Key Issues in Hymenoptera Venom Allergy: An Update.

In this review, the Hymenoptera Allergy Committee of the SEAIC analyzes the most recent scientific literature addressing problems related to the diagnosis of hymenoptera allergy and to management of venom immunotherapy. Molecular diagnosis and molecular risk profiles are the key areas addressed. The appearance of new species of hymenoptera that are potentially allergenic in Spain and the associated diagnostic and therapeutic problems are also described. Finally, we analyze the issue of mast cell activation syndrome closely related to hymenoptera allergy, which has become a new diagnostic challenge for allergists given its high prevalence in patients with venom anaphylaxis.

Insect Venom Immunotherapy: Analysis of the Safety and Tolerance of 3 Buildup Protocols Frequently Used in Spain.

INTRODUCTION: Hymenoptera venom immunotherapy (VIT) is an effective treatment but not one devoid of risk, as both local and systemic adverse reactions may occur, especially in the initial phases. We compared the tolerance to 3 VIT buildup protocols and analyzed risk factors associated with adverse reactions during this phase. MATERIALS AND METHODS: We enrolled 165 patients divided into 3 groups based on the buildup protocol used (3, 4, and 9 weeks). The severity of systemic reactions was evaluated according to the World Allergy Organization model. Results were analyzed using exploratory descriptive statistics, and variables were compared using analysis of variance. RESULTS: Adverse reactions were recorded in 53 patients (32%) (43 local and 10 systemic). Local reactions were immediate in 27 patients (63%) and delayed in 16 (37%). The severity of the local reaction was slight/moderate in 15 patients and severe in 13. Systemic reactions were grade 1-2. No significant association was found between the treatment modality and the onset of local or systemic adverse reactions or the type of local reaction. We only found a statistically significant association between severity of the local reaction and female gender. As for the risk factors associated with systemic reactions during the buildup phase, we found no significant differences in values depending on the protocol used or the insect responsible. CONCLUSIONS: The buildup protocols compared proved to be safe and did not differ significantly from one another. In the population studied, patients undergoing the 9-week schedule presented no systemic reactions. Therefore, this protocol can be considered the safest approach.

Longitudinal Validation of the Spanish Version of the Health-Related Quality of Life Questionnaire for Hymenoptera Venom Allergy (HRQLHA).

BACKGROUND AND OBJECTIVE: The Spanish version of the health-related quality of life questionnaire for allergy to hymenoptera venom (HRQLHA) has been shown to be reliable, internally consistent, and externally valid. The aim of this study was to complete the validation of the HRQLHA by analyzing its sensitivity to changes (longitudinal validity) using the sting challenge test (SCT) as the variable of change. PATIENTS AND METHODS: Patients over the age of 17 years with a systemic allergic reaction to Apis, Vespula, or Polistes venom were included during their first year of venom-specific immunotherapy. Patients were assigned to either a group that underwent the SCT or a control group that did not. All patients completed the HRQLHA at baseline and after a period of 2 to 4 months, during which time the SCT was performed in the active group, with no intervention in the control group. RESULTS: Fifty patients were included in the study: 25 in the SCT group and 25 in the control group. The patients in the SCT group showed a significant improvement in mean HRQLHA score (+0.35, P=.03) after the SCT, while those in the control group showed no significant changes in questionnaire scores. CONCLUSIONS: Our results demonstrate the sensitivity of the HRQLHA to changes and thus complete the longitudinal validation of the questionnaire. A well-tolerated SCT improves the quality of life of venom-allergic patients as it reduces anxiety associated with the fear of being stung.

Cross-Sectional Validation of a Quality of Life Questionnaire in Spanish for Patients Allergic to Hymenoptera Venom.

