Clinical relevance is associated with allergen-specific wheal size in skin prick testing.

BACKGROUND: Within a large prospective study, the Global Asthma and Allergy European Network (GA(2) LEN) has collected skin prick test (SPT) data throughout Europe to make recommendations for SPT in clinical settings. OBJECTIVE: To improve clinical interpretation of SPT results for inhalant allergens by providing quantitative decision points. METHODS: The GA(2) LEN SPT study with 3068 valid data sets was used to investigate the relationship between SPT results and patient-reported clinical relevance for each of the 18 inhalant allergens as well as SPT wheal size and physician-diagnosed allergy (rhinitis, asthma, atopic dermatitis, food allergy). The effects of age, gender, and geographical area on SPT results were assessed. For each allergen, the wheal size in mm with an 80% positive predictive value (PPV) for being clinically relevant was calculated. RESULTS: Depending on the allergen, from 40% (blatella) to 87-89% (grass, mites) of the positive SPT reactions (wheal size ≥ 3 mm) were associated with patient-reported clinical symptoms when exposed to the respective allergen. The risk of allergic symptoms increased significantly with larger wheal sizes for 17 of the 18 allergens tested. Children with positive SPT reactions had a smaller risk of sensitizations being clinically relevant compared with adults. The 80% PPV varied from 3 to 10 mm depending on the allergen. CONCLUSION: These 'reading keys' for 18 inhalant allergens can help interpret SPT results with respect to their clinical significance. A SPT form with the standard allergens including mm decision points for each allergen is offered for clinical use.

Comparison of five techniques of skin prick tests used routinely in Europe.

BACKGROUND: Skin prick tests represent indispensable tools in allergy, even more than 30 years after their introduction in clinical practice. OBJECTIVES: Few recent European studies have focused on this topic and we thus wanted to compare the instruments most often used today. METHODS: Four instruments were investigated: the 23G intravenous (IV) needle, the ALK Lancet, the Stallergenes (STG) Prick Lancet and the Stallerpoint(®) (using two different methods). Sensitivity, reproducibility, and acceptability were evaluated. In 22 subjects, we calculated the sensitivity and reproducibility (both intra- and interpatient) of these methods by testing the positive control five times. In 50 subjects, we tested the single-blind acceptability of these same five techniques. RESULTS: In terms of sensitivity, the IV needle (100%) and metal lancets (96% for the ALK Lancet and 98% for the STG Prick Lancet) were superior (P < 0.01) to the two Stallerpoint(®) methods (20% and 57%). Intrapatient reproducibility was 16.2%, 14.6%, 15.0%, 97.1% and 18.1%, respectively. The instruments that were best tolerated by the patients were the IV needle and the two metal lancets. CONCLUSION: Metal needles and/or lancets are the tools of choice for skin prick testing.

Clinical value of negative skin tests to iodinated contrast media.

BACKGROUND: Several studies have shown that skin tests are useful tools for the diagnosis of iodinated contrast medium (ICM) allergy, but the real number of false negative results is not known. OBJECTIVE: To evaluate the negative predictive value of ICM skin tests. MATERIAL AND METHODS: One hundred and fifty-nine patients tested in our department because of a previous ICM reaction over the last 9 years were called and asked standardized questions about ICM re-exposure. RESULTS: Twenty-nine patients had been re-exposed to ICM. There were 20 (69.0%) females and the median age was 55 (34-60) years. The median time interval between the reaction and skin testing was 11.9 (1.6-21.5) years. Twenty-four patients (82%) had an immediate reaction, four a non-immediate (13.8%) reaction and no data were available for one patient. Two patients had positive ICM skin tests previously and were re-exposed to a negatively skin-tested ICM and did not react. Only two patients presented a mild reaction during ICM re-injection: one immediate (generalized urticaria lasting for 3 days) and one non-immediate maculopapular reaction. The patient with urticaria was re-tested and re-challenged (negative). The other patient was unable to return for re-testing. CONCLUSION: Skin testing for ICM hypersensitivity has a negative predictive value of 96.6% (95% CI: 89.9-103.2) and none of the reactions in skin-test-negative patients were severe. Multi-centric large surveys are still needed for confirmation.

Determining the negative predictive value of provocation tests with beta-lactams.

