Francisca Gomez

Diagnosis of immediate hypersensitivity reactions to radiocontrast media

No consensus exists on the diagnostic approach for immediate hypersensitivity reactions (IHR) to radiocontrast media (RCM). We analyzed the diagnostic value of a skin test (ST), drug provocation test (DPT) and basophil activation test (BAT) in patients with symptoms compatible with IHR to RCM.

Diagnostic evaluation of patients with nonimmediate cutaneous hypersensitivity reactions to iodinated contrast media

Nonimmediate hypersensitivity reactions to iodinated contrast media (CM) are common. Allergological evaluation is necessary to confirm the diagnosis and to find a tolerated alternative. The aim of this study was to establish the role of skin testing and the drug provocation test (DPT) in the diagnosis of nonimmediate reactions to CM.

NSAID‐induced urticaria/angioedema does not evolve into chronic urticaria: a 12‐year follow‐up study

Nonsteroidal anti‐inflammatory drugs (NSAIDs) are the most frequent medicaments involved in drug hypersensitivity reactions, with NSAID‐induced urticaria/angioedema (NIUA) being the most frequent clinical entity. The natural evolution of NIUA has been suggested to lead to chronic urticaria (CU) in an important proportion of patients, such that NIUA may therefore precede CU. Our aim was to verify whether these entities are related by following up a large cohort of patients with NIUA as well as a control group over a long period of time.

Detailed characterization of Act d 12 and Act d 13 from kiwi seeds: implication in IgE cross-reactivity with peanut and tree nuts

Act d 12 (11S globulin) and Act d 13 (2S albumin) are two novel relevant allergens from kiwi seeds that might be useful to improve the diagnostic sensitivity and the management of kiwifruit‐allergic patients.

