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Histamine Release technic consists in calculating histamine liberated by blood cells in touch with an allergen. To this day, this method is only used in Hymenoptera venom allergy diagnosis. The principle of this study is to measure histamine released by activated basophils in surnageons of Basophil Activation Test (BAT) for different allergens: Hymenoptera venoms: Bee, White Faced Hornet, Vespula Wasp. Drugs: Cefaperos, Clamoxyl, Alfatil, Rapifen, Diprivan, Nesdonal, Mivacron. A threshold of positivity (amplification factor in comparison with the control) is determined for these two classes of allergens: 45 for Hymenoptera venoms and 9 for drugs. These results, compared to the other diagnosis technics (Histamine Release, Basophil Activation Test, Prick Tests) discloses very high correlation rates in each case. This method seems to be a reliable method for Hymenoptera venom allergy diagnosis and for drugs allergy diagnosis too. However, this study is based on a few number of patients, so a significant statistic conclusion can't be expressed but it opens an interesting way of research.

Allergy to Hymenoptera venom (VH) effects more and more patients in France. It is manifest in two main forms, which are Loco-regional (RLR) and Systemic reactions (SR). This allergy is detectable amongst others by the techniques of histamine release (HR) and release of leucotrienes C4 (LTC4). The aim of this work has been to fix a threshold that gives differentiation of RLR ad RS by the two techniques. We found in a positive population a threshold histamine release (HR) value of 25% and a concentration of LTC4 of 600 ng/ml. These are the thresholds above which a patient would be at around 70% risk of RS. This study has a predictive value for patients who are suspected of allergy of VH or who have already had clinical reactions and risk sensitization.

The basophil activation test (TAB) clearly shows evidence to Hymenoptera venoms. Comparison of the TAB value with the clinical history allows fixation of a threshold that will anticipate the type of clinical reaction by the TAB value. For the technique of TAB 3 dilutions are used. The basophil activation values produce a threshold for each dilution. For the first dilution the threshold is 50% activation: below this threshold, 70% of patients would have a local or systemic reaction and above this threshold, 70% of patients would have a systemic allergic reaction.

To diagnose insect venom allergy a good patient history is important. Allergological tests (skin test, specific IgE titre) confirm the diagnosis. Patients are advised on preventive measures (e.g. with respect to clothing and use of perfume). They are also instructed on medical treatment (antihistaminics, epinephrine) in case they are stung again. In patients having had a serious systemic reaction immunotherapy should be considered. Immunotherapy leads to complete protection in more than 98% of patients with wasp (yellow jacket) venom allergy and in 75-80% of patients with bee venom allergy. Serious adverse reactions to immunotherapy are rare. Immunotherapy lasts at least 3 to 5 years. After cessation of immunotherapy the frequency of systemic reactions to the sting of a wasp or bee is in the range of 5-15%. There are insufficient data on the long-term effect of immunotherapy.

Background: Changeover from Phadebas RAST to Pharmacia AutoCAP increased double-positivity to both honey-bee and common wasp (vespula) venom in our patients., Objective: We examined the frequency of IgE double-positivity, its clinical relevance and utility in investigating potentially allergic patients., Methods: One hundred and eighty-two patients with hymenoptera allergy were tested using RAST (n = 51) and AutoCAP (n = 131) assays over 4 years. Patients had a history of reactions to vespulae (22), honey-bee (10) and unidentified hymenoptera (vespinae) (7)., Results: After changing from RAST to AutoCAP double-positivity increased from 10 (5/ 51) to 30% (39/131) (P < 0.01). RAST and CAP assays gave similar median class results (vespula = 3, honey-bee = 2). Thirty-six CAP patients had systemic reactions of Mueller grade II and above. In vespula-allergic double-positive subjects, high CAP classes (> or = class 3) to honey-bee were common (30%). In 25% the CAP classes were equal. In honey-bee-allergic subjects, all vespula venom CAP IgE was low titre (class 1 or 2) and 20% were equal for both venoms. In 43% of vespinae-allergic patients the CAP class was equal to both (class 2 and 3). In contrast, intradermal skin test double-positivity was uncommon. Double-negative skin test results were common in the CAP double-positive population (22% of honey-bee-allergic, 13% of vespula-allergic and 43% of vespinae-allergic patients). Vespula allergic patients have higher bee-venom IgE than vice versa. Twenty-seven per cent of CAP double-positive patients (representing 8% of all venom allergic patients tested over this period) had equal class IgE to both venoms which was not helpful in diagnosis. Combination of skin testing and CAP is unhelpful in only 5/37 (14%) of patients with double-positive serology., Conclusion: If used in isolation CAP may be misleading, especially if only one venom is tested. Identification of the causative venom must utilize both clinical history and skin testing in these double-positive patients, and challenge testing if indicated.

