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Hornet (vespa crabro) sting allergy and life threatening reactions
J ALLERGY CLIN IMMUNOL VOLUME 109, NUMBER 1
Abstracts
$79
199 Ultraviolet Treatment and Mastocytosis:A Surveyof 39 Patients
01 tions Hornet (Vespa Crabro) Sting Allergy and Life Threatening Reac-
Stefanie Birte Bruns*, Ulrich Mrowietz§, Karin Hartmann* *University
Leonardo Antonicelli, Beatrice Bilb, Grazia Napoli, Caterina Colangelo, Floriano Bonifazi Department of Respiratory and Allergic Diseases,
of Cologne, Cologne, Germany §University of Kiel, Kiel, Germany Mastocytosis is a rare disease characterized by accumulation of mast cells in tissues. Clinical observation suggests that ultraviolet (UV) irradiation often leads to improvement of cutaneous mastocytosis, however, controlled studies evaluating the effect of UV therapy on mastocytosis are still missing. In the present study, a detailed questionnaire was sent out to 59 mastocytosis patients with a history of UV treatment and the results of 39 completed questionnaires were analyzed using the software SPSS. 22 patients had received oral PUVA therapy, 14 patients bath PUVA, 6 patients UVA 1, and 7 patients UVB (several patients had been treated with different UV irradiations). Mean duration of UV therapy was 12.9 months (range: 0.5-84 months). 25 patients (64.1%) observed improvement of mastocytosis symptoms in response to UV treatment, 11 patients (28.2%) described no change, and 3 patients (7.7%) experienced deterioration. Analyzing the different UV irradiations, 59.1% of the patients receiving oral PUVA therapy showed improvement, 71.4% of the patients receiving bath PUVA, 50.0% of the patients receiving UVA l, and 57.1% of the patients receiving UVB. Mean duration of improvement was 15.4 months for oral PUVA, 7.1 months for bath PUVA, 2.0 months for UVA1, and 12.5 months for UVB. Most frequent symptoms improving after UV treatment were cutaneous spots (76%), pruritus (68%), and hives (52%). The results of this survey suggest that UV treatment may be more effective than currently anticipated and that PUVA treatment appears superior to irradiation with UVAI or UVB. Controlled prospective studies investigating the effect of UV irradiation on mastocytosis are needed.
200
The Bee Venom Protease Allergen Containsa CUB Domain
Margit Schmidt*, Karen M Winningham*, Donald R HofJ~nan§ *East Carolina University, Greenville, NC §Brody School of Medicine at East Carolina University, Greenville, NC Venom proteases are important allergens in both bumblebee and paper wasp venoms. A protease of apparent molecular weight of 39000 is found in honeybee venom, but is difficult to purify without denaturation. This protein appears to be a significant allergen in immunoblotting studies of Kettner et al. and others. Previously we reported the cloned sequence of the protease domain of 245 amino acids obtained from 3" RACE cloning. It is a tryptic type protease with an unusual methionine residue at the opening of the substrate cleft. In order to obtain the complete cDNA, 5" RACE was used. Specific cDNA was tailed at the 3" end using dCTs and terminal deoxynucleotide transferase. 5" fragments were amplified using specific primers and a 5" anchor primer (Life Technologies). The sequences of the 5" fragment show that there are additional domains N-terminal to the serine protease domain. Immediately preceding the initial isoleucine is a serine protease propeptide sequence of about 11 amino acids ending with an arginine residue. A peptide corresponding to this region was isolated from a tryptic digest of the native molecule. This region follows a CUB domain of about 106 amino acids, of which 56 were confirmed by amino acid sequencing of 5 tryptic peptides isolated from the digest. CUB domains are important in developmental regulation, targeting and protein-protein associations. Other proteins with CUB domains include some reproductive proteases such as spermadhesins, proacrosins and ovochymases; developmental proteases including procollagen C-proteinase (tolloid), bone morphogenetic proteins, neuropilins and platelet derived growth factors C and D; a type I membrane protein LRP9, which is an apolipoprotein E receptor; the T cell adhesion and guidance protein, attractin; and the complement system proteases Clr, Cls, MASP-1 and 2. The honeybee venom protease is most similar to gene product CG2280 from Drosophila, which contains a CUB domain, propeptide regions and two serine protease domains.
