Definition, acronyms, nomenclature, and classification of angioedema (DANCE): AAAAI, ACAAI, ACARE, and APAAACI DANCE consensus.

BACKGROUND: Angioedema (AE) manifests with intermittent, localized, self-limiting swelling of the subcutaneous and/or submucosal tissue. AE is heterogeneous, can be hereditary or acquired, may occur only once or be recurrent, may exhibit wheals or not, and may be due to mast cell mediators, bradykinin, or other mechanisms. Several different taxonomic systems are currently used, making it difficult to compare the results of studies, develop multicenter collaboration, and harmonize AE treatment. OBJECTIVE: We developed a consensus on the definition, acronyms, nomenclature, and classification of AE (DANCE). METHODS: The initiative involved 91 experts from 35 countries and was endorsed by 53 scientific and medical societies, and patient organizations. A consensus was reached by online discussion and voting using the Delphi process over a period of 16 months (June 2021 to November 2022). RESULTS: The DANCE initiative resulted in an international consensus on the definition, classification, and terminology of AE. The new consensus classification features 5 types and endotypes of AE and a harmonized vocabulary of abbreviations/acronyms. CONCLUSION: The DANCE classification complements current clinical guidelines and expert consensus recommendations on the diagnostic assessment and treatment of AE. DANCE does not replace current clinical guidelines, and expert consensus algorithms and should not be misconstrued in a way that affects reimbursement of medicines prescribed by physicians using sound clinical judgment. We anticipate that this new AE taxonomy and nomenclature will harmonize and facilitate AE research and clinical studies, thereby improving patient care.

Altered levels of phospholipases C, diacylglycerols, endocannabinoids, and N-acylethanolamines in patients with hereditary angioedema due to FXII mutation.

BACKGROUND: Hereditary angioedema (HAE) is a rare genetic disorder characterized by local, self-limiting edema due to temporary increase in vascular permeability. HAE with normal C1 esterase inhibitor (C1INH) activity includes the form with mutations in the F12 gene encoding for coagulation factor XII (FXII-HAE) causing an overproduction of bradykinin (BK) leading to angioedema attack. BK binding to B2 receptors (BK2R) leads to an activation of phospholipase C (PLC) and subsequent generation of second messengers: diacylglycerols (DAGs) and possibly the endocannabinoids (eCBs), 2-arachidonoylglycerol (2-AG) and anandamide (AEA), and eCB-related N-acylethanolamines [palmitoylethanolamide (PEA) and oleoylethanolamide (OEA)]. To date, there are no data on the role of these lipid mediators in FXII-HAE. METHODS: Here, we analyzed plasma levels of PLC, DAGs, and eCBs in 40 patients with FXII-HAE and 40 sex- and age-matched healthy individuals. RESULTS: Plasma PLC activity was increased in FXII-HAE patients compared to controls. Concentrations of DAG 18:1-20:4, a lipid second messenger produced by PLC, were higher in FXII-HAE compared to controls, and positively correlated with PLC activity and cleaved high molecular kininogen (cHK). Also the concentrations of the DAG metabolite, 2-AG were altered in FXII-HAE. AEA and OEA were decreased in FXII-HAE patients compared to controls; by contrast, PEA, was increased. The levels of all tested mediators did not differ between symptomatic and asymptomatic patients. Moreover, C1INH-HAE patients had elevated plasma levels of PLC, which correlated with cHK, but the levels of DAGs and eCBs were the same as controls. CONCLUSIONS: BK overproduction and BKR2 activation are linked to alteration of PLCs and their metabolites in patients with FXII-HAE. Our results may pave way to investigations on the functions of these mediators in the pathophysiology of FXII-HAE, and provide new potential biomarkers and therapeutic targets.

Global influence of dupilumab on Quality of Life in a severe asthma patient with T2 multimorbidities: a case report on atopic dermatitis, chronic rhinosinusitis with nasal polyposis, and eosinophilic esophagitis.

