Galactose-α-1,3-galactose (alpha-gal) allergy: first pediatric case in a series of patients in Spain.

INTRODUCTION AND OBJECTIVES: Allergy to galactose-α-1,3-galactose (alpha-gal) is a peculiar form of food allergy generally manifesting as an anaphylactic reaction hours after mammalian meat consumption, due to the presence of specific IgE against this oligosaccharide. In addition, immediate anaphylaxis may develop after exposure to other sources of alpha-gal, such as monoclonal antibody cetuximab, vaccines, plasma expanders or anti-snake venoms. Sensitization to alpha-gal has also been implicated in the rapid degeneration of biological valve implants, and recognized as a cause of occupational disease in cattle raisers. The implication of tick bites in this type of sensitization has been accepted by all the research groups dedicated to this disease. PATIENTS AND METHOD: The present study describes the clinical and sensitization characteristics of 39 patients diagnosed with alpha-gal allergy in the hospitals of our province (Lugo, Monforte de Lemos and Burela, Spain). RESULTS: Most patients were middle-age males. Of note, is the fact that the series includes the first pediatric patient reported in Spain to date. The predominant clinical manifestations were urticaria or delayed anaphylaxis after consumption of mammalian meat. Seventy-four percent of the patients reported having suffered a previous tick bite, and the clinical presentation of anaphylaxis was significantly more prevalent in those with a persistent local reaction following the bite than in those with no such reaction (p = 0.032). CONCLUSIONS: A review is also made of the disorder which, due to its variable clinical expression, is referred to as alpha-gal syndrome. The study concludes that a diagnosis of alpha-gal allergy should be considered in patients with urticaria-anaphylaxis of uncertain origin or manifesting after the administration of vaccines or products of bovine/porcine origin.

Serum tryptase concentrations in beekeepers with and without Hymenoptera venom allergy.

BACKGROUND: Increased tryptase concentrations are a risk marker for the severity of reactions to Hymenoptera stings or venom immunotherapy OBJECTIVE: To investigate serum tryptase concentrations in beekeepers with and without Hymenoptera venom allergy (HVA). METHODS: Serum tryptase concentrations were measured in adult patients with HVA (n = 91, 37 of whom were beekeepers), beekeepers without HVA (n = 152), and control individuals from the general adult population (n = 246). RESULTS: Multivariate analyses revealed that serum tryptase levels were positively associated with beekeeping activities (P < .001) and HVA (P < .001). Tryptase levels were also positively associated with age (P < .001) and male'sex (P = .02), and negatively associated with alcoho consumption (P = .002). CONCLUSIONS: Beekeeping and HVA are independently associated with increased concentrations of serum tryptase.

Profilin as an aeroallergen by means of conjunctival allergen challenge with purified date palm profilin.

BACKGROUND: The role of profilin as a food allergen is well established, but little research has been done about its ability to elicit respiratory disease. Profilin is considered more of a confounding allergen on skin testing with whole pollen extracts than other airborne allergens. Our aim was to find out whether or not profilin can cause symptoms in sensitized individuals, which would be compatible with its role as an airborne allergen. METHODS: We performed conjunctival allergen challenges with date palm profilin in a series of consecutive pollen-allergic patients with rhino-conjunctivitis, divided in two groups: profilin sensitized (n = 17) and not sensitized (n = 14), who served as controls. We investigated the possible association between profilin sensitization and profilin allergy in these groups of patients. RESULTS: None of the patients from the not profilin-sensitized group had a positive result in conjunctival allergen challenges. In contrast, 65% of profilin sensitized patients had a positive conjunctival allergen challenge and were considered allergic to profilin. We found a significant statistical association between being profilin allergic and being profilin sensitized (χ(2) = 10.39, p < 0.005). CONCLUSIONS: Profilin seems to work as an aeroallergen in a significant proportion of profilin-sensitized patients. This might explain the uselessness of conjunctival challenges with whole pollen extracts to disclose genuine sensitization. In the future, the possibility of quantifying this allergen in pollen immunotherapy vaccines should be considered.

