Teresa Boyano-Martínez

Accidental allergic reactions in children allergic to cow's milk proteins

BACKGROUND Cows milk is the main cause of food allergy in children. Patients allergic to food frequently experience accidental exposure. There are few studies analyzing this problem, most of them concerning peanut allergy. OBJECTIVE We sought to calculate the frequency of accidental exposure reactions in children allergic to cows milk during a 12-month period, to analyze the clinical characteristics and circumstances surrounding the reactions, and to identify risk factors for severe reactions. METHODS Eighty-eight children allergic to cows milk (44 boys; median age, 32.5 months) were included in the study. A systematized questionnaire about accidental exposure was used. Reactions were classified as mild, moderate, and severe. Cows milk- and casein-specific IgE antibody titers were determined. RESULTS Thirty-five (40%) children had 53 reactions in the previous year (53% mild, 32% moderate, and 15% severe). Most reactions took place at home (47%) under daily life circumstances (85%). Specific IgE levels to cows milk were higher in children with severe reactions than in those with moderate (median, 37.70 vs 7.71 KUA/L; P = .04) or mild (3.37 KUA/L; P = .04) reactions. The frequency of severe reactions was 10-fold higher in asthmatic children (odds ratio, 10.2; 95% CI, 1.13-91.54). CONCLUSIONS Reactions to accidental exposure are frequent in children with cows milk allergy. The proportion of severe reactions was 15%. The risk factors for such reactions included very high levels of specific IgE to cows milk and casein and asthma.

Shellfish Allergy: a Comprehensive Review

Shellfish allergy is of increasing concern, as its prevalence has risen in recent years. Many advances have been made in allergen characterization. B cell epitopes in the major allergen tropomyosin have been characterized. In addition to tropomyosin, arginine kinase, sarcoplasmic calcium-binding protein, and myosin light chain have recently been reported in shellfish. All are proteins that play a role in muscular contraction. Additional allergens such as hemocyanin have also been described. The effect of processing methods on these allergens has been studied, revealing thermal stability and resistance to peptic digestion in some cases. Modifications after Maillard reactions have also been addressed, although in some cases with conflicting results. In recent years, new hypoallergenic molecules have been developed, which constitute a new therapeutic approach to allergic disorders. A recombinant hypoallergenic tropomyosin has been developed, which opens a new avenue in the treatment of shellfish allergy. Cross-reactivity with species that are not closely related is common in shellfish-allergic patients, as many of shellfish allergens are widely distributed panallergens in invertebrates. Cross-reactivity with house dust mites is well known, but other species can also be involved in this phenomenon.

Peanut seed storage proteins are responsible for clinical reactivity in Spanish peanut-allergic children

Background:  Seed storage proteins (SSP; Ara h 1, Ara h 2, Ara h 3) have been shown to be major peanut allergens, although recently, peanut lipid transfer protein has been reported to be an important allergen in the Mediterranean area. We sought to investigate the sensitization pattern to peanut SSP and vegetable pan‐allergens in a group of peanut‐allergic children compared with a peanut‐tolerant group.

Efficacy and safety of oral desensitization in children with cow's milk allergy according to their serum specific IgE level

BACKGROUND Oral desensitization in children allergic to cows milk proteins is not risk free. The analysis of factors that may influence the outcome is of utmost importance. OBJECTIVE To analyze the efficacy and safety of the oral desensitization according to specific IgE (sIgE) level and adverse events during the maintenance phase. METHODS Thirty-six patients allergic to cows milk (mean age, 7 years) were included in an oral desensitization protocol. Patients were grouped according to sIgE levels (ImmunoCAP) into groups 1 (sIgE <3.5 kU/L), 2 (3.5-17 kU/L), and 3 (>17-50 kU/L). Nineteen children were included as a control group. Serum sIgE levels to cows milk and its proteins were determined at inclusion and 6 and 12 months after finishing the desensitization protocol. RESULTS Thirty-three of 36 patients were successfully desensitized (200 mL): 100% of group 1 and 88% of groups 2 and 3. Desensitization was achieved in a median of 3 months (range, 1-12 months); 90% of the patients in group 1, 50% of the patients in group 2, and 30% of the patients in group 3 achieved tolerance in less than 3 months (P = .04). In the control group only 1 child tolerated milk in oral food challenge after 1 year. During the induction phase, there were 53 adverse events in 27 patients (75%). Patients of groups 2 and 3 had more severe adverse events compared with group 1. During the maintenance phase, 20 of 33 patients (60%) had an adverse event. CONCLUSION Oral desensitization is efficacious. Tolerance is achieved earlier when sIgE is lower. Severe adverse events are frequent, especially in patients with higher sIgE levels.

