The Combined Use of Chronological and Morphological Criteria in the Evaluation of Immediate Penicillin Reactions: Evidence From a Large Study.

BACKGROUND: Immediate hypersensitivity reactions to penicillins are often labeled on the basis of a similar set of symptoms, but a key feature of these reactions that can be reproduced in diagnostic testing may be the timing of a reaction in relation to the dose administration. OBJECTIVE: To determine whether the timing of a reaction in response to the last dose of a penicillin would predict the results of diagnostic testing. METHODS: We evaluated 1074 patients by performing skin tests, serum specific IgE assays (ImmunoCAP), and challenges. Patients who were evaluated by us more than 6 months after their reactions and found negative were reevaluated within 2 to 4 weeks. RESULTS: Patients who had reacted within 1 hour after the first dose, within 1 hour after subsequent doses, more than 1 hour to within 6 hours after the first dose, or more than 1 hour to within 6 hours after subsequent doses were classified as group A (758 individuals), B (92), C (67), or D (157), respectively. Penicillin hypersensitivity was diagnosed in 707 patients (65.8%) by skin tests (407 patients, 57.6%), ImmunoCAP (47, 6.6%), both tests (232, 32.8%), or challenges (21, 3%). A conversion to allergy-test positivity occurred in 7 of 10 patients with anaphylactic reactions and in 1 of 28 patients with other reactions who were reevaluated after negative challenges. The rate of penicillin-allergic patients in groups A, B, C, and D was 85%, 35.9%, 35.8%, and 3.8%, respectively. Only 1 of 107 patients reporting cutaneous reactions lasting more than 1 day had positive results to allergy tests. CONCLUSIONS: IgE-mediated hypersensitivity can be diagnosed by skin tests in about 70% of subjects who react within 1 hour (eg, patients from groups A and B). This hypersensitivity can be lost over time, as demonstrated by the negativization of allergy tests in follow-up studies. In subjects with anaphylactic reactions, however, it is advisable to not consider this phenomenon definitive. In fact, a conversion to allergy test positivity can be observed in up to 20% of such subjects retested after negative challenges.

Evaluating Immediate Reactions to Cephalosporins: Time Is of the Essence.

BACKGROUND: Few studies have assessed the diagnostic value of cephalosporin skin tests in patients with immediate reactions to these ß-lactams. OBJECTIVE: To evaluate the usefulness of skin tests and challenges in assessing such subjects. METHODS: We conducted a prospective study of 236 consecutive subjects who had suffered 249 immediate reactions (mostly anaphylaxis) to cephalosporins. Skin tests were performed with penicillin reagents and suspected cephalosporins. Serum specific IgE assays (ImmunoCAP) were also carried out for penicillins and cefaclor. Subjects with negative results underwent challenges with the suspected cephalosporins; patients with negative results who had been assessed more than 6 months after their reactions were reevaluated. RESULTS: In the first allergy workup, an IgE-mediated hypersensitivity to cephalosporins was diagnosed in 164 (69.5%) of the 236 patients on the basis of skin test (162 patients) or cefaclor ImmunoCAP positivity (2 patients). Of the 72 patients with negative results, 55 underwent cephalosporin challenges; 3 reacted. Twenty subjects were reevaluated after cephalosporin negative challenges, with a conversion to cephalosporin skin test positivity occurring in 5 of the 6 subjects who had had anaphylactic reactions and in none of the remaining 14 subjects with other reactions. Overall, an immediate hypersensitivity to cephalosporins was diagnosed in 172 patients (of whom it was diagnosed in 5 after retesting). CONCLUSIONS: Most immediate reactions to cephalosporins are IgE-mediated. Cephalosporin skin testing is a useful tool for evaluating these reactions. IgE-mediated cephalosporin hypersensitivity may be a transient condition; therefore, allergy examinations should be repeated in patients with negative results who experienced anaphylaxis more than 6 months before the allergy workup, including challenges.

Tolerability of Cefazolin and Ceftibuten in Patients with IgE-Mediated Aminopenicillin Allergy.