Act d 12 and Act d 13: Two novel, masked, relevant allergens in kiwifruit seeds

To the Editor: Kiwifruit (Actinidia deliciosa) is a common cause of IgE-mediated food allergy. Kiwifruit allergy has been associated with pollen, latex, and occupational baker’s allergy, and the main clinical manifestations range from local oral allergy syndrome to severe systemic reactions. Diagnosis of kiwifruit allergy has significantly improved during the last years. However, the main limitations in diagnosis are the low specificity of prick-to-prick tests and the low sensitivity of in vivo skin prick tests (SPTs) and in vitro serum specific IgE determinations. A current limitation of kiwifruit allergen–based in vitro diagnostics is that 35% of patients with kiwifruit allergy are overlooked as false-negative responders. To date, 11 kiwifruit allergens have been described according to the International Union of Immunological Societies allergen nomenclature subcommittee (www.allergen.org). Considering that all the currently known kiwifruit allergens, except Act d 10 (the lipid transfer protein), have been exclusively described in the pulp of kiwifruit, together with the fact that seeds are commonly ingested with the pulp, we hypothesized that novel key allergens in kiwi seeds might have been masked in the context of kiwifruit allergy. The aim of this study was to identify new relevant allergens in kiwi seeds that might help to increase diagnostic sensitivity. Fifty-five patients with kiwifruit allergy given diagnoses according to previously reported criteria were recruited from the Allergy Service of 3 different centers in Spain: Hospital Carlos Haya (M alaga) andHospitals Fundaci on Jim enez D ıaz and Infanta Leonor (Madrid). The study was approved by the ethics committees of the 3 hospitals, and written informed consent was obtained from all subjects. Fully detailed methods are described in the Methods section in this article’s Online Repository at www.jacionline.org. The general clinical characteristics of the 55 patients with kiwifruit allergy included in this study are summarized in Table E1 in this article’s Online Repository at www.jacionline.org. Themedian age of the patientswas 32.0 years (ranging from 16.0 to 71.0 years), with a predominance of female subjects (39 vs 16). Approximately 62% of the patients referred exclusively local symptoms, and 38.2% had immediate systemic reactions after ingestion of kiwifruit. Themost frequently reported symptoms were oral allergy syndrome (61.8%), anaphylaxis (16.3%), and angioedema (14.5%). Approximately 22% of the patients were only allergic to kiwifruit, and 78.2% had symptoms with other plant foods, such as members of the Rosaceae family (50.1%), tree nuts (41.8%), or peanut (30.9%). Only 50.9% and 43.6% of the patients had positive SPT and ELISA results with kiwifruit extract, respectively, which is in accordance with previous reports. To identify novel allergens in kiwi seeds, we grouped the patients with kiwifruit allergy according to positive (group 1) or negative (group 2) SPT responses to kiwifruit extract (see Table E1).We assayed in immunoblotting a pool of sera from each group against homemade total kiwifruit (pulp and seeds), pulp kiwifruit, and kiwi seed extracts prepared as previously described for each specific tissue (see the Methods section in this article’s Online Repository). The protein content of total and pulp kiwifruit extracts was very similar (Fig 1, A, lane CBS). Two main protein bands of approximately 51 and 12 kDa detected in kiwi seeds but not in total and pulp kiwifruit extracts were recognized by the 2 serum pools (Fig 1, A). The serum pool from group 2 exclusively reacted against the allergens contained in kiwi seed extract, whereas the pool from group 1 also reacted to different protein bands contained in total and pulp kiwifruit but not in kiwi seed extract. The IgE-reactive protein bands of 51 and 12 kDa contained in kiwi seeds were separated by means of SDS-PAGE (Fig 1, B, inset), excised from the gel, and digested with trypsin. The obtained peptides were analyzed by using Edman degradation, matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MS), and tandem mass spectrometry (MS/MS). The identified peptides from each protein are indicated in the MS profile (Fig 1,B). The comparison of these peptides with those from databases (see Fig E1 in this article’s Online Repository at www.jacionline.org) allowed the identification of the proteins of 51 and 12 kDa as an 11S globulin and a 2S albumin, respectively, which were named Act d 12 (UniProt accession no. C0HJF9) and Act d 13 (UniProt accession no. C0HJG0) according to the International Union of Immunological Societies Allergen Nomenclature Subcommittee. 11S globulins and 2S albumins have been previously described as potent food allergens able to induce primary sensitization at the gastrointestinal level. We tested all the sera against kiwi seed extract (Fig 1, C) and total kiwifruit extract (see Fig E2 in this article’s Online Repository at www.jacionline.org). Thirty-nine (70.9%) of the 55 patients reacted to the 51-kDa allergen (Act d 12) and 10 (18.2%) of the patients reacted to the 12-kDa allergen (Act d 13) from kiwi seeds (Fig 1, C). Approximately 71% of the patients from group 1 and only 18.5% from group 2 reacted to at least 1 allergen in total kiwifruit extract (see Fig E2). Act d 12 and Act d 13 were not detected in total or pulp kiwifruit extract, likely because of the poor extraction of such proteins when using conventional protocols to prepare aqueous extracts from fruits, which might well justify why patients from group 2 did not have positive SPT responses. We purified both allergens to homogeneity from kiwi seeds (Fig 2, A) according to conventional chromatographic procedures (see the Methods section in this article’s Online Repository). Purified Act d 12 and Act d 13 were recognized in ELISA by 65.5% and 25.5% of the patients, respectively (see Table E1). Patients 25, 30, and 44 had positive responses to purified Act d 12 in immunoblotting (data not shown) but not in ELISAs, suggesting the existence of potential internal epitopes. Patients 30, 34, 41, and 42 reacted to purified Act d 13 in ELISAs but not in immunoblotting, suggesting the existence of potential conformational epitopes. Act d 12 and Act d 13 demonstrated in vivo biological activity. Patients with kiwifruit allergy, but not healthy control subjects, had positive SPT responses to kiwi seed extract (4/4), purified Act d 12 (4/4), and purified Act d 13 (3/4; Fig 2, B). A representative figure of the forearm from a patient with kiwifruit allergy with a positive SPT response after challenge with the indicated allergens is shown (Fig 2, C). Considering that approximately 85% of the patients included in this study had positive responses to purified Act d 12 or Act d 13, the inclusion of whole kiwi seed extracts for in vitro clinical

Local allergic rhinitis: mechanisms, diagnosis and relevance for occupational rhinitis.

Purpose of reviewLocal allergic rhinitis (LAR) is a new form of allergic rhinitis that has caused a growing interest. The possibility of an occupational equivalent (occupational rhinitis) has not been yet explored. The purpose of this review is to summarize the most relevant and recent scientific evidence on LAR and occupational rhinitis. Recent findingsLAR is a prevalent entity well differentiated from allergic rhinitis, affecting patients from different countries, ethnic groups and ages. Occupational rhinitis appears earlier and more frequently than occupational asthma, especially for high molecular weight substances. Diagnosis of LAR is based on nasal allergen provocation test and/or detection of nasal specific IgE, and other techniques such as basophil activation test may support the diagnosis. Skin prick tests and immunological determinations are of limited use for diagnosis of occupational rhinitis caused by low molecular weight agents. Performance of nasal allergen provocation test for confirming diagnosis of occupational rhinitis is strongly recommended. Uncommon allergens should also be investigated. SummaryThe possibility of a local occupational rhinitis should be considered in workers with a clear history of occupational rhinitis and negative immunological test, especially in the case of high molecular weight allergens

Mortality and morbidity of heart failure treated with digoxin. A propensity-matched study.

Background:  The role of digoxin in the prognosis of patients with heart failure (HF) remains unclear.

