Abstract
Background
The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) pandemic, causing COVID‐19, is rapidly spread across the world, by posing novel challenges for all physicians. Cutaneous manifestations of COVID‐19 may be present in 20% of patients, but they are still now poorly characterized.
Methods
We search literature to describe all the various cutaneous manifestation observed during COVID‐19 pandemic.
Results
Different cutaneous clinical patterns were described, showing a wide polymorphism.
Conclusion
We provided an overview of all the various cutaneous manifestations of COVID‐19 described in the literature today, to improve our knowledge and lead a more prompt and accurate diagnosis, especially in asymptomatic or paucisymptomatic cases.
Keywords: COVID‐19, cutaneous manifestations, Kawasaki disease, pandemic, rash, skin lesions, urticaria, vesicles
Key Message.
Cutaneous manifestations of COVID‐19 may be present in up to 20% of patients; SARS‐CoV‐2 infection has been associated with several skin manifestations, mostly similar to those observed in other common viral infections; Cutaneous manifestation could represent an important finding to early diagnosis and intervention, especially in asymptomatic or paucisymptomatic cases.
1. INTRODUCTION
The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) pandemic, causing COVID‐19, poses novel challenges for all physicians since the novel coronavirus can often be responsible for unusual and unsuspected pictures. There have been increasing reports of various cutaneous manifestations for COVID‐19, until recent reports of Kawasaki disease, even if the virus does not seem dermatotropic.
In the beginning, cutaneous manifestations appeared as an infrequent presentation of COVID‐19: A Chinese study of 1099 cases provided the first evidence of skin manifestations in 2 patients with severe respiratory disease. 1 However, in a short time, there have been increasing reports of skin manifestations in patients with SARS‐CoV‐2 infection. Recalcati et al analyzed 88 Italian confirmed COVID‐19 patients (not including patients recently treated with new medicine) and reported a prevalence of 20.4% of skin manifestation. 2 However, the reported prevalence of skin involvement can be underestimated because of the lack of clinical images, due to safety concerns, and because lesions often occur in asymptomatic/mildly symptomatic or patients who could not perform the swab. 3
In order to rapidly collect all the reports to improve our knowledge to recognize the paucisymptomatic cases better, the American Academy of Dermatology (AAD) COVID‐19 Task Force launched an online COVID‐19 dermatology registry (available online at www.aad.org/covidregistry).
This article aimed to provide an overview of all the various cutaneous manifestations of COVID‐19 described today in the literature.
Different cutaneous clinical patterns were described, showing a wide polymorphism.
Erythematous rash
The evidence of erythematous rash was reported in several case series of COVID‐19 patients. In Italy, Recalcati et al described this finding in 14/18 patients (77.8%) with confirmed COVID‐19 and skin manifestations. 2
Maculopapular exanthem
A review article analyzed 6 case series and 12 case reports identified in the maculopapular exanthem (morbilliform) as the most common cutaneous manifestation of COVID‐19 since it was found to be present in 36.1% (26/72) patients. 3
Urticaria and urticaria‐like rush
Several case reports described urticaria or urticariform rush in COVID‐19 patients, mostly distributed in the trunk and often before the onset of fever or respiratory symptoms. 3 Among patients with confirmed COVID‐19 and skin manifestations, the prevalence of urticaria varies from 9.7% to 16.7%. 2 , 3
Chickenpox‐like vesicles
Case reports described varicella‐like papulovesicular exanthem. 4 In Italy, Recalcati et al described vesicles formation in 1/18 patients (5.6%) with confirmed COVID‐19 with skin manifestations. 2 Data from current reports show a higher prevalence of this manifestation, raising to 34.7%. 3
Acral ischemic lesions
As reported by Zhang et al, COVID‐19 could be responsible for coagulation disorders, increasing the D‐dimer and fibrinogen degradation products, and leading to acro‐ischemia with finger and toe cyanosis. 5 Other case reports described acro‐ischemia in children and critical patients, or acral ischemic lesions presenting as red‐purple papules. 5 Painful acral red‐purple papules were reported in 15.3% of patients with COVID‐19 and skin lesions. 3
Others
Other less frequent cutaneous manifestations were described, in adults and the pediatric population, such as livedo reticularis lesions, a rash mistaken for dengue, rash with petechiae, and confluent erythematous yellowish plaques in the heels. 3
Kawasaki‐like disease
Kawasaki disease (KD) is an acute febrile vasculitis that usually affects children <5 years old. Studies described an association between viral respiratory infections and KD. Sporadic cases of KD presenting with shock syndrome (KDSS) can be identified by the presence of circulatory dysfunction and macrophage activation syndrome (MAS). In general, this subgroup of patients shows a poor response to IV immunoglobulin therapy, older age, longer duration of fever, higher white blood cell count, neutrophils, inflammation indexes, serum cytokines, and D‐dimer; lower hemoglobin and albumin; and more severe hyponatremia and hypokalemia. 6
Kawasaki‐like disease has been described as an emerging complication during the COVID‐19 pandemic.