INTRODUCTION AND OBJECTIVES: The first quality of life questionnaire for Vespula-allergic patients (Vespid Allergy Quality of Life Questionnaire [VQLQ) was developed in 2002. Our objective was to perform the cross-sectional validation of the Spanish version of this questionnaire. PATIENTS AND METHODS: Using the original English-language version of the VQLQ as a starting point, the Spanish translation and cultural adaptation were performed and the first Spanish version was backtranslated into English and discussed with the authors of the original version. The result was the Spanish Health-related Quality of Life Questionnaire for Hymenoptera Venom-Allergic Patients (HRQLHA). Cross-sectional validation was carried out in a multicenter study using a test-retest design. Patients over the age of 14 diagnosed with systemic allergic reaction to venom from Apis, Vespula, or Polistes species were included. The test-retest reliability, external validity, and internal consistency of the questionnaire were measured. RESULTS: The sample comprised 116 patients. The mean HRQLHA score was 3.48. Test-retest reliability showed an intraclass correlation coefficient of 0.85. HRQLHA showed a positive correlation (0.5) with an external questionnaire, thus demonstrating its external validity. Analysis of the internal consistency of the HRQLHA yielded a Cronbach α of 0.95, which can be considered to be excellent. CONCLUSIONS: Statistical analysis revealed the high test-retest reliability, internal consistency, and external validity of the HRQLHA. The HRQLHA is the first validated questionnaire to include patients allergic to Polistes species, which is common in our area. Our findings show that the questionnaire is also valid for these patients.

Component-resolved diagnosis of vespid venom-allergic individuals: phospholipases and antigen 5s are necessary to identify Vespula or Polistes sensitization.

BACKGROUND: Cross-reactivity between hymenoptera species varies according to the different allergenic components of the venom. The true source of sensitization must therefore be established to ensure the efficacy of venom immunotherapy. OBJECTIVE: In the Mediterranean region, Polistes dominulus and Vespula spp. are clinically relevant cohabitating wasps. A panel of major vespid venom allergens was used to investigate whether serum-specific IgE (sIgE) could be used to distinguish sensitization to either vespid. METHODS: Fifty-nine individuals with allergic reactions to vespid stings and positive ImmunoCAP and/or intradermal tests to vespid venoms were studied. sIgE against recombinant and natural venom components from each wasp species was determined using the ADVIA Centaur(®) system. RESULTS: sIgE against recombinant antigen 5s sensitization to be detected in 52% of the patients tested (13/25). The sensitivity increased to 80% (20/25), when using natural antigen 5s, and to 100% with the complete panel of purified natural components, because the sIgE was positive to either the antigen 5s (Pol d 5/Ves v 5) or to the phospholipases (Pol d 1/Ves v 1) of the two vespids, or to both components at the same time. In 69% of cases, it was possible to define the most probable sensitizing insect, and in the rest, possible double sensitization could not be excluded. Vespula hyaluronidase was shown to have no additional value as regards the specificity of the assay. CONCLUSIONS: The major allergens of P. dominulus' and Vespula vulgaris' venom, namely phoshpholipases and antigen 5s, are required to discriminate the probable sensitizing species in vespid-allergic patients.

Significance of infrequent and unspecific pathologies recorded in the Spanish Survey Alergológica-2005.

BACKGROUND: There are infrequent or unspecific diseases that occupy an important part of time in the job of the allergists. OBJECTIVE: We sought to evaluate the frequency and to determine the characteristics of uncommon or unspecific diseases seen by allergists in Spain, and to compare these data with findings obtained in a similar study undertaken in 1992. MATERIAL AND METHODS: An observational, prospective and cross-sectional study named "Alergológica 2005" was carried out in Spain. A part of this study analyzed the demographic, healthcare and clinical aspects of infrequent or unspecific diseases categorized as "Other allergic diseases" (OAD) or "Other non-allergic diseases" (ONAD). RESULTS: The survey comprised 4991 patients. In OAD, 45 patients were included. In ONAD, 290 patients were included. Significant diagnoses were gastroallergic anisakiasis (10 patients), idiopathic anaphylaxis (7 patients), and hypersensitivity pneumonitis (2 patients). In the ONAD group, non allergic respiratory diseases were the most frequent diagnosis. Mean time spent to reach a diagnosis was 14.2 days. However, the median of this time was only 1 day. Main diagnostic methods employed were a clinical history/physical examination in 86% of patients and skin tests in 73.7%. CONCLUSION: Several unspecific diseases affected more than 60% of patients in the two groups together. Findings show the current knowledge of allergic disorders due to Anisakis simplex. Diagnoses of hypersensitivity pneumonitis seem to be as frequent as previously published. Idiopathic anaphylaxis seems to be less frequent. The wide-range of times needed to reach a diagnosis was in agreement with the mixture of diseases included in both groups.

