Chilblains-like Nonischemic Eruption During the COVID-19 Pandemic—Distinct Features in Adolescents | Adolescent Medicine | JAMA Network Open | JAMA Network
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Invited Commentary
Pediatrics
June 10, 2021

Chilblains-like Nonischemic Eruption During the COVID-19 Pandemic—Distinct Features in Adolescents

Author Affiliations
  • 1Department of Dermatology, University of California, Davis
  • 2Kaiser Permanente, South Sacramento Medical Center, Sacramento, California
JAMA Netw Open. 2021;4(6):e2111676. doi:10.1001/jamanetworkopen.2021.11676

COVID-19 has affected the entire world in many ways, and cutaneous eruptions during the illness are being reported extensively. At the beginning of the pandemic, it was widely suggested that so-called COVID toes were a late manifestation of COVID-19, caused by a delayed immune response to SARS-CoV-2 exposure. Later reports showed more conflicting results, questioning the direct association between chilblains-like eruptions and COVID-19. A case-control study of patients with or without chilblains showed a more than 3-fold higher odds of having positive immunoglobin G antibodies against the receptor-binding domain of SARS-CoV-2 spike protein among patients with chilblains (OR = 3.4; P = .01).1 Conversely, other reports, such as that by Herman et al,2 failed to show any evidence of such an association. Overall, most reports have not provided a clear conclusion on this matter, and there is no definitive conclusion on the causality of COVID-19 with a chilblains-like rash.

Elsewhere in JAMA Network Open, Discepolo et al3 describe distinct features in 17 adolescents, characterized by distal acral chilblains-like involvement during COVID-19. In their prospective study, they reported clinical, dermoscopic, and pathological features of the included patients, who showed a great degree of homogeneity.

The authors3 designed a small case series study and found this presentation likely to be independent of COVID-19, using polymerase chain reaction testing and antibody levels of immunoglobin M and G. A counterargument could be that conducting the antibody testing at the time of enrollment did not leave enough time for antibody development after a possible COVID-19 infection. There are no universally used antibody testing kits for COVID-19, thus leading to questions about the accuracy of the tests in different studies and, more importantly, the timing of antibody tests, which could falsely produce negative results if performed too early.

Discepolo et al3 used capillaroscopy, which is not commonly used in clinical practice, to investigate structural changes in peripheral microcirculation. A recent correspondence4 mentioned the importance of capillaroscopy in characterizing chilblain-like eruptions in patients with COVID-19. The lack of capillaroscopic features of a major vasculopathic event in the study by Discepolo et al3 argues against the ischemic nature of this disease and, thus, indicates that this presentation is not associated with systemic ischemia or an embolic event. These findings were further confirmed by laboratory tests.

Another distinct finding in the study by Discepolo et al3 is the dermoscopic triad of red dots, white rosettes, and white streaks on an erythematous background in the included patients. It would be informative to compare adolescents with this presentation to adults with similar disease and investigate whether the same dermoscopic features are present.

Another hallmark of this study is the finding of heel lesions in 7 patients (41%). This is not a classic presentation for chilblains and raises the possibility of a different pathophysiology. This is in alignment with previous reports of heel involvement in chilblains-like lesions in patients with COVID-19.5 Furthermore, the pathological features were not completely aligned with classic features of chilblains. Regardless of the causality between COVID-19 and acral lesions, they could be considered a secondary chilblains-like symptom with COVID-19, similar to other comorbidities, such as lupus, that can cause chilblains-like disease. In a systematic review and meta-analysis of individual patient-level data, Lee et al6 showed that chilblains-like rash and livedoid or ischemic rash are the fourth and fifth most common cutaneous presentations, respectively, among patients with COVID-19. Additionally, using a multivariate binary logistic regression analysis for the outcome of severe COVID-19, they concluded that the presence of livedoid or acroischemic lesions was associated with a high likelihood of severe COVID-19 (odds ratio, 31.94; 95% CI, 6.28-162.31, P < .001). In complete contrast, the presence of chilblains-like lesions was associated with a much lower chance of severe COVID-19 (odds ratio, 0.04; 95% CI, 0.003-0.68, P = .02). Hence, it is vital not to use these terms interchangeably. Interestingly, Lee et al6 also suggested that patients with chilblains-like rash were more likely to have an otherwise asymptomatic COVID-19 infection compared with those with other cutaneous presentations. This aligns with the study by Discepolo et al3 and other reports.

