Jacqueline Wassenberg

Parent perceived quality of life is age-dependent in children with food allergy

To cite this article: Wassenberg J, Cochard M‐M, DunnGalvin A, Ballabeni P, Flokstra‐de Blok BMJ, Newman CJ, Hofer M, Eigenmann PA. Parent perceived quality of life is age‐dependent in children with food allergy. Pediatr Allergy Immunol 2012: 23: 412–419.

Novel birch pollen specific immunotherapy formulation based on contiguous overlapping peptides

BackgroundSynthetic contiguous overlapping peptides (COPs) may represent an alternative to allergen extracts or recombinant allergens for allergen specific immunotherapy. In combination, COPs encompass the entire allergen sequence, providing all potential T cell epitopes, while preventing IgE conformational epitopes of the native allergen.MethodsIndividual COPs were derived from the sequence of Bet v 1, the major allergen of birch pollen, and its known crystal structure, and designed to avoid IgE binding. Three sets of COPs were tested in vitro in competition ELISA and basophil degranulation assays. Their in vivo reactivity was determined by intraperitoneal challenge in rBet v 1 sensitized mice as well as by skin prick tests in volunteers with allergic rhinoconjunctivitis to birch pollen.ResultsThe combination, named AllerT, of three COPs selected for undetectable IgE binding in competition assays and for the absence of basophil activation in vitro was unable to induce anaphylaxis in sensitized mice in contrast to rBet v 1. In addition no positive reactivity to AllerT was observed in skin prick tests in human volunteers allergic to birch pollen. In contrast, a second set of COPs, AllerT4-T5 displayed some residual IgE binding in competition ELISA and a weak subliminal reactivity to skin prick testing.ConclusionsThe hypoallergenicity of contiguous overlapping peptides was confirmed by low, if any, IgE binding activity in vitro, by the absence of basophil activation and the absence of in vivo induction of allergic reactions in mouse and human.Trial registrationClinicalTrials.gov NCT01719133

IL-17 receptor A and adenosine deaminase 2 deficiency in siblings with recurrent infections and chronic inflammation

BACKGROUND Data on patients affected by chronic mucocutaneous candidiasis underscore the preponderant role of IL-17 receptor A (IL-17RA) in preserving mucocutaneous immunity. Little is known about the role of adenosine deaminase (ADA) 2 in regulation of immune responses, although recent reports linked ADA2 deficiency with inflammation and vasculitis. OBJECTIVE We sought to investigate the mechanisms of chronic inflammation and vasculitis in a child lacking IL-17RA and ADA2 to identify therapeutic targets. METHODS We report a family with 2 siblings who have had recurrent mucocutaneous infections with Candida albicans and Staphylococcus aureus and chronic inflammatory disease and vasculitis since early childhood, which were refractory to classical treatments. Array-based comparative genomic hybridization analysis showed that both siblings are homozygous for a 770-kb deletion on chr22q11.1 encompassing both IL17RA and cat eye critical region 1 (CECR1). Immunologic studies were carried out by means of flow cytometry, ELISA, and RIA. RESULTS As expected, in the affected child we found a lack of IL-17RA expression, which implies a severe malfunction in the IL-17 signaling pathway, conferring susceptibility to recurrent mucocutaneous infections. Surprisingly, we detected an in vitro and in vivo upregulation of proinflammatory cytokines, notably IL-1β and TNF-α, which is consistent with the persistent systemic inflammation. CONCLUSIONS This work emphasizes the utility of whole-genome analyses combined with immunologic investigation in patients with unresolved immunodeficiency. This approach is likely to provide an insight into immunologic pathways and mechanisms of disease. It also provides molecular evidence for more targeted therapies. In addition, our report further corroborates a potential role of ADA2 in modulating immunity and inflammation.

