Allergy 1979, 34, 369-378
Immunotherapy in Bee Sting Hypersensitivity Bee Venom Versus Wholebody Extract U. MCLLER, U. THURNHEER, R. PATRIJKI, J. SPIESS and R. HOIGNE Medical Division, Zieglerspital Bern, Switzerland
Fifty-six patients with serologically confirmed bee sting hjpersensitivity were treated for I-S years with either bee venom (BV) 131 patients) or wholebody extract (WBE) C25 patients). Twelve patients in each group were re-exposed to a bee sting. Twenty-five per cent ol re-exposed patients on BV-therapy showed a diminished reacdon and 75% no traction. Thirty-three pet cent of re-exposed patients on WBE-therapy developed an unchanged or worse reaction, 42% a diminished reaction and 25% tio reaction at all. An initial rise in BV-specific IgE was observed in BV-treated patients, whereas IgE levels after 1 year of treatment lay significantly below pretreatment values in both treatment groups. BV-specific IgG increased markedly in patients on BV-therapy and decreased slightly in those on WSE-therapy. The initial IgE increase induced by BV-therapy was insignificant in patients with high preireatment levels of specific IgG-antibodies. Similarly, re-exposed patients with high BV-specific IgG showed no igE increase, whereas a substantial rise in specific IgE was observed in those with low IgG. On the basis of clinical and serological results immunotherapy with BV is considered to be clearly superior to immunotherapy with WBE AWcwrrf-i; bee ve]ioni; bee whole body extract; immunotherapy; insect sting h\'persensitivit>Accepted for pubitciUion II April 1979
Generalized allergic reactions to insect stings of the order Hymenoptera as a rule are of type I, and venom-specific IgE-antibodies may be detected in the serum of most of these patients (13, 18, 24). In Switzerland 2-4% of the adult population have experienced allergic reactions to hymenoptera stings once or several times during their life (21), The annual number of deaths due to hymenoptera stings varied between 0 and 10 with an average of 3.6 in the years 1952-1974(23), In hyposensitization therapy wholebody extracts of the implicated insect have been widely used during the last 40 years (3, 5, 8, II, 23). The recent observation that serological and skin tests with venoms dis0105-4538/79/060369-10 S02.50/0
criminate much better between patients with insect sting allergy and non-allergic controls (9, 15, 17, 25), prompted several authors to carry out immunotherapy with insect venoms instead of wholebody extracts (4, 7, 13, 19, 22). In this study 56 patients with bee sting allergy have been treated either with bee venom or with whoiebody extract for 1 to 3 years. Clinical and serological results of the treatment are reported. MATERIAL AND METHODS
Fifty-six patients were studied who had a history of general allergic reactions to bee © '9™ Munksgaard, Copenhagen
370
u. MOLLER ET AL.
stings, a reaction time of 30 min or less between sting and first allergic symptoms, and significant levels of bee venom-specific IgE-antibodies in their serum. Clinical and serological data of the patients are given in Table 1.
season of the insects (March until September) patients were hospitalized and a rush hyposensitization with four daily injections was peHbrmed. During the fall and winter the patients were treated in the outpatient department with twice weekly injections. With both BV- and WBE-treatment, when a .Antigens local reaction exceeding 5 cm in diameter Lyophilized bee venom (BV) and bee venom occurred, the dose was not increased; it was phosphoiipase A (BV-PLA) were purchased reduced by a factor 2-4 when general from Mack Nachf., Illertissen, Bayern, FRG. reactions were observed. After reaching the 1 mg of BV was dissolved in 1 ml of 0.996 maintenance dose the interval between injecsaline and sterilized by uitrafiltration. This tions was gradually lengthened up to 4 preparation served as a stem solution. weeks. Commercial 1% (w/v) bee wholebody extract Serohgical investigations. Blood samples were (WBE) was obtained from Bencard Allergy obtained from all patients on the day before Unit, Switzerland. From both BV and WBE starting treatment, and after 1 month, 2 10-fold dilutions up to 10~' of the stem months, 6 months and I year of treatment. solution were prepared in 0.9% saline. All antigen solutions were kept at -i-4°C. Stem IgE-antibodies against BV were estimated by solutions were discarded after 1 year, the Phadebas* RAST (Pharmacia Diagdilutions after 1 month. nostics AB, Uppsala, Sweden). IgE values are Treatment (Table 2}
given as a percentage of reference C in the Phadebas RAST reference system.