Hypersensitivity pneumonitis due to occupational inhalation of fungi-contaminated corn dust.

Hypersensitivity pneumonitis or extrinsic allergic alveolitis can be defined as a lung disease caused by a wide group of antigens that reach the lung by inhalation of organic and/or inorganic dust of various sources. The dust of the stored maize corn has been reported as cause of respiratory symptoms. During the storage process, maize corn dust can be contaminated by moulds and thermophilic actinomycetes, which have not been described until now as the causing antigens of these symptoms. We present a case of occupational hypersensitivity pneumonitis in an agricultural worker who cultured and stored maize corn. Clinical findings, precipitating antibodies, and evolution after having removed him from his work, confirmed the diagnosis. In our case, Aspergillus species contaminating the maize corn dust are probably the antigens that caused the disease.

Bread eating induced oral angioedema due to alpha-amylase allergy.

Inhalation of dust from different enzymes can be the cause of occupational asthma in exposed workers. Enzymes from different sources are being increasingly used in food. Few cases of food allergy to alpha-amylase induced by eating bread have been reported. Those cases were reported in bakery-related patients and in a pharmaceutical-industry worker. A 25-year-old farmer suffered sneezing, rhinorrhea, oropharyngeal itching, hoarseness, cough, and non-wheezy dyspnea after eating white bread. Skin prick tests (SPT) with common aeroallergens and food allergens revealed only sensitization to Olea europaea pollen. SPT response was positive to Aspergillus oryzae alpha-amylase. Specific IgE against alpha-amylase was positive. A double-blind placebo-controlled challenge with 5 mg of uncooked -amylase induced sneezing, cough, oral angioedema within 10 minutes. The provocation test with 50 g of white bread gave similar findings. This case indicates that alpha-amylase contained in bread may provoke IgE-mediated food allergy. It is worth noting that in this case, the only source of alpha-amylases sensitization was bread.

Evaluation of drug-related hypersensitivity reactions in children.

Patients with drug reactions are often referred to allergists for "allergy". Skin testing and clinical history seem to have a good negative predictive value, however, although drug challenge could be dangerous, it is the only way to confirm the diagnosis. We aimed to demonstrate that most children with a history of non-life-threatening drug reactions do not have a true drug allergy and examined the use of drug challenge in childhood. Patients with reactions were referred to our clinic by pediatricians. In 1 year, 354 reactions were studied in 239 children. Patients were classified according to their positive or negative history of drug allergy. Skin prick testing was done in all cases. Exclusion criteria for challenge included drug anaphylaxis, Stevens-Johnson syndrome, systemic reactions with severe concomitant illness, beta-inhibitor drug therapy or positive skin test to the implicated drug with a positive history. It was found that the beta-lactam antibiotics were involved in 50% of suspected reactions, aspirin in 10% and sulfonamides in 9%. Histories were considered positive only in 25%. Drug challenges confirmed only 4% of all reactions. It was concluded that drug challenge may be the gold standard for most childhood reactions that are considered to be allergic, non-life-threatening and drug-related. Only 4% of these suspected reactions were exclusively caused by drug allergy.

Occupational asthma due to carrot in a cook.

