Hymenoptera Venom Allergy: Management of Children and Adults in Clinical Practice.

Hymenoptera venom allergy is an epidemiologically underestimated condition and a major cause of morbidity worldwide. Preventing future allergic reactions in patients who experience a systemic reaction is based on the correct management of the emergency followed by an accurate diagnosis, prescription of adrenaline autoinjectors, and, where indicated, specific venom immunotherapy. Some epidemiological studies highlight our poor knowledge of this disease and the frequent inadequacy of its management. Moreover, they emphasize the importance of such a life-saving treatment as specific immunotherapy. The availability of high-quality hymenoptera venom extracts for diagnostic and therapeutic use has dramatically improved the prognosis and quality of life of allergic patients. Subcutaneous venom immunotherapy is currently the most effective form of allergen-based immunotherapy, with a carry-over effect lasting up to several years after its interruption. This report on the management of hymenoptera venom-allergic children and adults was prepared by a panel of Italian experts. The main objective of this consensus document is to review the scientific evidence related to diagnosis, therapy, and management of patients allergic to hymenoptera venom. Thus, we can improve our knowledge of the disease and promote good clinical practices. The present document provides practical suggestions for correct diagnosis, prescription of emergency therapy and immunotherapy, and strategies for patient care.

Hymenoptera venom allergy: management of children and adults in clinical practice

Hymenoptera venom allergy is an epidemiologically underestimated condition and a major cause of morbidity worldwide. Preventing future allergic reactions in patients who experience a systemic reaction is based on the correct management of the emergency followed by an accurate diagnosis, prescription of adrenaline autoinjectors, and, where indicated, specific venom immunotherapy. Some epidemiological studies highlight our poor knowledge of this disease and the frequent inadequacy of its management. Moreover, they emphasize the importance of such a life-saving treatment as specific immunotherapy. The availability of high-quality hymenoptera venom extracts for diagnostic and therapeutic use has dramatically improved the prognosis and quality of life of allergic patients. Subcutaneous venom immunotherapy is currently the most effective form of allergen-based immunotherapy, with a carry-over effect lasting up to several years after its interruption. This report on the management of hymenoptera venom-allergic children and adults was prepared by a panel of Italian experts. The main objective of this consensus document is to review the scientific evidence related to diagnosis, therapy, and management of patients allergic to hymenoptera venom. Thus, we can improve our knowledge of the disease and promote good clinical practices. The present document provides practical suggestions for correct diagnosis, prescription of emergency therapy and immunotherapy, and strategies for patient care

La alergia al veneno de himenópteros es una condición subestimada epidemiológicamente que representa una causa importante de morbilidad en todo el mundo. La prevención de reacciones alérgicas futuras en pacientes que han desarrollado una reacción sistémica se basa en el manejo correcto de la emergencia, seguido de un diagnóstico correcto, la prescripción de autoinyectores de adrenalina y, en el caso de estar indicada, la prescripción de inmunoterapia específica con veneno (VIT). Varios estudios epidemiológicos destacan el escaso conocimiento de esta enfermedad y un frecuente tratamiento insuficiente. Además, enfatizan la importancia de la inmunoterapia específica, un tratamiento que puede salvar la vida del paciente. La disponibilidad de extractos de veneno de himenóptera de alta calidad para uso diagnóstico y terapéutico ha mejorado drásticamente el pronóstico y la calidad de vida de estos enfermos. La VIT subcutánea representa la forma más efectiva de inmunoterapia con alérgeno actualmente disponible, con una eficacia persistente que dura hasta varios años después de su interrupción. Este consenso sobre la evaluación clínica tanto de niños como de adultos alérgicos al veneno de himenópteros ha sido elaborado por un panel de expertos italianos. Su objetivo principal es revisar la evidencia científica disponible en el diagnóstico, la terapia y la evaluación clínica de los pacientes alérgicos al veneno de himenópteros con el propósito de mejorar el conocimiento sobre esta enfermedad y promover buenas prácticas clínicas. Se incluyen sugerencias prácticas para un diagnóstico correcto, la prescripción de terapia de emergencia e inmunoterapia, así como estrategias para el manejo de los pacientes

The Importance of Complying with Vaccination Protocols in Developed Countries: "Anti-Vax" Hysteria and the Spread of Severe Preventable Diseases.

