key: cord-281060-1ud5hzlh authors: Méndez Maestro, Irune; Peña Merino, Lander; Udondo González del Tánago, Begoña; Aramburu González, Aida; Orbea Sopeña, Ana; Sánchez De Vicente, Javier; Ratón Nieto, Juan A.; Acebo Mariñas, Elvira; Gardeazabal García, Jesús title: Skin manifestations in patients hospitalized with confirmed COVID‐19 disease: a cross‐sectional study in a tertiary hospital date: 2020-09-24 journal: Int J Dermatol DOI: 10.1111/ijd.15180 sha: doc_id: 281060 cord_uid: 1ud5hzlh BACKGROUND: COVID‐19 cutaneous manifestations have been recently described and classified in five different clinical patterns, including acral erythema‐edema (pseudo‐chilblain), maculopapular exanthemas, vesicular eruptions, urticarial lesions, and livedo or necrosis. OBJECTIVES: The objective of this study was to examine the skin of hospitalized patients with a confirmed diagnosis of COVID‐19 disease and describe the real prevalence of skin manifestations. METHODS: A cross‐sectional study, which included hospitalized patients in Cruces University Hospital from April 14–30, 2020, with a laboratory‐confirmed diagnosis of COVID‐19 (with polymerase chain reaction and/or serology tests), was conducted. Entire body surface examination was performed by experienced dermatologists to search for cutaneous manifestations related to COVID‐19 disease. RESULTS: From a sample of 75 patients, 14 (18.7%) developed cutaneous manifestations possibly related to COVID‐19. We found six patients with acral erythema‐edema (pseudo‐chilblain) (42.8%), four patients with maculopapular exanthemas (28.6%), two patients with urticarial lesions (14.3%), one patient with livedo reticularis‐like lesions (7.15%), and one patient with vesicular eruption (7.15%). CONCLUSIONS: Our study provides a more plausible relationship between the main cutaneous patterns and COVID‐19 in hospitalized patients as all of them had a confirmatory laboratory test. Skin manifestations are frequent but mild with spontaneous resolution. These findings are nonspecific and can be similar to other viral infections and adverse drug reactions in hospitalized patients. On January 7, 2020, a novel coronavirus, SARS-CoV-2, was isolated in patients with pneumonia in Wuhan, China. 1 This virus spreads rapidly, and in March 2020, a pandemic was declared. The first clinical findings associated with this virus were respiratory symptoms and fever. Later, diarrhea, anosmia, and ageusia were included. 2, 3 It was not until March 26 that Recalcati's article 4 analyzed skin manifestations in COVID-19 patients for the first time. Since this date, a series of cases began to emerge in Spanish hospitals, and similar case series were reported. [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] For this reason, a nationwide study was conducted in Spain to describe the cutaneous manifestation patterns of COVID-19 disease. 17 Most of these articles include confirmed and suspected COVID-19 patients seen in an outpatient clinic and are restricted to patients with cutaneous manifestations. We decided to perform this study to describe the real prevalence and directly examine the skin findings in hospitalized patients in our institution with a confirmed diagnosis of COVID-19 disease. We performed a cross-sectional study, which included COVID- 19 Based on recent reports 4-16 and on the Spanish group classification in clinical patterns, 17 we included acral erythemaedema (pseudo-chilblain), maculopapular exanthemas, vesicular eruptions, urticarial lesions, and livedo or necrosis areas. To examine the patients, we entered their rooms using personal protective equipment (PPE) and transparent ziplock bags to protect photographic devices along with dispensable biopsy instruments, as performed in other hospitals. 9 We recruited a total of 75 patients admitted to the hospital because of clinical manifestations of COVID-19 disease. The mean age of the sample was 67.5 years old (CI 95 64.5-70.5), and 64% (CI 95 53.1-74.9%) were men (Table 1) . We collected data of prescribed treatments during their hospital stay. The most frequently used therapy was a combination of hydroxychloroquine, lopinavir/ritonavir, and methylpred- International Journal of Dermatology 2020 ª 2020 the International Society of Dermatology patients with areas of acral erythema-edema (pseudo-chilblain), which represents 42.8% of the cases (Fig. 1) ; four patients with maculopapular exanthemas (28.6% of the cases) (Fig. 2a,b) ; two patients with urticarial lesions; one patient with livedo reticularis-like lesions; and one patient with vesicular eruption. Acral erythema-edema lesions were mainly observed in feet. These lesions were very subtle and asymptomatic, so they were (Fig. 2c) . Additionally, we asked all patients about the existence of family members with cutaneous lesions with the above-mentioned patterns, and this was negative for all of them. Analyzing the collected demographic data, the mean age in our sample is 67.5 years old, and 64% are men. Compared with previous studies, 9, 17 our study includes older patients and a higher proportion of males. This can be explained because only hospitalized patients with laboratory confirmed SARS-CoV-2 were considered. As described in the existing literature, 18, 19 elderly men suffering from COVID-19 are more frequently hospitalized compared to women and young people. In this way, we aimed to achieve a representative sample of the profile of COVID-19 hospitalized patients. To our knowledge, this is the first series in which data collection has been directly performed by experienced dermatologists and with a systematic cutaneous exploration of all patients. All skin findings can be included in the recently described clinical patterns of cutaneous manifestations of COVID-19 disease. 