Cristobalina Mayorga

Update on the evaluation of hypersensitivity reactions to betalactams

Hypersensitivity reactions to betalactams (BLs) are classified as immediate or nonimmediate. The former usually appear within 1 h of drug‐intake and are mediated by specific IgE‐antibodies. Nonimmediate reactions are those occurring more than 1 h after drug‐intake, and they can be T‐cell mediated. The diagnostic evaluation of allergic reactions to BLs has changed over the last 5 years, for several reasons. Major and minor determinants are no longer commercially available for skin testing in many countries. In immediate allergic reactions, the sensitivity of skin testing and immunoassays is decreasing and new in vitro methods, such as the basophil activation test, are gaining importance for diagnosis. For nonimmediate reactions, skin testing appears to be less sensitive than previous results, although more studies need to be carried out in this direction. Nevertheless, the drug provocation test is still necessary for diagnosis.

Natural evolution of skin test sensitivity in patients allergic to β-lactam antibiotics

BACKGROUND Subjects with immediate reactions to penicillins and positive skin test responses may lose sensitivity if penicillin is avoided. The longer the interval between the reaction and the skin test, the greater the likelihood of having a negative result. OBJECTIVE We sought to study prospectively the evolution of skin test sensitivity in a group of subjects allergic to penicillin with positive skin test responses to different penicillin determinants. METHODS Skin tests were performed with major and minor determinants of benzylpenicillin (BPO/MDM), amoxicillin (AX), and ampicillin at the initial evaluation and repeated 1, 3, and 5 years later if the responses were still positive. Subjects were divided into 2 groups. Group A consisted of patients with a positive skin test response to benzylpenicilloyl or minor determinant mixture, and group B consisted of those with a selective response to amoxicillin and good tolerance to benzylpenicillin. RESULTS In group A (n = 31) after 1 year, 25 patients continued to have positive responses and 6 began to have negative responses; after 3 years, 18 continued to have positive responses, 5 began to have negative responses, and 2 were lost to follow-up; and after 5 years, 12 continued to have positive responses, 5 began to have negative responses, and 1 was lost to follow-up. In group B (n = 24) 12 had positive responses, and 12 had negative responses after 1 year; 6 had positive responses, 5 had negative responses, and 1 was lost to follow-up after 3 years; and no patients had positive responses, 5 had negative responses, and 1 was lost to follow-up after 5 years. Survival analysis showed significant differences between groups (log-rank test = 12.8; P <. 0003). CONCLUSION Patients with a selective response to amoxicillin tended to lose sensitivity faster than those who responded to several penicillin determinants, supporting the existence of at least 2 distinct types of IgE response in patients allergic to beta-lactam.

Diagnostic evaluation of a large group of patients with immediate allergy to penicillins: the role of skin testing

Background: Penicillin is no longer the most commonly prescribed β‐lactam, and the pattern of reactions has changed. We studied the diagnostic value of skin testing in penicillin‐allergic subjects from a population where benzylpenicillin is not now the most frequently used β‐lactam.

Clinical evaluation of Pharmacia CAP System™ RAST FEIA amoxicilloyl and benzylpenicilloyl in patients with penicillin allergy

Background: The diagnosis of IgE‐mediated immediate reactions to penicillins can be supported by in vivo or in vitro tests using classical benzylpenicillin determinants. The wide variety of β‐lactams and the description of new specificities requires a re‐evaluation of the different tests available. The objective was to evaluate the diagnostic capacity of Pharmacia CAP System™ RAST FEIA amoxicilloyl c6 (AXO) and benzylpenicilloyl c1 (BPO) in patients with a documented IgE‐mediated penicillin allergy.

In vitro T‐cell responses to β‐lactam drugs in immediate and nonimmediate allergic reactions

Background:β‐Lactam drugs may induce both cellular and humoral allergic reactions, and there is evidence that T cells play an important role in the pathogenesis of these reactions. The aim of this work was to assess the sensitivity and specificity of the lymphocyte transformation test (LTT) as an in vitro diagnostic tool, in patients with either an immediate or a nonimmediate reaction to penicillin G and/or amoxicillin.

The diagnostic interpretation of basophil activation test in immediate allergic reactions to betalactams

Background Basophil activation by allergens, including drugs, has been used to determine sensitivity and to study IgE recognition and cross‐reactivity.

Relevance of the determination of serum‐specific IgE antibodies in the diagnosis of immediate β‐lactam allergy

Background:  Allergic reactions to β‐lactams are the most frequent cause of adverse drug reactions mediated by specific immunologic mechanisms. They can be explored by in vivo and/or in vitro tests. The measurement of serum‐specific immunoglobulin E (IgE) presents several advantages: safety, simplicity, and availability to nonallergologist physicians.

The clinical utility of basophil activation testing in diagnosis and monitoring of allergic disease

The basophil activation test (BAT) has become a pervasive test for allergic response through the development of flow cytometry, discovery of activation markers such as CD63 and unique markers identifying basophil granulocytes. Basophil activation test measures basophil response to allergen cross‐linking IgE on between 150 and 2000 basophil granulocytes in <0.1 ml fresh blood. Dichotomous activation is assessed as the fraction of reacting basophils. In addition to clinical history, skin prick test, and specific IgE determination, BAT can be a part of the diagnostic evaluation of patients with food‐, insect venom‐, and drug allergy and chronic urticaria. It may be helpful in determining the clinically relevant allergen. Basophil sensitivity may be used to monitor patients on allergen immunotherapy, anti‐IgE treatment or in the natural resolution of allergy. Basophil activation test may use fewer resources and be more reproducible than challenge testing. As it is less stressful for the patient and avoids severe allergic reactions, BAT ought to precede challenge testing. An important next step is to standardize BAT and make it available in diagnostic laboratories. The nature of basophil activation as an ex vivo challenge makes it a multifaceted and promising tool for the allergist. In this EAACI task force position paper, we provide an overview of the practical and technical details as well as the clinical utility of BAT in diagnosis and management of allergic diseases.

Seasonal idiopathic rhinitis with local inflammatory response and specific IgE in absence of systemic response

Background:  Patients with idiopathic rhinitis (IR) are considered to be nonallergic because they have a negative skin prick test (SPT) and allergen specific‐IgE in serum. The concept of localized mucosal allergy in the absence of atopy has recently been proposed. The immunological mechanisms involved in seasonal IR have not been sufficiently studied. We examined nasal mucosa inflammation, the presence of nasal specific‐IgE and the response to nasal allergen provocation test (NAPT) in patients with seasonal IR who presented symptoms only in spring.

Negativization rates of IgE radioimmunoassay and basophil activation test in immediate reactions to penicillins

Background:  Skin test sensitivity in patients with immediate allergy to penicillins tends to decrease over time, but no information is available concerning in vitro tests. We analysed the negativization rates of two in vitro methods that determine specific immunoglobulin E (IgE) antibodies, the basophil activation test using flow cytometry (BAT) and the radioallergosorbent test (RAST), in immediate allergic reactions to penicillins.