Thirty-one patients were treated with BV, 25 with WBE. Half of each group was treated by intracutaneous injections in the forearm as proposed by Ordman (16), the other half by subcutaneous injections in the upper arm. Four injections of each concentration (0.1, 0.2, 0.4, 0.8 ml s.c. and 0.01, 0.02, 0.04, 0.08 ml i.e.) were given. During the flying
igG-antibodiei to BVPLA were estimated as described previously (14). Briefly, 0.1ml of patient serum diluted 1/10 in 0.1 m phosphate buffer pH 7.4 containing 0.2% bovine serum albumin, 0.196 Tween 20 and 0.05% NaN, was incubated in 0.5 ml of SepharoseProtein A (Pharmacia Fine Chemicals,
labie 1 Clinical and serological data of patients at the beginning of the treattnent Treatment
No. treated
Mean age
Severity of last general reaction 1
11
III
IV
Interval between sting and blood sample
Immunotherapy in Bee Sting Hypersensitivity Bee Venom Versus Wholebody Extract U. MCLLER, U. THURNHEER, R. PATRIJKI, J. SPIESS and R. HOIGNE Medical Division, Zieglerspital Bern, Switzerland
Fifty-six patients with serologically confirmed bee sting hjpersensitivity were treated for I-S years with either bee venom (BV) 131 patients) or wholebody extract (WBE) C25 patients). Twelve patients in each group were re-exposed to a bee sting. Twenty-five per cent ol re-exposed patients on BV-therapy showed a diminished reacdon and 75% no traction. Thirty-three pet cent of re-exposed patients on WBE-therapy developed an unchanged or worse reaction, 42% a diminished reaction and 25% tio reaction at all. An initial rise in BV-specific IgE was observed in BV-treated patients, whereas IgE levels after 1 year of treatment lay significantly below pretreatment values in both treatment groups. BV-specific IgG increased markedly in patients on BV-therapy and decreased slightly in those on WSE-therapy. The initial IgE increase induced by BV-therapy was insignificant in patients with high preireatment levels of specific IgG-antibodies. Similarly, re-exposed patients with high BV-specific IgG showed no igE increase, whereas a substantial rise in specific IgE was observed in those with low IgG. On the basis of clinical and serological results immunotherapy with BV is considered to be clearly superior to immunotherapy with WBE AWcwrrf-i; bee ve]ioni; bee whole body extract; immunotherapy; insect sting h\'persensitivit>Accepted for pubitciUion II April 1979
Generalized allergic reactions to insect stings of the order Hymenoptera as a rule are of type I, and venom-specific IgE-antibodies may be detected in the serum of most of these patients (13, 18, 24). In Switzerland 2-4% of the adult population have experienced allergic reactions to hymenoptera stings once or several times during their life (21), The annual number of deaths due to hymenoptera stings varied between 0 and 10 with an average of 3.6 in the years 1952-1974(23), In hyposensitization therapy wholebody extracts of the implicated insect have been widely used during the last 40 years (3, 5, 8, II, 23). The recent observation that serological and skin tests with venoms dis0105-4538/79/060369-10 S02.50/0
criminate much better between patients with insect sting allergy and non-allergic controls (9, 15, 17, 25), prompted several authors to carry out immunotherapy with insect venoms instead of wholebody extracts (4, 7, 13, 19, 22). In this study 56 patients with bee sting allergy have been treated either with bee venom or with whoiebody extract for 1 to 3 years. Clinical and serological results of the treatment are reported. MATERIAL AND METHODS
Fifty-six patients were studied who had a history of general allergic reactions to bee © '9™ Munksgaard, Copenhagen
370
u. MOLLER ET AL.
stings, a reaction time of 30 min or less between sting and first allergic symptoms, and significant levels of bee venom-specific IgE-antibodies in their serum. Clinical and serological data of the patients are given in Table 1.
season of the insects (March until September) patients were hospitalized and a rush hyposensitization with four daily injections was peHbrmed. During the fall and winter the patients were treated in the outpatient department with twice weekly injections. With both BV- and WBE-treatment, when a .Antigens local reaction exceeding 5 cm in diameter Lyophilized bee venom (BV) and bee venom occurred, the dose was not increased; it was phosphoiipase A (BV-PLA) were purchased reduced by a factor 2-4 when general from Mack Nachf., Illertissen, Bayern, FRG. reactions were observed. After reaching the 1 mg of BV was dissolved in 1 ml of 0.996 maintenance dose the interval between injecsaline and sterilized by uitrafiltration. This tions was gradually lengthened up to 4 preparation served as a stem solution. weeks. Commercial 1% (w/v) bee wholebody extract Serohgical investigations. Blood samples were (WBE) was obtained from Bencard Allergy obtained from all patients on the day before Unit, Switzerland. From both BV and WBE starting treatment, and after 1 month, 2 10-fold dilutions up to 10~' of the stem months, 6 months and I year of treatment. solution were prepared in 0.9% saline. All antigen solutions were kept at -i-4°C. Stem IgE-antibodies against BV were estimated by solutions were discarded after 1 year, the Phadebas* RAST (Pharmacia Diagdilutions after 1 month. nostics AB, Uppsala, Sweden). IgE values are Treatment (Table 2}
given as a percentage of reference C in the Phadebas RAST reference system.
Thirty-one patients were treated with BV, 25 with WBE. Half of each group was treated by intracutaneous injections in the forearm as proposed by Ordman (16), the other half by subcutaneous injections in the upper arm. Four injections of each concentration (0.1, 0.2, 0.4, 0.8 ml s.c. and 0.01, 0.02, 0.04, 0.08 ml i.e.) were given. During the flying
igG-antibodiei to BVPLA were estimated as described previously (14). Briefly, 0.1ml of patient serum diluted 1/10 in 0.1 m phosphate buffer pH 7.4 containing 0.2% bovine serum albumin, 0.196 Tween 20 and 0.05% NaN, was incubated in 0.5 ml of SepharoseProtein A (Pharmacia Fine Chemicals,
labie 1 Clinical and serological data of patients at the beginning of the treattnent Treatment
No. treated
Mean age
Severity of last general reaction 1
11
III
IV
Interval between sting and blood sample
