Urticarial vasculitis following <scp>mRNA anti‐COVID</scp> ‐19 vaccine

Abstract

Cutaneous adverse reactions following anti-COVID-19 vaccination are being increasingly reported and comprise a wide variety of clinical phenotypes.1, 2 Urticarial vasculitis (UV) has been observed both in patients with COVID-193 and in those undergoing vaccination, well before the advent of anti-COVID-19 vaccines.4 Herein, we report the case of a 27-year-old woman referred to the outpatient service of our Dermatology Unit for an itchy, diffuse, cutaneous eruption, which had appeared 10 days after the first dose of the Moderna anti-COVID-19 vaccine. Her medical history was noncontributory, as she denied either new drug intake or infectious episodes in the preceding months. Moreover, she did not recall of any similar episodes in the past. Upon physical examination, an erythematous, maculopapular, and partly pomphoid rash was appreciated on the patient's trunk, upper and lower limbs, and plantar surfaces (Figure 1A,B). Subjectively, the patient complained of an accompanying burning sensation. No angioedema could be observed. Dermoscopy was nonspecific, revealing only pale reddish-orangish, structureless areas with central blanching (Figure 1C). Laboratory examinations were within normal ranges. For over a month, such eruption had proved refractory to oral prednisone (37.5 mg/day tapered in about 3 weeks), full-dose antihistamine drugs, a short course with clarithromycin, and topical steroids, both prescribed by the patient's General Practitioner. Based on the integrated clinical and dermoscopic findings, a presumptive diagnosis of UV was made, and an incisional biopsy was performed for confirmation. On histology, edema, mild capillary vasodilation, and perivascular cuffing, with signs of vascular wall damage, were seen in the superficial and mid dermis. The infiltrates consisted mainly of lymphocytes, rare mastocytes, and numerous eosinophilic polymorphonucleates, which were also present in the interstitial area (Figure 1D). A final diagnosis of UV was rendered. A therapeutic trial with oral methylprednisolone (32 mg/day) slowly tapered over the course of 2 months led to an almost complete resolution of the lesions, with pigmentary residues on the lower limbs and rare wheals still appearing sporadically over the abdomen. Urticarial eruptions have been observed following anti-COVID-19 vaccinations,1, 2 with a median onset ranging between 3 and 8 days after the first and 2–5 days after the second dose of mRNA anti-COVID-19 vaccines.1 Recently, Dash et al. published the very first case of anti-COVID-19 vaccine-induced UV due to whole virion inactivated coronavirus vaccine. The lesions appeared just 1 day after the administration of the second dose and there was no prior history of drug intake or infection. Direct immunofluorescence was negative. After a 1-week course with oral indomethacin, topical calamine, and systemic levocetirizine, all the lesions had resolved with residual hyperpigmentation.5 Conversely, our case was hallmarked by a protracted course and proved refractory to most of the usual pharmacological interventions employed for UV.6 The timing was consistent with a primary, adaptive, immune response, whereas the report by Dash et al. suggests a secondary response in a previously sensitized individual. Classically, UV is thought to result from a Type III hypersensitivity reaction, in which antigen–antibody complexes are deposited in the vascular lumina and trigger complement activation and neutrophil infiltration.6 Anti-COVID-19 vaccines induce potent adaptive immune responses, with conspicuous—yet decreasing—antibody production in the months following their administration.7 Depending on the subject's genetic background or possibly on molecular mimicry, this may lead to the aforementioned cascade of events. Although the pathophysiology of anti-COVID-19 vaccine-related UV is still incompletely understood, longer treatment with systemic steroids may be required in a proportion of these cases, especially during the period of peak antibody production. In conclusion, we reported the second case of anti-COVID-19 vaccine-induced UV, illustrating a longer course of disease than previously observed. Further research is warranted to better define the clinicopathological features of this entity. The authors declare no potential conflict of interest. All authors have made substantial contributions to the work and have approved the final version of this article. Gianluca Nazzaro and Carlo Alberto Maronese contributed to study conception and design and data analysis. Carlo Alberto Maronese reviewed the pertaining literature. Gianluca Nazzaro and Carlo Alberto Maronese edited and approved the final draft. Written informed consent was obtained from the patient for publication of this report and accompanying images. Data sharing is not applicable to this article as no new data were created or analyzed in this study. Data sharing is not applicable to this article as no new data were created or analyzed in this study.

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