Patterns of response and drugs involved in hypersensitivity reactions to beta-lactams in children.

BACKGROUND: Beta-lactams generate different allergenic determinants that induce selective or cross-reactive drug hypersensitivity reactions (DHRs). We aimed to identify the drugs involved, the selectivity of the response, the mechanism, and the value of the different diagnostic tests for establishing a diagnosis in children evaluated for DHRs to beta-lactams. METHODS: Prospective study evaluating children aged under 16 years reporting DHRs to beta-lactams. Reactions were classified as immediate and non-immediate reactions. The workup included sIgE, skin testing, and drug provocation tests (DPTs) for immediate reactions and patch testing and DPTs for non-immediate ones. RESULTS: Of the 510 children included, 133 were evaluated for immediate reactions and confirmed in 8.3%. Skin test/in vitro IgE contributed to diagnosing half of the cases. Selective reactions occurred with amoxicillin (63%), followed by common penicillin determinants (27%) and cephalosporins (0.9%). Among non-immediate reactions (11.4% of the 377 children evaluated), most required DPTs, 52.7% of which were positive at 6-7 days of drug challenge. Selective reactions were identified with amoxicillin (80%), penicillin G (7.5%), cephalosporins (7.5%), and clavulanic acid (5%). Urticaria and maculopapular exanthema were the most frequent entities. CONCLUSIONS: There were few confirmed cases of either type of reaction. Skin testing proved less valuable in non-immediate reactions, over half of which would also have been lost in a short DPT protocol. Selective responders to amoxicillin were more likely to have non-immediate reactions, while clavulanic acid selectivity was exclusive to the non-immediate typology. Over half the cases with DPTs required 6-7 days of treatment for DHR confirmation.

Clavulanic Acid Is a Leading Culprit Beta-Lactam in Immediate Allergic Reactions to Penicillins.

PURPOSE: Clavulanate, a beta-lactam associated with amoxicillin, is frequently prescribed in patients at all ages. Recent data implicate amoxicillin-clavulanate in up to 80% of beta-lactam allergy cases. We assessed clavulanate's role in inducing allergic reactions to this combination treatment, with a focus on selective immediate reactions. METHODS: Adults (≥ 16 years) reporting a history of immediate reactions to amoxicillin-clavulanate were evaluated through a beta-lactam allergological workup, using modified European Academy of Allergy and Clinical Immunology guidelines. Patients first underwent skin testing, and if negative, drug provocation tests. Expected outcomes were: Group A, subjects with immediate reaction to classical penicillin group determinants (penicilloyl polylysine, minor determinants mixture, and/or penicillin G); Group B, subjects with selective immediate reaction to amoxicillin; Group C, subjects with selective immediate reaction to clavulanate and Group D, those immediate reactions with co-sensitization to clavulanate plus penicillin group determinants or amoxicillin. RESULTS: Of 1,170 included patients, 104 had immediate reactions: 36.5% to penicillin group determinants (Group A), 26.9% to amoxicillin (Group B), 32.7% to clavulanate (Group C), and 3.8% to clavulanate plus penicillin determinants or amoxicillin (Group D). Diagnosis was made by skin testing in 79%, 75% and 47% of the patients, respectively, in the first 3 groups (P < 0.001). Drug provocation tests were necessary to establish most other diagnoses. Anaphylaxis predominated over urticaria/angioedema in all groups. CONCLUSIONS: Selective immediate reactions to clavulanate accounted for over a third of cases with confirmed reactions after amoxicillin-clavulanate intake, with more than half experiencing anaphylaxis. Within this group, skin test sensitivity was below 50%. People taking amoxicillin-clavulanate may also be co-sensitized to both drugs.

Acetyl Salicylic Acid Challenge in Children with Hypersensitivity Reactions to Nonsteroidal Anti-Inflammatory Drugs Differentiates Between Cross-Intolerant and Selective Responders.

