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Dermatologic manifestations and complications of COVID-19

      Abstract

      The novel coronavirus disease of 2019 (COVID-19) is associated with significant morbidity and mortality. While much of the focus has been on the cardiac and pulmonary complications, there are several important dermatologic components that clinicians must be aware of.

      Objective

      This brief report summarizes the dermatologic manifestations and complications associated with COVID-19 with an emphasis on Emergency Medicine clinicians.

      Discussion

      Dermatologic manifestations of COVID-19 are increasingly recognized within the literature. The primary etiologies include vasculitis versus direct viral involvement. There are several types of skin findings described in association with COVID-19. These include maculopapular rashes, urticaria, vesicles, petechiae, purpura, chilblains, livedo racemosa, and distal limb ischemia. While most of these dermatologic findings are self-resolving, they can help increase one's suspicion for COVID-19.

      Conclusion

      It is important to be aware of the dermatologic manifestations and complications of COVID-19. Knowledge of the components is important to help identify potential COVID-19 patients and properly treat complications.

      Keywords

      1. Introduction

      Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the underlying cause of the novel coronavirus disease of 2019 (COVID-19), which has resulted in over 3.8 million infected patients worldwide [
      • World Health Organization
      ]. While the majority of patients will experience respiratory complaints with congestion, cough, and shortness of breath, some patients may present without any pulmonary symptoms [
      • Guan W.J.
      • Ni Z.Y.
      • Hu Y.
      • et al.
      Clinical characteristics of coronavirus disease 2019 in China.
      ,
      • Long B.
      • Brady W.J.
      • Koyfman A.
      • Gottlieb M.
      Cardiovascular complications in COVID-19 [published online ahead of print, 2020 Apr 18].
      ,
      • Bridwell R.
      • Long B.
      • Gottlieb M.
      Neurologic complications of COVID-19 [published online ahead of print, 2020 May 16].
      ]. As the disease has progressed, literature has described involvement of other organ systems, including the cardiovascular, gastrointestinal, renal, and neurologic systems. Recently, there has been increasing recognition of the dermatologic complications of COVID-19.

      2. Methods

      This brief report outlines the underlying pathophysiology and dermatologic manifestations of COVID-19 with an emphasis on the ED clinician. A literature review of the PubMed and Google Scholar databases was performed from inception to May 2nd, 2020 for articles using the keywords COVID-19, SARS-CoV-2, dermatolog*, and skin for production of this brief report. Authors included case reports and series, retrospective and prospective studies, systematic reviews and meta-analyses, clinical guidelines, and narrative reviews. Commentaries and letters were also included. The initial literature search revealed 1553 articles. Authors reviewed all relevant articles and decided which studies to include for the brief report by consensus, with focus on emergency medicine-relevant articles. A total of 41 resources were selected for inclusion in this review.

      3. Discussion

      3.1 Pathophysiology and clinical features

      SARS-CoV-2 is an RNA virus that may enter cells through the angiotensin-converting enzyme 2 (ACE2) receptor found on lung alveolar epithelial cells, small intestine enterocytes, and vasculature, as well as neurologic, endocrine, and cardiac systems [
      • Hamming I.
      • Timens W.
      • Bulthuis M.L.
      • Lely A.T.
      • Navis G.
      • van Goor H.
      Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis.
      ,
      • Zhang H.
      • Penninger J.M.
      • Li Y.
      • Zhong N.
      • Slutsky A.S.
      Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target.
      ]. ACE2 plays several key roles in normal physiology, including breakdown of angiotensin II [
      • Zhang H.
      • Penninger J.M.
      • Li Y.
      • Zhong N.
      • Slutsky A.S.
      Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target.
      ]. SARS-CoV-2 may cause direct lung injury and systemic inflammation, as well as increased coagulation [
      • Huang C.
      • Wang Y.
      • Li X.
      • et al.
      Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China.
      ,
      • 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.
      ,
      • Wang D.
      • Hu B.
      • Hu C.
      • et al.
      Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China.
      ]. These factors can result in multiorgan dysfunction. Recent literature suggests ACE2 is also located in the skin, which may explain some of the dermatologic manifestations in the setting of COVID-19 infection [
      • Li M.Y.
      • Li L.
      • Zhang Y.
      • Wang X.S.
      Expression of the SARS-CoV-2 cell receptor gene ACE2 in a wide variety of human tissues.
      ].
      Some case reports have noted that dermatologic findings may present prior to respiratory symptoms, though most studies suggest skin manifestations present several days after the onset of other symptoms [
      • Recalcati S.
      Cutaneous manifestations in COVID-19: a first perspective.
      ,
      • Henry D.
      • Ackerman M.
      • Sancelme E.
      • Finon A.
      • Esteve E.
      Urticarial eruption in COVID-19 infection.
      ,
      • Genovese G.
      • Colonna C.
      • Marzano A.V.
      Varicella-like exanthem associated with COVID-19 in an 8-year-old girl: a diagnostic clue?.
      ]. These signs and symptoms may assist clinicians in considering the disease before the development of respiratory symptoms and may also be used to identify complications requiring treatment.

