Page 631 - Clinical Immunology_ Principles and Practice ( PDFDrive )

CHaPtEr 43 Allergic Reactions to Stinging and Biting Insects 607

intradermal test result remains positive longer than that of sIgE. commonly used expression marker is CD63. The sensitivity and
However, there is currently no reliable test that predicts the risk specificity of BAT seems to be superior to skin tests and venom-
of future SRs in untreated or treated patients. Despite a history specific sIgE. It may also have better predictive value. The test
of typical SRs to stings, a few patients have no detectable sIgE must, however, be performed with fresh blood; it is expensive
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and have negative skin test results. This may be attributed to and not yet well standardized: there are few data on specificity
insufficient sensitivity of the available tests, a long interval between and predictive value in relation to a sting reexposure during or
the SR and testing with spontaneous decrease of sensitization, after venom immunotherapy.
or non–IgE-mediated pathogenesis.
Specificity may cause problems: more than 20% of people Allergen-Specific IgG
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without a history of SR have a positive diagnostic test result. The presence of sIgG and IgG4 primarily reflects exposure to
Although it is difficult to exclude sensitization after a previous the respective venom. sIgG titers increase after a sting, irrespective
sting, this positivity may reflect cross-reactivity (see below). of the presence or absence of an allergic sting reaction. Venom
For skin testing and venom immunotherapy for fire ant (S. immunotherapy induces a rise in sIgG. However, there is no
invicta) stings, only whole-body extracts are currently available. close correlation between the concentration of sIgG or the sIgE/
These extracts have good sensitivity but low specificity. Therefore sIgG ratio and the clinical response to a resting during or after
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they should only be used in patients with a history of systemic venom immunotherapy. Routine assessment of sIgG is therefore
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sting reactions, at least 30 days after the SR. In contrast, venoms not recommended but may be helpful if the responsible insect
of M. pilosula have been shown to have excellent sensitivity and is unidentified.
specificity. 4
Baseline Serum Tryptase
Cross-Reactivity Because elevated baseline serum tryptase levels (>11.4 µg/L) are
Cross-reactivity between venom allergens is strong between species associated with severe, sometimes IgE-negative, systemic sting
within a family, for example, among Vespula, Dolichovespula, reactions and with cutaneous or systemic mastocytosis, this
and Vespa, but only limited between Vespinae and Polistinae or enzyme should be determined in all patients with a history of
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between honeybees and bumblebees. There is some homology SRs. The commercially available fluorescence immunoassay
at the protein level between bee and vespid venoms, with ~50% measures total tryptase. α-Tryptase is secreted continuously and
sequence identity between the hyaluronidases and dipeptidyl- reflects whole-body mast cell load. Elevated values are seen in
peptidases of the two families, but double-positivity with cutaneous and systemic mastocytosis. β-Tryptase is released
diagnostic tests to both venoms is frequently observed. This may during mast cell activation and is a marker of anaphylaxis.
reflect true double-sensitization or cross-reactivity. Cross-reacting
carbohydrate determinants (CCDs) are present in many major Sting Challenge Tests
Hymenoptera venom allergens, such as hyaluronidase, acid Sting challenge with a live insect is not recommended as a
phosphatase, and phospholipase A2, but also in many plant diagnostic tool in untreated patients, but a sting challenge under
proteins (e.g., rapeseed pollen or bromelain). CCDs are certainly well-supervised clinical conditions may be helpful in evaluating
responsible for a significant proportion of the double-positivity the efficacy of venom immunotherapy. 21,29 However, a tolerated
of diagnostic tests to bee and vespid venoms. They may also sting challenge does not definitely exclude a reaction to future
explain why individuals with no history of SRs have positive test stings after immunotherapy, especially if these are repeated. 17
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results. The CCDs are probably of no clinical relevance. The
radioallergosorbent test (RAST)for venoms and CCDs can help PREVENTION AND TREATMENT
distinguish between true double-sensitization and cross-reactivity
but is not always conclusive. Prevention
Assessing IgE antibodies to species-specific nonglycosylated, All patients with a history of SRs should receive detailed instruc-
recombinant major allergens (Api m1 [phospholipase A2] of tion on the avoidance of future stings and measures to take if
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bee venom and Ves v5 [antigen 5] of Vespula venom) reduces stung. Bee stings occur most often when walking barefoot on
the rate of double-positivity very significantly and is helpful in grass, and wasp stings occur when eating outdoors, in orchards
choosing venoms for immunotherapy. 6,25,28 with fallen fruits, and near open waste-bins. The risk of a sting
Some cross-reactivity between allergens of vespid venoms is especially high near beehives or vespid nests. While gardening,
and those of S. invicta has also been documented. 3,6 wearing long trousers, shirts with long sleeves, and gloves are
recommended. Strongly scented perfumes, sun creams, or
Cellular Tests shampoos, as well as brightly colored garments, should be avoided.
If routine tests in patients with a history of SRs are negative,
cellular tests may be helpful to demonstrate sensitization. 2 Treatment of Large Local Reactions
In the basophil histamine release test peripheral blood leukocytes Oral antihistamines and cooling of the sting site (e.g., with ice
are incubated with venom allergens. The reaction with cell-bound cubes) reduces local swelling, pain, and itching. Antiinflam-
IgE antibodies leads to histamine release from basophils. In the matory ointments or topical corticosteroids may diminish the
cellular antigen stimulation test (CAST), leukocytes of patients local inflammatory process. In cases of severe swellings, oral
are prestimulated with interleukin-3 (IL-3) and exposed to venom corticosteroids together with antihistamines over several days
allergens. The released sulfidoleukotrienes are determined by are recommended. 10
using enzyme-linked immunosorbent assay (ELISA).
The basophil activation test (BAT) is based on flow-cytometric Systemic Allergic Reactions
demonstration of an altered membrane phenotype of basophils Sympathomimetics, antihistamines, and corticosteroids are the
stimulated by IL-3 and allergen exposure. At present, the most most effective drugs for symptomatic treatment of SRs. All patients