Outcomes of drug provocation tests in Korean children with suspected drug hypersensitivity reaction

PURPOSE: Drug provocation tests (DPT) are the gold standard for confirming the diagnosis of drug hypersensitivity reactions (DHRs). However, there are little studies of DPT in children. The purpose of this study was to evaluate DPT results and safety as diagnostic methods of DHR in Korean children. METHODS: We reviewed the medical records of 39 children under 18 years of age with a suspected DHR and performed DPT between January 2010 and May 2016 at Asan Medical Center. RESULTS: Total 110 DPT were performed in 39 children (20 boys and 19 girls) with a history of DHR. Clinical presentation of DHR included skin rash (n=7), pruritus (n=3), urticaria (n=18), angioedema (n=19), dyspnea (n=5), hoarseness (n=1), hypothermia (n=1), and anaphylaxis (n=5). The median age at the time of DPT was 9 years. Positive DPT were observed in 21 of 39 children (53.8%) and 28 of 110 cases (25.5%). Drugs causing positive reactions were acetaminophen in 50% (9 of 18), nonsteroidal anti-inflammatory drugs in 29.2% (14 of 48), cephalosporin in 9.1% (1 of 11), trimethoprim/sulfamethoxazole in 50% (1 of 2), local anesthetics in 10% (1 of 10), and others (levodropropizine and idursulfase) in 15.4% (2 of 13). There was no statistical difference between children who had positive and negative results in sex, age, personal and parental history of allergic disease, eosinophil count, or total IgE level. Children with positive DPT did not develop anaphylaxis during the DPT procedure. CONCLUSION: Drug provocation test is safe, and it can be considered in children with suspected DHRs.

Usefulness of drug provocation tests in children with a history of adverse drug reaction / 소아과

PURPOSE: There are very few reports of adverse drug reactions (ADR) and almost no study of drug provocation test (DPT) in Korean children. We aimed to assess the role of DPT in children with unpredictable ADRs, and compare the causative drugs and clinical characteristics between detailed history of ADRs and result of DPTs. METHODS: We included 16 children who were experienced ADRs referred to pediatric allergy clinic at Ajou University Hospital (January 2006 to December 2009). With various suspected drugs, 71 DPTs were done in 16 patients using our own protocol, and skin tests to antibiotics were combined in ADRs to antibiotics in medical history. RESULTS: There were 17 (23.9%) positive DPTs results out of 71 individual DPTs, and 11 patients (68.8%) from 16 patients were positive to at least one drug. Drugs causing positive reactions were acetaminophen in 5 (31%), Non-steroidal anti-inflammatory drugs in 4 (25%), penicillin in 3 (19%), cephalosporin in 2 (13%), and cotrimoxazole, macrolide and lactose in 1 each. CONCLUSION: DPT seems a safe and useful procedure to confirm causative drug and identify safely administering alternative drugs in children with ADR.

Testes de provocação com drogas: positividade e segurança / Drug Provocation Tests: positivity and safety

O teste de provocação com droga (TPD) é o padrão-ouro para diagnóstico das reações adversas a drogas (RAD). Analisamos resultados de TPD e discutimos os riscos de reações sistêmicas.Método: Estudo retrospectivo e descritivo no qual foram avaliados os prontuários de 500 pacientes com história de RAD no período de janeiro de 2005 a abril de 2009 e selecionados aqueles submetidos a TPD simples cego placebo controlado. Foram realizados TPD com antibióticos (ATB), anti-inflamatórios não esteroidais (AINE), anestésicos locais (A L) e outros. Caracterizamos esta população quanto ao sexo, idade, testes positivos e ocorrência de reações graves. Resultados: Foram realizados 243 TPD em 198 pacientes, 80,8% mulheres e a média de idade de 39,9 anos. Dentre os TPD, realizamos 19 testes com ATB, 26 com AINE seletivos da COX2, 7 com dipirona, 4 com ácido acetil salicílico, 44 com paracetamol, 93 com AL e 17 com outras medicações. Ocorreram 10 TPD positivos (4,1%) e 4 (1,6%) duvidosos. Os testes positivos ocorreram com ATB (2/19), AINE seletivos da COX 2 (2/26), paracetamol (3/44), AL (3/93). Ocorreram 2 reações graves, sendo 1 choque anafilático por cefalexina e 1 anafilaxia sem choque por bupivacaína. Em 4 pacientes (1,6%) houve positividade para o placebo antes da administração da droga ativa.Conclusões: Testes de provocação com drogas são seguros para realização na prática clínica. Os testes devem ser controlados com placebo e supervisionados por um alergista experiente em provocações com drogas.

