Dermatologic Findings in COVID-19

Authors: Brit Long, MD (@long_brit, Attending Emergency Physician, San Antonio, TX) and Michael Gottlieb, MD (@MGottliebMD, Attending Emergency Physician, Ultrasound Fellowship Director, Rush Medical Center) // Reviewed by: Alex Koyfman, MD (@EMHighAK)

Case:

A 30-year-old female presents with bilateral lower extremity pain and skin rash. She has had 5 days of cough, shortness of breath, fevers, myalgias, and congestion as well. She has no past medical history.  On exam, she has a temperature of 101F but is normoxic. Her skin exam reveals erythematous papules and macules, bullae, and digital swelling on her feet. You suspect COVID-19 with her symptoms, but what about her rash?

We are in the midst of the COVID-19 pandemic due to SARS-CoV-2. Most patients present with respiratory symptoms, fever, and myalgias, but other systems affected include the cardiovascular, gastrointestinal, neurologic, and dermatologic systems (1,2). Multiple case reports have brought to light skin findings associated with COVID-19.

 

Why can skin findings occur?

While the angiotensin-converting enzyme 2 (ACE2) receptor is found on lung alveolar epithelial cells, small intestine enterocytes, and vasculature, it is also present in the skin, which can account for the dermatologic symptoms found in patients with COVID-19 (3-8). The virus may be associated with diffuse microvascular vasculitis with complement system activation which may result in rash, but the virus may have a direct effect and cause lymphocyte infiltration, epidermal spongiosis, and papillary dermal edema (5-15). 

Several studies suggest skin findings present several days after other symptoms. These skin findings can occur in up to 20% of patients, though this ranges depending on the study, with one study finding 18 of 88 patients had a rash and another 5 of 103 patients (2,9,12) .

 

The Rashes

Perhaps the most significant challenge associated with COVID-19 rashes is the myriad of presentations. First, the rash can involve a variety of body regions, most commonly the trunk, followed by the extremities. Lesions typically appear within 3 days and are gone within 8 days. The individual rashes also are associated with wide differentials (9,16).

Table 1. Potential Causes of Each Dermatologic Finding

With that out of the way, let’s discuss some of the rashes…

 

Maculopapular

Defined by erythematous macules covered with small papules (or larger plaques), maculopapular rashes have been reported in multiple patients (15-20). The rash can be confluent with scaling as well. This rash has been reported in 16% of patients and has a mean duration of 9 days in COVID-19 patients (9,14-22).  The rash may occur on the extremities, trunk, or diffusely. The rash has been described as starting on the trunk and then spreading distally as well (12,15,22-27).

Urticaria

Acute, swollen, read wheals/plaques with pruritis characterize urticaria characterize urticaria. This can affect all age groups and has been reported to occur along all regions of the body, including the trunk, head, and extremities, but no palms or soles (9,10,12,17,25,26,38-31). The rash often migrates. A study of 73 patients with COVID-19 and urticaria found the trunk was most commonly involved, and pruritis occurred in 92% (20). The rash typically lasts for just under 7 days, and urticaria can occur concomitantly with other COVID-19 symptoms. Interestingly, urticaria was associated with increased mortality in one study of patients with COVID-19 (20).

Vesicular

Small, fluid-filled blisters on an erythematous base define vesicular rash. These may occur in approximately 1% of patients, and vesicles are typically scattered, though diffuse involvement can occur (9,16,32). Vesicles most commonly affect the trunk and extremities and last approximately 10 days (11,17,20). One study found vesicles preceded other symptoms and were small and monomorphic with hemorrhagic content, which differs from chicken pox (20).

Petechiae and Purpura

Small subdermal hemorrhages characterize petechiae, while purpura are larger variants. These are less common than other rashes (33). One case report found petechiae occurred in a patient with thrombocytopenia, and another found purpura isolated to flexural areas (33,34). Keep in mind that petechiae and purpura can be associated with vasculitis and/or thrombocytopenia and is a less common rash found in COVID-19.

Chilblains (COVID Toes)

Pernio or perniosis is another term for chilblains, which present as erythematous or violaceous papules and macules, bullae, and/or digital swelling (35). These typically occur due to an abnormal response to a cold environment, with distal vascular constriction leading to pruritic, tender areas on the extremities. This is one of the rashes most commonly associated with COVID-19, with over 100 cases described (17,20,35,36). These lesions most commonly affect the hands or feet and are asymmetric, with approximately 30% associated with pain and 30% with pruritis (20,35). This rash is also more commonly present in younger patients (< 32 years) (32).

