Background: In children with egg protein allergy (EA), the probability of overcoming the allergy decreases with age, and the possibility of suffering severe adverse reactions as a consequence of dietetic transgressions results in worsened quality of life. One treatment option in such cases is oral immunotherapy (OIT) with foods. Methods: We present a cohort of children with EA scheduled for OIT with pasteurized raw egg white, describing their clinical and allergic characteristics before the start of OIT. Results: The median age was six years, and 93% of the patients also suffered other allergies (58% asthma and 38.6% allergy to more than two food groups). In the last year, 14.8% had suffered a severe reaction due to dietetic transgression with egg. The median IgE specific of egg white titer was 38.5 KM. A double-blind placebo-controlled food challenge with cooked egg white was performed, and if the test proved positive, it was repeated with pasteurized raw egg white. The mean symptoms-provoking dose was 1.26 g and 0.55 g for cooked egg white and raw egg white, respectively. An IgE specific of ovomucoid titer of <2.045 kU/l differentiated those patients that tolerated cooked egg white. Conclusions: OIT with egg is regarded as an option in patients with persistent egg allergy. In the previous challenge test, an IgE specific of ovomucoid titer of <2.045 kU/l differentiates those patients that tolerate cooked egg white. (C) 2018 SEICAP. Published by Elsevier Espana, S.L.U. All rights reserved.

Background: Leukotrienes (LT), isoprostanes, and nitrites/nitrates are biomarkers of airway infl ammation and oxidative stress that can be detected in exhaled breath condensate (EBC). The aim of this study was to evaluate LTB4, LTE4, 8-isoprostane, and nitrite/nitrate levels in the EBC of healthy and wheezing preschool children. Methods: We included 21 healthy nonatopic children and 25 patients with recurrent wheezing episodes in a cross-sectional study. LTB4, LTE4, and 8-isoprostane concentrations were measured directly in EBC using a specifi c enzyme immunoassay; nitrite/nitrate concentrations were measured using a colorimetric assay. Results: LTB4 concentrations were higher in children with wheezing episodes than in healthy controls (76 pg/mL vs 20 pg/mL, P<.001). LTE4 was increased in children with wheezing episodes than in healthy controls (68 pg/mL vs 35 pg/mL, P<.001). Nitrite concentrations were higher in children with wheezing episodes than in healthy controls (14 pg/mL vs 9.7 pg/mL, P<.03). We found no differences in 8-isoprostane and nitrate concentrations between the patients and the healthy controls. Conclusions: Our fi ndings suggest that EBC is a suitable noninvasive method for the assessment of airway infl ammation and oxidative stress in preschool children. Levels of LTB4, LTE4, and nitrites were higher in children with recurrent wheezing episodes than in healthy controls.

Orange (Citrus sinensis) fruit and juice are widely consumed in Europe. Oranges belong to the Rutaceae family, members of which are found in warm regions worldwide and also include limes, lemons, tangerines, and grapefruit. Despite their wide consumption, sensitization to Rutaceae is rare, but the diagnosis should not be overlooked.1Barasona Villarejo M.J. García Núñez I. Moreno Aguilar C. Guerra Pasadas F. Sensibilización a naranja y limón.J Investig Allergol Clin Immunol. 2011; 21: 243Google ScholarOranges are clinically relevant allergenic fruits. Reports describe allergic reactions from eating fresh orange skin and pulp or drinking juice or soda,1Barasona Villarejo M.J. García Núñez I. Moreno Aguilar C. Guerra Pasadas F. Sensibilización a naranja y limón.J Investig Allergol Clin Immunol. 2011; 21: 243Google Scholar, 2Ibáñez M.D. Sastre J. Martínez San Ireneo M. Laso M.T. Barber D. Lombardero M. Different patterns of allergen recognition in children allergic to orange.J Allergy Clin Immunol. 2004; 113: 175-177Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar with symptoms including oral allergy syndrome, urticaria, and atopic dermatitis. Systemic reactions are reported, and case reports describe the development of food-dependent, exercise-induced anaphylaxis after orange ingestion.3Morimoto K. Tanaka T. Sugita Y. Hide M. Food-dependent exercise-induced anaphylaxis due to ingestion of orange.Acta Derm Venereol. 