BACKGROUND: Side-chain similarities or identities constitute the predominant factor for cross-reactivity between penicillins and cephalosporins, whereas differences in the side-chain structure seem to account for the absence of such cross-reactivity. OBJECTIVE: We sought to assess the cross-reactivity between penicillins and 2 cephalosporins (ie, cefazolin and ceftibuten) that have side chains different from those of penicillins, as well as to evaluate the possibility of using these cephalosporins in penicillin-allergic subjects. METHODS: We conducted a prospective study of 131 consecutive subjects who had suffered 170 immediate reactions (mostly anaphylaxis) to penicillins and had positive skin test results to at least 1 penicillin reagent. All patients underwent skin tests with cefazolin and ceftibuten. Patients with negative results were challenged with them. RESULTS: One participant had positive skin test results to cefazolin and ceftibuten, as well as to all other reagents tested, including aztreonam and carbapenems. All 129 subjects who underwent challenges with cefazolin and ceftibuten tolerated them. One subject refused cephalosporin challenges. CONCLUSIONS: Subjects with an IgE-mediated hypersensitivity to penicillins could be treated with cephalosporins such as cefazolin and ceftibuten, which are among the cephalosporins that have side-chain determinants different from those of penicillins. Nevertheless, in patients with such hypersensitivity who need these alternative ß-lactams, pretreatment skin tests are advisable because of the possibility of coexisting sensitivities or, much less frequently, of a sensitivity to an antigenic determinant of the common ß-lactam ring.

IgE-mediated hypersensitivity to cephalosporins: Cross-reactivity and tolerability of alternative cephalosporins.

BACKGROUND: Studies regarding the cross-reactivity and tolerability of alternative cephalosporins in large samples of subjects with an IgE-mediated hypersensitivity to cephalosporins are lacking. OBJECTIVE: We sought to evaluate the possibility of using alternative cephalosporins in subjects with cephalosporin allergy who especially require them. METHODS: One hundred two subjects with immediate reactions to cephalosporins and positive skin test results to the responsible drugs underwent serum specific IgE assays with cefaclor and skin tests with different cephalosporins. Subjects were classified in 4 groups: group A, positive responses to 1 or more of ceftriaxone, cefuroxime, cefotaxime, cefepime, cefodizime, and ceftazidime; group B, positive responses to aminocephalosporins; group C, positive responses to cephalosporins other than those belonging to the aforementioned groups; and group D, positive responses to cephalosporins belonging to 2 different groups. Group A subjects underwent challenges with cefaclor, cefazolin, and ceftibuten; group B participants underwent challenges with cefuroxime axetil, ceftriaxone, cefazolin, and ceftibuten; and group C and D subjects underwent challenges with some of the aforementioned cephalosporins selected on the basis of their patterns of positivity. RESULTS: There were 73 subjects in group A, 13 in group B, 7 in group C, and 9 in group D. Challenges with alternative cephalosporins (ceftibuten in 101, cefazolin in 96, cefaclor in 82, and cefuroxime axetil and ceftriaxone in 22 subjects) were well tolerated. CONCLUSIONS: Cephalosporin hypersensitivity does not seem to be a class hypersensitivity. Subjects with cephalosporin allergy who especially require alternative cephalosporins might be treated with compounds that have side-chain determinants different from those of the responsible cephalosporins and have negative pretreatment skin test responses.

Molecular allergology approach to allergic diseases in the paediatric age.

Identification, characterization, and purification of allergens are essential for the structural and immunologic studies needed to understand how these molecules induce specific IgE antibody production by the human immune system. Advances in molecular biology techniques have led to the production of recombinant allergens having constant properties, allowing detection of specific IgE directed against different molecular components of an allergenic source. Presence of homologous allergens in different sources is the reason for cross-reaction. Molecule-based diagnostic tools can lead to better interpretation of poly-sensitizations, observed by ST and in vitro tests using allergenic extracts as they were made before. Some examples IgE sensitization to major genuine allergens and panallergens will be presented.