Anaphylaxis in the 21st century: phenotypes, endotypes, and biomarkers

Abstract

Anaphylaxis is the most serious of all allergic reactions and can be fatal. The diagnosis is frequently delayed, and misdiagnosis often occurs with asthma or urticaria. Biomarkers such as tryptase are not routinely checked, and appropriate treatment with epinephrine is not administered in a majority of cases, increasing the risk of poor outcomes. The objective of this review is to provide a better understanding of the pathophysiology of anaphylaxis with a description of phenotypes, endotypes, and biomarkers available in both the clinical and research settings. Expanding knowledge with regard to the presentation, causes, and triggers for anaphylaxis among health care providers will improve its diagnosis and management, increase patient safety, and decrease morbidity and mortality.

Keywords: anaphylaxis; autoimmune progesterone dermatitis; epinephrine; hypersensitivity reactions; precision medicine; tryptase.

Figure 1

Pathways of anaphylaxis. Note: Reprinted from the Journal of Allergy and Clinical Immunology, Volume 140/Edition 2, Castells M. Diagnosis and management of anaphylaxis in precision medicine, pages 321–333, Copyright 2017, with permission from Elsevier. Abbreviations: IgE, immunoglobulin E; IgG, immunoglobulin G; IL, interleukin; PAF, platelet-activating factor; TNF-α, tumor necrosis factor alpha.

Figure 2

Mast cell activation syndrome. Notes: Adapted from original provided by Dr Raied Talal Hufdi, Division of Rheumatology, Immunology and Allergy; Department of Medicine, Brigham and Women’s Hospital, Boston, MA, USA. Abbreviations: AHN, associated hematologic neoplasm; BM, bone marrow; EDS, Ehlers-Danlos Syndrome; GI, gastro-intestinal; IgE, immunoglobulin E; IgG, immunoglobulin G; IL, interleukin; MC, mast cell; MCAS, mast cell activation syndrome; MCL, mast cell leukemia; MMAS, monoclonal mast cell activation syndrome; NSAIDs, nonsteroidal anti-inflammatory drugs; PAF, platelet-activating factor; POTS, Postural Orthostatic Tachycardia Syndrome; RCM, radio contrast medium; SM, systematic mastocytosis; TMPE, telangiectasia macularis eruptiva perstans; TNF-α, tumor necrosis factor alpha; WHO, World Health Organization.

Figure 3

Mast cell defects may collectively lead to increased risk for anaphylaxis in response to hymenoptera venom in patients with clonal mast cell disease. Note: Reproduced from The Journal of Allergy and Clinical Immunology: In Practice, Volume 3 (Edition 3), Castells MC, Hornick JL, Akin C. Anaphylaxis after hymenoptera sting: is it venom allergy, a clonal disorder, or both? Pages 350–355, Copyright 2015, with permission form Elsevier. Abbreviations: IgE, immunoglobulin E; LTC4, leukotriene C4; PGD2, prostaglandin D2.

Figure 4

Onset of symptoms in patients during the menstrual cycle in progesterone hypersensitivity. Note: Adapted from Fertility and Sterility, Volume 95 (Edition 3), Prieto-Garcia A, Sloane DE, Gargiulo AR, Feldweg AM, Castells M. Autoimmune progesterone dermatitis: clinical presentation and management with progesterone desensitization for successful in vitro fertilization, Pages 1121.e9–e13, Copyright 2011, with permission from Elsevier.

Figure 5

Acute treatment of anaphylaxis. Abbreviations: ACE, angiotensin-converting enzyme; CV, cardiovascular; GI, gastrointestinal; IV, intravenous.