BACKGROUND: Few previous reports of carrot-induced asthma have been confirmed by objective tests. Hypersensitivity to carrot is frequently associated with allergy to Apiaceae spices and sensitization to birch and mugwort pollens. CLINICAL CASE: A 40-year-old cook woman was seen with sneezing, rhinorrhea, contact urticaria and wheezing within few minutes of handling or cutting raw carrots. She needed to leave out of the kitchen while the other cooks cut raw carrots. METHODS AND RESULTS: Skin tests were positive to carrot, celery, aniseed and fennel. Rubbing test with fresh carrot was positive. Specific IgE to carrot was 4.44 kU/L. Determinations of specific IgE to mugwort, grass and birch pollens were negative. Inhalative provocation test, performed as a handling test, was positive. The IgE-immunoblotting showed two bands in carrot extract: a band with apparent molecular weight of 30 kd and other band of 18 kd. This band of 18 kd was Dau c 1. The band of 30 kd could correspond a phenylcoumaran benzylic ether reductase. Dau c 1 did not appear to be the unique allergen in this case. Additional allergens may induce the sensitization. Primary sensitization due to airborne allergens of foods and the lack of pollen allergy in this patient are notorious events.

[Sensitization to Castanea sativa pollen and pollinosis in northern Extremadura (Spain)]. / Sensibilización a polen de castaño y polinosis en el norte de Extremadura.

BACKGROUND: Castanea sativa pollen allergy has generally been considered to be uncommon and clinically insignificant. In our geographical area (Plasencia, Cáceres, Spain) Castanea sativa pollen is a major pollen. OBJECTIVE: To determine the atmospheric fluctuations and prevalence of patients sensitized to Castanea pollen in our region and to compare this sensitization with sensitizations to other pollens. METHODS: Patients with respiratory symptoms attending our outpatient clinic for the first time in 2003 were studied. The patients underwent skin prick tests with commercial extracts of a battery of inhalants including Castanea sativa pollen. Serologic specific IgE to Castanea sativa pollen was determined using the CAP system (Pharmacia and Upjohn, Uppsala, Sweden). Airborne pollen counts in our city were obtained using Cour collection apparatus over a 4-year period (2000 to 2003). RESULTS: The most predominant pollens detected were (mean of the maximal weekly concentrations over 4 years in pollen grains/m3): Quercus 968, Poacea 660, Olea 325, Platanus 229, Pinus 126, Cupresaceae 117, Plantago 109, Alnus 41, Populus 40, Castanea 32. We studied 346 patients (mean age: 24.1 years). In 210 patients with a diagnosis of pollinosis, the percentages of sensitization were: Dactylis glomerata 80.4%, Olea europea 71.9%, Fraxinus excelsior 68%, Plantago lanceolata 62.8%, Chenopodium album 60.9%, Robinia pseudoacacia 49%, Artemisia vulgaris 43.8%, Platanus acerifolia 36.6%, Parietaria judaica 36.1%, Populus nigra 32.3%, Betula alba 27.6%, Quercus ilex 21.4%, Alnus glutinosa 20.9%, Cupressus arizonica 7.6% and Castanea sativa 7.1%. Fifteen patients were sensitized to Castanea sativa and 14 had seasonal rhinoconjunctivitis and asthma. Ten patients had serum specific IgE to Castanea pollen (maximum value: 17.4 Ku/l). Castanea pollen is present in our area in large amounts from the 23rd to the 28th weeks of the year, with a peak pollen count in the 25th week. CONCLUSIONS: The most important allergenic pollens in northern Extremadura were Poaceae, Olea europaea and Plantago sp. The prevalence of sensitization to Castanea sativa pollen was very low (7.1%). Most sensitized patients had asthma and polysensitization. Castanea sativa pollen is not a major cause of pollinosis in our area.

Familial presentation of occupational hypersensitivity pneumonitis caused by aspergillus-contaminated esparto dust.

