We have described five cutaneous clinical patterns and several subpatterns associated with COVID-19. These patterns appear at different times in the disease, and are associated with different duration, severity and probably prognosis.
Previous publications have described some of these patterns but are based on very few cases. They also lack photography or use inadequate terms, like 'chickenpox-like' for monomorphic lesions or 'acro-ischaemic' for acral areas of erythema–oedema with some vesicles or pustules. No temporal relationship with symptoms or prognosis has previously been described.
One strength of our study is that the description of clinical patterns has been done by experts based only on morphology. The resulting patterns were shown to allow for easy classification of patients and to correlate with differences in demographics and severity.
Given the large number and distribution of participants, the sample is likely to be representative of the overall distribution of cutaneous lesions in COVID-19. However, we cannot define the source population, and, lacking a denominator, we have no measures of the incidence of clinical manifestations, only relative ones. We have omitted patients in the spectrum of severe disease due to difficulties in obtaining consent. This explains the low case fatality rate. However, descriptions of the lesions in these patients are less useful for diagnosis, as their diagnosis is usually obvious. Patients in the general population without clinical or virological confirmation of COVID-19 disease were also under-represented. We thought that this restrictive admission of reports was needed to increase the specificity of the results.
During the study period, testing was not done in most cases of mild disease. As we aimed to describe the lesions in less severe cases, we accepted both confirmed and suspected cases in our study. The results show that both groups showed similar cutaneous lesions (Appendix S1; see Supporting Information) and epidemiological results (Table S1 and Table S2; see Supporting Information). Patients excluded for lack of COVID-19 diagnostic criteria (n = 31) also had similar patterns, confirming that the inclusion of suspected patients did not bias the results.
As the study describes a short period of follow-up, it is better defined as a cross-sectional design rather than a cohort. Data on the duration and severity of the disease and the outcome are limited to the time when the patient was observed. It is possible that some of the patients with less severe disease will worsen with time. Against this limitation, the data show that the less severe forms were described late in the evolution of the disease, and have a longer duration, so it is unlikely that they will worsen over time.
Our study included any unexplained cutaneous lesions in patients with COVID, so it is possible that some of them have alternative causes. Pseudo-chilblain may look like perniosis, and as these lesions appear later in the evolution and are less commonly associated with virological confirmation, it is possible that they are not related to the COVID-19. We think that the pseudo-chilblain pattern is linked to COVID-19 because pseudo-chilblain appeared in a warm weather period, dermatologists perceived a greatly increased incidence, and patients frequently had COVID-19 contacts. Only one of the 71 patients had a previous history of chilblain. Overall, 29 of 71 (41%) had SARS-CoV-2 confirmed and we found three simultaneous familial clusters. The late appearance of pseudo-chilblains might explain the frequently negative polymerase chain reaction results. Monomorphic disseminated vesicular lesions and acral vesicular–pustulous lesions are probably quite specific and their appearance is coherent with lesions in other viral exanthemas.
Most of the urticarial and maculopapular lesions might not be very helpful for diagnosis, as these are common and may have many different causes. Drug reactions may be an important and difficult differential diagnosis. The patients with these presentations had more severe disease and received more drugs. Regarding their relationship with the other manifestations, urticarial and maculopapular lesions may be considered similar.
Livedoid and necrotic lesions were relatively uncommon, and appeared mostly in elderly patients and those with severe disease. As the number of patients is lower for this subset the information is less precise. In two case reports livedoid lesions were transient. These might be primary lesions of COVID-19 or simply indicate complications leading to vascular occlusion, as COVID-19 has been linked to alterations in coagulation and vascular damage.[6,16,17]
It is unusual, from our previous experience with cutaneous manifestations of viral diseases, that a single virus can lead to several different clinical patterns, especially as different patterns do not coexist in the same patient. Patients who may be classified as having more than one pattern are very uncommon. A hypothesis to explain this polymorphism may be that some of them have alternative causes, or there are differences in the virus or the host. The fact that some of the lesions, even in patients with confirmed COVID-19, are similar to those in other viral infections (notably parvovirus), and the perceived increased number of cases of zoster, raises the possibility of some of these being the result of coinfection and uncertainty as to whether SARS-CoV-2 is responsible for this.
