Misconceptions about medication use in chronic urticaria (CU) are widespread on social media and in clinical practice, potentially leading to treatment failure and preventable adverse effects. Understanding the evidence behind antihistamine paradoxes, corticosteroid limitations, vaccine safety, and drug hypersensitivity is essential because appropriate medication management can prevent disease exacerbation and improve patient outcomes in this common condition caused by excessive cutaneous mast cell activation.

Christophe Vermeulen, MD, dermatologist and venereologist in Annecy, France, highlighted the scope of misinformation during the 2025 Dermatology Days of Paris conference in Paris, France, in a session entitled Chronic Urticaria: Myths and Realities.

“On social media, people regularly blame antihistamines of being completely ineffective at best or, worse, of triggering urticaria flares,” he said. “Others routinely described using corticosteroids whenever they had a severe urticaria episode, perhaps without realizing the rebound phenomenon. Vaccines, too, particularly on X, are accused of causing true epidemics of dermatoses, including CU.”

Drawing on published data, Florence Tétart, MD, dermatologist at Rouen University Hospital in Rouen, France, and secretary of the Urticaria Group of the French Society of Dermatology, addressed each of these issues in detail.

Antihistamine Paradox

Tétart recalled that second-generation antihistamines are the cornerstone of management for chronic spontaneous urticaria (CSU). However, she emphasized that there are rare cases of antihistamine-induced paradoxical urticaria.

“It is important to know that this can happen. These paradoxical urticarias are rare and difficult to diagnose,” she said.

A publication from Tenon Hospital in Paris, France, described 16 cases, including nine from Tenon Hospital and seven reported in the literature. These paradoxical reactions involved all classes of antihistamines, but mainly piperazines (43%), piperidines (40%), and alkylamines (10%).

Another notable finding was that these patients were intolerant to nonsteroidal anti-inflammatory drugs (NSAIDs). In most cases, the patients had an atopic background and type 1 autoallergic CU, according to a team from Charité - Universitätsmedizin in Berlin, Germany.

Several pathophysiologic hypotheses have been proposed, including mast cell activation via the complement pathway, alteration of arachidonic acid metabolism under the effect of antihistamines, and a shift of the histamine H1 receptor toward its active rather than inactive form.

According to Tétart, from a diagnostic standpoint, urticaria occurs within 5 hours of antihistamine ingestion. Beyond this period, the flare should be considered unrelated to antihistamines.

Targeted allergy investigations, including skin and oral provocation tests with suspected antihistamines or alternative agents, should be conducted.

Corticosteroid Concerns

Tétart noted that corticosteroid therapy is associated with excessive adverse effects and considerable uncertainty, as shown in a 2024 literature review.

This meta-analysis pooled data from eight studies on acute urticaria and four studies on CU, primarily in adults, using variable regimens, including oral and intravenous corticosteroids administered for 1, 4, or 7 days.

The probability of achieving good CSU control with the addition of corticosteroids compared with no corticosteroids was only 2.2% higher. The number of treatments required to achieve a meaningful difference was 45 patients. In contrast, adverse effects increased by 14.8% after corticosteroid use. The serious adverse effects reported were seven.

The analysis also showed that systemic corticosteroids used to treat acute urticaria or exacerbations of CU have limited efficacy and are associated with adverse effects such as dyspeptic symptoms, headache, anxiety, and fatigue.

Tétart concluded, “These results confirm what is stated in the French urticaria guidelines: Corticosteroids are not recommended for urticaria because of insufficient evidence.”

Vaccination Effects

“There is no contraindication to vaccination of any kind in patients with CU,” Tétart emphasized. However, many patients remain concerned that vaccination may trigger urticaria flare-ups.

According to a global study of urticaria reported as secondary to vaccination using data from the World Health Organization international pharmacovigilance database, among 3474 reports of CU from all causes, 1898 reports were associated with vaccination between 2010 and 2023.

This increase in reporting was particularly pronounced in men and older individuals. No deaths were reported in patients with vaccine-associated CU.

Researchers have reported a sharp increase in CU reports associated with vaccination since 2020, driven by messenger RNA (mRNA) vaccines against COVID. “There is clearly a pre- and post-COVID period,” noted Tétart.

mRNA COVID vaccines were associated with the highest number of reported CU cases (reporting odds ratio [ROR], 26.52), followed by human papillomavirus vaccines (ROR, 4.23), influenza (ROR, 3.09), adenovirus type 5 vector COVID (ROR, 2.82), and herpes zoster (ROR, 2.28) vaccines.

“We are seeing a particular distrust toward new vaccines,” said Tétart.

Despite the limited understanding of the pathogenic mechanisms underlying CU, particularly in the context of vaccine effects, emerging data suggest that autoimmunity may play a central role in its development.

“It is therefore possible that there is a link between vaccination and urticaria, but it is difficult to know whether these patients would not have developed CU even without vaccination,” she said.

Flare Risk

Can vaccines exacerbate existing diseases beyond induction?

“Some patients with preexisting CSU report an exacerbation after vaccination,” Tétart said, adding that all available publications on this topic concern COVID vaccination, with variable rates across studies.

In a cohort of omalizumab-treated patients with severe CU, approximately 15% reported exacerbations after COVID vaccination.

Similarly, in the COVAC-CU, an international multicenter study of Urticaria Centers of Reference and Excellence in patients with CU that retrospectively evaluated the effects of COVID vaccination and collected data from patients receiving different doses of COVID vaccines, approximately 1 in 10 patients experienced exacerbation after vaccination. However, recurrence after the second dose was not observed. Nearly half of the affected patients did not experience new exacerbations after the second dose.

The identified risk factors for exacerbation included CU duration of less than 2 years, female sex, and NSAID intolerance.

Patients should be reassured about these possible exacerbations. “We should tell them that it can happen, but that it is not serious,” Tétart said. According to the French Society of Dermatology, there are no contraindications to COVID vaccination in patients with CU, and no specific precautions are required.

Drugs to Avoid

Another important issue is that patients with CU are potentially prone to hypersensitivity reactions. According to a 2019 study, 37.5% of patients with CU reported drug allergies compared with 23.6% of individuals without CU.

NSAIDs and opioids are the main contributors to hypersensitivity. NSAID intolerance affects approximately 1% of the population but up to one third of patients with CSU.

There is a clear pathophysiologic rationale for this. The MRGPRX2 receptor on mast cells is sensitive to opioids, neuromuscular blocking agents, and fluoroquinolone antibiotics. NSAIDs can also directly affect mast cell activation.

Therefore, selective COX-1 inhibitors and opioids should be avoided in these patients. Many patients tolerate aspirin at antiplatelet doses, and selective COX-2 inhibitors can be considered, Tétart said.

If necessary, NSAID reintroduction under antihistamine cover can be attempted in a specialized setting. In a study of patients with CSU, NSAID intolerance was confirmed after testing, and approximately three quarters tolerated NSAIDs while receiving antihistamine treatment.

In conclusion, Tétart emphasized the importance of avoiding self- and overmedication in patients with CU. She also underscored the need for a rigorous clinical approach, including allergy investigations when appropriate, “because some patients can develop anaphylaxis.”

None of the speakers reported having any relevant conflicts of interest.

This story was translated from Medscape’s French edition.