Skin reactions to COVID-19 vaccines: An American Academy of Dermatology/International League of Dermatological Societies registry update on reaction location and COVID vaccine type
Authors: Esther E. Freeman, Qisi Sun, Devon E. McMahon, Rhea Singh, Ramie Fathy, Anisha Tyagi, Kimberly Blumenthal, George J. Hruza, Lars E. French, Lindy P. Fox
Journal: Journal of the American Academy of Dermatology (2021)

To the Editor: We thank the authors for their reply to our article and would like to clarify the concerns described.1McMahon D.E. Amerson E. Rosenbach M. et al.Cutaneous reactions reported after Moderna and Pfizer COVID-19 vaccination: a registry-based study of 414 cases.J Am Acad Dermatol. 2021; 85: 46-55Abstract Full Text Full Text PDF PubMed Scopus (609) Google Scholar The letter noted that the distribution of COVID-19 vaccine skin reactions was unclear and suggested we delineate each reaction pattern as local, distant, or generalized.1McMahon D.E. Amerson E. Rosenbach M. et al.Cutaneous reactions reported after Moderna and Pfizer COVID-19 vaccination: a registry-based study of 414 cases.J Am Acad Dermatol. 2021; 85: 46-55Abstract Full Text Full Text PDF PubMed Scopus (609) Google Scholar While we did not specify the body part affected by each reaction, we would also like to highlight the challenges with adopting the proposed local/distant/generalized approach. Patients often experienced multiple reactions simultaneously, including reactions both local and distant to the injection site. For instance, patients can exhibit concurrent, delayed large local reactions at the injection site and papulovesicles of the elbow/hand.2Blumenthal K.G. Freeman E.E. Saff R.R. et al.Delayed large rocal Reactions to mRNA-1273 vaccine against SARS-CoV-2.N Engl J Med. 2021; 384: 1273-1277Crossref PubMed Scopus (211) Google Scholar Others had local reactions combined with generalized morbilliform eruptions.1McMahon D.E. Amerson E. Rosenbach M. et al.Cutaneous reactions reported after Moderna and Pfizer COVID-19 vaccination: a registry-based study of 414 cases.J Am Acad Dermatol. 2021; 85: 46-55Abstract Full Text Full Text PDF PubMed Scopus (609) Google Scholar We do agree that at the level of the reaction pattern, certain eruptions were typically more generalized (such as morbilliform, urticaria, or vaccine-related eruption of papules and plaques3McMahon D.E. Kovarik C.L. Damsky W. et al.Clinical and pathologic correlation of cutaneous COVID-19 vaccine reactions including V-REPP: a registry-based study.J Am Acad Dermatol. September 10, 2021; https://doi.org/10.1016/j.jaad.2021.09.002Abstract Full Text Full Text PDF Scopus (105) Google Scholar), while others usually occurred at/near the injection site (local injection site reactions and delayed large local reactions). Others are harder to classify with regard to location: erythema multiforme and vasculitis, for example, could be either distal, in one location (for example, hands/feet only) or generalized. Our study also captured an extensive vaccine reactogenicity profile. Reactogenicity is defined as a subset of reactions occurring shortly after vaccination, including local signs and symptoms, such as pain, redness, swelling and induration, and systemic manifestations, such as fever, myalgia, headache, and rash.4Hervé C. Laupèze B. Del Giudice G. Didierlaurent A.M. Tavares Da Silva F. The how's and what's of vaccine reactogenicity.NPJ Vaccines. 2019; 4: 1-11PubMed Google Scholar We described reactogenicity for each dose of the Moderna/Pfizer vaccines, including fatigue, myalgia, headache, fever, arthralgia, nausea, chills, lymphadenopathy, diarrhea, vomiting, nasal congestion, and others.1McMahon D.E. Amerson E. Rosenbach M. et al.Cutaneous reactions reported after Moderna and Pfizer COVID-19 vaccination: a registry-based study of 414 cases.J Am Acad Dermatol. 2021; 85: 46-55Abstract Full Text Full Text PDF PubMed Scopus (609) Google Scholar We would also like to highlight new data on skin reactions to other COVID-19 vaccines, including AZD1222, Johnson & Johnson's Ad26.COV2.S, Sputnik V, and Sinovac-Coronavac (Table I). As of August 16, 2021, the American Academy of Dermatology/International League of Dermatological Societies registry included 2063 cutaneous vaccine reactions from 870 patients. We identified 24 reactions after AZD1222 vaccination, most commonly local erythema and pain. Johnson & Johnson's Ad26.COV2.S, another adenovirus vector vaccine, generated 15 reactions, including pityriasis rosea and alopecia. One individual developed urticaria and pruritus to the Sputnik V vaccine. Our data on skin reactions to other vaccine classes, such as the inactivated virus-based vaccine, Sinovac's CoronaVac, are limited. Four cases of reactions have been reported to the registry, including pityriasis rosea and zoster. Clinical trials frequently lump skin reactions into a nonspecific "rash" category, but real-world data better characterizing these cutaneous manifestations can provide mechanistic clues.Table ICharacteristics of dermatologic vaccine reactions reported after COVID-19 vaccination to the AAD/ILDS COVID-19 Dermatology Registry∗December 24, 2020—August 16, 2021.Moderna dose 1Moderna dose 2Pfizer dose 1Pfizer dose 2Astrazeneca dose 1Astrazeneca dose 2Johnson & JohnsonSputnik V dose 1Sputnik V dose 