Portal de Periódicos da CAPES

Current practice of venom immunotherapy in the UK

2008; Wiley; Volume: 38; Issue: 10 Linguagem: Inglês

10.1111/j.1365-2222.2008.03077.x

1365-2222

Aidan A. Long, Carlos A. Camargo,

Contact Dermatitis and Allergies

Warm weather activities such as outdoor eating and drinking, outdoor sports, walking barefoot, cutting hedges or flowers, picking fruit and removing nests from attics or windows increase the risk of an insect sting. While the great majority of such stings result in minor local reactions and resolve without specific treatment, life-threatening allergic reactions occur in approximately 0.4–0.8% of children and 3% of adults, over the course of a lifetime [1, 2]. Indeed, anaphylactic reactions to insect stings account for approximately 50 deaths per year in the US, and 5 of the 20 reported annual fatal anaphylactic reactions in the UK [2, 3]. Although a history of atopy is a risk factor for the development of anaphylaxis, most patients have no warning and many have tolerated past stings with little or no reaction. While insect sting related anaphylactic reactions occur at any age, they are more common among individuals younger than 20 years and among males (2 : 1 ratio), likely due to higher rates of exposure in these groups [4]. Up to 75% of patients with a history of insect sting related anaphylaxis will develop systemic symptoms again when re-stung [5, 6]. In patients with a history of a systemic allergic reaction to stinging insects, in whom specific IgE to venom can be documented, the benefits of venom immunotherapy (VIT) are well documented. Venom immunotherapy reduces the risk of systemic reactions from stinging insects of the vespid family with an efficacy of 95–97%, and in those who do experience systemic reactions, these are typically significantly milder than those experienced before VIT [4, 7–10]. The data for bee sting induced reactions suggest rates of protection in the order of 80–85% [11, 5]. The protection against future sting-induced anaphylaxis, conferred by VIT over 3–5 years, is usually long lasting [12]. These epidemiological and clinical observations emphasize the importance of insect sting related allergic reactions and the benefits of VIT. Diwakar et al. [13], in this issue of the Clinical and Experimental Allergy examine the practice of VIT in the UK. Their survey results provide grounds for both optimism and concern. Before discussing the specific results of their audit, it is instructive to summarize key information about VIT for the diverse readership of the journal. Two key steps in caring for a patient with a history of systemic allergic reaction to stinging insects are (1) confirmatory diagnostic testing (to look for the presence of venom-specific IgE), and (2) consideration of VIT, including selection of allergens (venoms), dosage and duration of immunotherapy. Commercially available, purified venoms are used for injection therapy. There is a relatively large body of information relating to these two steps and it has been critically reviewed by experts and formulated into practice guidelines, both in USA [14] and in Europe [6, 15]. The US and European recommendations concur on many points. For example, both documents recommend the following. VIT is indicated in patients with a history of a sting-induced severe systemic allergic reaction with documented venom sensitization either by skin testing or measurement of serum-specific IgE. VIT is not indicated, except in extenuating circumstances, for patients who have only experienced large local reactions. VIT is not recommended where the results of testing to document sensitization are negative. Testing for venom-specific IgE with all commercially available bee and vespid venom vaccines is necessary as the insect that caused the sting reaction cannot usually be reliably identified. Skin testing by the intradermal/intracutaneous route is recommended as the most reliable method to identify venom-specific IgE. Further, subsequent evaluation by in vitro testing is indicated in the patient with a history of a severe systemic reaction and negative skin test results. Selection of venom(s) for VIT should be based on the results of appropriate testing for venom-specific IgE. Dosage of each venom, at each maintenance injection, should be 100 mcg. VIT should be continued for at least 3–5 years, and possibly longer in patients who have a history of severe anaphylaxis with shock or loss of consciousness. With that background, we now return to the results of the national audit by Diwakar et al. [13]. While the number of survey respondents who actually carry out VIT was quite small (n=45 as per Diwakar et al., 2007), the results are provocative. With respect to diagnostic testing, 55% use in vitro testing as the first line of diagnostic testing for the presence of venom-specific IgE and only 50% use intradermal testing for documenting venom-specific IgE. Furthermore, when intradermal testing is undertaken, 40% use concentrations 10 times higher than that recommended by the US guidelines, a concentration at which false positives are likely [14]. With respect to patient selection for VIT, most respondents appear to follow international guidelines but a significant number do not. For example, 8% report that they would initiate VIT despite undetectable venom-specific IgE. Strikingly, 11% report that they would initiate VIT despite undetectable venom-specific IgE but in the presence of an elevated tryptase, a finding that suggests an alternative diagnosis. During VIT, 11% aim for concentrations of venom higher than recommended by guidelines and 22% elect not to treat with both but only with either bee or vespid venoms when both are positive by specific testing. The results of this numerically small survey suggest important variances in VIT practice from that recommended in the US and European guidelines [6, 14, 15]. These differences are of particular concern given the prevalence and the reported outcomes of stinging insect allergy in the UK [3]. The reasons for such variances are not elucidated by this survey but might relate to the small sample size, the 62% response rate or perhaps the uniqueness of practice of allergy/immunology in the UK. Small sample sizes are known to yield large 95% confidence intervals. For example, the 11% of respondents who would initiate VIT despite undetectable venom-specific IgE (but presence of elevated tryptase) actually has a 95% confidence interval of 4–24%. The <80% response rate contributes to this problem but, more importantly, it introduces the possibility of systematic error (bias). Without a comparison of data from respondents and non-respondents, we cannot know if the non-respondents differed in a systematic way from those who responded. For example, it is possible that those who are most familiar with the international VIT standards were more likely to respond and that the survey actually presents a best-case scenario of VIT practice. This possibility requires further study. The authors of the survey also point to some unique aspects of allergy/immunology care in the UK that might differentiate it from other countries. For example, the authors identified only 86 clinicians practising immunotherapy from the British Society of Allergy and Immunology website, and even then, 15% of the respondents indicated that they did not carry out VIT. Thus, the available number of practitioners to treat patients with VIT appears very, very small relative to the population of the UK and the known prevalence of this disease [2]. Additionally, mention is made of the entomological differences and differences in health systems between the UK and other countries. There are very few UK specialists trained exclusively in allergy; clinical care in the discipline of allergy/immunology is sometimes provided by physicians from other fields including dermatology, respiratory medicine and paediatrics. Given the apparent discrepancies between self-reported practice and evidence-based recommendations, at least with respect to management of patients with insect sting allergy, there appear to be significant educational opportunities in the practice of allergy/immunology in the UK.