Background: Epidemiologic studies of Hymenoptera venom allergy in adults show a prevalence of positive venom skin test results, RASTs of 15% to 25%, or both, but most such individuals have had no systemic reactions to stings. The clinical significance and natural history of this apparently common sensitivity is uncertain., Objective: We sought to determine the natural history of venom sensitization by observing the rate of decrease or increase in sensitivity in normal adults over 5 to 10 years. The clinical significance of these findings is related to the frequency of systemic reactions to stings during the period of observation., Methods: Serial observations were planned in 520 volunteers and randomly selected subjects. Two follow-up visits were attempted, once after 2 to 3 years and again after 5 to 9 years, to perform repeat venom skin tests and RASTs and to review any history of interim stings and their outcomes., Results: Follow-up visits were conducted with 398 subjects (375 early visits and 205 late visits). Overall, in the 398 subjects with one or more visits after a mean of 4 years, skin test responses changed from positive to negative in 44 of 98 (45%) and from negative to positive in 27 of 309 (8.7%) of the subjects. Skin test responses changed from positive to negative in 29 of 87 (33%) subjects after 2.5 years and in 43 of 54 (80%) after 6.8 years. Even when the skin test response became negative, venom-specific IgE remained positive in 11 of 29 (38%) subjects after 2.5 years and in 13 of 43 (30%) after 6.8 years. The rate of loss of sensitivity was 12% per year, similar to retrospective estimates. Skin test sensitivity to venoms disappears more rapidly in these subjects without symptoms (half-life, 4 years) than in patients receiving venom immunotherapy (half-life, 7 years). Skin test responses changed from negative to positive in 23 of 288 (8%) subjects after 2.5 years and in 9 of 151 (6%) after 6.8 years. Insect stings caused no reaction in 120 subjects with a negative skin test response, but 17% (11 of 65) of subjects with a positive skin test response (but with a negative history) had systemic reactions when stung. There was no difference between the early and late visits in the frequency of systemic reactions reported. The risk may be higher than 17% for the specific individuals (67% after 2.5 years and 20% after 6.8 years) whose positive skin test responses persist for years. This risk is lower than that of patients with a positive history (50%) but higher than that of "normal" adults or venom-treated patients (<2%). It is still not clear whether any subset of adults with a positive skin test response but a negative history can be identified, in whom the risk of systemic sting reaction would justify venom immunotherapy even before any reaction occurs., Conclusion: Asymptomatic venom sensitization in adults is common but transient, disappearing at the rate of 12% per year. However, the risk of a systemic reaction to a subsequent sting is significant in adults without symptoms but with positive venom skin test responses (17%) and may be higher when skin test sensitivity does persist for years.

In this study, we performed 150 desensitizations in 139 Hymenoptera venom allergic patients (109 Yellow jacket allergic patients, 19 Honey bee allergic patients and 11 patients sensitized to both insects, who received a dual desensitization). We used a rush protocol, allowing injection of a total cumulated dose of 125,1 (Honey bee) to 175,1 (Yellow jacket) microgram of venom in 30 hours. Patients were hospitalized, with all emergency precautions for treating systemic reactions. The protocol was well tolerated in 147/150 cases; 3 patients had a benign systemic reaction. Patients received monthly maintenance doses of 100 micrograms venom. 39 patients experienced a field sting during immunotherapy; 2 of them (5%) had a benign systemic reaction. Thus, our rush desensitization protocol seems to be safe and effective.