In terms of arousing suspicion of COVID-19, we feel that pseudo-chilblain and vesicular lesions may be useful as indicators of disease. They uncommonly (10 of 373 cases with data) presented preceding other symptoms in our sample. Pseudo-chilblain lesions more commonly appear later during the disease and are not associated with severe disease, so they might be more useful as epidemiological markers than for diagnosis. It is possible that the sampling strategy might bias this result, and pseudo-chilblain might appear without other COVID-19 symptoms more commonly in the general population. Urticarial lesions may be due to many causes and mostly did not precede other symptoms in our study, so they are unlikely to lead to diagnosis. Regarding maculopapular lesions, they tend to co-occur with other symptoms, and most of them are not specific. A few subtypes, such as the pseudovesicular type (Figure 2b) and those resembling erythema elevatum diutinum (Appendix S1; see Supporting Information) or erythema multiforme (Figure 2c), could lead to suspicion of a diagnosis. Livedoid or necrotic lesions occur late in the evolution and are probably unhelpful for diagnosis. However, they fit nicely with the idea of vascular damage due to COVID-19.
In conclusion, we provide a description of the cutaneous manifestations associated with COVID-19. These may help clinicians approach patients with the disease and recognize cases with few symptoms. The usefulness of these patterns for diagnosis should be confirmed in clinical use. We suggest that further research could be improved by having more tests to confirm COVID-19 and to exclude other infections, and by describing clinicopathological correlation and some of the patterns that have been grouped in our study.
M.A. Descalzo-Gallego provided support with data management and analysis. We thank the following Spanish dermatologists for their generous contributions: E. Cruz Gómez, L. Carnero, Z. Martínez de Lagrán, A. Do Campo, A. Estébanez Corrales, A. González Quesada, A. Mateos Mayo, A. Perea Polak, A. Pulido, A. Tuneu Valls, A.C. Villanueva Álvarez-Santullano, A.G. Angulo, A.M. Rosell Díaz, C. Nadal, D. Caro Gutiérrez, D. Jiménez Gallo, E. Fernández Cogolludo, E. Roo Rodríguez, E. San Juan Lasser, G. Mele i Ninot, G. Sais, H. Perandones, I. Molina López, I. Poveda, I. Balaguer Franch, J. Boix, J. Galán Sánchez, J. Melgosa, J. Tercedor, J.A. Llamas Carmona, J.L. López Estebaranz, M. Ara, L. Galvany Rossell, L. Marqués Martín, L. Navarro, M. de Troya, J.L. Galán, M. Elosua, M. Escoda, M. García Bustunduy, M. Martín Dorado, M. Nieto Benito, M. Sidro, M.A. Arregui, M.C. Fuente Lázaro, M.V. Ara Martín, N. Eiris, P. Burgos-Blasco, P. Pasquali, G. Petiti, E. Ledo, R. Linares Navarro, R. Taberner Ferrer, A. Juárez Martín, S. Aparicio Fernández, A. Juárez Martín, T. Toledo Pastrana, Y. Yelamos, A. González Quesada, A. Viñolas, A. Suárez, A. Estébanez, M. Ubals, B. Espadafor, P. Fernández, M.L. Fernández, T. Repiso, E. Agut, X. García Navarro, G. Ruiz Carrillo, D. Jiménez, L.M. Nieto Benito, J. Monte Serrano, M. Alegre, M. Ferrer, V. García-Patos Briones, M. Velasco Guidonet, Á. Gómez Tomás, P. Castro García, V. Cabezas Calderón, D. Vega-Díez, R. Pérez-Mesonero and M. González-Cañete. This work is part of the PhD degree of Alba Catalá, in the Department of Medicine, Dermatology, Universidad Autónoma de Barcelona.
The analysis and technical support for this study were done by the Spanish Academy of Dermatology (Research Unit).
The British Journal of Dermatology. 2020;183(1):71-77. © 2020 Blackwell Publishing