The Dermatological Spectrum of Coronavirus Disease-19 Disease: Cutaneous Signs for Diagnostics and Prognosis and an Expanded Classification
COVID-19 and skin
DOI:
https://doi.org/10.3889/oamjms.2020.5091Keywords:
Coronavirus disease-19 pandemic, Severe acute respiratory syndrome- coronavirus-2, Cutaneous signs, Acro-ischemic lesions, Rash, Chilblain-like eruptions, Androgenetic alopeciaAbstract
During severe acute respiratory syndrome coronavirus (CoV)-2- induced CoV disease (COVID)-19 pandemic cutaneous signs of the disease gained increasing interest for early diagnosis, to establish a prognosis and for differential diagnoses. The present review aims to summarize current knowledge on cutaneous findings in COVID-19. The findings are classified and described clinically. The spectrum of cutaneous signs include acro-ischemic lesions, rash, chilblain-like eruptions, and androgenetic alopecia. Their significance is given, and treatment options are presented. This may allow the clinicians to support triage and optimal treatment for COVID-19 patients.
Key Bullets
• _The COVID-19 pandemic has affected patients world-wide. Despite the leading symptoms are in the respiratory, cardiovascular, hematologic, and neurologic systems, cutaneous manifestations are increasingly be observed.
• _Cutaneous findings in COVID-19 patients may have prognostic and therapeutic consequences. This review attempts to classify cutaneous symptoms, document the observed frequency of their occurrence, the significance for triage of COVID-19-patients, and the treatment of cutaneous manifestations.
Downloads
Metrics
Plum Analytics Artifact Widget Block
References
Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, et al. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med. 2020;382(8):727-33. PMid:31978945
Cevik M, Bamford CG, Ho A. COVID-19 pandemic-a focused review for clinicians. Clin Microbiol Infect. 2020;6(7):842-7.
De Toni L, Garolla A, Di Nisio A, Rocca MS, Foresta C. Caution in the management of SARS-CoV-2 infection in males. Andrology. 2020;2020:12829. https://doi.org/10.1111/andr.12829
Wu D, Wu T, Liu Q, Yang Z. The SARS-CoV-2 outbreak: What we know. Int J Infect Dis. 2020;94:44-8. PMid:32171952
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(10223):497-506. https://doi.org/10.1016/s0140-6736(20)30183-5
Holshue ML, DeBolt C, Lindquist S, Lofy KH, Wiesman J, Bruce H, et al. First case of 2019 novel coronavirus in the United States. N Engl J Med. 2020;382(10):929-36. PMid:32004427
Hess DC, Eldahshan W, Rutkowski E. COVID-19-related stroke. Transl Stroke Res. 2020;11(3):322-5. https://doi.org/10.1007/s12975-020-00818-9
Long B, Brady WJ, Koyfman A, Gottlieb M. Cardiovascular complications in COVID-19. Am J Emerg Med. 2020;38(7):1504-7. PMid:32317203
Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. 2020;323(11):1061-9. https://doi.org/10.1001/jama.2020.1585 PMid:32031570
Grasselli G, Pesenti A, Cecconi M. Critical care utilization for the COVID-19 outbreak in Lombardy, Italy: Early experience and forecast during an emergency response. JAMA. 2020;2020:4031. https://doi.org/10.1001/jama.2020.4031 PMid:32167538
World Health Organization. Preliminary Assessment of the Severity of COVID-19 in Germany Based on the Transmitted Cases According to German Infection Protection Act. Geneva, Switzerland: World Health Organization; 2020.
