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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.

Background: Hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs) can affect children, with the mechanism proposed being inhibition of the cyclooxygenase enzyme-1 (COX-1). In these patients nonchemically related NSAIDs, including COX-2 inhibitors, can induce the reaction, hampering treatment of fever and inflammatory processes., Objectives: To analyse retrospectively tolerance to etoricoxib, a selective COX-2 inhibitor, and to meloxicam, a preferential COX-2 inhibitor, in children with hypersensitivity to NSAIDs., Methods: Clinical records of children (aged 1-14 years) diagnosed with hypersensitivity reactions to NSAIDs from January 2006 to January 2013 were included. The diagnosis was confirmed by oral drug provocation test (DPT) with the culprit NSAIDs and acetylsalicylic acid (ASA). Tolerance to paracetamol, etoricoxib and meloxicam was also evaluated., Results: The study included 41 children with a positive DPT with ASA and the culprit NSAID. DPT with paracetamol and etoricoxib was negative in all children, although two (4.9%) children developed a reaction after the administration of meloxicam., Conclusions: These data indicate that both etoricoxib and meloxicam are good alternatives for treatment in older children with hypersensitivity to NSAIDs., (© 2013 British Association of Dermatologists.)

Introduction: Hypersensitivity reactions to beta-lactams (BLs) are often reported in children, with amoxicillin and, to a lesser extent, cephalosporins being the most frequent drugs involved. Although many of these children are considered to be allergic, a careful evaluation only confirms a low percentage., Objectives: To analyse the clinical data, sensitization profile and diagnostic methods used in a large group of children with a clinical history of hypersensitivity reactions to BLs., Methods: The study included children aged 1-14 yr with symptoms suggestive of hypersensitivity to BLs from January 2006-December 2012. Diagnosis was confirmed from a clinical history, specific IgE determination, skin testing and, if necessary, a drug provocation test (DPT)., Results: Of a total of 783 patients studied, only 62 (7.92%) were confirmed as being allergic, 9 (14.52%) with immediate and 53 (85.48%) with non-immediate reactions. In those with immediate reactions, 2 (22.22%) were diagnosed by in vitro test, 2 (22.22%) by skin testing and 5 (55.56%) by DPT; in those with non-immediate reactions, 2 (3.77%) were diagnosed by skin testing and 51 (96.23%) by DPT. In all cases, DPT was positive to the culprit drug (29 AX-CLV, 26 AX, 1 cefixime and 1 cefaclor), and the most usual symptoms were exanthema in 43 cases, urticaria in 12, urticaria-angio-oedema in 1 and erythema in 1 case., Conclusion: After an allergological work-up, over 90% of the children evaluated were finally confirmed as tolerant to BLs. Most reactions were of the non-immediate type, and DPT was an essential tool for diagnosis., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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., (© 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.)

The cutaneous symptoms in non-immediate reactions to drugs are not always clinically distinguishable from those induced by viruses, especially during the early phase of the reaction. Moreover, viral infections and drug reactions often coexist and identification of the etiological agent is necessary. Discerning the differences in the immunological response between both may help in the diagnosis. The aim of this study was to determine possible differences in the immunological response in non-immediate cutaneous reactions to drugs versus cutaneous viral-induced diseases in children. Two groups of children were evaluated: one with non-immediate drug-induced cutaneous reactions (DICR) and another with virus-induced cutaneous reactions (VICR). A third group of children taking the same drugs as the DICR group and with no cutaneous disease or viral infections was included as controls. The lymphocyte markers CD3, CD4, CD8, CD16, CD19, CLA, CD25, CD69, CD45RO, CD45RA were determined by flow cytometry. IL-2, IL-4, IL-5, IFN-gamma, TNF-alpha and IL-10 mRNA were measured by RT-PCR. Data were compared by non-parametric and chi(2) statistical analysis. In DICR group (n=8) the diagnosis was established by temporal association, improvement after drug withdrawal, patch testing, and in some cases by controlled administration. All patients in the VICR group (n=10) were diagnosed based on a positive viral serology: the presence of IgM antibodies or seroconversion of IgG antibodies. There were significant differences between the three groups in peripheral lymphocytes expressing the skin homing receptor CLA (P < 0.01), the early activation marker CD69 (P < 0.001), and the memory (CD3+CD45RO+) (P < 0.02) and naive (CD3+CD45RA+) (P < 0.03) T cell subsets. Children with DICR showed a TH1 mRNA cytokine pattern whereas those with VICR showed a TH0 pattern. In lymphocyte subpopulations from children, differences in the immunological response between DICR and VICR can be detected in the expressions of the activation marker CD69 and the cutaneous homing receptor CLA, and in cytokine mRNA profiles.

Cytarabine (Cyt) is an antimetabolite used primarily in the treatment of leukemia, and both immediate and delayed hypersensitivity reactions have been reported. We studied a 9-year-old girl with lymphoblastic leukemia, who developed three anaphylactoid reactions during Cyt treatment courses over a 1-year period. Three years later, Cyt was required again. Although a skin test was negative to Cyt at the concentration of 4 micrograms/ml, we decided on placebo-controlled administration of the drug. The Cyt was well tolerated, and urine values of N-methylhistamine showed no important variations throughout this period compared to those during the placebo administration. Skin tests carried out 14 days after the study were positive at the concentration of 4 micrograms/ml. The history of different episodes of allergic reactions to Cyt, the last one being the most severe, indicated the possible participation of an immediate hypersensitivity phenomenon, but because no studies had been carried out initially, we could not establish the presence of IgE antibodies. These results indicate that good tolerance existed after the control administration procedure. The long interval, 3 years, between the allergic episode and our protocol and the appearance of a positive skin test 14 days after the protocol indicated that the subject had lost sensitivity and become resensitized after the controlled administration procedure.