Skin Diseases Associated With COVID-19: A Narrative Review
COVID-19 is an infectious disease caused by SARS-CoV-2, which emerged in China in 2019 and rapidly spread worldwide to become a pandemic in March 2020. Although the most severe manifestations concern the lower respiratory tract, COVID-19 is a multiorgan disease that also affects the skin. Several types of skin lesions have been reported to be associated with SARS-CoV-2 infection, though their causal relationship with the virus has not yet been well documented. In addition to the cutaneous manifestations that develop in patients with COVID-19—thought to be caused by the virus—other findings associated with the pandemic in a broader sense include dermatoses triggered or aggravated by the infection, the adverse cutaneous effects due to the drugs and protective devices used to prevent or fight the infection, and the adverse cutaneous effects of COVID-19 vaccines. We provide an overview of these dermatoses associated with the COVID-19 pandemic.
Practice Points
- During the COVID-19 pandemic, several skin diseases were reported in association with this new infectious disease and were classified mainly according to their morphologic aspect. However, the pathogenetic mechanisms often are unclear and the causal link of the culprit virus (SARS-CoV-2) not always well established.
- Currently, most skin manifestations related to COVID-19 are reported after vaccination against COVID-19; remarkably, many of them are similar to those attributed to the natural infection.
• Morbilliform rash: represents delayed hypersensitivity reactions (0.1% of postvaccination reactions) that appear mostly after the first dose (72%), on average 3 days after vaccination, always with an mRNA-based vaccine.70
• Herpes zoster: usually develops after the first vaccine dose in elderly patients (69% of cases) on average 4 days after vaccination and constitutes 0.1% of postvaccination reactions.71
• Bullous diseases: mainly bullous pemphigoid (90%) and more rarely pemphigus (5%) or bullous erythema pigmentosum (5%). They appear in elderly patients on average 7 days after vaccination and constitute 0.04% of postvaccination reactions.72
• Chilblainlike lesions: several such cases have been reported so far73; they constitute 0.03% of postvaccination reactions.70 Clinically, they are similar to those associated with natural COVID-19; they appear mostly after the first dose (64%), on average 5 days after vaccination with the mRNA or adenovirus vaccine, and show a female predominance. The appearance of these lesions in vaccinated patients, who are a priori not carriers of the virus, strongly suggests that CBLLs are due to the immune reaction against SARS-CoV-2 rather than to a direct effect of this virus on the skin, which also is a likely scenario with regards to other skin manifestations seen during the successive COVID-19 epidemic waves.73-75
• Reactions to hyaluronic acid–containing cosmetic fillers: erythema, edema, and potentially painful induration at the filler injection sites. They constitute 0.04% of postvaccination skin reactions and appear 24 hours after vaccination with mRNA-based vaccines, equally after the first or second dose.76
• Pityriasis rosea–like rash: most occur after the second dose of mRNA-based vaccines (0.023% of postvaccination skin reactions).70
• Severe reactions: these include acute generalized exanthematous pustulosis77 and Stevens-Johnson syndrome.78 One case of each has been reported after the adenoviral vector vaccine 3 days after vaccination.
Other more rarely observed manifestations include reactivation/aggravation or de novo appearance of inflammatory dermatoses such as psoriasis,79,80 leukocytoclastic vasculitis,81,82 lymphocytic83 or urticarial84 vasculitis, Sweet syndrome,85 lupus erythematosus, dermatomyositis,86,87 alopecia,37,88 infection with Trichophyton rubrum,89 Grover disease,90 and lymphomatoid reactions (such as recurrences of cutaneous T-cell lymphomas [CD30+], and de novo development of lymphomatoid papulosis).91
FINAL THOUGHTS
COVID-19 is associated with several skin manifestations, even though the causative role of SARS-CoV-2 has remained elusive. These dermatoses are highly polymorphous, mostly benign, and usually spontaneously regressive, but some of them reflect severe infection. They mostly were described during the first pandemic waves, reported in several national and international registries, which allowed for their morphological classification. Currently, cutaneous adverse effects of vaccines are the most frequently reported dermatoses associated with SARS-CoV-2, and it is likely that they will continue to be observed while COVID-19 vaccination lasts. Hopefully the end of the COVID-19 pandemic is near. In January 2023, the International Health Regulations Emergency Committee of the World Health Organization acknowledged that the COVID-19 pandemic may be approaching an inflexion point, and even though the event continues to constitute a public health emergency of international concern, the higher levels of population immunity achieved globally through infection and/or vaccination may limit the impact of SARS-CoV-2 on morbidity and mortality. However, there is little doubt that this virus will remain a permanently established pathogen in humans and animals for the foreseeable future.92 Therefore, physicians—especially dermatologists—should be aware of the various skin manifestations associated with COVID-19 so they can more efficiently manage their patients.
