Risk of severe allergic reactions to COVID‐19 vaccines among patients with allergic skin diseases – practical recommendations. A position statement of ETFAD with external experts

Dear Editor,

Since the introduction of active vaccination against SARS‐CoV‐2 infection, there has been a debate about the risk of developing severe allergic or anaphylactic reactions among individuals with a history of allergy. ¹ , ² Indeed, rare cases of severe allergic reactions have been reported in the United Kingdom and North America. ³ By February 2021, a rate of 4.5 severe allergic reactions occurred among 1 million patients vaccinated with the mRNA‐based COVID‐19 vaccines, ¹ , ³ which is higher than the generally expected rate of severe allergic reactions to vaccinations of around one in 1 million. ⁴ , ⁵

Warnings have subsequently been issued that ‘persons with severe allergies’ should not be vaccinated, leading to confusion among patients and vaccinating physicians.

Therefore, the European Task Force Atopic Dermatitis (ETFAD) – in addition to a statement on the use of systemic immunomodulatory treatments for atopic dermatitis (AD) during COVID‐19 vaccination ⁶ – discusses the putative risk of severe allergic reactions to COVID‐19 vaccines for patients suffering from allergic skin diseases and give practical recommendations.

Generally, systemic allergic reactions to vaccines are rare, and due to hypersensitivity to components of the formulation of the vaccine such as conjugating agents, preservatives, metals, stabilizers, adjuvants and contaminants. ⁵ In the case of COVID‐19 vaccines, apart from the mRNA, the protein or the vector, one possible elicitor of anaphylaxis could be other ingredients as, for example, polyethylene glycol (PEG) present both in the BioNTech/Pfizer (Comirnaty) and the Moderna (mRNA‐1273) vaccines; other additives may be contained in vaccines under development like AZD‐1222, NVX.CoV2373 or Ad26.DOV2.S. Based on the available data, the safety and tolerability of COVID‐19 vaccines appear to be better than that of, for example, smallpox vaccines. ⁷ , ⁸

The general recommendation is that AD patients should be vaccinated according to their local or national vaccination plan. ⁶ , ⁷ Patients suffering from allergic skin diseases including AD do not per se have an increased risk of anaphylactic reactions to any COVID‐19 vaccine. Precautions should be taken where patients have a history of anaphylaxis to drugs in general, especially to vaccinations, and in patients with systemic mastocytosis or idiopathic anaphylaxis. All these patients should undergo a drug allergy diagnostic work‐up for allergy prior to vaccination. ² , ⁵

Patients with an acute flare of eczema should be actively treated for their AD but vaccination should not be delayed in these patients. The same holds true for patients with urticaria and other allergic diseases. ⁵

In selected cases, the use of anti‐allergic medication prior to vaccination, such as combined histamine H1 and H2 receptor antagonists plus oral glucocorticoids – may be considered, as it is done in peri‐operative anaphylaxis or severe reactions to radiographic contrast media. ⁹ Such patients should be observed for 30 min after the vaccine injection.

Clear contraindications exist at the moment only for patients with documented severe allergic reactions to ingredients of the respective COVID‐19 vaccine.

In the case of anaphylaxis, acute treatment includes intramuscular epinephrine as main pharmacotherapy. Epinephrine auto‐injectors should be available at the vaccination centres as well as other anti‐allergic drugs and balanced electrolyte solutions for volume replacement. ⁹ , ¹⁰

Nearly all patients with allergic skin diseases can be vaccinated with the registered COVID‐19 vaccines available today. Precautionary measures should be taken in a very small subgroup of patients, especially in those with possible severe allergy to ingredients of the vaccine. Knowledge about anaphylactic side‐reactions should be improved among physicians and medical health personnel in COVID‐19 vaccination centres.

Funding sources

None.