INTRODUCTION: Interleukin (IL)-4 and IL-13 are considered key drivers of type 2 inflammatory diseases. Dupilumab is a fully human monoclonal antibody that blocks the shared receptor component for IL-4 and IL-13, thus inhibiting signaling of both cytokines. CASE STUDY: We report a case of a patient with uncontrolled severe asthma and other T2 inflammatory diseases (atopic dermatitis, chronic rhinosinusitis with nasal polyposis and eosinophilic esophagitis) treated with dupilumab. RESULTS: After one year of treatment, dupilumab improved asthma control together with lung function parameters and airway inflammation. Additionally, a positive impact on quality of life (QoL), evaluated by validated questionnaires, across all the diseases was observed. CONCLUSION: In this case report, a positive and objectively measurable of global improvement on QoL across all four T2 comorbidities was observed after treatment with dupilumab, demonstrating the important role of IL-4 and IL-13 and the existence of a unifying pathological mechanism in T2 diseases.

Long-Term Omalizumab in Elderly Patients with Chronic Urticaria: Is It a Safe Therapy?

BACKGROUND: Biologics have revolutionized the treatment of many diseases. In this regard, omalizumab (OMA), an anti-IgE monoclonal antibody, is the recommended therapeutic option for patients with chronic spontaneous urticaria (CSU) refractory to second-generation H1-antihistamines. Several studies confirm the efficacy and safety of the drug. However, the literature focusing on the elderly population is scarce, as this age group is often excluded from clinical trials. Therefore, the pharmacological treatment of CSU in elderly patients is a challenge that is increased by their comorbidities and consequent polypharmacy. OBJECTIVES: We describe the real-life safety profile of OMA in elderly patients (≥70 years) with CSU and chronic inducible urticaria (CIndU). We aimed to provide data for daily clinical practice in this vulnerable patient group. METHOD: A retrospective review was performed of the records of patients with CSU/CIndU from May 2003 to December 2019 in the Hospital Universitario La Paz. We describe qualitative and quantitative data according to measures of central tendency. Comparisons between qualitative and quantitative data were performed with the Mann-Whitney U test and the Fisher's test for qualitative variables. A p value <0.05 was considered statistically significant. RESULTS AND CONCLUSIONS: Eighty-nine patients were included, divided into two groups (<70 vs. ≥70 years). The overall rate of adverse events (AEs) was 48%, mainly mild. No association between age and AE was found (p = 0.789). No serious AE such as anaphylaxis was detected. CSU predominated in both groups. CIndU was less prevalent in the elderly (p = 0.017). There was no association between age and the other variables. Although the frequency of neoplasms was slightly higher in the elderly with OMA, we found no difference compared to the incidence of neoplasms in the general population. Therefore, our data suggest that OMA may be a safe treatment in elderly people with CSU/CIndU for prolonged periods of treatment, although further studies with larger samples are needed to corroborate our observations.

The Icatibant Outcome Survey: 10 years of experience with icatibant for patients with hereditary angioedema.

In patients with hereditary angioedema (HAE), bradykinin causes swelling episodes by activating bradykinin B2 receptors. Icatibant, a selective bradykinin B2 receptor antagonist, is approved for on-demand treatment of HAE attacks. The Icatibant Outcome Survey (IOS; NCT01034969) is an ongoing observational registry initiated in 2009 to monitor the effectiveness/safety of icatibant in routine clinical practice. As of March 2019, 549 patients with HAE type 1 or 2 from the IOS registry had been treated of 5995 total attacks. This article reviews data published from IOS over time which have demonstrated that the effectiveness of icatibant in a real-world setting is comparable to efficacy in clinical trials; one dose is effective for the majority of attacks; early treatment (facilitated by self-administration) leads to faster resolution and shorter attack duration; effectiveness/safety of icatibant has been shown across a broad range of patient subgroups, including children/adolescents and patients with HAE with normal C1 inhibitor levels; and tolerability has been demonstrated in patients aged ≥65 years. Additionally, this review highlights how IOS data have provided valuable insights into patients' diagnostic journeys and treatment behaviours across individual countries. Such findings have helped to inform clinical strategies and guidelines to optimise HAE management and limit disease burden. This research was sponsored by Takeda Development Center Americas, Inc. Takeda Development Center Americas, Inc., provided funding to Excel Medical Affairs for support in writing and editing this manuscript.