      3.2 Dermatologic manifestations

      While the most common symptoms of COVID-19 include congestion, cough, dyspnea, and fever, skin symptoms can occur in up to 20.4% of patients [
      • Recalcati S.
      Cutaneous manifestations in COVID-19: a first perspective.
      ]. One early study found that only 2 of 1099 patients had a “rash”, but investigators may have missed several patients [
      • Guan W.J.
      • Ni Z.Y.
      • Hu Y.
      • et al.
      Clinical characteristics of coronavirus disease 2019 in China.
      ]. A more recent study found rash occurred in 18 of 88 patients, with 8 of these patients having rash at onset, while another study found that rash occurred in 5 out of 103 patients [
      • Recalcati S.
      Cutaneous manifestations in COVID-19: a first perspective.
      ,
      • 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.
      ].
      There are several proposed etiologies for rash in patients with COVID-19. The first is diffuse microvascular vasculitis, resulting from complement system activation. One study found significant complement protein deposition in the dermal capillaries, as well as interstitial and perivascular neutrophilia with prominent leukocytoclasia, suggesting a vasculitic phenomenon [
      • Magro C.
      • Mulvey J.J.
      • Berlin D.
      • et al.
      Complement associated microvascular injury and thrombosis in the pathogenesis of severe COVID-19 infection: a report of five cases.
      ]. Others have suggested that this occurs as a direct effect of the virus. This has been based on high concentrations of lymphocytes without eosinophils, papillary dermal edema, epidermal spongiosis, and lymphohistiocytic infiltrates [
      • 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.
      ,
      • Sanchez A.
      • Sohier P.
      • Benghanem S.
      • et al.
      Digitate papulosquamous eruption associated with severe acute respiratory syndrome coronavirus 2 infection.
      ].
      A rash associated with COVID-19 can involve various body regions, most commonly the trunk, but extremity involvement may also occur [
      • Recalcati S.
      Cutaneous manifestations in COVID-19: a first perspective.
      ]. Pruritus is often minimal but depends on the type of rash, and lesions typically heal quickly, appearing within 3 days and disappearing within 8 days [
      • Recalcati S.
      Cutaneous manifestations in COVID-19: a first perspective.
      ,
      • Marzano A.V.
      • Genovese G.
      • Fabbrocini G.
      • et al.
      Varicella-like exanthem as a specific COVID-19-associated skin manifestation: multicenter case series of 22 patients.
      ].
      A challenging aspect of rash associated with COVID-19 is the myriad types of presentation. Many of these rashes have a broad differential diagnosis. However, it is important to consider COVID-19, especially in the patient with upper respiratory or systemic symptoms (Table 1).
      Table 1Potential causes of each dermatologic finding.
      Dermatologic findingPotential causes
      Maculopapular rashViral exanthem, Scarlet fever, measles, rubella, medication reaction, secondary syphilis, heat rash, leukemia, graft-versus-host disease
      UrticariaAllergic reaction, anaphylaxis, angioedema, autoimmune disease (e.g., systemic lupus erythematosus), hypereosinophilia, chronic urticaria, malignancy
      VesicularVaricella zoster (i.e., chickenpox), herpes zoster (i.e., shingles), herpes simplex, Rhus dermatitis (e.g., poison ivy, poison oak, poison sumac), pemphigoid
      Petechiae/purpuraThrombocytopenia, systemic lupus erythematosus, leukemia, disseminated intravascular coagulation, hemolytic uremic syndrome, thrombotic thrombocytopenic purpura, vasculitis, vitamin C deficiency
      ChilblainsRaynaud's phenomenon, systemic lupus erythematosus, systemic sclerosis, Buerger's disease
      Livedo racemosaAntiphospholipid antibody syndrome, Sneddon syndrome, cryoglobulinemia, multiple myeloma, disseminated intravascular coagulation, hemolytic uremic syndrome, deep venous thrombosis, systemic lupus erythematosus, rheumatoid arthritis, polyarteritis nodosa, Sjogren's syndrome, multiple sclerosis, Parkinson's disease, cancer (e.g., renal cell cancer, breast cancer, lymphoma, leukemia)
      Distal ischemia/necrosisArterial ischemia, disseminated intravascular coagulation, Buerger's disease