Lupine-induced anaphylaxis in a child without known food allergy

BACKGROUND Lupine allergy is caused by ingestion of the flour of a plant called Lupinus albus, a member of the Leguminosae family. Lupine allergy has been described in adult patients previously known to have peanut allergy (cross-reactivity). OBJECTIVE To describe the first case of an anaphylactic reaction caused by ingestion of lupine flour in a pediatric patient without a known peanut allergy. METHODS Symptom assessment, nutritional history, and skin and blood tests. RESULTS An otherwise healthy 8-year-old boy had nose and eye discharge followed by facial edema and difficulty breathing 30 minutes after eating an industrially prepared waffle containing eggs, sugar, and lupine flour. He had no history of food allergy and was eating a normal diet, including peanuts and other legumes. Results of skin prick tests using commercial extracts were positive to peanuts and negative to eggs, soy, and nuts; results of a prick-to-prick test using lupine flour were strongly positive (+ + + +). His total IgE level was 1,237 UI/mL. Specific IgE antibodies were positive to lupine seeds (20.8 kU/L) and peanuts (> 100 kU/L). CONCLUSIONS To our knowledge, we describe the first case of an anaphylactic reaction after ingestion of lupine flour in a child without known allergy. In the case of peanut allergy or any anaphylactic reaction without evident cause, especially after industrially prepared food ingestion, lupine should be considered in the list of allergens tested. Lupine is increasingly used in industrially prepared food but is not regularly declared in the composition, leading to difficulties in allergen avoidance.

Comparison of two oral probiotic preparations in a randomized crossover trial highlights a potentially beneficial effect of Lactobacillus paracasei NCC2461 in patients with allergic rhinitis

BackgroundThere is promising but conflicting evidence to recommend the addition of probiotics to foods for prevention and treatment of allergy. Based on previous studies with fermented milk containing Lactobacillus paracasei NCC2461, we aimed to compare the effect of a powder form of the latter probiotic with the effect of a blend of Lactobacillus acidophilus ATCC SD5221 and Bifidobacterium lactis ATCC SD5219 in patients with allergic rhinitis.MethodsA double-blind, randomized, cross-over study, involving 31 adults with allergic rhinitis to grass pollen, was performed outside the grass pollen season (registration number: NCT01233154). Subjects received each product for 4-weeks in two phases separated by a wash-out period of 6 to 8 weeks. A nasal provocation test was performed before and after each 4-week product intake period, and outcome parameters (objective and subjective clinical symptoms; immune parameters) were measured during and/or 24 hours after the test.ResultsOut of the 31 subject enrolled, 28 completed the study. While no effect was observed on nasal congestion (primary outcome), treatment with NCC2461 significantly decreased nasal pruritus (determined by VAS), and leukocytes in nasal fluid samples, enhanced IL-5, IL-13 and IL-10 production by peripheral blood mononuclear cells in an allergen specific manner and tended to decrease IL-5 secretion in nasal fluid, in contrast to treatment with the blend of L. acidophilus and B. lactis.ConclusionsDespite short-term consumption, NCC2461 was able to reduce subjective nasal pruritus while not affecting nasal congestion in adults suffering from grass pollen allergic rhinitis. The associated decrease in nasal fluid leukocytes and IL-5 secretion, and the enhanced IL-10 secretion in an allergen specific manner may partly explain the decrease in nasal pruritus. However, somewhat unexpected systemic immune changes were also noted. These data support the study of NCC2461 consumption in a seasonal clinical trial to further demonstrate its potentially beneficial effect.

Predicting positive food challenges in children sensitised to peanuts/tree nuts

Children with atopic diseases in early life are frequently found with positive IgE tests to peanuts/tree nuts without a history of previous ingestion. We aimed to identify risk factors for reactions to nuts at first introduction.

