Advances and novel developments in drug hypersensitivity diagnosis

Abstract

The diagnosis of drug hypersensitivity reactions (DHRs) has important implications for both patients and health system. 1 Mainly because an allergy label, whether true or not, implies the avoidance of medications that may be essential, the performance of unnecessary desensitization procedures, or the use of alternative medications. All these alternatives can lead to a less effective treatment, more potential adverse effects, and costs for health systems. 2 Moreover, in the case of antibiotics, it results in bacterial resistance. 3 Considering that there are no specific tests to distinguish between a viral infection and DHRs in the acute phase, a diagnostic work-up should be performed to remove a false label of hypersensitivity. 4 DHRs diagnosis is complex, time consuming, needs to be done by trained staff, and it is not standardized for many drugs. It is mainly based on skin testing (ST) and drug provocation tests (DPTs),

Single‐dose prolonged drug provocation test, without previous skin testing, is safe for diagnosing children with mild non‐immediate reactions to beta‐lactams

“…Therefore, DPT is the gold standard for diagnosis, 1,2,19,23,28,38, [54][55][56] although it is a costly, time-consuming and not risk-free procedure. 51 Currently, there is a lack of consensus on the DPT protocol for investigating NIRs, particularly regarding the dosing schedule for DPT, the number of days needed and the need of performing STs before it.…”

Model Based Evaluation of Hypersensitivity Adverse Drug Reactions to Antimicrobial Agents in Children

“…Other algorithms and causality assessment tools have been developed to aid identifying the causative drugs such as the Naranjo scale (Naranjo et al, 1981). Algorithms to guide management of DHRs are available and always include careful medical history, skin testing, in vitro testing and DPT (Ariza et al, 2020). However, the clinical presentation of DHRs is always variable and complicated by polypharmacy, concomitant infection and other diseases.…”

Medical algorithm: Diagnosis and treatment of hypersensitivity reactions to cancer chemotherapy

“…This might seem simple, but the spectrum of DHRs is rather labyrinthine, with a large array of clinical presentations and mechanisms to be considered. 4,7,9,10 Even severity is difficult to grade, as not all DHRs have straightforward anaphylactic symptoms (e.g., DHRs to taxanes can cause back pain). Classification is becoming ever so complicated, and current grading systems are rendered inadequate, which promotes heterogeneity.…”

“…4,7 DPT is the gold standard to confirm or to rule out hypersensitivity, and as such, it is the ultimate tool for de-labelling patients. 4,7,9,10 Virtually all data on DPT before RDD with chemotherapy come from the large cohort from Ramon y Cajal University Hospital (RCUH), Spain. 1,2 However, other groups have successfully implemented this technique, 6 while some use different versions of DPT at different points within their pathways.…”

“…3,4,10 From a practical perspective, DHRs are classified as immediate (I-DHRs, onset within 1-6 hours after drug exposure) and nonimmediate (NI-DHRs, onset after 1 hour of drug exposure). 9,11 This simple solution is controversial, as inevitably both categories overlap, but a strict cut-off point is difficult to define. 11 Even if some drugs like cyclophosphamide have been described to cause anaphylaxis hours after the infusion, fortunately, most I-DHRs to chemotherapy happen within 1 hour of finishing the infusion.…”