The classic histopathological presentation of chilblains includes superficial and deep perivascular lymphoid infiltrate, what is known as fluffy edema and the expansion of vessel walls without fibrin deposition that are more prominent in deep dermal vascular structures, and papillary dermal edema. Eosinophils can be present in early lesions. Fibrinoid changes and thrombosis are not classic findings. In the study by Discepolo et al,3 12 patients (71%) underwent punch biopsy procedures, which mostly showed endothelial hyperplasia, mild lymphocytic infiltrate and vessels’ architecture disruption with no papillary dermal edema, or eosinophilic or neutrophilic infiltrate. Additionally, the pathology did not show ischemic changes, which further argues against systemic vasculopathy. Thus, this study3 provides further evidence against the thromboembolic nature of the presented pattern in adolescents during the COVID-19 pandemic.

The time to resolution for the cutaneous lesions varied widely and took as long as 145 days in included patients. More than 40% relapsed during colder seasons. These findings show the chronicity of this presentation. Overall, this study has characterized chilblains-like changes to be milder than classic chilblains in adolescents.

It would be valuable to investigate further questions about environmental factors. A larger study would help us answer other important questions. For example, do adolescents tend to walk barefoot? What were the average temperatures of their houses during the pandemic in each season, and do temperature changes correlate with the prevalence of this disease? Is this disease associated with sex or race/ethnicity? Why is this unique presentation more common in adolescents? We need to characterize chilblains-like disease during the COVID-19 pandemic further in a larger study with appropriate controls and differentiate it from similar cutaneous presentations in adults and in patients during the post–COVID-19 era.

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Article Information

Published: June 10, 2021. doi:10.1001/jamanetworkopen.2021.11676

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2021 Gorouhi F. JAMA Network Open.

Corresponding Author: Farzam Gorouhi, MD, Kaiser Permanente, South Sacramento Medical Center, 6600 Bruceville Rd, Sacramento, CA 95835 (gorouhif@gmail.com).

Conflict of Interest Disclosures: None reported.

References
1.
Ortega-Quijano  D, Fernandez-Nieto  D, Jimenez-Cauhe  J,  et al.  Association between COVID-19 and chilblains: a case-control study.   J Eur Acad Dermatol Venereol. 2021. doi:10.1111/jdv.17195PubMedGoogle Scholar
2.
Herman  A, Peeters  C, Verroken  A,  et al.  Evaluation of chilblains as a manifestation of the COVID-19 pandemic.   JAMA Dermatol. 2020;156(9):998-1003. doi:10.1001/jamadermatol.2020.2368PubMedGoogle ScholarCrossref
3.
Discepolo  V, Catzola  A, Pierri  L,  et al.  Bilateral chilblain-like lesions of the toes characterized by microvascular remodeling in adolescents during the COVID-19 pandemic.   JAMA Netw Open. 2021;4(6):e2111369. doi:10.1001/jamanetworkopen.2021.11369Google Scholar
4.
Mehta  P, Bunker  CB, Ciurtin  C,  et al.  Chilblain-like acral lesions in long COVID-19: management and implications for understanding microangiopathy.   Lancet Infect Dis. Published online March 8, 2021.PubMedGoogle Scholar
5.
Landa  N, Mendieta-Eckert  M, Fonda-Pascual  P, Aguirre  T.  Chilblain-like lesions on feet and hands during the COVID-19 pandemic.   Int J Dermatol. 2020;59(6):739-743. doi:10.1111/ijd.14937PubMedGoogle ScholarCrossref
6.
Lee  DS, Mirmirani  P, McCleskey  PE, Mehrpouya  M, Gorouhi  F.  Cutaneous manifestations of COVID-19: a systematic review and analysis of individual patient-level data.   Dermatol Online J. 2020;26(12):13030/qt7s34p8rw. doi:10.2139/ssrn.3677917PubMedGoogle Scholar
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