Site Under Construction

Cutaneous manifestations in SARS-CoV-2 (COVID-19) infection: A review of clinical, histopathologic features, and management

Terese Monette O. Aquino, MD, DPDS, DDSP-PDS Fendi EJ R. Bautista, MD, Patricia Angelica Pastrana-Mabanta, MD, MBA, DPDS

Abstract

BACKGROUND Numerous studies have demonstrated various information about COVID-19 infection. With this, the authors intend to abridge, present, and synthesize current available information, focusing on the cutaneous manifestations of COVID-19 infection, to help guide dermatologists in understanding the dermatologic aspect of this disease.

OBJECTIVE This s tudy a ims to review t he d ifferent c utaneous m anifestations of COVID-19 by m orphology a nd to evaluate the lesions seen in the different age groups. Furthermore, this study aims to discuss cutaneous findings together with histologic evidence and hypothesized pathophysiology, and to review the management used in treating COVID-19-related cutaneous manifestations.

METHODS OVID® and PubMed databases were used to search in detail for COVID-19-induced skin lesions across all ages and their management.

DISCUSSION COVID-19 affects the skin, hair and nails of patients. These may be attributed to the different virologic phases as well as the immune response of the body. Histopathologic findings of these lesions vary depending on the clinical presentation.
Use of corticosteroid therapy and antihistamines as treatment for some cutaneous manifestations of COVID-19 showed good response.

CONCLUSION COVID-19 infection-associated cutaneous manifestations present with different morphologies. It is important for dermatologists to gain better understanding of this disease in order to promptly identify and suspect the possibility of this illness, as well as provide appropriate actions.

KEYWORDS COVID-19, coronavirus, skin, cutaneous manifestations, COVID-19 management

References

1. Coronavirus Disease (COVID-19): Pathophysiology, Epidemiology, Clinical Management and Public Health Response [Internet]. Frontiers

Research Topic. Available from: https://www.frontiersin.org/research-topics/13377/coronavirus-disease-covid-19-pathophysiology-epidemiology-clinical-management-and-public-health-resp.

2. Sanghvi AR. COVID-19: An overview for dermatologists. Int J Dermatol. 2020 Dec;59(12):1437–49. DOI: 10.1111/ijd.15257.

3. Tang K, Wang Y, Zhang H, Zheng Q, Fang R, Sun Q. Cutaneous manifestations of the Coronavirus Disease 2019 ( COVID ‐19): A brief review. Dermatologic Therapy [Internet]. 2020 Jul [cited 2021 Apr 9];33(4). Available from: https://onlinelibrary.wiley.com/doi/10.1111/dth.13528.

4. Brancaccio G, Gussetti N, Sasset L, Alaibac M, Tarantello M, Salmaso R, et al. Cutaneous manifestations in a series of 417 patients with SARS-CoV-2 infection: epidemiological and clinical correlates of chilblain like lesions. Pathogens and Global Health. 2021 Mar 17;1–4. DOI: 10.1080/20477724.2021.1901040.

5. Guan W, Ni Z, Hu Y, Liang W, Ou C, He J, et al. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020 Apr 30;382(18):1708– 20. DOI: 10.1056/NEJMoa2002032.

6. Jamshidi P, Hajikhani B, Mirsaeidi M, Vahidnezhad H, Dadashi M, Nasiri MJ. Skin Manifestations in COVID-19 Patients: Are They Indicators for Disease Severity? A Systematic Review. Front Med. 2021 Feb 16;8:634208. DOI: 10.3389/fmed.2021.634208.

7. De Giorgi V, Recalcati S, Jia Z, Chong W, Ding R, Deng Y, et al. Cutaneous manifestations related to coronavirus disease 2019 (COVID-19): A prospective study from China and Italy. Journal of the American Academy of Dermatology. 2020 Aug;83(2):674–5. DOI: 10.1016/j.jaad.2020.05.073.

8. Recalcati S. Cutaneous manifestations in COVID-19: a first perspective. J Eur Acad Dermatol Venereol [Internet]. 2020 Mar 26 [cited 2020 May 1]; Available from: http://doi.wiley.com/10.1111/jdv.16387.

9. Marzano AV, Genovese G, Moltrasio C, Gaspari V, Vezzoli P, Maione V, et al. The clinical spectrum of COVID-19–associated cutaneous manifestations: An Italian multicenter study of 200 adult patients. Journal of the American Academy of Dermatology. 2021 Jan;S0190962221001663. DOI: 10.1016/j.jaad.2021.01.023.