Postmarketing study for assessment of tolerability of a grass allergen immunotherapy tablet (GRAZAX) in patients with rhinitis or rhinoconjunctivitis.

BACKGROUND AND OBJECTIVE: Many patients with grass pollen allergy in Spain have concomitant sensitization to other allergens such as profilin. Since this type of sensitization is more common in Mediterranean countries than in countries where most patients were enrolled in clinical trials on GRAZAX (Phleum pratense 75,000 SQ-T/2, 800 BAU, ALK), the aim of this study was to analyze tolerability to GRAZAX under clinical practice conditions in patients with grass pollen allergy. METHODS: A total of 155 patients were enrolled consecutively in a prospective, open-label, observational study. Adverse reactions were recorded during the first month of treatment at 3 different timepoints: after the first dose, when patients were kept under observation for 30 minutes, and on days 15 and 30 after starting treatment RESULTS: With the first dose, 117 adverse reactions were recorded in 63 patients (40.7%). The commonest reactions (>10% patients) were oral pruritus (25.2%) and throat irritation (24.5%). Ear pruritus was recorded in 7.7%. All reactions but 1 occurred within 30 minutes of administration and all were mild-to-moderate. At the end of treatment, the percentage of patients with adverse reactions had decreased significantly (21.3%). Most adverse reactions (95.2%) were mild-to-moderate and only 3 (1.4%) were severe. No serious adverse reactions were recorded. CONCLUSION: GRAZAX seems to be well tolerated, and most reactions were mild-to-moderate. Many of these reactions occur with the first dose. Therefore, according to the Summary of Product Characteristics, the first dose has to be administered under medical supervision.

Exhaled nitric oxide predicts control in patients with difficult-to-treat asthma.

We aimed to evaluate the accuracy of baseline exhaled nitric oxide fraction (F(eNO)) to recognise individuals with difficult-to-treat asthma who have the potential to achieve control with a guideline-based stepwise strategy. 102 consecutive patients with suboptimal asthma control underwent stepwise increase in the treatment with maximal fluticasone/salmeterol combination dose for 1 month. Then, those who remained uncontrolled received oral corticosteroids for an additional month. With this approach, 53 patients (52%) gained control. Those who achieved control were more likely to have positive skin results (60.4% versus 34%; p = 0.01), positive bronchodilator test (57.1% versus 35.8%; p = 0.02) and peak expiratory flow variability > or =20% (71.1% versus 49.1%; p = 0.04). Conversely, depression was more frequent in those who remained uncontrolled (18.4 % versus 43.4 %; p = 0.01). An F(eNO) value > or =30 ppb demonstrated a sensitivity of 87.5% (95% CI 73.9-94.5%) and a specificity of 90.6% (95% CI 79.7-95.9%) for the identification of responsive asthmatics. The current results suggest that F(eNO) can identify patients with difficult-to-treat asthma and the potential to respond to high doses of inhaled corticosteroids or systemic steroids.

Double (honeybee and wasp) immunoglobulin E reactivity in patients allergic to Hymenoptera venom: the role of cross-reactive carbohydrates and alcohol consumption.

BACKGROUND: Immunoglobulin (Ig) E-mediated sensitization to N-glycans (cross-reactive carbohydrate determinants, CCDs) may induce double IgE reactivity to honeybee venom (HBV) and yellow jacket venom (YJV) in patients who are monosensitized to either of these venoms. Alcohol consumption is associated with increased IgE levels and possibly with sensitization to CCDs in the general population. OBJECTIVES: This study investigated the factors associated with double (HBV and YJV) IgE reactivity in patients who are allergic to Hymenoptera venom, and in particular, alcohol consumption. METHODS: Ninety-one patients with Hymenoptera allergy (68 to HBV, 19 to YJV, and 4 to both venoms) were studied. Determinations included a multiallergen IgE test and IgE to HBV, YJV, natural (glycosylated) HBV phospholipase-A2 (nPLA2), recombinant (nonglycosylated) HBV phospholipase-A2 (rPLA2), MUXF (the N-glycan from bromelain), natural (glycosylated) rubber latex, total IgE. Double reactivity was defined as an IgE level > 0.35 kU(A)/L to HBV and YJV. RESULTS: Double reactivity was observed in 28/87 (32%) clinically monosensitized patients. Double reactivity was associated with high levels of total IgE, MUXF-specific IgE, nPLA2-specific IgE, latex-specific IgE, and false-positive results in the multiallergen IgE test, but not with rPLA2-specific IgE. Alcohol consumption was associated with double reactivity and with high levels of IgE to glycosylated allergens after adjusting for confounders in the multivariate analysis. CONCLUSIONS: Sensitization to CCDs and clinically irrelevant double (honeybee and wasp) IgE reactivity are common among Hymenoptera venom-allergic patients who drink alcohol. A simple questionnaire about alcohol consumption could be useful when interpreting levels of specific IgE in these patients.

