Are basophil activation and sulphidoleukotriene determination useful tests for monitoring patients with peach allergy receiving sublingual immunotherapy with a Pru p 3-enriched peach extract?

INTRODUCTION: Treatment of food allergy essentially consists of food avoidance, but immunotherapy with food is emerging as a new therapeutic option. OBJECTIVE: To evaluate clinical improvement and immunological changes in patients with peach allergy following sublingual immunotherapy (SLIT) with a Prup3 quantified peach extract. METHODS: A randomized, double-blind, placebo-controlled clinical trial with peach SLIT was conducted. We assessed clinical efficacy after 6 months of treatment by means of double-blind, placebo-controlled oral challenges with peach and also evaluated immunological changes (basophil activation test [BAT] and determination of sulphidoleukotriene production) following stimulation with peach peel and pulp, rPrup3, rMald 1, and rMal d 4 stimulation. We also measured specific IgE and IgG4 to Pru p3. RESULTS: After 6 months of SLIT (T6), the active group showed a 3-fold improvement in tolerance to Prup3 and a significant increase in IgE to rPrup3 and in sLT production following stimulation with peach peel and rPrup3. There was also a significant increase in BAT results after stimulation with rPrup3 at 1 month of SLIT (T1). Statistically significant between-group differences were only observed for BAT with peach peel and pulp at T1 and T6 and for BAT with rPru p3 at T6. No changes were observed in BAT with rMal d 1 or rMal d 4 or in IgG4 levels to nPrup3. CONCLUSIONS: SLIT with a Pru p 3 quantified peach extract is clinically effective and leads to an increase in basophil activation and sulphidoleukotriene production following stimulation with rPru p3 and peach peel in the first months of treatment.

[Henna tattooing in children: natural or temporary?]. / Tatuaje de henna en niños: ¿natural y temporal?

BACKGROUND: Tattoos of natural red/brown henna obtained from the indigenous tree Lawsonnia have been traditionally performed with a few side-effects. Nowadays black henna tattoos are usually performed even in children. The addition of several chemical agents to improve its cosmetic properties has increased the risk of developing contact dermatitis after exposure. Our aim is to determine the causative agents of contact dermatitis in two children wearing henna tattoos. MATERIAL AND METHODS: Case 1: A 12-year-old girl with no atopy presented local vesicles 10 hours after a black henna tattoo was applied. She had presented similar symptoms with a previous tattoo. Case 2: A 7-year-old atopic boy presented vesicles 2 weeks after a black henna tattoo was applied. He had dyed his hair previously without side effects. Both patients cured, after 3-4 weeks of treatment with topic corticosteroids, with residual hypo-pigmentation. Skin prick test with natural and commercial henna and epicutaneous test with TRUE-TEST, PABA derivatives compounds tests, textile dyes and natural and commercial henna were performed. RESULTS: The epicutaneous tests were positive for p-Metilaminophenol, p-Aminobencene, p-Phenilendiamine and p-Toluenodiamine in both patients. The first patient had also positive tests for Benzocaine, Hydroquinone, Isobutyl p-aminobenzoate, Yellow 1 and Orange 1 disperse; the second one for Red 1 and Orange 1 disperse. In both cases the prick and epicutaneous tests for henna were negative. CONCLUSIONS: Two children presented contact dermatitis after black henna tattoo due to added additives such as paraphenilendiamine.

[Hypersensitivity Pneumonitis (extrinsic allergic alveolitis)]. / Neumonitis por hipersensibilidad (alveolitis alérgica extrínseca).

Farmer's lung was first described in 1932. We can define hypersensitivity pneumonitis as a pulmonary and systemic disease that is accompanied by dyspnoea and coughing; it is caused by an immunological type of inflammation of the alveolar walls and the terminal airways and it is secondary to the repeated inhalation of a variety of antigens by a susceptible host. It can be said that it is an underdiagnosed disease and only a high degree of clinical manifestations and a detailed history of exposure can lead to an early diagnosis and satisfactory treatment. A combination among clinical-radiological, functional, cytological or pathological findings leads in some cases to a diagnosis. Treatment is based on avoiding further exposure to the causal agent and in the more serious cases the administration of systemic corticoid treatment.

