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Three Part Question

In [a 16 year old] are [topical corticosteroids more effective than oral histamine antagonists] in the [alleviation of symptoms of seasonal allergic rhinitis]?

Clinical Scenario

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.

Search Strategy

PubMed, Secondary sources – Consensus statement European Academy of Allergology and Clinical Immunology.
[allergic rhinitis AND adrenal-cortex-hormones AND meta-analysis] (MeSH-Terms)

Search Outcome

Two articles were found, one original meta-analysis.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Weiner J et al, 1998,	Total of 2267 subjects (mean age 32 years, range 12 to 75 years)	Meta-analysis of 16 RCT Level of evidence 1a (SR with (predominantly) homogeneity of RCT)	Comparison intranasal corticosteroids (INC) vs. oral H1 receptor antagonists (OH1A) on nasal symptoms (itch, nasal blockage, nasal discharge, and sneezing)	INC give greater relief of total nasal symptoms than OH1ACombined standardised mean difference -0.42 (95% CI -0.53 to -0.32)	Analysis based on Cochrane methodology (albeit language bias) Meta-analysis of 11 RCT, OH1A could be beneficial ancillary to INC for treatment of eye symptoms Individual studies suggest cost effectiveness Safety issues were considered
			Comparison INC vs. OH1A on eye symptoms	No significant difference between INC and OH1A in relieving eye symptoms
			Comparison INC vs. OH1A on cost effectiveness	INC are more cost effective than OH1A
			Total outcome	INC are recommended as 1st line treatment of allergic rhinitis
van Cauwenberge P et al, 2000,		Consensus statement Level 5: Expert opinion without explicit critical appraisal	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 J et al.

Comment(s)

The meta-analysis by Weiner J 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 Cauwenberge P 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 J 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 is a concise document dealing with all issues and treatment options related to SAR. However, the author gives 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 above study by Weiner J et al, the result of the primary literature search. With regards to the effectiveness and safety of OH1A and 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®), loratadine (Clarityn®) are not metabolised via the cytochrome P450 system and 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 is protective towards systemic drug concentrations potentially causing hypothalamic pituitary adrenal axis suppression, a serious complication of systemic corticosteroid treatment. No systemic side effects are recognised for fluticasone propionate and budesonide, which 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. A variety of INC preparations is available. Costs vary from £5.85 (budesonide aequos spray, Rhinocort Aqua®) to £11.43 (fluticasone proprionate, Filxonase®) in the UK. Only 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 mcgr OD to be more effective to the compared INC. Budesonide has a good safety profile and is cost effective.

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.

References

1. Weiner JM, Abramson MJ, Puy RM. Intranasal corticosteroids versus oral H1 receptor antagonists in allergic rhinitis: systematic review of randomised controlled trials. BMJ 1998;317:1624-29.
2. van Cauwenberge P, Bachert C, Passalacqua G et al. Consensus statement on the treatment of allergic rhinitis. European Academy of Allergology and Clinical Immunology. Allergy 2000;55(2):116-34.