      3.3 Maculopapular rash

      There are multiple reports of patients presenting with a maculopapular rash, characterized by erythematous macules covered with small papules, or with large plaques (Fig. 1) [
      • Sanchez A.
      • Sohier P.
      • Benghanem S.
      • et al.
      Digitate papulosquamous eruption associated with severe acute respiratory syndrome coronavirus 2 infection.
      ,
      • Bouaziz J.D.
      • Duong T.
      • Jachiet M.
      • et al.
      Vascular skin symptoms in COVID-19: a french observational study.
      ,
      • Amatore F.
      • Macagno N.
      • Mailhe M.
      • et al.
      SARS-CoV-2 infection presenting as a febrile rash.
      ,
      • Gisondi P.
      • Piaserico S.
      • Conti A.
      • Naldi L.
      Dermatologists and SARS-CoV-2: the impact of the pandemic on daily practice.
      ]. The rash may also be perifollicular and associated with scaling and confluence, which may cause it to be mistaken for pityriasis rosea [
      • 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.
      ]. This type of rash has been suggested to have a mean duration of approximately 9 days [
      • 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.
      ]. One study of 88 patients in Italy found that a maculopapular rash was present in 14 patients (16%) [
      • Recalcati S.
      Cutaneous manifestations in COVID-19: a first perspective.
      ].
      There are several descriptions of the rash in the literature. Four case reports comprising 7 patients described this as diffuse [
      • 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.
      ,
      • Amatore F.
      • Macagno N.
      • Mailhe M.
      • et al.
      SARS-CoV-2 infection presenting as a febrile rash.
      ,
      • Hunt M.
      • Koziatek C.
      A case of COVID-19 pneumonia in a young male with full body rash as a presenting symptom.
      ,
      • Najarian D.J.
      Morbilliform Exanthem associated with COVID-19.
      ]. Some have identified this most commonly on the limbs and trunk [
      • Ahouach B.
      • Harant S.
      • Ullmer A.
      • et al.
      Cutaneous lesions in a patient with COVID-19: are they related?.
      ,
      • Mahé A.
      • Birckel E.
      • Krieger S.
      • Merklen C.
      • Bottlaender L.
      A distinctive skin rash associated with Coronavirus Disease 2019?.
      ,
      • 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).
      ,
      • Rivera-Oyola R.
      • Koschitzky M.
      • Printy R.
      • et al.
      Dermatologic findings in two patients with COVID-19.
      ]. Others have described this on the face [
      • 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.
      ] or bilateral heels [
      • Estébanez A.
      • Pérez-Santiago L.
      • Silva E.
      • Guillen-Climent S.
      • García-Vázquez A.
      • Ramón M.D.
      Cutaneous manifestations in COVID-19: a new contribution.
      ]. Two studies have described this as centrifugal in nature, initially starting in the periumbilical or trunk region before spreading distally [
      • Sanchez A.
      • Sohier P.
      • Benghanem S.
      • et al.
      Digitate papulosquamous eruption associated with severe acute respiratory syndrome coronavirus 2 infection.
      ,
      • 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).
      ].

      3.4 Urticaria

      Urticaria presents with acute, swollen, red wheals or plaques, typically associated with pruritis (Fig. 2). They occur due to a variety of causes and have been documented to occur with COVID-19. One study by Recalcati found urticaria in 3 of 88 COVID-19 patients [
      • Recalcati S.
      Cutaneous manifestations in COVID-19: a first perspective.
      ]. There have been other reports of urticaria affecting various regions of the body in patients of all age groups infected with COVID-19. These cases describe involvement of the trunk, extremities, and head, as well as rash migration, with sparing of the palms and soles [
      • Henry D.
      • Ackerman M.
      • Sancelme E.
      • Finon A.
      • Esteve E.
      Urticarial eruption in COVID-19 infection.
      ,
      • 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.
      ,
      • Bouaziz J.D.
      • Duong T.
      • Jachiet M.
      • et al.
      Vascular skin symptoms in COVID-19: a french observational study.
      ,
      • 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).
      ,
      • Rivera-Oyola R.
      • Koschitzky M.
      • Printy R.
      • et al.
      Dermatologic findings in two patients with COVID-19.
      ,
      • 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.
      ,
      • 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.
      ,
      • 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.
      ,
      • van Damme C.
      • Berlingin E.
      • Saussez S.
      • Accaputo O.
      Acute urticaria with pyrexia as the first manifestations of a COVID-19 infection.
      ]. One of the largest series of 73 COVID-19 positive patients with urticaria found that the trunk was most commonly involved, and pruritus occurred in 92% of cases [
      • 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.
      ]. The mean duration of symptoms was 6.8 days [
      • 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.
      ]. This study also found that urticaria generally occurred concomitantly with other symptoms in the majority of cases and was associated with more severe disease in this study, with a 2% mortality rate in this population [
      • 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.
      ].

