CoV‐2 infection has not yet been established, and it has been mainly speculated in relation to the epidemiological context and the unusual onset in spring 7 .…”

Section: Introductionmentioning

confidence: 99%

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RNAscope in situ hybridization and RT‐PCR for detection of SARS‐CoV‐2 in chilblain‐like lesions: A clinical, laboratory and histopathological study

Test

Sena

Locatelli

et al. 2022

Pediatric Dermatology

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Background Since the beginning of the coronavirus disease 2019 (COVID‐19) pandemic, an increasing number of chilblain‐like lesions (ChLL) have been increasingly reported worldwide. To date, the causal link between ChLL and SARS‐CoV‐2 infection has not been unequivocally established. Methods In this case series, we present demographic, clinical, laboratory, and histopathological information regarding 27 young patients with a clinical diagnosis of ChLL who referred to the Dermatology Unit of Papa Giovanni XXIII Hospital, Bergamo, Italy, from 1 April 2020 to 1 June 2020. Results The mean age was 14.2 years, and 21 patients (78%) experienced mild systemic symptoms a median of 28 days before the onset of cutaneous lesions. ChLL mostly involved the feet (20 patients – 74%). Among acral lesions, we identified three different clinical patterns: (i) chilblains in 20 patients (74%); (ii) fixed erythematous macules in 4 children (15%); (iii) erythrocyanosis in 3 female patients (11%). Blood examinations and viral serologies, including parvovirus B19, cytomegalovirus (CMV), Epstein‐Barr virus (EBV), and coxsackievirus were normal in all. Three patients (11%) underwent nasopharyngeal swab for RT‐PCR for SARS‐CoV‐2 showing only 1 positive. Histopathological examinations of 7 skin biopsies confirmed the clinical diagnosis of chilblains; vessel thrombi were observed only in 1 case. Our findings failed to demonstrate the direct presence of SARS‐CoV‐2 RNA in skin biopsies, both with real‐time polymerase chain reaction (RT‐PCR) and RNAscope in situ hybridization (ISH). Limitations Limited number of cases, unavailability of laboratory confirmation of COVID‐19 in all patients, potential methodological weakness, and latency of skin biopsies in comparison to cutaneous lesions onset. Conclusions These observations may support the hypothesis of an inflammatory pathogenesis rather than the presence of peripheral viral particles. Although, we could not exclude an early phase of viral endothelial damage followed by an IFN‐I or complement‐mediated inflammatory phase. Further observations on a large number of patients are needed to confirm this hypothesis.

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Epidemiology and clinical evolution of non-multisystem inflammatory syndrome (MIS-C) dermatological lesions in pediatric patients affected by SARS-CoV-2 infection: A systematic review of the literature

et al. 2022

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COVID-19 can present with a range of skin manifestations, some of which specific of the pediatric age. The aim of this systematic literature review was to determine the type, prevalence, time of onset, and evolution of cutaneous manifestations associated with COVID-19 in newborns, children, and adolescents, after excluding multisystem inflammatory syndrome in children (MIS-C). PubMed, Tripdatabase, ClinicalTrials, and Cochrane Library databases were searched using an ad hoc string for case reports/series and observational studies, published between December 2019 and February 2022. Study quality was assessed using the STROBE and CARE tools. Seventy-three (49 case reports/series and 24 studies) out of 26,545 identified articles were included in the analysis. Dermatological lesions were highly heterogeneous for clinical presentation, time of onset, and association with other COVID-19 manifestations. Overall, they mainly affected the acral portions, and typically presented a favorable outcome. Pseudo-chilblains were the most common. Conclusions : Mucocutaneous manifestations could be the only/predominant and early manifestation of COVID-19 that could precede other more severe manifestations by days or weeks. Therefore, physicians of all disciplines should be familiar with them. What is Known: • A variety of cutaneous manifestations have been reported in association with COVID-19. • Urticaria, maculopapular, or vesicular rashes can occur at any age, while chilblains and erythema multiforme are more common in children and young patients. What is New: • Skin lesions related to SARS-CoV-2 infection often show a peculiar acral distribution. • Mucocutaneous lesions of various type may be the only/predominant manifestation of COVID-19; they could present in paucisymptomatic and severely ill patients and occur at different stages of the disease. Supplementary Information The online version contains supplementary material available at 10.1007/s00431-022-04585-7.

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Chilblain-like lesions and COVID-19 infection: A prospective observational study at Spain's ground zero

Cited by 9 publications

References 5 publications

Are the chilblain‐like lesions observed during the COVID‐19 pandemic due to severe acute respiratory syndrome coronavirus 2? Systematic review and meta‐analysis

Are the chilblain‐like lesions observed during the COVID‐19 pandemic due to severe acute respiratory syndrome coronavirus 2? Systematic review and meta‐analysis

RNAscope in situ hybridization and RT‐PCR for detection of SARS‐CoV‐2 in chilblain‐like lesions: A clinical, laboratory and histopathological study

Epidemiology and clinical evolution of non-multisystem inflammatory syndrome (MIS-C) dermatological lesions in pediatric patients affected by SARS-CoV-2 infection: A systematic review of the literature

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