Diagnostic value of the skin-prick test and RAST assay in insect sting allergy

The results of skin-prick tests to four concentrations of venom (0.1, 1, 10 and 1000 μg/ml) carried out on two occasions were analysed in relation to the history of adverse reactions to stings and to the level of venom-specific IgE antibody in serum, in forty-two subjects allergic to insect stings (sixteen to bee and twenty-six to wasp). Fifty control subjects (some of whom had never been stung by bee or wasp) with no history of adverse reaction to stings were also studied. No subject gave a positive skin-test reaction to 0.1 μg/ml, and small numbers reacted to either 1 or 10 μg/ml. The lowest concentration of venom to which most subjects had a positive skin test was 100 μg/ml. Our data suggest that in wasp-allergic patients a positive skin test to 100 μg/ml is normally significant (reflecting the presence of specific IgE), whereas in bee-allergic patients a skin test reaction to 100 μg/ml is usually non-specific for the following reasons. (i) In the allergic patients when skin tests were repeated, a reaction to 100 μg/ml bee venom often became negative (in six of eight), whereas for wasp venom the reaction became more positive (at 10 or 1 μg/ml) in seven of eight patients. Whilst this might reflect lack of reproducibility, the consistent direction of change for either bee or wasp venom suggests responses to this concentration of these venoms may have different interpretations. (ii) In bee-allergic patients, where positive skin tests to 100 μg/ml wasp venom were found they were repeatable in all patients, and occurred only in patients who had been stung by a wasp. In wasp-allergic patients, skin test reactions to 100 μg/ml bee venom were not reproducible between studies in any patient and often occurred in subjects never stung by a bee. (iii) A better correlation between skin test and RAST occurred for wasp venom when a skin-test reaction to 100 μg/ml was included as a positive (rather than reactions to 1 or 10 μg/ml only). For bee venom the correlation did not improve when skin-test reactions to 100 μg/ml were included. (iv) In the control group, skin-test reactions to 100 μg/ml bee venom were often false positives (seven of eight had never been stung by a bee). Four out of fifty controls reacted to wasp venom 100 μg/ml, but three of these had received a wasp sting. These findings suggest that in routine clinical practice skin tests should be carried out over the range 1–10 μg/ml in bee-allergic subjects but in wasp-allergic patients 100 μg/ml should also be included. Extracts of 0.1 μg/ml need not be used.     

Debilitating beliefs, emotional distress and quality of life in patients given immunotherapy for insect sting allergy

BACKGROUND: Patients who receive immunotherapy for systemic reaction to insect stings are told that once they reach maintenance dose they are almost 100% protected against future systemic reactions. However, we have observed that some patients continued to perceive themselves as highly debilitated by the allergy, and this perception had a significant impact on their quality of life. OBJECTIVE: To validate this clinical observation and to explore possible reasons for such an undesired psychological reaction. METHODS: The study group consisted of 97 patients who regularly attended an allergy outpatient clinic for venom immunotherapy, and who had been under medical surveillance for up to 8 years. They completed a questionnaire measuring debilitating beliefs, preoccupation with the systemic reaction event, emotional distress, perceived restriction by allergy, and perceived quality of life. We also recorded the duration of immunotherapy, physician-graded severity of the systemic reaction and the frequency at which immunotherapy was administered. The reference group consisted of patients who had not reached maintenance dose and were still at risk of recurrent systemic reactions. RESULTS: As many as one-third of the patients held self-imposed debilitating beliefs, were preoccupied with the systemic reaction event, perceived a moderate to severe impairment in their quality of life, and manifested symptoms of emotional distress. These psychological responses did not correlate with the immunotherapy dosage that had been reached. Patients who reached a full maintenance dose were doing no better psychologically than those in the reference group. Moreover, the length of time on immunotherapy did not result in attenuation of the psychological responses. CONCLUSION: This study demonstrates for the first time, the long-lasting psychological impact of a threatening systemic reaction. It suggests a need for intervention aimed at dispelling patients' unfounded and persisting debilitating beliefs.     

Comparison of diagnostic tests for hymenoptera sting allergy

The authors examined correlations among individual Hymenoptera venom skin tests, venom radioallergosorbent tests (RAST), venom-induced leukocyte histamine release (LHR) assays and individual Hymenoptera whole body extract (WBE) skin tests in 37 patients with histories of systemic reactions to Hymenoptera stings. Significant positive correlations were seen between the venom skin test results and results from either the venom RAST or the LHR assay for most venoms. There was a relatively high frequency of positive WBE skin tests in association with other negative tests. The ultimate diagnostic test for stinging insect sensitivity is a deliberate sting challenge; in lieu of such a sting the clinical history and the venom skin test appear to provide the best estimate of clinical Hymenoptera sting sensitivity.     

Specific allergen induced motility of peripheral blood mononuclear cells and polymorphonuclear leukocytes in insect sting allergy.