Drug provocation test (DPT) is considered the gold standard to establish the diagnosis of adverse drug reactions (ADR). We analyzed DPTs results and we discuss severe systemic reactions to them.Methods: A retrospective analysis was conducted on medicai record of 500 patients with ADR history between January of 2005 and April of 2009. Provocation tests, which were single-blind placebo controlled, are reported. There were DPTs with antibiotics, local anesthetics, non¬steroldal antiinflammatory drugs, among other drugs. Patient's features, DPT positivity and its severe adverse reactions were analyzed. Results: The study sample included 243 DPTs in 198 patients (80.8% women) and the mean age was 39.9 years. Ninety-three DPTs were done with local anesthetics, 19 with antibiotics, 44 with acetaminophen, 26 with COX 2 inhibitors, 7 with dipyrone, 4 with aspirin and 17 with other drugs. There were 10 (4.1%) positive and 4 (1,6%) inconclusive tests. The positive tests were due to antibiotics (2/19), COX 2 inhibitors (2/26), acetaminophen (3/44) and local anesthetics (3/93). Two reactions were severe: one anaphylactic shock due to cephalexin and one anaphylaxis without shock due to bupivacaine. Four patients (1,6%) had placebo reaction, before drug administration.Conclusions: Drug provocation tests are safe to be performed in clinicai practice. They should be placebo controlled and done under allergist supervisiono.

Teste de provocação em indivíduos com suspeita de hipersensibilidade a anestésicos locais - Proposta de uma abordagem prática / Provocatíon test in patíents wíth suspected local anesthetícs hypersensítívíty - A practícal proposal approach

Objetivo: Os anestésicos locais (AL) podem desencadear grande variedade de eventos adversos, mas raramente são responsáveis por hipersensibilidade alérgica IgE mediada. Ainda são causa de grande preocupação para profissionais de saúde e para pacientes. O teste de provocação com a droga (TPD) constitui método de escolha para prover alternativa se¬gura para estes pacientes. Outras causas de hipersensibilidade alérgica, como a alergia ao látex, podem mimetizar as reações aos AL e devem ser investigadas. Propomos uma abordagem prática para a realização do TPD diante da suspeita de hiper¬sensibilidade alérgica aos AL. Pacientes e Métodos: Foram estudados 33 pacientes com suspeita de hipersensibilidade a AL, submetidos a TPD. Estes pacientes foram atendidos em nosso serviço entre julho de 2003 e julho de 2006. Os TPD foram indicados e realizados de acordo com as orientações da European Network for Orug Allergy (ENDA) e a droga testada foi escolhida a partir da his¬tória clínica. Todos os pacientes foram avaliados (história clí¬nica e testes in vivo e vitro) para se verificar alergia ao látex previamente à realização do TPD. Foi procedido contato telefó¬nico com estes pacientes em abril de 2007 a fim de verificar se a droga disponibilizada havia sido utilizada e se houve intercor¬rências com a sua utilização. Resultados: Foram realizadas 33 provocações em pacien¬tes com suspeita de reação a AL (18 com Bupivacaína e 15 com Lidocaína), todos negativos. Dois desses pacientes tive¬ram avaliação para látex positiva. Foi verificado por contato telefónico que todos os pacientes utilizaram sem intercorrên¬cias o AL testado...

Objective: Although local anesthetic (LA) drugs can elicit variety of adverse reactions, but true allergic hypersensitivi' reactions are uncommon. It still constitutes a concern fi health professionals and for patients. The drug provocation te (DPT) is a determinant method to provide a safe alternative these patients. Other allergic hypersensitive causes (eg. lats allergy) can mimic LA reactions and must be investigated. VI suggest a practical approach based on DPT to be used when LA allergic hypersensitivity is suspected. Pacients and Methods: We stud ied 33 patients with SUSI: cion of local anesthetic hypersensitivity evaluated in our clin between July 2003 and July 2006. Ali of them underwent DP which was performed based on European Network for OrL Allergy (EN DA) orientations and the choice of the drug to t tested was based on the clinical history. Ali patients we avallied (clinical history and in vivo and in vitro tests) in ord to investigate latex allergy before the drug provocation. VI proceeded phone contact to ali these patients in April 2007 order to check if the medication we tested was used and if thr had reactions with it. Results: We proceeded 33 drug provocation tests in pai ents with suggestive history of local anesthetic reaction (: with Bupivacaine and 15 with Lidocaine), ali negative. Two these patients, who underwent DPT with Bupivacaine and wi Lidocaine, had positive evaluation to latex allergy. We conta ted ali patients and verified that the tested drug was used I ali of them with no problems. Conclusion: We demonstrated that DPT is an importa method to provide a safe alternative drug to patients with su picion of allergic hypersensitivity to LA and latex allergy Inve tigation has always to be proceeded. Therefore, the practic approach we use helps us to provide a correct, safe and inc vidualized orientation to each patient.