Dermatological manifestations of COVID-19 and its therapies: a review
Keywords:COVID-19, SARS-CoV2, Cutaneous manifestation, COVID toes, Acrocyanosis, Vasculitis
In the beginning of the COVID-19 pandemic when we were still getting used to the rising cases every day and limited resources to deal them with, the focus was to get a hold of the situation as quickly as possible. Seven months into the pandemic, the cases are still on the rise but we have gathered some knowledge through the researches getting published every day, most of which are focused on the involvement of respiratory system, cardiovascular system, central nervous system, and gastrointestinal system. Dermatological manifestations have not been given their due importance. Lately, many patients have started presenting with dermatological manifestation sometimes preceding or sometimes during COVID-19 infection with or without involvement of other systems. This may be beneficial to clinicians all over the world, to determine potential dermatological signs in COVID-19 and also help in earlier suspection of the COVID-19 infection. Many cutaneous adverse drug reactions (ADR) to drugs advocated in COVID-19 treatment are also being reported every day, which are discussed in this review.
Here we attempt to review dermatological manifestations of COVID-19 infections and drug reactions by the drugs advocated for its treatment and an understanding in its path mechanisms reported thus far. This will help clinicians to get an insight into what to expect and when to expect in terms of dermatological manifestation of COVID-19 and its drugs.
Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395:497-506.
Lovato A, Filippis C. Clinical presentation of COVID-19: a systematic review focusing on upper airway symptoms. Ear Nose Throat J. 2020;99(9):569-76.
Fang Z, Yi F, Wu K, Laic K, Suna X, Zhong N et al. Clinical characteristics of coronavirus pneumonia 2019 (COVID-19): an updated systematic review. medRxiv. 2020.
Liang W, Feng Z, Rao S, Xiao C, Xue X, Lin Z et al. Diarrhoea may be underestimated: a missing link in 2019 novel coronavirus. Gut. 2020;69:1141-3.
Xydakis M, Dehgani-Mobaraki P, Holbrook E et al. Smell and taste dysfunction in patients with COVID-19. Lancet Infect Dis. 2020.
Mahé A, Birckel E, Krieger S, Merklen C, Bottlaender L. A distinctive skin rash associated with coronavirus disease 2019? J Eur Acad Dermatol Venereol. 2020;34(6):e246-7.
Henry D, Ackerman M, Sancelme E, Finon A, Esteve E. Urticarial eruption in COVID-19 infection. J Eur Acad Dermatol Venereol. 2020;34(6):e244-5.
Marzano AV, Genovese G, Fabbrocini G, Pigatto P, Monfrecola G, Piraccini BM. Varicella-like exanthem as a specific COVID-19-associated skin manifestation: multicenter case series of 22 patients. J Am Acad Dermatol. 2020;83(1):280-5.
Al Ramthan A, Al Daraji W. A case of COVID-19 presenting in clinical picture resembling chilblains disease. First report from the Middle East. Clin Exp Dermatol. 2020;45(6):746-8.
Manalo IF, Smith MK, Cheeley J, Jacobs R. A dermatologic manifestation of COVID-19: transient livedo reticularis. J Am Acad Dermatol. 2020;83(2):700.
Zhang Y, Cao W, Xiao M, Li YJ, Yang Y, Zhao J et al. Clinical and coagulation characteristics of 7 patients with critical COVID-2019 pneumonia and acro-ischemia. Zhonghua Xue Ye Xue Za Zhi. 2020;41:E006.
Zhang Y, Xiao M, Zhang S. Coagulopathy and antiphospholipid antibodies in patients with COVID-19. N Engl J Med. 2020;382(17):e38.
Türsen Ü, Türsen B, Lotti T. Coronavirus-days in dermatology. Dermatol Ther. 2020;33(4):e13438.
Casas GC, 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;183(1):71-7.
Recalcati S. Cutaneous manifestations in COVID-19: a first perspective. J Eur Acad Dermatol Venereol. 2020;34(5):e212-3.
Fernandez-Nieto D, Ortega-Quijano D, Segurado-Miravalles G. Comment on: Cutaneous manifestations in COVID-19: a first perspective. Safety concerns of clinical images and skin biopsies. J Eur Acad Dermatol Venereol. 2020;34(6):e252-4.
Jimenez-Cauhe J, Ortega-Quijano D, Prieto-Barrios M, et al. Reply to “COVID-19 can present with a rash and be mistaken for Dengue, Petechial rash in a patient with COVID-19 infection. J Am Acad Dermatol. 2020;83(2):e141-2.
Estébanez A, Pérez-Santiago L, Silva E, et al. Cutaneous manifestations in COVID-19: a new contribution. J Eur Acad Dermatol Venereol 2020.
