Interpretation
Although rhinitis and urticaria have been traditionally studied separately, similar pathogenetic mechanisms may exist in one or more endotypes.68 For instance, histamine and platelet activating factor (PAF) are both known as the main mediators in the pathophysiology of rhinitis and urticaria, which might explain the clinical phenomenon of their co-existence.69 In multiple clinical trials, anaphylaxis has been reported to relieve rhinitis or urticaria with H1-antihistamines, including bilastine and rupatadine, further supporting the close association between rhinitis and urticaria.69-72 Meanwhile, the potential monotherapy for patients with these two diseases has been investigated continuously.
We observed no significant differences in the association between urticaria and AR or non-AR. The frequency of AR symptoms has been classified as intermittent or persistent, and the severity of AR is rated as mild, moderate, or severe in the Allergic Rhinitis and its Impact on Asthma guidelines.73,74 This disease has been divided as either seasonal or perennial traditionally, yet this classification is no longer recommended for many limitations.5,73,75 According to the statistical analysis, the pooled prevalence of urticaria was 10% (95% CI, 8.0%–12.0%) and 7% (95% CI, −4.0%–17.0%) among patients with persistent rhinitis and intermittent rhinitis, respectively. Only 2 studies reported both AR severity and risk of urticaria developmnt. One study34 suggested that patients with persistent, moderate, or severe AR were more likely to present co-morbidities, including asthma and atopic dermatitis, except for urticaria and food allergy. However, based on the data from 35 Italian Centers, Franco and colleagues demonstrated that patients with mild AR had a higher frequency of having no co-morbidities, while patients with moderate-to-severe AR had a higher frequency of having two or more co-morbidities, including urticaria.35 Few studies have reported data on AR severity in patients with urticaria. More researches should evaluate the association between AR severity and risk of developing urticaria.
There is a consensus that the clinical classification of urticaria should be based on duration and causes/triggers.76-78AU is defined as a recurrent development of wheals with/without angioedema within 6 weeks, while the recurrent period of >6 weeks is identified as chronic urticaria (CU).78Whether CU is classified as either CSU or chronic inducible urticaria (CIndUs) depends on the skin lesions that appear spontaneously or are induced by a specific trigger.79 The following are the common subtypes of CindUs, which are defined as physical urticarias: cold-/heat-induced urticarias, pressure-induced delayed urticaria, solar urticaria, and symptomatic dermographism. Contact urticaria, aquagenic urticaria, and cholinergic urticaria are non-physical CIndUs. In this meta-analysis, the occurrence of rhinitis in AU was significantly higher than that in CU. Moreover, the difference between the prevalence of rhinitis between patients with CSU (33.4%; 95% CI, 8.3%–58.5%) and those with CIU (34.6%; 95% CI, 17.3%–51.9%) was insignificant. However, the number of studies supporting our findings on the association between rhinitis and more delicate classifications of urticaria is limited.
Rhinitis and urticaria are highly similar, and both of their pathogeneses are complex. For example, the occurrence of IgE-sensitization often appears in both patients with rhinitis and those with urticaria. Clinical researches have revealed that over half of the patients with AR have a personal history of an atopic disease, including urticaria and asthma, as well as an elevated serum IgE level.36,39 Mast cells, which contain a myriad of preformed and pre-activated mediators, including cytokines, histamine, and chemokines, are widely known to play a key role in urticaria.76,80 These mediators have also been demonstrated to be critical in the mechanism of rhinitis.81,82 Rupatadine, as the international evidence-based guidelines recommend second generation H1-antihistamines (sgAH) owing to their dual affinity for PAF and histamine H1- receptors, has been proven to be effective in patients with AR and those with CSU.69 Recently, more biomarkers have been identified for both rhinitis and urticaria, including (interleukin) IL-33, IL-6, brain-derived neurotrophic factor, and serum amyloid A.80,83-86
This study has some limitations. First, urticaria and rhinitis were diagnosed based on different criteria between studies, varying from self-reporting to diagnosis by a physician, possibly resulting in a potential misclassification of these two diseases. Second, the scope of study populations is different between studies, varying from school- and hospital-wide to nation-wide populations. Third, our study excluded studies written in languages other than English, potentiall affecting the generalization of results. Third, only two studies have reported on the activity of rhinitis and risk of developing urticaria. The linear relationship between rhinitis activity and risk of developing urticaria needs further research. Last, only two studies had data on the co-occurrence of rhinitis and AU, which could have biased our results. Further research on this matter is warranted.