What 2012 diagnosis atopy

WHAT YOU SHOULD HAVE READ BUT….2012 diagnosis of atopyAttilio BonerUniversity ofVerona, Italy

• Local allergy• Hidden allergy

Practical guide to skin prick tests in allergy to Aeroallergens. Bousquet, Allergy 2012;67:18 Performance of skin prick tests.

Practical guide to skin prick tests in allergy to Aeroallergens. Bousquet, Allergy 2012;67:18 Common errors in skin prick tests.

Practical guide to skin prick tests in allergy to Aeroallergens. Bousquet, Allergy 2012;67:18Inhibitory effect of various treatments on skin prick tests.

Practical guide to skin prick tests in allergy to Aeroallergens. Bousquet, Allergy 2012;67:18Global Allergy and Asthma European Network-suggested panel of allergens to be tested in all patients in Europe.

Practical guide to skin prick tests in allergy to Aeroallergens. Bousquet, Allergy 2012;67:18Which results are regarded as positive?• Only the wheal is needed. The largest size of the wheal is considered to be sufficient.• Wheal diameters ≥3 mm are considered positive in skin prick tests. It is considered that small wheals ≤3 mm of diameter are not significant in clinical studies whereas they are considered to be positive in epidemiologic studies.• Very large reactions are not necessarily associated with more severe disease.

Practical guide to skin prick tests in allergy to Aeroallergens. Bousquet, Allergy 2012;67:18How do skin tests compare to serum-specific IgE?• Serum-specific IgE, skin prick tests and allergen challenge do not have the same biological and clinical relevance and are not interchangeable.• There may be age-dependent differences, and elderly people may more commonly have negative skin tests or tests of a smaller size.• Low levels of serum-specific IgE are less often associated with symptoms than higher levels, but they do not exclude allergic symptoms, particularly in very young children.• Some allergens exhibit poor allergenic activity and skin testing may be useful to identify such allergens.

Practical guide to skin prick tests in allergy to Aeroallergens. Bousquet, Allergy 2012;67:18How to interpret skin test results?• False-positive skin tests may result from dermographism or may be caused by ‘irritant’ reactions or a nonspecific enhancement from a nearby strong reaction.• False-negative skin tests can be caused by the following:1. Extracts of poor initial potency or subsequent loss of potency;2. Drugs modulating the allergic reaction;3. Diseases attenuating the skin response;4. Improper technique (no or weak puncture);5. Limited local production of allergen-specific IgE only in the nose or in the eye.

Practical guide to skin prick tests in allergy to Aeroallergens. Bousquet, Allergy 2012;67:18What is the role of skin tests in primary care?• Allergic rhinitis is a growing primary care challenge because most patients consult primary care physicians.• General practitioners play a major role in the management of allergic rhinitis as they make the diagnosis, start the treatment, give relevant information and monitor most of the patients.• A structured allergy history appears to be insufficient when assessing patients with asthma and rhinitis in general practice. However, performing and interpreting skin prick tests requires adequate training.

Phadiatop Infant detects IgE-mediated diseases among pre-school children: a prospective study Nilsson, Pediatr Allergy Immunol 2012;23:159BackgroundIgE-sensitization to food and inhalantallergens may precede and accompany theappearance of clinical symptoms of allergicdiseases. 2.26%The aim was to study the diagnostic capacity 2.02of Phadiatop Infant (Phinf) for detectingIgE-sensitization at 5 yr of age and furtherto evaluate the predictive capacity of Phinflongitudinally with regard to sensitization andallergic symptoms in pre-school children.