Follow-up of venom immunotherapy (VIT) based on conventional techniques and monitoring of immunoglobulin E to individual venom allergens.

OBJECTIVES: To assess the efficacy of venom immunotherapy (VIT) and monitor changes in in vivo and in vitro test results after 5 years of treatment and subsequent follow-up. To study the profile of immunoglobulin (Ig) E to individual allergens prior to treatment and 1 year afterwards. METHODS: We studied 562 patients with hymenoptera venom allergy (438 to bee, 124 to wasp), all of whom underwent immunotherapy with Apis or Vespula extract. The patients were followed up using conventional in vivo and in vitro tests, and in 51 cases, specific IgE against the main hymenoptera allergens was measured before starting and after 1 year of treatment. RESULTS: Of the 387 patients who completed VLT, 130 sensitized to Apis and 68 to Vespula suffered spontaneous re-stings during treatment. Of these, 123 (94.6%) did not suffer any reaction and 64 (94.1%) suffered only a local reaction. Sixty-two patients sensitized to Apis and 14 sensitized to Vespula suffered spontaneous re-stings after stopping treatment. Only 3 patients suffered a systemic reaction (grade I Müller). At the end of treatment, the results of skin tests and specific IgE to whole extract improved significantly. Reductions in IgE to the main allergens were observed after 1 year of treatment (median differences in Ves v 5, -238.0, P = .0425; and in Api m 1, -183.0, P = .0024). CONCLUSION: The high rate of spontaneous re-stings shows that efficacy is maintained for years after completing treatment in a real-world setting. Determination of IgE to individual venom allergens may offer new perspectives in the diagnosis and follow-up of these patients.

House dust mite species and allergen levels in Galicia, Spain: a cross-sectional, multicenter, comparative study.

BACKGROUND AND OBJECTIVES: Mites are important sources of allergens in Galicia, Spain. The objective of this study were to identify the main mite species and to determine allergen levels in mattresses from different locations in Galicia. MATERIAL AND METHODS: Dust samples were collected with a portable vacuum cleaner for 2 minutes from 2 m2 of the surface of the mattress used by mite allergic patients and controls. After collection, samples were immediatel frozen. Mite species were collected, identified, and counted, and the results expressed as mites per gram of dust. Mite allergen levels (Der p 1 and Der f 1) were measured using monoclonal antibodies. All individuals answered a questionnaire about the characteristics of their homes. RESULTS: A total of 332 dust samples were collected (112 from mite allergic patients and 220 from controls). Thirty-two species were identified. The mean age +/-SD of all the participants was 32.4 +/- 20.8 years and of the mattresses 7.6 +/- 5.9 years. The geometric mean of the total mite counts was 910.2 mites per gram (896.2 mites per gram in the mattresses of mite allergic patients and 917.3 in the mattresses of control subjects; P > .05). The main species was Dermatophagoides pteronyssinus, which was present in 97.6% of the samples (geometric mean, 584.7 mites per gram). The geometric mean level of Der p 1 was 13.1 microg/g of dust: 11.9 in the mattresses of mite allergic patients and 13.8 in the mattresses of control subjects. The geometric mean level of Der f1 was 1.1 microg/g: 1.5 in the mattresses of mite allergic patients and 0.8 in the mattresses of control subjects. Environmental risk factors associated with high mite counts included obvious signs of humidity in the bedroom and the age of the mattress. CONCLUSIONS: The mite fauna in Galicia is comprised of many species, several of which are known to be of allergologic importance. The total population is exposed to very high levels of mite allergens.