Snack seeds allergy in children

Care Unit, revealing the presence of a high number of neutrophils (64%) and activated eosinophils (10%), with a normal TCD4+/TCD8+ ratio (1.9), normal values for BAL in the healthy subjects: 80–95% macrophages, <15% lymphocytes, 2–5% neutrophils, <1% eosinophils and basophils (5). At least 3 weeks after the acute episodes, an allergological study was performed. Skin prick tests were performed with irbesartan (150 mg/ml), HCT (50 mg/ml), and latex in patien1, and amiloride (5 mg/ ml), HCT (50 mg/ml) and latex in patient 2. All drugs were tested in three healthy control subjects. All skin tests elicited negative results. Single-blind oral challenge tests with irbesartan in patient 1 and amiloride in patient 2 were negative. A basophil activation test using CD63 as a marker for activated basophils (Basotest , ORPEGEN Pharma, Heidelberg, Germany) was performed with HCT, including dilutions from 50 lg/ml to 50 mg/ml. An activation of 21.9%, of CD63 activated basophils, for patient 1 and an activation of 20.6% for patient 2 were obtained at 50 mg/ml concentration (baselinel activation of 9.2% and 4.6%, respectively). A maximum basophil activation of 10.4% at a 50 mg/ml concentration was obtained in a control subject. Gamboa et al. (6) describe a negative Basophil Activation Test at two concentrations of hydrochlorothiazide (0.025 and 1 mg/ ml) in a patient with acute noncardiogenic pulmonary edema caused by hydrochlorothiazide. The discrepancy with our results may be due to the concentration used, as we obtained positive results at higher concentration. In conclusion, we describe two cases of noncardiogenic HCT-induced pulmonary edema in which positive results in basophil activation test were obtained, suggesting basophil participation in the reaction and its potential role as a diagnostic tool. The results of a bronchoalveolar lavage in one of the patients seem to corroborate the hypothesis that neutrophenia may occur because of pulmonary sequestration of neutrophils, although the mechanisms involved remain unknown. Editorial assistance was kindly provided by Oliver Shaw. *Servicio de Alergologı́a Fundación Jiménez Dı́az Madrid, Spain CIBER de Enfermedades Respiratorias. CIBERES Tel.: 34-915498225 Fax: 34-915499498 E-mail: jsastre@fjd.es

Paediatric oral peanut challenges: a comparison of practice in London and Western Switzerland

There are guidelines on how to develop a food challenge protocol, but at present there is no gold standard guidance on method, and separate units produce differing protocols.