Phadiatop Infant detects IgE-mediated diseases among pre-school children: a prospective study Nilsson, Pediatr Allergy Immunol 2012;23:159 In positive Phinf test at 2 yr OR for 201 children with complete data on sIgE 40 – testing for 10 individual allergens 30 – 2.26% 35.6 Phinf analyses, and 20 – clinical evaluations at 2 and 5 yr of age 10 – 14.7 0 IgE-sensitization any allergic symptom at 5 yrs of age

Phadiatop Infant detects IgE-mediated diseases among pre-school children: a prospective study Nilsson, Pediatr Allergy Immunol 2012;23:159 In positive Phinf test Phinf at 2 yr OR for 201 children with complete data be sIgE seems to on a 40 – reliable tool for testing for 10 individual allergens predicting future 30 – 2.26% 35.6 sensitization as well Phinf analyses, and 20 – as allergic clinical evaluations at 2 and 5 yr of age young symptoms in 10 – 14.7 child 0 IgE-sensitization any allergic symptom at 5 yrs of age

• IgE specifiche

Significance of ovomucoid- and ovalbumin-specific IgE/IgG4 ratios in egg allergy Caubet, JACI 2012;129:739 IgE/IgG4 ratio to O V A L B U 107 egg-allergic children M I (mean age 6.9 years) N Challenged to baked egg Specific IgE and IgG4 to O V ovomucoid (OVM) and O ovalbumin (OVA) M U C O I D

Significance of ovomucoid- and ovalbumin-specific IgE/IgG4 ratios in egg allergy Caubet, JACI 2012;129:739 IgE/IgG4 ratio to O V A The balance L B between IgE U 107 egg-allergic children M and IgG4 to (mean age 6.9 years) I N OVA and Challenged to baked egg OVM has Specific IgE and IgG4 to functional O V ovomucoid (OVM) and O consequences ovalbumin (OVA) M U C O I D

Patients suffering from non-IgE-mediated cow’s milk protein intolerance cannot be diagnosed based on IgG subclass or IgA responses to milk allergens Hochwallner H, Allergy 2011;66:1201Background: Cow’s milk is one of the most common causes of foodallergy. In two-thirds of patients, adverse symptoms following milkingestion are caused by IgE-mediated allergic reactions, whereasfor one-third, the mechanisms are unknown.Aim of this study was to investigate whether patients sufferingfrom non-IgE-mediated cow’s milk protein intolerance can bedistinguished from persons without cow’s milk protein intolerancebased on serological measurement of IgG and IgA specific forpurified cow’s milk antigens.

Patients suffering from non-IgE-mediated cow’s milk protein intolerance cannot be diagnosed based on IgG subclass or IgA responses to milk allergens Hochwallner H, Allergy 2011;66:1201 IgG1–4 subclass and IgA antibody to recombinant αS1-casein, Cow’s milk protein αS2-casein, β-casein, κ-casein, intolerant patients α-lactalbumin, and β-lactoglobulin. cannot be distinguished from Patients with IgE-mediated cow’s persons without milk allergy (CMA, n = 25), cow’s milk protein patients with non-IgE-mediated intolerance (CMPI, n = 19), intolerance on the patients with gastrointestinal basis of symptoms not associated with IgG subclass or cow’s milk ingestion (GI, n = 15) IgA reactivity to and control persons (C, n = 26) cow’s milk allergens.

Componentresolveddiagnosis

Comparison of conventional and component-resolved diagnostics by two different methods(Advia-Centaur- Microarray-ISAC) in pollen allergy Lizaso Ann Allergy Asthma Immunol 2011;107:35BackgroundComponent-resolved diagnostics (CRD) has recently beenintroduced into clinical allergology.ObjectiveThe aim of this study was to assess the contribution that thisnew diagnostic technique makes to conventional diagnosis inpatients with pollen allergy, comparing CRD with conventionaltechnologies, and to compare 2 CRD methods, Advia-Centaurand Microarray-ISAC.

