Diagnosis and management of the drug hypersensitivity reactions in Coronavirus disease 19: An EAACI Position Paper

Abstract

Coronavirus disease 2019 (COVID‐19), a respiratory tract infection caused by a novel human coronavirus, the severe acute respiratory syndrome coronavirus 2, leads to a wide spectrum of clinical manifestations ranging from asymptomatic cases to patients with mild and severe symptoms, with or without pneumonia. Given the huge influence caused by the overwhelming COVID‐19 pandemic affecting over three million people worldwide, a wide spectrum of drugs is considered for the treatment in the concept of repurposing and off‐label use. There is no knowledge about the diagnosis and clinical management of the drug hypersensitivity reactions that can potentially occur during the disease. This review brings together all the published information about the diagnosis and management of drug hypersensitivity reactions due to current and candidate off‐label drugs and highlights relevant recommendations. Furthermore, it gathers all the dermatologic manifestations reported during the disease for guiding the clinicians to establish a better differential diagnosis of drug hypersensitivity reactions in the course of the disease.

A compendium answering 150 questions on COVID‐19 and SARS‐CoV‐2

“…Several skin manifestations can be potentially associated with the disease: (1) Local skin inflammation is often connected with the antibody response toward viral nucleotides and presents as morbilliform rash, maculopapular lesions, vesicular exanthems, urticaria, and erythema multiforme; (2) systemic inflammation is associated with vasculitis and thrombosis, which are shown as peripheral cyanosis, livedo reticularis, and chilblain-like lesions; and (3) hypersensitivity reactions to drugs may occur more often during the pandemic due to the increased use of drugs and drug interactions, which can result in morbilliform rash, erythroderma, exanthematous pustulosis, and anaphylaxis in hypersensitivity reactions. Most reactions are nonimmediate, and further studies are required to clarify whether this increased frequency is caused by the drug immunogenicity or simply derives from a greater consumption as compared to other treatments 160.…”

Management of Allergic Diseases During COVID-19 Outbreak

“…Also, in case of specific antibiotics and if no effective alternative drug is available, it may be considered the preferent allergology study [5 •• ]. Additionally, DA has to be considered as a differential diagnosis against skin lesions due to COVID-19 that could be related to thrombovascular events (i.e., petechiae, acro-ischemia, dry gangrene) or to typical viral infections (i.e., erythematous rash, urticaria, maculopapular exanthema) [30], being a difficult distinction during the acute phase. Diagnosis relies mostly on clinical observations.…”

“…General recommendations for DA patients during COVID-19 outbreak and prioritize allergology drug study [30]…”

“…They can result from local inflammation due to circulating immune complexes or from systemic manifestations leading to vasculitis and thrombosis [33]. Furthermore, COVID-19 patients are also at increased risk of drug hypersensitivity lesions [30]. There is no evidence that patients with barrier defects such as atopic eczema have a higher risk for SARS-CoV-2 infection or skin complications during COVID-19.…”

“…The immunomodulatory drugs, including azithromycin, hydroxychloroquine/chloroquine, and IFNs, are the ones most frequently involved in hypersensitivity reactions. Most reactions are non-immediate, and further studies are required to clarify whether this will probably be associated with a rise in the number of drug-related adverse effects, some of which have an immunological basis [ 30 ].…”