BACKGROUND: Vaccines are very effective medical tools for disease prevention and life span increase. Controversies have raised concern about their safety, from autism to polio vaccine contamination with simian virus 40 (SV-40). Hysteria surrounding vaccine-associated risks has resulted in a declining number of vaccinations in developed countries. Outbreaks of vaccine-preventable diseases (e.g. measles) have occurred in Europe and North America, causing also some causalities. OBJECTIVES: In this review, data on safety and efficacy of vaccines are discussed, showing that the benefits of vaccines far outweigh the risks and that it is important to comply with vaccination protocols, to avoid spreading of severe, preventable diseases. METHODS: Those opposed to vaccinations suggest that scientific literature supporting vaccines is influenced by pharmaceutical companies. In this review, studies on influenza produced by independent scientists and those authored by those who received some kind of benefit from the industry are discussed separately. All the chosen papers were selected through a MEDLINE research. RESULTS: Vaccination rates are decreasing, even though they are effective public health tools. Influenza, for example, is responsible for 250,000-500,000 deaths each year, according to the WHO. Yet, campaigns to extend influenza vaccine to all elderly subjects report little success, because of the vaccine scare and because not all patients develop immunity following vaccination. CONCLUSIONS: This review proves that vaccine hysteria is detrimental because: 1) it causes an increased morbidity and mortality from preventable diseases; 2) it jeopardizes research for new vaccines; 3) patients are reluctant to accept any form of immune-therapy, commonly referred to as "vaccination".

A case of hypocomplementemic urticarial vasculitis syndrome successfully treated with omalizumab

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Role of TNF-alpha polymorphism in patients with nickel allergy: a marker of susceptibility to contact polysensitization.

OBJECTIVE: Nickel allergy is the most frequent contact allergy in the industrialized country. In allergic contact dermatitis after the presentation of haptenated peptides by resident or newly recruited skin cells, activated CD8+ T cells release IFN-γ and TNF-α, these cytokines are potent activator of keratinocytes. The role of specific cytokines in nickel allergy is not yet fully elucidated. The adenine nucleotide at position -308 in the promoter region of the TNFA gene is associated with an increased production of TNF-α, that is a potent activator of keratinocytes. PATIENTS AND METHODS: To evaluate the expression of TNF-α polymorphism in patients with allergic contact dermatitis and in healthy people, 41 patients with allergic contact dermatitis to nickel and 40 healthy controls were enrolled. A total of 81 subjects (41 cases and 40 controls) underwent genotyping for the 308 genetic polymorphism in the TNFA gene. RESULTS: The distribution of TNF genotypes TNF-α 308 G/A polymorphism in cases didn't differ significantly in the controls group. The genotype GA was present in the 75% of the patients with polysensitization. In one patient was observed the rare genotype A/A. CONCLUSIONS: The carriage of the TNFA-308 A/A and GA genotype may act as a marker of enhanced susceptibility to contact polysensitization, indicating that TNF-α is a key regulator of the initiation of delayed-type hypersensitivity reactions, the polymorphism seems to be not enough for the development of nickel monosensitization.

Cross-reactivity and Tolerability of Ertapenem in Patients With IgE-Mediated Hypersensitivity to ß-Lactams.

BACKGROUND AND OBJECTIVE: Administration of carbapenems to ß-lactam-allergic patients has always been considered potentially harmful because of a 47.4% rate of cross-reactivity to imipenem reported in a single study. Nevertheless, recent studies have shown that the rate of cross-reactivity of imipenem and meropenem with penicillins is lower than 1%. The aim of this study was to evaluate the possibility of using ertapenem in patients with an established IgE-mediated ß-lactam allergy. PATIENTS AND METHODS: We studied all participants who came to our allergy unit and had a clinical history of immediate hypersensitivity reactions to ß-lactams. The inclusion criteria were a positive skin test result to at least 1 ß-lactam molecule and/or positive specific IgE (when available). All participants underwent immediate-type skin tests with several ß-lactam molecules including ertapenem. Challenges with intravenous ertapenem were performed on 2 different days in patients with negative skin test results. RESULTS: We examined 49 patients with a clinical history of immediate reactions to ß-lactams. All the patients had positive skin tests and/or positive specific IgE to at least 1 ß-lactam reagent and negative carbapenem skin tests. Thirty-six patients agreed to undergo the challenges and 35 tolerated the full dose of ertapenem. CONCLUSIONS: The practice of avoiding carbapenems in patients with ß-lactam allergy should be abandoned considering the very low rate of cross-reactivity. ß-Lactam-allergic patients who need ertapenem therapy should undergo skin tests and, if negative, a graded challenge to assess tolerability.

