COVID-19-associated dermatologic manifestations

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Nuha Al-Howthi, MD[2] Ogechukwu Hannah Nnabude, MD

Overview

COVID-19 infections is caused by the novel corona virus or also known as SARS-2 virus. The disease is believed to incline towards respiratory organs due to the high expression of ACE receptors. However, skin rashes have been uncommonly described in patients with COVID-19 infection. Dermatologic manifestations of COVID-19 include an erythematous exanthem (including a lacy pattern and a petechial, dengue-like rash), livedo reticularis, cutaneous vasculitis acute urticaria, chickenpox-like blisters.

Pathophysiology

• The exact mechanisms of COVID-19 induced cutaneous manifestations are not yet well known,
• The viral particles present in the cutaneous blood vessels could lead to a lymphocytic vasculitis.
• Keratinocytes may be a secondary target after Langerhans cells activation.
• Immune response to infection leads to Langerhans cells activation, resulting in a state of vasodilation and spongiosis.
• Microthrombosis and DIC originating in other organs results in livedo reticularis.
  • Hypoxia-related accumulation of deoxygenated blood in blood vessels.
  • Vasculopathy with deposition of C5b-9 and C4d.

Histology

On microscopic histopathological analysis characteristic findings of dermatologic manifestations of COVID-19 include:

• Classic dyskeratotic cells
• Ballooning multinucleated cells
• Sparse necrotic keratinocytes with lymphocytic satellitosis
• Parakeratosis
• Acanthosis
• Pseudo-herpetic features

Differentiating COVID-19 Dermatologic manifestations with other Diseases

• COVID-19 can present with a rash and be mistaken for Dengue.

Epidemiology and Demographics

• The incidence of dermatologic manifestations with COVID-19 infections increases with age; the median age at diagnosis is 53 years.
• Males are more commonly affected than females.

History and Symptoms

• The timing of skin lesions depends on various factors and not really known but 3 days before diagnosis to 13 days after diagnosis.
• The most common cutaneous manifestation of COVID-19 is a maculopapular exanthem (morbilliform).
• The other cutaneous manifestations included:
  • Papulovesicular rash
  • Urticaria
  • Painful acral red purple papules
  • Livedo reticularis lesions
  • Petechiae
  • Acral eruption of erythemato‐violaceous papules and macules, with possible bullous evolution, or digital swelling.
• Majority of lesions were localized on the trunk, however, some patients experienced cutaneous manifestations in the hands and feet.
• Skin lesion development occurred before the onset of respiratory symptoms or COVID-19 diagnosis in 12.5% (9/72) of the patients, and lesions spontaneously healed in all patients within 10 days.
• Majority of the studies reported no correlation between COVID-19 severity and skin lesions.

Lesions may be classified as acral areas of erythema with vesicles or pustules (Pseudo‐chilblain) (19%), other vesicular eruptions (9%), urticarial lesions (19%), maculopapular eruptionThe most common cutaneous manifestation of COVID-19 was found to be maculopapular exanthem (morbilliform), presenting in 36.1% (26/72) patients. The other cutaneous manifestations included: a papulovesicular rash (34.7%, 25/72), urticaria (9.7%, 7/72), painful acral red purple papules (15.3%, 11/72) of patients, livedo reticularis lesions (2.8%, 2/72) and petechiae (1.4%, 1/72). Majority of lesions were localized on the trunk (66.7%, 50/72), however, 19.4% (14/72) of patients experienced cutaneous manifestations in the hands and feet. Skin lesion development occurred before the onset of respiratory symptoms or COVID-19 diagnosis in 12.5% (9/72) of the patients, and lesions spontaneously healed in all patients within 10 days. Majority of the studies reported no correlation between COVID-19 severity and skin lesions. Lesions s (47%) and livedo or necrosis (6%). Vesicular eruptions appear early in the course of the disease (15% before other symptoms). The pseudo‐chilblain pattern frequently appears late in the evolution of the COVID‐19 disease (59% after other symptoms), while the rest tend to appear with other symptoms of COVID‐19. Severity of COVID‐19 shows a gradient from less severe disease in acral lesions to most severe in the latter groups. Results are similar for confirmed and suspected cases, both in terms of clinical and epidemiological findings. Alternative diagnoses are discussed but seem unlikely for the most specific patterns (pseudo‐chilblain and vesicular).