The international WAO/EAACI guideline for the management of hereditary angioedema-The 2021 revision and update.

Hereditary angioedema (HAE) is a rare and disabling disease for which early diagnosis and effective therapy are critical. This revision and update of the global WAO/EAACI guideline on the diagnosis and management of HAE provides up-to-date guidance for the management of HAE. For this update and revision of the guideline, an international panel of experts reviewed the existing evidence, developed 28 recommendations, and established consensus by an online DELPHI process. The goal of these recommendations and guideline is to help physicians and their patients in making rational decisions in the management of HAE with deficient C1 inhibitor (type 1) and HAE with dysfunctional C1 inhibitor (type 2), by providing guidance on common and important clinical issues, such as: (1) How should HAE be diagnosed? (2) When should HAE patients receive prophylactic on top of on-demand treatment and what treatments should be used? (3) What are the goals of treatment? (4) Should HAE management be different for special HAE patient groups such as children or pregnant/breast-feeding women? and (5) How should HAE patients monitor their disease activity, impact, and control? It is also the intention of this guideline to help establish global standards for the management of HAE and to encourage and facilitate the use of recommended diagnostics and therapies for all patients.

Demographic and clinical characteristics of patients with hereditary angioedema in Canada.

BACKGROUND: Data on the clinical and demographic features of Canadian patients with hereditary angioedema (HAE) are lacking. OBJECTIVE: To describe the clinical and demographic features in a large Canadian HAE cohort and compare them with patients with HAE in other countries. METHODS: An online questionnaire was distributed to the members of 2 Canadian HAE patient groups to collect information on demographics and HAE clinical characteristics. All participants 18 years of age or older with HAE type I or II were eligible. Frequency, location, prodromes, and triggers of HAE attacks, including types of HAE treatment, were characterized. RESULTS: Among the 90 participants who completed the online survey, 57% self-identified as having HAE type 1 and 26% HAE type II. The average diagnostic delay was 11 years. In the preceding 6 months, 24% of the participants had no attacks and 35% experienced greater than 5 attacks. The most frequently affected regions of the body were the abdomen (83%), arms orlegs (63%), face (41%), and larynx or throat (41%). Approximately 87% of the participants reported having access to C1 inhibitor at home, and 69% reported using it for long-term prophylaxis. CONCLUSION: Canadian patients with HAE share common clinical characteristics with patients with HAE in other countries. They had a delay in HAE diagnosis and a high burden of disease, as indicated by the high frequency of attacks in the preceding 6 months. This study provides a better understanding of the demographic and clinical characteristics of Canadian patients with HAE.

Consensus on treatment goals in hereditary angioedema: A global Delphi initiative.

BACKGROUND: Hereditary angioedema (HAE) is a rare, life-threatening genetic disorder characterized by recurrent episodes of subcutaneous or submucosal angioedema. The ultimate goals of treatment for HAE remain ill-defined. OBJECTIVES: The aim of this Delphi process was to define the goals of HAE treatment and to examine which factors should be considered when assessing disease control and normalization of the patient's life. METHODS: The Delphi panel comprised 23 participants who were selected based on involvement with scientific research on HAE or coauthorship of the most recent update and revision of the World Allergy Organization/European Academy of Allergy and Clinical Immunology guideline on HAE. The process comprised 3 rounds of voting. The final round aimed to aggregate the opinions of the expert panel and to achieve consensus. RESULTS: Two direct consensus questions were posed in round 2, based on the responses received in round 1, and the panel agreed that the goals of treatment are to achieve total control of the disease and to normalize the patient's life. For the third round of voting, 21 statements were considered, with the participants reaching consensus on 18. It is clear from the wide-ranging consensus statements that the burdens of disease and treatment should be considered when assessing disease control and normalization of patients' lives. CONCLUSIONS: The ultimate goal for HAE treatment is to achieve no angioedema attacks. The availability of improved treatments and disease management over the last decade now makes complete control of HAE a realistic possibility for most patients.