Epidemiology of urticaria in Spain.

BACKGROUND: In spite of the frequency of chronic urticaria there are very few epidemiological studies of its prevalence and distribution. OBJECTIVE: We wanted to approach the real prevalence of chronic urticaria in a population-based study and to depict demographic distribution and personal perception of the disease. We also wanted to describe the frequency of acute urticaria episodes in the population studied. METHODS: We conducted a population-based study among adults in Spain. We questioned 5003 individuals after calculating a sample size for a maximum variability (conservative approach p=q=0.5). RESULTS: We found a 0.6% (95% CI: 0.4-0.8) prevalence of chronic urticaria. The prevalence is significantly higher in women than in men with a OR=3.82 (95%CI 1.56-9.37). Chronic urticaria is a self-limited disease, yet in 8.7% of cases chronic urticaria lasts from one to 5 years and in 11.3%, for more than 5 years. The average age of onset is 40 years. CONCLUSIONS: We offer large epidemiology study data on the prevalence of chronic urticaria. The prevalence of chronic urticaria has not yet been defined in an adult population-based study. With this work we offer such data to describe the prevalence and features of this disease.

Respiratory allergy to peach leaves and lipid-transfer proteins.

BACKGROUND: Several lipid-transfer proteins (LTPs) have been identified as important food allergens, especially in fruits of the Rosaceae family. The major peach (Prunus persica) allergen has been identified, sequenced and designated Pru p 3. OBJECTIVE: To present Pru p 3 as an aeroallergen able to induce occupational asthma. METHODS: A thorough investigation was performed in a fruit grower with occupational asthma. Skin prick-prick tests with peach leaves and prick tests with perennial respiratory allergens and pollens, fruits and peach leaf extracts were done. Serum-specific IgE was tested for peach leaf, peach fruit, peach skin and respiratory allergens that were positive in skin prick tests. Specific bronchial provocation tests (BPTs) with extracts of peach leaf were also done. Before and 24 h after the BPT, BPTs with methacholine and sputum induction were done. The IgE reactivity pattern to peach leaf and fruit extracts and to Pru p 3 was identified by using SDS-PAGE and immunoblotting. Blotting inhibition of peach leaf extract by Pru p 3 was also performed. The putative allergen was quantified in leaf and fruit skin extracts with ELISA based on an anti-Pru p 3 antibody. RESULTS: Skin tests were positive for peach leaf and fruit. The BPT was positive, with immediate and delayed response. This test induced a decrease in PD20 (dose of agonist that induces a 20% fall in FEV1) methacholine and an increase in eosinophils and eosinophil cationic protein in sputum. Peach leaf extract contained concentrations of Pru p 3 similar to those found in peach skin. Specific IgE immunodetection showed that patient's sera reacted with Pru p 3, and with a single major band from the peach leaf extract fully inhibited by Pru p 3. CONCLUSION: Pru p 3 from peach leaves can act as a respiratory allergen and cause occupational rhinoconjunctivitis and asthma.

Diversity of asparagus allergy: clinical and immunological features.