Comparison of conventional and component-resolved diagnostics by two different methods (Advia-Centaur- Microarray-ISAC) in pollen allergy Lizaso Ann Allergy Asthma Immunol 2011;107:35 % cases in whom the diagnosis was modified by component resolved diagnostics Serum samples from 120 30 – pollen-allergic patients. 20 – 30% IgE to total extracts (CAP System) and individual allergens using both Component- 10 – resolved diagnostics methods 00

Comparison of conventional and component-resolved diagnostics by two different methods (Advia-Centaur- Microarray-ISAC) in pollen allergy Lizaso Ann Allergy Asthma Immunol 2011;107:35 % cases in whom the diagnosis was modified by component resolved diagnostics Either by detecting new Serum samples from 120 relevant sensitizations 30 – pollen-allergic patients. (mainly to Olea) or by 30% IgE to total out clinically ruling extracts 20 – (CAP System) sensitizations irrelevant and individual allergens usingpanallergens. caused by both Component- 10 – resolved diagnostics methods 00

Identification of a new major dog allergen highly cross-reactive with Fel d 4 in a population of cat- and dog-sensitized patients Hilger, JACI 2012;129:1149 Allergy to cat and dog are frequently associated Reports have shown IgE cross-reactivity between cat and dog danderin sensitized patients It is important to distinguish cosensitization from IgEcross-reactivity to cat and dog allergens Three lipocalins have been isolated from dog dander(Can f 1, Can f 2, and Can f 4) Two lipocalins have been characterized from cat (Fel d 4 and Fel d 7)

Identification of a new major dog allergen highly cross-reactive with Fel d 4 in a population of cat- and dog-sensitized patients Hilger, JACI 2012;129:1149 44 patients (mean age 33.5 years) In addition to cat and dog with (+) SPTs to cat & dog serum albumins and the 32 with rhinitis and/or lipocalins asthma related to cat Fel d 4 and Can f 6 now and/or dog exposure shown to be 5 patients with atopic cross-reactive with a eczema possibly related sequence identity between to cat and/or dog Can f 6 and exposure Fel d 4 of 67%.

Pollen-food syndrome is related to Bet v 1/PR-10 protein sensitization, but not all patients have spring rhinitis Rashid, Allergy 2011;66:1391  The pollen-food syndrome (PFS) results from sensitisation to panallergens that are common to pollen and edible plant products, typically manifesting as oral symptoms upon exposure to Rosaceae fruits.  The panallergen molecules comprise three protein clusters: Bet v 1/PR-10; profilins; non-specific lipid transfer proteins (nsLTP).

Pollen-food syndrome is related to Bet v 1/PR-10 protein sensitization, but not all patients have spring rhinitis Rashid, Allergy 2011;66:1391 Foods reported to cause symptoms in 24 patients with pollen-food syndrome

Pollen-food syndrome is related to Bet v 1/PR-10 protein sensitization, but not all patients have spring rhinitis Rashid , Allergy 2011;66:1391 Component-resolved diagnosis demonstrated ubiquitous Foods reported to cause symptoms in 24 patients sensitisation to the Bet v 1/PR-10 protein cluster with pollen-food syndrome

Pollen-food syndrome is related to Bet v 1/PR-10 protein sensitization, but not all patients have spring rhinitis Rashid , Allergy 2011;66:1391 Component-resolved diagnosis demonstrated ubiquitous sensitisation to the Bet v 1/PR-10 protein cluster Despite this finding, 4 of 24 had no history (past or present) of spring rhinitis: of these, 2 had symptoms restricted to the summer months only, 1 had chronic rhinitis with house dust mite allergy and 1 had no history of rhinitis

Tropomyosin IgE-positive results are a good predictor of shrimp allergy Gàmez, Allergy 2011;66:1375 Background: Shrimp is a common cause of food allergy. Our aims were to determine the value of IgE antibodies in the diagnosis of shrimp allergy and to study red shrimp (Solenocera melantho) tropomyosin both as a new allergen and as a crossreactive IgE-binding protein.