Cross-reactivity and tolerability of Ertapenem in patients with IgE-mediated hypersensitivy to Beta-lactams

Background and Objective: Administration of carbapenems to β-lactam-allergic patients has always been considered potentially harmful because of a 47.4% rate of cross-reactivity to imipenem reported in a single study. Nevertheless, recent studies have shown that the rate of cross-reactivity of imipenem and meropenem with penicillins is lower than 1%. The aim of this study was to evaluate the possibility of using ertapenem in patients with an established IgE-mediated β-lactam allergy. Patients and Methods: We studied all participants who came to our allergy unit and had a clinical history of immediate hypersensitivity reactions to β-lactams. The inclusion criteria were a positive skin test result to at least 1 β-lactam molecule and/or positive specific IgE (when available). All participants underwent immediate-type skin tests with several β-lactam molecules including ertapenem. Challenges with intravenous ertapenem were performed on 2 different days in patients with negative skin test results. Results: We examined 49 patients with a clinical history of immediate reactions to β-lactams. All the patients had positive skin tests and/or positive specific IgE to at least 1 β-lactam reagent and negative carbapenem skin tests. Thirty-six patients agreed to undergo the challenges and 35 tolerated the full dose of ertapenem. Conclusions: The practice of avoiding carbapenems in patients with β-lactam allergy should be abandoned considering the very low rate of cross-reactivity. β-Lactam-allergic patients who need ertapenem therapy should undergo skin tests and, if negative, a graded challenge to assess tolerability (AU)

Introducción y Objetivo: Siempre se ha considerado peligrosa la administración de carbapenems a pacientes alérgicos a betalactámicos por la presencia de reactividad cruzada en el 47,4% de los casos descrita en un estudio previo. Sin embargo, estudios recientes han mostrado que la reactividad cruzada de imipenem y meropenem con penicilinas es inferior al 1%. El objetivo de este estudio es valorar el uso de ertapenem en pacientes diagnosticado de alergia IgE mediada a betalactámicos. Pacientes y Métodos: Se incluyeron todos los pacientes que acudieron a nuestra unidad de Alergia con historia clínica de alergia inmediata a betalactámicos. Los criterios de inclusión fueron prueba cutánea positiva con al menos un betalactámico y/o IgE específica positiva (cuando estuviese disponible). Se realizaron pruebas cutáneas con betalactámicos, incluyendo ertapenem, con lectura inmediata en todos los pacientes. Se realizaron pruebas de provocación endovenosas con ertapenem en los pacientes con pruebas cutáneas negativas frente al mismo en dos días diferentes. Resultados: Se incluyeron 49 pacientes con historia clínica de alergia inmediata a betalactámicos. Todos los pacientes tenían pruebas cutáneas positivas y/o IgE específica positiva al menos a uno de los betalactámicos así como prueba cutánea negativa con carbapenémicos. Treinta y seis pacientes aceptaron la realización de pruebas de provocación con ertapenem que fueron tolerados por treinta y cinco de dichos pacientes. Conclusión: El hecho de recomendar evitar carbapenems en pacientes con alergia a betalactámicos debería ser abandonado, dada la baja reactividad cruzada que presentan. En los pacientes con alergia a betalactámicos que necesiten ertapenem se deberían realizar pruebas cutáneas con el fármaco y en caso de ser negativas, realizar un test de exposición progresiva para confirmar su tolerancia (AU)

Fondaparinux in pregnancy: Could it be a safe option? A review of the literature.

During pregnancy thrombo-prophylaxis could be required in high risk women. If a severe allergic reaction to low-molecular-weight-heparin (LMWH) or a heparin-induced-thrombocytopenia (HIT) occurs, it's mandatory to stop the drug. Fondaparinux could be an effective option. In the present review, the maternal and pregnancy outcomes of 65 pregnancies in women using Fondaparinux were reported. It was well-tolerated and rate of pregnancy complications was similar to that observed in general population. Regarding congenital malformations, further studies are necessary to investigate the safety of the drug.

A case of heparin allergy with good tolerability to fondaparinux during pregnancy

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Cross-reactivity and tolerability of cephalosporins in patients with cell-mediated allergy to penicillins.