High efficacy and absence of severe systemic reactions after venom immunotherapy.

The efficacy of immunotherapy with venom (ITV) is supported by many studies. However, the key point for ITV is the balance between safety and efficacy, as concern for adverse events may restrict its use, and limit the administration of this treatment to the hospital, exclusively. The objectives of the present study were, first, to analyze the characteristics and incidence of ITV-related adverse events and to determine whether the administration of this treatment exclusively in hospitals is justified, and second, to assess the efficacy of a semi-rush dosage schedule, which is being used in our department. We analyzed the data of 241 patients with known allergy to hymenoptera venom (208 sensitive to Apis mellifera and 33 to Vespula spp.), who were treated with ITV (Pharmalgen, ALK-ABELLO) for an average period of 32 months. The initial treatment was performed at the Allergy Department, administering nine increasing doses of the venom once or twice a week. Maintenance treatment, whenever possible, was performed at primary care centers (PCCs). In this study, 95 patients (39%) were referred to their corresponding PCC. A total of 3697 doses were administered, and 37 systemic reactions (SR) and 37 local reactions (LR) were recorded; the overall frequency of occurrence of adverse events was 1.97%, 1% corresponding to SR, and 1% related to LR. The severity of most of SR was mild and the response to treatment with oral antihistamines and corticoids was good. Administration of adrenaline was required in 14 cases. Regarding the maintenance treatment administered at PCCs, only two adverse events were recorded, one case of vaso-vagal symptomatology and one case of urticaria-like reaction two hours after the administration. Eighty-four cases of spontaneous field stings, corresponding to 58 patients, were reported; in 82 cases (97.6%) the reaction was less severe than that experienced before the administration of ITV. The severity of the other two reactions was the same as previously recorded, though they occurred in patients during the build-up phase of the treatment. In any case, a reaction with a higher grade of severity was recorded. The dosage schedule administered is efficient, the frequency of occurrence of adverse events is low, their intensity is generally mild, and minimum medication is required to control them (antihistamines, corticosteroids). Taking into account the tolerance observed during the maintenance treatment, we consider that its administration at PCCs is appropriate.

Factors influencing the clinical picture and the differential sensitization to house dust mites and storage mites.

Sensitization to house dust mites and storage mites has been studied in a number of papers, but several environmental factors and clinical conditions that differently affect sensitization to these mites are still controversial. The purpose of this study was to determine the influence of climatic conditions, occupation and patient age in the differential sensitization to house dust and storage mites, and also to search for possible different symptoms caused by each group of mites. Eighty patients sensitized to mites but not to other inhalant allergens were studied by case history and by skin prick test and serum IgE to Dermatophagoides pteronyssinus. Dermatophagoides farinae, Lepidoglyphus destructor and Tyrophagus putrescentiae. Home conditions, including content of the allergens Der p 1, Der f 1, Lep d 2 and Tp, were determined for all patients. Human activities, such as farming or similar occupations, and humidity are conditions for preferential sensitization to storage mites, while we found no difference between living in rural or urban areas. Mean age for the onset of sensitization was 6.7 years for house dust mites and 18.7 years for storage mites. Conjunctivitis was more frequent in patients allergic to storage mites, whereas perioral syndrome (itching of the tongue and swelling of the lips) was only seen in patients sensitized to T. putrescentiae. We concluded that climatic and damp conditions and human activity, but not urban or rural living environments, influence the differential sensitization to house dust mites and storage mites.

[Childhood asthma and viral infection: interactions and therapeutic possibilities]. / Asma infantil e infección vírica: interacciones y posibilidades terapéuticas.

