key: cord-0823578-ijks7zfk
authors: Ocampo‐Candiani, Jorge; Ramos‐Cavazos, Cesar Jair; Arellano‐Mendoza, Maria Ivonne; Arenas‐Guzmán, Roberto; Beirana‐Palencia, Angélica; Salmon‐Demongin, Alfredo; Welsh‐Hernández, Esperanza; Cabo, Horacio A.; Gómez‐Flores, Minerva; Dominguez‐Cherit, Judith; Criado, Paulo Ricardo; Castro‐López, Helena; Alfaro‐Sánchez, Abraham Benjamin; García‐Vargas, Alejandro; Cohen‐Sabban, Emilia N.; del Solar, Manuel; Fich, Félix; Galimberti, Gastón; Gatti, Carlos Fernando; López‐Estebaranz, José Luis; Lupi, Omar; Olmos‐Pérez, Miguel; Pérez‐Alfonzo, Ricardo
title: International registry of dermatological manifestations secondary to COVID‐19 infection in 347 Hispanic patients from 25 countries
date: 2021-05-08
journal: Int J Dermatol
DOI: 10.1111/ijd.15632
sha: e8d5273257cd88787690f28cc3516fd7f5b214f2
doc_id: 823578
cord_uid: ijks7zfk

BACKGROUND: The infection by coronavirus disease 2019 (COVID‐19) has been associated with multiple cutaneous manifestations, although characterization of them in Hispanic patients with darker skin phototypes is lacking. The objective of this study is to characterize the clinical dermatological manifestations associated with COVID‐19 infection in cases with few or without general symptoms in patients from Latin America. METHODS: Cross‐sectional study using a questionnaire that was made for health professionals (physicians with a specialty in dermatology) to investigate dermatological lesions associated with COVID‐19 infection in patients from 25 countries of Latin America. The survey was active from June 9 to July 30, 2020. RESULTS: In this study, information was collected from a total of 347 patients. We found a female gender predominance: 179/347 (51.6%). The mean age at presentation was 40.87 years. The most frequent dermatological manifestations were maculopapular rash and urticarial lesions, followed by papulovesicular lesions, vesicular lesions, chilblain‐like lesions, papular lesions, ecchymosis, petechial purpura, pityriasis rosea‐like lesions, pruritus, palmoplantar dysesthesias, transient livedo, acral necrosis, palpable purpura, livedo racemosa, and retiform purpura. As far as we know, there are no previous reports of pruritus and palmoplantar dysesthesias. CONCLUSIONS: This registry emphasizes skin manifestations as an important criterion for establishing the diagnosis of COVID‐19 infection in Latin American countries. This information will be useful for the early identification of suspected cases by health professionals (dermatologists and nondermatologists) and will allow contact tracing to mitigate the impact on health systems at different levels.

Pandemic coronavirus disease (Coronavirus disease 2019, ) is caused by a new pathogen, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), isolated for the first time in December 2019 in Wuhan, China. 1 The most common clinical presentation is respiratory, but other organs can also be affected, including the skin. It is estimated that approximately 20% of patients affected by COVID-19 have skin lesions, 45% at onset and 55% during hospitalization or over the course of the disease, and there is no evidence to date that skin lesions occur by viral replication in situ. The dermatological manifestations do not seem to be related to the viral load, although acro-ischemic lesions have been described more frequently in paucisymptomatic (oligosymptomatic) young patients. 2, 3 There is also a relationship between some cutaneous manifestations and the overall prognosis of the patient, such as necrotic and ecchymotic forms associated with more severe disease. 4 As far as we know, there have been no descriptions of skin manifestations of COVID-19 infection in Latin American patients; thus, we are lacking information in patients of skin of color (Fitzpatrick phototypes III-V). The characterization of these patterns can help dermatologists and attending physicians in Latin American countries to identify paucisymptomatic patients.

To fill this gap, we performed a cross-sectional study using a questionnaire. Additionally, questions used to obtain the method of diagnosis, the symptomatology and treatment of COVID-19, and a description of the associated dermatological lesions were included. The opportunity to attach photographs of these lesions was provided. This proposed questionnaire was circulated among a group of experts and then a panel was held to adapt it and their commentaries were added. The final version was uploaded to an online platform for distribution through an electronic link to all dermatological societies and the main dermatological hospitals and services in the region. The 

