Antihistamines
Antihistamines are available as oral, intranasal, and ocular preparations. Oral first generation, sedating antihistamines are no longer recommended for the treatment of pediatric rhinitis due to their impaired safety profile often associated with cardiac arrhythmias, drowsiness, confusion, vision, and mental disorders etc. Of importance, a recent report using data from the World Health Organization (WHO) database, showed that the use of certain antihistamines has been strongly associated with severe and unexpected reactions, more so in preschoolers, where off-label use is frequent [98]. Second generation antihistamines present a significantly improved safety profile due to their high H1-receptor selectivity, low brain permeability and longer duration of action [99]. Recently, cardiac rhythm safety was documented for certain 2nd generation antihistamines, such as bilastine, cetirizine, levocetirizine, ebastine, fexofenadine, loratadine, desloratadine, mizolastine and rupatadine, even in the case of quadrupling the recommended standard dose [100]. Antihistamines, act predominantly on neutrally mediated symptoms such as sneeze, rhinorrhea, and nasal itch. They should be used continuously, rather than no-demand in persistent rhinitis patients [93]. Topical/nasal antihistamines have rapid onset of action and minimum side effects [101]. In addition, azelastine has been shown to have mast cell-stabilizing, anti-leukotriene, anti-inflammatory and immunomodulatory effects [102].
Intranasal corticosteroids (INCs)
INSc are the mainstay, particularly for moderate-to-severe allergic rhinitis, due to their anti-inflammatory properties and significant attenuation of late phase allergic reaction, thus acting on nasal congestion [59, 103]. In respect to non-allergic rhinitis, a recent Cochrane review showed that INCs use has only short term beneficial effects on symptom severity, potentially depending on individual phenotypic characteristics [104]. INCs have a rapid onset of action, while the newer preparations such as mometasone furoate, fluticasone furoate (FP) and fluticasone propionate present negligible systemic absorption, thus they are mostly suitable for children [105]. On-demand use can be an efficacious alternative in children with seasonal AR symptoms, especially in families with safety concerns on daily CS use, in order to increase adherence [106]. Recently, an ARIA-EAACI statement suggested that, based on current evidence, patients with COVID-19 infection should not discontinue their INCS prescribed for AR symptoms [107].
The recently formulated combination of azelastine and fluticasone propionate (FP) has shown short and long term efficacy, with superiority over FP both in speed of action and symptom relief, in children with AR [108, 109]. Safety and tolerability have been documented in children over 4-years of age, with minimal local adverse reactions such as dysgeusia [110]. The combination has been granted approval for use in children over 6 years of age by the U.S. Food and Drug Administration [111].
Antagonists of leukotriene receptors (LTRA) block cysteinyl leukotrienes receptors, which are important mediators of the inflammatory response in both AR and asthma [112]. Several studies have shown inferiority of LTRA compared to INCS and SGHA as therapeutic choices in AR, while as of 03/04/2020 FDA required a boxed warning, based on limited data reporting serious mental health side effects, thus restricting montelukast use for AR [113].