Tropomyosin IgE-positive results are a good predictor of shrimp allergy Gàmez, Allergy 2011;66:1375 1) Shrimp allergy was confirmed in 18 shrimp-allergic patients.45 subjects; 2) Skin prick test and IgE antibodies to shrimp were positive in all shrimp-allergicSkin prick test (SPT) patients.and specific IgE (sIgE) toshrimp, recombinant and 3) sIgE to rPen a 1 was detected innatural shrimp 98% of these patients.tropomyosins rPen a 1 andnPen m 1, recombinant 4) Of the 18 shrimp-tolerantDer p 10, and patients, 61% had positive SPT toDermatophagoides shrimp, 55% were IgE-positive topteronyssinus shrimp, and 33% showed IgE antibodies to rPen a 1.

Tropomyosin IgE-positive results are a good predictor of shrimp allergy Gàmez, Allergy 2011;66:1375 1) Shrimp allergy was confirmed in 18 shrimp-allergic patients.45 subjects; 2) Skin prick test and IgE antibodies to shrimp were IgE levels positive in all shrimp-allergicSkin prick test (SPT) patients.and specific IgEa 1 to rPen (sIgE) to providedshrimp, recombinant and 3) sIgE to rPen a 1 was detected innatural shrimp value additional 98% of these patients.tropomyosinsdiagnosis and to the rPen a 1 ofnPen m 1, recombinant 4) Of the 18 shrimp-tolerantDer p shrimp allergy. 10, and patients, 61% had positive SPT toDermatophagoides shrimp, 55% were IgE-positive topteronyssinus shrimp, and 33% showed IgE antibodies to rPen a 1.

Component-resolved diagnosis of vespid venom-allergic individuals: phospholipases and antigen 5s are necessary to identify Vespula or Polistes sensitization. Polistes Monsalve, Allergy 2012;67:528 VespulaBackground: Cross-reactivity between hymenoptera species variesaccording to the different allergenic components of the venom.The true source of sensitization must therefore be establishedto ensure the efficacy of venom immunotherapy.Objective: In the Mediterranean region, Polistes dominulus & Vespulaspp. are clinically relevant cohabitating wasps. A panel of majorvespid venom allergens was used to investigate whetherserum-specific IgE (sIgE) could be used to distinguish sensitizationto either vespid.

Component-resolved diagnosis of vespid venom-allergic individuals: phospholipases and antigen 5s are necessary to identify Vespula or Polistes sensitization. Polistes Monsalve, Allergy 2012;67:528 Vespula 1) sIgE was positive to either the antigen 5s (Pol d 5/Ves v 5) or 59 individuals with to the phospholipases allergic reactions to vespid (Pol d 1/Ves v 1) of the 2 stings and positive ImmunoCAP vespids, or to both components and/or intradermal tests at the same time. to vespid venoms. 2) In 69% of cases, it was sIgE against recombinant possible to define the most probable sensitizing insect, and and natural venom components in the rest, possible double using the ADVIA Centaur® sensitization could not be system. excluded.

Component-resolved diagnosis of vespid venom-allergic individuals: phospholipases and antigen 5s are necessary to identify Vespula or Polistes sensitization. Polistes Monsalve, Allergy 2012;67:528 Vespula 1) sIgE was positive to either the antigen 5s (Pol d 5/Ves v 5) or Vespula 59 individuals with to the phospholipases hyaluronidase allergic reactions to vespid (Pol d 1/Ves v 1) of the 2 was shown to have stings and positive ImmunoCAP vespids, or to both components and/or intradermal tests at the same time. no additional value toas regards the vespid venoms. 2) In 69% of cases, it was sIgEspecificity against recombinant possible to define the most probable sensitizing insect, and and natural assay. of the venom components in the rest, possible double using the ADVIA Centaur® sensitization could not be system. excluded.