2004; 143: 152-153Crossref Scopus (19) Google Scholar Oropharyngeal symptoms (oral allergy syndrome), an association with hay fever, and sensitization to other plant foods are the most common manifestation of orange allergy.4López Torrejón G. Ibáñez M.D. Ahrazem O. Sánchez-Monge R. Sastre J. Lombardero M. et al.Isolation, cloning and allergenic reactivity of natural profilin Cit s 2, a major orange allergen.Allergy. 2005; 60: 1424-1429Crossref PubMed Scopus (61) Google ScholarThree major allergens have been described to date in orange peel and pulp: Cit s 1 (germin-like protein, 23 kDa), Cit s 2 (profilin, 14 kDa), and Cit s 3 (nonspecific lipid transfer protein [LTP], 9 kDa).4López Torrejón G. Ibáñez M.D. Ahrazem O. Sánchez-Monge R. Sastre J. Lombardero M. et al.Isolation, cloning and allergenic reactivity of natural profilin Cit s 2, a major orange allergen.Allergy. 2005; 60: 1424-1429Crossref PubMed Scopus (61) Google Scholar, 5Ahrazhem O. Ibáñez M.D. López Torrejón G. Sánchez Monge R. Sastre J. Lombardero M. et al.Lipid transfer proteins and allergy to oranges.Int Arch Allergy Immunol. 2005; 137: 201-210Crossref PubMed Scopus (62) Google Scholar, 6Crespo J.F. Retzek M. Foetisch K. Sierra-Maestro E. Cid-Sanchez A.B. Pascual C.Y. et al.Germin-like protein Cit s 1 and profilin Cit s 2 are major allergens in orange (Citrus sinensis) fruits.Mol Nutr Food Res. 2006; 50: 282-290Crossref PubMed Scopus (43) Google Scholar Although most reported cases of orange allergy are due to ingestion of fresh fruit or derived products (eg, juice and jam), contact allergy to citrus peel oil should be considered in patients with hand dermatitis who are occupationally exposed to citrus fruits.7Cardullo A.C. Ruszkowski A.M. DeLeo V.A. Allergic contact dermatitis resulting from sensitivity to citrus peel, geraniol, and citral.J Am Acad Dermatol. 1989; 21: 395-397Abstract Full Text PDF PubMed Scopus (52) Google Scholar Occupational asthma in persons employed in removing the peel from oranges to produce the enzyme (pectinase and glucanase) solution used in soaking the fruits has been reported.8Sen D. Wiley K. Williams J.G. Occupational asthma in fruit salad processing.Clin Exp Allergy. 1998; 28: 363-367Crossref PubMed Scopus (19) Google Scholar However, no cases of allergic respiratory symptoms caused by orange peel allergens have been reported.Fruits with thick peels, such as oranges, are classified as hesperidia, and contain an inner layer of peel called the mesocarp (the white albedo or pith) and an outer layer of peel called the exocarp (flavedo or zest), which together form the peel. Flavedo is mostly composed of cellulosic material but also contains other components, including essential oils, paraffin waxes, steroids and triterpenoids, fatty acids, pigments (carotenoids, chlorophylls, and flavonoids), bitter principles (limonene), and enzymes (α-D-glucosidase, α-D-mannosidase, α-L-arabinosidase, β-D-glucosidase, β-D-xylosidase, and β-D-galactosidase).We report the case of a 22-year-old woman with a family history of atopy. The medical history revealed perennial rhinoconjunctivitis and persistent moderate bronchial asthma caused by sensitization to dust mites (Dermatophagoides pteronyssinus and Dermatophagoides farinae). The patient received specific immunotherapy for 5 years with a mix of Dermatophagoides species, but rhinitis and symptoms of mild intermittent asthma persisted. Currently, she requires occasional symptomatic treatment and also presents with discrete seasonal exacerbations during the spring caused by allergy to Parietaria species pollen.Some months ago, the patient presented with intense dyspnea, coughing, and wheezing triggered by the handling (peeling) of oranges or after entering a room where different varieties of freshly picked or bought-in oranges were being peeled, resulting in having to leave the room. The symptoms disappeared after inhalation of a dose of terbutaline. The patient reports tolerating orange pulp and juice well.Skin tests for common aeroallergens in the Valencia region were positive for mites (D pteronyssinus and D farinae) and Parietaria species