Ancona, Italy Honeybee sting is a risk factor for severe allergic reaction but some reports pointed out the role of hornet. The aim of the study was to evaluate the risk of severe reaction after hornet sting. We studied 157 patients (115 male 42 female) with case history positive for systemic reaction after hymenoptera sting, consecutively seen in our department in the last two years. Skin test and case history were used to identify the insect culprit of systemic reaction. Since the venoms of yellow jacket (vespula spp) and hornet (vespa crabro) show a very high level of cross-reactivity and the hornet is 3-4folds bigger than yellow jacket, the recognition of the culprit insect was based on case history. Based upon these guidelines the patients are separated in three groups: 97 patients were allergic to vespula spp (M/F: 68/29; mean age: 41_+16 SD), 35 were allergic to vespa crabro (M/F: 27/8; mean age: 56_+13 SD) 25 were allergic to apis mellifera (M/F: 20/5; mean age: 47_+12 SD). The relative risk of severe systemic reaction (grade 4 of Mueller classification) compared with lower grades (1, 2, 3 of Mueller classification) was threefold higher in hornet stung patients than in those stung by yellow jacket (p< 0.0001) and by honeybee (p< 0.0002). Since the hornet stung patients were significantly older than the other two groups (hornet vs. yellow jacket: p<0.001; hornet vs. honeybee: p<0.02) the age could be the cause of the severity of the reactions. Therefore each group of patients were divided in two groups: age<50 yrs and age>51 yrs. The relative risk of grade 4 reaction after hornet sting was confirmed, because it was twofold compared with the other insects in each age level. No significant difference was observed between yellow jacket and honeybee stung patients. These data suggests the role of hornet in life threatening reactions in Italy. The great dose of venom injected by the hornet sting could be related to this effect. Because of the high level of crossreactivity between both venoms, hornet sting could be a risk of severe reactions in patients previous sensitized by yellow jacket sting, which is the most common clinical condition.
' ~ AnaphylactoidShock After Hymenoptera Stingsas a Presenting V ~-- Symptom of Indolent Mastocytosis Bilb Maria Beatrice, Antonicelli Leonardo, Cinti Barbara, Brianzoni Feliciana, Bonifazi Floriano Department of Respiratory and Allergic Diseases, Ancona, Italy Systemic reactions resembling anaphylaxis may occur in patients with urticaria pigmentosa or systemic mastocytosis after hymenoptera stings. We report a case of a 38-year-old man who presented in September 2000 with a history of severe anaphylactic reaction, resulting in loss of consciousness, 510 rain after three wasp stings one month before. He was subsequently restung by a single wasp without any reaction. Intracutaneous skin test were done with hymenoptera venom (Vespula sp, Polistes sp, Apis mellifera: Stallergenes; Polistes dominulus, Vespa crabro: Anallergo) ranging from 0,001 to 1 mcg/ml; skin tests were repeated three times, one month, three months and ten months after the anaphylactic reaction. Venom specific IgE antibodies were not detectable in serum (UniCAP-Pharmacia CAPSystem). A sensitive fluoro immunoassay (UniCAP tryptase; Pharmacia & Upjohn) revealed a markedly elevated serum mast cell tryptase level of 54.6 mcg/L (September 2000), 59.7 mcg/L (November 2000) and 57.6 mcg/L (June 2001) (95th percentile in normals 13.5 mcg/L). Patient was completely asymptomatic; there was no skin involvement, no anemia or thrombocytopenia. Echogramme of liver and spleen was negative. Bone biopsy showed the presence of histologically proven abnormal numbers of mast cells with typical configurations in bone marrow. Indolent mastocytosis was diagnosed. Our conclusion are that, in cases of anaphylactoid reaction to hymenoptera sting, especially when there is no IgE detectable, the diagnosis of mastocytosis should be considered, also in absence of the clinical hallmarks of urticaria pigmentosa.