Component-resolved diagnosis of vespid venom-allergic individuals: phospholipases and antigen 5s are necessary to identify Vespula or Polistes sensitization. Polistes Monsalve, Allergy 2012;67:528 Vespula 1) sIgE was positive to either the The major allergens antigen 5s (Pol d 5/Ves v 5) or 59of P.dominulus’ and individuals with to the phospholipases allergic reactions to vespid Vespula vulgaris’ (Pol d 1/Ves v 1) of the 2 stings and positive ImmunoCAP venom, namely vespids, or to both components and/or intradermal tests phospholipases and at the same time. to vespid venoms. antigen 5s, are required 2) In 69% of cases, it was to discriminate the possible to define the most sIgE against recombinant probable sensitizing probable sensitizing insect, and andspecies in vespid- natural venom components in the rest, possible double using the ADVIA Centaur® allergic patients. sensitization could not be system. excluded.

Ovomucoid (Gal d 1) specific IgE detected by microarray system predict tolerability to boiled hen’s egg and an increased risk to progress to multiple environmental allergen sensitization. Alessandri, Clin Exp Allergy 2012;42:441 % subjects 68 children with a suspected 60 – egg allergy. 50 – 51.4% Double-blind, 40 – placebo-controlled food challenge 30 – with boiled & raw eggs. 28% 20 – sIgE to egg allergens 20.5% 10 – available on the immunosolid phase 00 allergen chip (ISAC) Reactive to both Reactive to Tolerated both raw&boiled egg raw egg only raw&boiled egg 103 microarray.

Ovomucoid (Gal d 1) specific IgE detected by microarray system predict tolerability to boiled hen’s egg and an increased risk to progress to multiple environmental allergen sensitization. Alessandri, Clin Exp Allergy 2012;42:441 % Gal d 1 negative subjects 68 children 100 – with a suspected egg allergy. 94% 90 – 80 – Double-blind, 70 – placebo-controlled 60 – food challenge 50 – with boiled & raw eggs. 40 – sIgE to egg allergens 30 – available on the 20 – immunosolid phase 10 – allergen chip (ISAC) 0 103 microarray. tolerated boiled egg

Ovomucoid (Gal d 1) specific IgE detected by microarray system predict tolerability to boiled hen’s egg and an increased risk to progress to multiple environmental allergen sensitization. Alessandri, Clin Exp Allergy 2012;42:441 % Gal d 1 negative subjects 68 children 100 – with a suspected egg allergy. 94% 90 – Double-blind, negative Gal d 1 80 – 70 – children have placebo-controlled 60 – food challenge a high frequency 50 – with boiled & raw eggs. of tolerance 40 – sIgE to egg allergens to boiled egg. 30 – available on the 20 – immunosolid phase 10 – allergen chip (ISAC) 0 103 microarray. tolerated boiled egg

Ovomucoid (Gal d 1) specific IgE detected by microarray system predict tolerability to boiled hen’s egg and an increased risk to progress to multiple environmental allergen sensitization. Alessandri, Clin Exp Allergy 2012;42:441 % Gal d 1 positive subjects 68 children 100 – with a suspected egg allergy. 95% 90 – 80 – Double-blind, 70 – placebo-controlled 60 – food challenge 50 – with boiled & raw eggs. 40 – sIgE to egg allergens 30 – available on the 20 – immunosolid phase 10 – allergen chip (ISAC) 0 103 microarray. reacting to raw eggs

Ovomucoid (Gal d 1) specific IgE detected by microarray system predict tolerability to boiled hen’s egg and an increased risk to progress to multiple environmental allergen sensitization. Alessandri, Clin Exp Allergy 2012;42:441 % Gal d 1 positive subjects 68 children 100 – with a suspected egg allergy. 95% 90 – 80 – Double-blind,1 positive Gal d 70 – placebo-controlled children have food challenge 60 – witha high frequency boiled & raw eggs. 50 – of hen’s egg allergy. sIgE to egg allergens 40 – 30 – available on the 20 – immunosolid phase 10 – allergen chip (ISAC) 0 103 microarray. reacting to raw eggs

Is epitope recognition of shrimp allergens useful topredict clinical reactivity? Ayuso, Clin Exp Allergy 2012;42:293Background Shrimp is a frequent cause of severeallergic reactions world-wide. Due to issues such ascross reactivity, diagnosis of shrimp allergy is stillinaccurate, requiring the need for double-blind,placebo-controlled food challenges (DBPCFC).A better understanding of the relationship betweenlaboratory findings and clinical reactivity is needed.Objective To determine whether sensitization to certainshrimp allergens or recognition of particular IgE epitopesof those allergens are good biomarkers of clinical reactivityto shrimp.

