Livedoid and Purpuric Skin Eruptions Associated With Coagulopathy in Severe COVID-19 | Dermatology | JAMA Dermatology | JAMA Network
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Figure.  Clinical and Pathologic Findings
Clinical and Pathologic Findings

A, Fixed, nonblanching livedo racemosa involving the left plantar foot and toes. B, This biopsy specimen reveals a pauci-inflammatory thrombogenic vasculopathy (hematoxylin-eosin, original magnification ×400).

Table.  Summary of Cases
Summary of Cases
1.
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.   Br J Dermatol. Published online April 29, 2020. PubMedGoogle Scholar
2.
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.   Transl Res. 2020;220:1-13. doi:10.1016/j.trsl.2020.04.007 PubMedGoogle ScholarCrossref
3.
Panigada  M, Bottino  N, Tagliabue  P,  et al.  Hypercoagulability of COVID-19 patients in intensive care unit: a report of thromboelastography findings and other parameters of hemostasis.   J Thromb Haemost. Published online April 17, 2020. PubMedGoogle Scholar
4.
Klok  FA, Kruip  MJHA, van der Meer  NJM,  et al.  Incidence of thrombotic complications in critically ill ICU patients with COVID-19.   Thromb Res. 2020;191:145-147. doi:10.1016/j.thromres.2020.04.013 PubMedGoogle ScholarCrossref
5.
Yin  S, Huang  M, Li  D, Tang  N.  Difference of coagulation features between severe pneumonia induced by SARS-CoV2 and non-SARS-CoV2.   J Thromb Thrombolysis. Published online April 3, 2020. PubMedGoogle Scholar
6.
Thachil  J, Tang  N, Gando  S,  et al.  ISTH interim guidance on recognition and management of coagulopathy in COVID-19.   J Thromb Haemost. 2020;18(5):1023-1026. doi:10.1111/jth.14810 PubMedGoogle ScholarCrossref
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    Research Letter
    August 5, 2020

    Livedoid and Purpuric Skin Eruptions Associated With Coagulopathy in Severe COVID-19

    Author Affiliations
    • 1Department of Dermatology, NewYork-Presbyterian/Weill Cornell Medical College, New York
    • 2Division of Hematology and Oncology, Department of Medicine, NewYork-Presbyterian/Weill Cornell Medical College, New York
    • 3Department of Pathology and Laboratory Medicine, NewYork-Presbyterian/Weill Cornell Medical College, New York
    JAMA Dermatol. 2020;156(9):1-3. doi:10.1001/jamadermatol.2020.2800

    As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection spreads globally, dermatologists are recognizing a variety of cutaneous manifestations in patients with coronavirus disease 2019 (COVID-19). A recent Spanish report1 categorized skin findings in 375 patients with suspected and confirmed COVID-19, including livedoid and necrotic eruptions, which were noted in patients with more severe disease. The authors suggested that these skin manifestations may be associated with occlusive vascular disease.

    Methods

    In this case series, we describe the experience of 4 patients from 2 academic hospitals in New York City from March 13 to April 3, 2020, who presented with severe COVID-19 (confirmed by SARS-CoV-2 real-time polymerase chain reaction using Panther Fusion or Roche Cobas tests) and acute respiratory distress syndrome requiring intubation. The patients had skin findings of acral fixed livedo racemosa and retiform purpura, for which the dermatology department was consulted. This study was deemed exempt from formal institutional review board approval by NewYork-Presbyterian/Weill Cornell Medical College because it is a report of clinical care and is not considered human participants research. Written informed consent for skin biopsy was obtained from health care proxies because all patients were intubated and required sedation.

    Results

    Punch biopsies were performed for all 4 patients (age range, 40-80 years). The results of each biopsy demonstrated a pauci-inflammatory thrombogenic vasculopathy involving capillaries, venules, and/or arterioles or small arteries (Figure). In 3 of 4 patients, dermal arterial thrombosis was noted, reminiscent of antiphospholipid syndrome, without any diagnostic confirmation of these antibodies.

    All 4 patients had d-dimer levels of more than 3 μg/mL (normal range, 0-0.229 μg/mL) (to convert to nanomoles per liter, multiply by 5.476) and a suspected pulmonary embolus within 1 to 5 days of the reported skin findings (Table). All 4 patients initiated a standard prophylactic dose of anticoagulation therapy at admission, and all received therapeutic anticoagulation owing to increasing d-dimer levels and suspected thrombotic events.