High Prevalence of Lipid Transfer Protein Sensitization in Apple Allergic Patients with Systemic Symptoms

Background Apple allergy manifests as two main groups of clinical entities reflecting different patterns of allergen sensitization: oral allergy syndrome (OAS) and generalized symptoms (GS). Objective We analysed the sensitization profile to a wide panel of different components of food allergens (rMal d 1, Mal d 2, rMal d 3, rMal d 4, rPru p 3, rBet v 1 and Pho d 2) for a population of Mediterranean patients with OAS and GS to apple. Methods Patients (N = 81) with a history of apple allergy that could be confirmed by positive prick-prick test and/or double-blind-placebo-controlled food challenge (DBPCFC), were included. Skin prick test (SPT) and ELISA were performed using a panel of inhalant, fruit and nut allergens. ELISA and ELISA inhibition studies were performed in order to analyse the sensitization patterns. Results Thirty-five cases (43.2%) had OAS and 46 (56.8%) GS. SPT showed a significantly higher number of positive results with peach, cherry and hazelnut in those with GS. ELISA showed a significantly high percentage of positive cases to rMal d 3, rMal d 4, rPru p 3 and Pho d 2 in patients with OAS and GS compared to controls, and to rBet v 1 in patients with OAS vs controls and between OAS and GS patients. Three different patterns of recognition were detected: positive to LTP (rMal d 3 or rPru p 3), positive to profilin (rMal d 4 and Pho d 2), or positive to both. There were also patients with rMal d 1 recognition who showed cross-reactivity to rBet v 1. Conclusion In an apple allergy population with a high incidence of pollinosis different patterns of sensitization may occur. LTP is most often involved in those with GS. Profilin, though more prevalent in patients with OAS, has been shown to sensitise patients with both types of symptoms.

Effect of Pru p 3 on dendritic cell maturation and T-lymphocyte proliferation in peach allergic patients.

BACKGROUND Pru p 3 is the major peach allergen and the most frequent cause of food allergy in adults in the Mediterranean area. Although its allergenicity is well characterized, its ability to generate a T-cell response is not completely known. OBJECTIVE To investigate the influence of Pru p 3 allergen on dendritic cell (DC) maturation and specific T-cell response (T(H)1/T(H)2) in peach allergic patients. METHODS Peach allergic patients (n = 11) and tolerant controls (n = 14) were included in the study. Monocyte-derived DC maturation after incubation with Pru p 3 was evaluated by the increase of maturational markers (CD80, CD86, and CD83) by flow cytometry. Lymphocyte proliferation was evaluated by coculturing monocyte-derived DCs and 5,6-carboxyfluorescein diacetate N-succinimidyl ester-stained lymphocytes with different concentrations of Pru p 3 (25, 10, and 1 μg/mL) by flow cytometry and cytokine production. RESULTS Pru p 3 induced a significant increase in the CD80, CD86, and CD83 expression on stimulated DCs from patients compared with controls. The lymphocyte proliferative response after Pru p 3 stimulation was also significantly higher along with an increase in interleukin 8 in patients compared with tolerant controls. CONCLUSION Pru p 3 allergen induces changes in DC maturational status mainly in peach allergic patients. An increase in lymphocyte proliferative response accompanied with a different cytokine pattern was also observed compared with healthy controls.

Consultation between specialists in Internal Medicine and Family Medicine improves management and prognosis of heart failure.

BACKGROUND AND OBJECTIVE To evaluate if consultation between specialists in Internal Medicine and family doctors (CIMFD) improves the clinical management and prognosis of patients with heart failure (HF). METHODS DESIGN prospective case-control study (5 years of follow-up). SETTING community-based sample within the area of a university teaching hospital. SUBJECTS 1857 patients (> or = 14 years) diagnosed for the first time with HF (1stDxHF), in the CIMFD. CONTROL GROUP 1981 patients (from health centres not covered by the CIMFD), 1stDxHF, in the external consultations of the hospital. MAIN OUTCOME MEASURES mortality rate (MR). Admissions (HA). Emergency services visits (ESV). Delays in receiving specialist attention (DRSA), and the resolution of the process (DRP). Number (NTP) and delays in reporting (DTP) tests performed. Proportion (PRC) and delay (DRC) in resolving cases. RESULTS We observed a reduction of: MR (by 10.8%, CI 95%, 8.6-13.0, p < 0.005); HA, per patient per year (ppy) (by 1.8, 1.3-2.3, p < 0.01); ESV, ppy (by 1.9, 1.2-2.6, p < 0.01); DRSA (by 26.5 days, 21.8-31.2, p < 0.001); DRP (by 21.0 days, 18.3-23.7, p < 0.001), and DRC (by 25.8 days, 20.3-31.4, p < 0.01). The PRC (17.2%, CI 95%, 15.5-18.9, p < 0.01) was higher for the CIMFD. CONCLUSION The CIMFD approach improves prognosis and efficacy in the clinical management of patients with HF because it reduces mortality and morbidity (HA and ESV), shortens the delays in receiving care and in resolving the diagnostic and therapeutic process (DRSA, DRP, DRC), and increases the proportion of diagnosed and treated patients.