Erythema nodosum following the first dose of AstraZeneca COVID-19 vaccine

Erythema nodosum (EN) is a type IV delayed hypersensitivity reaction to a variety of antigens stimuli. In fact, EN is commonly caused by a range of conditions, including infections and vaccines. EN induced by COVID-19 vaccines is rarely reported. Herein, we report an original clinical observation of EN occurring after the first dose of AstraZeneca COVID-19 vaccine (vaxzevria), a viral vector vaccine, without recurrence after the second dose. This case was notified on August 2021 to Tunisian National Centre of Pharmacovigilance and was analyzed according to the French updated method for the causality assessment of adverse drug reactions. A 46-year-old woman with no medical history, presented with diffuse erythematous painful and nodular lesions, located symmetrically over her legs. Eleven days before, she had received the first dose of vaxzevria which was followed by a sudden asthenia, and oedema over her lower limbs. The patient reported no recent infectious episodes. She had no known drug allergy. Skin examination showed multiple, tender, erythematous nodules, which ranged from 3 to 4 cm in diameter located over the tibial area. Some were regressive according to biligenesis shades. Laboratory tests including a complete blood count, renal and hepatic tests and antistreptolysin O titer were carried out and were negative except an elevated c-reactive protein of 45 mg/dL. The dermatological examination found lesions on both legs to be consistent with EN and started therapy with prednisone 40 mg daily for one week, subsequently gradually tapered and suspended, with complete regression of lower limb skin lesions within 10 days. No skin biopsy was performed due to the typical clinical presentation, color evolution and a complete response to steroid therapy. The patient subsequently received the second dose after two months without the reappearance of EN. In this case the role of vaccine was suspected in front of a temporal association between the first dose of vaccine and the onset of EN and the absence of another etiology. However, the good evolution of this skin manifestation will help reassure patients in the safety of vaccine administration.