ABSTRACT
PURPOSE OF REVIEW: To analyze recent findings on antibiotic hypersensitivity reactions in children focusing on betalactams, with regard to clinical entities, antibiotics involved and diagnostic methods. RECENT FINDINGS: Betalactams are the most frequent cause of antibiotic hypersensitivity, more specifically amoxicillin alone or with clavulanic acid, with selective reactions to clavulanic acid also recently reported. Cephalosporins are the second most frequent group involved, especially in countries with high consumption. Other antibiotics such as sulphamides and macrolides although involved are less common. There are two types of reactions, immediate and nonimmediate, the latter being more frequent. Diagnosis is complex and is confirmed in less than 10% of children evaluated, twice as often in immediate than in nonimmediate reactions. Clinical history is often unreliable. Regarding other methods, skin testing and in-vitro methods can be useful for immediate reactions; however, most nonimmediate reactions need drug provocation tests for diagnosis. There are different degrees of cross-reactivity between penicillin and cephalosporins, with the side-chain being critical for determination. SUMMARY: Betalactams are the antibiotics most frequently involved in hypersensitivity reactions with amoxicillin being the main culprit drug. Immediate reactions, although less frequent, are more often confirmed, with skin testing still relevant for their diagnosis. Nonimmediate reactions are usually diagnosed by drug provocation test.
Subject(s)
Anti-Bacterial Agents/immunology , Drug Hypersensitivity/immunology , beta-Lactams/immunology , Anti-Bacterial Agents/adverse effects , Child , Cross Reactions , Desensitization, Immunologic , Drug Hypersensitivity/diagnosis , Humans , Skin Tests , beta-Lactams/adverse effectsABSTRACT
INTRODUCTION: Hypersensitivity reactions to non-steroidal anti-inflammatory drugs (NSAIDs) are the most frequently reported reaction to drugs. They can be induced by pharmacological mechanisms (cyclooxygenase inhibition), with patients classified as cross-intolerant (CI), or by specific immunological mechanisms, IgE or T cell, with patients classified as selective reactors (SR). OBJECTIVE: To analyse a large group of children with a history of NSAID hypersensitivity diagnosed by drug provocation test (DPT). METHODS: A group of 63 children with a history of NSAID hypersensitivity were evaluated by DPT. The children were classified as CI or SR depending on the acetyl salicylic acid (ASA) response in DPT. The atopic status was also assessed by prick tests and total IgE in serum. RESULTS: Using DPT, 68.2% were confirmed as having hypersensitivity, 58.1% classified as CI and 41.9% as SR. Of the 119 DPT performed, 73 were positive (53.4% to ibuprofen, 37% to ASA, 8.2% to metamizol and 14% to paracetamol); angio-oedema was present in 86.3% of cases. All CI cases tolerated the administration of paracetamol. A significant number of the CI children were atopic compared with the SR children and non-allergic controls. CONCLUSION: In these children, CI hypersensitivity to NSAIDs was the most frequent type of hypersensitivity reaction. Ibuprofen was the drug most often involved, angio-oedema the most common entity, and frequently associated with atopy. DPT proved a safe approach for diagnosing these patients.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Drug Hypersensitivity/diagnosis , Hypersensitivity, Immediate/diagnosis , Immunologic Tests , Administration, Oral , Adolescent , Age Factors , Angioedema/chemically induced , Angioedema/diagnosis , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/immunology , Biomarkers/blood , Chi-Square Distribution , Child , Child, Preschool , Cross Reactions , Drug Hypersensitivity/blood , Drug Hypersensitivity/etiology , Drug Hypersensitivity/immunology , Female , Humans , Hypersensitivity, Immediate/blood , Hypersensitivity, Immediate/chemically induced , Hypersensitivity, Immediate/immunology , Immunoglobulin E/blood , Infant , Intradermal Tests , Male , Predictive Value of Tests , Single-Blind Method , Surveys and QuestionnairesABSTRACT
T cells are known to develop a critical role in the pathogenesis of atopic dermatitis (AD) and bronchial asthma. T cells involved in AD express the skin homing receptor CLA, but no lung homing receptor has been identified in bronchial asthma. We compared different cell markers and the cytokine production in T cells from children with AD or bronchial asthma. We studied the involvement of CLA+ and CLA- T-cell subpopulations in these diseases. We studied 20 children with acute AD lesions, 15 with mild persistent asthma, and 15 non-atopic controls. All patients were sensitized to house dust mite (DP) and evaluated during the acute phase. Total and specific IgE were measured by immunoassay and the expression of different cell markers and the cytokine production was analyzed by flow cytometry in peripheral blood mononuclear cells. Total IgE was significantly higher in AD children and IgE to DP in the asthmatic children. There was a significant increase in CD25+ CD4+ cells in asthmatic children and in HLA-DR+ CD4+ and HLA-DR+ CD8+ cells in AD. In the CD4+ subsets, there was an increase in IL-13, IL-5 and TNF-alpha in AD compared to controls, a decrease in IFN-gamma in asthmatic children compared to controls, and an increase in IL-13, IL5, IL2, TNF-alpha, and IFN-gamma in the AD compared to asthmatic children. Changes in cytokine production were mainly detected in CLA+ cells in AD and in CLA- cells in asthma. Differences exist in total and specific IgE, activation markers, and cytokine patterns between AD children and children with asthma, with the former expressing a Th2 pattern whereas in asthmatic children we only detected a decrease in IFN-gamma. Moreover, the subpopulations (CLA+ vs. CLA-) expressing these changes were different, indicating that the underlying mechanisms in the two diseases are not exactly the same.