10. Freeman EE, McMahon DE, Lipoff JB, Rosenbach M, Kovarik C, Desai SR, et al. The spectrum of COVID-19–associated dermatologic manifestations: An international registry of 716 patients from 31 countries. Journal of the American Academy of Dermatology. 2020 Oct;83(4):1118–29. DOI: 10.1016/j.jaad.2020.06.1016.

11. AvellanaMorenoR,EstelaVillaLM,AvellanaMorenoV,EstelaVillaC,MorenoAparicioMA,AvellanaFontanellaJA.Cutaneousmanifestationof COVID-19 in images: a case report. J Eur Acad Dermatol Venereol. 2020 Jul;34(7):e307–9. DOI: 10.1111/jdv.16531.

12. Galván Casas C, Català A, Carretero Hernández G, Rodríguez-Jiménez P, Fernández-Nieto D, Rodríguez‐Villa Lario A, et al. Classification of the cutaneous manifestations of COVID-19: a rapid prospective nationwide consensus study in Spain with 375 cases. Br J Dermatol. 2020 Jul;183(1):71–7. DOI: 10.1111/bjd.19163.

13. Català A, Galván-Casas C, Carretero-Hernández G, Rodríguez-Jiménez P, Fernández-Nieto D, Rodríguez-Villa A, et al. Maculopapular eruptions associated to COVID-19: A subanalysis of the COVID-Piel study. Dermatologic Therapy [Internet]. 2020 Nov [cited 2021 Apr 5];33(6). Available from: https://onlinelibrary.wiley.com/doi/10.1111/dth.14170. DOI: 10.1111/dth.14170.

14. Joob B, Wiwanitkit V. COVID-19 can present with a rash and be mistaken for dengue. Journal of the American Academy of Dermatology. 2020 May;82(5):e177. DOI: 10.1016/j.jaad.2020.03.036.

15.     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. Journal of the American Academy of Dermatology. 2020 Apr;S0190962220305569. DOI: 10.1016/j.jaad.2020.04.016.

16. Ahouach B, Harent S, Ullmer A, Martres P, Bégon E, Blum L, et al. Cutaneous lesions in a patient with COVID-19: are they related? Br J Dermatol [Internet]. 2020 Aug [cited 2021 Apr 2];183(2). Available from: https://onlinelibrary.wiley.com/doi/10.1111/bjd.19168. DOI: 10.1111/bjd.19168.

17. Gianotti R, Recalcati S, Fantini F, Riva C, Milani M, Dainese E, et al. Histopathological Study of a Broad Spectrum of Skin Dermatoses in Patients Affected or Highly Suspected of Infection by COVID-19 in the Northern Part of Italy: Analysis of the Many Faces of the Viral-Induced Skin Diseases in Previous and New Reported Cases. The American Journal of Dermatopathology. 2020 Aug;42(8):564–70. DOI: 10.1097/DAD.0000000000001707.

18. Zengarini C, Orioni G, Cascavilla A, Horna Solera C, Fulgaro C, Misciali C, et al. Histological pattern in COVID-19-induced viral rash. J Eur Acad Dermatol Venereol [Internet]. 2020 Sep [cited 2021 Apr 2];34(9). Available from: https://onlinelibrary.wiley.com/doi/10.1111/jdv.16569. DOI: 10.1111/ jdv.16569.

19. Garrido Ruiz MC, Santos-Briz Á, Santos-Briz Á, Sánchez A, Alonso-Riaño M, Burgos J, et al. Spectrum of Clinicopathologic Findings in COVID-19-induced Skin Lesions: Demonstration of Direct Viral Infection of the Endothelial Cells. American Journal of Surgical Pathology [Internet]. 2021 Jan 4 [cited 2021 Apr 3];Publish Ahead of Print. Available from: https://journals.lww.com/10.1097/PAS.0000000000001634.

20. Torrelo A, Andina D, Santonja C, Noguera-Morel L, Bascuas-Arribas M, Gaitero-Tristán J, et al. Erythema multiforme-like lesions in children and COVID‐19. Pediatr Dermatol. 2020 May;37(3):442–6. DOI: 10.1111/pde.14246.

21. 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. J Eur Acad Dermatol Venereol. 2020 Jul;34(7):e299–300. DOI: 10.1111/jdv.16519.