The motility of peripheral blood mononuclear cells (MNC) and polymorphonuclear (PMN) leukocytes from normal and bee venom allergic subjects was investigated by a modified Boyden micropore filter method. The study comprised MNC locomotion in bee venom and histamine gradients and PMN locomotion in bee venom and fMLP gradients. We demonstrated statistically significant increase in MNC and PMN motility towards bee venom in allergic patients group. This effect disappeared after the preincubation of MNC with anti-human IgE antibodies. We observed no such effect in PMN leukocytes. Increased MNC motility in histamine gradient was observed only in control subjects group. Similarly significant increase in PMN locomotion towards fMLP was found in both allergic and control subjects. The results here demonstrated suggest that a specific allergen might be a chemoattractant for peripheral blood MNC and PMN leukocytes from atopics and could be capable to induce non-infectious inflammatory reactions as a result of its interaction with these sensitive cells.     

Allergic reactions following first insect sting exposure

Over a 10-year period, 750 patients were evaluated because of anaphylaxis following insect stings. Sixty-five patients were identified who had reactions after their first sting exposure. Their clinical features and symptoms of anaphylaxis were the same as the much larger group of patients who had allergic reactions following prior exposure to insect stings. When evaluated following the sting reaction, the majority of these patients had venom-specific IgE detected by skin test or in the serum by the RAST. Fifty-three re-stings occurred in 31 patients. In untreated or whole body extract-treated patients, there were 43 re-stings resulting in 13 reactions. There were no reactions following 10 re-stings in venom-treated patients. In a subgroup of 15 patients with undetectable venom-specific IgE, there were 16 re-stings in eight patients, leading to three systemic reactions. The occurrence of allergic reactions following first sting exposure adds further support to the thesis that some sting reactions are non-IgE-mediated.     

Insect sting allergy with negative venom skin test responses

BACKGROUND: In our 1976 controlled venom immuno rapy trial, 33% of 182 patients with a history of systemic reactions to insect stings were excluded because of negative venom skin test responses. There have been reports of patients with negative skin test responses who have had severe reactions to subsequent stings. OBJECTIVE: Our aim is to increase awareness about the patient with a negative skin test response and insect sting allergy and to determine the frequency and significance of negative skin test responses in patients with a history of systemic reactions to insect stings. METHODS: We prospectively examined the prevalence of negative venom skin test responses in patients with a history of systemic reactions to stings. In patients who gave informed consent, we analyzed the outcome of retesting and sting challenge. RESULTS: Of 307 patients with positive histories screened for our sting challenge study, 208 (68%) had positive venom skin test responses (up to 1 microg/mL concentration), and 99 (32%) had negative venom skin test responses. In 36 (36%) of the 99 patients with negative skin test responses, the venom RAST result was a low positive (1-3 ng/mL), or repeat venom skin test responses were positive; another 7 (7%) patients had high venom-specific IgE antibody levels (4-243 ng/mL). Notably, 56 (57%) of 99 patients with positive histories and negative skin test responses had negative RAST results. In patients with positive skin test responses, sting challenges were performed in 141 of 196 patients, with 30 systemic reactions. Sting challenges were performed on 37 of 43 patients with negative skin test responses and positive venom-specific IgE and in 14 of 56 patients with negative skin test responses and negative RAST results. There were 11 patients with negative skin test responses who had systemic reactions to the challenge sting: 2 had negative RAST results, and 9 had positive RAST results at 1 ng/mL. The frequency of systemic reaction was 21% in patients with positive skin test responses and 22% in patients with negative skin test responses (24% in those with positive RAST results and 14% in those with negative RAST results). CONCLUSIONS: Venom skin test responses can be negative in patients who will subsequently experience another systemic sting reaction. Venom skin test responses are negative in many patients with a history of systemic allergic reactions to insect stings and may be associated with positive serologic test responses for venom-specific IgE antibodies (sometimes strongly positive results). Venom skin test responses should be repeated when negative, along with a serologic IgE antivenom test. Better diagnostic skin test reagents are urgently needed.     

Prognosis of patients reacting with urticaria to insect sting

Insect sting challenge in 14 patients with urticarial reaction to last insect sting resulted in two systemic reactions (95% confidence limits 0-6 patients), a reaction rate of 14%. Skin prick test, basophil histamine release, RAST, and allergen-specific IgG, alone or in conjunction, could not indicate the patients to react systemically after sting challenge. Further, the systemic reactions were uninfluenced by type of insect and time elapsed since last insect sting. It is concluded that the reaction to future insect stings cannot be predicted by the immunological tests presently available.     