Livedo Racemosa

This rash is a violaceous web/net-like skin patterning that appears similar to livedo reticularis, except livedo racemosa appears diffusely (livedo reticularis is typically gravity-dependent) (37). The rash has a mean duration of 9.4 days, and is more common in older patients (mean age 63 years) (17,20,38).  Unfortunately, this rash is associated with more severe disease and a mortality rate of 10% (20).

Distal Ischemia

One of the most severe dermatologic complications is distal ischemia, which can result in necrosis (39). A case series of 7 patients described ischemia with finger/toe cyanosis, bullae, and dry gangrene (39). A second report discussed distal finger ischemia, one with toe ischemia, and one with necrotic purpura (17,40,41). If distal ischemia is present, vascular surgery consultation is recommended.

Back to the Case…

With the patient’s symptoms, you are concerned with COVID-19, and her rash is consistent with chilblains or pernio. She appears otherwise well and improves with symptomatic therapy in the ED, and you discharge her home.

 

Key Points:

  • COVID-19 can result in multiorgan involvement that includes the skin.
  • Skin findings may occur due to diffuse microvascular thrombosis or viral exanthem.
  • Rashes reported in COVID-19 include maculopapular rash, urticaria, vesicular rash, petechia, purpura, chilblains, livedo racemosa, and distal ischemia.
  • These rashes should prompt consideration of COVID-19.
  • Severe rashes include livedo racemosa, purpura, and distal ischemia.

 

References/Further Reading:

  1. World Health Organization. Situation Report 110. Available at: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports/ Last accessed: May 9, 2020.
  2. Guan WJ, Ni ZY, Hu Y, et al. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020;382(18):1708‐
  3. Hamming I, Timens W, Bulthuis ML, Lely AT, Navis G, van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol. 2004 Jun;203(2):631-7.
  4. Zhang H, Penninger JM, Li Y, Zhong N, Slutsky AS. Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target. Intensive Care Med. 2020 Apr;46(4):586-590.
  5. Huang C, Wang Y, Li X et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. 2020;395:497-506.
  6. Zhou F, Yu T, Du R et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020 Mar 28;395(10229):1054-1062.
  7. Wang D, Hu B, Hu C et al. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA. 2020 Feb 7. doi: 10.1001/jama.2020.1585. [Epub ahead of print]
  8. Li MY, Li L, Zhang Y, Wang XS. Expression of the SARS-CoV-2 cell receptor gene ACE2 in a wide variety of human tissues. Infect Dis Poverty. 2020;9(1):45. Published 2020 Apr 28. doi:10.1186/s40249-020-00662-x
  9. Recalcati S. Cutaneous manifestations in COVID-19: a first perspective [published online ahead of print, 2020 Mar 26]. J Eur Acad Dermatol Venereol. 2020;10.1111/jdv.16387. doi:10.1111/jdv.16387.
  10. Henry D, Ackerman M, Sancelme E, Finon A, Esteve E. Urticarial eruption in COVID-19 infection [published online ahead of print, 2020 Apr 15]. J Eur Acad Dermatol Venereol. 2020;10.1111/jdv.16472. doi:10.1111/jdv.16472
  11. Genovese G, Colonna C, Marzano AV. Varicella-like exanthem associated with COVID-19 in an 8-year-old girl: A diagnostic clue? [published online ahead of print, 2020 Apr 21]. Pediatr Dermatol. 2020;10.1111/pde.14201. doi:10.1111/pde.14201
  12. Hedou M, Carsuzaa F, Chary E, Hainaut E, Cazenave-Roblot F, Masson Regnault M. Comment on “Cutaneous manifestations in COVID-19: a first perspective” by Recalcati S [published online ahead of print, 2020 Apr 21]. J Eur Acad Dermatol Venereol. 2020;10.1111/jdv.16519. doi:10.1111/jdv.16519
  13. Magro C, Mulvey JJ, Berlin D, et al. Complement associated microvascular injury and thrombosis in the pathogenesis of severe COVID-19 infection: a report of five cases [published online ahead of print, 2020 Apr 15]. Transl Res. 2020;S1931-5244(20)30070-0. doi:10.1016/j.trsl.2020.04.007
  14. Gianotti R, Veraldi S, Recalcati S, et al. Cutaneous Clinico-Pathological Findings in three COVID-19-Positive Patients Observed in the Metropolitan Area of Milan, Italy [published online ahead of print, 2020 Apr 21]. Acta Derm Venereol. 2020;10.2340/00015555-3490. doi:10.2340/00015555-3490
  15. Sanchez A, Sohier P, Benghanem S, et al. Digitate Papulosquamous Eruption Associated With Severe Acute Respiratory Syndrome Coronavirus 2 Infection [published online ahead of print, 2020 Apr 30]. JAMA Dermatol. 2020;10.1001/jamadermatol.2020.1704. doi:10.1001/jamadermatol.2020.1704
  16. Marzano AV, Genovese G, Fabbrocini G, et al. Varicella-like exanthem as a specific COVID-19-associated skin manifestation: multicenter case series of 22 patients [published online ahead of print, 2020 Apr 16]. J Am Acad Dermatol. 2020;S0190-9622(20)30657-5. doi:10.1016/j.jaad.2020.04.044
  17. Bouaziz JD, Duong T, Jachiet M, et al. Vascular skin symptoms in COVID-19: a french observational study [published online ahead of print, 2020 Apr 27]. J Eur Acad Dermatol Venereol. 2020;10.1111/jdv.16544. doi:10.1111/jdv.16544
  18. Amatore F, Macagno N, Mailhe M, et al. SARS-CoV-2 infection presenting as a febrile rash [published online ahead of print, 2020 Apr 24]. J Eur Acad Dermatol Venereol. 2020;10.1111/jdv.16528. doi:10.1111/jdv.16528
  19. Gisondi P, Piaserico S, Conti A, Naldi L. Dermatologists and SARS-CoV-2: The impact of the pandemic on daily practice [published online ahead of print, 2020 Apr 22]. J Eur Acad Dermatol Venereol. 2020;10.1111/jdv.16515. doi:10.1111/jdv.16515
  20. Galván Casas C, Català A, Carretero Hernández G, et al. Classification of the cutaneous manifestations of COVID-19: a rapid prospective nationwide consensus study in Spain with 375 cases [published online ahead of print, 2020 Apr 29]. Br J Dermatol. 2020;10.1111/bjd.19163. doi:10.1111/bjd.19163
  21. Hunt M, Koziatek C. A Case of COVID-19 Pneumonia in a Young Male with Full Body Rash as a Presenting Symptom [published online ahead of print, 2020 Mar 28]. Clin Pract Cases Emerg Med. 2020;10.5811/cpcem.2020.3.47349. doi:10.5811/cpcem.2020.3.47349
  22. Najarian DJ. Morbilliform Exanthem Associated with COVID-19 [published online ahead of print, 2020 Apr 20]. JAAD Case Rep. 2020;10.1016/j.jdcr.2020.04.015. doi:10.1016/j.jdcr.2020.04.015
  23. Ahouach B, Harant S, Ullmer A, et al. Cutaneous lesions in a patient with COVID-19: are they related? [published online ahead of print, 2020 Apr 30]. Br J Dermatol. 2020;10.1111/bjd.19168. doi:10.1111/bjd.19168