Perplexing cases of allergy to salami

TO THE EDITOR: Patients can often present with perplexing allergies to processed foods that in other simpler component forms they can tolerate. In general, further investigation of the ingredients list to isolate the offending agent is necessary. Salamis and some washed rind cheeses (such as raclette cheese) have molds used in their skins and rinds for preservation or to add certain tastes and textures. It must not be forgotten that these molds can and do cause allergic reactions. Salami is a fermented, cured sausage. During the drying and curing phase the skin of the salami is often sprayed with a Penicillium species mold starter to promote flavor and to try to prevent harmful bacteria from multiplying. The type of mold used is different in various production regions (Illtud Llyr Dunsford [Charcutier Ltd], personal communication, June 26, 2012). Salami has also been found to contain house dust mites (HDMs) that can occasionally thrive during the curing process. We present a 5-year-old boy with atopic dermatitis, seasonal allergic rhinitis, and pollen-food syndrome and no history of b-lactam allergy who developed urticaria and swollen eyelids shortly after eating Salami Tipo Milano (Ticino, Switzerland), a generic supermarket brand of salami that he had not previously ingested. Second, a 10-year-old boy with peanut allergy, seasonal allergic rhinitis, atopic dermatitis, and sensitisation to HDM, and no history of b-lactam allergy developed retrosternal pain and the sensation of food blockage after eating Salametto Milano (Rapelli SA, Ticino, Switzerland). He had previously experienced similar feelings after eating raclette cheese. Both children tolerated the foods listed as ingredients in these salamis (including pork, beef, salt, skimmed milk powder, sugar, spices, pepper, garlic, ascorbic acid, sodium nitrite, potassium nitrite). In the first boy, skin prick tests with standard solutions (ALK-Abello, Horsholm, Denmark) to pork, milk, and wheat were negative. Prick-to-prick testing with the salami meat was negative, but testing with the skin of the salami was positive with a 5-mm wheal. After correspondence, the manufacturers stated that there was mold in the salami skin which they identified as Penicillium chrysogenum/notatum. Specific IgE to P chrysogenum/notatum was positive at 1.24 kU/L. Skin prick test and specific IgE were negative to HDMs and other molds. In the case of the second boy, an endoscopy showed eosinophilic esophagitis, with histology showing more than 15 eosinophils per high-powered field. Skin prick testing was negative to the foods listed as ingredients in the salami and Aspergillus. Prickto-prick testing was negative to salami meat, but positive to the skin of the salami with a 9-mm wheal. On investigation P chrysogenum/notatum was again present in the salami skin. Specific IgE results in this boy were P notatum IgE 12.7 kU/L, Dermatophagoides pteronyssinus 2.32 kU/L, Dermatophagoides farinae 3.02kU/L, Acarus siro 0.4kU/L, and Glycophagus domesticus <0.35 kU/L. The mold on these salami skins is the strain of Penicillium first discovered by Alexander Fleming in 1928 and named Penicillium rubrum but was later identified in the 1930s as P notatum. When further work was done on P notatum, it was found to be identical to the previously characterised P chrysogenum. Because P chrysogenum is the older name, the correct title for this mold is P chrysogenum; nevertheless, they are often used interchangeably in the literature. P chrysogenum went on to be manufactured into the drug penicillin for treatment of festering wounds during the Second World War (1939-1945). The main allergen in P notatum is Pen n 13. It is an alkaline serine protease that shares 39% identical residues with other molds and has been designated in group 13 of the fungal genera. It has similar binding epitopes to Penicillium citrinum, and all the serine protease family possess similar protein structure and strong cross reactivity. Skins, or casings, of salami-like sausages are commonly sprayed with Penicillium starter cultures to promote flavor development and to inhibit the growth of undesirable molds. Mold growth on the surface of dry cured meat products is the result of their tolerance to low water activity, low pH, and high salt concentration. A known link exists between occupationally exposed workers and the development of respiratory and skin symptoms from the molds on salami sausages. Several case studies were reported of people in charcuteries who work closely with salami and develop allergic skin reactions, either IgE or non-IgE mediated. In addition, cases of salami factory workers are reported to develop occupational asthma from aerosolised mold in inadequately ventilated factories, and a mouse model suggested that inhaled P chrysogenum could be implicated in the pathogenesis of asthma. To our knowledge there are no reports of the ingestion of salami that causes reactions secondary to the cultured molds. However, several cases are described of HDMs present in salami causing allergic reactions in patients. Note that the second patient, who was sensitized to both P notatum and HDM, manifested esophageal symptoms. The role of aeroallergens has been discussed in eosinophilic esophagitis, but there are no reports of patients with eosinophilic esophagitis and esophageal symptoms linked to ingested rather than inhaled molds or aeroallergens. When clinicians are presented with patients who have experienced allergic reactions to salami, the causal agent is often thought to be pork itself, or milk and wheat used as binding agents or in the salami casing and often not recognized in the ingredient list. We suggest using skin prick tests to the salami skin and specific

Predicting Positive Food Challenges at the Introduction of Nuts in Sensitised Children

Rationale: Children with atopic diseases in early life are frequently found with positive IgE tests to nuts, without a history of previous ingestion. We aimed to identify risk factors for reactions to nuts at their first introduction. Methods: A detailed retrospective case note and database analysis was performed. Inclusion criteria were: patients aged 3 to 16 years who had had a standardized food challenge to peanut and/or tree nuts due to primary sensitisation to the nut (positive specific IgE or SPT). A detailed assessment was performed of factors relating to food challenge outcome with univariate and multivariate logistic regression analysis. Results: There were 98 food challenges (48% peanut, 52% tree nut) with 29 positive, 67 negative and 2 inconclusive challenges. A positive maternal history and a specific IgE > 2 kU/l were strongly associated with a significantly increased risk of a positive food challenge (OR 3.54; 95% CI 1.28 to 9.81; and OR 4.82; 95% CI 1.57 to 14.86; respectively). There was no significant association between the type of nut, age, presence of other food allergies, paternal or sibling atopic history, other atopic conditions or severity of previous reaction to other foods. Conclusions: We have demonstrated an association between the presence of a maternal atopic history and a specific IgE > 2 kU/l, and a significant increase in the likelihood of a positive food challenge in children with primary sensitisation to nuts. Although requiring further prospective validation we suggest these easily identifiable components should be considered when deciding the need for a nut challenge.