BACKGROUND AND OBJECTIVE: 13-Lactams are the most commonly used antibiotics but they can cause hypersensitivity reactions. We sought to estimate cross-reactivity and tolerability of cephalosporins in patients with cell-mediated allergy to penicillins. METHODS: We studied 97 patients with a clinical history of nonimmediate reactions to a penicillin and a positive patch test result to at least 1 of the penicillins tested. All patients also underwent patch testing with several cephalosporins. Patients with a negative patch test to a cephalosporin underwent test dosing in order to assess tolerability. RESULTS: We recorded 129 reactions. The most commonly involved drugs were aminopenicillins, and the most widely reported symptoms were delayed urticaria and maculopapular exanthema. Seventeen patients had positive patch test results for cephalosporins, mostly for cephalexin (n=10), cefaclor (n=9), and cefuroxime axetil (n=5). All the patients-except 4 who experienced an exanthema after the challenge test with cephalexin-tolerated a therapeutic dose of the cephalosporin tested without any adverse effects. CONCLUSIONS: Our data show that cross-reactivity between penicillins and cephalosporins may be as high as 10.9% for first-generation cephalosporins and 1.1% for third-generation cephalosporins, possibly due to the involvement of similar side chains. Patch tests are a useful diagnostic tool to assess cross-reactivity, but a graded challenge is mandatory because a negative patch test does not always mean tolerability.

Cross-reactivity and tolerability of cephalosporins in patients with cell-mediated allergy to penicillins

Background and objective: b-Lactams are the most commonly used antibiotics but they can cause hypersensitivity reactions. We sought to estimate cross-reactivity and tolerability of cephalosporins in patients with cell-mediated allergy to penicillins. Methods: We studied 97 patients with a clinical history of nonimmediate reactions to a penicillin and a positive patch test result to at least 1 of the penicillins tested. All patients also underwent patch testing with several cephalosporins. Patients with a negative patch test to a cephalosporin underwent test dosing in order to assess tolerability. Results: We recorded 129 reactions. The most commonly involved drugs were aminopenicillins, and the most widely reported symptoms were delayed urticaria and maculopapular exanthema. Seventeen patients had positive patch test results for cephalosporins, mostly for cephalexin (n=10), cefaclor (n=9), and cefuroxime axetil (n = 5). All the patients-except 4 who experienced an exanthema after the challenge test with cephalexin—tolerated a therapeutic dose of the cephalosporin tested without any adverse effects. Conclusions: Our data show that cross-reactivity between penicillins and cephalosporins may be as high as 10.9% for first-generation cephalosporins and 1.1% for third-generation cephalosporins, possibly due to the involvement of similar side chains. Patch tests are a useful diagnostic tool to assess cross-reactivity, but a graded challenge is mandatory because a negative patch test does not always mean tolerability (AU)

Introducción y objetivo: Los antibióticos betalactámicos son los más comúnmente utilizados y pueden ser responsables del desarrollo de reacciones de hipersensibilidad. Este estudio pretende estimar la reactividad cruzada y la tolerancia a las cefalosporinas en pacientes con alergia mediada por células a penicilinas. Métodos: Estudiamos 97 pacientes con historia clínica de reacciones no inmediatas a penicilina y que habían tenido una prueba de parche positiva al menos frente a una de las penicilinas testadas. También se realizó parche frente a alguna cefalosporina en todos ellos. Los pacientes con negatividad en esta prueba se sometieron a la prueba de tolerancia. Resultados: Se recopilaron 129 reacciones, la mayoría de los medicamentos implicados fueron aminopenicilinas, siendo los síntomas más frecuentes la urticaria de aparición tardía y el exantema máculo-papular. Diecisiete pacientes arrojaron resultados positivos en la prueba del parche a cefalosporinas, cefalexina (10 casos), ceflacor (9) y acetil-cefuroxima (5). Todos los pacientes excepto 4 (los cuales tuvieron un eccema tras la provocación con cefalexina), toleraron la dosis terapéutica de la cefalosporina probada sin ningún efecto dañino. Conclusiones: Según nuestros resultados, la reactividad cruzada entre penicilinas y cefalosporinas es de 10,9% para las cefalosporinas de primera generación y de 1,1% para las de tercera generación. Esto puede ser debido a las cadenas similares implicadas. La prueba del parche es una herramienta diagnóstica útil para evaluar la reactividad cruzada, pero necesita una provocación gradual, dado que una prueba del parche negativa no implica tolerancia (AU)

Nickel free-diet enhances the Helicobacter pylori eradication rate: a pilot study.