Abstracts
$79
199 Ultraviolet Treatment and Mastocytosis:A Surveyof 39 Patients
01 tions Hornet (Vespa Crabro) Sting Allergy and Life Threatening Reac-
Stefanie Birte Bruns*, Ulrich Mrowietz§, Karin Hartmann* *University
Leonardo Antonicelli, Beatrice Bilb, Grazia Napoli, Caterina Colangelo, Floriano Bonifazi Department of Respiratory and Allergic Diseases,
of Cologne, Cologne, Germany §University of Kiel, Kiel, Germany Mastocytosis is a rare disease characterized by accumulation of mast cells in tissues. Clinical observation suggests that ultraviolet (UV) irradiation often leads to improvement of cutaneous mastocytosis, however, controlled studies evaluating the effect of UV therapy on mastocytosis are still missing. In the present study, a detailed questionnaire was sent out to 59 mastocytosis patients with a history of UV treatment and the results of 39 completed questionnaires were analyzed using the software SPSS. 22 patients had received oral PUVA therapy, 14 patients bath PUVA, 6 patients UVA 1, and 7 patients UVB (several patients had been treated with different UV irradiations). Mean duration of UV therapy was 12.9 months (range: 0.5-84 months). 25 patients (64.1%) observed improvement of mastocytosis symptoms in response to UV treatment, 11 patients (28.2%) described no change, and 3 patients (7.7%) experienced deterioration. Analyzing the different UV irradiations, 59.1% of the patients receiving oral PUVA therapy showed improvement, 71.4% of the patients receiving bath PUVA, 50.0% of the patients receiving UVA l, and 57.1% of the patients receiving UVB. Mean duration of improvement was 15.4 months for oral PUVA, 7.1 months for bath PUVA, 2.0 months for UVA1, and 12.5 months for UVB. Most frequent symptoms improving after UV treatment were cutaneous spots (76%), pruritus (68%), and hives (52%). The results of this survey suggest that UV treatment may be more effective than currently anticipated and that PUVA treatment appears superior to irradiation with UVAI or UVB. Controlled prospective studies investigating the effect of UV irradiation on mastocytosis are needed.
200
The Bee Venom Protease Allergen Containsa CUB Domain
Margit Schmidt*, Karen M Winningham*, Donald R HofJ~nan§ *East Carolina University, Greenville, NC §Brody School of Medicine at East Carolina University, Greenville, NC Venom proteases are important allergens in both bumblebee and paper wasp venoms. A protease of apparent molecular weight of 39000 is found in honeybee venom, but is difficult to purify without denaturation. This protein appears to be a significant allergen in immunoblotting studies of Kettner et al. and others. Previously we reported the cloned sequence of the protease domain of 245 amino acids obtained from 3" RACE cloning. It is a tryptic type protease with an unusual methionine residue at the opening of the substrate cleft. In order to obtain the complete cDNA, 5" RACE was used. Specific cDNA was tailed at the 3" end using dCTs and terminal deoxynucleotide transferase. 5" fragments were amplified using specific primers and a 5" anchor primer (Life Technologies). The sequences of the 5" fragment show that there are additional domains N-terminal to the serine protease domain. Immediately preceding the initial isoleucine is a serine protease propeptide sequence of about 11 amino acids ending with an arginine residue. A peptide corresponding to this region was isolated from a tryptic digest of the native molecule. This region follows a CUB domain of about 106 amino acids, of which 56 were confirmed by amino acid sequencing of 5 tryptic peptides isolated from the digest. CUB domains are important in developmental regulation, targeting and protein-protein associations. Other proteins with CUB domains include some reproductive proteases such as spermadhesins, proacrosins and ovochymases; developmental proteases including procollagen C-proteinase (tolloid), bone morphogenetic proteins, neuropilins and platelet derived growth factors C and D; a type I membrane protein LRP9, which is an apolipoprotein E receptor; the T cell adhesion and guidance protein, attractin; and the complement system proteases Clr, Cls, MASP-1 and 2. The honeybee venom protease is most similar to gene product CG2280 from Drosophila, which contains a CUB domain, propeptide regions and two serine protease domains.