Decreasing Attacks and Improving Quality of Life through a Systematic Management Program for Patients with Hereditary Angioedema.

INTRODUCTION: Prevention of attacks is a major goal in management of patients with hereditary angioedema (HAE). We aimed to investigate the effects of a systematic intervention for HAE patients. METHODS: Thirty-three patients with HAE with C1-inhibitor deficiency, belonging to a single family, participated in a management program coordinated by an allergist/immunologist. Angioedema attacks before intervention were ascertained by interviews and emergency room charts and recorded prospectively by patients or caregivers after enrollment. Mean number of attacks/month was compared at 12 months preintervention and 8 and 14 months within intervention. Patient-reported outcome instruments were used to assess quality of life, including HAE Quality of Life (HAE-QoL) questionnaire, psychological conditions, and work impairment, at baseline and 8 and 14 months within intervention. Data were stored in REDCap platform and analyzed by adjusted Bayesian models of double Poisson regression. RESULTS: Mean number of attacks/month significantly decreased (95% credible interval [CrI] excluding 0) from 1.15 preintervention to 0.25 and 0.23, 8 and 14 months within intervention, with mean decreases of -0.89 (95% CrI: -1.21 to -0.58) and -0.92 (95% CrI: -1.22 to -0.60), respectively. HAE-QoL scores showed mean total increases of 15.2 (95% CrI: 1.23-29.77) and 26 (95% CrI: 14.56-39.02) at 8 and 14 months within the study, as compared to baseline, revealing marked improvement in quality of life. Significant increase in role-emotional and reduction of depression, stress, and anxiety were observed at 14 months. CONCLUSION: A systematic approach integrating HAE-specific care with effective handling of psychological issues decreased the number of attacks and improved quality of life, targets for best practice in HAE.

Quality of life in patients with hereditary angioedema in Canada.

BACKGROUND: Hereditary angioedema (HAE) is associated with decreased quality of life (QoL), which has typically been measured using a generic non-disease-specific questionnaire. OBJECTIVE: We aimed to assess the QoL in patients with HAE type I and II in Canada using a previously validated HAE-specific questionnaire. METHODS: An online questionnaire was sent to the members of two Canadian HAE patient groups to collect data on demographics, HAE clinical course, and QoL scores. All patients 18 years of age or older with HAE type I or II were eligible. The impact of the available clinical factors on the QoL scores was evaluated. Multiple linear regression was performed using clinically relevant factors to predict HAE QoL outcome. RESULTS: Among the 72 patients in the study, the mean total HAE QoL score was 102 (±23) (SD) on a scale of 25 to 135, with higher scores indicating better QoL. Although the total QoL scores correlated positively with patients' level of satisfaction and perceived control (P < .001 for both), it correlated negatively with the number of acute attacks (P = .03). Yet, the types of treatment did not have an impact on the QoL. Predictors, including sex, comorbidities, and the number of attacks, only explained 12% of the variance in the total QoL scores. CONCLUSION: HAE continues to impair QoL in Canadian patients despite receiving recommended treatment. Although the frequency of attacks affects QoL, patients' experience with their HAE care also affects QoL substantially. The study highlights the importance of considering patients' experience with their HAE care as physicians develop an appropriate management plan.

Patient-reported Outcome Measures for Angioedema: A Literature Review.