Peach allergy in spanish children: tolerance to the pulp and molecular sensitization profile

Peach allergy is the main cause of vegetable food allergy in the Mediterranean area. Pru p 3 is the major allergen, and it is mainly found in the peel.

Clinical presentation, allergens, and management of wheat allergy

ABSTRACT IgE-mediated allergy to wheat proteins can be caused by exposure through ingestion, inhalation, or skin/mucosal contact, and can affect various populations and age groups. Respiratory allergy to wheat proteins is commonly observed in adult patients occupationally exposed to flour, whereas wheat food allergy is more common in children. Wheat allergy is of growing importance for patients with recurrent anaphylaxis, especially when exercise related. The diagnosis of wheat allergy relies on a consistent clinical history, skin prick testing with well-characterized extracts and specific IgE tests. The accuracy of wheat allergy diagnosis may be improved by measuring IgE responses to several wheat components. However, a high degree of heterogeneity has been found in the recognition pattern of allergens among patient groups with different clinical profiles, as well as within each group. Thus, oral provocation with wheat or the implicated cereal is the reference test for the definitive diagnosis of ingested wheat/cereal allergy.

Trimethoprim–sulfamethoxazole (cotrimoxazole) desensitization in an HIV-infected 5-yr-old girl

To the Editor, Opportunistic infections are a major cause of morbidity and mortality in HIV-infected patients. Trimethoprim–sulfamethoxazole (TMP-SMX) (cotrimoxazole) has been shown to dramatically reduce the risk of opportunistic infections, particularly Pneumocystis carinii pneumonia, and has been used extensively in their treatment and prevention (1). Since 2006, WHO has recommended cotrimoxazole preventive therapy for all HIV-exposed infants and children born to mothers living with HIV, and continuing until cessation of risk of HIV transmission (cessation of breastfeeding) and infection can be exclude (2). In HIV-infected patients, cotrimoxazole use causes a higher rate of adverse drug reactions than in the general population (20–100% compared with 5–8% of healthy individuals) (3, 4). Hypersensitivity to cotrimoxazole is the most frequent drug reaction among HIV-infected patients, typically manifesting as a maculopapular rash, with or without fever, and usually occurring 1–2 wk after commencing treatment (5). IgE-mediated hypersensitivity is rare. The pathogenesis of TMP-SMX reactions is complex, multifactorial, and not completely understood. One or more metabolic, toxic, immunologic, or viral factors are likely to contribute, and the typical explanation is based on the variability in metabolic parameters for N-acetylation and N-oxidation (HIV-infected patients are more likely to have a slow acetylator phenotype, which results in greater oxidation and the formation of toxic intermediate SMX-derived metabolites thereby stimulating an immune response) (3, 5, 6). There are three options for the clinical management of hypersensitivity to cotrimoxazole in these patients: treating through the reaction (continuing therapy despite adverse reaction), rechallenge, or desensitization (4). Although a variety of cotrimoxazole desensitization protocols have emerged for HIV-infected patients, there is a lack of desensitization protocols for use in pediatric patients (4). A 5-yr-old Nigerian girl, with no known allergies, who was infected with HIV at birth (MTCT) was referred to the allergy department because a pruritic erythematous maculopapular rash had appeared on her face, chest, and limbs after 2 wk of treatment with cotrimoxazole, 7 ml/day, 3 times/wk (Septrim Pediatric oral suspension : 8 mg trimethoprim/40 mg sulfamethoxazole/1 ml). The reaction had occurred 15 days before she was first seen in the allergy department. She did not present fever or systemic symptoms. Hematological analysis showed a leukocyte count of 6.02 9 10/ll with 44.5% (2.68 9 10/ll) neutrophils and 43.9% (2.64 9 10/ll) lymphocytes. The CD4 T lymphocyte (CD4) count was 6% (158.4 9 10/ll). As CD4 cell count was <200 cells/mm (<200 cells/ll), prophylaxis with cotrimoxazole for at least 6 months was mandatory. After informed consent was obtained, the patient underwent a routine allergy work-up (skin tests) following the protocol of the Drug Allergy Interest Group of European Academy of Allergy and Clinical Immunology (7). Afterward, an oral desensitization protocol was carried out. The procedure was performed at the hospital, with a physician and nurse in attendance and emergency medications readily available. The results of skin prick test (SPT) with trimethoprim (10 mg/ml; Almofarma SL, Barcelona, Spain), and SPT (10 mg/ml), and intradermal test (IDT) with sulfamethoxazole (10 mg/ml; Almofarma SL) were negative. As the reaction related to cotrimoxazole use was very likely a hypersensitivity drug reaction, an oral challenge test was not performed. Instead, an oral desensitization protocol was carried out (Table 1). On the first day, gradually increasing doses of cotrimoxazole (Septrim Pediatric oral suspension ) at 15-min intervals (1 and 5 ml of dilution 1/200 and 1 and 2 ml of dilution 1/20) were tolerated. On the second day, the patient received 3 and 4 ml of 1/20 dilution at 15-min intervals with good tolerance, and on the third day, 2 undiluted doses of 0.5 and 1 ml at 45-min intervals were tolerated. On the fourth day, 30 min after the undiluted dose of 4 ml was administered (cumulative dose 6 ml), she developed a generalized pruritic erythematous maculopapular rash. The reaction immediately subsided after oral administration of dexchlorpheniramine and