17 Results show a similar percentage of skin manifestations to other case series. 4 In our sample, the most frequently observed cutaneous pattern was acral erythema-edema (pseudo-chilblain), and the second in frequency was the maculopapular exanthema. One of the latest studies 17 reported the pseudo-chilblain pattern appeared in young patients, later in the course of the disease, was associated with less severe infection, and included patients who did not require hospitalization. As mentioned above, we carried out an exhaustive dermatological exploration on all admitted patients. For this reason, we may have included some lesions as pseudo-chilblain patterns that could be explained by other causes or which were not exactly manifestations but rather a variety of normal skin conditions. Therefore, we may have overestimated the number of patients with acral erythema-edema. We would like to highlight that all the skin manifestations observed, regardless of the clinical pattern, were mild, did not affect mucous membranes, and did not cause epidermal detachment. In addition, these lesions did not require any specific treatment nor did they change the course, management, prognosis, or hospitalization days of the patients as they resolved spontaneously. As described in other studies, 17 it would appear that each clinical dermatological pattern has a time of onset in the disease: vesicular lesions precede other symptoms, urticarial and maculopapular lesions concur with respiratory symptoms, and pseudo-chilblain pattern appears later in the course of the disease. Given our low number of patients with skin findings, we are not able to make any conclusion on this area. Galv an et al. 17 referred there might be a correlation between the clinical patterns and the severity of the disease. In our study, we did not correlate the severity of the COVID-19 disease with the different skin patterns because all of the patients we included had very similar clinical characteristics of COVID-19 (moderate-severe infection that required hospitalization). We are aware that our study has its limitations. Firstly, the limitations are inherent to a cross-sectional study; it does not allow a monitoring over time; and it cannot determine cause and effect relationship. Secondly, we could not analyze other possible or alternative causes of skin manifestations such as medications. Finally, we are not able to correlate skin patterns with the time of onset of the disease and severity of the infection. Well-designed prospective studies are needed to explore the cause-effect relationship of these skin manifestations. This study provides a more plausible relationship between COVID-19 disease and its main cutaneous patterns in hospitalized patients, since all of them had a confirmatory laboratory test. It seems important to emphasize that skin manifestations in this subgroup of patients are frequent but mild in nature and in all cases with spontaneous resolution. Furthermore, they are nonspecific because they are similar to other viral infections and drug reactions observed in patients admitted to the hospital. The novel coronavirus originating in Wuhan, China: challenges for global health governance European Centre for Disease Prevention and Control. Case definition and European surveillance for COVID-19, as of 2 Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China Cutaneous manifestations in COVID-19: a first perspective Chilblainlike lesions on feet and hands during the COVID-19 Pandemic Cutaneous lesions in a patient with COVID-19: are they related? Comment on "Cutaneous manifestations in COVID-19: a first perspective " by Recalcati S Cutaneous manifestations in COVID-19: a new contribution Comment on: cutaneous manifestations in COVID-19: a first perspective. Safety concerns of clinical images and skin biopsies Urticarial eruption in COVID-19 infection Acral cutaneous lesions in the time of COVID-19 the International Society of Dermatology Acute urticaria with pyrexia as the first manifestations of a COVID-19 infection Characterization of acute acro-ischemic lesions in nonhospitalized patients: a case series of 132 patients during the COVID-19 outbreak A case of COVID-19 presenting in clinical picture resembling chilblains disease. First report from the Middle East Viral exanthem in COVID-19, a clinical enigma with biological significance Vascular skin symptoms in COVID-19: a French observational study Classification of the cutaneous manifestations of COVID-19: a rapid prospective nationwide consensus study in Spain with 375 cases Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study COVID-19 patients' clinical characteristics, discharge rate, and fatality rate of metaanalysis The patients in this manuscript have given oral informed consent to publication of their case details. The authors did not receive any funding sources.