Angioedema and hereditary angioedema are characterized by swelling of the subcutaneous and/or submucosal tissue, resulting in localized oedema. The rarity, but also the diverse clinical presentation, of these conditions can be challenging regarding diagnosis, treatment, and management. Patient-reported outcome measures (PROMs) are data received directly from the patient, providing the patient's perspective on various subjects regarding health and well-being. PROMs can be helpful tools to optimize treatment and long-term management of conditions. A major challenge regarding the consistent use of PROMs in clinical settings in Scandinavia is language availability; many of the validated PROMs for hereditary angioedema and angioedema lack translations into the Nordic languages. The litterature search yielded 9 different PROM tools for angioedema and hereditary angioedema. Five were found suitable for use in clinical practice in Europe. Even though several PROMs exist they are not used consistent. Accessible electronic PROMs and careful planning is required to implement PROMs optimally in routine care processes.

Complement Factor D (adipsin) Levels Are Elevated in Acquired Partial Lipodystrophy (Barraquer-Simons syndrome).

Complement overactivation has been reported in most patients with Barraquer-Simons syndrome (BSS), a rare form of acquired partial lipodystrophy. Complement Factor D (FD) is a serine protease with a crucial role in the activation of the alternative pathway of the complement system, which is mainly synthesized by adipose tissue. However, its role in the pathogenesis of BSS has not been addressed. In this study, plasma FD concentration was measured in 13 patients with BSS, 20 patients with acquired generalized lipodystrophy, 22 patients with C3 glomerulopathy (C3G), and 50 healthy controls. Gene expression and immunohistochemistry studies were assayed using atrophied adipose tissue from a patient with BSS. We found significantly elevated FD levels in BSS cases compared with the remaining cohorts (p < 0.001). There were no significant differences in FD levels between sexes but FD was strongly and directly associated with age in BSS (r = 0.7593, p = 0.0036). A positive correlation between FD and C3 was seen in patients with C3G, characterized by decreased FD levels due to chronic C3 consumption, but no correlation was detected for BSS. Following mRNA quantification in the patient's adipose tissue, we observed decreased CFD and C3 but elevated C5 transcript levels. In contrast, the increased FD staining detected in the atrophied areas reflects the effects of persistent tissue damage on the adipose tissue, thus providing information on the ongoing pathogenic process. Our results suggest that FD could be a reliable diagnostic biomarker involved in the pathophysiology of BSS by promoting unrestrained local complement system activation in the adipose tissue environment.

Prevention of Hereditary Angioedema Attacks with a Subcutaneous C1 Inhibitor.

BACKGROUND: Hereditary angioedema is a disabling, potentially fatal condition caused by deficiency (type I) or dysfunction (type II) of the C1 inhibitor protein. In a phase 2 trial, the use of CSL830, a nanofiltered C1 inhibitor preparation that is suitable for subcutaneous injection, resulted in functional levels of C1 inhibitor activity that would be expected to provide effective prophylaxis of attacks. METHODS: We conducted an international, prospective, multicenter, randomized, double-blind, placebo-controlled, dose-ranging, phase 3 trial to evaluate the efficacy and safety of self-administered subcutaneous CSL830 in patients with type I or type II hereditary angioedema who had had four or more attacks in a consecutive 2-month period within 3 months before screening. We randomly assigned the patients to one of four treatment sequences in a crossover design, each involving two 16-week treatment periods: either 40 IU or 60 IU of CSL830 per kilogram of body weight twice weekly followed by placebo, or vice versa. The primary efficacy end point was the number of attacks of angioedema. Secondary efficacy end points were the proportion of patients who had a response (≥50% reduction in the number of attacks with CSL830 as compared with placebo) and the number of times that rescue medication was used. RESULTS: Of the 90 patients who underwent randomization, 79 completed the trial. Both doses of CSL830, as compared with placebo, reduced the rate of attacks of hereditary angioedema (mean difference with 40 IU, -2.42 attacks per month; 95% confidence interval [CI], -3.38 to -1.46; and mean difference with 60 IU, -3.51 attacks per month; 95% CI, -4.21 to -2.81; P<0.001 for both comparisons). Response rates were 76% (95% CI, 62 to 87) in the 40-IU group and 90% (95% CI, 77 to 96) in the 60-IU group. The need for rescue medication was reduced from 5.55 uses per month in the placebo group to 1.13 uses per month in the 40-IU group and from 3.89 uses in the placebo group to 0.32 uses per month in the 60-IU group. Adverse events (most commonly mild and transient local site reactions) occurred in similar proportions of patients who received CSL830 and those who received placebo. CONCLUSIONS: In patients with hereditary angioedema, the prophylactic use of a subcutaneous C1 inhibitor twice weekly significantly reduced the frequency of acute attacks. (Funded by CSL Behring; COMPACT EudraCT number, 2013-000916-10 , and ClinicalTrials.gov number, NCT01912456 .).