BACKGROUND: Asparagus (Asparagus officinalis) is an extensively grown and consumed vegetable. To a lesser extent than other Liliaceae vegetables, allergic contact dermatitis (ACD) due to asparagus has been reported. However, only a few case reports of asparagus IgE-mediated allergy have been published. In a previous study, we demonstrated that two lipid transfer proteins (LTPs) (Aspa o 1.01 and Aspa o 1.02) were relevant allergens of asparagus. OBJECTIVE: We retrospectively analysed the 27 patients diagnosed with asparagus allergy during the last 5 years. All of them reported adverse symptoms after either asparagus ingestion or handling. We describe their clinical features and evaluate whether they were associated to immunological findings (immunoblot pattern and skin reactivity to LTPs). METHODS: Patients underwent skin prick and patch tests with standard panels of vegetables and aeroallergens. Besides crude asparagus extract, two purified LTPs were prick and patch tested. Total and specific IgE measurements and asparagus extract IgE immunoblotting were performed. Patients reporting asthma symptoms underwent specific inhalation challenge to asparagus. RESULTS: Of the 27 subjects, eight had ACD, 17 had IgE-mediated allergy and two had both ACD- and IgE-mediated allergy. Positive patch tests with the crude asparagus extract but not with LTPs were observed in subjects with ACD (n=10). Of 19 patients with IgE-mediated disease, 10 had contact urticaria after asparagus handling. Of them, five subjects and five others without skin allergy showed respiratory symptoms; of them, eight were diagnosed with occupational asthma confirmed by positive asparagus inhalation challenge, whereas the remaining two had isolated rhinitis. Four patients suffered from immediate allergic reactions related to asparagus ingestion (food allergy); three of them reported anaphylaxis whereas the other had oral allergic syndrome. Positive IgE immunoblotting (bands of 15 and 45-70 kDa) was observed in 10 subjects. Of 10 subjects with positive prick test to LTPs, six showed bands at 15 kDa. Either IgE-binding bands or positive prick tests to LTPs were observed in asthma (62%) and anaphylaxis (67%). CONCLUSION: Asparagus is a relevant source of occupational allergy inducing ACD and also IgE-mediated reactions. Severe disease (anaphylaxis or asthma) is common and LTPs seem to play a major role. The clinical relevance of LTP sensitization among patients with mild disease or symptom-free subjects should be addressed in prospective studies.

Occupational asthma from natural rubber latex. Specific inhalation challenge test and evolution.

BACKGROUND: Natural rubber latex (NRL) is the most frequent cause of occupational respiratory problems in hospital workers. OBJECTIVE: To describe the diagnostic methodology, including the specific inhalation challenge (SIC), used on patients diagnosed as having occupational asthma due to NRL in our Allergy Department during a 6-year period from 1989 to 1995. METHODS: In 19 patients diagnosed as having occupational asthma due to NRL, clinical severity was assessed with a combined score for symptoms and medication use. Skin prick tests with aeroallergens, latex, papain, kiwi and chestnut, total IgE, serum-specific latex IgE, respiratory function study, methacholine test, specific conjunctival test, and SIC test with latex were done. RESULTS: All but three patients worked in hospitals. All presented urticaria and rhinoconjunctivitis, and six also suffered anaphylaxis, usually preceded by asthma. Clinical fruit allergy was present in eight patients. The latency period was variable (0.25-27 years). The intensity of symptoms was low to moderate. Specific IgE, skin prick, and conjunctival tests to latex were positive in all cases. SICs were done in 12 patients. All of them presented isolated immediate reactions. No adverse reactions were observed. Duration of follow-up ranged from 1 to 7 years. Twenty-six percent of the patients kept their job, 26% changed jobs but remained in health care, and 48% switched to jobs unrelated to health care. Only 16% were free of symptoms without treatment, while 32% needed bronchodilators and 52% needed inhaled steroids. The specific bronchial challenge test was safe, but it did not predict the course of the illness. Duration of exposure and intensity of symptoms did correlate with prognosis, however. CONCLUSIONS: NRL acts as a common aerollergen. Minor symptoms often precede occupational asthma. The SIC test was safe in the hands of trained technicians. Occupational asthma due to NRL seems to have a poor prognosis.

[Epicutaneous test with inhalers in the study of atopic dermatitis]. / Test epicutáneos con inhalantes en el estudio de la dermatitis atópica.