BACKGROUND: The beta-lactam allergic work-up is mostly standardized. However, the negative predictive value of drug provocation tests is not yet well established. METHOD: A historical-prospective multicentre cohort study was conducted in four centres (one in France, one in Portugal, two in Italy) to assess the negative predictive value of provocation tests with beta-lactams in patients initially tested for a suspicion of drug allergy/hypersensitivity. Patients were contacted at least 6 months after the work-up, between 2003 and 2007. A new allergic work-up was proposed to reacting patients. RESULTS: Among the 457 patients included, 365 (79.9%) were followed up (159 [79.1%] from France, 153 [82.7%] from Italy and 53 [74.6%] from Portugal). Only 118 (25.8%) were re-exposed to the negatively tested beta-lactam. Nine (7.6%) reported a non-immediate (occurring more than 1 h after drug administration) reaction: five urticaria, three exanthema and one undefined cutaneous reaction. None were severe. Only four accepted a re-challenge, negative in two cases and positive in the two others. The negative predictive value was 94.1% (89.8-98.3) (111 out of 118 patients). CONCLUSION: Although the negative predictive value of drug provocation tests may not be 100%, none of the false negative patients experienced a life-threatening reaction. This should reassure doctors who might hesitate to prescribe beta-lactams, even in patients with negative allergic work-ups.

GA2LEN skin test study III: minimum battery of test inhalent allergens needed in epidemiological studies in patients.

BACKGROUND: The number of allergens to be tested in order to identify sensitized patients is important in order to have the most cost-effective approach in epidemiological studies. OBJECTIVE: To define the minimal number and the type of skin prick test (SPT) allergens required to identify a patient as sensitized using results of the new Pan-European GA(2)LEN skin prick test study. METHOD: In a large Pan-European multicenter (17 centers in 14 countries) patient based study, a standardized panel of 18 allergens has been prick tested using a standardized procedure. Conditional approach allowed to determine the allergens selection. RESULT: Among the 3034 patients involved, 1996 (68.2%) were sensitized to at least one allergen. Overall, eight allergens (grass pollen, Dermatophagoides pteronyssinus, birch pollen, cat dander, Artemisia, olive pollen, Blatella and Alternaria) allowed to identified more than 95% of sensitized subjects. However, differences were observed between countries, two allergens being sufficient for Switzerland (grass pollen and cat dander) as opposed to nine for France (grass pollen, Dermatophagoides pteronyssinus, olive pollen, cat dander, Blatella, cypress, dog dander, alder and [Artemisia or Alternaria]). According to country, up to 13 allergens were needed to identify all sensitized subjects. CONCLUSION: Eight to ten allergens allowed the identification of the majority of sensitized subjects. For clinical care of individual patients, the whole battery of 18 allergens is needed to appropriately assess sensitization across Europe.

GA(2)LEN skin test study I: GA(2)LEN harmonization of skin prick testing: novel sensitization patterns for inhalant allergens in Europe.

BACKGROUND: Skin prick testing is the standard for diagnosing IgE-mediated allergies. However, different allergen extracts and different testing procedures have been applied by European allergy centres. Thus, it has been difficult to compare results from different centres or studies across Europe. It was, therefore, crucial to standardize and harmonize procedures in allergy diagnosis and treatment within Europe. AIMS: The Global Asthma and Allergy European Network (GA(2)LEN), with partners and collaborating centres across Europe, was in a unique position to take on this task. The current study is the first approach to implement a standardized procedure for skin prick testing in allergies against inhalant allergens with a standardized pan-European allergen panel. METHODS: The study population consisted of patients who were referred to one of the 17 participating centres in 14 European countries (n = 3034, median age = 33 years). Skin prick testing and evaluation was performed with the same 18 allergens in a standardized procedure across all centres. RESULTS: The study clearly shows that many allergens previously regarded as untypical for some regions in Europe have been underestimated. This could partly be related to changes in mobility of patients, vegetation or climate in Europe. CONCLUSION: The results of this large pan-European study demonstrate for the first time sensitization patterns for different inhalant allergens in patients across Europe. The standardized skin prick test with the standardized allergen battery should be recommended for clinical use and research. Further EU-wide monitoring of sensitization patterns is urgently needed.