pollen. We performed specific skin prick tests for the flavedo, albedo, pulp, and juice of orange, lemon, and grapefruit. Skin prick test responses for orange albedo, pulp, and juice and lemon and grapefruit flavedo, albedo, and pulp were negative. However, the skin prick test response for orange flavedo was positive, resulting in a 3-mm wheal (histamine control of 5 mm). The same skin prick tests were carried out in 5 healthy control subjects, all with negative results.We carried out challenge tests (peeling oranges, lemons, and grapefruit) with baseline and postchallenge spirometric controls. Test responses for lemon and grapefruit were negative. However, the challenge test result for oranges was positive: the patient had clinical symptoms (cough, dyspnea, and expiratory wheezing in both lungs) within 2 minutes. Spirometry showed a 23% reduction in FEV1 from baseline, which was reversed after administration of bronchodilators.We performed SDS-PAGE according to the method described by Laemmli9Laemmli U.K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4.Nature. 1970; 227: 680-685Crossref PubMed Scopus (206048) Google Scholar and immunoblotting with extracts of orange flavedo, albedo, and pulp from 3 varieties (Navel Lane, Navel Late and Valencia Late). IgE immunoblotting of sera revealed 2 IgE-binding bands of approximately 9 to 10 kDa and 23 kDa in the flavedo of the 3 orange varieties, which are not present in pulp or albedo (Fig 1).We believe this is the first report of selective sensitization to allergens of the outer layer of orange peel (flavedo), which manifests with acute bronchospasm triggered by peeling oranges. We identified 2 allergens (of 9-10 and 23 kDa, respectively) in orange flavedo that are not present in the albedo or pulp, which explains the tolerance to orange pulp. These allergens, by reason of their molecular weight, might correspond to orange Cit s 1 (germin-like protein, 23 kDa) and Cit s 3 (nonspecific LTP, 9 kDa). Although Crespo et al6Crespo J.F. Retzek M. Foetisch K. Sierra-Maestro E. Cid-Sanchez A.B. Pascual C.Y. et al.Germin-like protein Cit s 1 and profilin Cit s 2 are major allergens in orange (Citrus sinensis) fruits.Mol Nutr Food Res. 2006; 50: 282-290Crossref PubMed Scopus (43) Google Scholar reported the presence of these allergens in pulp, none of the study subjects showed IgE binding to a 9- to 10-kDa band in orange pulp extract. Further studies could evaluate whether Cit s 3 is predominantly present in orange peel.Positive responses induced by Cit s 1 in some subjects suggest potential clinical relevance in some patients with orange allergy. The presence of a single N-glycan, which is the target of IgE response to this protein, and the apparent lack of polypeptide epitopes, might explain its equivocal nature as a clinically relevant allergen. LTPs are located in the outer layers of the plants and are especially abundant in the peels of many fruits. Cit s 3 is present both in orange pulp and peel, but the latter is a stronger reactive. These data, together with the fact that oranges are eaten peeled, could explain both the low prevalence and mild symptoms in allergic responses after ingestion, but when peeled, they could act as a respiratory allergen and patients could be sensitized through respiratory exposure.In conclusion, inhalation of airborne orange peel proteins with an LTP-equivalent IgE-binding pattern can cause respiratory allergy in sensitized patients. A detailed medical history is vital to the correct diagnosis of this condition, which might have an occupational origin. Orange (Citrus sinensis) fruit and juice are widely consumed in Europe. Oranges belong to the Rutaceae family, members of which are found in warm regions worldwide and also include limes, lemons, tangerines, and grapefruit. Despite their wide consumption, sensitization to Rutaceae is rare, but the diagnosis should not be overlooked.1Barasona Villarejo M.J. García Núñez I. Moreno Aguilar C. Guerra Pasadas F. Sensibilización a naranja y limón.J Investig Allergol Clin Immunol. 2011; 21: 243Google Scholar Oranges are clinically relevant allergenic fruits. Reports describe allergic reactions from eating fresh orange skin and pulp or drinking juice or soda,1Barasona Villarejo M.J. García Núñez I. Moreno Aguilar C. Guerra Pasadas F. Sensibilización a naranja y limón.J Investig Allergol Clin Immunol. 