Epidemiology

Urticaria affects all age groups, however, acute urticaria appears more common in infants and young children while chronic urticaria appears more prevalent in adult patients. However, published data from paediatric patients remains scarce. In the 18-month Early Prevention of Asthma in Atopic Children (EPAAC) study involving 510 atopic children aged between 12 and 24 months, 42% of children receiving placebo experienced urticaria (Simons, 2007a; Zuberbier et al., 2018). Outside of this atopic patient population, significant variation in the prevalence of acute and chronic urticaria has been observed (Figure 1).

Figure 1: Prevalence of paediatric urticaria.

Figure 1: Prevalence of paediatric urticaria (UK: Greaves, 2000 and Khakoo, 2008; Denmark: Kjaer et al., 2008; Germany: Brüske et al., 2014; Thailand: Tuchinda et al., 1986; S. Korea: Lee et al., 2017)

Chronic urticaria is considered to be less prevalent in children than adults with a point prevalence of 0.1% to 0.3% identified in the UK (Khakoo et al. 2008), although higher incidences have been observed in other studies (Tuchinda et al., 1986; Choi et al., 2015). The significant variation that has been observed within the published prevalence of paediatric urticaria around the world is likely to be influenced by different patient populations, clinical settings and diagnostic criteria. However, while the reported prevalence of urticaria within children has been variable, a number of consistencies have also been identified. Unlike the adult population where women are more likely to develop CSU than men, in the paediatric population urticaria appears to be distributed equally between both sexes (Brüske et al., 2014; Chanskaulporn et al., 2014; Lee et al., 2016; Netchipourouk et al., 2017).

Although patient sex may not influence the incidence of paediatric urticaria, it does appear to change with age (Figure 2). A study consisting of 9088 German new-borns from two prospective birth cohorts identified the incidence of urticaria as approximately 1% per year of age. However, the incidence for both sexes was highest during the second year of life and was typically higher in preschool children than in school-aged children (Brüske et al., 2014).

Figure 2: Incidence of urticaria by age and sex.

Figure 2: Incidence of urticaria by age and sex (Brüske et al., 2014)

Aetiology: acute urticaria

The most common trigger for acute urticaria in children is infection. While these are typically viral infections of the upper respiratory tract, gastrointestinal and urinary infections, as well as bacterial and parasitic infections, have also been implicated (Pite et al., 2013). The association between infection and acute urticaria is underlined by their seasonality with peaks in acute urticaria being observed to coincide with rises in viral respiratory infections (Konstantinou et al., 2011).

Other reported causes of acute urticaria in children include drug hypersensitivity and food allergy. However, detailed work-ups in two studies suggested that >90% of children with suspected drug hypersensitivity were able to tolerate the medication (Rebelo Gomes et al., 2008; Seitz et al., 2011). Meanwhile, food allergy was cited as the cause of urticaria in 2.7% and 6.3% of paediatric patients (Sackesen et al., 2004; Ricci et al., 2010).

Aetiology: chronic urticaria

Determining a trigger for paediatric chronic urticaria (spontaneous and inducible) can be difficult with reported identification rates ranging from 21% to 83% (Marrouche and Grattan, 2012).

While viral infection has been implicated as an exacerbating factor for chronic urticaria in children, it is not believed to play a causal role as has been indicated in acute urticaria (Church et al., 2011). Meanwhile, the role of bacterial infections in paediatric CSU remains uncertain with many studies suggesting it is unlikely to play a significant role (Marrouche and Grattan, 2012).

However, like adult CSU, autoimmunity does appear to be a critical factor in a significant number of patients. In fact, the frequency of autoimmune CSU appears to be similar between paediatric and adult patients (Marrouche and Grattan, 2012). In a Thai study of 94 paediatric CSU patients, 38% of patients were found to have a positive autologous serum skin test (ASST) (Jirapongsananuruk et al., 2010), while in an Italian study, 45% of children with CSU (22 of 49) were identified as having autoimmunity as the underlying cause (Brunetti et al., 2004).

Chronic inducible urticaria is the most common chronic urticaria subtype in children with dermographic urticaria and cholinergic urticaria being the two most frequently observed forms (Marrouche and Grattan, 2012; Pite et al., 2013). While cold urticaria is less common in paediatric patients, it is important to note that in one study of 30 patients, one-third of patients experienced anaphylactic reactions alongside their urticaria (Alangari et al., 2004).

Clinical presentation

As with adult CSU, hives and/or angioedema are the key symptoms in paediatric urticaria. However, the relative ratios of these symptoms at presentation remains less clear in younger patients. An early study indicated that 78.4% of paediatric patients experienced hives alone, while 6.6% suffered from angioedema alone and the remaining 15% had both (Volonakis et al., 1992). A similar incidence of angioedema was observed in a recent prospective study that identified concomitant angioedema in 28% of CSU patients younger than 17 years of age (Netchiporouk et al., 2017). 

In contrast, a prospective study of 94 Thai children with CSU revealed that 51% had both hives and angioedema (Jirapongsananuruk et al., 2010) while a follow-up study from the same centre revealed 59.8% of children with chronic urticaria to suffer from hives and angioedema (Chansakulporn et al., 2014). It is apparent that further research is required to establish the typical clinical presentation ratios within paediatric CSU.

Duration

The natural history of paediatric chronic urticaria remains uncertain. In one study, 25% of chronic urticaria patients went into remission during the three-year observation period (Du Toit et al., 2006). In a more recent study, 18.5%, 54% and 72.1% of chronic urticaria patients were in remission 1, 3 and 5-years after the onset of symptoms (Chansakulporn et al., 2014). Unsurprisingly, it appears that the underlying cause may influence remission rates. In a study of 139 patients with chronic urticaria under the age of 18, a resolution rate of 10.3 per 100 patient-years was observed. However, patients with a positive basophil activation test (BAT), indicative of autoimmune urticaria, were twice as likely to resolve after 1 year than those with negative BAT results (HR, 2.33; 95% CI, 1.08–5.05). Conversely, the presence of basophils decreased the likelihood of resolution (HR, 0.40; 95% CI, 0.20–0.99) (Figure 3) (Netchiporouk et al., 2017).

Figure 3: Impact of BAT levels and presence of basophils on the probability of chronic urticaria resolution in patients under 18 years of age.

Figure 3: Impact of BAT levels and presence of basophils on the probability of chronic urticaria resolution in patients under 18 years of age (Netchiporouk et al., 2017).

 

Expert Insights

Chronic urticaria in childhood

Doctor Montse Alvaro gives an introduction to chronic urticaria in children including its prevalence.

 

Epidemiology of paediatric urticaria

Epidemiological data on paediatric CSU is very limited. Doctor Montse Alvaro describes an epidemiological study carried out at Hospital Sant Joan de Déu, Universitat de Barcelona which was recently presented at PAAM 2017.