Chronic spontaneous urticaria and dermographism following
COVID-19 booster vaccination: a case series
To the Editor,
To date, more than 3.6 million persons in Denmark have received booster
doses of COVID-vaccine, of which the majority have been the
Pfizer-BioNTech’s “Comirnaty” (86.5%) and Moderna’s “Spikevax”
(13.5%) vaccines (1). While adverse events following vaccination with
the first two doses of COVID-vaccine have been reported, only a handful
of cases documenting adverse events after receiving a booster
vaccination have been published (2-5). In private dermatology practice,
we have noticed an increasing number of patients with chronic
spontaneous urticaria and dermographism.
This case series is based on 15 consecutive patients cared for in a
single private dermatology practice having a catchment area of 90000
patients. Clinical and demographic data are presented in Table 1. Twelve
patients had no previous medical history of urticaria and developed
inducible urticaria post vaccination (Figure 1) and seven of these
patients also had coexisting spontaneous urticaria. The remaining three
patients developed an exacerbation of their preexisting urticaria with
newly developed dermographism in two patients. All patients developed
symptoms within one day to three weeks following vaccination with a
median time of 14 days. Most patients had severe symptoms with six
requiring acute doctor visits and two being admitted to the emergency
department. All patients were treated with high-dose antihistamines, and
three patients received oral prednisolone. Three patients received
further treatment with omalizumab due to lack of response to high dose
antihistamines/oral steroids. In all cases the most likely provoking
factor of the chronic spontaneous urticaria and dermographism was
believed to be the COVID-vaccine, as no other plausible cause was found,
despite a thorough medical history and routine blood tests following
international EAACI/GA2LEN/EUROGuiDerm/APAAACI
guideline.
We performed a literature research and found four other case studies
reporting chronic spontaneous urticaria or dermographism following
booster vaccination with COVID mRNA-vaccines (2-5). The mechanism is not
elucidated, but it does not appear to be consistent with a true type I
allergic reaction. We hypothesize that the generation of interleukins or
other factors, in addition to T-cell activation, may lead to a
non-IgE-mediated mast cell degranulation. A delayed hypersensitivity
reaction against vaccine excipients or the mRNA component has already
been suggested as the cause of localized injection-site reactions to the
Spikevax vaccine (6). Most of our patients (73.3%) received a booster
vaccination with Spikevax. Out of a total of 3.629.799 Danes who have
received booster vaccinations, only 489.037 (13.5%) were vaccinated
with Spikevax (1). It may be possible that Spikevax is more likely to
stimulate an immunologic response leading to urticaria. Due to different
booster dosages of Comirnaty (0.3 mL containing 30 micrograms of mRNA)
and Spikevax (0.25 mL containing 50 micrograms of mRNA), Spikevax
contains more mRNA, which could support this hypothesis, but more
research is needed.
It is important to identify and distinguish between different
hypersensitivity reactions, which can include anaphylaxis, angioedema or
acute urticaria, and delayed reactions, which consists of delayed
urticarial reactions, late local reactions, and injection site reactions
(“COVID-arm”). The Centers for Disease Control and Prevention
recommends that patients who experience immediate hypersensitivity
reactions within 4 hours of receiving a COVID vaccine postpone the
subsequent dose until after consulting with a specialist (6).
This study describes booster vaccinations with COVID mRNA-vaccine
leading to the development of chronic spontaneous urticaria and
dermographism, which is a distinct clinical picture. These symptoms can
be treated similar to chronic spontaneous urticaria and are not a
contraindication to future vaccination. As many countries now are
administrating a third or even fourth dose of COVID-vaccine, we hope
this letter makes clinicians aware of this potential adverse effect,
especially following booster vaccination with Spikevax.
Jakob Lillemoen Drivenes1
Aleena Banerji2
Anette Bygum3
1Vestfold Hospital Trust, Tønsberg, Norway
2Division of Rheumatology, Allergy, and Immunology,
Massachusetts General Hospital, Harvard Medical School, Boston
3Department of Clinical Genetics, Odense University
Hospital, Odense, Denmark & Clinical Institute, University of Southern
Denmark, Odense, Denmark