2011; 21: 243Google Scholar, 2Ibáñez M.D. Sastre J. Martínez San Ireneo M. Laso M.T. Barber D. Lombardero M. Different patterns of allergen recognition in children allergic to orange.J Allergy Clin Immunol. 2004; 113: 175-177Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar with symptoms including oral allergy syndrome, urticaria, and atopic dermatitis. Systemic reactions are reported, and case reports describe the development of food-dependent, exercise-induced anaphylaxis after orange ingestion.3Morimoto K. Tanaka T. Sugita Y. Hide M. Food-dependent exercise-induced anaphylaxis due to ingestion of orange.Acta Derm Venereol. 2004; 143: 152-153Crossref Scopus (19) Google Scholar Oropharyngeal symptoms (oral allergy syndrome), an association with hay fever, and sensitization to other plant foods are the most common manifestation of orange allergy.4López Torrejón G. Ibáñez M.D. Ahrazem O. Sánchez-Monge R. Sastre J. Lombardero M. et al.Isolation, cloning and allergenic reactivity of natural profilin Cit s 2, a major orange allergen.Allergy. 2005; 60: 1424-1429Crossref PubMed Scopus (61) Google Scholar Three major allergens have been described to date in orange peel and pulp: Cit s 1 (germin-like protein, 23 kDa), Cit s 2 (profilin, 14 kDa), and Cit s 3 (nonspecific lipid transfer protein [LTP], 9 kDa).4López Torrejón G. Ibáñez M.D. Ahrazem O. Sánchez-Monge R. Sastre J. Lombardero M. et al.Isolation, cloning and allergenic reactivity of natural profilin Cit s 2, a major orange allergen.Allergy. 2005; 60: 1424-1429Crossref PubMed Scopus (61) Google Scholar, 5Ahrazhem O. Ibáñez M.D. López Torrejón G. Sánchez Monge R. Sastre J. Lombardero M. et al.Lipid transfer proteins and allergy to oranges.Int Arch Allergy Immunol. 2005; 137: 201-210Crossref PubMed Scopus (62) Google Scholar, 6Crespo J.F. Retzek M. Foetisch K. Sierra-Maestro E. Cid-Sanchez A.B. Pascual C.Y. et al.Germin-like protein Cit s 1 and profilin Cit s 2 are major allergens in orange (Citrus sinensis) fruits.Mol Nutr Food Res. 2006; 50: 282-290Crossref PubMed Scopus (43) Google Scholar Although most reported cases of orange allergy are due to ingestion of fresh fruit or derived products (eg, juice and jam), contact allergy to citrus peel oil should be considered in patients with hand dermatitis who are occupationally exposed to citrus fruits.7Cardullo A.C. Ruszkowski A.M. DeLeo V.A. Allergic contact dermatitis resulting from sensitivity to citrus peel, geraniol, and citral.J Am Acad Dermatol. 1989; 21: 395-397Abstract Full Text PDF PubMed Scopus (52) Google Scholar Occupational asthma in persons employed in removing the peel from oranges to produce the enzyme (pectinase and glucanase) solution used in soaking the fruits has been reported.8Sen D. Wiley K. Williams J.G. Occupational asthma in fruit salad processing.Clin Exp Allergy. 1998; 28: 363-367Crossref PubMed Scopus (19) Google Scholar However, no cases of allergic respiratory symptoms caused by orange peel allergens have been reported. Fruits with thick peels, such as oranges, are classified as hesperidia, and contain an inner layer of peel called the mesocarp (the white albedo or pith) and an outer layer of peel called the exocarp (flavedo or zest), which together form the peel. Flavedo is mostly composed of cellulosic material but also contains other components, including essential oils, paraffin waxes, steroids and triterpenoids, fatty acids, pigments (carotenoids, chlorophylls, and flavonoids), bitter principles (limonene), and enzymes (α-D-glucosidase, α-D-mannosidase, α-L-arabinosidase, β-D-glucosidase, β-D-xylosidase, and β-D-galactosidase). We report the case of a 22-year-old woman with a family history of atopy. The medical history revealed perennial rhinoconjunctivitis and persistent moderate bronchial asthma caused by sensitization to dust mites (Dermatophagoides pteronyssinus and Dermatophagoides farinae). The patient received specific immunotherapy for 5 years with a mix of Dermatophagoides species, but rhinitis and symptoms of mild intermittent asthma persisted. Currently, she requires occasional symptomatic treatment and