In some 80% of patients with atopic dermatitis, the presence of specific IgE is found when facing food or environmental allergens. It has also been demonstrated in a sub-group of patients with atopic dermatitis that the dermatitis lesions are exacerbated following the ingestion or inhalation of allergens, and that they improve with reduction of exposure to allergens. Although the prick method and the determination of specific IgE in serum are highly sensitive techniques, epicutaneous tests, applying the allergen directly to the skin, might be the ideal diagnostic method since they reproduce the characteristic inflammatory response of the disease on the affected organ itself, the skin. However, there is great variability in the results obtained through epicutaneous tests with aeroallergens, basically due to methodological differences, which are reviewed in this paper. Finally, we present the results of carrying out epicutaneous tests with inhalant allergens on our patients with atopic dermatitis and controls, where some 27% of positive patches were obtained, basically with acari, and in those patients with more severe dermatitis, without there being complete concordance with the prick technique. For this reason, the epicutaneous test appears to be a method of allergological diagnosis that might be useful and complementary to the routine techniques of the prick method and the determination of specific IgE in serum, but it is in need of suitable standardization.

[Latex allergy. Clinical manifestations in the general population and reactivity crossed with foodstuffs]. / Alergia al látex. Manifestaciones clínicas en la población general y reactividad cruzada con alimentos.

Because of widespread latex manufacturing in the last decades, latex allergy has become an important clinical problem, not only in high-risk groups (health-workers) but also among the general population. Latex is used to produce a large variety of natural rubber products (medical equipment, household gloves, condoms, balls and balloons, footwear, baby pacifiers...) employed in the ordinary life, with high risk for patients allergic to latex. Among general population, children affected by myelomeningocele or spina bifida, have a higher risk to develop latex allergy. Clinical manifestations range from local reactions(contact dermatitis, urticaria), rhino-conjunctivitis, asthma, pharyngeal edema to severe systemic reactions such anaphylactic shock. Furthermore, latex can crossreact with some plant foods, and patients suffering from latex allergy often associate food allergy.

[Immunotherapy with grouped doses]. / Inmunoterapia con pautas agrupadas.

Once the efficacy and safety of immunotherapy with allergen extracts has been shown, recently it has become evident the need for perfecting those aspects of the treatment that can be improved, such as its dosage form. The conventional dosage of subcutaneous immunotherapy in the phase of dose increase is slow in reaching an efficient level. For this reason other alternative dosages to the conventional one have been tried out, such as grouped dosages, which shorten this period of dose increase. On condition that the safety of the treatment is guaranteed, these doses offer the advantages of reducing the economic cost and the time involved, of reducing the discomfort of the treatment and of improving the patient's adherence to the treatment, and possibly of reaching clinical efficacy more rapidly. Nonetheless, it is not easy to determine the suitable dosage of administration (the shortest and with the least number of adverse reactions) and this article reviews the existing problems when it comes to designing these grouped doses. Finally, we present the results of a comparative study between the conventional dose and a grouped dose, with a double blind design, carried out by us, which shows that the grouped dose is quicker in achieving the desired clinical efficacy, shortens the times of reduction of cutaneous sensitivity to the allergen and of modification of the immunological parameters, all with a low frequency of adverse reactions that is similar to that registered with the conventional dosage.

[Treatment perspectives: immunotherapy with latex]. / Perspectivas de tratamiento: inmunoterapia con látex.