Rhinovirus infections are the main cause of wheezing in children and adults. Studies carried out with experimental infections report that at least in certain conditions, this infection may spread to the lower respiratory tract as the virus acts on the respiratory epithelium. In vitro experiments with cells from the immune system and lower respiratory tract suggest that the mechanisms of action are directly linked to the production of pro-inflammatory cytokines. Both in vivo and in vitro evidence shows that rhinoviruses may stimulate bronchial epithelial cells to produce cytokines and pro-inflammatory chemokines. They may also stimulate the cholinergic and non-cholinergic nervous system, increasing the production of ICAM-1 and may give rise to a T-lymphocyte non-specific response or to T-lymphocyte replication in direct relation with viral infection. In addition, greater production of cysteinyl leukotrienes has been observed in the secretions of patients with bronchospasm. Experimental infection with Rhinovirus increases clinical symptomatology and bronchial hyperreactivity. The latter is associated with increased eosinophils and cationic proteins in sputum. The above findings suggest that multiple cellular pathways are involved in the induction of exacerbations of asthma induced by the virus. In addition, the possible stimulating role of exposure to allergens in sensitized patients would also increase allergic inflammation. Because of the limited therapeutic efficacy of steroids in reducing exacerbations, new treatment strategies based on greater insight into the physiopathology of the role of viruses in asthma are needed.

[Preventive immunotherapy]. / Inmunoterapia preventiva.

Allergen specific immunotherapy has been shown to be effective in rigorous double-blind placebo-controlled clinical trials in both children and adults A recent WHO position paper stated that immunotherapy is an effective treatment for patients with allergic rhinitis/conjunctivitis, allergic asthma and allergic reactions from stinging insects and is thought to be more effective in children than in adults. When speaking about children there are several questions that are important regarding the natural course of the disease. One of the most important is whether immunotherapy can prevent asthma, either by preventing sensitisation to allergens related to the development of asthma or by preventing the inflammation in the lungs caused by allergen exposure. Another point could be to establish the differences in the long term outcome of those patients treated with immunotherapy and medication during childhood, compared to the long term outcome of those with comparable asthma features who received only antiasthmatic medication The PAT study is a European multi-center study. The end-point is to show in what capacity allergen specific subcutaneous immunotherapy can prevent the development of asthma in children who only have rhinoconjunctivitis secondary to grass or birch pollen sensitisation. Two hundred and ten children aged from 5 to 13 years were included in the study. Children were randomised to the active treatment group receiving allergen specific immunotherapy with birch and/or timothy pollen allergen extract or to the control group receiving only pharmacotherapy. It is important to highlight that the main criteria to be included was that the children should never have had any asthmatic symptom. Immunotherapy has been effective in terms of decreasing significantly the amount of symptoms in the active group compared to the control one. It was safe with no serious adverse reactions and reduced the risk of the onset of asthma. After two years of treatment more children in the control group developed clinical asthma than in the active group: p = 0.004. Des Roches et al reported the results of a prospective non randomised trial of immunotherapy with Dermatophagoides pteronyssinus in 44 asthmatic children younger than six years of age who were sensitive only to dust mites. The purpose of the study was to assess whether immunotherapy could reduce the development of new sensitisation during a period of three years of follow up. Specific immunotherapy was given with only D. Pteronyssinus extract. All 22 children in the control group developed new sensitivities as determined by skin testing and in vitro tests, while 10 (45%) of 22 children who received mite immunotherapy did not develop additional sensitivities. The findings of this study suggests that immunotherapy may alter the natural course of the allergic sensitisation reducing the risk of developing new sensitisation in mono sensitive children. A limited number of studies have examined the long terms effects of immunotherapy on the clinical presentation of asthma and rhinoconjunctivitis, and have shown a long lasting efficacy decreasing the amount of symptoms 6-10 years after termination. In a retrospective study of children treated with immunotherapy during childhood for at least three years, that were re-evaluated in early adulthood, the control patients who were treated with medication and no immunotherapy suffered almost 3.5 times more symptoms than the active group treated with immunotherapy. The current findings suggest that immunotherapy should be considered earlier in the course of allergic disease to prevent progression or to prevent the development of new sensitisation. Further studies with long term follow up particularly in children could address this possibility.