also presents with discrete seasonal exacerbations during the spring caused by allergy to Parietaria species pollen. Some months ago, the patient presented with intense dyspnea, coughing, and wheezing triggered by the handling (peeling) of oranges or after entering a room where different varieties of freshly picked or bought-in oranges were being peeled, resulting in having to leave the room. The symptoms disappeared after inhalation of a dose of terbutaline. The patient reports tolerating orange pulp and juice well. Skin tests for common aeroallergens in the Valencia region were positive for mites (D pteronyssinus and D farinae) and Parietaria species pollen. We performed specific skin prick tests for the flavedo, albedo, pulp, and juice of orange, lemon, and grapefruit. Skin prick test responses for orange albedo, pulp, and juice and lemon and grapefruit flavedo, albedo, and pulp were negative. However, the skin prick test response for orange flavedo was positive, resulting in a 3-mm wheal (histamine control of 5 mm). The same skin prick tests were carried out in 5 healthy control subjects, all with negative results. We carried out challenge tests (peeling oranges, lemons, and grapefruit) with baseline and postchallenge spirometric controls. Test responses for lemon and grapefruit were negative. However, the challenge test result for oranges was positive: the patient had clinical symptoms (cough, dyspnea, and expiratory wheezing in both lungs) within 2 minutes. Spirometry showed a 23% reduction in FEV1 from baseline, which was reversed after administration of bronchodilators. We performed SDS-PAGE according to the method described by Laemmli9Laemmli U.K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4.Nature. 1970; 227: 680-685Crossref PubMed Scopus (206048) Google Scholar and immunoblotting with extracts of orange flavedo, albedo, and pulp from 3 varieties (Navel Lane, Navel Late and Valencia Late). IgE immunoblotting of sera revealed 2 IgE-binding bands of approximately 9 to 10 kDa and 23 kDa in the flavedo of the 3 orange varieties, which are not present in pulp or albedo (Fig 1). We believe this is the first report of selective sensitization to allergens of the outer layer of orange peel (flavedo), which manifests with acute bronchospasm triggered by peeling oranges. We identified 2 allergens (of 9-10 and 23 kDa, respectively) in orange flavedo that are not present in the albedo or pulp, which explains the tolerance to orange pulp. These allergens, by reason of their molecular weight, might correspond to orange Cit s 1 (germin-like protein, 23 kDa) and Cit s 3 (nonspecific LTP, 9 kDa). Although Crespo et al6Crespo J.F. Retzek M. Foetisch K. Sierra-Maestro E. Cid-Sanchez A.B. Pascual C.Y. et al.Germin-like protein Cit s 1 and profilin Cit s 2 are major allergens in orange (Citrus sinensis) fruits.Mol Nutr Food Res. 2006; 50: 282-290Crossref PubMed Scopus (43) Google Scholar reported the presence of these allergens in pulp, none of the study subjects showed IgE binding to a 9- to 10-kDa band in orange pulp extract. Further studies could evaluate whether Cit s 3 is predominantly present in orange peel. Positive responses induced by Cit s 1 in some subjects suggest potential clinical relevance in some patients with orange allergy. The presence of a single N-glycan, which is the target of IgE response to this protein, and the apparent lack of polypeptide epitopes, might explain its equivocal nature as a clinically relevant allergen. LTPs are located in the outer layers of the plants and are especially abundant in the peels of many fruits. Cit s 3 is present both in orange pulp and peel, but the latter is a stronger reactive. These data, together with the fact that oranges are eaten peeled, could explain both the low prevalence and mild symptoms in allergic responses after ingestion, but when peeled, they could act as a respiratory allergen and patients could be sensitized through respiratory exposure. In conclusion, inhalation of airborne orange peel proteins with an LTP-equivalent IgE-binding pattern can cause respiratory allergy in sensitized patients. A detailed medical history is vital to the correct diagnosis of this condition, which might have an occupational origin.

