Review shows no increased risk of allergic disease after childhood vaccination

28th July 2021

A review of studies found no evidence of an increased risk of allergic disease following the administration of common childhood vaccinations.

According to the World Allergy Organisation, the allergy prevalence among the whole population ranges from 10 to 40%. Moreover, the number people in the UK with allergies, appears to be increasing by 5% every year. One possible cause of the increased prevalence of allergic disease is childhood vaccination although the available evidence is inconsistent. Nevertheless, any perception that childhood vaccination might increase the risk for the development of allergic diseases jeopardises the attainment of herd immunity and the attendant risk of outbreaks of the particular vaccine-controlled infection disease. With gaps in the current evidence, a team from the Faculty of Medicine, Department of Community Medicine, University of Peradeniya, Kandy, Sri Lanka, decided to undertake a systemic review and meta-analysis to examine the relationship between childhood vaccination and allergy. The team performed a search of the main databases such as PubMed and EMBASE for original studies examining exposure (in this case childhood vaccination) and allergic outcome. They restricted the review to randomised controlled trials and prospective cohort studies although did not exclude any studies where there were differences in the timing, number of doses or if the comparators were placebo, controlled vaccine or even no vaccine. The exposure of interest was defined as any childhood vaccination and the primary outcomes of interest were asthma/wheeze, rhino conjunctivitis, allergic rhinitis, atopic eczema, food allergy and allergic sensitisation.

Findings
A total of 42 eligible studies were included in the analysis covering vaccination with BCG, pertussis, MMR and DTP. This comprised 35 cohort studies and 7 randomised controlled trials. In their analysis, the authors found that none of the randomised trials found any evidence of an association between BCG or pertussis and allergic manifestations. In fact, two randomised trials observed a reduction in the risk of developing eczema (Risk ratio, RR = 0.83, 95% CI 0.73–0.93) but not for food allergy or asthma. Among cohort studies, childhood vaccination against measles was also associated with a reduced risk of eczema (RR = 0.65, 95% CI 0.47–0.90), asthma (RR = 0.78) and a non-significant reduction in allergic sensitisation (RR = 0.78, 95% CI 0.61–1.01). There was a trend towards a protective effect of measles vaccination against asthma (RR = 0.97), eczema (RR = 0.70) but a slight increased risk for allergy, though none of these associations were statistically significant.

In discussing their findings, the authors noted that there was no clear evidence that childhood vaccination was associated with an increased risk of allergic disease for the commonly given immunisations. In fact, if anything, the opposite was true, with the data suggesting a small, but potentially protective role against the development of eczema, particularly for measles. They concluded that while more studies are required to confirm these findings, it was important to promote the continuation of childhood vaccination to prevent the development of vaccine-preventable disease.

Citation
Navaratna S et al. Childhood vaccination and allergy: A systematic review and meta-analysis. Allergy 2021

Uncertainty over the efficacy of up-dosing antihistamine in chronic urticaria

27th November 2020

Between 0.5 and 1% of the population experience chronic spontaneous urticaria (CSU) which is characterised by recurrent pruritic wheals and/or angioedema that can persist for up to six weeks.

While the precise cause of CSU remains unclear, contemporary European guidelines advocate the use of second-generation antihistamines as a first-line treatment for the condition. Although these drugs can be effective, for patients in which symptom control remains inadequate, the guidance recommends up-dosing to four times the recommended dose as a second-line treatment option.

This latter commendation is based on expert opinion and for this study, a team from the Allergology Department, Complexo Hospital, A Coruna, Spain, set out to review the available evidence to support this approach. They included studies published in English or Spanish with patients at least 12 years of age with CSU on regular (as opposed to “on-demand”) therapy with a second-generation antihistamine. Other inclusion criteria were that the study should have a single antihistamine (rather than a combination), a placebo arm and using the drug at a higher than recommended dosage.

Findings
In total and after removal of duplicates and exclusions, only 14 articles were analysed in detail including 20 to 439 patients. Six studies focused on fexofenadine (up-dosing to 720 mg), 2 on cetirizine, levocetirizine, rupatadine, desloratadine and 1 trial with either ebastine or bilastine. Furthermore, only 5 of these trials were placebo controlled and all studies lasted between 2 and 8 weeks except for one fexofenadine trial which lasted 16 weeks. A higher dose of fexofenadine produced a dose-dependent significant response and controlled CSU in the majority of patients. Commenting on their findings, the authors noted that of the 14 trials, only 6 were of high quality and that the high level of heterogeneity in sample size, design, duration etc, which made it very difficult to make comparisons. Interestingly, they also note that despite current guideline recommendations, most studies did not find a significant impact on symptom control from up-dosing.

The authors concluded that while up-dosing appears both effective and safe, there is a lack of evidence to support this approach and called for further studies to validate the recommendations in guidelines.

Reference
Iriarte SP T et al. Up-dosing antihistamines inn chronic spontaneous urticaria: efficacy and safety. A systematic review of the literature. J Investig Allergol Clin Immunol 2020 doi: 10.18176/jiaci.0649