Background: Beekeeping has progressed recently to where bee sting exposure is an important public health problem in Turkey., Objective: To investigate the status of bee and wasp sting allergy in a region of Turkey., Methods: We conducted a questionnaire-based study of 786 subjects (cellulose paper factory personnel and family members older than 16 years of age) in Cay town of Afyon. Skin prick test with common aeroallergens and measurements of total IgE and specific IgE for bee and wasp venom were performed in 212 randomly selected subjects., Results: Cumulative lifetime sting rate was 94.5% (geometric mean: 6.1 times), and last year bee sting rate was 20.4% (geometric mean: 1.6 times). Subjects who had beehives had higher risk of bee sting (P < .05) in the last year, whereas there was no significant difference among the groups for the cumulative lifetime sting exposure. Severe and mild systemic reactions were noted in 2.2% and 5.3%, respectively. Emergency room visits were reported in 9.3%, and familial Hymenoptera allergy in 10.2%. Fatal potential of bee sting was known by 81%. There was no mortality related with Hymenoptera allergy in records of the last 5 years. In 24 subjects with multiple sting exposures, allergic reactions changed severity in the latter exposures, which became less severe in five and more severe in 19 subjects. Atopy rate detected by prick testing was 20.3%. Specific IgE levels were class 1 in 22, class 2 in 11, and class 3 in 2 subjects for bee; and class 1 in 24 and class 2 in 2 subjects for wasp. Nobody had received immunotherapy for venom allergy. None of the factors including atopy, sex, occupation, smoking and family history of bee sting was significantly related with severity of the systemic reaction (P > .05)., Conclusions: Bee and wasp stings are prevalent in Turkey. Severe systemic reactions complicating the sting are frequent (2.2%). Public awareness of potential fatality and treatment of the allergic reaction is not adequate.

We studied 97 consecutive patients who had received Hymenoptera venom rush immunotherapy in our department. There were 53 males and 44 females, whose mean age was 46 years (8-74 years). Most study patients had experienced severe anaphylaxis induced by a Hymenoptera sting: the reaction was Müller stage IV in 48 patients. Skin tests were positive for Vespula venom in 85 cases, Polistes venom in 23, and bee venom in 23. Radioallergosorbent test values exceeded 0.70 kIU/l in 60 cases. Immunotherapy was performed with Vespula venom alone in 73 cases, bee venom alone in five cases, and both Vespula and bee venom in 19 cases. A cutaneous reaction was seen at the injection site in most patients. Four patients also had skin manifestations in areas remote from the injection site. Blood pressure elevation was seen in 11 patients, moderate hypotension in two, rhinitis in one, asthenia or headache in seven, visual disorders and vertigo in two, and transient dyspnea in two. Our protocol has proved very safe, epinephrine never being required in the 97 reported cases.

Background: A majority of subjects allergic to bee venom are beekeepers, their relatives, or neighbors. Predetermining systemic reactivity to honeybee stings and risk assessment through laboratory tests have been unsatisfactory., Objective: To estimate the prevalence and type of sting reactions, and especially to evaluate potential risk factors of systemic reactions in beekeepers., Methods: A questionnaire concerning sting reactions and potential risk factors was mailed to all members of the regional beekeepers' association; 191 beekeepers were included in the study., Results: Systemic bee sting reactions were present in 50 (26%) and large local reactions in 73 (38%) of the beekeepers. Similar reactions following wasp stings were present in 2% and 13%, respectively. Twenty-four (48%) of the systemic reactors and 39 (28%) of the remaining subjects had a history of atopic symptoms (allergic rhinitis, allergic bronchial asthma, or atopic dermatitis). While working at hives, nasal and eye symptoms were present in 54% of the systemic reactors and in 23% of the remaining subjects. Systemic reactors were younger and had been beekeepers for a shorter period than nonreactive subjects. Multiple logistic regression analysis showed that the risk of systemic sting reaction increased fourfold when nasal or eye symptoms were present while working at hives and twofold when the years in beekeeping were less than 15., Conclusions: The occurrence of systemic and large local reactions after bee stings is high among beekeepers. A history of atopy is associated with systemic reactions. Both the presence of nasal or eye symptoms while working at hives and a history of beekeeping less than 15 years significantly increase the risk of systemic reactions.