The data of the ISAAC project in Spain show a prevalence of childhood asthma ranging from 7.1% to 15.3%, with regional differences; a higher prevalence, 22.6% to 35.8%, is described for rhinitis, and atopic dermatitis is found in 4.1% to 7.6% of children. The prevalence of food allergy is 3%. All children in Spain have the right to be visited in the National Health System. The medical care at the primary level is provided by pediatricians, who have obtained their titles through a 4-yr medical residency training program. The education on pediatric allergy during that period is not compulsory and thus very variable. There are currently 112 certified European pediatric allergists in Spain, who have obtained the accreditation of the European Union of Medical Specialist for proven skills and experience in pediatric allergy. Future specialists in pediatric allergy should obtain their titles through a specific education program to be developed in one of the four accredited training units on pediatric allergy, after obtaining the title on pediatrics. The Spanish Society of Pediatric Allergy and Clinical Immunology (SEICAP) gathers over 350 pediatric allergists and pediatricians working in this field. SEICAP has a growing activity including yearly congresses, continued education courses, elaboration of technical clinical documents and protocols, education of patients, and collaboration with other scientific societies and associations of patients. The official journal of SEICAP is Allergologia et Immunophatologia, published every 2 months since 1972. The web site of SEICAP, http://www.seicap.es, open since 2004, offers information for professionals and extensive information on pediatric allergic and immunologic disorders for the lay public; the web site is receiving 750 daily visits during 2011. The pediatric allergy units are very active in clinical work, procedures as immunotherapy or induction of oral tolerance in food allergy, contribution to scientific literature, and collaboration in international projects.

Montesinos E, Martorell A, Félix R, Cerdá JC. Egg white specific IgE levels in serum as clinical reactivity predictors in the course of egg allergy follow‐up.
Pediatr Allergy Immunol 2010: 21: 634–639.
© 2009 John Wiley & Sons A/S

BACKGROUND:Due to the age when it becomes apparent and the treatment needed, cow's milk proteins (CMP) allergy requires an accurate diagnosis to avoid labelling infants falsely as allergic and subjecting them to unnecessary diets. The objective of this multi-centre study carried out at the Allergy Units of 14 Children's Hospitals was to discover the epidemiological, clinical and evolutionary characteristics of cow's milk protein allergy (CMPA).METHODS AND RESULTS:Infants suspected of CMPA who attended allergy clinics at the hospitals taking part during the study period were studied and a detailed clinical history was collected on all of them. Prick tests were done with cow's milk and its proteins and specific IgE anti-bodies were determined by means of CAP with the same allergens as the Prick test. The challenge test with cow's milk was carried out unless contraindicated by the diagnostic protocol. Two different challenge regimens were used: one of them carried out in 3 days and the other in one day. 409 infants with suspected CMPA were included and the diagnostic challenge test was performed on 286 patients (70 %) and not carried out on 123, as it was not indicated according to the protocol. IgE-mediated allergy was confirmed in 234 infants (58 %) and in 15 (4 %) non-IgE-mediated hypersensitivity was diagnosed. The two challenge regimens were equally secure. The average age when the reaction to cow's milk formula took place was 3.5 months (10 days-10 months). The symptoms appeared in the first week of introduction in 95 % of cases and appeared in 60 % with the first feeding with the formula. The most frequent clinical signs were cutaneous in 94 % of cases and the majority of cases appeared within 30 minutes of the feed. 99 % had been breast fed and 44 % had received some cow's milk supplement during the lactation period. Sensitization to egg not given in the feed was noted in 30 % and to beef in 29 %, being well tolerated in all of these.CONCLUSIONS:Carrying out an appropriate diagnostic protocol in infants attending for suspected CMPA allows allergy to be ruled out in a high percentage of cases.