The Safety of the Direct Drug Provocation Test in Beta-Lactam Hypersensitivity in Children: A Systematic Review and Meta-Analysis

Srisuwatchari, Witchaya; Phinyo, Phichayut; Chiriac, Anca Mirela; Saokaew, Surasak; Kulalert, Prapasri

doi:10.1016/j.jaip.2022.11.035

Cited by 16 publications

(12 citation statements)

References 66 publications

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“…In the case of DH in children, the target population consists mainly of patients referred to pediatric allergy units after a suspected episode. The frequency with which DH is confirmed in these populations is low, generally below 10% for penicillins and around 20% for NSAIDs 10–17,36,37 . These percentages may be similar to the prevalence of the disease in that population (pre‐test probability), conditioning the positive PV of any test, however precise, which decreases markedly when the prevalence is very low (Figure 1).…”

Section: Predictive Value Of Dptmentioning

confidence: 78%

“…The frequency with which DH is confirmed in these populations is low, generally below 10% for penicillins and around 20% for NSAIDs. [10][11][12][13][14][15][16][17]36,37 These percentages may be similar to the prevalence of the disease in that population (pre-test probability), conditioning the positive PV of any test, however precise, which decreases markedly when the prevalence is very low (Figure 1). This problem also affects penicillin skin tests to a greater extent, as they are likely to be less sensitive and less specific than DPT, which increases the proportion of false positives, that is, incorrect diagnoses based on skin tests.…”

Section: Pred I C Tive Value Of Dp Tmentioning

confidence: 85%

“…61,62 Drug provocation test has a good safety profile, and positive tests usually produce only mild symptoms. 20,36,37,63 While this is reassuring for pediatric allergy units, it may also reflect a very low threshold for considering a test as positive, leading to prompt discontinuation of the test when the observed symptoms are attributed to the drug administered. Although the risk of a serious and potentially life-threatening reaction is very low, performing a DPT generates a certain degree of anxiety and alertness in healthcare staff, which may F I G U R E 1 Graphical representation of the variation in positive and negative predictive value (e.g., of an open DPT with drugs), as a function of disease prevalence, assuming a sensitivity and specificity of 98% each.…”

Section: Interpre Tati On Of a P Os Itive Dp T: Obs Erver B Ia Smentioning

confidence: 99%

“…This phenomenon is known as observer bias and can distort the results of a study or test 61,62 . Drug provocation test has a good safety profile, and positive tests usually produce only mild symptoms 20,36,37,63 . While this is reassuring for pediatric allergy units, it may also reflect a very low threshold for considering a test as positive, leading to prompt discontinuation of the test when the observed symptoms are attributed to the drug administered.…”

Section: Interpretation Of a Positive Dpt: Observer Biasmentioning

confidence: 99%

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Drug provocation tests in children: All that glitters is not gold

Moral,

Mori

2023

Pediatric Allergy Immunology

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A proper allergy work‐up, based on the gold standard drug provocation test (DPT), usually rules out suspected drug hypersensitivity in children. These tests are generally open, given their high efficiency compared with double‐blind placebo‐controlled DPTs. Although their negative predictive value is excellent, no studies have calculated their positive predictive value, highly dependent on the prevalence of the disease. Most studies have found a rate of <5%–10% of true beta‐lactam hypersensitivity in children. Given this low prevalence (pre‐test probability), a few false‐positive results can significantly reduce the estimated positive predictive value. False positives may arise from the nocebo effect during the test, including nocebo by proxy, or from observer bias, which depends on professional expertise and organizational circumstances. Some studies have found a high rate of tolerance on a second DPT in children who failed the first, but these results may be affected by the interval between the two tests, of a year or more in most cases, reflecting a loss of hypersensitivity over time. Taking into account the low rate of positive DPTs, with commonly mild reactions, we suggest confirming nonsevere positive DPTs with a second provocation performed soon after the first, especially in the case of beta‐lactam antibiotics, in order to improve the diagnostic accuracy, de‐label more patients, and achieve a better estimation of true drug hypersensitivity prevalence. In case of mild immediate reactions, the potential benefits of a second DPT should be carefully weighed against the risk of anaphylaxis.

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Section: Predictive Value Of Dptmentioning

confidence: 78%

Section: Pred I C Tive Value Of Dp Tmentioning

confidence: 85%

Section: Interpre Tati On Of a P Os Itive Dp T: Obs Erver B Ia Smentioning

confidence: 99%

Section: Interpretation Of a Positive Dpt: Observer Biasmentioning

confidence: 99%

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Drug provocation tests in children: All that glitters is not gold

Moral,

Mori

2023

Pediatric Allergy Immunology

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“…2,3 In some patients, in vivo tests could be even contraindicated, as in severe cutaneous reactions or anaphylaxis. Although many authors suggest direct DPT in children as a safe and reliable procedure, 4,5 especially in mild-to-moderate reactions, it has to be remembered that DPT is a time-consuming procedure that must be performed in well-being conditions. Furthermore, DPT requires qualified personnel and proper settings, and may expose children to unpleasant reactions.…”

Section: Introductionmentioning

confidence: 99%

In vitro diagnostic testing for drug allergy in children

Saretta

Tomei

Mori

et al. 2023

Pediatric Allergy Immunology

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Diagnosing Drug Hypersensitivity Reactions (DHRs) could be a complicated process especially in children, since allergic-like manifestation at this age is more often the expression of concomitant infections rather than a actual DHRs. In vivo tests are usually suggested as a first step; however, prick and intradermal tests could be painful and have shown different sensitivity and specificity among published studies. In some cases, in vivo tests such as Drug Provocation test (DPT) could be even contraindicated. Therefore, the need for in vitro testing is compelling, to add useful information along the diagnostic pathway and to limit the need of DPT. In this review, we analyze the different types of in vitro tests, focusing on those used more widely such as specific IgE and on those that are still for research settings, such as basophil activation test and lymphocyte transformation test, but that have shown some useful diagnostic potential.

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