Is epitope recognition of shrimp allergens useful topredict clinical reactivity? Ayuso, Clin Exp Allergy 2012;42:293 % of patients with a positive challenge to shrimps 100 – 37 patients with 90 – shrimp allergy. 80 – 70 – Skin prick 60 – test, sIgE, DBPCF 50 – C. 46% 40 – IgE binding to synthetic 30 – peptides 20 – (Lit v1, Lit v2, Lit v3, Lit v4). 10 – 17/37 0

Is epitope recognition of shrimp allergens useful topredict clinical reactivity? Ayuso, Clin Exp Allergy 2012;42:293 % of patients with a positive challenge to shrimps 37 patientsmicroarray, By with 100 – 90 – patients shrimp allergy. 80 – with positive 70 – Skin prick test, challenges showed specific IgE determinations, 60 – DBPCFC. intense binding more 50 – to shrimp peptides. 46% 40 – IgE binding to synthetic Particularly peptides (Lit v1, Lit v2, 30 – 20 – Lit v3, LitLit v1 & Lit v2 for v4). 10 – 17/37 epitopes. 0

Is epitope recognition of shrimp allergens useful topredict clinical reactivity? Ayuso, Clin Exp Allergy 2012;42:293 % of patients with a positive challenge to shrimps 100 – 37 patients with 90 – IgE antibodies shrimp allergy. 80 – Skin prick these shrimp to test, 70 – epitopes could be used specific IgE determinations, 60 – DBPCFC. biomarkers for as 50 – 46% 40 – IgE prediction of clinical binding to synthetic 30 – reactivity. peptides (Lit v1, Lit v2, 20 – Lit v3, Lit v4). 10 – 17/37 0

Identification of a Dau c PRPlike protein (Dau c 1.03)as a new allergenic isoform in carrots (cultivar Rodelika). Wangorsch, Clin Exp Allergy 2012;42:156 1) Carrot (Daucus carota) allergy is one of the most common types of birch pollen-related food allergy in central Europe. 2) Approximately 24% of food allergic subjects suffer from allergic symptoms after ingestion of carrots. 3) Adverse reactions to carrots are elicited due to cross-reactive IgE-epitopes between the major birch pollen allergen, Bet v 1 and homologous food proteins. 4) Bet v 1 and the major carrot allergen Dau c 1 belong to the family of pathogenesis related proteins 10 (PR-10).

Identification of a Dau c PRPlike protein (Dau c 1.03)as a new allergenic isoform in carrots (cultivar Rodelika). Wangorsch, Clin Exp Allergy 2012;42:156 •The Dau c PRPlike proteinObjective To investigate was identified as a newpotential allergenic properties allergenic isoform, Dau cof a Dau c PRPlike protein, 1.03, in carrot roots.a novel isoform of thepathogenesis related proteins •68% of carrot allergic10 (PR-10) protein family in patients were sensitized tocarrot. rDau c 1.03.

Identification of a Dau c PRPlike protein (Dau c 1.03)as a new allergenic isoform in carrots (cultivar Rodelika). Wangorsch, Clin Exp Allergy 2012;42:156 Dau c 1.03 appears •The Dau c PRPlike protein to contribute to the was identified as a newObjective To investigate allergenicity allergenic isoform, Dau cpotential carrots and should of allergenic properties 1.03, in carrot roots.of a Dau cbe considered PRPlike protein,a novel isoform ofsilencing for gene the PR-10 •68% of carrot allergicprotein family in carrot. of carrot allergens. patients were sensitized to rDau c 1.03.

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What 2012 diagnosis atopy

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