Latex allergy currently constitutes a serious problem because of the severity of its symptoms and the at-risk groups it affects. Since complete avoidance of this substance is practically impossible, in the last few years intense efforts have been made to standardize a latex extract with the aim not only of improving clinical diagnosis but also of being able to offer other therapeutic alternatives, such as specific immunotherapy.Since 1998, reports of immunotherapy with oral (three patients) subcutaneous (one patient) and sublingual latex desensitization (one patient) have been published. In all cases, clinical improvement was evident. In 2000, Laynadier published the first pilot study, a phase IIB multicenter, randomized, double-blind, placebo-controlled trial that evaluated the efficacy and safety of specific immunotherapy with latex in patients with occupational allergy. Twenty health care workers without obvious latex exposure and with latex allergy-induced symptoms of rhinitis and/or asthma were included. Treatment started with a 2-day course of rush immunotherapy in hospital and maintenance therapy was continued for 1 year. Efficacy was assessed by symptom and medication scores and by variation in the conjunctival reactivity threshold. The safety of the extract was also evaluated. In the overall analysis of symptom score, the treated group showed a marked improvement and the medication score was significantly lower in patients in the active treatment group than in the placebo group. Concerning safety, almost half the patients receiving active treatment showed local reactions starting with the first injection and four of the nine patients in this group suffered moderate-to-severe systemic reactions. In view of this first clinical trial, it can be concluded that this treatment is effective but that its tolerance is low.A second clinical trial with the same characteristics and extract is currently underway. Its aim is to validate the previous protocol, confirm the efficacy of specific immunotherapy with latex, improve its safety and, if possible, determine the optimal dose.J. Sastre et al. have recently (Formigal 2002) presented the results of the first double-blind study with latex immunotherapy using an extract standardized by the ALK-Abelló-España group. The authors included 24 patients with latex sensitization and symptoms of occupational allergy. To diagnose respiratory allergy, an inhalation challenge was performed in a closed 7-m2 chamber and, in case of contact urticaria, glove-wearing and rubbing tests were performed, using a vinyl glove as negative control. Treatment consisted of a first phase of incremental doses for 14 weeks, with 18 injections, followed by maintenance doses for 6 months. Sixteen patients received active treatment and 8 received placebo. Of the 578 doses administered, adverse effects were observed in 41 (7.1 %). There were 21 immediate systemic reactions (5.7 % of the doses) and 10 delayed systemic reactions (2.6 % of the doses). Adverse effects were more frequent in patients with underlying respiratory disease (p < 0.05). After 6 months' treatment, a clear improvement in the cutaneous response index was found in the active treatment group and in the rubbing and glove-wearing tests. The authors conclude that the immunotherapy tested was a high-risk treatment and that the greatest clinical improvement was found in cutaneous symptoms.In conclusion, although effective, latex immunotherapy is currently a high-risk treatment.

Liposome-entrapped D. pteronyssinus vaccination in mild asthma patients: effect of 1-year double-blind, placebo-controlled trial on inflammation, bronchial hyperresponsiveness and immediate and late bronchial responses to the allergen.

BACKGROUND: Allergen vaccination is effective in mite-allergic asthma. Liposomes are immunological adjuvants that can act as allergen carriers. OBJECTIVE: To evaluate the immunological and functional effects of a liposome-entrapped D. pteronyssinus vaccine on mite monosensitive, mild asthma patients. METHODS: A double-blind, placebo-controlled trial was conducted on 26 asthma patients who randomly received vaccination or placebo for 1 year. The levels of exposure to Der p 1 allergen were constant during the study. Allergen bronchial challenge was made at the beginning (T0) and after 1 year of treatment (T12). The day before and 24 h after the allergen provocation, patients were challenged with methacholine (Mth) (until FEV1 fell by 40%) and blood and sputum samples were obtained. Dose-response curves to Mth were evaluated in terms of Mth-PD20 (dose of Mth that induced 20% drop in FEV1), slope (Mth-DRS) and level of plateau. Blood and sputum eosinophils and serum levels of eosinophil cationic protein (ECP) and intercellular adhesion molecule-1 (ICAM-1) were measured. RESULTS: Groups were comparable at the start of the trial. At TI2, previous to the allergen challenge, the active group showed higher values of both FEV1 and Mth-PD20 and lower values of Mth-DRS. The number of patients presenting a level of plateau increased in the active group (from two to four) and decreased in the placebo group (from two to one). At T12, before the allergen challenge, serum ECP levels increased in the placebo group and blood eosinophils showed a trend towards lower numbers in the active one. The immediate response and the changes in Mth-DRS values, sputum eosinophils and serum ECP levels following the allergen challenge were attenuated in the active group. CONCLUSION: Liposome-entrapped D. Pteronyssinus vaccination: (i) protects mild asthma patients from the worsening of asthma due to sustained mite exposure; and (ii) reduces the functional and inflammatory changes induced by allergen bronchial provocation.

