Clinical review

Venom allergy

Pamela W Ewan. 

Stings from bees and wasps, the most common stinging insects in Britain, can cause severe allergic reactions, including anaphylaxis. Coroners' data suggest that an average of four deaths from bee or wasp stings occur each year in the United Kingdom, but this is almost certainly an underestimate because venom anaphylaxis is not always recognised as the cause of death.

View larger version (129K): [in this window] [in a new window]   Honey bee (Apis mellifera): 1.5 cm long, fairly hairy and brown with abdominal bands

	Hymenoptera insects

Classification
The hymenoptera are subdivided into families, including the Apidae (honey bees and bumble bees) and the Vespidae (wasps, hornets, and paper wasps). In Britain most reactions are caused by stings from wasps (the Vespula species) rather than from bees. Reactions to bee stings are almost always associated with the honey bee.

Venoms
Bee and wasp venoms are different, each containing distinct major allergens, which are well defined. Phospholipase A2 and mellitin occur only in bee venom, and antigen 5 only in wasp venom, but both venoms contain hyaluronidases. Patients allergic to wasp venom are rarely allergic to bee venom.

View larger version (86K): [in this window] [in a new window]   Wasp, also known as yellow jacket (Vespula spp): 1.5 cm long; yellow and black striped abdomen; typical waist; and little hair

	Sensitisation

Most people, unless they have a specific occupational risk, are rarely stung by wasps, perhaps once every 10-15 years. Sensitisation to wasp venom requires only a few stings, and can occur after a single sting.

In contrast, allergy to bee venom occurs mainly in people who have been stung frequently by bees. Thus almost all patients who are allergic to bees are beekeepers or their families, or sometimes their neighbours.

	Clinical features

The normal effect of a bee or wasp sting is to cause intense local pain, some immediate erythema, and often a small area (up to 1 cm diameter) of oedema. Allergic reactions can be either local or generalised.

View larger version (74K): [in this window] [in a new window]   Patient with angio-oedema of the left forearm: local allergic reaction to a bee sting

Local reactions
Local reactions involve oedema at the site of the sting. This comes on over several hours and varies in size, but it can affect a hand or even an entire limb. In a dependent area this can lead to blistering and sometimes secondary infection. Such oedema is not dangerous unless it affects the airway.

Generalised reactions
Generalised (or systemic) reactions vary greatly in severity. Early features are erythema and pruritus, followed by urticaria and facial or generalised angio-oedema. Patients with more severe generalised reactions often feel extremely ill, as if they are going to die ("a sense of impending doom"). Dyspnoea often occurs and can be due either to laryngeal oedema or to asthma. In severe reactions hypotension occurs, causing lightheadedness, giddiness, fainting, or loss of consciousness. Other less common features are abdominal pain, incontinence, central chest pain, or visual disturbances.

View larger version (84K): [in this window] [in a new window]   Patient with angio-oedema and blistering of the ankle: local allergic reaction to a bee sting

	Diagnosis

Venom allergy is diagnosed from the history of the allergic reaction, backed up by tests for venom-specific IgE antibodies. It is important to check the basis of the patient's assertion about the type of insect responsible for the sting. Many patients say the sting is from a bee when it is in fact a wasp sting. The vast majority of patients (except beekeepers etc) will be wasp allergic. Accurate diagnosis is important as it has implications for management.

The history should be confirmed by demonstrating, by skin test or blood test, specific IgE; this is essential if desensitisation is considered as a treatment. Skin testseither skin prick tests or intradermal tests with bee and wasp venom and the appropriate positive and negative controlsare more accurate but should be done by allergists as skin tests for venom are more difficult to interpret than skin tests for inhaled allergens. Alternatively, serum bee-specific and wasp-specific IgE can be measured by a radioallergosorbent test (RAST), CAP-RAST, or other assays.

It is important to be aware that since the introduction of the more sensitive CAP-RAST, there have been more (up to 30%) false positive resultsthat is, patients with serum IgE to both bee and wasp venom (double positives) when they are allergic to only one venom. However, double positives can occur even with the radioallergosorbent test (in about 6% of cases). The term allergy refers to a state of clinical reactivity and is not the same as sensitisation (presence of specific IgE antibodies), which can occur without clinical reactivity. Patients are rarely allergic to both bee and wasp venom. This means that if the history is not checked, and venom IgE to only a single venom is measured, the wrong diagnosis can result. Studies in the general population show that some subjects who have a history of stings but no reactions have venom-specific IgE.