Background: Recognition of antigen bound to the major histocompatibility complex by the T cell receptor is insufficient to lead to T cell proliferation and effector function, which require co-stimulatory signals, such as those resulting from the interaction of CD28 expressed on T lymphocytes and CD80/CD86 expressed on APCs. Lack of interaction between these accessory molecules during antigen stimulation leads to a state of antigen-specific lymphocyte unresponsiveness. Previous studies have shown that rush venom immunotherapy decreases venom-specific T cell proliferation very early after the initiation of the rush., Objective: In order to see whether this hyporeactivity was associated with a down regulation of accessory molecules, we studied CD28 surface expression on T lymphocytes from 10 non-atopic controls and from 10 non-atopic patients undergoing rush venom immunotherapy., Methods: Peripheral blood samples were collected before the rush (day 0), at the end of the rush (day 1), at day 15 and at day 45. CD28 expression was analysed using flow cytometry with double labelling of the CD4+ and CD8+ lymphocyte subpopulations., Results: At baseline CD28 was expressed at a higher level on T lymphocytes from allergic patients than from control subjects (P < 0.04) and in particular on the CD8 subset (P < 0.01), reflecting a decrease in the suppressive CD8+CD28- subpopulation. No changes were found in the percentages of total CD28+ T cells, CD4+CD28+ or CD8+CD28+ cells at the different time points after the initiation of of immunotherapy., Conclusion: These results suggest that the CD28 pathway is probably involved in the development of allergic reactions, but at least at the phenotypic level, CD28 expression remained unchanged after rush venom immunotherapy.

Allergy to hymenoptera venoms may produce anaphylactic reactions that are severe in 0.8 - 5% of the adult population, according to different epidemiological studies. The risk of a severe reaction in allergic patients who have not been desensitized is 50%. This risk falls to 5 - 10% for allergy to wasp and to 10 - 20% for allergy to bee (1, 2, 3, 4). Because of this serious and vital risk, there is a consensus to prescribe an emergency kit that contains auto-injectable adrenaline (5). An enquiry was made of the allergists of ANAFORCAL and their patients to find the actual practice in comparison with this consensus... 80 physicians and 181 patients replied. It seems that adrenalin is almost always prescribed, together with other products (antihistamines and corticosteroids the most frequent). On the other hand, the following of prescriptions by the patient is not always perfect. It is important therefore to check that the kit is regularly carried, that it is still valid and to be sure that the patient always knows how to manage the product.

Background: Venom immunotherapy is a generally accepted treatment for serious allergy to bee and yellow jacket venom. However, it is not precisely known to whom venom immunotherapy should be offered., Objective: The purpose of this study was to determine whether an in-hospital insect sting challenge (IHC) can be used as a criterion for application or omission of venom immunotherapy., Methods: An IHC was carried out in a group of 479 patients (136 sensitized to bee venom and 343 sensitized to yellow jacket venom). The patients with a negative IHC response were interviewed about their experience with subsequent stings under natural circumstances., Results: A total of 76 of 136 bee-sensitized patients (56%) and 284 of 343 yellow jacket-sensitized patients (83%) had a negative IHC response. All of the patients who had a systemic reaction after the IHC were advised to receive venom immunotherapy. The success rate of this therapy was 96.4% for patients allergic to bee venom (54 of 56) and 91.4% for patients allergic to yellow jacket venom (53 of 58). Of a total of 76 bee-sensitized patients with negative IHC responses, 41 were subsequently stung in the field; six patients had a mild (Mueller grade I) systemic reaction (14.6%). Of a total of 284 yellow jacket-sensitized with negative IHC responses, 127 were subsequently stung in the field; nine patients had a mild (Mueller grades I and II) systemic reaction (7.1%), and four patients had a severe (Mueller grades III and IV) systemic reaction (3.1%). Without an IHC as a selection criterion for venom immunotherapy, the percentage of patients unnecessarily treated was calculated to be 48% for bee venom-sensitized patients and 74% for yellow jacket-sensitized patients. However, with a negative test IHC response as a selection criterion for the omission of venom immunotherapy, 14.6% of the bee venom-sensitized patients and 10.2% of the yellow jacket-sensitized patients were proven to be at risk for systemic reactions on subsequent field stings., Conclusion: Venom immunotherapy with bee or yellow jacket venom is justifiable only after a positive response to an IHC is observed.

Insects make up 80% of the animal kingdom with over 800,000 species worldwide. Allergic reactions to bee or wasp stings are common and they may rarely be fatal. Patients who experience systemic sting reactions must receive effective treatment and assessment.

