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You receive a call from one of your adolescent patients, a 16 year old boy with a longstanding history of seasonal allergic rhinitis (SAR). He is currently treating his mainly nasal symptoms with an oral histamine antagonist (OH1A). His symptoms are getting increasingly difficult to control. He is worried about the upcoming hay fever season and asks for other treatment options.
Structured clinical question
In a 16 year old [patient] are topical corticosteroids [intervention] more effective than oral histamine antagonists [comparison intervention] in the alleviation of symptoms of seasonal allergic rhinitis [outcome]?
Search strategy and outcome
Search engine—PubMed: “allergic rhinitis and adrenal-cortex-hormones and meta-analysis” (MeSH-Terms).
Search results—two articles found, one original meta-analysis.
Secondary sources—Consensus Statement, European Academy of Allergology and Clinical Immunology.
See table 1.
The meta-analysis by Weiner et al was easily identified using the search terms from the structured clinical question. Once the internet database PubMed was accessed the paper could be reviewed online through the BMJ website (http://bmj.com). The secondary source of van Cauwenberge et al was suggested by a medical colleague and was likewise viewed on the internet through its publisher’s website (http://www.blackwell-synergy.com). Both papers were readily available, but of very different quality and use to our clinical scenario. The meta-analysis by Weiner et al gives detailed information about the process of identification and review of the primary data. In particular, it is structured along the rigorous methodology of a Cochrane review. The findings are presented in easily comprehensible tables and the limitations of the individual results are discussed in satisfactory detail. The consensus statement by van Cauwenberge et al is a concise document dealing with all issues and treatment options related to SAR. However, the authors give no details on the identification and review process of the evaluated literature. The paper therefore ranks lowest (level 5) in the hierarchy of evidence for clinical decision making. Its clinical bottom line is partially based on the study by Weiner et al, the result of the primary literature search.
With regard to the effectiveness and safety of OH1A and intranasal corticosteroids (INC), both come in once daily to twice daily applications, depending on the preparation used. First generation antihistamines have significant sedative and anticholinergic side effects. Such side effects are less pronounced in second generation antihistamines. In patients with liver disease or concomitant treatment with drugs metabolised through the cytochrome P450 system (antifungal agents or macrolide antibiotics) significantly increased drug concentrations are associated with serious side effects. In particular, terfenadine and astemizole have been associated with fatal cardiac side effects. Newer antihistamines (cetirizine (Zirtek), fexofenadine (Telfast), and loratadine (Clarityn)) are not metabolised via the cytochrome P450 system and are considered safe if drug specific recommendations are followed. Topical corticosteroids are known to occasionally cause predominantly mild local side effects (crusting, dryness, epistaxis). The topical application of low drug doses and low drug availability avoids high systemic drug concentrations and potential hypothalamic pituitary adrenal axis suppression, a serious complication of systemic corticosteroid treatment. No systemic side effects are recognised for fluticasone propionate and budesonide; systemic side effects have been described for dexamethasone spray and betamethasone drops only. However, caution is warranted in patients with a co-morbidity of asthma when inhaled corticosteroids are used alongside nasal corticosteroid preparations to avoid cumulative doses.
▸CLINICAL BOTTOM LINE
Nasal symptoms are significantly more effectively controlled by intranasal corticosteroids than oral histamine antagonists.
For eye symptoms, intranasal corticosteroids and oral histamine antagonists are at least equally effective.
Treatment of allergic rhinitis with intranasal corticosteroids is safe and cost effective.
A variety of INC preparations are available. Costs vary from £5.85 (budesonide aequos spray, Rhinocort Aqua) to £11.43 (fluticasone proprionate, Filxonase) in the UK. Few comparative studies are available on the effectiveness of different steroid preparations. Most of these studies are limited to perennial SAR. All INC are effective in alleviating nasal symptoms but aqueous preparations seem to be favoured by the majority of patients. Most studies describe treatment with budesonide 256 μg once daily to be more effective than the comparison INC. Budesonide has a good safety profile and is cost effective.
Table 1 Topical corticosteroids v systemic histamine antagonists in treatment of allergic seasonal rhinitis
Citation Study group and type (level of evidence) Outcome Key results Comment
Weiner et al (1998) Meta-analysis of 16 RCT (total of 2267 subjects; mean age 32 years, range 12 to 75 years) Comparison INC v OH1A on nasal symptoms (itch, nasal blockage, nasal discharge, and sneezing) INC give greater relief of total nasal symptoms than OH1A Analysis based on Cochrane methodology (albeit language bias) Combined standardised mean difference -0.42 (95% CI -0.53 to -0.32). Level of evidence 1a (SR with (predominantly) homogeneity of RCT) Comparison INC v OH1A on eye symptoms No significant difference between INC and OH1A in relieving eye symptoms Meta-analysis of 11 RCT, OH1A could be beneficial ancillary to INC for treatment of eye symptoms. Comparison INC v OH1A on cost effectiveness INC are more cost effective than OH1A Individual studies suggest cost effectiveness Total outcome INC are recommended as 1st line treatment of allergic rhinitis Safety issues were considered van Cauwenberge et al (2000) Consensus statement Advice on treatment of seasonal allergic rhinitis INC are recommended as 1st line treatment of moderate to severe symptoms of SAR No comment on identification of primary data or appraisal of the underlying evidence. Recommendation partially based on Weiner et al Level 5: expert opinion without explicit critical appraisal
INC, intranasal corticosteroids; OH1A, oral H1 receptor antagonists.