Reactive Angioendotheliomatosis Following Ad26.COV2.S Vaccination
Practice points
- Reactive angioendotheliomatosis (RAE) is a rare benign vascular proliferation of endothelial cells lining blood vessels that clinically appears similar to Kaposi sarcoma and must be differentiated by microscopic evaluation.
- An increasing number of reports link SARS-CoV-2 viral infection or vaccination against this virus with various cutaneous manifestations. Our case offers a link between RAE and Ad26.COV2.S vaccination.
Prior cases of RAE have been treated with laser therapy, topical or systemic corticosteroids, excisional removal, or topical β-blockers, such as timolol.12 β-Blocking agents act on β-adrenergic receptors on endothelial cells to inhibit angiogenesis by reducing release of blood vessel growth-signaling molecules and triggering apoptosis. In this patient, topical steroids and oral antihistamines were sufficient treatment.
Vaccine-related adverse events have been reported but remain rare. The benefits of Ad26.COV2.S vaccination for protection against COVID-19 outweigh the extremely low risk for adverse events.13 For that reason, the Centers for Disease Control and Prevention recommends a booster for individuals who are eligible to maximize protection. Intramuscular injection of Ad26.COV2.S resulted in a lower incidence of moderate to severe COVID-19 cases in all age groups vs the placebo group. Hypersensitivity adverse events were reported in 0.4% of Ad26.COV2.S-vaccinated patients vs 0.4% of patients who received a placebo; the more common reactions were nonanaphylactic.13
There have been 12 reports of cerebral venous sinus thrombosis with thrombocytopenia after Ad26.COV2.S vaccination, which sparked nationwide controversy over the safety of the Ad26.COV2.S vaccine.14 After further investigation into those reports, the US Food and Drug Administration and the Centers for Disease Control and Prevention concluded that the benefits of the Ad26.COV2.S vaccine outweigh the low risk for associated thrombosis.15
Although adverse reactions are rare, it is important that health care providers take proper safety measures before and while administering any COVID-19 vaccine. Patients should be screened for contraindications to the COVID-19 vaccine to mitigate adverse effects seen in the small percentage of patients who may need to take alternative precautions.
The broad tissue tropism and high transmissibility of SARS-CoV-2 are the main contributors to its infection having reached pandemic scale. The spike (S) protein on SARS-CoV-2 binds to ACE2, the most thoroughly studied SARS-CoV-2 receptor, which is found in a range of tissues, including arterial endothelial cells, leading to its transfection. Several studies have proposed that expression of the S protein causes endothelial dysfunction through cytokine release, activation of complement, and ultimately microvascular occlusion.16
Recent developments in the use of viral-like particles, such as vesicular stomatitis virus, may mitigate future cases of RAE that are associated with endothelial cell transfection. Vesicular stomatitis virus is a popular model virus for research applications due to its glycoprotein and matrix protein contributing to its broad tropism. Recent efforts to alter these proteins have successfully limited the broad tropism of vesicular stomatitis virus.17
The SARS-CoV-2 virus must be handled in a Biosafety Level 3 laboratory. Conversely, pseudoviruses can be handled in lower containment facilities due to their safe and efficacious nature, offering an avenue to expedite vaccine development against many viral outbreaks, including SARS-CoV-2.18
