New aspects of allergic reactions to betalactams: crossreactions and unique specificities

Blanca, Miguel; Vega, José M.; Garcı́a, J.J.; Miranda, A.; Carmona, Marı́a José; Juárez, C.; Terrados, S.; Fernández, J.

doi:10.1111/j.1365-2222.1994.tb00928.x

Cited by 114 publications

(94 citation statements)

References 55 publications

(61 reference statements)

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“…These include the side chain, the thiazolidine ring and the so-called new antigenic determinant (NAD) formed when the (3-lactam ring reacts with protein amino groups. The significance of these results has been highlighted by studies in humans suggesting that some patients can devel op an anaphylactic response to amoxicillin (AX) but still tolerate other penicillins [9][10][11]. Preliminary studies have suggested that this is because their IgE antibody binds to the haptenic structure dominated by the side chain of AX, re sulting in a specific response [12].…”

Section: Introductionmentioning

confidence: 94%

Studies of the Specificities of IgE Antibodies Found in Sera from Subjects with Allergic Reactions to Penicillins

Moreno¹,

Blanca²,

Mayorga³

et al. 1995

Int Arch Allergy Immunol

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Penicillins are immunogenic when administered to humans and in some instances they can also be allergenic, inducing specific IgE antibodies. Whilst the major haptenic group, the penicilloyl, is well characterised, less is known about the relative importance of the different parts of the structure for antibody binding and how this can influence the specificity of patients response. In order to investigate this further, sera from subjects who had suffered an IgE-mediated reaction to penicillins were studied using the radioallergosorbent test (RAST) and RAST inhibition. The assays employed reagents related to the penicillins causing the reaction. Using 173 sera, positive RAST results were only found with reagents based on benzyl penicillin (BP) and amoxicillin (AX). Fifty-three positive sera were selected for further studies and categorized into three groups: (A) sera only RAST positive to AX, (B) sera only positive to BP and (C) sera positive to both penicillins. RAST inhibition studies were then carried out using monomeric penicilloyl conjugates and compounds representing parts of the penicilloyl structures of BP and AX. For all three groups, monomeric penicilloyl conjugates were the most efficient inhibitors but there were differences for the other compounds. Group A sera were also inhibited by the side chain of amoxicillin, whereas group B sera were poorly inhibited by all other inhibitors. Group C sera showed two patterns of inhibition, both consistent with their more cross-reactive profile. Some group C sera were similar to group B, showing inhibition with monomeric penicilloyl conjugates only, whilst others were similar to group A showing inhibition with side-chain-related compounds, although in these cases all the side chain compounds inhibited all the assays. We conclude that in sera from patients allergic to penicillins, IgE antibodies of different specificities can be found reflecting the involvement of the penicillins in inducing the allergic reaction. Detailed inhibition analysis indicates that two main groups of antibodies can be distinguished: one where the side chain contributes a unique specificity to the antigen binding site and in which they are positive to AX, and another where most of the structure is required for optimal inhibition. However, a considerable variation in the pattern of recognition of the antigenic determinant was seen. No coexisting antibodies of different specificities were detected in the same patient.

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Section: Introductionmentioning

confidence: 94%

Studies of the Specificities of IgE Antibodies Found in Sera from Subjects with Allergic Reactions to Penicillins

Moreno¹,

Blanca²,

Mayorga³

et al. 1995

Int Arch Allergy Immunol

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“…Over time, these changes have entailed modifications of the immune response, mainly because of differences among the side-chain antigenic determinants of the various p-Iactams. Several studies have emphasized the importance of such determinants and thus the need to use in diagnosis the suspect p-Iactams themsel ves, particularly cephalosporins, in addition to PPL and MOM (5,(8)(9)(10)(11). Therefore, the reagents used for skin testing have changed.…”

