Hypersensitivity reactions to biologics (part II): classifications and current diagnostic and treatment approaches

Abstract

Purpose Biotechnological substances (BS) have rapidly expanded their clinical use. In parallel, there is an increase in expected or unexpected immunological or non-immunological adverse effects. In this part of the review, the current nomenclature of BSs, the classification of hypersensitivity reactions (HSR), as well as diagnostic and treatment approaches are documented to provide the tools to understand the nomenclature used throughout the databases and the need to harmonize it where applicable. Methods Detailed searches were performed on Pubmed, Web of Science, and Google Scholar to include all available publications. The search terms, such as specific BS, allergy, anaphylaxis, hypersensitivity, reactions, classification, diagnosis, grading, management, and desensitization, were determined for the search. Case reports, articles, and reviews on this subject were included. Results Today, a variety of non-standardized methods are used to support the clinical diagnosis. These include prick-to-prick tests and intradermal tests with the drug itself and its potentially allergenic ingredients. More rarely, anti-drug antibodies are detected and basophil activation tests are used by centers with research facilities. Although the treatment protocols for acute conditions vary, the overall approach is the same. Conclusion HSRs to BS are gradually increasing with the widening of their clinical use and indications. It is very important to prevent HSRs and to know the degree of severity as well as the emergency treatment algorithm. This review summarizes the diagnostic tests that should be applied: (a) immediately during/after a reaction, and (b) subsequently, and in the case that a switch of BS is not possible, desensitization is an option.

Biologics for atopic diseases: Indication, side effect management, and new developments

“…However, a comprehensive review of databases and scientific literature has shown that, on the one hand, the nomenclature of hypersensitivity reactions to biologicals is not harmonized, so that data on the prevalence and incidence of “real” allergic and anaphylactic reactions to the various biologicals cannot be reliably collected [ 88 , 89 ]. Furthermore, the symptomatology of anaphylaxis may vary between different biologicals [ 87 ].…”

“…However, additives such as polysorbate, mannitol, albumin, latex, trometamol, and papain [ 89 , 97 ] can also cause allergic reactions to biologicals and should be included in the allergological investigation.…”

“…The diagnostic measures to detect a rather rare IgE-mediated adverse reaction are, in addition to the medical history (occurrence and progression of the reaction in the course of therapy, relative independence from the administered dose, method of application, duration of therapy and therapy pause, if applicable life in an alphaGAL sensitization endemic area, mammalian meat allergy), the prick and intradermal test with the suspected biological, which, however, corresponds to an off-label use about which the patient should have been informed and given written consent. In general, allergy diagnostics should be performed within 4 – 6 weeks after the event to be meaningful [ 89 ].…”

Allergische Reaktionen auf COVID-19-Impfungen – Was HNO-Ärzte wissen sollten – Teil 1: Allgemeine Aspekte von Allergien auf Impfstoffe, immunologische Grundlagen von Allergien auf Impfstoffe, Immunmechanismen von allergischen und pseudoallergischen Reaktionen; Teil 2: Charakteristiken der mRNA-Impfstoffe BNT162b2 und mRNA-1273 zur Prophylaxe von COVID-19, weitere Impfstoff-Kandidaten und assoziierte Immunphänomene; Teil 3: Praktische Aspekte der Prophylaxe, Diagnostik und Therapie von Allergien auf COVID-1

“…Wir kennen allergische und anaphylaktische Reaktionen auf Wirk-und Zusatzstoffe von jeder Art von Impfstoffen, aber auch von Biologika und vielen anderen Medikamenten [28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44].…”

Allergische Reaktionen auf COVID-19-Impfungen – Was HNO-Ärzte wissen sollten – Teil 1: Immunologische Grundlagen von Allergien auf Impfstoffe, Immunmechanismen von allergischen und pseudoallergischen Reaktionen; Teil 2: Charakteristika der mRNA-Impfstoffe BNT162b2- und mRNA-1273 zur Prophylaxe von COVID-19 und assoziierte Immunphänomene; Teil 3: Praktische Aspekte der Prophylaxe, Diagnostik und Therapie von Allergien auf COVID-19-Impfstoffe

“…Die Häufigkeit anaphylaktischer Reaktionen hat in den letzten Jahren deutlich zugenommen [5,6]. Auch andere allergische Reaktionen auf Medikamente und Impfstoffe wurden beschrieben, insbesondere wurde über schwere Anaphylaxien auf Nahrungsmittel und Medikamente berichtet [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26].…”