key: cord-1010209-shmlqwx2 authors: Ohsawa, Risa; Sano, Hozumi; Ikeda, Mitsunori; Sano, Shigetoshi title: Clinical and histopathological views of morbilliform rash after COVID-19 mRNA vaccination mimic those in SARS-CoV-2 virus infection-associated cutaneous manifestations date: 2021-06-11 journal: J Dermatol Sci DOI: 10.1016/j.jdermsci.2021.06.006 sha: 41b60203b7cf7b0d15379a542b9ecbf104f3ba78 doc_id: 1010209 cord_uid: shmlqwx2 nan suffered from pain at the injection site without skin lesion or systemic symptom. Two days after the injection, that was 55 hours of post-injection, pruritic papules and erythematous lesions developed over the entire body except for the face. She was treated with topical betamethasone dipropionate and oral antihistamine, which were, however, ineffective. She presented herself to our department on the day 6 after the vaccine administration with mild pruritic vesicopapular, erythematous macular and morbilliform eruption on the bilateral flanks and extremities (Fig. 1A Further, MxA, one of the type I interferon signatures, was highly expressed in the epidermis, cell infiltrates and vascular endothelium (Fig. 2D ), as previously shown in COVID-19-associated chilblain-like lesions [8] . Laboratory testing revealed all normal in blood cell counts, liver, renal function, except for an increase of prothrombin(PT) time (118.4%), which represents a reported feature of COVID-19-associated coagulation dysfuntion [9] . She was then treated with 15mg of oral predonisolone, by which all the rash resolved in a week. She did not receive the second dose of the vaccine because of expected recurrence of rash or other unfavorable reaction. To our knowledge, only one report described a case of morbilliform rash following administration of Pfizer COVID-19 vaccine [6] . Their case of morbilliform rash emerged after the initial and second dose, and the latent time after each vaccination was 48 hours, which was similar to our case. Morbilliform rash is a predictable rash of SARS-CoV-2 infection [10] , although skin biopsies have never found viral RNA or proteins [3] , suggesting an immune activation-mediated skin response. Immunohistochemical features J o u r n a l P r e -p r o o f in our case strikingly mimicked those found in COVID-19-assocated skin lesions [2] [7] [8] . More importantly, our case was similar to SARS-CoV-2-associated conditions of not only skin rash such as microvascular thrombi, but also PT time elongation, the sign of coagulation abnormality [9] . Together, plausible underlying conditions of this case with Pfizer COVID-19 vaccination to develop skin rash are as follows; 1) Viral proteins (spike protein) might be expressed within 2 days of mRNA vaccination. 2) The recipient might have been infected and immunized with previous coronavirus (either conventional or Wuhan-derived coronavirus), whose spike protein might be a cross-react antigen with the one that the mRNA vaccine encoded. 3) The abrupt immune responses raised by the mRNA vaccine mimicked those by SARS-CoV-2 infection and might cause the similar symptoms not only in the skin but also systemically, particular, coagulation dysfunction. Therefore, if the COVID-19-related rash develops after the initial dose of vaccination, we suggest that the second dose is unnecessary, since anti-viral immunity would have been already established, or even should be avoided because of any risk for recurrence of cutaneous disease and emergence of systemic symptom such as coagulation tendency. As a number of people over the world are receiving COVID-19 vaccines, dermatologists need to be aware of post-dose rashes to verify if they mimic COVID-19-associated cutaneous manifestations. There was no funding source for this work. The authors have no conflict of interest to declare The authors have no conflict of interest to declare. Report of three cases and a review of literature Clinical and histopathological study of skin dermatoses in patients affected by COVID-19 infection in the Northern part of Italy Cutaneous manifestations in patients with coronavirus disease 2019: clinical and histological findings Delayed Localized Hypersensitivity Reactions to the Moderna COVID-19 Vaccine: A Case Series Skin manifestations of the BNT162b2 mRNA COVID-19 vaccine in healthcare workers Morbilliform rash after administration of Pfizer-BioNTech COVID-19 mRNA vaccine Histopathological Study of a Broad Spectrum of Skin Dermatoses in Patients Affected or Highly Suspected of Infection by COVID-19 in the Northern Part of Italy: Analysis of the Many Faces of the Viral-Induced Skin Diseases in Previous and New Reported Cases Type I Interferon Signature in Chilblain-Like Lesions Associated with the COVID-19 COVID-19 and coagulation dysfunction in adults: A systematic review meta-analysis Morbilliform Rash: An Uncommon Herald of SARS-CoV-2 We thank Ms. Reiko Kamijima for technical assistance and Dr. Soichi Nukuzuma for helpful discussion.