Otto MA. Skin manifestations are emerging in the coronavirus pandemic. Dermatology News April 3, 2020. Available at: https://www.mdedge.com/ dermatology/article/220183/coronavirus-updates/skin-manifestations-are-emerging-coronavirus-pandemic. Accessed on 6 May 2020.
Joob B, Wiwanitkit V. COVID-19 can present with a rash and be mistaken for Dengue. J Am Acad Dermatol. 2020;82(5):e177.
Gianotti R, Veraldi S, Recalcati S, Cusini M, Ghislanzoni M, Boggio F, et al. Cutaneous Clinico-Pathological Findings in three COVID-19-Positive Patients Observed in the Metropolitan Area of Milan, Italy. Acta Derm Venereol. 20203;100(8):adv00124.
De Perosanz-Lobo D, Fernandez-Nieto D, Burgos-Blasco P, Selda-Enriquez G, Carretero I, Moreno C, et al. Urticarial vasculitis in COVID-19 infection: A vasculopathy-related symptom? J. Eur Acad Dermatol Venereol. 2020;34(10):e566-8.
Mahé A, Birckel E, Merklen C, Lefèbvre P, Hannedouche C, Jost M, Droy-Dupré L. Histology of skin lesions establishes that the vesicular rash associated with COVID-19 is not 'varicella-like'. J Eur Acad Dermatol Venereol. 2020;34(10):e559-e561.
Cordoro KM, Reynolds SD, Wattier R, McCalmont TH. Clustered Cases of Acral Perniosis: Clinical Features, Histopathology and Relationship to COVID-19. Pediatr. Dermatol. 2020;37(3):419-23.
Drago F, Ciccarese G, Gasparini G. Contemporary infectious exanthems: an update. Future Microbiol. 2017;12:171‐93.
Chen Y, Liu Q, Guo D. Emerging coronaviruses: genome structure, replication, and pathogenesis. J Med Virol. 2020;92(4):418-23.
Prompetchara E, Ketloy C, Palaga T. Immune responses in COVID-19 and potential vaccines: lessons learned from SARS and MERS epidemic. Asian Pac J Allergy Immunol. 2020;38(1):1–9.
Sharlala H, Adebajo A. Virus‐induced vasculitis. Curr Rheumatol Rep. 2008; 10(6): 449‐ 452.
Gansner JM, Berliner N. The rheumatology/hematology interface: CAPS and MAS diagnosis and management. Hematology Am Soc Hematol Educ Program. 2018;2018(1):313–7.
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;203(2):631–7.
Soler MJ, Batlle M, Riera M, Campos B, Ortiz-Perez JT, Anguiano L, et al. ACE2 and ACE in acute and chronic rejection after human heart transplantation. Int J Cardiol. 2019;275:59–64.
Varga Z, Flammer AJ, Steiger P, Haberecker M, Andermatt R, Zinkernagel AS, et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet. 2020;395(10234):1417-8.
Heurich A, Hofmann-Winkler H, Gierer S, Liepold T, Jahn O, Pöhlmann S. TMPRSS2 and ADAM17 cleave ACE2 differentially and only proteolysis by TMPRSS2 augments entry driven by the severe acute respiratory syndrome coronavirus spike protein. J Virol. 2014;88(2):1293-307.
Mousavizadeh L, Ghasemi S. Genotype and phenotype of COVID-19: their roles in pathogenesis. J Microbiol Immunol Infect. 2020.
Wambier CG, Goren A. SARS-COV-2 infection is likely to be androgen mediated. J Am Acad Dermatol. 2020;83(1):308-9.
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. Transl Res. 2020;220:1-13.
COVID-19 Treatment Guidelines Panel. Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. National Institutes of Health. Available at https://www.covid19treatmentguidelines.nih.gov/. Accessed 10 November 2020.
Velthuis AJ, van den Worm SH, Sims AC, Baric RS, Snijder EJ, van Hemert MJ. Zn(2+) inhibits coronavirus and arterivirus RNA polymerase activity in vitro and zinc ionophores block the replication of these viruses in cell culture. PLoS Pathog. 2010;6(11):e1001176.
Altarelli M, Ben-Hamouda N, Schneider A, Berger MM. Copper Deficiency: Causes, Manifestations, and Treatment. Nutr Clin Pract. 2019;34(4):504-13.
Wei XB, Wang ZH, Liao XL, et al. Efficacy of vitamin C in patients with sepsis: an updated meta-analysis. Eur J Pharmacol. 2020;868:172889.
Fisher BJ, Seropian IM, Kraskauskas D, et al. Ascorbic acid attenuates lipopolysaccharide-induced acute lung injury. Crit Care Med. 2011;39(6):1454-60.