Jones et al described the case of a 6‐month‐old infant with fever and minimal respiratory symptoms diagnosed with classic KD and positive screening for SARS‐CoV‐2. 7
Another recent study reports a cluster of 8 children presenting with KDSS with atypical KD clinical features: persistent fever, variable skin rash, conjunctivitis, peripheral edema, and generalized pain in the extremities, with significant gastrointestinal symptoms. 8 Most of these children did not show significant respiratory involvement, although 7/8 patients required mechanical ventilation for cardiovascular stabilization. A significant proportion of these children presented a positive swab or serology for the SARS‐CoV‐2 or history of contact with affected patients, on admission, or in the weeks before onset. 8 In these children, an exaggerated inflammatory response due to cytokine storm comes probably as a post‐infectious disease in the third or fourth week following the infection, as observed in COVID‐19. The high incidence of these forms in highly endemic areas for SARS‐CoV‐2 infection confirms a possible association between COVID‐19 and KD. Recently, Verdoni et al reported a 30‐fold increased incidence of Kawasaki‐like disease shortly after the spread of SARS‐CoV‐2 in Bergamo, an Italian province extensively affected by the novel coronavirus pandemic. 9 The authors demonstrated that children diagnosed after the SARS‐CoV‐2 epidemic showed an immune response to the virus, were older, had a higher rate of cardiac involvement, and had features of MAS, suggesting that SARS‐CoV‐2 might cause a severe form of Kawasaki‐like disease. 9
The early recognition of KD and KDSS and the prompt referral to a hospital setting is essential to prevent complications and to improve the outcome of these patients. However, even if data suggest an association between SARS‐CoV‐2 infection and KD, some caution is needed in concluding that the novel coronavirus is a trigger for KD.
2. DISCUSSION
It is quite unusual that a single virus may lead to such a wide polymorphism of skin patterns. A possible explanation may be that some manifestations associated with SARS‐CoV‐2 infection have alternative causes. The similarity between some of the lesions observed in COVID‐19 and other viral infections (ie, Parvovirus) raises the hypothesis that some of these might be the result of co‐infection. Two major pathogenic mechanisms at the basis of cutaneous manifestations in COVID‐19 have been proposed: (a) immune response to viral nucleotides in patients showing manifestations similar to other viral exanthemas, and (b) systemic consequences caused (directly or indirectly) by COVID‐19 in cutaneous eruptions, especially vasculitis and thrombotic vasculopathy. 10 Furthermore, patients with COVID‐19 are more likely to develop adverse drug reactions. Therefore, it is essential to identify clues supporting either viral cause or drug eruption to allow the early recognition of cutaneous manifestations associated with severe complications.
A recent review article reported data from different case series and case reports, by including in total 72 patients with COVID‐19 and cutaneous manifestations: Lesions spontaneously healed in all patients within 10 days, and the majority of the studies reported no correlation between COVID‐19 severity and skin lesions analyzed. 3 Skin lesion development occurred before the onset of respiratory symptoms or COVID‐19 diagnosis in 12.5% (9/72) of the patients, suggesting that skin lesions may aid in the timely diagnosis of this infection. 3
Additional clinical studies regarding skin manifestations in COVID‐19 are needed to understand the exact cutaneous features and to lead to more prompt and accurate diagnosis, especially in asymptomatic or paucisymptomatic cases.
CONFLICT OF INTEREST
The authors have no conflict of interest to declare.
AUTHOR CONTRIBUTIONS
Elena Galli: Conceptualization (lead); Writing‐review & editing (equal). Francesca Cipriani: Data curation (equal); Writing‐review & editing (equal). Giampaolo Ricci: Writing‐review & editing (equal). Nunzia Maiello: Conceptualization (equal); Data curation (equal); Writing‐original draft (equal); Writing‐review & editing (equal).
Peer Review
The peer review history for this article is available at https://publons.com/publon/10.1111/pai.13384.
Galli E, Cipriani F, Ricci G, Maiello N. Cutaneous manifestation during COVID‐19 pandemic. Pediatr Allergy Immunol. 2020;31(Suppl.26):89–91. 10.1111/pai.13384
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