Microarrayed Jug r 1 shows the best diagnostic performance in walnut allergy

Several walnut (WN) allergens have been identified to date: Jug r 1 (2S albumin), Jug r 2 (7S globulin), Jug r 3 (LTP), Jug r 4 (11S globulin) and Jug r 5 (profilin), but their clinical significance is still to be determined in some cases. Allergen microarray (ISAC) provides information for three of these allergens. The aim of the study was to determine the importance of component resolved diagnosis in WN allergic patients. Ninety children suspected to have allergy to fruit, nuts and/or legumes were selected. Patients were classified as allergic if they presented at least 2 reactions unequivocally related to WN ingestion in the last 2 years. Patients were defined as tolerant if they consumed WN on a regular basis. Clinical questionnaire, skin prick test (SPT), total and specific IgE and ImmunoCAP ISAC (Thermo Fisher) were performed. Thirty-one patients (18 males) were defined as allergic and 59 (36 males) tolerant. WN-SPT wheal size (median diameter 5.25 mm; IQR: 4-7 vs. 0 mm; IQR: 0-2, p=0.000) and WN-sIgE (median 5.35 kU/L; IQR: 3.52-12.84 vs. 0.65 kU/L; IQR: 0.08-1.86, p=0.000) were significantly greater in allergic than in tolerant children. Positive Jug r 1-sIgE was significantly more frequent in allergic patients (80.65% vs. 5.08%, p=0.000). Jug r 1-sIgE values were also significantly higher in allergic children (median 2.5 ISU; IQR: 0-7.6 vs. 0 ISU; IQR: 0-0, p=0.000). This was not found for Jug r 2 or Jug r 3. ROC curves were constructed for the three allergens showing Jug r 1 the best diagnostic performance (AUC: 0.876, 95%CI: 0.788-0.965, p=0.000) (Figure ​(Figure11 and Table ​Table11). Figure 1 ROC curves for Walnut allergens Table 1 Diagnostic performance of walnut allergens (MAISAC) In conclusion, Jug r 1-sIgE is the best discriminating allergen in WN allergic patients.

Household almond and peanut consumption is related to the development of sensitization in young children.

