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Figure.  Clinical Presentation of Exanthem and Enanthem in a Patient With Severe Acute Respiratory Syndrome Coronavirus 2 Infection
Clinical Presentation of Exanthem and Enanthem in a Patient With Severe Acute Respiratory Syndrome Coronavirus 2 Infection

This patient presented with coalescing purpuric macules distributed in a periflexural pattern, mainly around the buttocks and inguinal area (A), and enanthem on hard and soft palate consisting of millimetric petechiae without erythema (B).

Table.  Clinical and Laboratory Findings of 6 Patients With COVID-19 and Enanthem
Clinical and Laboratory Findings of 6 Patients With COVID-19 and Enanthem
1.
Recalcati  S.  Cutaneous manifestations in COVID-19: a first perspective.   J Eur Acad Dermatol Venereol. 2020;34(5):e212-e213. doi:10.1111/jdv.16387PubMedGoogle ScholarCrossref
2.
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.   J Am Acad Dermatol. Published online April 10, 2020. doi:10.1016/j.jaad.2020.04.016PubMedGoogle Scholar
3.
Manalo  IF, Smith  MK, Cheeley  J, Jacobs  R.  A dermatologic manifestation of COVID-19: transient livedo reticularis.   J Am Acad Dermatol. Published online April 10, 2020. PubMedGoogle Scholar
4.
Zhang  Y, Cao  W, Xiao  M,  et al.  Clinical and coagulation characteristics of 7 patients with critical COVID-2019 pneumonia and acro-ischemia.  Article in Chinese.  Zhonghua Xue Ye Xue Za Zhi. 2020;41(0):E006. doi:10.3760/cma.j.issn.0253-2727.2020.0006PubMedGoogle Scholar
5.
Drago  F, Paolino  S, Rebora  A,  et al.  The challenge of diagnosing atypical exanthems: a clinico-laboratory study.   J Am Acad Dermatol. 2012;67(6):1282-1288. doi:10.1016/j.jaad.2012.04.014PubMedGoogle ScholarCrossref
6.
Jimenez-Cauhe  J, Ortega-Quijano  D, Carretero-Barrio  I,  et al.  Erythema multiforme-like eruption in patients with COVID-19 infection: clinical and histological findings.   Clin Exp Dermatol. Published online May 9, 2020. doi:10.1111/ced.14281PubMedGoogle Scholar
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    Research Letter
    July 15, 2020

    Enanthem in Patients With COVID-19 and Skin Rash

    Author Affiliations
    • 1Dermatology Department, Hospital Universitario Ramon y Cajal, IRYCIS, Madrid, Spain
    JAMA Dermatol. Published online July 15, 2020. doi:10.1001/jamadermatol.2020.2550

    Recalcati1 recently reported skin manifestations in 18 patients in Italy with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, or coronavirus disease 2019 (COVID-19), describing “erythematous rash,” “widespread urticaria,” and “chickenpox-like vesicles.” Additional reports have described other rashes, including petechial and purpuric changes,2 transient livedo reticularis,3 and acro-ischemic lesions.4 Whether these manifestations are directly related to COVID-19 remains unclear, since both viral infections and adverse drug reactions are frequent causes of exanthems. An important clue to distinguish between both entities is the presence of enanthem (oral cavity lesions).5 However, owing to safety concerns, many patients with suspected or confirmed COVID-19 do not have their oral cavity examined. Herein we describe variants of enanthem in a series of patients with COVID-19.

    Methods

    We included 21 consecutive patients from a tertiary care hospital who had skin rash and COVID-19, confirmed by real-time reverse transcriptase–polymerase chain reaction from a nasopharyngeal swab, and who required dermatology consultation from March 30 to April 8, 2020. The oral cavities of patients presenting with skin rash were systematically examined. Enanthems were classified into 4 categories: petechial, macular, macular with petechiae, or erythematovesicular.5 This study was approved by the institutional review board of Ramon y Cajal University Hospital in Madrid. Accordingly, informed consent was obtained verbally from all patients before examination, and they have been deidentified through omission of individual age and sex.

    Results

    Of 21 patients with COVID-19 and skin rash, 6 patients (29%) had enanthem. The age range of these patients was between 40 and 69 years, and 4 of the 6 (66%) were women. The morphology of the skin rash was papulovesicular, purpuric periflexural, and erythema multiforme–like in 1, 2, and 3 patients, respectively. The clinical and histologic findings of the erythema multiforme–like exanthem have been reported elsewhere.6 No enanthem was observed in patients with urticarial or typical maculopapular rashes. The enanthem was macular in 1 patient, petechial in 2 patients, and macular with petechiae in 3 patients, and was located in the palate in all patients (Figure). No patient presented with an erythemato-vesicular enanthem. The mean (range) time between the onset of COVID-19 symptoms and the appearance of mucocutaneous lesions was 12.3 days (range, −2 to 24 days). Interestingly, this latency was shorter in patients with petechial enanthem compared with those with a macular lesion with petechiae appearance. Drug intake and laboratory findings were not associated with any enanthem type (Table).