	Acute management

Local reactions
Acute management should be with oral antihistamines, which may be required for several days. A quick acting drug should be used (for example, one of the newer, non-sedative antihistamines). Very large swellings may require intramuscular antihistamines and steroids. Prevention is more effective, and the patient should take a large dose of an antihistamine (double the standard dose) immediately after being stung, before the localised reaction is established, to abrogate incipient angio-oedema.

Generalised allergic reactions
Management depends on the severity and the particular features of the reaction, as for any systemic allergic reaction. Cutaneous reactions require oral antihistamines or injected chlorpheniramine. Moderate reactions often require intramuscular chlorpheniramine and hydrocortisone, and treatment for asthmafor example, inhaled 2 agonistsmay be necessary. Severe reactions, including those with marked respiratory difficulty or hypotension, should be treated with adrenaline (intramuscular) followed by chlorpheniramine and hydrocortisone. Other measures, including intravenous fluids, may also be required, but, provided that treatment is started soon after the onset of the reaction, the drugs above are usually all that are needed.

	Further management

After a generalised reaction, patients need further advice and ideally should be referred to an allergy clinic specialising in venom allergy. As there are not many of these in Britain, general practitioners should be aware that there are two options for further management: patients can either be desensitised or be given the appropriate drugs to treat a reaction themselves. To choose the appropriate management, it helps to classify general reactions by severity.

Who should be desensitised?

Desensitisation (immunotherapy)
Among patients with generalised reactions, those with severe reactions usually require desensitisation, those with mild reactions do not, and those with moderate reactions may or may not. Other factorssuch as the risk of a future sting, the interval from the last sting, other medical problems, the ability of the patient to treat himself or herself, and access to medical helpmay influence the decision.

Before desensitisation is given the nature of the sting must be accurately diagnosed and venom-specific IgE demonstrated.

The indications in Britain for desensitisation are conservative (in some countries any patient with a generalised reaction, no matter how trivial, would be desensitised). This is because, although immunotherapy for hymenoptera venom is highly effective, the high incidence of spontaneous improvement, as well as the side effects of treatment, has to be taken into account. Venom immunotherapy carries a risk (of about 10%) of inducing systemic allergic reactions and can produce anaphylaxis. It should therefore be performed only in specialist centres treating an adequate number of patients each year.

Self medication for future reactions
Those not being desensitised should be given oral antihistamines to take if they are stung again. They should take the antihistamines as soon as they are stung to modify or abort reactions. In a patient with a mild generalised reaction this is normally sufficient. Those with moderate or severe reactions should also be given syringes preloaded with adrenaline. They administer a dose of 0.3 mg (0.3 ml of 1/1000 strength) intramuscularly for adults and children from age 5 years. A syringe containing a smaller dose (0.15 mg) suitable for younger children is available, but children with venom allergy rarely need this. If other drugs are required these should be given by doctors or paramedics. All patients should seek the assistance of an adult as soon as they are stung, in case medical help is required.

What does immunotherapy involve?
Various regimens are available. Conventional immunotherapy, the standard one, entails an initial course of weekly injections over three months, starting with low doses of venom and reaching the highest dose of 100 µg (equivalent to two stings). Thereafter, maintenance injections of the same dose are given at monthly or longer intervals for three years. The treatment can be given only in specialist centres, where resuscitation facilities exist, to conform with the guidelines of the Committee on the Safety of Medicines (1986 and 1994), because of the risk of side effects. Drugs to treat anaphylaxis must be immediately available, and patients have to be kept under observation for one hour after each injection.

Mechanism of immunotherapy
T cells secrete cytokines which orchestrate the immune response. T helper (Th) cells are subdivided into Th1 and Th2 subsets, on the basis of their cytokine secreting profile in response to stimulation with antigen or allergen.

	Acknowledgments

The table on classification of systemic reactions is adapted from Allergy and Allergic Diseases, Kay AB, ed (Insect-sting allergy (Ewan PW)): Blackwell Science, 1997.    

Pamela W Ewan is a Medical Research Council clinical scientist and honorary consultant in allergy and clinical immunology at Addenbrooke's Hospital, Cambridge.    

The ABC of allergies is edited by Stephen Durham, honorary consultant physician in respiratory medicine at the Royal Brompton Hospital, London. It will be published as a book later in the year.