Background: Asthma, together with, in some cases, anaphylaxis, was observed in seven subjects following ingestion of royal jelly, a secretion of honey bees which is used as a health tonic., Objective: To determine if reactions were IgE-mediated and to identify allergenic components of royal jelly., Methods: Skin-prick tests, immunoassays for specific IgE antibodies and protein blotting studies using patients' sera and anti-IgE second antibodies were employed., Results: Immunoassays detected IgE antibodies to royal jelly proteins in sera of subjects who reacted to the substance. A total of 18 different IgE-binding components were detected on blots following electrophoretic separation of royal jelly under dissociating conditions. Examination of 63 sera from subjects allergic to bee venom showed that there is no direct relationship between IgE antibody reactivity to bee venom allergens and to royal jelly proteins although 38% of the sera reacted with a royal jelly solid phase. IgE antibody reactivity to royal jelly proteins was also detected in 52% of 75 subjects with allergies to inhalant and/or food allergens. Antibody binding of blotted royal jelly proteins was most marked in the molecular weight region 25-55 kDa and one component of MW approximately 55 kDa was detected by all of the reactive sera from royal jelly-allergic and control allergic subjects., Conclusions: Symptoms of asthma and anaphylaxis seen in subjects following ingestion of royal jelly were true IgE-mediated hypersensitivity reactions. The clinical significance of the antibodies found in the sera of control subjects is not known but they may arise in response to common inhalant allergens that show allergenic cross-reactivity with royal jelly.

Markers of immediate-type hypersensitivity such as histamine and tryptase were measured in the plasma of nonallergic volunteers and patients with a history of hymenoptera venom anaphylaxis. No significant differences in histamine or tryptase were found between patients and controls. Norepinephrine, an important compound involved in the control of cardiovascular functions and blood pressure, was the same in patients and nonallergic volunteers. In addition, components of the renin-angiotensin system were determined. Patients with hymenoptera venom anaphylaxis showed significantly lower plasma angiotensinogen concentrations as compared to healthy nonallergic controls (p < 0.007), whereas plasma ACE activity was the same. Likewise, the plasma levels of angiotensin I and angiotensin II were significantly reduced in patients as compared to controls (p < 0.04 and p < 0.003, respectively). These findings suggest that the renin-angiotensin system may play an important role as a counteracting factor in hymenoptera venom anaphylaxis.

Tryptase, a neutral protease, is selectively concentrated in the secretory granules of human mast cells, and its release into the circulation serves as a clinical marker of mast cell activation. The current study describes a new, more sensitive ELISA utilizing a newly developed, mouse monoclonal IgG1 antibody for capture called B12 and capable of detecting tryptase in normal plasma and serum. The greater sensitivity of the new immunoassay results in part from a greater portion of tryptase being detected. Mean levels of tryptase in serum from normal subjects from Richmond, Virginia (4.9 ng/ml; n = 56), Munich, Germany (3.8 ng/ml; n = 19), and Amersfoort, The Netherlands (1.9 ng/ml; n = 8) were as indicated. In 62 subjects with ongoing allergic rhinitis, tryptase levels were no different in serum than for 19 normal controls, indicating that local mast cell activation is not necessarily reflected in the circulation. In 61 subjects sensitive to honey bee or yellow jacket venom by history, the 17 destined to have a severe, hypotensive response to a sting challenge had higher levels of tryptase at baseline than mild reactors, nonreactors, and controls, suggesting that baseline levels of tryptase may predict the severity of the clinical response to allergen in sensitive subjects.

It is currently recommended to administer a maintenance dose of 100 micrograms of venom at 4-6 week intervals for Hymenoptera venom immunotherapy (VIT). Because the optimal duration of therapy is not known, we decided to progressively prolong the interval between maintenance injections instead of accepting the risk of anaphylactic reactions when VIT is discontinued after a predetermined period. We report here on the results of a first phase of this interval extension programme, covering the gradual increase of the interval from 1-12 weeks over 19 months in 178 patients. A 12-week interval maintenance VIT could be achieved in 117/128 (91%) of yellow jacket venom (YJV) and in 35/50 (70%) of honeybee venom (HBV) allergic patients. At the time of the interview these 152 patients had been treated with 12-weekly 100 microgram venom injections for an average period of 2 years without any untoward reaction to VIT. During this period 48 YJV allergy sufferers experienced 77 field re-stings without systemic reaction (SR), and 17 HBV allergic subjects were restung at least 213 times in total, with one patient developing a very large local reaction and one a mild systemic reaction. In 26 of the 178 patients the interval of 12 weeks was not reached for various reasons, with a higher failure rate among the HBV allergic patients. Most Hymenoptera venom allergic patients can thus be safely and effectively treated with 12-weekly injections of 100 micrograms venom.