Ancona, Italy Honeybee sting is a risk factor for severe allergic reaction but some reports pointed out the role of hornet. The aim of the study was to evaluate the risk of severe reaction after hornet sting. We studied 157 patients (115 male 42 female) with case history positive for systemic reaction after hymenoptera sting, consecutively seen in our department in the last two years. Skin test and case history were used to identify the insect culprit of systemic reaction. Since the venoms of yellow jacket (vespula spp) and hornet (vespa crabro) show a very high level of cross-reactivity and the hornet is 3-4folds bigger than yellow jacket, the recognition of the culprit insect was based on case history. Based upon these guidelines the patients are separated in three groups: 97 patients were allergic to vespula spp (M/F: 68/29; mean age: 41_+16 SD), 35 were allergic to vespa crabro (M/F: 27/8; mean age: 56_+13 SD) 25 were allergic to apis mellifera (M/F: 20/5; mean age: 47_+12 SD). The relative risk of severe systemic reaction (grade 4 of Mueller classification) compared with lower grades (1, 2, 3 of Mueller classification) was threefold higher in hornet stung patients than in those stung by yellow jacket (p< 0.0001) and by honeybee (p< 0.0002). Since the hornet stung patients were significantly older than the other two groups (hornet vs. yellow jacket: p<0.001; hornet vs. honeybee: p<0.02) the age could be the cause of the severity of the reactions. Therefore each group of patients were divided in two groups: age<50 yrs and age>51 yrs. The relative risk of grade 4 reaction after hornet sting was confirmed, because it was twofold compared with the other insects in each age level. No significant difference was observed between yellow jacket and honeybee stung patients. These data suggests the role of hornet in life threatening reactions in Italy. The great dose of venom injected by the hornet sting could be related to this effect. Because of the high level of crossreactivity between both venoms, hornet sting could be a risk of severe reactions in patients previous sensitized by yellow jacket sting, which is the most common clinical condition.
' ~ AnaphylactoidShock After Hymenoptera Stingsas a Presenting V ~-- Symptom of Indolent Mastocytosis Bilb Maria Beatrice, Antonicelli Leonardo, Cinti Barbara, Brianzoni Feliciana, Bonifazi Floriano Department of Respiratory and Allergic Diseases, Ancona, Italy Systemic reactions resembling anaphylaxis may occur in patients with urticaria pigmentosa or systemic mastocytosis after hymenoptera stings. We report a case of a 38-year-old man who presented in September 2000 with a history of severe anaphylactic reaction, resulting in loss of consciousness, 510 rain after three wasp stings one month before. He was subsequently restung by a single wasp without any reaction. Intracutaneous skin test were done with hymenoptera venom (Vespula sp, Polistes sp, Apis mellifera: Stallergenes; Polistes dominulus, Vespa crabro: Anallergo) ranging from 0,001 to 1 mcg/ml; skin tests were repeated three times, one month, three months and ten months after the anaphylactic reaction. Venom specific IgE antibodies were not detectable in serum (UniCAP-Pharmacia CAPSystem). A sensitive fluoro immunoassay (UniCAP tryptase; Pharmacia & Upjohn) revealed a markedly elevated serum mast cell tryptase level of 54.6 mcg/L (September 2000), 59.7 mcg/L (November 2000) and 57.6 mcg/L (June 2001) (95th percentile in normals 13.5 mcg/L). Patient was completely asymptomatic; there was no skin involvement, no anemia or thrombocytopenia. Echogramme of liver and spleen was negative. Bone biopsy showed the presence of histologically proven abnormal numbers of mast cells with typical configurations in bone marrow. Indolent mastocytosis was diagnosed. Our conclusion are that, in cases of anaphylactoid reaction to hymenoptera sting, especially when there is no IgE detectable, the diagnosis of mastocytosis should be considered, also in absence of the clinical hallmarks of urticaria pigmentosa.