Time for a new grading system for allergic reactions?
Authors: B. Niggemann, K. Beyer
Journal: Allergy (2015)

The term 'anaphylaxis' was introduced in 1902 by Richet & Portier 1, while the term 'allergy' was established in 1906 by the Austrian paediatrician Clemens von Pirquet 2. Already from an etymological point of view, the two terms relate to different conditions: the translation of allergy from the Greek is 'different or strange reaction', and for anaphylaxis, it is 'missing protection'. The differentiation between IgE- and non-IgE-mediated allergic reactions became possible when immunoglobulin E (IgE) was discovered in 1966 3, and 1967 4. Since the new classification from 2001 5, the umbrella term 'allergy' covers all protein-induced, immunological reactions, irrespective of whether they are IgE- or non-IgE-mediated 6. It is not intended to reopen the discussion on the exact diagnosis or definition of anaphylaxis, which is covered by widely in the literature 7. Furthermore, subjective symptoms such as anxiety, malaise, weakness or dizziness should not be criteria for grading an allergic reaction. Similarly, the criteria for the positive assessment of an allergic reaction are not addressed here 8. There seems to be agreement that anaphylaxis represents 'a severe, life-threatening, generalized or systemic hypersensitivity reaction' 5, 9. However, the most frequently cited classifications use grading systems that include urticaria as a grade 1 reaction of anaphylaxis 10, 11, which definitively does not reflect a life-threatening situation. Few authors have criticized this or tried to establish other classifications 12, 13. The historical classifications tend to overestimate gastrointestinal symptoms. Today, especially in the case of children and adolescents, respiratory reactions account for the cases of death from anaphylaxis 14. Advocates of the historical classifications argue that a generalized urticaria may develop into full anaphylaxis, and therefore, systemic skin symptoms should be classed as grade 1 anaphylaxis. This is an anticipatory view, with usually negative performance. Furthermore, most cases of acute urticaria are infection-related. The various organ systems involved in allergic reactions can be ranked by increasing risk of death beginning with local or systemic skin symptoms (nobody dies from), through more or less subjective mild systemic symptoms (e.g. feeling unwell, anxiety) to gastrointestinal symptoms (e.g. vomiting, diarrhoea), to respiratory symptoms (e.g. wheezing, stridor), neurological symptoms (e.g. cerebral palsy), cardiovascular collapse and shock, and finally even to death from respiratory or cardiac arrest 15. Problems arise from the incorrect application of the two approaches to grading: A grading system should fulfil at least the following criteria: We propose a modified, consistent grading system that meets these prerequisites (Fig. 1). The three-grade system is simple and applicable for all kind of allergic reactions, as it considers (large) local allergic reactions (e.g. to insect stings, as a side-effect of specific immunotherapy injections or as contact urticaria to foods) as well as systemic reactions from all organ systems and severities (including life-threatening reactions such as cardiovascular shock). It includes anaphylaxis as the most severe allergic and potentially life-threatening reaction. The various organ systems (skin, gastrointestinal tract, respiratory tract, cardiovascular symptoms, other) are appraised equally. Our new grading proposal for allergic reactions tries to overcome disadvantages of the existing systems and avoids the problem of grading 'anaphylaxis' without systemic allergic symptoms. The responsible societies and institutions may find this proposal useful as a basis for their discussions. There are no conflict of interests for both authors.