Letter re: SARS-CoV-2 vaccine in patients with thymic epithelial tumours with and without active or pre-existing autoimmune disorders: Brief report of a TYME network safety analysis.

We read the article by Giugliano et al. [[1]Giugliano F. Zucali P.A. Gallie G. Ballatore Z. Corti C. Aliaga P.T. et al.SARS-CoV-2 vaccine in patients with thymic epithelial tumours with and without active or pre-existing autoimmune disorders: brief report of a TYME network safety analysis.Eur J Cancer. 2022; 166 (doi: 10.1016%2Fj.ejca.2022.02.011): 202-207Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar] entitled 'SARS-CoV-2 vaccine in patients with thymic epithelial tumours with and without active or pre-existing autoimmune disorders: brief report of a TYME network safety analysis,' published in the European Journal of Cancer, with great interest. The authors suggested that SARS-CoV-2 mRNA vaccines were safe in patients with thymic epithelial tumours, even in those with active or pre-existing autoimmune disorders; however, the safety of coronavirus disease 2019 (COVID-19) vaccination in such patients should be further discussed and evaluated. In this letter, we present a rare case of atypical erythema multiforme (EM) that occurred after COVID-19 vaccination and was possibly associated with thymoma. A 50-year-old Japanese woman visited our department complaining of multiple erythematous skin eruptions that developed 7 d after receiving the second dose of the COVID-19 mRNA vaccine (Comirnaty, BioNTech, Mainz, Germany; Pfizer, NY, USA), which was administered 3 weeks after the first dose. Physical examination revealed comet-like erythematous rashes disseminated on the upper and lower limbs (Fig. 1a, b). Skin biopsy showed mild liquefaction degeneration and perivascular lymphocytic infiltration in the superficial dermis (Fig. 1c). Vacuolar interface dermatitis was diagnosed histopathologically. Although topical corticosteroids and antihistamines were administered for 7 weeks, no improvement was observed. Systemic investigations, including computed tomography (CT), 18F-fluorodeoxyglucose (FDG)-positron emission tomography (FDG-PET), and gastrointestinal endoscopy, were performed to identify the cause of skin lesions. A nodule, 25 mm × 34 mm in size, in the anterior mediastinum was revealed on CT (Fig. 1d). Elevated FDG uptake was observed in this nodule, whereas moderate FDG uptake was noted in the enlarged left subclavicular lymph nodes near the vaccination site (Fig. 1e, f). The patient underwent thymectomy 12 weeks after the second vaccination, and a histopathological diagnosis of type-AB thymoma was made. Her skin lesions, which were unchanged at the time of the surgery, completely disappeared 3 weeks after thymectomy (Fig. 1g). The final diagnosis was COVID-19 vaccination-induced atypical EM. EM, an inflammatory skin condition, is associated with infections (most commonly with herpes simplex virus or mycoplasma), drugs, immunisations, and internal disorders [[2]Buján Bonino C. Moreiras Arias N. López-Pardo Rico M. Pita da Veiga Seijo G. Rosón López E. Suárez Peñaranda J.M. et al.Atypical erythema multiforme related to BNT162b2 (Pfizer-BioNTech) COVID-19 vaccine.Int J Dermatol. 2021; 60: e466-e467https://doi.org/10.1111/ijd.15894Crossref PubMed Scopus (17) Google Scholar]. Several cases of EM as a cutaneous adverse event (AE) of COVID‐19 vaccination have been reported. These cases comprise newly developed lesions and flare-ups of pre-existing inflammatory dermatoses, categorised as Th1-polarised cutaneous inflammations [[3]Niebel D. Novak N. Wilhelmi J. Ziob J. Wilsmann-Theis D. Bieber T. et al.Cutaneous adverse reactions to COVID-19 vaccines: insights from an immuno-dermatological perspective.Vaccines (Basel). 2021; 9: 944https://doi.org/10.3390/vaccines9090944Crossref PubMed Scopus (49) Google Scholar]. Previous reports have shown that all cases of EM induced by a COVID-19 vaccine, excluding cases with an unknown prognosis, improved with topical steroids and oral antihistamines treatment [[4]Kobyashi Y. Adachi T. Arakawa H. Takeuchi M. Inazumi T. Erythema multiforme following vaccination for SARS-CoV-2: report of a case and review of the literature - secondary publication.Australas J Dermatol. 2022; 63: e381-e385https://doi.org/10.1111/ajd.13917Crossref PubMed Scopus (1) Google Scholar]. In the present case, skin lesions developed 7 d after the second vaccination, persisted for more than 14 (11 + 3) weeks, and completely disappeared within 3 weeks after thymectomy. Thymoma, the most common neoplasm of the anterior mediastinum, comprises neoplastic epithelial cells and non-neoplastic T lymphocytes in varying ratios. Thymoma is often associated with autoimmune diseases such as myasthenia gravis (MG), autoimmune thyroid diseases, systemic lupus erythematosus, pemphigus, and cutaneous graft-versus-host disease-like erythroderma [[5]Yano M. Autoimmune diseases associated with thymoma.J Vis Surg. 2020; 6: 6https://doi.org/10.21037/jovs.2019.10.04Crossref Google Scholar]. Giugliano et al. reported 126 patients with thymoma or thymic carcinoma who received COVID-19 vaccines. Although 51% of patients experienced AEs, including fever, fatigue, muscle pain, and chills, no cases of the development or reactivation of autoimmune disorders and cutaneous lesions were recorded. On the other hand, two patients developed MG, the cause of which was determined to be unrelated to vaccination [[1]Giugliano F. Zucali P.A. Gallie G. Ballatore Z. Corti C. Aliaga P.T. et al.SARS-CoV-2 vaccine in patients with thymic epithelial tumours with and without active or pre-existing autoimmune disorders: brief report of a TYME network safety analysis.Eur J Cancer. 2022; 166 (doi: 10.1016%2Fj.ejca.2022.02.011): 202-207Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar]. Virgilio et al. recently published a case report of late-onset MG and thymoma. The authors suggest that the patient's MG symptoms may have been triggered by interactions between the COVID-19 vaccine, acetylcholine receptor antibodies, and the thymic tumour [[6]Virgilio E. Tondo G. Montabone C. Comi C. COVID-19 vaccination and late-onset myasthenia gravis: a new case report and review of the literature.Int J Environ Res Public Health. 2022; 20: 467https://doi.org/10.3390/ijerph20010467Crossref PubMed Scopus (1) Google Scholar]. It seems necessary to examine in detail whether the two previously described cases were not causally related to COVID-19 vaccination. To the best of our knowledge, this is the first report of cutaneous AE following COVID-19 vaccination in a patient with thymoma, with complete disappearance of cutaneous lesions observed after thymectomy. We believe that thymoma is related to the development of cutaneous lesions following COVID-19 vaccination; however, the accumulation of similar cases is required to elucidate the immunological relation between cutaneous AEs of COVID-19 vaccination and thymoma. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.