      3.5 Vesicular

      Vesicular rashes include small, fluid-filled blisters, often on an erythematous base (Fig. 3). Numerous case reports have documented vesicular rashes in patients with COVID-19, with the study by Recalcati et al. finding vesicles in 1.1% of patients [
      • Recalcati S.
      Cutaneous manifestations in COVID-19: a first perspective.
      ]. Vesicles are more commonly scattered, rather than diffuse in appearance, with one series finding scattered lesions in 16 of 22 patients and diffuse lesions in the remaining six patients [
      • Marzano A.V.
      • Genovese G.
      • Fabbrocini G.
      • et al.
      Varicella-like exanthem as a specific COVID-19-associated skin manifestation: multicenter case series of 22 patients.
      ]. Other case reports have described the appearance of vesicles [
      • Bouaziz J.D.
      • Duong T.
      • Jachiet M.
      • et al.
      Vascular skin symptoms in COVID-19: a french observational study.
      ,
      • Tammaro A.
      • Adebanjo G.A.R.
      • Parisella F.R.
      • Pezzuto A.
      • Rello J.
      Cutaneous manifestations in COVID-19: the experiences of Barcelona and Rome.
      ], with one discussing diffuse involvement of the face and limbs in an 8-year-old [
      • Genovese G.
      • Colonna C.
      • Marzano A.V.
      Varicella-like exanthem associated with COVID-19 in an 8-year-old girl: a diagnostic clue?.
      ]. A separate case series found that the vesicular rash occurred for a mean duration of 10.4 days, with vesicles appearing mostly on the trunk and extremities [
      • 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.
      ]. They also noted that the lesions appeared small and monomorphic as opposed to chickenpox and had hemorrhagic content [
      • 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.
      ]. In most cases, the vesicular rash preceded other symptoms [
      • 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.
      ].

      3.6 Petechiae/purpura

      Petechiae are small, subdermal hemorrhages, while purpura are larger variants of this (Fig. 4). This rash is less commonly described than some of the other rashes, though there are a few case reports describing this in the literature. One case report described a patient with petechiae who was initially misdiagnosed as dengue fever (in an endemic area), but later discovered to have COVID-19 [
      • Joob B.
      • Wiwanitkit V.
      COVID-19 can present with a rash and be mistaken for dengue.
      ]. In this case, the patient was also noted to be significantly thrombocytopenic [
      • Joob B.
      • Wiwanitkit V.
      COVID-19 can present with a rash and be mistaken for dengue.
      ]. Another case described a patient with extensive purpura isolated to flexural areas [
      • Jimenez-Cauhe J.
      • Ortega-Quijano D.
      • Prieto-Barrios M.
      • Moreno-Arrones O.M.
      • 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.
      ]. Thrombocytopenia is not a common complication in COVID-19, so this may reflect a less common complication, or the rash may be due to an alternate etiology such as vasculitis.