Yao XH, Li TY, He ZC, Ping YF, Liu HW, Yu SC, et al. A pathological report of three COVID-19 cases by minimal invasive autopsies. Zhonghua Bing Li Xue Za Zhi. 2020;49(5):411-7. PMid:32172546
Sekulic M, Harper H, Nezami BG, Shen DL, Sekulic SP, Koeth AT, et al. Molecular detection of SARS-CoV-2 infection in FFPE samples and histopathologic findings in fatal SARS-CoV-2 cases. Am J Clin Pathol. 2020;154(2):190-200. https://doi.org/10.1093/ajcp/aqaa091 PMid:32451533
Su H, Yang M, Wan C, Yi LX, Tang F, Zhu HY, et al. Renal histopathological analysis of 26 postmortem findings of patients with COVID-19 in China. Kidney Int. 2020;98(1):219-27. https://doi.org/10.1016/j.kint.2020.04.003 PMid:32327202
Wichmann D, Sperhake JP, Lütgehetmann M, Steurer S, Edler C, Heinemann A, et al. Autopsy findings and venous thromboembolism in patients with COVID-19. Ann Intern Med. 2020;2020:M20-2003. PMid:32374815
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. https://doi.org/10.1016/s0140-6736(20)30937-5 PMid:32325026
Xue X, Mi Z, Wang Z, Pang Z, Liu H, Zhang F. High expression of ACE2 on the keratinocytes reveals skin as a potential target for SARS-CoV-2. J Invest Dermatol. 2020;2020:87. https://doi.org/10.1016/j.jid.2020.05.087 PMid:32454066
Venkatakrishnan AJ, Puranik A, Anand A, Zemmour D, Yao X, Wu X, et al. Knowledge synthesis of 100 million biomedical documents augments the deep expression profiling of coronavirus receptors. Elife. 2020;9:e58040. https://doi.org/10.7554/elife.58040 PMid:32463365
Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020;382(18): 1708-20.
Wollina U, Karadağ AS, Rowland-Payne C, Chiriac A, Lotti T. Cutaneous signs in COVI-19 patients: A review. Dermatol Ther. 2020;10:e13549. https://doi.org/10.1111/dth.13549 PMid:32390279
Freeman EE, McMahon DE, Fitzgerald ME, Fox LP, Rosenbach M, Takeshita J, et al. The AAD COVID-19 Registry: Crowdsourcing Dermatology in the Age of COVID-19. J Am Acad Dermatol. 2020;83(2):509-10. https://doi.org/10.1016/j.jaad.2020.04.045 PMid:32305438
Galván Casas C, Català A, Hernández GC, Rodríguez- Jiménez R, Fernández-Nieto D, Lario AR, 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. https://doi.org/10.1111/bjd.19163 PMid:32348545
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 Rep. 2020;6(6):489-92. https://doi.org/10.1016/j.jdcr.2020.04.011 PMid:32363225
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):739-43. https://doi.org/10.1111/ijd.14937 PMid:32329897
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;37(3):406-11. https://doi.org/10.1111/pde.14215 PMid:32386460
Bouaziz JD, Duong T, Jachiet M, Velter C, Lestang P, Cassius C, et al. Vascular skin symptoms in COVID-19: A French observational study. J Eur Acad Dermatol Venereol. 2020;27:16544. https://doi.org/10.1111/jdv.16544 PMid:32339344
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. 2020;34(7):e291-3. https://doi.org/10.1111/jdv.16526 PMid:32330334
de Masson A, Bouaziz JD, Sulimovic L, Cassius C, Jachiet M, Ionescu MA, et al. Chilblains are a common cutaneous finding during the COVID-19 pandemic: A retrospective nationwide study from France. J Am Acad Dermatol. 2020;3(2):667-70. PMid:32380219
