Francesco Gaeta

Diagnosing immediate reactions to cephalosporins

Background After penicillins, cephalosporins are the betalactams that most often induce IgE‐mediated reactions. The development of diagnostic tests has been delayed, however, because the cephalosporin allergenic determinants have not been properly identified.

IgE-mediated hypersensitivity to cephalosporins: Cross-reactivity and tolerability of penicillins, monobactams, and carbapenems

BACKGROUND There have been few studies regarding the cross-reactivity and tolerability of penicillins, aztreonam, and carbapenems in large samples of subjects with cephalosporin allergy. OBJECTIVE We sought to evaluate the possibility of using penicillins, monobactams, and carbapenems in subjects with cephalosporin allergy who especially require them. METHODS We conducted a prospective study of 98 consecutive subjects who had 106 immediate reactions (mostly anaphylactic shock) to cephalosporins and had positive skin test results for these drugs. To assess the cross-reactivity with penicillins, monobactams, and carbapenems and the tolerability of such alternative β-lactams, all subjects underwent skin tests and serum-specific IgE assays with penicillin reagents, as well as skin tests with aztreonam, imipenem/cilastatin, and meropenem. Subjects with negative test results were challenged with meropenem, imipenem/cilastatin, aztreonam, and amoxicillin. RESULTS Positive allergologic test results to penicillins were displayed by 25 (25.5%) subjects, including 1 with positive results to all reagents tested and another with a positive result to aztreonam. Another subject had positive results to both ceftazidime and aztreonam. A reaction to cephalosporins with side-chain structures similar or identical to those of penicillins was a significant predictor of cross-reactivity because of an increased 3-fold risk of positive results on allergologic tests with penicillin determinants. Challenges with alternative β-lactams were tolerated, with the exception of 1 urticarial reaction to imipenem/cilastatin. CONCLUSIONS About 25% of subjects with cephalosporin allergy had positive results to penicillins, 3.1% to aztreonam, 2% to imipenem/cilastatin, and 1% to meropenem. In those who especially require alternative β-lactams, pretreatment skin tests are advisable because negative results indicate tolerability of the β-lactam concerned.

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

To cite this article: Demoly P, Romano A, Botelho C, Bousquet‐Rouanet L, Gaeta F, Silva R, Rumi G, Rodrigues Cernadas J, Bousquet PJ. Determining the negative predictive value of provocation tests with beta‐lactams. Allergy 2010; 65: 327–332.

Diagnosing Hypersensitivity Reactions to Cephalosporins in Children

OBJECTIVES. The goals were to evaluate the usefulness of skin tests, patch tests, serum specific IgE assays, and challenges in diagnosing hypersensitivity reactions to cephalosporins and to clarify the pathogenic mechanism of such reactions. METHODS. Children with immediate manifestations (within 1 hour) underwent immediate-reading skin tests with penicillin reagents and any suspect cephalosporins, serum specific IgE assays, and challenges; some children underwent reevaluations. Children with nonimmediate manifestations (after >1 hour) were assessed with patch tests, delayed-reading skin tests, and challenges. RESULTS. We evaluated 148 children with hypersensitivity reactions to cephalosporins, mainly cefaclor and ceftriaxone; 105 had experienced nonimmediate manifestations (mostly urticarial eruptions and maculopapular rashes) and 43 immediate manifestations (anaphylactic shock, urticaria and/or angioedema, and erythema). None of the nonimmediate reactors demonstrated positive results in patch tests and/or delayed skin tests; only 1 subject displayed immediate positive responses to penicillin skin-test reagents. Among the 104 patients with negative results, 96 underwent challenges; 95 tolerated the challenges, and 1 reacted to the cefaclor pediatric suspension and tolerated the challenge with a cefaclor capsule. In the first allergologic evaluation, 33 of the 43 children with immediate reactions displayed skin-test positivity. Of the 10 patients with negative results, 7 underwent challenges, followed by therapeutic courses and reevaluations for 4. All challenges and therapeutic courses were tolerated; in the reevaluation, 1 girl demonstrated positive skin-test results for both the responsible cephalosporin and penicillin reagents. Overall, IgE-mediated hypersensitivity was diagnosed for 34 (79%) of 43 subjects. CONCLUSIONS. Extremely few nonimmediate manifestations associated with cephalosporin therapy are actually hypersensitivity reactions, whereas most immediate reactions to cephalosporins are IgE-mediated. Cephalosporin skin testing is a useful tool for evaluating such reactions.

Lipid transfer proteins: the most frequent sensitizer in Italian subjects with food-dependent exercise-induced anaphylaxis

Specific food‐dependent exercise‐induced anaphylaxis (S‐FDEIAn) is a distinct form of food allergy in which symptoms are elicited by exercise performed after ingesting food to which the patient has become sensitised. Non‐specific FDEIAn (NS‐FDEIAn) is a syndrome provoked by exercise performed after ingesting any food.

Tolerability of meropenem in children with IgE‐mediated hypersensitivity to penicillins

Background:  Administration of meropenem to penicillin‐allergic patients who might benefit from this treatment is usually avoided because of a 47.4% rate of cross‐reactivity to imipenem, the prototype of the carbapenem class of β‐lactam antibiotics, demonstrated in a single study on the basis of positive responses to skin tests with imipenem reagents. However, recent studies of ours have demonstrated a very low rate of cross‐reactivity between penicillins and both meropenem and imipenem in adults.

A comparison of the performance of two penicillin reagent kits in the diagnosis of beta-lactam hypersensitivity

Background:  Skin testing with penicilloyl polylysine (PPL) and minor determinant mixture (MDM) represents the first‐line method for diagnosing β‐lactam hypersensitivity. However, in 2004, Allergopharma and Hollister‐Stier announced their decision to stop the production of penicillin reagents (Allergopen® and PrePen®, respectively) within 1 year. Therefore, we decided to compare PPL and MDM from Allergopharma (Allergopen) with those from Diater (DAP®).

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 β‐lactam hypersensitivity and may produce negative consequences.

Assessing potential determinants of positive provocation tests in subjects with NSAID hypersensitivity

Background Provocation tests (PTs) with the suspected compounds are considered the ‘gold standard’ for establishing or excluding a diagnosis of hypersensitivity to non‐steroidal anti‐inflammatory drugs (NSAIDs). However, only a few studies have evaluated the potential determinants of positive responses to PTs.

Patch Testing in Non-Immediate Drug Eruptions

The present review addresses the literature regarding the sensitivity and specificity of the various diagnostic methods for evaluating non-immediate (ie, occurring more than 1 hour after drug administration) hypersensitivity reactions associated with β-lactams and other antibiotics, anticonvulsants, heparins, iodinated contrast media, etc. Such reactions include several clinical entities, which range from mild reactions, such as maculopapular rash and delayed-appearing urticaria, to severe ones, such as acute generalized exanthematous pustulosis (AGEP), Stevens-Johnson syndrome, and toxic epidermal necrolysis (TEN). Clinical and laboratory studies indicate that a cell-mediated pathogenic mechanism is often involved in maculopapular rashes. However, this mechanism has also been demonstrated in other non-immediate reactions, such as urticarial and/or angioedematous manifestations, TEN, bullous exanthems, and AGEP. Patch tests, together with delayed-reading intradermal tests, lymphocyte transformation tests, and challenges, are useful tools for evaluating non-immediate drug eruptions. Patch tests can be performed with any form of commercial drugs and are safer than intradermal tests. However, patch tests are less sensitive than intradermal tests, and their sensitivity may vary, depending on the vehicle used.