  24. Mahé A, Birckel E, Krieger S, Merklen C, Bottlaender L. A distinctive skin rash associated with Coronavirus Disease 2019 ? [published online ahead of print, 2020 Apr 15]. J Eur Acad Dermatol Venereol. 2020;10.1111/jdv.16471. doi:10.1111/jdv.16471
  25. Morey-Olivé M, Espiau M, Mercadal-Hally M, Lera-Carballo E, García-Patos V. Cutaneous manifestations in the current pandemic of coronavirus infection disease (COVID 2019) [published online ahead of print, 2020 Apr 27]. An Pediatr (Engl Ed). 2020;10.1016/j.anpede.2020.04.002. doi:10.1016/j.anpede.2020.04.002
  26. Rivera-Oyola R, Koschitzky M, Printy R, et al. Dermatologic findings in two patients with COVID-19 [published online ahead of print, 2020 Apr 28]. JAAD Case Rep. 2020;10.1016/j.jdcr.2020.04.027. doi:10.1016/j.jdcr.2020.04.027
  27. Estébanez A, Pérez-Santiago L, Silva E, Guillen-Climent S, García-Vázquez A, Ramón MD. Cutaneous manifestations in COVID-19: a new contribution [published online ahead of print, 2020 Apr 15]. J Eur Acad Dermatol Venereol. 2020;10.1111/jdv.16474. doi:10.1111/jdv.16474
  28. Lu S, Lin J, Zhang Z, et al. Alert for non-respiratory symptoms of Coronavirus Disease 2019 (COVID-19) patients in epidemic period: A case report of familial cluster with three asymptomatic COVID-19 patients [published online ahead of print, 2020 Mar 19]. J Med Virol. 2020;10.1002/jmv.25776. doi:10.1002/jmv.25776
  29. Fernandez-Nieto D, Ortega-Quijano D, Segurado-Miravalles G, Pindado-Ortega C, Prieto- Barrios M, Jimenez-Cauhe J. Comment on: Cutaneous manifestations in COVID-19: a first perspective. Safety concerns of clinical images and skin biopsies [published online ahead of print, 2020 Apr 15]. J Eur Acad Dermatol Venereol. 2020;10.1111/jdv.16470. doi:10.1111/jdv.16470
  30. Quintana-Castanedo L, Feito-Rodríguez M, Valero-López I, Chiloeches-Fernández C, Sendagorta-Cudós E, Herranz-Pinto P. Urticarial exanthem as early diagnostic clue for COVID-19 infection [published online ahead of print, 2020 Apr 29]. JAAD Case Rep. 2020;10.1016/j.jdcr.2020.04.026. doi:10.1016/j.jdcr.2020.04.026
  31. van Damme C, Berlingin E, Saussez S, Accaputo O. Acute urticaria with pyrexia as the first manifestations of a COVID-19 infection [published online ahead of print, 2020 Apr 24]. J Eur Acad Dermatol Venereol. 2020;10.1111/jdv.16523. doi:10.1111/jdv.16523
  32. Tammaro A, Adebanjo GAR, Parisella FR, Pezzuto A, Rello J. Cutaneous manifestations in COVID-19: the experiences of Barcelona and Rome [published online ahead of print, 2020 Apr 24]. J Eur Acad Dermatol Venereol. 2020;10.1111/jdv.16530. doi:10.1111/jdv.16530
  33. Joob B, Wiwanitkit V. COVID-19 can present with a rash and be mistaken for dengue. J Am Acad Dermatol. 2020;82(5):e177. doi:10.1016/j.jaad.2020.03.036
  34. Jimenez-Cauhe J, Ortega-Quijano D, Prieto-Barrios M, Moreno-Arrones OM, Fernandez- Nieto D. Reply to “COVID-19 can present with a rash and be mistaken for Dengue”: Petechial rash in a patient with COVID-19 infection [published online ahead of print, 2020 Apr 10]. J Am Acad Dermatol. 2020;S0190-9622(20)30556-9. doi:10.1016/j.jaad.2020.04.016
  35. Recalcati S, Barbagallo T, Frasin LA, et al. Acral cutaneous lesions in the Time of COVID- 19 [published online ahead of print, 2020 Apr 24]. J Eur Acad Dermatol Venereol. 2020;10.1111/jdv.16533. doi:10.1111/jdv.16533
  36. Landa N, Mendieta-Eckert M, Fonda-Pascual P, Aguirre T. Chilblain-like lesions on feet and hands during the COVID-19 Pandemic [published online ahead of print, 2020 Apr 24]. Int J Dermatol. 2020;10.1111/ijd.14937. doi:10.1111/ijd.14937
  37. Uthman IW, Khamashta MA. Livedo racemosa: a striking dermatological sign for the antiphospholipid syndrome. J Rheumatol. 2006;33(12):2379‐
  38. Manalo IF, Smith MK, Cheeley J, Jacobs R. A Dermatologic Manifestation of COVID-19: Transient Livedo Reticularis [published online ahead of print, 2020 Apr 10]. J Am Acad Dermatol. 2020;S0190-9622(20)30558-2. doi:10.1016/j.jaad.2020.04.018
  39. Zhang Y, Cao W, Xiao M, et al. Zhonghua Xue Ye Xue Za Zhi. [Clinical and coagulation characteristics of 7 patients with critical COVID-2019 pneumonia and acro-ischemia]. 2020;41(0):E006. doi:10.3760/cma.j.issn.0253-2727.2020.0006.
  40. Alramthan A, Aldaraji W. A case of COVID-19 presenting in clinical picture resembling chilblains disease. First report from the Middle East [published online ahead of print, 2020 Apr 17]. Clin Exp Dermatol. 2020;10.1111/ced.14243. doi:10.1111/ced.14243
  41. Mazzotta F, Troccoli T. Acute Acro-ischemia in the child at the time of COVID-19. Dermatologia Pediatrica. 2020. Available at: https://www.ejpd.com/images/acroischemia- ENG.pdf. Last accessed: May 9, 2020.

 

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