Colonna C, Monzani NA, Rocchi A, Gianotti R, Boggio F, Gelmetti C. Chilblains-like lesions in children following suspected Covid-19 infection. Pediatr Dermatol. 2020;37(3):437-41. https://doi.org/10.1111/pde.14210 PMid:32374033
Docampo-Simón A, Sánchez-Pujol MJ, Juan-Carpena G, Palazón-Cabanes JC, Vergara-De Caso E, Berbegal L, et al. Are chilblain-like acral skin lesions really indicative of COVID-19? A prospective study and literature review. J Eur Acad Dermatol Venereol. 2020;37(3):435-6. https://doi.org/10.1111/jdv.16665
Genovese G, Colonna C, Marzano AV. Varicella-like exanthem associated with COVID-19 in an 8-year-old girl: A diagnostic clue? Pediatr Dermatol. 2020;37(3):435-6. https://doi.org/10.1111/pde.14201 PMid:32315079
Guarneri C, Rullo EV, Pavone P, Berretta M, Ceccarelli M, Natale A, et al. Silent COVID-19: What your skin can reveal. Lancet Infect Dis. 2020;2020:30402-3. https://doi.org/10.1016/s1473-3099(20)30402-3 PMid:32437697
Ruggiero G, Arcangeli F, Lotti T. Therapy for probable covid- 19 associated erythema pernio-like lesions in pediatric age. Case report. Dermatol Ther. 2020;2020:e13616. https://doi.org/10.1111/dth.13616
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. J Am Acad Dermatol. 2020;83(1):280-5. https://doi.org/10.1016/j.jaad.2020.05.072 PMid:32305439
Ortega-Quijano D, Jimenez-Cauhe J, Burgos-Blasco P, Jimenez- Gomez N, Fernandez-Nieto D. Reply to “Varicella-like exanthem as a specific COVID-19-associated skin manifestation: multicenter case series of 22 patients”: Discussing specificity. J Am Acad Dermatol. 2020;83(1):e87. https://doi.org/10.1016/j.jaad.2020.04.156 PMid:32380215
Llamas-Velasco M, Rodríguez-Jiménez P, Chicharro P, De Argila D, Muñoz-Hernández P, Daudén E. Reply to “Varicella-like exanthem as a specific COVID-19-associated skin manifestation: Multicenter case series of 22 patients”: To consider varicella-like exanthem associated with COVID-19, virus varicella zoster and virus herpes simplex must be ruled out. J Am Acad Dermatol. 2020;2020:30943-9. https://doi.org/10.1016/j.jaad.2020.04.180 PMid:32442700
Bouaziz JD, Duong T, Jachiet M, Velter C, Lestang P, Cassius C, et al. Vascular skin symptoms in COVID-19: A French observational study. J Eur Acad Dermatol Venereol. 2020;2020:16544. https://doi.org/10.1111/jdv.16544 PMid:32339344
Zhang JJ, Dong X, Cao YY, Yuan YD, Yang YB, Yan YQ, et al. Clinical characteristics of 140 patients infected with SARS-CoV-2 in Wuhan, China. Allergy. 2020;75(7):1730-41. https://doi.org/10.1111/all.14238 PMid:32077115
Sachdeva M, Gianotti R, Shah M, Bradanini L, Tosi D, Veraldi S, et al. Cutaneous manifestations of COVID-19: Report of three cases and a review of literature. J Dermatol Sci. 2020;98(2):75- 81. https://doi.org/10.1016/j.jdermsci.2020.04.011 PMid:32381430
Dastoli S, Bennardo L, Patruno C, Nisticò SP. Are erythema multiforme and urticaria related to a better outcome of COVID 19? Dermatol Ther. 2020;2020:13681. https://doi.org/10.1111/dth.13681 PMid:32447798
Jimenez-Cauhe J, Ortega-Quijano D, Carretero-Barrio I, Suarez-Valle A, Saceda-Corralo D, Del Real CM, et al. Erythema multiforme-like eruption in patients with COVID-19 infection: Clinical and histological findings. Clin Exp Dermatol. 2020;2020:14281. https://doi.org/10.1111/ced.14281 PMid:32385858