To the Editor: Nut allergy is one of the most common and severe food allergies in children. Therefore understanding the causes of nut allergy is essential to establishing primary preventive measures to avoid the onset of this condition. The most significant risk factor for children in terms of having food allergy is atopic dermatitis (AD). Food allergy has also been associated with genetic, molecular, dietary, and environmental factors. The early introduction of allergenic foods in children’s diets appears to prevent the development of allergy. Moreover, in recent years, several studies have shown that there is a clear relationship between household peanut consumption and allergy, especially in children with eczema or other skin barrier function disorders, which supports the concept of a transcutaneous sensitization pathway. The aim of this study was to assess the association between consumption of various types of nuts (almonds, walnuts, and peanuts) in domestic settings by family members who live with the children and sensitization to these foods in children younger than 18 months who had not yet had the foods introduced to their diets. A prospective study was conducted on children between the ages of 3 and 18 months who had not eaten peanuts or tree nuts and were not known to be sensitized or allergic. The consumption of nuts at home by relatives who lived with the children was recorded by using a questionnaire administered by the allergist before performing allergy testing. SPTs with almond, walnut, and peanut extracts were performed on all the children. A child was considered sensitized if he or she had a positive SPT response (see the Methods section in this article’s Online Repository at www. jacionline.org). A total of 96 children were included in the study. The primary clinical characteristics are listed in Table E1 in this article’s Online Repository at www.jacionline.org. Data on the consumption of nuts are listed in Table E2 in this article’s Online Repository at www.jacionline.org. Twenty-four (25%) of the children were sensitized to 1 or more of the analyzed foods. A total of 35 sensitizations in the 96 children were detected: 17 to almond, 13 to peanut, and 5 to walnut. Table E3 in this article’s Online Repository at www.jacionline. org shows the distribution of children sensitized to almond, walnut, and peanut based on households consuming almond, walnut, and peanut, respectively. The sensitization rate was greater for almond (26.2%) and peanut (21.7%) than for walnut (6.9%; almond vs walnut, P 5 .002; peanut vs walnut, P 5 .014). Data from the univariate analysis are shown in Table I. Home consumption of almonds, AD (presence and severity), and egg sensitization had a statistically significant association with sensitization to this nut. The results of the peanut sensitization analysis are similar to those of the almond analysis. Regarding walnut consumption, a similar numeric trend was observed; however, a statistically significant association was not found, probably because of the low number of children sensitized. The results of the analysis stratified by AD (presence and severity) and egg sensitization are presented in Table E4 in this article’s Online Repository at www.jacionline.org. As shown, these covariates behaved as modifying factors on the effect of almond consumption in sensitization to this nut, so that the association between consumption and sensitization is only held in one of the stratum (children with AD, children with higher severity scores, and children sensitized to egg) but not the others. These results were similar in the case of peanut. Assessment of the magnitude of the association between consumption and sensitization to nuts and the modifying effect of covariates on this association was not possible because of the absence of sensitized children among the unexposed subjects. Additionally, the sensitization rate in the children from homes consuming almonds or peanuts ‘‘very often’’ was greater than in those consuming them ‘‘often’’ or ‘‘not often.’’ This difference was also observed between those with consumption ‘‘very often’’ or ‘‘often’’ and those with ‘‘not often’’ or no consumption (Table II). No differences were found in the rate of children sensitized according to the family members/relatives who ate the nuts. For more than a decade, several authors have demonstrated that peanut sensitization in young children can occur through the transcutaneous pathway. In 2003, Lack et al showed that applying peanut oil cream during the first 6 months of life and history of eczema were risk factors for allergy to this food, suggesting the possibility of sensitization through inflamed skin. Various studies have subsequently encountered a clear association between home consumption of peanuts and allergy to this food. Fox et al demonstrated that the weekly consumption of peanuts by all family members in the first year of a child’s life was significantly higher for children with peanut allergy than for healthy control subjects and high-risk control subjects. Brough et al showed that environmental exposure to peanut in early life was associated with greater risk of both peanut sensitization and allergy in atopic children or children with a filaggrin loss-offunction mutation and that this risk was higher the greater the concentration of peanut proteins in household dust. Moreover, the authors showed that the effect was greater in children with AD and those with more severe forms of this disorder, suggesting that exposure to peanuts through skin with an altered barrier function could be a sensitization pathway. The results of our study support this idea. In the group of children younger than 18 months, a clear relationship was found between nut consumption by relatives and IgE-mediated sensitization. The respective food had been consumed in all homes of children sensitized to almond, peanut, or walnut. None of the children who were not exposed showed sensitization. This strong association between consumption and sensitization suggests that environmental exposure can be a risk factor involved in the pathogenesis of hypersensitivity to almond, peanut, and possibly other tree nuts in young children who have not had these foods introduced to their diets. Additionally, the sensitization rate was significantly higher for children from homes in which almonds, walnuts, or peanuts were consumed ‘‘very often’’ than from those homes with consumption rates of ‘‘often’’ or ‘‘not often.’’ AD (presence and severity) and sensitization to egg were also identified as risk factors in the studies by Brough et al. AD could facilitate transcutaneous sensitization, and sensitization to

Sensitization to microarrayed species-specific plant components precedes that of cross-reacting allergens

Microarrayed allergen immunoassays are increasingly being used to determine sensitization to multiple allergenic components1. However, there is scarce data on the development and progression of sensitization to vegetal allergens in early life. This study aimed to detect the profile of sensitization to allergenic components from vegetal foods and pollens using ISAC-IgE microarray (ISAC-IgE) (Thermo Fisher Scientific, Uppsala, Sweden) over 4 years in children diagnosed with allergy to cows milk proteins (CMPA). This article is protected by copyright. All rights reserved.