A 77-year-old Japanese woman presented with peripheral oedema following COVID-19 vaccination. Three weeks before, the day after the second dose of BNT162b2 mRNA COVID-19 vaccination, she presented with low-grade fever, peripheral oedema and arthralgia of the bilateral foot joint. Fever and arthralgia were relieved spontaneously within a week. Since there was no improvement in the peripheral oedema, she was referred to our department. Her medical history revealed type 2 diabetes mellitus and dyslipidaemia, for which she had been prescribed 500 mg/day of metformin and 10 mg/day of atorvastatin. Physical examination revealed symmetrical non-pitting oedema of her legs (Figure 1a). Laboratory tests showed blood eosinophilia (3750/μl). The serum IgM level was within normal. Non-episodic angioedema with eosinophilia (NEAE) was diagnosed. Her symptoms improved quickly with prednisolone administration (20 mg/day) (Figure 1b). She has been recurrence-free after tapering off prednisolone.
Figure 1.
(a) Physical examination revealed symmetrical non-pitting oedema of her legs; (b) her symptoms improved quickly with prednisolone administration (20 mg/day).
Angioedema with eosinophilia is of two types: episodic angioedema with eosinophilia (EAE; Gleich’s syndrome) and NEAE.1–3 EAE has been reported mainly in Europe and the USA, whereas NEAE in Korea and Japan.4 EAE is characterized by recurrent episodes of angioedema, urticaria, fever and increased body weight, with markedly high peripheral blood eosinophil count and serum IgM levels.1,2 NEAE is characterized by a single episode of persistent oedema of the extremities, peripheral eosinophilia, transient arthralgia, lack of increased serum IgM levels and a less severe clinical course than that of EAE.2,3 NEAE can occur after influenza vaccination; however, NEAE after COVID-19 vaccination has not been previously reported.5 NEAE is also characterized by the effectiveness of low-dose prednisone or spontaneous remission within 2–3 months.2,3
In conclusion, non-pitting oedema of the extremities with eosinophilia should be considered eosinophilic angioedema, which can occur after COVID-19 vaccination.
Conflict of interest. None declared.
References
- 1. Gleich GJ, Schroeter AL, Marcoux JP, Sachs MI, O'Connell EJ, Kohler PF. Episodic angioedema associated with eosinophilia. N Engl J Med 1984; 310:1621–6. [DOI] [PubMed] [Google Scholar]
- 2. Matsuda M, Fushimi T, Nakamura A, Ikeda S. Nonepisodic angioedema with eosinophilia: a report of two cases and a review of the literature. Clin Rheumatol 2006; 25:422–5. [DOI] [PubMed] [Google Scholar]
- 3. Chikama R, Hosokawa M, Miyazawa T, Miura R, Suzuki T, Tagami H. Nonepisodic angioedema associated with eosinophilia: report of 4 cases and review of 33 young female patients reported in Japan. Dermatology 1998; 197:321–5. [DOI] [PubMed] [Google Scholar]
- 4. Chu H, Youn DY, Park HS, Ye YM, Park YB, Ban GY. Non-episodic angioedema with eosinophilia successfully treated with reslizumab. Allergy Asthma Immunol Res 2020; 12:371–4. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5. Hayashi R, Shimomura N, Hosojima M, Sakai A, Shigehara Y, Abe R. A case of non-episodic angioedema with eosinophilia induced by influenza vaccine. Eur J Dermatol 2017; 27:554–5. [DOI] [PubMed] [Google Scholar]