GA(2)LEN skin test study II: clinical relevance of inhalant allergen sensitizations in Europe.

BACKGROUND: Skin prick testing is the standard for diagnosing IgE-mediated allergies. A positive skin prick reaction, however, does not always correlate with clinical symptoms. A large database from a Global Asthma and Allergy European Network (GA(2)LEN) study with data on clinical relevance was used to determine the clinical relevance of sensitizations against the 18 most frequent inhalant allergens in Europe. The study population consisted of patients referred to one of the 17 allergy centres in 14 European countries (n = 3034, median age = 33 years). The aim of the study was to assess the clinical relevance of positive skin prick test reactions against inhalant allergens considering the predominating type of symptoms in a pan-European population of patients presenting with suspected allergic disease. METHODS: Clinical relevance of skin prick tests was recorded with regard to patient history and optional additional tests. A putative correlation between sensitization and allergic disease was assessed using logistic regression analysis. RESULTS: While an overall rate of >or=60% clinically relevant sensitizations was observed in all countries, a differential distribution of clinically relevant sensitizations was demonstrated depending on type of allergen and country where the prick test was performed. Furthermore, a significant correlation between the presence of allergic disease and the number of sensitizations was demonstrated. CONCLUSION: This study strongly emphasizes the importance of evaluating the clinical relevance of positive skin prick tests and calls for further studies, which may, ultimately, help increase the positive predictive value of allergy testing.

Benzylpenicillin skin testing is still important in diagnosing immediate hypersensitivity reactions to penicillins.

BACKGROUND: The fact that both Hollister-Stier and Allergopharma ceased the production of penicilloyl-polylysine (PPL) and minor determinant mixture (MDM) in 2004 is severely hampering the diagnosis of beta-lactam hypersensitivity and may produce negative consequences. OBJECTIVE: To assess the contribution of skin testing with benzylpenicillin to the diagnosis of immunoglobulin E-mediated hypersensitivity to penicillins, in order to determine how much such testing could compensate for PPL and MDM unavailability. METHODS: We selected patients with histories of immediate reactions to penicillins and positive results to skin tests for one or more penicillin reagents (PPL, MDM, or benzylpenicillin), one or more semi-synthetic penicillins (ampicillin, amoxicillin, or piperacillin), or both. RESULTS: A total of 300 patients were selected, 105 in the French center and 195 in the Italian centers. Amoxicillin and ampicillin were the main responsible drugs. The most common clinical manifestation was anaphylaxis. The reagents most frequently positive to skin tests were amoxicillin (188, 62.7%), ampicillin (151, 50.3%), and benzylpenicillin (111, 37.0%). Among the 300 subjects, 113 (37.7%) were positive only to semi-synthetic penicillins, 109 (36.3%) to both semi-synthetic penicillins and the classic penicillin reagents, and 78 (26.0%) only to the latter. In the last group, 64 (21.3% of the 300 subjects) were positive only to PPL and/or MDM and 14 (4.7%) to benzylpenicillin, of whom 8 (2.7%) were positive only to the latter. CONCLUSIONS: Skin testing with benzylpenicillin can partially compensate for PPL and MDM unavailability. Moreover, it can slightly increase the allergologic workup's sensitivity and therefore reduce the number of potentially dangerous challenges.

Las pruebas cutáneas con bencilpenicilina siguen siendo importantes en el diagnóstico de las reacciones inmediatas de hipersensibilidad a las penicilinas / Benzylpenicillin skin testing is still important in diagnosing immediate hypersensitivity reactions to penicillins