BACKGROUND: Hypersensitivity reactions to nonsteroidal anti-inflammatory drugs (NSAIDs) in children are becoming a great concern. Most studies have focused on adults, with noted discrepancies observed in the classification of hypersensitivity reactions to NSAIDs in children when compared with adults. OBJECTIVE: To phenotype a group of children with hypersensitivity reactions to NSAIDs, including paracetamol, and analyze the degree of agreement with the entities reported in adults and how they fit the proposed classifications. METHODS: The study comprised 116 children aged 0.5 to 14 years, with a clinical history indicative of hypersensitivity reactions to NSAIDs. They all underwent a single-blind oral provocation test with acetyl salicylic acid, except in those cases when this was the suspected drug, in which case the challenge was done first with ibuprofen. If positive, cross-intolerance was established and if negative, an oral provocation test with the culprit drug was performed to establish a selective response or exclude allergy. RESULTS: Of the 26% diagnosed as hypersensitive to NSAIDs, 83% were cross-intolerant and 17% selective reactors. The highest significant differences between reactors and nonreactors were observed in the time to reaction after drug intake and the clinical entity (P < .0001), followed by drug involved and age (P < .01). CONCLUSIONS: From the total number of cases confirmed with NSAID hypersensitivity, 83% were cross-intolerant. In cross-intolerant reactions, both cutaneous and respiratory manifestations are common. Acetyl salicylic acid challenge as the first approach proved to be safe and useful to establish the diagnosis.

Practical approach to the treatment of NSAID hypersensitivity.

INTRODUCTION: Non-steroidal anti-inflammatory drugs (NSAIDs) are the most frequently involved in drug hypersensitivity reactions (DHR). NSAIDs are prescribed for different processes and some NSAIDs can be obtained over the counter. Areas covered: We analyse the practical approaches for managing and treating NSAID-DHR considering the five major groups of entities recognised, divided into two categories: those responding to strong COX-1 inhibitors and possibly weak COX-1 or selective COX-2 inhibitors named cross-intolerant (CI), and those induced by a single drug or drug group with good tolerance to strong COX-1 inhibitors, known as allergic reactions (SR). An analysis of the recent literature indicates that two approaches can be followed for CI: to give acetyl salicylic acid to confirm NSAID hypersensitivity or to give alternative drugs to provide a solution for the treatment of pain, fever, inflammation or other conditions. Desensitisation approaches have been undertaken, but mainly for CI cases with respiratory airway involvement and they are very rarely used for CI with cutaneous involvement or SR. Expert commentary: DHR to NSAIDs are now recognised as one of the most important problems in the evaluation and management of drug allergy. Because no diagnostic tests exist, important resources are needed to evaluate these patients.

Asthma and Rhinitis Induced by Selective Immediate Reactions to Paracetamol and Non-steroidal Anti-inflammatory Drugs in Aspirin Tolerant Subjects.

In subjects with non-steroidal anti-inflammatory drugs (NSAIDs)- exacerbated respiratory disease (NERD) symptoms are triggered by acetyl salicylic acid (ASA) and other strong COX-1 inhibitors, and in some cases by weak COX-1 or by selective COX-2 inhibitors. The mechanism involved is related to prostaglandin pathway inhibition and leukotriene release. Subjects who react to a single NSAID and tolerate others are considered selective responders, and often present urticaria and/or angioedema and anaphylaxis (SNIUAA). An immunological mechanism is implicated in these reactions. However, anecdotal evidence suggests that selective responders who present respiratory airway symptoms may also exist. Our objective was to determine if subjects might develop selective responses to NSAIDs/paracetamol that manifest as upper/lower airways respiratory symptoms. For this purpose, we studied patients reporting asthma and/or rhinitis induced by paracetamol or a single NSAID that tolerated ASA. An allergological evaluation plus controlled challenge with ASA was carried out. If ASA tolerance was found, we proceeded with an oral challenge with the culprit drug. The appearance of symptoms was monitored by a clinical questionnaire and by measuring FEV1 and/or nasal airways volume changes pre and post challenge. From a total of 21 initial cases, we confirmed the appearance of nasal and/or bronchial manifestations in ten, characterized by a significant decrease in FEV1% and/or a decrease in nasal volume cavity after drug administration. All cases tolerated ASA. This shows that ASA tolerant subjects with asthma and/or rhinitis induced by paracetamol or a single NSAID without skin/systemic manifestations exist. Whether these patients represent a new clinical phenotype to be included within the current classification of hypersensitivity reactions to NSAIDs requires further investigation.

Purpura fulminans / Purpura fulminans

Se presenta el caso de una paciente de 65 años con púrpura fulminans se cecundaria a coagulación intra vascular diseminada posterior a una sepsis de origen urinario. Se hace revisión de la literatura.