COVID-19 Toes

“COVID TOES” and Other Skin Changes of COVID-19 There have been many reports that the COVID-19 virus can have effects on the skin. The first official reports came out of Italy and were published in March 2020 that about 20% of patients with COVID-19 were experiencing skin issues. The skin changes related to COVID-19 can look many different ways, and we are learning more about this almost on a daily basis. There have been reports of the following skin changes with COVID-19: “Covid toes” (or covid hands) – similar to the type of cold related changes we have seen in the feet of people for many years, but often occurring in places where the conditions are not cold and damp. These seem to happen more commonly in younger patients. Rash with our without small blisters Widespread hives (urticaria) Small bruises and broken blood vessels (petechiae) Although these skin findings are not currently listed as symptoms to look out for that should make you consider getting tested for COVID-19, you may want to add them to your list of things to look out for. As time goes on, we will likely have more information about why these skin changes happen with COVID-19 and when in the timing of exposure to the virus do they seem to occur.

chilblain‐like lesions

the lesion was red–purple papules on the dorsal aspect of the fingers on both hands and diffused erythema in the subungual area of thumb.

• in Qater,two cases of COVID‐19 presenting with cutaneous lesions, specifically, chilblain‐like lesions.
• Hunt and Koziatek reported a case of COVID‐19 presenting with fever and morbilliform rash as the primary presenting symptoms.

• while Joob and Wiwanitkit reported a case of COVID‐19 presenting initially with a petechial skin rash in Thailand.
• pathophysiology
  • Degeneration and necrosis of parenchymal cells and formation of hyaline thrombi in small vessels were observed in lung and other organs.

Acute acro-ischemia in the child

• the presentations of acro-ischemia including finger/toe cyanosis, skin bulla and dry gangrene.

• Mazzotta and Troccoli reported a few dozen cases, initially presenting with red–purple papules on the feet and hands, which either evolved into haemorrhagic bullae or developed a blackish crust.
• they could be the expression of secondary microthrombosis due to endothelial damage and vascular disorders.
• lab results:
  • D-dimer, fibrinogen and fibrinogen degradation product (FDP) were significantly elevated in most patients.
  • Prothrombin time was prolonged in 4 patients. D-dimer and FDP levels progressively elevated consistent with COVID-2019 exacerbation.
  • Four patients were diagnosed with disseminated intravascular coagulation (DIC) .
  • Low molecular weight heparin (LMWH) was administrated in 6 patients, which reduced D-dimer and FDP rather than improved clinical symptoms.

References

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5. Joob B, Wiwanitkit V. COVID-19 can present with a rash and be mistaken for dengue. J Am Acad Dermatol. 2020;82(5):e177.https://doi.org/10.1016/j.jaad.2020.03.036

6. Hoehl S, Rabenau H, Berger A, et al. Evidence of SARS-CoV-2 infection in returning travelers from Wuhan, China. N Engl J Med. 2020;382(13):1278-1280.

7.https://dermatology.ca/public-patients/covid-19-patient-updates/ Ryan Rivera-Oyola, MS, Merav Koschitzky, BA, Rachel Printy, PA-C, Stephanie Liu, DO, MBA, Roselyn Stanger, MD, Alexandra K. Golant, MD, and Mark Lebwohl, MD (2020)."Dermatologic findings in 2 patients with COVID-19" https://doi.org/10.1016/j.jdcr.2020.04.027

8.Yan Ling Apollonia Tay, Medical Student, University of Otago, Wellington, New Zealand. DermNet NZ Editor in Chief: Adjunct A/Prof Amanda Oakley, Dermatologist, Hamilton, New Zealand. Copy edited by Gus Mitchell. March 2020. Reviewed by Dr Louise Reiche, Dermatologist, Palmerston North, New Zealand. Latest update 12 June 2020. "COVID-19 and dermatology patients" https://dermnetnz.org/topics/covid-19/

9.https://www.healio.com/news/dermatology/20200424/dermatology-expert-weighs-in-on-covid-toes-tracking-dermatologic-symptoms-of-covid19

10.https://www.jaadcasereports.org/article/S2352-5126(20)30310-6/fulltext

11.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7189855/

12.https://onlinelibrary.wiley.com/doi/10.1111/bjd.19163

13.https://jamanetwork.com/journals/jamadermatology/fullarticle/2765612

1. https://www.practiceupdate.com/content/aad-establishes-registry-for-skin-manifestations-of-covid-19/99622