Components of the renin angiotensin system, namely renin, angiotensinogen, angiotensin I and II and aldosterone were measured in plasma of patients with hymenoptera venom anaphylaxis (n = 50) and healthy non-allergic controls (n = 25). Patients with a history of anaphylactic reactions to hymenoptera venom who did not undergo immunotherapy showed significantly reduced renin, angiotensinogen, angiotensin I and angiotensin II in plasma as compared with controls (P < 0.05). There was no difference in the aldosterone concentration between patients and controls. Angiotensin I, angiotensin II, renin and angiotensinogen levels were the same in male and female patients. There was also no difference in the angiotensin I, II, renin or angiotensinogen levels between young and older patients. A significant inverse correlation between the severity of clinical symptoms and the plasma levels of renin (r = -0.382, P < 0.001), angiotensinogen (r = -0.567, P < 0.0001), angiotensin I (r = -0.656, P < 0.0001) and angiotensin II (r = 0.0762, P < 0.0001) was found: the lower the levels the more severe the clinical symptoms. No correlation was found for aldosterone. Hymenoptera venom allergic patients with repeated anaphylactic reactions during hyposensitization did not tolerate the sting of a living insect (n = 6). In these patients, renin, angiotensinogen, angiotensin I and II remained significantly lower than in healthy non-allergic controls. Patients with successful immunotherapy (n = 27) who tolerated the sting of a living insect had renin, angiotensin I and II significantly higher than patients without immunotherapy. These findings suggest a possible role of the renin angiotensin system in hymenoptera venom anaphylaxis.

We compared the results obtained with a new specific IgE assay (Pharmacia CAP system) to those of RAST and intradermal skin tests (ST) performed in 87 patients with a history of generalized reaction to honeybee or yellow jacket venom. When CAP and RAST were compared with positive ST performed with honeybee venom, CAP sensitivity was not significantly higher (98%) than that of RAST (95%). When yellow jacket venom was tested, CAP sensitivity (93%) was clearly superior to that of RAST (40%). When we compared the specificities of RAST and CAP to bee venom, RAST was positive in 21% of the 24 subjects with negative ST, and CAP in 42%. Among the 29 patients with negative ST to yellow jacket venom, RAST was positive in 17% and CAP in 28%. These results do not reflect a lower specificity of CAP, because CAP positivities could be inhibited in vitro, and because, in three patients with a history of anaphylactic reaction (one to honeybee, two to yellow jacket), CAP was the only positive test confirming the clinical observation. Among the 53 patients who were able to identify the offending insect (honeybee, 31; yellow jacket, 22), the cause of the anaphylactic reaction was usually confirmed by ST and CAP: honeybee venom 97% for both ST and CAP; yellow jacket venom 82% for ST, 86% for CAP. This was not the case for RAST, which confirmed honeybee venom hypersensitivity in 87% and yellow jacket venom hypersensitivity in only 41%. Thus, CAP is both more sensitive and more rapid than RAST, without losing specificity.

Hymenoptera stings are common and potentially serious. The clinical, paraclinical and therapeutic aspects of allergy to hymenoptera venom are being better and better understood. A retrospective descriptive enquiry of hymenoptera stings in 270 consultations in a Central General Hospital has established three risk factors in the possibility of a serious reaction (R.A.G.): Men: 2.4 times more allergic reactions (R.A.). Severity of R.A. increases with age, especially after 50 years. Hornet stings have a risk 5 times greater than that of bees and 4.3 times greater than wasp.

We describe a case of multiple African bee stings in which the exceptionally high dose suggests a direct effect of hymenoptera venom on the renal tubules. The case does not follow the previously reported pattern of hypovolemic or anaphylactic shock, hemolysis and/or rhabdomyolysis, despite the potentially lethal amount of venom injected.