    Discussion

    The etiological diagnosis of exanthems can be challenging for dermatologists. Some useful clues are the rash morphology, the associated symptoms, and the presence of enanthem.5 Pustular morphology and dusky lesions are suggestive of drug etiology, while petechial or vesicular pattern, involvement of buttocks or acral sites, and enanthem suggest an infectious etiology, especially viral.5 In a large series of patients with atypical exanthems,5 only 9% of patients with enanthem had a drug reaction, whereas 88% had an infectious etiology, most frequently viral. Enanthems may present with petechiae, macules, papules, or vesicles in the mouth. Erythemato-vesicular and petechial patterns were most commonly associated with viral infections, the latter being more frequent in adults.5 This is consistent with the present series, in which 5 patients (83%) had petechiae as a main component of the enanthem. Furthermore, the 2 patients with a pure petechial enanthem developed these lesions 2 days before and 2 days after the onset of COVID-19 symptoms, making association with the drug intake unlikely.

    This work describes preliminary observations and is limited by the small number of cases and the absence of a control group. Despite the increasing reports of skin rashes in patients with COVID-19, establishing an etiological diagnosis is challenging. However, the presence of enanthem is a strong clue that suggests a viral etiology rather than a drug reaction, especially when a petechial pattern is observed.

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    Article Information

    Accepted for Publication: May 19, 2020.

    Corresponding Author: Juan Jimenez-Cauhe, MD, Dermatology Department, Hospital Universitario Ramon y Cajal, Carretera Colmenar Viejo km 9.100, 28034 Madrid, Spain (jjimenezc92@gmail.com).

    Published Online: July 15, 2020. doi:10.1001/jamadermatol.2020.2550

    Author Contributions: Dr Jimenez-Cauhe had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

    Concept and design: Jimenez-Cauhe, Ortega-Quijano, de Perosanz-Lobo, Vañó-Galván, Fernandez-Guarino.

    Acquisition, analysis, or interpretation of data: Jimenez-Cauhe, Burgos-Blasco, Vañó-Galván, Fernandez-Nieto.

    Drafting of the manuscript: Jimenez-Cauhe, Ortega-Quijano, de Perosanz-Lobo, Fernandez-Nieto.

    Critical revision of the manuscript for important intellectual content: de Perosanz-Lobo, Burgos-Blasco, Vañó-Galván, Fernandez-Guarino, Fernandez-Nieto.

    Statistical analysis: Ortega-Quijano, Burgos-Blasco, Vañó-Galván.

    Administrative, technical, or material support: Jimenez-Cauhe, Burgos-Blasco.

    Supervision: de Perosanz-Lobo, Vañó-Galván, Fernandez-Guarino.

    Conflict of Interest Disclosures: None reported.

    Additional Contributions: We thank the pictured patient for granting permission to publish this information.

    References
    1.
    Recalcati  S.  Cutaneous manifestations in COVID-19: a first perspective.   J Eur Acad Dermatol Venereol. 2020;34(5):e212-e213. doi:10.1111/jdv.16387PubMedGoogle ScholarCrossref
    2.
    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.   J Am Acad Dermatol. Published online April 10, 2020. doi:10.1016/j.jaad.2020.04.016PubMedGoogle Scholar
    3.
    Manalo  IF, Smith  MK, Cheeley  J, Jacobs  R.  A dermatologic manifestation of COVID-19: transient livedo reticularis.   J Am Acad Dermatol. Published online April 10, 2020. PubMedGoogle Scholar
    4.
    Zhang  Y, Cao  W, Xiao  M,  et al.  Clinical and coagulation characteristics of 7 patients with critical COVID-2019 pneumonia and acro-ischemia.  Article in Chinese.  Zhonghua Xue Ye Xue Za Zhi. 2020;41(0):E006. doi:10.3760/cma.j.issn.0253-2727.2020.0006PubMedGoogle Scholar
    5.
    Drago  F, Paolino  S, Rebora  A,  et al.  The challenge of diagnosing atypical exanthems: a clinico-laboratory study.   J Am Acad Dermatol. 2012;67(6):1282-1288. doi:10.1016/j.jaad.2012.04.014PubMedGoogle ScholarCrossref
    6.
    Jimenez-Cauhe  J, Ortega-Quijano  D, Carretero-Barrio  I,  et al.  Erythema multiforme-like eruption in patients with COVID-19 infection: clinical and histological findings.   Clin Exp Dermatol. Published online May 9, 2020. doi:10.1111/ced.14281PubMedGoogle Scholar
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