Antecedentes. El hecho de que tanto Hollister-Stier como Allergopharma haya cesado la producción de penicilil-polilisina (PPL) y la mezcla de determinantes menores (MDM) en 2004, es un obstáculo importante en el diagnóstico de la hipersensibilidad a los ß-lactámicos y puede producir consecuencias negativas. Objetivo. Evaluar la contribución de las pruebas cutáneas con bencilpenicilina para el diagnóstico de la hipersensibilidad a penicilina mediada por IgE, con el fin de determinar cuánto podría compensar esta prueba cutánea la falta de disponibilidad de PPL y MDM. Métodos. Se seleccionaron pacientes con antecedentes de reacciones inmediatas a penicilina y test cutáneo para uno o más reactivos de penicilina (PPL, MDM o bencilpenicilina), una o más penicilinas semisintéticas (ampicilina, amoxicilina o piperacilina) o ambos. Resultados. Se seleccionaron en total 300 pacientes, 105 en el centro de Francia y 195 en los centros italianos. Las principales drogas responsables fueron la amoxicilina y ampicilina. La manifestación clínica más común fue la anafilaxia. Las pruebas cutáneas más frecuentemente positivas fueron con amoxicilina (188; 62,7%), ampicilina (151; 50,3%) y bencilpenicilina (111; 37,0%). Entre los 300 sujetos, 113 (37,7%) fueron positivos sólo para las penicilinas semisintéticas, 109 (36,3%) a ambas penicilinas semi-sintéticas y el clásico reactivo penicilina y 78 (26,0%) sólo a este último. En el último grupo, 64 (21,3% de los 300 sujetos) fueron positivos sólo a PPL y/o MDM y 14 (4,7%) a bencilpenicilina, de los cuales 8 (2,7%) fueron positivos sólo a este último Conclusiones. Las pruebas cutáneas con bencilpenicilina pueden compensar en parte la falta de PPL y de MDM. Por otra parte, puede aumentar ligeramente la sensibilidad del estudio diagnóstico alergológico y, por lo tanto, reducir el número de desafíos potencialmente peligrosos(AU)

Oral challenges are needed in the diagnosis of beta-lactam hypersensitivity.

BACKGROUND: beta-lactams continue to remain the most commonly involved drug family in allergic drug reactions. They are often essential and there is a cost-effective and favourable risk-benefit ratio for the exploration of all suspicions of beta-lactam allergy. A firm diagnosis is always based on skin tests and sometimes on provocation tests. Recommendations have been published by allergy societies and distinguished scientists but they are not always concordant and can lead to some confusion for the practicing allergologist. The situation has even worsened since the world wide withdrawal of these penicillin determinants and since the predominance of amoxicillin and cephalosporin prescriptions in most countries. OBJECTIVE - METHOD: In a recent article, it was stated that patients with a penicillin allergy history and negative skin tests to major and minor penicillin determinants are at a low risk of relapse (0-5%) when receiving a beta-lactam. In this paper, our Drug Allergy and Hypersensitivity Database, a cohort database, was used to demonstrate that this statement is false. Standardized European Network for Drug Allergy questionnaires, skin test and challenge procedures were followed. RESULTS: One-thousand two-hundred and eighteen subjects, 69.8% of female, 51.7% of atopics, were included. 21.1% had a true beta-lactam allergy confirmed by skin tests (178, 69.3%) or by drug provocation (79, 30.7%). 17.4% of the patients with negative skin tests to major and minor penicillin determinants were positive for a beta-lactam. CONCLUSION: In the diagnosis of beta-lactams allergy, if all skin tests are negative, skin tests with other determinants and provocation tests under strict surveillance are mandatory.

ARIA (Allergic Rhinitis and Its Impact on Asthma) classification of allergic rhinitis severity in clinical practice in France.

BACKGROUND: The Allergic Rhinitis and Its Impact on Asthma (ARIA) workshop proposes a classification of allergic rhinitis severity. It does not take into account impairment in quality of life and treatment should be adapted accordingly. METHODS: Two cross-sectional surveys were designed:a spring survey, for which 1,321 practitioners enrolled 3,026 patients consulting for seasonal allergic rhinitis and an autumn-winter survey, for which 1,346 practitioners enrolled 3,507 patients consulting for perennial allergic rhinitis. Simple quality of life parameters were included and logistic regressions were performed in order to assess the impairment of quality of life. RESULTS: The majority of the patients were experiencing an impairment on their quality of life (92.2%). Except for cough, these patients had significantly more nasal, lung and ocular symptoms. In a multivariate analysis, rhinorrhea, nasal itching, red eyes, dyspnea, change in voice, fatigue and headache were correlated to impairment of quality of life. Persistent rhinitis was associated only with subjects who expressed difficulties in reading, and intermittent rhinitis with those who had to blow their nose and who expressed an impact on their professional activities. CONCLUSIONS: The proposal of the ARIA expert panel defining the severity of allergic rhinitis based on quality of life parameters is likely to simplify daily physician practice.