Venom immunotherapy (VIT) for Hymenoptera allergy is accepted as safe and effective. However, widely varying success rates and frequencies of side effects are reported. Differences between various Hymenoptera species could account for these diverging results. We therefore analyzed 205 patients with a history of systemic allergic reactions to either honeybee (148 patients) or yellow jacket stings (57 patients) during VIT. All patients had a positive skin test to the respective venom before VIT, were monitored for side effects of VIT, and submitted to a sting challenge while they were receiving VIT. Patients with honeybee-venom allergy had a higher sensitivity in both skin tests (p less than 0.05) and RAST (p less than 0.001) than patients with yellow jacket-venom allergy. They developed systemic side effects to VIT injections significantly more often (41% versus 25%; p less than 0.01) and also reacted more frequently to the sting challenge (23% versus 9%; p less than 0.01) than patients with yellow jacket-venom allergy. We conclude that results obtained from studies on the allergy to one Hymenoptera venom cannot be extrapolated to allergies to other Hymenoptera venoms.

In a double-blind placebo-controlled trial on 52 patients with bee venom allergy we studied the effect of a pretreatment with terfenadine 120 mg twice daily on the occurrence of local and systemic allergic side effects from rush-immunotherapy. Large local reactions were significantly reduced by terfenadine pretreatment (P less than 0.01), while systemic side effects were observed with similar frequencies in both groups. Analysis of individual systemic allergic manifestations showed that cutaneous symptoms like itching (P less than 0.025) and urticaria/angioedema (P less than 0.05) were significantly reduced, while respiratory or cardiovascular symptoms were not influenced. A lower consumption of additional anti-allergic medication was found during terfenadine pretreatment (P less than 0.05). Pretreatment with antihistamines during immunotherapy may thus be helpful in the management of patients with cutaneous side effects.

The authors discuss an exceptional case of allergy to bee venom in a zoo-technician working on a morphological analysis of bees. During her work, the zoo-technician was repeatedly stung, initially with only small local reaction. After six-year period of work, the symptoms that followed stinging had all the characteristics of general oedema. Next years of exposure to bee venom resulted in collapse in the patient. Allergological examinations indicated work-related hypersensitivity to bee venom. The case history was supplemented with prophylactic recommendations. General principles of controlling the shock were provided.

In general, specific immunotherapy with hymenoptera venoms can be considered as safe, but occasionally there are patients who cannot reach the maintenance dose due to repeated systemic reactions (RSR) or who suffer from RSR during maintenance therapy. In a multicenter retrospective study comprising seven departments in Germany, Austria and Switzerland 23 patients with RSR were reported from approximately 3000 patients treated with hymenoptera venoms (bee and wasp venom to approximately equivalent frequency). From these, 22 were allergic to bee venom and only one to vespid venom. In general the clinical symptoms of RSR were milder than the initial reaction. But 4/23 (18%) exhibited cardiovascular reactions up to full shock. Neither anamnestic details, reactivity in skin tests or in vitro tests revealed a special pattern of patients with RSR. In some patients, however, an extremely high reactivity in the skin test was found and may indicate the possibility of further RSR.

In this study, on a population of 26 patients with systemic reactions after hymenoptera stings, different immunobiological tests have been used to confirm the sensitivity to hymenoptera venom. These 26 patients were divided into two groups according to the stage of their immunotherapy: group 1 (n = 8) included all assessments from day 0 (before IT) and group 2 (n = 16) the assessments at 1 and 2 years during IT. In general, there was a good correlation between skin tests, RAST and histamine release. The results show that the IgE level seems to be more informative than histamine release and that measurement of the specific IgE level is more sensitive with Allerbio allergen compared with other allergens. However these preliminary results must be confirmed on a statistically significant number of patients. HL by Agf is less sensitive than that done with Ags.

Natural or iatrogenic causes of anaphylaxis are significant risk factors in pregnancy. A 3% to 5% risk of sting anaphylaxis in any pregnant woman with insect-sting allergy untreated with venom immunotherapy (VIT) can be calculated. Insect-sting anaphylaxis has allegedly caused severe fetal abnormalities and is a potential cause of fetal loss and severe maternal morbidity and/or mortality. Hymenoptera anaphylaxis is a highly preventable cause of anaphylaxis, but VIT may itself carry a risk potential, with an appropriate 5% reaction during buildup and 1% reaction risk during maintenance VIT. To assess the safety of VIT in pregnancy, we have gathered data from 26 women with 43 pregnancies. All the women were receiving VIT. One woman was stung early in pregnancy with anaphylaxis resulting. Outcome of pregnancy was normal. Thirty-six of the pregnancies ended normally. There were two mild adverse reactions to VIT, neither of which required treatment. One child was born with multiple congenital abnormalities of unknown cause. Since congenital malformations may occur as frequently as one in 40 live births, these data do not suggest a significant increased risk from VIT during pregnancy.