    Discussion

    These cases add to a growing body of literature supporting livedo racemosa and retiform purpura as cutaneous findings in patients with COVID-19.2 Livedo racemosa and retiform purpura are hallmark manifestations of cutaneous thrombosis, with livedo racemosa representing partial occlusion of cutaneous blood vessels and retiform purpura representing full occlusion of cutaneous blood vessels. All patients had marked d-dimer level elevations and suspected pulmonary emboli, suggesting that these skin findings may be a clinical clue to an underlying thrombotic state. The features of the 4 patients are not consistent with other conditions predisposing to thrombosis, including typical disseminated intravascular coagulation or thrombotic microangiopathy, given the normal or increased fibrinogen level, normal haptoglobin level, lack of persistent severe thrombocytopenia, and absence of schistocytes on results of peripheral blood smear testing.

    The exact pathophysiologic features of the coagulopathy in these patients was not yet clear; however, in all skin biopsy samples, there were deposits of complement including C5b-9, suggesting a critical role for complement activation in the pathogenesis of the thrombotic diathesis. Coagulopathy in the context of severe inflammation (elevated d-dimer, fibrinogen, or C-reactive protein levels) has been reported in patients with COVID-19.3 Because of the increased incidence of thrombotic events reported in severely ill patients with COVID-194 and recent data suggesting a survival benefit in such patients who receive anticoagulants,5 treatment algorithms for severely ill patients with COVID-19 are including therapeutic anticoagulation at many institutions.6 Despite initiation of prophylactic anticoagulation therapy at admission for all 4 patients, all developed cutaneous thrombosis and a clinically suspected pulmonary embolism.

    The limitations of this report include our inability to confirm the precise timing of rash onset owing to limited full skin examinations. In addition, we did not perform imaging for pulmonary emboli because of efforts to minimize staff exposure.

    The findings suggest that clinicians caring for patients with COVID-19 should be aware of livedoid and purpuric rashes as potential manifestations of an underlying hypercoagulable state. If these skin findings are identified, a skin biopsy should be considered because the result may guide anticoagulation management. Even in the absence of other thrombotic events, consultation with hematology staff, along with escalation of anticoagulation, should be considered.

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    Article Information

    Accepted for Publication: June 1, 2020.

    Published Online: August 5, 2020. doi:10.1001/jamadermatol.2020.2800

    Correction: This article was corrected on September 23, 2020, to fix an error in the byline.

    Corresponding Author: Joanna Harp, MD, Department of Dermatology, NewYork-Presbyterian/Weill Cornell Medical College, 1305 York Ave, 9th Floor, New York, NY 10021 (joh9090@med.cornell.edu).

    Author Contributions: Drs Droesch and Harp had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

    Concept and design: Droesch, Magro, Harp.

    Acquisition, analysis, or interpretation of data: All authors.

    Drafting of the manuscript: Droesch, Do, Lee, Harp.

    Critical revision of the manuscript for important intellectual content: Droesch, DeSancho, Lee, Magro, Harp.

    Statistical analysis: Harp.

    Administrative, technical, or material support: Magro, Harp.

    Supervision: Magro, Harp.

    Conflict of Interest Disclosures: Dr DeSancho reported serving on the Advisory Boards for Bio Products Laboratory and Sanofi-Genzyme. No other disclosures were reported.

    References
    1.
    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.   Br J Dermatol. Published online April 29, 2020. PubMedGoogle Scholar
    2.
    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.   Transl Res. 2020;220:1-13. doi:10.1016/j.trsl.2020.04.007 PubMedGoogle ScholarCrossref
    3.
    Panigada  M, Bottino  N, Tagliabue  P,  et al.  Hypercoagulability of COVID-19 patients in intensive care unit: a report of thromboelastography findings and other parameters of hemostasis.   J Thromb Haemost. Published online April 17, 2020. PubMedGoogle Scholar
    4.
    Klok  FA, Kruip  MJHA, van der Meer  NJM,  et al.  Incidence of thrombotic complications in critically ill ICU patients with COVID-19.   Thromb Res. 2020;191:145-147. doi:10.1016/j.thromres.2020.04.013 PubMedGoogle ScholarCrossref
    5.
    Yin  S, Huang  M, Li  D, Tang  N.  Difference of coagulation features between severe pneumonia induced by SARS-CoV2 and non-SARS-CoV2.   J Thromb Thrombolysis. Published online April 3, 2020. PubMedGoogle Scholar
    6.
    Thachil  J, Tang  N, Gando  S,  et al.  ISTH interim guidance on recognition and management of coagulopathy in COVID-19.   J Thromb Haemost. 2020;18(5):1023-1026. doi:10.1111/jth.14810 PubMedGoogle ScholarCrossref
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