Ehsani AH, Nasimi M, Bigdelo Z. Pityriasis rosea as a cutaneous manifestation of COVID-19 infection. J Eur Acad Dermatol Venereol. 2020;2020:16579. https://doi.org/10.1111/jdv.16579 PMid:32359180
Balestri R, Termine S, Rech G, Girardelli CR. Late onset of acral necrosis after SARS-CoV-2 infection resolution. J Eur Acad Dermatol Venereol. 2020;2020:16668. https://doi.org/10.1111/jdv.16668 PMid:32455499
Zhang Y, Cao W, Xiao M, Li YJ, Yang Y, Zhao J, et al. Clinical and Coagulation Characteristics in 7 Patients With Critical COVID-2019 Pneumonia and Acro-Ischemia. Zhonghua Xue Ye Xue Za Zhi. 2020;41(4):302-7. PMid:32220276
Iba T, Levy JH, Levi M, Connors JM, Thachil J. Coagulopathy of Coronavirus Disease 2019. Crit Care Med. 2020;2020:4458. https://doi.org/10.1097/ccm.0000000000004458 PMid:32467443
Ogura T, Eguchi T, Amano M, Sano T, Nishioka N, Miyano A, et al. Multicenter clinical experience with recombinant soluble thrombomodulin for disseminated intravascular coagulation associated with severe acute cholecystitis. Thromb Res. 2019;176:74-8. https://doi.org/10.1016/j.thromres.2018.12.025 PMid:30780007
Upadhya SR, Mahabala C, Kamat JG, Jeganathan J, Kumar S, Prabhu MV. Plasmapheresis in sepsis-induced thrombotic microangiopathy: A case series. Indian J Crit Care Med. 2020;24(3):195-9. https://doi.org/10.5005/jp-journals-10071-23374 PMid:32435099
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. https://doi.org/10.1111/jdv.16471 PMid:32294259
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 PMid:32213305
Nunthavichitra S, Prapaso S, Luvira V, Muangnoicharoen S, Leaungwutiwong P, Piyaphanee W. Case report: COVID-19 presenting as acute undifferentiated febrile illness a tropical world threat. Am J Trop Med Hyg. 2020;103(1):83-5. https://doi.org/10.4269/ajtmh.20-0440 PMid:32419694
Wollina U. Schamberg-like purpuric eruptions and tonsillitis in mild COVID-19.. Dermatol Ther. 2020;2020:e13766. https://doi.org/10.1111/dth.13766 PMid:32500580
Wu D, Lu J, Liu Q, Ma X, He W. To alert coinfection of COVID- 19 and dengue virus in developing countries in the dengue-endemic area. Infect Control Hosp Epidemiol. 2020;2020:187. https://doi.org/10.1017/ice.2020.187 PMid:32362302
Ribeiro VS, Telles JP, Tuon FF. Arboviral diseases and COVID- 19 in Brazil: Concerns regarding climatic, sanitation and endemic scenario. J Med Virol. 2020;2020:26079. https://doi.org/10.1002/jmv.26079 PMid:32462677
Navarro JC, Arrivillaga-Henríquez J, Salazar-Loor J, Rodriguez-Morales AJ. COVID-19 and dengue, co-epidemics in Ecuador and other countries in Latin America: Pushing strained health care systems over the edge. Travel Med Infect Dis. 2020;2020:101656. https://doi.org/10.1016/j.tmaid.2020.101656 PMid:32268196
Yan G, Lee CK, Lam LT, Yan B, Chua YX, Lim AY, et al. Covert COVID-19 and false-positive dengue serology in Singapore. Lancet Infect Dis. 2020;20(5):536. https://doi.org/10.1016/s1473-3099(20)30158-4 PMid:32145189
Labé P, Ly A, Sin C, Nasser M, Chapelon-Fromont E, Ben Saïd P, et al. Erythema multiforme and Kawasaki disease associated with COVID-19 infection in children. J Eur Acad Dermatol Venereol. 2020;2020:16666. https://doi.org/10.1111/jdv.16666 PMid:32455505
