Rare case of NEAE reported after COVID-19 vaccination
Non-episodic angioedema associated with eosinophilia resolved in 2 months
A 26-year-old woman developed a rare case of non-episodic angioedema associated with eosinophilia (NEAE) following her second dose of the Pfizer-BioNTech COVID-19 vaccine, according to a study from Japan.
Eosinophilia refers to higher-than-normal levels of a type of immune cells called eosinophils.
Her NEAE symptoms were resolved completely two months after vaccination without the need for treatment with anti-inflammatory and immunosuppressive corticosteroids.
This case adds to three previous reports suggesting that COVID-19 vaccines, in rare instances, may promote the development of NEAE. These cases highlight the need for more studies “to elucidate the incidence, risk factors, clinical course and immunological responses after COVID-19 vaccination,” the researchers wrote.
The case study, “Nonepisodic Angioedema with Eosinophilia Following Receipt of the BNT162b2 mRNA COVID-19 Vaccine,” was published in the journal Internal Medicine.
Angioedema with eosinophilia is a subtype of angioedema characterized by high levels of eosinophils, a type of immune cell responsible for the body’s defense against parasites and other infectious agents, as well as triggers of allergic reactions.
The condition can be classified as episodic or non-episodic based on whether symptoms — such as tissue swelling, fever, and weight gain — occur in repeated episodes (episodic) or in a single episode. Notably, NEAE is more common among young women in East Asian countries, including Japan and Korea.
Vaccines work by training the body’s immune system to recognize a specific microbe, allowing a faster and more potent immune response in case of an infection, with the potential to prevent severe disease.
In rare cases, vaccines may alter the body’s immunological balance and lead to disorders characterized by eosinophilia.
Cases of vaccine-releated NEAE reported
To date, two cases of NEAE following vaccination against the influenza virus have been reported, along with three women in Japan and South Korea who developed NEAE after receiving a COVID-19 mRNA vaccine.
Now, researchers at the University of Tokyo, in Japan, described the case of a 26-year-old woman who developed self-resolving, but severe, NEAE after receiving the second dose of the Pfizer-BioNTech COVID-19 mRNA vaccine.
The woman, who had no other health conditions, developed swelling and an itchy, skin rash on her left foot one week after her second shot of the COVID-19 vaccine.
She was seen at a clinic and given antibiotics for suspected cellulitis, a deep infection of the skin caused by bacteria. However, the swelling gradually spread to her right leg and both arms, affecting her ability to walk and creating the need for a wheelchair.
Seven weeks after the vaccination, she was examined at another clinic due to marked swelling and weight gain. She also showed higher-than-normal eosinophil levels.
A week later, she was admitted to the researchers’ hospital, which physical examination revealing a pitting edema — when the swelling forms a pit after pressure that lingers for a few seconds — in her shinbones and a non-pitting edema in her hands. She did not have a fever or complain of itchy, skin rash or joint pain.
High levels of white blood cells
Lab work showed abnormally high levels of white blood cells, including eosinophils, and slightly elevated levels of IgE, an allergy marker. There were no signs of thyroid, heart, kidneys, or liver problems.
Lab tests for parasites and several viruses were negative, as were tests for the presence of self-reacting antibodies. Genetic blood disorders also were ruled out following genetic tests.
MRI scans revealed prominent under-the-skin swelling and a biopsy of the left hand confirmed the presence of inflammatory cells in the dermis, the skin’s middle layer.
Based on the clinical and lab findings, she was diagnosed with NEAE, which the physicians believed was triggered by the second COVID-19 vaccination.
Tissue swelling and eosinophilia gradually eased with supportive care alone — rest, attentive nursing, and medication to ease pain or fever — without the need for corticosteroid treatment.
Two of the three other reported cases of post-COVID-19 vaccine NEAE needed such treatment, while the other was managed with anti-allergic medication.
Two weeks later — roughly two months after the last vaccine shot — her symptoms resolved completely. At a five-month follow-up her eosinophil counts were within normal range.
The woman’s disease course “suggests that a [temporary] immunological process was triggered by vaccination,” the researchers wrote, adding that this case is “interesting from the perspective of immunological reactions after COVID-19 vaccination.”
They also noted that more research is needed to better understand the immunological responses to COVID-19 vaccines and a potential link between these vaccines and NEAE.