Although 730 questionnaires were received, only 347 were fully processed due to missing data. In this study, we found a pre- confusion, 3.5%. Ten percent of the cases were reported as asymptomatic. It is important to mention that the health professionals were able to select more than one option; therefore, the frequencies and percentages reflect the number of times the answer was chosen. The treatments administered were as follows: only supportive care in 69.5% of cases, followed by antibiotics (48.4%), glucocorticoids (25.9%), ivermectin (21%), antimalarials (9.5%), IL-6 inhibitors (2.9%), lopinavir/ritonavir (1.7%), JAK inhibitors (1.7%), intravenous immunoglobulin (IVIG, 1.4%), convalescent plasma (0.9%), remdesivir (0.9%), and ciclesonide (0.6%). No Regarding complications associated with COVID-19 infection, 67.4% did not report any complications. However, acute respiratory distress syndrome (ARDS) occurred in 21% of patients, with sepsis in 6.3%, myocarditis or heart failure in 0.9%, concomitant or secondary lung infection in 3.5%, acute kidney injury in 5.5%, and thrombotic events in 2.6%. Regarding the latter, 4% of patients had a personal history of thrombophilia or a state of hypercoagulability; 67.4% hadn't had such history, and in 24.5%, it was unknown.

In 323 patient records, there was information about the mortality of the disease. A total of 13.3% of the patients died from COVID-19 or associated complications (Table 2 ).

We collected a total of 730 questionnaires in both Spanish and Portuguese with information regarding 347 patients from 25 countries in the Latin American region. To the best of our knowledge, it is the largest registry of its kind in the region. other: lesions similar to livedo reticularis on the thighs; follicular petechial purpura on the limbs, torso and, less frequently, the face. The report also described rashes similar to pityriasis rosea, dengue (with low platelet count), infectious erythema, and eruptive pseudoangiomatosis. Some hospitalized patients presented with miliaria crystallina/rubra and folliculitis.

In the United States, a similar study was carried out with patients from 31 countries (the majority from the United States, 89%) and found that among patients with laboratory-confirmed COVID-19, the most common morphologies were morbilliform The respondents could select more than one option.

International Journal of Dermatology 2021 ª 2021 the International Society of Dermatology common in patients with moderate disease, while retiform purpura presented exclusively in severely hospitalized patients.

The vast majority of respondents concluded that the dermatological manifestations of their patients were probably related to COVID-19 infection, and PCR was the most frequently used confirmatory method. In our study, the main dermatological patterns were maculopapular rash, urticarial lesions, papulovesicular rash, vesicular rash, and pseudo-chilblain lesions, which coincides with previous reports in the literature 2,4 and represents a spectrum of manifestations as broad as that reported by Freeman et al. 4 We also report previously undescribed symptoms: pruritus and palmoplantar dysesthesias. Some hypotheses that could explain the pruritus are the exacerbation of preexisting itchy disorders, secondary reactions to personal protective equipment (PPE), psychological stress-induced itch, and directly related to the dermatoses associated with the COVID-19 infection. 5 The newly described manifestations in this study are bolded.

The majority of our patients had mild signs and symptoms of the disease, which correlates with the greater frequency of clinical manifestations related to COVID-19, probably associated with hypersensitivity to virus particles. 7 Most maculopapular rashes occurred during the active phase of the disease, which may correlate to the viremia phase; regarding the prevalence of cutaneous manifestations associated with symptomatic cases of COVID-19 infection, it is suggested that SARS-CoV-2 infection lead to hypercytokinemia and expression of interferon-inducible genes which have multiple immunopathogenic potentials including overexpression of genes involved in inflammation, which can explain most of the cutaneous signs and symptoms. 8 It is worth noting that no patient received interferon or bevacizumab, the former of which is associated in some case reports with pseudo-chilblain manifestations. [9] [10] [11] The majority of the patients recovered and required mostly supportive treatment. However, age and the presence (or absence) of comorbidities are determinants of the implementation of different therapeutic strategies.

The knowledge and identification of dermatological manifestations in patients infected with the SARS-CoV-2 virus can benefit dermatologists and first-contact physicians, who should become familiar with these symptoms. This registry emphasizes skin manifestations as an important criterion for establishing the diagnosis of COVID-19 infection in Hispanic patients. This information will be useful for the early identification of suspected cases by health professionals (nondermatologists), which will allow to make recommendations regarding isolation measures for asymptomatic or paucisymptomatic patients, also allowing contact tracing to mitigate the impact of the disease on the health systems at different levels.

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The spectrum of COVID-19-associated dermatologic manifestations: an international registry of 716 patients from 31 countries

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We thank all the dermatologist societies of the participating countries, the more than 700 dermatologists involved, all health professionals, and all patients who have become ill from this disease. We also thank Galderma who supported the construction of the digital platform for the questionnaires.

Additional Supporting Information may be found in the online version of this article:Supplementary Material Spanish version of the questionnaire used in order to create this registry. Adapted from: Skin signs of Covid-19. Dr. Noufal Raboobee.