Conflict of interests

Dr. Ring has been an advisor or speaker for AbbVie, Allergika, Sanofi‐Genzyme, Pfizer, Bencard, LEO Pharma, and Mylan. Dr. Thyssen has attended advisory boards for Eli‐Lilly, Regeneron, Pfizer, LEO Pharma, Abbvie and Sanofi‐Genzyme, received speaker honorarium from LEO Pharma, Abbvie, Regeneron, and Sanofi‐Genzyme, and received research grants from Regeneron and Sanofi‐Genzyme. Dr. Vestergaard has been investigator, speaker, or consultant for Novartis, Abbvie, Sanofi, LeoPharma and Eli Lilly. Dr Barbarot has been a principal investigator, advisory board member, or consultant for Pierre Fabre Laboratory, Bioderma, Laboratoire La Roche Posay, Sanofi‐Genzyme, Abbvie, Novartis, Janssen, Leo‐Pharma, Pfizer, Amgen, Lilly. Dr. de Bruin‐Weller has been a consultant, advisory board member, and/or speaker for AbbVie, Almirall, Arena, Eli Lilly, Galderma, Janssen, Leo Pharma, Pfizer, Regeneron, and Sanofi‐Genzym. Dr. Bieber has been a principal investigator, advisory board member, or consultant for Regeneron, Sanofi, GSK, Celgene, Abbvie, AnaptysBio, MedImmune, Chugai, Pierre Fabre, Novartis, Asana Biosciences, LEO, Galapagos/MorphoSys, BioVerSys, Galderma, Kymab, Glenmark, Astellas, Daiichi‐Sankyo, Lilly, Pfizer, MenloTx, Dermavant, Allmiral. Dr. T. Bieber was speaker, and/or consultant and/or Investigator for AbbVie, Allmiral, AnaptysBio, Arena, Asana Biosciences, Astellas, BioVerSys, Böhringer‐Ingelheim, Celgene, Daichi‐Sankyo, Dermavant/Roivant, DermTreat, DS Pharma, RAPT/FLX Bio, Galapagos/MorphoSys, Galderma, Glenmark, GSK, Incyte, Kymab, LEO, Lilly, L´Oréal, MenloTx, Novartis, Pfizer, Pierre Fabre, Sanofi/Regeneron, UCB. T. Bieber is founder of the non‐profit biotech company “Davos Biosciences”. Dr. Gutermuth has been a consultant, advisory board member and/or speaker for AbbVie, Almirall, Eli Lilly, Galderma, Janssen, Leo Pharma, Pfizer, Regeneron, and Sanofi‐Genzyme. Dr Taïeb has been a consultant or investigator for Pierre Fabre, Galderma, Novartis, Johnson and Johnson, Incyte, Abbvie, Modilac, Pfizer, Lilly, Arena, Bioderma, Sanofi. Dr. Seneschal has been an investigator, speaker, or consultant for Novartis, Abbvie, Sanofi, LeoPharma and Eli Lilly. Dr. Weidinger has received institutional research grants from LEO Pharma and L‘Oreal, has performed consultancies for Sanofi‐Genzyme, Regeneron, LEO Pharma, Incyte, Lilly, Abbvie and Novartis, has lectured at educational events sponsored by Sanofi‐Genzyme, Regeneron, LEO Pharma, Abbvie and Galderma, and is involved in performing clinical trials with pharmaceutical industries that manufacture drugs used for the treatment of atopic dermatitis. Dr. Trzeciak has been a speaker, consultant, investigator or advisory board member for LEO Pharma, Pierre Fabre, Pfizer, La Roche Posay, Sanofi Genzyme, Novartis, Bioderma, Mead Johnson. Dr. Cork is an Investigator and/or consultant Consultant for Regeneron, Sanofi Genzyme, Pfizer, LEO, Galapagos, Novartis, Boots, L’Oreal, Reckitt Benckiser, Oxagen, Johnson&Johnson, Hyphens, Kymab, Astellas, Galderma, Procter&Gamble, Abbvie, Lilly, Galderma, Menlo, Perrigo. Dr Paul has received grants and been a consultant for Allmiral, Amgen, Abbvie, Boehringer, Celgene, Eli Lilly & Co, Novartis, Janssen, Pfizer, LEO Pharma, Merck, UCB pharma, Pierre Fabre, Regeneron, Sanofi‐Genzyme. Dr Flohr is chief investigator of the UK National Institute for Health Research‐funded TREAT (ISRCTN15837754) and SOFTER (Clinicaltrials.gov: NCT03270566) trials as well as the UK‐Irish Atopic eczema Systemic Therapy Register (A‐STAR; ISRCTN11210918) and a principal investigator in the European Union Horizon 2020‐funded BIOMAP Consortium (http://www.biomap‐imi.eu/). His department has also received investigator‐led funding from Sanofi‐Genzyme. Dr. Heratizadeh reports personal fees from Leo Pharma, personal fees from Novartis, personal fees from Pierre Fabre, personal fees from Sanofi‐Genzyme, personal fees from Beiersdorf, personal fees from Hans Karrer, personal fees from Nutricia, personal fees from Meda, personal