Ani s 11-Like Protein Is a Pepsin- and Heat-Resistant Major Allergen of Anisakis spp. and a Valuable Tool for Anisakis Allergy Component-Resolved Diagnosis.

BACKGROUND: Anisakis simplex is a fish parasite responsible for gastrointestinal and allergic symptoms in humans. The Ani s 11-like protein has been proposed as an Anisakis allergen because its primary structure is similar to that of Ani s 11. The aims of this work were to analyse the frequency of detection of the Ani s 11-like protein and assess its diagnostic value. METHODS: rAni s 11-like protein, rAni s 5 and rAni s 4 were expressed in Escherichia coli and rAni s 1 was produced in Pichia pastoris. Recombinant allergen detection patterns in 37 Anisakis-sensitised patients were determined. The stability to pepsin digestion and heat treatment of rAni s 11-like protein was also analysed by IgE immunoblotting. RESULTS: Ani s 11-like protein is a major allergen detected by 78% of Anisakis-allergic patients, and 13.5% of patients detect only the rAni s 11-like allergen. This allergen is heat stable because it retains its capability of binding IgE after boiling for 30 min and it is resistant to pepsin digestion for 120 min. CONCLUSIONS: These data indicate that the Ani s 11-like protein is a pepsin- and heat-resistant major allergen (Ani s 11.0201) of Anisakis spp. and a valuable tool for Anisakis allergy component-resolved diagnosis.

Misdiagnosis trends in patients with hereditary angioedema from the real-world clinical setting.

BACKGROUND: Hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE) causes swelling in the skin and upper airways and pain in the abdomen because of mucosal swelling. C1-INH-HAE is frequently misdiagnosed, leading to delays in diagnosis, inadequate treatment, and unnecessary procedures. OBJECTIVE: To evaluate the history of misdiagnosis in patients participating in the Icatibant Outcome Survey (IOS). METHODS: The IOS is an observational study in which safety and effectiveness of icatibant have been evaluated since 2009. As part of the IOS, patients record any misdiagnoses received before being diagnosed as having C1-INH-HAE. RESULTS: In January 2016, a total of 418 of 633 IOS patients with C1-INH-HAE type I or II had provided misdiagnosis data. Of these, 185 of 418 (44.3%) received 1 or more prior misdiagnoses. The most common misdiagnoses were allergic angioedema (103 of 185) and appendicitis (50 of 185). A variety of other misdiagnoses were reported, including a substantial number of gastrointestinal disorders (excluding appendicitis). Misdiagnosis rates were similar between males (41.1%) and females (46.5%) and between C1-INH-HAE type I (43.7%) and type II (51.6%). Patients with family members diagnosed as having C1-INH-HAE were significantly less likely to be misdiagnosed than patients without a family history (140 of 366 [41.7%] vs 38 of 58 [65.5%], respectively; P = .001). Patients with a prior misdiagnosis had longer median delay to C1-INH-HAE diagnosis (13.3 years) than patients without (1.7 years; P < .001). CONCLUSION: From this large database, approximately 50% of patients with C1-INH-HAE type I or II have previously had their conditions misdiagnosed, most commonly as allergic angioedema or appendicitis. Misdiagnosis results in marked delays in receiving the correct diagnosis, during which time patients cannot access effective, lifesaving treatment. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01034969.