BACKGROUND: The Helicobacter pylori eradication rate with standard triple therapy is very low. H. pylori is known to require the nickel-containing metalloenzymes urease and NiFe-hydrogenase to survive at the low pH environment in the stomach. AIM: To compare the H. pylori eradication rate of a nickel free-diet associated with standard triple therapy and standard triple therapy alone as the first-line regimen. METHODS: Fifty-two sex- and age-matched patients at the first diagnosis of H. pylori infection were randomized 1:1 into two different therapeutic schemes: (1) standard LCA (26 patients): lansoprazole 15 mg bid, clarithromycin 500 mg bid and amoxicillin 1,000 mg bid for 7 days with a common diet; (2) standard LCA plus a nickel free-diet (NFD-LCA) (26 patients). Patients followed 30 days of a nickel-free diet plus a week of lansoprazole 15 mg bid, clarithromycin 500 mg bid and amoxicillin 1,000 mg bid starting from day 15 of the diet. RESULTS: All patients completed the study. A significantly higher eradication rate was observed in the NFD-LCA group (22/26) versus LCA group (12/26) (p < 0.01). Only a few patients (9 of 52) reported the occurrence of mild therapy-related side effects, without any significant differences between the two groups. CONCLUSIONS: The addition of a nickel-free diet to standard triple therapy significantly increases the H. pylori eradication rate. The reduction of H. pylori urease activity due to the nickel-free diet could expose the bacterium to gastric acid and increase H. pylori's susceptibility to amoxicillin. Further studies are necessary to confirm this preliminary result.

Gene expression profiling of patients with latex and/or vegetable food allergy.

BACKGROUND: The prevalence of individuals allergic to latex, exhibiting cross-hypersensitivity with plant-derived food has been frequently reported as the so-called latex-fruit syndrome. Nonetheless, molecular mechanisms underlying allergy to latex and/or fruit are poorly understood. AIM: The aims of this study were to identify candidate genes that may be associated with the pathogenesis of allergy to latex and/or vegetable food, and to assess if similar molecular pathways are involved in both types of hypersensitivity. MATERIALS AND METHODS: DNA microarray analysis was performed to screen the molecular profiles of peripheral blood mononuclear cells isolated from patients with allergy to latex, to fruit, or with latex-fruit syndrome, and from control healthy subjects. RESULTS: Molecular profiling identified an overlapping dataset of genes commonly regulated in all the atopic patients enrolled in this study, suggesting that similar molecular mechanisms are involved in the pathogenesis of allergy to the fruit and/or latex. Several regulators of the innate and acquired immunity reported to polarize the immunological response towards a Th2-mediated immune response were overexpressed in the patients. Evidences suggested that the expression of T-regulatory cells might be defective in allergic patients, as a consequence of a dysregulation of some inflammatory cytokines. Finally, several transcription factors that may be responsible for the Th1/Th2 imbalance were modulated in allergic patients. CONCLUSIONS: This study identified relevant genes that may help to elucidate the molecular mechanisms underlying allergic disease. Knowledges of critical targets, along with transcription factors regulating gene activity may facilitate the development of new therapeutic options.

The clinical meaning of positive latex sIgE in patients with food/pollen adverse reactions.

Natural rubber latex allergy (NRL-A) is an international problem of public health. About 50-60% of NRL-A patients may present adverse reactions after ingestion of cross-reacting vegetable foods. This condition, called "Latex-fruit Syndrome", is a matter of research. The aim of our study is to distinguish between clinical/subclinical latex-fruit syndrome and cross-sensitization to latex and food/pollen allergens on the basis of latex recombinant allergens. We studied 51 patients with food hypersensitivity and serological evidence of NRL sensitization. The subjects underwent an accurate allergological evaluation (skin prick test with latex, food and pollen extracts, specific IgE to latex and recombinant allergens, challenge provocation tests). The patients were divided in two groups: group A) 34 patients with clinical and serological latex and fruit/vegetable allergies; group B) 17 patients allergic to fruits/vegetables and/or pollens, with serological, but not clinical NRL-A. All the latex challenge tests resulted positive in group A patients and only two patients of group B presented positive cutaneous challenge tests. Moreover, specific IgE-antibodies were detected to rHev b 5, to rHev b 6.01, to rHev b 6.02 and to rHev b 8 (and other profilins) of group A patients, while in group B we observed a monosensitization to Hev b8, probably linked to a cross-sensitization to pollens and foods. At the present state of knowledge, we need a multi-parametric approach based on a combination of clinical history, diagnostic tests (CRD) and latex challenge tests to make diagnosis of latex-fruit syndrome.