2Sinovac-Coronavac dose 1Sinovac-Coronavac dose 2Unknown dose 1Unknown dose 2TotalNumber of individuals427214114140921101311921870Patient age (Median, IQR)49 (37-66)47 (37-61)46 (35-56)51 (37-64)49 (44.5-55.5)39.5 (37-42)51 (28-60)-3842 (19-85)4261 (45-75)60 (49-75)-Patient sex (F)366 (85.7%)181 (84.5%)77 (67.5)103 (73.6%)5 (55.5%)1 (50%)10 (90.9%)-0 (0)3 (100%)1 (100%)16 (84.2%)13 (61.9%)776 (89.2%)Number of vaccine reactions99852620822822215023127312063Local reactions Local swelling151971214201000022281 Local erythema1691011315301000032307 Local pain116811414300000012231 Delayed local hypersensitivity reaction230501217200000012314Distal and/or generalized reactions Pruritus138642325202010053263 Urticaria28222421102010002101 Morbilliform2617161510100003281 Zoster195111301100104459 Vesicular148111400000000047 Pityriasis rosea1063520100112031 Pernio/chilblains735700000004026 Erythema multiforme1331410000001124 Bullous disease715900100000023 Erythromelalgia772400000000020 Filler reaction771200000000017 Angioedema653020000000016 Contact dermatitis530500000000114 Vasculitis315100000000111 Alopecia12110020000029 Petechiae13310000000008 Reaction in breast-fed infant01210000000004 Livedo reticularis00300000000014 New dermatologic condition7†Moderna first dose: lichen planus (4); psoriasis (1); possible leukocytoclastic vasculitis (1); Acne vulgaris (1).3‡Moderna second dose: granuloma annulare (1); lichen planus (1); psoriasis (1).1§Pfizer first dose: herpes zoster (1).8‖Pfizer second dose: lichen planus (2), granuloma annulare (1), morphea (1), Raynaud (1), pityriasis lichenoides (1); "lichen striatus versus inflammatory linear verrucous epidermal nevus versus Wolf isotopic response" (1); unspecified toe rash (1).000000002¶Unknown second dose: granuloma annulare (1); sarcoidosis (1).21 Flare of existing dermatologic condition91315910000000249 Other24232023213001012100F, Female; IQR, interquartile range.∗ December 24, 2020—August 16, 2021.† Moderna first dose: lichen planus (4); psoriasis (1); possible leukocytoclastic vasculitis (1); Acne vulgaris (1).‡ Moderna second dose: granuloma annulare (1); lichen planus (1); psoriasis (1).§ Pfizer first dose: herpes zoster (1).‖ Pfizer second dose: lichen planus (2), granuloma annulare (1), morphea (1), Raynaud (1), pityriasis lichenoides (1); "lichen striatus versus inflammatory linear verrucous epidermal nevus versus Wolf isotopic response" (1); unspecified toe rash (1).¶ Unknown second dose: granuloma annulare (1); sarcoidosis (1). Open table in a new tab F, Female; IQR, interquartile range. Poulas and Farsalinos3McMahon D.E. Kovarik C.L. Damsky W. et al.Clinical and pathologic correlation of cutaneous COVID-19 vaccine reactions including V-REPP: a registry-based study.J Am Acad Dermatol. September 10, 2021; https://doi.org/10.1016/j.jaad.2021.09.002Abstract Full Text Full Text PDF Scopus (105) Google Scholar hypothesized the spike glycoprotein from vaccination drives these skin phenomena, but the underlying mechanism is likely multifaceted and may vary by vaccine reaction. For instance, delayed large local reactions suggest a delayed hypersensitivity response to vaccination or a T-cell-mediated response resulting from molecular mimicry to viral epitopes. Other manifestations, such as viral reactivation, bullous pemphigoid, and leukocytoclastic vasculitis, may be explained by off-target immune activation postvaccination.3McMahon D.E. Kovarik C.L. Damsky W. et al.Clinical and pathologic correlation of cutaneous COVID-19 vaccine reactions including V-REPP: a registry-based study.J Am Acad Dermatol. September 10, 2021; https://doi.org/10.1016/j.jaad.2021.09.002Abstract Full Text Full Text PDF Scopus (105) Google Scholar RNA-mediated activation of innate immunity via Toll- and RIG-like receptors could also result in type I interferon release. Analysis of the underlying mechanisms for each pattern of skin reaction and systematic characterization of these cutaneous manifestations are paramount to understanding how these side effects influence vaccine adoption, particularly as additional doses, boosters, and vaccine mixing become increasingly common. Drs Freeman, Hruza, and Fox are part of the American Academy of Dermatology (AAD) COVID-19 Ad Hoc Task Force. Dr French is the President of the ILDS. Dr Freeman is an author of COVID-19 dermatology for UpToDate. Drs Sun, McMahon, and Blumenthal have no conflicts of interest to declare. Authors Singh, Fathy, and Tyagi have no conflicts of interest to declare. Response to McMahon et al's "Cutaneous reactions reported after Moderna and Pfizer COVID-19 vaccination: A registry-based study of four hundred fourteen cases"Journal of the American Academy of DermatologyVol. 86Issue 4PreviewTo the Editor: McMahon et al1 reported cutaneous reactions that occurred after the administration of messenger RNA (mRNA) COVID-19 vaccines. The authors recorded 414 unique patients and observed a broad spectrum of reactions after vaccination, from local injection site reactions and delayed large local reactions to urticaria and morbilliform eruptions. Several unusual reactions (erythromelalgia, pernio/chilblains, filler reactions, and pityriasis rosea-like eruptions) were also observed. All these lesions were characterized as local (near the injection site), according to the authors. Full-Text PDF