Q&A: Nine percent of chronic urticaria patients see exacerbations with COVID-19 vaccines
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Key takeaways:
- 70% of patients with exacerbations responded to antihistamines.
- Concerns about adverse events were associated with exacerbations.
- Communication about risks and benefits is essential.
Nine percent of patients with chronic urticaria experienced exacerbations after getting a COVID-19 vaccination, according to a study published in The Journal of Allergy and Clinical Immunology.
These exacerbations included wheals (68.4%), wheals and angioedema (22.8%) and angioedema alone (5.5%), with 59.2% happening within 48 hours and 17.9% within 6 hours.
Considering these adverse events, Healio spoke with Emek Kocatürk, MD, professor in the Urticaria Center of Reference and Excellence (UCARE) of the department of dermatology at Koç University School of Medicine in Istanbul, Turkey, and researcher in Charite University Institute of Allergology, Berlin, to find out more.
Healio: What prompted this study?
Kocatürk: Chronic urticaria (CU) is a persistent skin disorder characterized by the recurring appearance of wheals on the skin and/or deeper swellings called angioedema in the mucosal surfaces. The spontaneous and unexpected nature of the disease, coupled with the potential for exacerbations, lends it a challenging and unpredictable character.
Affected individuals grapple with the sudden emergence of wheals or hives on their skin, often without any apparent trigger. This creates a heightened sense of sensitivity in patients and predisposes them to worry that vaccines might trigger immune responses that could exacerbate their CU symptoms or induce new skin reactions. Moreover, the fear of the unknown, potential allergens present in vaccines — or worries about potential interactions between their condition and vaccine components — can all contribute to the hesitation.
These concerns not only existed among the patients but also in the physicians treating them during the massive COVID-19 vaccination period. We as urticaria experts practicing in specialized centers for urticaria care known as UCARE received many questions about the safety of COVID-19 vaccines in patients with CU.
The convergence of worries among patients and physicians combined with the lack of information based on real-life experiences prompted us to perform the COVAC-CU study among the UCARE Network, which includes more than 150 dedicated urticaria care centers. The study aimed to investigate the rates and risk factors for CU exacerbation and the frequency of adverse reactions including allergic reactions in patients with CU vaccinated against COVID-19 in a worldwide, large and diverse patient population.
Healio: Were there any particularly surprising or significant findings you would like to spotlight?
Kocatürk: The high participation rate among UCARE centers was very pleasing for us. Fifty percent of UCAREs worldwide participated in the study, which shows high enthusiasm for answering the study question.
The study included a diverse population of almost 3,000 patients with CU from all over the world who received mainly two doses of different types of COVID-19 vaccines.
The high rate of patients with good control of urticaria (more than 50% reported complete control) highlighted the importance of specialized patient care centers when we look at previous studies showing that almost 80% of patients were not controlled.
None of the six patients who reported a history of vaccine allergy had a systemic reaction to COVID-19 vaccines.
Interestingly, the rate of CU exacerbations was higher when the patients received premedication before vaccination, such as adding antihistamine tablets or glucocorticosteroids to ongoing CU treatment. This might be due to the bias that the patients who had premedication were the more anxious ones.
Opposed to the expected, control of urticaria was not associated with disease exacerbation. Both well-controlled and uncontrolled patients had similar rates of exacerbation, but patients who were on omalizumab (Xolair; Genentech, Novartis) treatment had less disease exacerbation. This might be linked to the anti-inflammatory effect of the medication, which might have prevented vaccine-related disease exacerbations.
Half of the patients with CU were anxious about getting vaccinated, possibly due to fear of having their disease exacerbated or other allergic reactions. This prevented some patients from getting a second dose of the vaccine. However, the concerns seemed to decrease as the patients received subsequent vaccine doses.
Although mRNA vaccines have been associated with more systemic allergic reactions, more cutaneous adverse effects and autoimmune disease exacerbations, adenovirus viral vector vaccines were associated with more CU exacerbations in our study.
Of the patients who had CU exacerbations after the first dose, half did not have any exacerbations after the second dose. However, there still was an increased risk for exacerbations with following doses if the patient had an exacerbation with a previous vaccine dose.
Given that 10% of the vaccinated patients did not have any exacerbations after the first or second doses but did after the third dose, it is not possible to tell patients with CU that they will not have a disease exacerbation after vaccination if they did not have any exacerbations after the previous vaccine doses.
CU exacerbations were more common in patients who had constitutional symptoms after vaccination, which supports the notion that the disease exacerbations are not hypersensitivity reactions but possibly associated with nonspecific immune response triggered by vaccine components.
Similar to studies that reported increased adverse effects after second vaccine doses, CU exacerbation rates also increased with later vaccine doses.
The rate of adverse reactions (43.5%) was lower than the reported adverse effect rate in observational studies and in clinical trials (around 60%). We believe this is linked to the effects of CU treatment received by the patients — either antihistamines, omalizumab or other medications.
Seven patients reported systemic reactions. But whether these reactions were true anaphylaxis remained to be clarified, because these were patient-reported reactions, and none of them said they sought adrenaline treatment. Risk factors for systemic reactions included a history of allergy such as drugs, pollen or dust and a previous episode of anaphylaxis.