Profilin desensitization in two patients with plant-derived food allergy.

Profilins are "panallergens", responsible for many cross-reactivities between inhalant, latex and plant-derived food allergens. We evaluated the effectiveness and the safety of sublingual desensitization treatment (SLIT) in two patients with allergic respiratory and food diseases. Skin prick tests, IgE and IgG4 assays to pollens, some plant-derived foods, profilin, non-lipid specific transfer protein and PR 10 proteins were performed. The patients also underwent double-blind placebo-controlled challenge (DBPCFC) with the culprit foods and profilin and then a SLIT with it. Both the patients had positive SPT, specific IgE and DBPCFCs with profilin and some vegetables referred in anamnesis. They therefore underwent SLIT with profilin extract. At the end of treatment, the patients had negative DBPCFCs with culprit foods and a decrease of specific IgE levels for profilin and vegetable foods. Profilin desensitization allowed our patients to manage their diet without restriction, eating several foods previously not tolerated.

Human basophils: a unique biological instrument to detect the allergenicity of food.

BACKGROUND: Labeling of major food allergens is mandatory for the safety of allergic consumers. Although enzyme-linked immunosorbent assay, polymerase chain reaction, and mass spectrometry are sensitive and specific instruments to detect trace amounts of food proteins, they cannot measure the ability of food constituents to trigger activation of mast cells or basophils. AIM: We evaluated the basophil activation test as an instrument to determine the allergenic potential of trace amounts of food allergens in complex matrices. Peanut (Arachis hypogaea) allergy was selected as a proof-of-concept model. METHODS: The study population comprised 5 severely peanut-allergic patients (3 males/2 females; median age, 12 years) all sensitized to 3 major peanut allergens (Ara h 1, Ara h 2, and Ara h 3) and 5 peanut-tolerant individuals (2 males/3 females; median age, 8 years). Basophils from patients and controls were stimulated with pure peanut extract and blank and peanut-spiked (0.1, 0.01, and 0.001 ppm) biscuits (baking time 11, 16, 21, 26 minutes) and chocolate extracts. RESULTS: Blank biscuits and chocolate did not induce cell activation in patients or controls. A comparison between patients and controls showed significantly higher activation of basophils after stimulation with 0.1 and 0.01 ppm of peanut-spiked biscuit at all baking times and peanut-spiked chocolate (P < .05). CONCLUSIONS: The basophil activation test is a highly sensitive and specific tool to detect traces of functionally active food allergens. For biscuits, its accuracy seems independent of baking time. Furthermore, it allows even the most sensitive patients to be included in study protocols.

Tolerability of aztreonam in patients with cell-mediated allergy to ß-lactams.

BACKGROUND: Cross-reactivity between aztreonam and ß-lactams is poor, but tolerability of aztreonam has been assessed in a few groups of patients suffering from IgE-mediated allergy to ß-lactams. The aim of this study was to assess the cross-reactivity of aztreonam with other ß-lactams and its tolerability in patients with cell-mediated allergy to these drugs. METHODS: We studied 78 patients with cell-mediated allergy to ß-lactams who underwent skin prick, immediate and delayed-reading intradermal tests as well as patch tests with penicilloyl-polylysine, minor determinant mixture, semi-synthetic penicillins, cephalosporins, aztreonam and imipenem. Patients with negative allergy testing with aztreonam underwent an intramuscular test dosing and were observed for 3 h. RESULTS: Our patients experienced 94 non-immediate reactions; delayed-onset urticaria (34 cases), maculopapular exanthema (13 cases), urticaria/angioedema (15 cases) and itching erythema (13 cases) were the most reported symptoms. Amoxicillin (35 cases), ampicillin (28 cases) and bacampicillin (18 cases) were the most involved drugs. All patients had a positive patch test and/or a positive delayed-reading intradermal test to at least 1 ß-lactam antibiotic and none had a positive patch or delayed-reading intradermal test to aztreonam. Then, 65 patients underwent intramuscular test dosing with aztroenam, and none of them had a clinical reaction. CONCLUSIONS: Our data confirm the lack of cross-reactivity between ß-lactams and aztreonam in patients with cell-mediated allergy to these drugs. Delayed-reading intradermal tests and patch tests with aztreonam represent a simple and rapid diagnostic tool to establish tolerability in ß-lactam-allergic patients.