Immunotherapy with hymenoptera venoms is safe and effective in most patients but treatment failures have been reported. Five patients experienced systemic symptoms of anaphylaxis when they were in maintenance immunotherapy with honey bee venom. In one case, the patient presented a severe life-threatening reaction when stung by a honey bee. Three others had the development of new clinical sensitivity suggesting a re-sensitization. This occurred in the fifth patient after a severe viral infection. By means of a rush protocol and monthly doses of 200 to 400 micrograms of honey bee venom, the patients were subsequently protected efficiently. In most cases these reactions might have been predicted since patients experienced large local reactions prior to the systemic reactions when allergens were injected. Further, in four cases there was an increased skin test reactivity or raised serum honey bee venom IgE levels or both. In all patients, the levels of serum honey bee venom IgG was under 200 U/mL (IgG Pharmacia RAST).

Beekeepers often present allergic symptoms and represent a natural and experimental model of anaphylaxis and specific immunotherapy. Two hundred BKs were investigated. Both allergic and nonallergic subjects were selected very carefully in terms of immunologic status and exposure to bee stings. They were surveyed by a questionnaire, the titration of total serum IgE, and bee venom-specific IgE and IgG. Skin tests to HBV were performed in 176 subjects. Skin test sensitivity to HBV and allergic symptoms were significantly (p less than 0.0001) related to the estimated number of annual stings. BKs did not have allergy for more than 200 bee stings received in a year, and skin tests were negative in all cases. Many subjects who received between 50 and 200 annual stings had positive skin tests, and 9% of them had a systemic allergic history. Systemic anaphylaxis was present in 20% of BKs who received between 25 to 50 annual stings, and in 45% of BKs who are stung less than 25 times a year. Specific IgE was present in 42% of BKs whatever the number of stings received, but the titer was lower when the number of stings increased. The presence of specific IgE in subjects who are stung numerous times and who do not present allergic symptoms at the time of the stings suggests that outbreaks of anaphylaxis may be possible in nonallergic BKs. Specific IgG titrated by the Pharmacia IgG-RAST was less than 150 U/ml in most allergic subjects and over this level in most nonallergic BKs.(ABSTRACT TRUNCATED AT 250 WORDS)

Severe anaphylaxis is reported in a bee venom-sensitive 31-year-old male while receiving propranolol. His anaphylactic reaction was mainly respiratory and was refractory to emergency treatment. We believe that his use of beta-blockers contributed to the severity of his anaphylaxis and refractoriness to treatment. We suggest that beta-blockers should be contraindicated or alternate medications used in hymenoptera allergic patients.

In 50 patients who had severe allergic general reactions after a bee sting clinical and immunological parameters were examined under the desensitisation with apitoxin. Under the introduction of the hospital treatment 25 patients showed side effects. 14 of these patients had milder general reactions also during the further continuation of the ambulatory treatment. In no case the treatment had to be stopped. The behaviour of the specific IgE and IgG antibodies does not allow a prognostic evidence concerning possible side effects and is little suited for the individual case also as objective parameter of success. 17 patients who during the first weeks after the beginning of the therapy spontaneously had been stung by a bee did not show any reactions or only reduced reactions. This result shows that the desensitization of desensitized patients gives a secure protection from life-threatening incidents. Open remains among others the problem of the objective judgment of the therapy and thus the question of the duration of the treatment.

Bee venom allergy is a common problem in South Africa, and although most patients develop only local reactions after a sting, generalized life-threatening reactions may occur. Immunotherapy with purified bee venom has proved effective in preventing subsequent sting anaphylaxis. However, because of side-effects during a course of desensitization, the high cost of this form of therapy and the extended period for which therapy may be required, careful patient selection is essential. Only patients with documented generalized reactions should be considered for therapy. Patients with severe local reactions, and those with urticaria or other cutaneous symptoms, should not undergo desensitization. Although it is not yet known for how long desensitization should continue, a negative skin test 3-6 years after the initiation of therapy suggests that desensitization can be discontinued.