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.