Section: )mentioning

confidence: 99%

Immediate Allergic Reactions to β-Lactams: Diagnosis and Therapy

Romano

Mondino²,

Viola³

et al. 2003

Int J Immunopathol Pharmacol

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-Lactams are the antibiotics which most frequently provoke adverse reactions mediated by specific immunological mechanisms. These reactions, classifiable as immediate or non-immediate, can be produced by the four classes of~-Iactams (penicillins, cephalosporins, carbapenems and monobactams) currently available, which share a common~-lactarn ring structure. Immediate reactions occur within the first hour after drug administration and are characterized by urticaria, angioedema, rhinitis, bronchospasm, and anaphylactic shock. Immediate reading skin tests are the quickest and most reliable method for demonstrating the presence of~-Iactam specific IgE antibodies. It is crucial to use in diagnosis the suspected~-Iactams themselves, particularly cephalosporins, in addition to penicillin determinants. Serum specific IgE assays can be used as complementary tests. Negative test results should be interpreted in light of the time elapsed from the last exposure to the responsible~-Iactam. In fact, both in vivo and in vitro test sensitivity is known to decrease over time. In some diagnostic work-ups, patients with a positive history and negative skin and in vitro tests with classic reagents undergo a controlled administration of the suspected~-Iactam. The management of immediate allergic reactions should take into consideration their severity and type. Adrenaline is the drug of choice in the treatment of anaphylactic shock. In addition to adrenaline, corticosteroids and antihistamines should be administered. Histamine HI receptor antagonists are the mainstay of the treatment of immediate allergic reactions such as urticaria, rhinitis and conjunctivitis.-Lactams are the antibiotics which most frequently provoke adverse reactions mediated by specific immunological mechanisms. These reactions are classifiable as immediate or nonimmediate according to the time interval between drug administration and their onset (1). Immediate reactions occur within the first hour after drug administration and are characterized by urticaria, angioedema, rhinitis, bronchospasm, and anaphylactic shock (2,3). They are generally the most dangerous and are IgE-mediated. A combination of the drug or a drug metabolite with a carrier reacts with IgE bound to the plasma membrane of mast cells, leading to activation, degranulation, and release of mast cell mediators. Such reactions may be produced by the four classes of~-lactams (penicillins, cephalosporins, carbapenems and monobactams) currently available, which share a common~-lactam ring structure. Sometimes different~-lactam antibiotics also share identical or very similar side-chain structures, but, in most cases, the latter are different. DIAGNOSISImmediate-reading skin tests are the quickest and most reliable method for demonstrating the presence of~-lactam specific IgE antibodies (2-

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“…Specific IgE antibodies to penicillin and other beta-lactam antibiotics appear to recognize a multitude of antigenic determinants. Some beta-lactam-allergic individuals exhibit specific IgE antibodies to structures of the beta-lactam ring and may show cross-reactivity to other beta-lactam antibiotics, but others are highly selective in their recognition pattern and have IgE antibodies specific to side chains and thus react only to a single or few beta-lactam antibiotics [17][18][19]. Examples of other IgE-mediated drug hypersensitivities include reactions to immunoglobulins, insulins, chemotherapeutic agents and streptomycin [6,20].…”

Section: Ige-mediated Drug Allergymentioning

confidence: 99%

Adverse Drug Reactions: Mechanisms and Assessment

Ring

Brockow

2002

Eur Surg Res

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Adverse drug reactions (ADR) are an important clinical problem. They account for about 5% of all hospital admissions and cause death in approximately 0.01% of surgical patients. The mechanisms leading to ADR beyond IgE-mediated allergy are still poorly understood. The importance of chemically reactive drug metabolites and the involvement of T-lymphocytes in many drug hypersensitivity reactions have been highlighted in recent years. ADR are diagnosed on clinical grounds and the temporal relation between drug intake and the appearance of the symptoms. Allergy tests are required in the further assessment of the reaction. By means of skin tests, in vitro tests and provocation tests information about the culprit drug, the mechanism involved and possible alternatives can be obtained.

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New aspects of allergic reactions to betalactams: crossreactions and unique specificities

Cited by 114 publications

References 55 publications

Studies of the Specificities of IgE Antibodies Found in Sera from Subjects with Allergic Reactions to Penicillins

Studies of the Specificities of IgE Antibodies Found in Sera from Subjects with Allergic Reactions to Penicillins

Immediate Allergic Reactions to β-Lactams: Diagnosis and Therapy

Adverse Drug Reactions: Mechanisms and Assessment

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