Rush venom immunotherapy: a 3-day programme for hymenoptera sting allergy

In a series of 102 patients consulting for allergic reactions following hymenoptera sting, fifty-two of them, who had experienced one or more severe systemic adverse reactions were selected for rush immunotherapy. The method employed made it possible to attain the maintenance dose of 100 μg of venom in 3 days. Patient tolerance was excellent, no serious side-effect was observed; immunotherapy never had to be stopped. Clinical effectiveness seems to be very satisfactory, since no abnormal reaction was reported in seven patients who later were spontaneously stung, and in fourteen patients who received an induced insect sting. The level of IgG antivenom antibodies rose regularly from the first month onwards to remain at a stable level. Because of its safety and effectiveness, it appears that this method should be recommended for immunotherapy in patients who are allergic to hymenoptera stings.     

Position paper The sting challenge test in Hymenoptera venom allergy

Ruëff F, Przybilla B, Müller U, Mosbech H. The sting challenge test in Hymenoptera venom allergy. Position paper of the Subcommittee on Insect Venom Allergy of the European Academy of Allergology and Clinical Immunology. Allergy 1996: 51: 216–225. © Munksgaard 1996.     

Risk factors and indicators of severe systemic insect sting reactions

Hymenoptera venom allergy ranks among the top three causes of anaphylaxis worldwide, and approximately one-quarter of sting-induced reactions are classified as severe. Fatal sting reactions are exceedingly rare, but certain factors may entail a considerably higher risk. Delayed administration of epinephrine and upright posture are situational risk factors which may determine an unfavorable outcome of the acute anaphylactic episode and should be addressed during individual patient education. Systemic mastocytosis and senior age are major, unmodifiable long-term risk factors and thus reinforce the indication for venom immunotherapy. Vespid venom allergy and male sex likewise augment the risk of severe or even fatal reactions. Further studies are required to assess the impact of specific cardiovascular comorbidities. Available data regarding potential effects of beta-blockers and/or ACE inhibitors in coexisting venom allergy are inconclusive and do not justify recommendations to discontinue guideline-directed antihypertensive treatment. The absence of urticaria/angioedema during sting-induced anaphylaxis is indicative of a severe reaction, serum tryptase elevation, and mast cell clonality. Determination of basal serum tryptase levels is an established diagnostic tool for risk assessment in Hymenoptera venom-allergic patients. Measurement of platelet-activating factor acetylhydrolase activity represents a complementary approach but is not available for routine diagnostic use.     

The evaluation of the common diagnostic methods of hypersensitivity for bee and yellow jacket venom by means of an in-hospital insect sting

Between 1979 and 1983 230 patients visited our clinic in connection with allergic reactions after insect stings. One hundred six patients were subjected to a diagnostic provocation test with a live insect; 86 of these patients had a history of systemic reactions and a positive skin test and RAST with insect venom. Thirty-one of these patients, including one patient with a negative RAST and another with a negative skin test, demonstrated a generalized reaction and were subjected to immunotherapy with pure insect venom. Comparison of the diagnostic data from 31 patients with reactions with those of the 57 nonreacting patients from the 86 patients aforementioned reveals that at this time only a provocation test with a live insect can provide the evidence of an allergy to insect venom leading to such a severe generalized reaction that admission to probably lifelong immunotherapy is justified. The measurement of the venom-specific IgG, the ratio of IgG/IgE, and (for bee patients) the serum antibody titer against the bee venom components phospholipase A and hyaluronidase did not improve the diagnosis of a current hypersensitivity against insect venom.     

Respiratory allergy to the indoor ant (Monomorium pharaonis) not related to sting allergy.

BACKGROUND: Many studies are available on systemic reactions to ant sting, but few have described the direct role of ants in respiratory allergy. The nonstinging house ant, Monomorium pharaonis (pharaoh ant), is a highly infesting species in indoor environments. OBJECTIVE: To determine whether the pharaoh ant is an indoor source of aeroallergens. METHODS: Two patients with asthma who lived in homes with ant infestation were enrolled. Pharaoh ants were collected at the patients' homes, and crude extracts were prepared. Skin prick tests with ant extracts were performed. Specific IgE to pharaoh ant was measured by enzyme-linked immunosorbent assay (ELISA), and the allergenic components were determined by using immunoblot analysis. Cross-reactivity among pharaoh ant, imported fire ant, Pachycondyla chinensis ant, and other indoor allergens was evaluated by ELISA inhibition tests. Specific bronchial challenge testing was performed using pharaoh ant extracts. RESULTS: Both patients had positive skin test reactions to pharaoh ant extract and high levels of specific IgE antibodies to pharaoh ant. The ELISA inhibition test results demonstrated significant inhibition by pharaoh ant; however, P. chinensis, cockroach, and house dust mite showed no inhibition of the IgE binding to pharaoh ant. Two important IgE-binding components, 9.4 and 34 kDa, were identified by using immunoblot analysis. Pharaoh ant bronchial challenge test results showed typical early asthmatic reactions in 1 patient and dual asthmatic reactions in the other patient. CONCLUSIONS: Ants can induce IgE-mediated bronchoconstriction regardless of sting in sensitized patients. Ants should be taken into consideration as a cause of respiratory allergy in patients living in homes with visual evidence of infestation.