Tolerance of immunotherapy with a standardized extract of Alternaria tenuis in patients with rhinitis and bronchial asthma.

We studied the safety of immunotherapy with an Alternaria extract in patients with rhinitis and bronchial asthma. The few studies that have investigated immunotherapy with mold allergens suggest that they cause adverse reactions more frequently than do other extracts. All treatments prescribed by our allergology service with Alternaria immunotherapy between 1988 and 1996 were recorded and analyzed. In all cases a biologically standardized depot extract of Alternaria tenuis containing 5 BU/ml was used according to a conventional immunotherapy schedule. During the study period 129 patients received immunotherapy with Alternaria extract. Of the 3,892 doses given, 1.95% led to adverse reactions, which occurred in 39.5% of the patients. Most of the adverse reactions were systemic and mild, and reproduced the underlying disease. The risk of adverse reactions was significantly higher in children, patients with asthma, and during the initial phase of treatment. Patients who suffered from adverse reactions had a significantly higher level of total and specific IgE. It was concluded that tolerance of Alternaria mold extract was worse than for other allergenic extracts, although most reactions recorded were mild. The risk of adverse reactions was greater in children and patients with asthma, and during the initial phase of immunotherapy.

Occupational allergic contact dermatitis due to airborne spiramycin.

We report the case of a man who worked in a feed factory. He developed allergic contact dermatitis due to airborne spiramycin, a commonly used antibiotic in veterinary medicine. The patient suffered recurrent outbreaks of eczematous lesions on uncovered areas during working periods. Diagnosis was made based on history, positive patch tests to spiramycin and to some feed compounds containing spiramycin, and on disappearance of lesions on leaving the work place.

Anaphylaxis from cow's milk casein.

The case of a 35-year-old woman who suffered anaphylaxis after the ingestion of milk or milk-containing products is presented. Symptoms also appeared after the patient used a cosmetic which contained casein. Skin prick tests, specific IgE measurement, and immunoblotting were carried out with cow's milk extract, and its purified proteins: casein, beta-lactoglobulin, and alpha-lactalbumin. Specific IgE to cow's milk casein was detected with the three tests. Immunoblotting revealed one band of 24 kDa approximately corresponding to the beta-fraction of casein. Negative results to beta-lactoglobulin and alpha-lactalbumin were obtained with the three methods. Symptoms were controlled by rigorous dietary and behavior measures.

Diversity of allergens causing occupational asthma among cereal workers as demonstrated by exposure procedures.

BACKGROUND: Occupational asthma among cereal workers is frequently due to cereals but other allergens can also be responsible. OBJECTIVE: We evaluated the allergens causing occupational asthma in the patients who had been diagnosed in our Department during the last 5 years. Specific bronchial reactivity to the implicated allergens was assessed and compared by standardized bronchial challenge. METHODS: Twenty-one patients (12 bakers, three millers and six farmers) were studied. We carried out in vivo tests (skin and challenge tests) and in vitro tests (specific IgE measurement) with cereals, enzymes, soyabean, storage mites and egg. A definitive diagnosis was established by means of specific bronchial provocation tests (BPT), except in three patients in whom it could not be carried out due to the severity of their asthma. In these cases the causative agent had to be determined by means of conjunctival challenge. RESULTS: Cereals were the main sensitizers among bakers (75%) and farmers (66%). Bakers were also sensitive to alpha-amylase (41%) and soyabean (25%), and farmers, to soyabean (33%) and storage mites (33%). Occupational asthma was due to cereals, soyabean and storage mites among millers. CONCLUSIONS: Besides cereals, other allergens such as enzymes, leguminous, egg and storage mites can be the causative agents of occupational asthma among cereal workers. Sensitization to different allergens in the different jobs is very likely due to differences in exposure.