Treatment of HAE Attacks in the Icatibant Outcome Survey: An Analysis of Icatibant Self-Administration versus Administration by Health Care Professionals.

BACKGROUND: Icatibant, a selective bradykinin B2 receptor antagonist for the treatment of acute hereditary angio-oedema (HAE) attacks in adults, can be administered by health care professionals (HCPs) or self-administered. This analysis compared characteristics and outcomes of acute HAE attacks treated with self-administered and HCP-administered icatibant in a real-world setting. METHODS: The Icatibant Outcome Survey (Shire, Zug, Switzerland; NCT01034969) is an international observational study monitoring the safety and effectiveness of icatibant treatment. Descriptive retrospective analyses were performed (February 2008 to December 2012). RESULTS: Icatibant was used in 652 attacks in 170 patients with HAE type I/II. Most icatibant injections were self-administered (431/652, 68.5%). The proportion of self-treated attacks increased over time (40.3% in 2009 vs. 89.7% in 2012). The median time to administration was significantly shorter in self- versus HCP-treated attacks (1.5 vs. 2.4 h; p = 0.016). Earlier treatment (<2 h after onset) was significantly associated with a shorter median time to resolution (2.5 vs. 5.0 h; p = 0.032) and attack duration (3.0 vs. 14.0 h; p < 0.0001), regardless of administration method. Patients self-administered icatibant for attacks of all severities; overall, 34.7% of severe and 30.2% of very severe attacks were HCP treated. Logistic regression analysis did not find use of long-term prophylaxis, attack location or gender to be predictive for self-administration. CONCLUSIONS: The proportion of HAE attacks treated with self-administered icatibant increased over time. Patients successfully self-administered icatibant for a wide variety of HAE attacks, demonstrating that icatibant is generally well tolerated and effective for self-administration. Self-administration of icatibant provides a complementary option to HCP administration, enabling optimization of patient care.

Utility of specific IgE to Ara h 6 in peanut allergy diagnosis.

BACKGROUND: Specific IgE to Ara h 2 has been shown to be useful in the diagnosis of peanut allergy, whereas the peanut lipid transfer protein, Ara h 9, has been suggested to be responsible for peanut allergy in the Mediterranean population. OBJECTIVE: To better characterize peanut allergy in children from a Mediterranean area and determine the value of specific IgE to Ara h 6 (conglutinin, 2S albumin) for the diagnosis of peanut allergy. METHODS: Ninety-one children with suspected allergy to edible vegetables were included in the study. They were classified as allergic or tolerant to peanut. Specific IgE to peanut allergens was measured by a commercially available microarray (ImmunoCAP ISAC 112, ThermoFisher, Uppsala, Sweden). RESULTS: Patients allergic to peanut showed positive specific IgE changes to peanut seed storage proteins (Ara h 1, Ara h 2, Ara h 3, and Ara h 6) more frequently than tolerant subjects. Ara h 9 showed a similar frequency of reactivity in the 2 groups. Ara h 6 was the allergen most frequently recognized by patients with allergy. Four patients with allergy were found to be mono-sensitized to Ara h 6. Ara h 2 and Ara h 6 showed similar diagnostic accuracy (areas under the curve 0.792 and 0.852). A combined cutoff point for Ara h 2 (≥0.1 ISU) and Ara h 6 (≥2 ISU) yielded the best diagnostic performance (sensitivity 0.77, specificity 0.97, positive predictive value 0.89, negative predictive value 0.93). CONCLUSION: Peanut allergy cannot be ruled out without obtaining a negative determination of Ara h 6.