22. Recalcati S, Barbagallo T, Frasin LA, Prestinari F, Cogliardi A, Provero MC, et al. Acral cutaneous lesions in the time of COVID-19. J Eur Acad Dermatol Venereol [Internet]. 2020 Aug [cited 2021 Mar 27];34(8). Available from: https://onlinelibrary.wiley.com/doi/10.1111/jdv.16533. DOI: 10.1111/jdv.16533.

23. Piccolo V, Neri I, Filippeschi C, Oranges T, Argenziano G, Battarra VC, et al. Chilblain-like lesions during COVID-19 epidemic: a preliminary study on 63 patients. J Eur Acad Dermatol Venereol [Internet]. 2020 Jul [cited 2021 Mar 27];34(7). Available from: https://onlinelibrary.wiley.com/doi/ abs/10.1111/jdv.16526. DOI: 10.1111/jdv.16526.

24. Estébanez A, Pérez-Santiago L, Silva E, Guillen-Climent S, García-Vázquez A, Ramón MD. Cutaneous manifestations in COVID-19: a new contribution. J Eur Acad Dermatol Venereol [Internet]. 2020 Apr 15 [cited 2020 May 2]; Available from: http://doi.wiley.com/10.1111/jdv.16474. DOI: 10.1111/jdv.16474.

25. Locatelli AG, Robustelli Test E, Vezzoli P, Carugno A, Moggio E, Consonni L, et al. Histologic features of long-lasting chilblain-like lesions in a paediatric COVID-19 patient. J Eur Acad Dermatol Venereol [Internet]. 2020 Aug [cited 2021 Apr 7];34(8). Available from: https://onlinelibrary. wiley.com/doi/10.1111/jdv.16617. DOI: 10.1111/jdv.16617.

26. Kolivras A, Dehavay F, Delplace D, Feoli F, Meiers I, Milone L, et al. Coronavirus (COVID-19) infection–induced chilblains: A case report with histopathologic findings. JAAD Case Reports. 2020 Jun;6(6):489–92. DOI: 10.1016/j.jdcr.2020.04.011.

27. Cappel MA, Cappel JA, Wetter DA. Pernio (Chilblains), SARS-CoV-2, and COVID Toes Unified Through Cutaneous and Systemic Mechanisms. Mayo Clinic Proceedings. 2021 Jan;S002561962100046X. DOI: 10.1016/j.mayocp.2021.01.009.

28. van Damme C, Berlingin E, Saussez S, Accaputo O. Acute urticaria with pyrexia as the first manifestations of a COVID-19 infection. J Eur Acad Dermatol Venereol. 2020 Jul;34(7):e300–1. DOI: 10.1111/jdv.16523.

29. Henry D, Ackerman M, Sancelme E, Finon A, Esteve E. Urticarial eruption in COVID-19 infection. J Eur Acad Dermatol Venereol. 2020 Jun;34(6):e244–5. DOI: 10.1111/jdv.16472.

30. Tammaro A, Adebanjo G a. R, Parisella FR, Pezzuto A, Rello J. Cutaneous manifestations in COVID-19: the experiences of Barcelona and Rome. J Eur Acad Dermatol Venereol. 2020 Jul;34(7):e306–7. DOI: 10.1111/jdv.16530.

31. Marzano AV, Genovese G, Fabbrocini G, Pigatto P, Monfrecola G, Piraccini BM, et al. Varicella-like exanthem as a specific COVID-19–associated skin manifestation: Multicenter case series of 22 patients. Journal of the American Academy of Dermatology. 2020 Jul;83(1):280–5. DOI: 10.1016/j.jaad.2020.04.044.

32. Magro C, Mulvey JJ, Berlin D, Nuovo G, Salvatore S, Harp J, et al. Complement associated microvascular injury and thrombosis in the pathogenesis of severe COVID-19 infection: A report of five cases. Translational Research. 2020 Jun;220:1–13. DOI: 10.1016/j.trsl.2020.04.007.

33. Chen H, Guo J, Wang C, Luo F, Yu X, Zhang W, et al. Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records. The Lancet. 2020 Mar 7;395(10226):809–15. DOI: 10.1016/S0140-6736(20)30360-3.

34. Chen Y, Peng H, Wang L, Zhao Y, Zeng L, Gao H, et al. Infants Born to Mothers With a New Coronavirus (COVID-19). Front Pediatr [Internet]. 2020 [cited 2021 Apr 9];8. Available from: https://www.frontiersin.org/articles/10.3389/fped.2020.00104/full. DOI: 10.3389/fped.2020.00104.

