Guideline for the diagnosis of drug hypersensitivity reactions

Abstract

Drug hypersensitivity reactions are unpredictable adverse drug reactions. They manifest either within 1–6 h following drug intake (immediate reactions) with mild to life-threatening symptoms of anaphylaxis, or several hours to days later (delayed reactions), primarily as exanthematous eruptions. It is not always possible to detect involvement of the immune system (allergy). Waiving diagnostic tests can result in severe reactions on renewed exposure on the one hand, and to unjustified treatment restrictions on the other. With this guideline, experts from various specialist societies and institutions have formulated recommendations and an algorithm for the diagnosis of allergies. The key principles of diagnosing allergic/hypersensitivity drug reactions are presented. Where possible, the objective is to perform allergy diagnostics within 4 weeks–6 months following the reaction. A clinical classification of symptoms based on the morphology and time course of the reaction is required in order to plan a diagnostic work-up. In the case of typical symptoms of a drug hypersensitivity reaction and unequivocal findings from validated skin and/or laboratory tests, a reaction can be attributed to a trigger with sufficient confidence. However, skin and laboratory tests are often negative or insufficiently reliable. In such cases, controlled provocation testing is required to clarify drug reactions. This method is reliable and safe when attention is paid to indications and contraindications and performed under appropriate medical supervision. The results of the overall assessment are discussed with the patient and documented in an „allergy passport“ in order to ensure targeted avoidance in the future and allow the use of alternative drugs where possible.

Allergenicity and safety of recombinant human C1 esterase inhibitor in patients with allergy to rabbit or cow's milk

“…SPT and ICT with immediate readings are commonly used for investigation of immediate hypersensitivity reactions in drug allergy. 12 Plasma-derived C1INH has been administered intravenously for several decades, and recent studies applying the SC route of administration for these preparations indicate that similar safety results can be expected for these 2 routes of administration. 13 In a previous study in 130 patients with hereditary angioedema and 14 healthy controls, 5 subjects had preexisting anti-rabbit epithelium IgE antibodies; 1 of them was a healthy subject with an undisclosed RA, who developed an allergic reaction upon intravenous infusion with rhC1INH.…”

“…It is essential that nonirritant test concentrations are used and many drugs or drug classes are therefore diluted 1:10 or more for ICT to avoid irritant test concentrations. 11,12 For rhC1INH, the threshold of irritant test concentrations for intradermal testing was not established because this would require a drug and/or formulation-only challenge in subjects with positive skin test result. This was not the aim of this study and not intended in the study protocol.…”

Basophil Activation Test Application in Drug Hypersensitivity Diagnosis: An Empirical Approach

“…In the remaining 40 challenges, we administered an alternative drug selected on clinical history and BAT results, and according to the possibility of cross-reactivity based on chemical similarity. Under close monitoring, the patients were submitted to progressive administration of the target drug [13].…”

Evaluation of immediate reactions to β lactam antibiotics using a comprehensive diagnostic protocol

“…6,7 Hence, there is a need for a simple yet effective diagnostic protocol to determine these reactions as it could prevent severe complications, which are easily avoidable.…”