Esparto grass (Stipa tenacissima), which is commonly found in the Mediterranean area, has a wide variety of uses. Five plaster workers from the same family developed cough, dyspnea, malaise, and fever after exposure to the esparto fiber used in their work for the previous few years. They showed a significant decrease in symptoms when away from work. Precipitating antibodies against an esparto extract were found in the sera of all patients. Specific IgG antibodies against Aspergillus fumigatus were detected. A. fumigatus was identified after microbiologic evaluation of esparto fiber samples. The dust derived from fungi-contaminated esparto fibers can cause hypersensitivity pneumonitis in exposed subjects. The causative antigen is A. fumigatus. When esparto fibers were strongly contaminated by fungi, all the workers developed a clinical picture compatible with hypersensitivity pneumonitis. The coincidental finding of an occupational and a familiar condition is unusual.

Anaphylactoid reaction to carboplatin: successful "desensitization".

Carboplatin (CP) hypersensitivity reactions have been reported in nearly 12 % of patients treated with this drug. The pathophysiologic mechanisms of these reactions have not been entirely elucidated. Various hypotheses are under discussion. CP hypersensitivity reactions could be IgE-mediated, caused by low-molecular platinum compounds acting as haptens. Platinum salts are also able to release histamine from basophils and mast cells, and some events seem to be non-immune-mediated direct histamine release. We report a case of CP tolerance induction in a 65-year-old man. During the third course of CP he experienced an anaphylactic reaction. Skin testing was negative. Suspecting the possibility of an anaphylactoid reaction due to histamine release, we developed a protocol to induce tolerance. Pre-medication with corticosteroid and antihistaminic was performed before intravenous CP infusion. The bag with CP was first infused 60 ml/h for 30 minutes; the infusion was well tolerated and infusion was continued at 100 ml/h for the next 60 minutes and thereafter at 120 ml/h until the bag was finished. Following this "desensitization", monthly courses of CP using the same protocol have been well tolerated.

Carbamazepine induced transient monoclonal gammopathy and immunodeficiency.

Immune abnormalities have been found in many patients receiving anti-epileptic drugs. However, the effects of carbamazepine are still conflicting. We report the case of a 31-year-old woman who began carbamazepine treatment because of idiopathic epilepsy of adulthood. After three years of treatment she developed arthralgias and malaise. Complete immunologic evaluation showed a total absence of immunoglobulin M with decreased levels of immunoglobulin A, positive antinuclear antibodies and monoclonal paraproteinemia type IgG-kappa. The possibility of B cell lymphoma or myeloma was ruled out. Skin testing was negative. Bone marrow examination was normal. After carbamazepine discontinuation, levels of IgA and IgM increased until reaching normal values over 3 years. The monoclonal gammopathy of undetermined significance also disappeared over this period. During this period of immunodeficiency, the patient did not complain of any infectious complications.

[Latex sensitization in 28 patients]. / Sensibilización a látex en 28 pacientes.

We present a review of 28 cases of sensitization to latex. Skin prick test for latex was performed in subjects suspected of having allergy to latex and many fruits. Recently, many publications have evidenced the importance of sensitization to latex. There are well documented cases of intraoperatory anaphylaxis. Frequently, this happens to children with congenital urologic malformations, spina bifida or myelomeningocele, who undergo numerous surgical operations and vesical catheterizations. Latex-induced allergy also affects health professionals, since they are continuously in contact with latex-derived materials. There are other studies that relate latex-induced allergy to several fruit allergies (mainly chestnuts, bananas and avocados). In recent literature some discrepancy exists about the reliability of the prick test and the sensibility of in vitro diagnostic methods. We analyze 28 cases of latex sensitization from our clinic, comparing the most severe cases with the remaining subjects. Atopia antecedents were present in 82%, sub-clinical sensitization in 10 cases, urticaria/angioderma in 5, anaphylaxis in 9, and contact dermatitis in 4. Women were majority, with 22 cases versus 6 males. In patients with latex-induced anaphylaxis, the significantly most frequent feature was previous professional exposure to latex (p = 0.004). Specific IgE was measured by radioallergosorbent test (RAST), finding the highest values in the most severe clinical cases (p=0.0016), comparable to the results of the prick test, which still is the best diagnostic method. In our experience, banana and chestnut-induced allergies were the allergies most frequently associated to latex-induced allergy. There were no adverse reactions in any patient after the prick test.