35. Zhu H, Wang L, Fang C, Peng S, Zhang L, Chang G, et al. Clinical analysis of 10 neonates born to mothers with 2019-nCoV pneumonia. Transl Pediatr. 2020 Feb;9(1):51–60. DOI: 10.21037/tp.2020.02.06.

36. Garcia-Manau P, Garcia-Ruiz I, Rodo C, Sulleiro E, Maiz N, Catalan M, et al. Fetal Transient Skin Edema in Two Pregnant Women With Coronavirus Disease 2019 (COVID-19). Obstetrics & Gynecology. 2020 Nov;136(5):1016–20. DOI: 10.1097/AOG.0000000000004059.

37. Lavery MJ, BouvierCA, Thompson B. Cutaneous manifestations of COVID-19 in children (and adults): A virus that does not discriminate. Clinics in Dermatology [Internet]. 2020 Nov 1 [cited 2021 Apr 9]; Available from: https://www.sciencedirect.com/science/article/pii/S0738081X2030211X. DOI: 10.1016/j.clindermatol.2020.10.020.

38. Bursal Duramaz B, Yozgat CY, Yozgat Y, Turel O. Appearance of skin rash in pediatric patients with COVID‐19: Three case presentations. Dermatol Ther [Internet]. 2020 May 25 [cited 2021 Apr 9]; Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7261998/. DOI: 10.1111/dth.13594.

39. Ng SM. Prolonged dermatological manifestation 4 weeks following recovery of COVID-19 in a child. BMJ Case Rep. 2020 Aug;13(8):e237056. DOI: 0.1136/bcr-2020-237056.

40.     Andina D, Noguera-Morel L, Bascuas-Arribas M, Gaitero-Tristán J, Alonso-Cadenas JA, Escalada-Pellitero S, et al. Chilblains in children in the setting of COVID-19 pandemic. Pediatr Dermatol. 2020 May;37(3):406–11. DOI: 10.1111/pde.14215

41. Swali RN, Lee EB, Adams JL. Gianotti-crosti syndrome in the setting of recent coronavirus disease-19 infection. Pediatr Dermatol. 2021 Feb 28;pde.14518. DOI: 10.1111/pde.14518.

42. Wu P, Liang L, Chen C, Nie S. A child confirmed COVID-19 with only symptoms of conjunctivitis and eyelid dermatitis. Graefes Arch Clin Exp Ophthalmol. 2020 Apr 24;1–2. DOI: 10.1007/s00417-020-04708-6.

43. Trüeb RM, Dutra Rezende H, Gavazzoni Dias MFR. What can the hair tell us about COVID-19? Exp Dermatol. 2021 Feb;30(2):288–90. DOI: 10.1111/ exd.14259.

44. Müller Ramos P, Ianhez M, Amante Miot H. Alopecia and grey hair are associated with COVID-19 Severity. Exp Dermatol. 2020 Dec;29(12):1250–2. DOI: 10.1111/exd.14220.

45. Goren A, Vaño-Galván S, Wambier CG, McCoy J, Gomez-Zubiaur A, Moreno-Arrones OM, et al. A preliminary observation: Male pattern hair loss among hospitalized COVID-19 patients in Spain – A potential clue to the role of androgens in COVID-19 severity. J Cosmet Dermatol. 2020 Jul;19(7):1545–7. DOI: 10.1111/jocd.13443.

46. Wambier CG, Vaño-Galván S, McCoy J, Gomez-Zubiaur A, Herrera S, Hermosa-Gelbard Á, et al. Androgenetic alopecia present in the majority of patients hospitalized with COVID-19: The “Gabrin sign.” Journal of the American Academy of Dermatology. 2020 Aug;83(2):680–2. DOI: 10.1016/j. jaad.2020.05.079.

47. Montopoli M, Zumerle S, Vettor R, Rugge M, Zorzi M, Catapano CV, et al. Androgen-deprivation therapies for prostate cancer and risk of infection by SARS-CoV-2: a population-based study (N = 4532). Annals of Oncology. 2020 Aug;31(8):1040–5. DOI: 0.1016/j.annonc.2020.04.479.

48. Novak N, Peng W, Naegeli MC, Galvan C, Kolm-Djamei I, Brüggen C, et al. SARS-CoV-2, COVID-19, skin and immunology – What do we know so far? Allergy. 2021 Mar;76(3):698–713. DOI: 10.1111/all.14498.

