Stinging insect allergy

Safe, effective immunotherapy is available

MJA 1999; 171: 649-650

The prevalence of anaphylaxis to bee stings in Australia is high at 2.7%,² with an attributed mortality of about two persons each year, although these figures may be low due to unexplained deaths.³ A recent postal survey identified a 2.4% prevalence of systemic reactions after jumper ant or bull ant stings in rural southeastern Victoria,⁴ only slightly lower than the reported bee allergy prevalence. Atopic individuals are at no greater risk than non-atopic individuals of developing IgE-mediated anaphylaxis in response to insect bites or drugs. People with asthma have more severe anaphylactic reactions than non-asthmatics and account for a disproportionate number of those having severe anaphylactic reactions to Hymenoptera stings. Anaphylaxis is more common in under-20-year-olds, but deaths are more common in older-age groups, sometimes due to underlying cardiac or respiratory disease⁵ or the effects of medications such as -blockers.⁶

A diagnosis of stinging insect allergy is based on clinical history, with confirmation by detection of insect venom- specific IgE by skinprick tests with diluted specific venom extract or by serological testing. Up to 25% of normal individuals have transient, detectable specific IgE after an insect sting,⁷ so testing is usually performed four or more weeks after a sting. This time lag also allows repletion of mast cells, to prevent false negative skin tests. Cross-reactivity between insect families is minimal, but cross-reactivity between the venoms of Vespula species (wasps and hornets) is quite extensive.⁸

Sting reactions are classified as normal, unusual, anaphylactic, toxic or large local⁵ (see Table). Therapy varies according to the particular reaction⁹ and, contrary to popular belief, reactions seldom escalate with subsequent stings. Systemic life-threatening reactions accompanied by hypotension, angioedema or respiratory symptoms must be treated promptly with adrenaline.⁹ Corticosteroids and antihistamines are second-line treatments aimed at minimising the risk of rebound (relapsing) anaphylaxis, which occurs in about 20% of patients,¹⁰ and in our experience they are clinically effective. However, although these drugs unequivocally suppress experimentally induced biphasic reactions (ie, reactions in which there is a second single episode of anaphylaxis), they cannot be relied upon to suppress recurrent or prolonged anaphylaxis, and there have been no controlled trials of their impact on the second phase of clinical anaphylaxis.¹⁰ Deaths accompanying anaphylaxis from rebound responses have been reported up to 24 hours after exposure to the stimulus, with biphasic responses usually reaching a peak in 4 to 8 hours.

Data suggest that delayed-onset anaphylaxis (ie, where the reaction begins more than 30 minutes after the stimulus) is more frequently complicated by recurrent or refractory manifestations than anaphylaxis of immediate onset.¹⁰ As biphasic and protracted anaphylaxis is not uncommon despite glucocorticoid therapy, patients with anaphylaxis characterised by cardiovascular or respiratory compromise (hypotension, laryngeal oedema and/or bronchospasm) or associated significant comorbidity are usually admitted to hospital for 24 hours' observation after the sting.⁹

Patients with known life-threatening allergy to stinging insects should be prescribed an anaphylaxis emergency kit,¹¹ educated in its use, and taught how to minimise risk of subsequent insect stings.

Patients with life-threatening sting reactions, confirmed venom-specific IgE and no contraindication (such as pregnancy) should be offered specific allergen immunotherapy. The clinical protection rate on subsequent sting using 100-µg maintenance doses is 98% for wasps and 80% for bees.^8,12 The reason for the lower protection rate against bees is unknown. Various regimens are available, but, in Australia, subcutaneous injection in the upper arm via a "rush" schedule (with incremental dose increases ["updosing"] over 4 to 5 days) is favoured. With a systemic adverse reaction rate of 20% to 40% for bee venom desensitisation and 15% for wasp venom,⁸ it is recommended that patients be updosed in hospital in specialist allergy units and continued on maintenance injections as outpatients with the assistance of their family practitioner. Maintenance doses are usually given monthly for 3 to 5 years.⁸ Immunotherapy should only be administered in a clinic with staff and facilities capable of managing anaphylaxis,¹³ and the patient should be observed for 45 minutes after each injection.

It is of major concern that, while allergic diseases are so prevalent in Australia, there is an acute shortage of specialist allergists and clinical immunologists.¹⁴ Rural areas, where bees and wasps are most common, are severely underserviced, with the result that many patients who would benefit from venom immunotherapy are denied this option.

Despite the efficacy of conventional immunotherapy, many patients can not reach maintenance doses without systemic reactions. Research initiatives are exploring safer and more effective therapies, following identification of the pivotal role of the T cell in control of the immune response to allergens. Evaluation of successful immunotherapy consistently shows altered cytokine production by allergen-stimulated T cells.^15,16 Alternative strategies for desensitisation using hypoallergenic mutants retaining T-cell-dominant determinants (epitopes) or peptide vaccines that stimulate T cells yet fail to bind IgE (minimising the risk of anaphylaxis) are under development, and early results are promising.¹⁷ Such vaccines may ultimately prove safer and avoid the need for expensive hospital admission or specialist centres for updosing.

We do not yet have all the answers, but if therapies currently available are used in a timely and appropriate manner no patient should die of a known insect sting allergy.

Robyn E O'Hehir
Director of Allergy, Asthma and Clinical Immunology

Jo A Douglass
Head, Asthma and Allergy Unit
Department of Allergy, Asthma and Clinical Immunology
Alfred Hospital, and Monash University, Melbourne, VIC

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