Patients who were concerned about getting vaccinated had an increased risk for disease exacerbations, which suggested the role of immunization stress response syndrome, where anxiety about receiving a vaccine can stimulate a physical reaction.
Healio: What makes these findings surprising or significant?
Kocatürk: From this study, we wanted to give exact figures to our patients and to our colleagues who ask about the possibility of exacerbations with COVID-19 vaccination. Will I have systemic reactions? Will I have more adverse reactions than people who don’t have urticaria? Who is more prone to having disease exacerbations after getting COVID-19 vaccination?
Now we have the answers, and we are very happy to say that the risk for exacerbations after COVID-19 vaccination is 9% in patients with CU. I believe this is a very relieving message for these patients. Disease exacerbation will not occur in more than 90% of patients. And even if exacerbations occur, they respond to antihistamines in more than 70% of patients, and they lasted for a few weeks or less.
Healio: Which patients with CU are at risk for getting disease exacerbations after vaccination?
Kocatürk: Female patients and patients with chronic spontaneous urticaria, rather than chronic inducible urticaria, are more prone to having disease exacerbations, as well as patients with NSAID intolerance and patients who have concerns about getting vaccinated. Adenovirus viral vector vaccines also were associated with higher risks for CU exacerbation, whereas omalizumab treatment and Latino/Hispanic ethnicity lowered the risk.
Healio: Can patients get further vaccine doses if they experienced exacerbations after the first dose?
Kocatürk: There is a 50% possibility that patients with CU who had disease exacerbation after the first dose will have exacerbations after the second dose. Although we did not report it in the manuscript, the risk for CU exacerbations seemed to decrease when there was a switch to another type of vaccine with the following dose.
Healio: How can doctors use these findings to improve care?
Kocatürk: The results of our study will help physicians answer questions from their patients and relieve patient concerns. Our results will serve as valuable insights that inform health care professionals, guiding them in making evidence-based decisions tailored to the specific needs of patients with CU.
With a better understanding of how COVID-19 vaccines interact with this patient population, health care providers can offer more accurate and personalized advice regarding vaccination. Our study helps to identify any patterns of adverse reactions or exacerbations related to the vaccines, enabling health care teams to anticipate and manage potential challenges effectively.
Moreover, the dissemination of positive safety outcomes from these studies can help alleviate vaccine hesitancy among patients with CU, assuaging concerns and encouraging more individuals to confidently receive the COVID-19 vaccine. Ultimately, this knowledge empowers health care providers to deliver optimal care by considering the unique medical intricacies of patients with CU when navigating vaccination decisions.
Healio: You emphasized the role of communication in easing patient concerns about vaccines. Do you have any suggestions for improving communication?
Kocatürk: We found that patients who are concerned about getting vaccinated due to their fear of adverse effects or of getting their disease aggravated had an increased risk for disease exacerbations after COVID-19 vaccination. This finding tells a lot about the role of mind and body interactions in diseases. Easing patient concerns might even prevent disease exacerbations in these patients, so communication is key.
Improving communication between patients with CU and physicians is pivotal in addressing patient concerns about getting vaccinated. Providing accurate and detailed information about COVID-19 vaccines, emphasizing their safety and benefits, is critical, and our study serves as an important source for this kind of information.
Additionally, physicians should engage in one-on-one discussions with patients to understand their unique medical history, concerns and specific triggers. If patients have had adverse reactions to vaccines in the past, addressing these experiences is important. Reassuring patients that their individual medical history is being considered can build confidence. Also, discussing the potential risks and benefits with patients may alleviate their anxiety and make them feel heard.
By sparing a few minutes to listen to their concerns and provide thorough information, physicians can establish a foundation of trust and effective communication that empowers patients with CU to make informed decisions about COVID-19 vaccination, while also addressing their specific concerns and needs.
Healio: What is the next step in this research?
Kocatürk: Our study could provide information about the rates of disease exacerbation and factors associated with it while also presenting the rates of other adverse effects including systemic reactions. However, we could not identify the mechanisms underlying disease exacerbations and what is happening in the cellular level. Molecular studies are needed to identify these mechanisms and clarify the interactions between mast cells and vaccine components while demonstrating the immune pathways enrolled in these interactions.
Another issue with COVID-19 vaccines is the emergence of new onset urticaria after vaccination, which was not the focus of our study but will be investigated in a future UCARE Project called ‘UNITACT’ that we hope will provide insights into differences between non-vaccine-induced urticaria and vaccine-induced urticaria and shed light into underlying pathomechanisms.
References:
- Beatty AL, et al. JAMA Netw Open. 2021;doi:10.1001/jamanetworkopen.2021.40364.
- Ganesan S, et al. Front Public Health. 2022;doi:10.3389/fpubh.2022.876336.
- Kocatürk E, et al. J Allergy Clin Immunol. 2023;doi:10.1016/j.jaci.2023.07.019.
- Mauer M, et al. Clin Exp Allergy. 2017;doi:10.1111/cea.12900.
- Xu W, et al. Vaccines (Basel). 2023;doi:10.3390/vaccines11061118.
For more information:
Emek Kocatürk, MD, can be reached at emek.kocatuerk@charite.de.