Follow‐up of patients with negative drug provocation tests to betalactams

Abstract

Drug allergy work-up in betalactam (BL) allergy is probably the most-developed drug-allergy evaluation at present. 1 During the last few years, the debate on whether 1-day or several-day (prolonged) drug provocation test (DPT) should be performed in non-immediate reactions (ie, occurring >1 hour after the last administered dose) in order to increase sensitivity has been ongoing and groups working in drug allergy diagnosis have been deploying pro and con arguments and studies in favour of either option. [2][3][4][5] The most acceptable way to validate a negative DPT is by studying its negative predictive value (NPV) in patients who are re-challenged to the negatively tested drug, in real-life therapeutic conditions. 6,7 Because therapeutic conditions imply underlying infectious disease (and therefore, a differential diagnosis responsible of cutaneous eruptions, independent of medication), performing a follow-up of tested patients including retest if necessary is advisable, under the hypothesis that not all reactions occurring upon retaking the drug are drug-related.The number needed to harm (NNH) is a measure of the harm caused by an intervention. More specifically, it is a measure of how many people need to be exposed to an intervention, (eg, DPT) in order for one person to have a particular adverse effect (eg, a DHR):the larger the value of the number needed to harm, the lower the risk of the adverse effect. In the specific case of DPT, prolonged DPT deliver courses of antibiotics in subjects that are otherwise healthy and this intervention may have additional drawbacks at a higher overall level (eg, microbial resistance and economic costs). If the NNH is high, and considering that prolonged DPT pick up merely mild reactions (as confirmed by the studies performing prolonged DPT 2-4 ), prolonged DPT might not be an effective intervention as compared to 1-day DPT. Between December 2014 and June 2016, a multicentre (NCT02844712) study was conducted in two allergy units, Hôpital Arnaud de Villeneuve (Montpellier, France) and Complesso Integrato Columbus (Rome, Italy). Patients with a complete and negative allergy work-up for a BL were contacted and asked to answer a questionnaire regarding re-administration of a negatively tested BL, as previously described. 6 Both centres perform 1-day DPT in both immediate and in mild/moderate non-immediate suspicions of BL drug hypersensitivity reactions (DHR), in a similar manner (including contraindications for DPT). Data were expressed either as numbers and percentage (with 95% CIs) or as medians (with interquartile range). Comparisons were made using chi-square tests for categorical variables. Clinical risk factors for developing a reaction upon subsequent re-challenge in real-life were searched using multivariate logistic regression. A total of 950 patients, 208 (21.9%) from Rome and 742 (78.1%) from Montpellier, answered and returned the questionnaire. The index reaction had been immediate in 152 (16%) of patients, and non-immediate (or of unknown chronology) for the rem...

Skin tests are important in children with β‐lactam hypersensitivity, but may be reduced in number

“…These protocols refer to children reporting a history of mild reactions, and the authors suggest that increasing the duration of DPT may improve its diagnostic performance without increasing the risk of severe reactions during the observation period or at home. From our personal experience, there is no advantage in the predictive value of DPT if performed over a 1‐day period (followed by 48 hours of surveillance at home) or over a more prolonged time . Also, in these cases, it seems essential either to examine patients during the reaction or to be able to properly classify it as immediate or non‐immediate, and mild‐moderately (or potentially) severe by means of anamnesis (interview of the parents, and photographies of the reaction).…”

“…From our personal experience, there is no advantage in the predictive value of DPT if performed over a 1-day period (followed by 48 hours of surveillance at home) or over a more prolonged time. 20 Also, in these cases, it seems essential either to examine patients during the reaction or to be able to properly clas- could be helpful in pediatric settings, regardless the chronology of the initial reaction.…”

Towards a more precise diagnosis of hypersensitivity to beta‐lactams — an EAACI position paper

“…Nonimmediate reactions following a negative 1‐day or prolonged DPT are described as mild/moderate. Nevertheless, in the studies that carried out 1‐day DPT, the rate of subjects who have taken again the BL concerned in real‐life conditions ranged from 22% to 39%, whereas in the studies that performed prolonged DPT with BL, such rate ranged from 52% to 71% . Moreover, Ratzon et al found that 100% (n = 18/18) of the patients who had undergone prolonged DPT and needed a BL used it, compared with only 76% (n = 16/21) of patients who had undergone 1‐day DPT.…”

Advances and novel developments in drug hypersensitivity diagnosis

“…If no reaction occurs, DPT is resumed at home with therapeutic doses for several days. [50][51][52][53] Regarding NSAIDs, it was suggested to consider their absorption speed to determine steps for DPT. 54 The optimal total cumulative dose for DPT is also under debate.…”