fees from Lilly, grants from Janssen, outside the submitted work. Dr. Darsow gave advice to or received an honorarium for talks or research grant from the following companies: ALK‐Abello, Bencard, Meda, Novartis, and Sanofi‐Regeneron outside the submitted work. Dr. Simon has been an investigator, advisory board member, or consultant for AbbVie, AstraZeneca, Galderma, Lilly, Pfizer, Roche Pharma, Sanofi Genzyme. Dr. Torrelo has acted as advisor and/or participant in clinical trials for Sanofi, Lilly, Pfizer, Abbvie, and Mylan. Dr. Chernyshov, Dr. Stalder, Dr. Svensson and Dr. Kunz reports no conflict of interest. Dr. Gelmetti has acted as advisor and/or participant in clinical trials for Bayer, Sanofi/Regeneron, Galderma and has lectured at educational events sponsored by Pfizer and Leo Pharma. Dr Szalai has performed consultancies for Sanofi‐Genzyme, Regeneron, LEO Pharma, Novartis, has lectured at educational events sponsored by Nutricia, is involved in performing clinical trials with pharmaceutical industries that manufacture drugs used for the treatment of psoriasis and atopic dermatitis. Dr. von Kobyletzki has been an investigator, speaker, or consultant for Pfizer, Sanofi, LeoPharma and Eli Lilly. Dr. De Raeve is a consultant, member of scientific advisory boards and/ or received personal fees and non‐financial support from LEO Pharma, Pierre Fabre, Sanofi‐Genzyme and Bioderma. Dr. Fölster‐Holst reports being consultant/Advisor for Beiersdorf AG, Johnson&Johnson, LEO Pharma, Neubourg, Novartis Pharma AG, Nutricia, Pfizer Inc., Regeneron, Sanofi‐Aventis as well as speaker for Beiersdorf AG, LEO Pharma, Neubourg, Novartis Pharma AG, Pierre Fabre Laboratories, Pfizer, Procter&Gamble, Regeneron, Sanofi‐Aventis. Dr Christen‐Zaechs has been an advisor, speaker or investigator for Galderma, L’Oreal, La Roche Posey, Pierre Fabre, Procter and Gamble and Sanofi‐Genzyme. Dr. Hijnen has been investigator, speaker, or consultant for Abbvie, Eli Lilly, Incyte, LeoPharma, MedImmune/Astrazeneca, Pfizer, Sanofi, ThermoFisher. Dr. Gieler has received institutional research grants from Galderma, has performed consultancies for Sanofi‐Genzyme, Regeneron, LEO Pharma, Lilly, Abbvie and Novartis, has lectured at educational events sponsored by Sanofi‐Genzyme, Abbvie, Novartis, Sebamed and Galderma, and is involved in the organization of atopic dermatitis education programs in Germany for the treatment of atopic dermatitis. Dr. Bangert has been a consultant or speaker for Bayer, Mylan, LEO Pharma, Pfizer, Sanofi Genzyme, Eli Lilly, Novartis, Celgene and AbbVie and principal investigator for Merck, Novartis, Sanofi, Abbvie, Elli Lilly, and Galderma. Dr. Spuls has done consultancies in the past for Sanofi 111017 and AbbVie 041217 (unpaid), received departmental independent research grants from pharmaceutical industries different since December 2019 for the TREAT NL registry, is involved in performing clinical trials with many pharmaceutical industries that manufacture drugs used for the treatment of e.g. psoriasis and atopic dermatitis, for which financial compensation is paid to the department/hospital and, is Chief Investigator (CI) of the systemic and phototherapy atopic eczema registry (TREAT NL) for adults and children and one of the main investigator of the SECURE‐AD registry. Dr. Wollenberg has been a principal investigator, advisory board member, or consultant for AbbVie, Almirall, Galderma, Hans Karrer, LEO Pharma, Lilly, MedImmune, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc. and Sanofi Genzyme, and received speaker honoraria from Chugai, Galderma, LEO Pharma, Lilly, Loreal, MedImmune, Pfizer, Pierre Fabre, Regeneron Pharmaceuticals, Inc. and Sanofi Genzyme. Dr. Deleuran has been a principal investigator, speaker, advisory board member, or consultant for LEO Pharma, AbbVie, Almirall, Lilly, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Sanofi Genzyme, and Pierre Fabre. This research was performed independently through the authors’ academic university and hospital affiliations.