49. Wambier CG, Vaño-Galván S, McCoy J, Pai S, Dhurat R, Goren A. Androgenetic alopecia in COVID-19: Compared to age-matched epidemiologic studies and hospital outcomes with or without the Gabrin sign. Journal of the American Academy of Dermatology. 2020 Dec;83(6):e453–4. DOI: 10.1016/j.jaad.2020.07.099.

50. Rizzetto G, Diotallevi F, Campanati A, Radi G, Bianchelli T, Molinelli E, et al. Telogen efluvium related to post severe Sars-Cov-2 infection: Clinical aspects and our management experience. Dermatologic Therapy [Internet]. 2021 Jan [cited 2021 Apr 9];34(1). Available from: https:// onlinelibrary.wiley.com/doi/10.1111/dth.14547. DOI: 10.1111/dth.14547.

51. Alobaida S, Lam JM. Beau lines associated with COVID-19. CMAJ. 2020 Sep 8;192(36):E1040–E1040. DOI: 10.1503/cmaj.201619.

52. Shin JY, Cho BK, Park HJ. A Clinical Study of Nail Changes Occurring Secondary to Hand-Foot-Mouth Disease: Onychomadesis and Beau’s Lines. Ann Dermatol. 2014;26(2):280. DOI: 10.5021/ad.2014.26.2.280.

53. Neri I, Guglielmo A, Virdi A, Gaspari V, Starace M, Piraccini BM. The red half-moon nail sign: a novel manifestation of coronavirus infection. J Eur Acad Dermatol Venereol [Internet]. 2020 Nov [cited 2021 Mar 28];34(11). Available from: https://onlinelibrary.wiley.com/doi/10.1111/jdv.16747. DOI: 10.1111/jdv.16747.

54. Tammaro A, Adebanjo GAR, Erasmus H, Chello C, Pezzuto A, Ramirez-Estrada S, et al. Transverse orange nail lesions following SARS-CoV-2 infection. Dermatologic Therapy [Internet]. 2021 Jan [cited 2021 Mar 28];34(1). Available from: https://onlinelibrary.wiley.com/doi/10.1111/ dth.14688. DOI: 10.1111/dth.14688.

55. Wiese OJ, Allwood BW, Zemlin AE. COVID-19 and the renin-angiotensin system (RAS): A spark that sets the forest alight? Medical Hypotheses. 2020 Nov;144:110231. DOI: 10.1016/j.mehy.2020.110231.

56. Magro C, Mulvey JJ, Berlin D, Nuovo G, Salvatore S, Harp J, et al. Complement associated microvascular injury and thrombosis in the pathogenesis of severe COVID-19 infection: A report of five cases. Translational Research. 2020 Jun;220:1–13. DOI: 10.1016/j.trsl.2020.04.007.

57. Magro CM, Mulvey JJ, Laurence J, Sanders S, Crowson AN, Grossman M, et al. The differing pathophysiologies that underlie COVID-19-associated perniosis and thrombotic retiform purpura: a case series. Br J Dermatol. 2021 Jan;184(1):141–50. DOI: 10.1111/bjd.19415.

58. Genovese G, Moltrasio C, Berti E, Marzano AV. Skin Manifestations Associated with COVID-19: Current Knowledge and Future Perspectives. Dermatology. 2021;237(1):1–12. DOI: 10.1159/000512932.

59. Karaca Z, Yayli S, Çalışkan O. A unilateral purpuric rash in a patient with COVID-19 infection. Dermatologic Therapy [Internet]. 2020 Jul [cited 2021 Apr 9];33(4). Available from: https://onlinelibrary.wiley.com/doi/10.1111/dth.13798. DOI: 10.1111/dth.13798.

60. 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. J Eur Acad Dermatol Venereol [Internet]. 2020 Jun [cited 2021 Apr 9];34(6). Available from: https://onlinelibrary.wiley.com/doi/10.1111/jdv.16470. DOI: 10.1111/jdv.16470.

61. Najarian DJ. Morbilliform exanthem associated with COVID-19. JAAD Case Reports. 2020 Jun;6(6):493–4. DOI: 10.1016/j.jdcr.2020.04.015.

62. Shanshal M. Low- dose systemic steroids, an emerging therapeutic option for COVID-19 related urticaria. Journal of Dermatological Treatment. 2020 Jul 16;1–2. DOI: 10.1080/09546634.2020.1795062.

63. Schaefer P. Acute and Chronic Urticaria: Evaluation and Treatment. 2017;95(11):8.

REquesting Permission

Cutaneous manifestations in SARS-CoV-2 (COVID-19) infection: A review of clinical, histopathologic features, and management