Toubiana J, Poirault C, Corsia A, Bajolle F, Fourgeaud J, Angoulvant F, et al. Outbreak of Kawasaki disease in children during COVID-19 pandemic: A prospective observational study in Paris, France. BMJ. 2020;369:m2094. https://doi.org/10.1136/bmj.m2094 PMid:32493739
Kamali Aghdam M, Jafari N, Eftekhari K. Novel coronavirus in a 15-day-old neonate with clinical signs of sepsis, a case report. Infect Dis (Lond). 2020;52(6):427-9. https://doi.org/10.1080/23744235.2020.1747634 PMid:32233816
Chiotos K, Bassiri H, Behrens EM, Blatz AM, Chang J, Diorio C, et al. Multisystem Inflammatory Syndrome in Children during the COVID-19 pandemic: A case series. J Pediatric Infect Dis Soc. 2020;2020;piaa069. https://doi.org/10.1093/jpids/piaa069 PMid:32463092
Janah H, Zinebi A, Elbenaye J. Atypical erythema multiforme palmar plaques lesions due to Sars-Cov-2. J Eur Acad Dermatol Venereol. 2020;9(3):373-5. https://doi.org/10.1111/jdv.16623 PMid:32386446
Deza Leon MP, Redzepi A, McGrath E, Abdel-Haq N, Shawaqfeh A, Sethuraman U, et al. COVID-19 associated pediatric multi-system inflammatory syndrome. J Pediatr Infect Dis Soc. 2020;9(3):407-8. https://doi.org/10.1093/jpids/piaa061 PMid:32441749
Taşkın B, Vural S, Altuğ E, Demirkesen C, Kocatürk E, Çelebi I, et al. COVID-19 Presenting with atypical sweet’s syndrome. J Eur Acad Dermatol Venereol. 2020;2020:16662. https://doi.org/10.1111/jdv.16662 PMid:32452542
Herrero-Moyano M, Capusan TM, Andreu-Barasoain M, Alcántara-González J, Ruano-Del Salado M, Uceda ME, et al. A clinicopathological study of 8 patients with COVID-19 pneumonia and a late-onset exanthema. J Eur Acad Dermatol Venereol. 2020;2020:16631. https://doi.org/10.1111/jdv.16631 PMid:32426864
Robustelli Test E, Vezzoli P, Carugno A, Raponi F, Gianatti A, Rongioletti F, et al. Acute generalized exanthematous pustulosis with erythema multiforme-like lesions in a COVID-19 woman. J Eur Acad Dermatol Venereol. 2020;2020:16613. https://doi.org/10.1111/jdv.16613 PMid:32386448
Litaiem N, Hajlaoui K, Karray M, Slouma M, Zeglaoui F. Acute generalized exanthematous pustulosis after COVID- 19 treatment with hydroxychloroquine. Dermatol Ther. 2020;2020:e13565. https://doi.org/10.1111/dth.13565 PMid:32401410
Schwartz RA, Janniger CK. Generalized pustular figurate erythema: A newly delineated severe cutaneous drug reaction linked with hydroxychloroquine. Dermatol Ther. 2020;2020:e13380. https://doi.org/10.1111/dth.13380 PMid:32253799
Wambier CG, Vaño-Galván S, McCoy J, Gomez-Zubiaur A, Herrera S, Hermosa-Gelbard A, et al. Androgenetic alopecia present in the majority of hospitalized COVID-19 patients the “gabrin sign”. J Am Acad Dermatol. 2020;83(2):680-2. https://doi.org/10.1016/j.jaad.2020.05.079 PMid:32446821
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;19(7):1545-7. https://doi.org/10.1111/jocd.13443 PMid:32301221
Wollina U. Challenges of COVID-19 pandemic for dermatology. Dermatol Ther. 2020;2020:e13430. PMid:32314460
Downloads
Published
How to Cite
Issue
Section
Categories
License
Copyright (c) 2020 Uwe Wollina, Anca Chiriac, Ayse Serap Karadag (Author)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
http://creativecommons.org/licenses/by-nc/4.0