      3.7 Chilblains

      Chilblains (also known as pernio or perniosis) is an abnormal response to cold, wherein distal arteries and veins constrict, which can lead to pruritic and tender wounds on the extremities (Fig. 5). Patients can present with erythematous or violaceous papules and macules, bullae, or digital swelling [
      • Recalcati S.
      • Barbagallo T.
      • Frasin L.A.
      • et al.
      Acral cutaneous lesions in the time of COVID-19.
      ]. This has been increasingly recognized in association with COVID-19. There have been nearly 100 cases of chilblains associated with COVID-19 already described in the literature [
      • Bouaziz J.D.
      • Duong T.
      • Jachiet M.
      • et al.
      Vascular skin symptoms in COVID-19: a french observational study.
      ,
      • 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.
      ,
      • Recalcati S.
      • Barbagallo T.
      • Frasin L.A.
      • et al.
      Acral cutaneous lesions in the time of COVID-19.
      ,
      • Landa N.
      • Mendieta-Eckert M.
      • Fonda-Pascual P.
      • Aguirre T.
      Chilblain-like lesions on feet and hands during the COVID-19 Pandemic.
      ]. Galván Casas et al. described 71 cases which had a mean duration of 12.7 days [
      • 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.
      ]. The authors noted that it typically presented in the hands or feet and was usually asymmetrical [
      • 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.
      ]. Thirty-two percent of cases were painful and 30% had associated pruritus [
      • 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.
      ]. Compared with other rashes, chilblains typically occurred later in the disease course and after other symptoms had presented [
      • 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.
      ]. The authors also noted that this was more common in younger patients (mean age 32 years) than the other rashes in their study [
      • 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.
      ]. This was also evidenced by Recalcati who described 14 cases occurring in mostly children and young adults [
      • Recalcati S.
      • Barbagallo T.
      • Frasin L.A.
      • et al.
      Acral cutaneous lesions in the time of COVID-19.
      ]. In this latter case series, 10 patients had feet involvement, while only 6 had hand involvement [
      • Recalcati S.
      • Barbagallo T.
      • Frasin L.A.
      • et al.
      Acral cutaneous lesions in the time of COVID-19.
      ].

      3.8 Livedo racemosa

      Livedo racemosa (LR) is a violaceous web or net-like patterning of the skin similar to livedo reticularis; however, this is found diffusely, compared to livedo reticularis that is found in gravity-dependent areas (Fig. 6) [
      • Uthman I.W.
      • Khamashta M.A.
      Livedo racemosa: a striking dermatological sign for the antiphospholipid syndrome.
      ]. Reports have described LR or retiform purpura (branching grouping of purpura) in 3 patients in one series [
      • Magro C.
      • Mulvey J.J.
      • Berlin D.
      • et al.
      Complement associated microvascular injury and thrombosis in the pathogenesis of severe COVID-19 infection: a report of five cases.
      ], as well as several other case reports [
      • Bouaziz J.D.
      • Duong T.
      • Jachiet M.
      • et al.
      Vascular skin symptoms in COVID-19: a french observational study.
      ,
      • Manalo I.F.
      • Smith M.K.
      • Cheeley J.
      • Jacobs R.
      A dermatologic manifestation of COVID-19: transient livedo reticularis.
      ]. One series of 21 cases found that the rash had a mean duration of 9.4 days [
      • 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.
      ]. LR was more common in older patients, with a mean age of 63 years [
      • 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.
      ]. LR was also associated with more severe disease (10% mortality rate) [
      • 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.
      ].

      3.9 Distal ischemia and necrosis

      Perhaps one of the most severe complications includes distal ischemia resulting in tissue necrosis (Fig. 7). One case series described seven patients with acro-ischemia including finger and toe cyanosis, skin bullae, and dry gangrene [
      • Zhang Y.
      • Cao W.
      • Xiao M.
      • et al.
      Clinical and coagulation characteristics of 7 patients with critical COVID-2019 pneumonia and acro-ischemia.
      ]. Another report of two patients described the appearance of red and purple papules on the distal fingers due to distal ischemia, which occurred before the appearance of other symptoms [
      • Alramthan A.
      • Aldaraji W.
      A case of COVID-19 presenting in clinical picture resembling chilblains disease. First report from the Middle East.
      ]. Other case reports describe a 13-year-old with distal toe ischemia presenting with blistering and necrosis [
      • Mazzotta F.
      • Troccoli T.
      Acute Acro-ischemia in the child at the time of COVID-19.
      ], as well as one patient with necrotic purpura [
      • Bouaziz J.D.
      • Duong T.
      • Jachiet M.
      • et al.
      Vascular skin symptoms in COVID-19: a french observational study.
      ]. Given the coagulopathic impact of SARS-CoV-2, these findings necessitate discussion with vascular surgery specialists and consideration of intravenous thrombolytics.

      4. Conclusion

      Patients with COVID-19 most commonly present with respiratory symptoms, but multiorgan involvement can occur, with multiple skin manifestations. Dermatologic findings may include a maculopapular rash, urticaria, vesicular rash, petechia, purpura, chilblains, livedo racemosa, and distal ischemia. These rashes should trigger consideration of COVID-19, and understanding these manifestations is important to help identify potential COVID-19 patients and properly treat complications.

      Meetings

      None.

      Grants

      None.

      Author contributions

      None except listed.

      Declaration of competing interest

      None.

      Acknowledgements

      This review does not reflect the views or opinions of the U.S. government, Department of Defense, U.S. Army, U.S. Air Force, Brooke Army Medical Center, or SAUSHEC EM Residency Program.

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