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

Figures & data

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.¹⁴
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.

Table 1 Proposed criteria for mast cell activation syndrome (all 3 must be present)

1) Episodic multisystem symptoms consistent with mast cell activation

2) Appropriate response to medications targeting mast cell activation

3) Documented increase in validated markers of mast cell activation systemically (ie, either in serum or urine) during a symptomatic period, compared with the patient’s baseline values*

* Notes: Documentation of a single meaningful increase in tryptase level is sufficient, whereas it is recommended to document at least two measurements of increased levels of other markers. Reproduced from Journal of Allergy and Clinical Immunology, Volume 140 (Edition 2), Akin C. Mast cell activation syndromes, pages 349–355, Copyright 2017, with permission from Elsevier.¹³⁴

Table 2 WHO criteria for SM

SM criteria
Major SM criteria
Multifocal dense infiltrates of MCs (>15 MCs in aggregates) in BM biopsies and/or in sections of other extra-cutaneous organ(s) including gastrointestinal tissues
Minor SM criteria
1) In total, 25% of all MCs are atypical cells (types I or II) on BM smears, or are spindle-shaped in MC infiltrates detected on sections of visceral organs
2) KIT point mutation at codon 816 in the BM or another extra-cutaneous organ
3) MCs in BM or another extra-cutaneous organ expressed CD25 and/ or CD2
4) Baseline serum tryptase level >20 ng/mL (in case of an unrelated myeloid neoplasm, item 4 is not valid as an SM criterion)
If at least one major and one minor or three minor SM criteria are fulfilled, a diagnosis of SM can be established
SM criteria were defined by the WHO in 2001 and have been confirmed in the WHO updates of 2008 and 2016

Note: Adapted with permission of American Society of Hematology, from Mastocytosis: 2016 updated WHO classification and novel emerging treatment concepts, Valent P, Akin C, Metcalfe DD, Colume 129(Edition 11), 2017; permission conveyed through Copyright Clearance Center, Inc.¹³⁵

Abbreviations: MCs, mast cells; BM, bone marrow; SM, systemic mastocytosis; 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.¹⁴²
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.¹⁸⁶

Figure 5 Acute treatment of anaphylaxis.

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

Table 3 Preventive treatment of anaphylaxis

Long-term treatment and prophylaxis
• Education
• Immunotherapy: environmental, food, Hymenoptera
• Anti-IgE
• Tyrosine kinase inhibitor (clonal mast cell diseases)
• Desensitization (drugs, chemotherapy, mAbs, iron, progesterone)

Abbreviation: IgE, immunoglobulin E.

CastellsMDiagnosis and management of anaphylaxis in precision medicineJ Allergy Clin Immunol2017140232133328780940

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AkinCMast cell activation syndromesJ Allergy Clin Immunol2017140234935528780942

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ValentPAkinCMetcalfeDDMastocytosis: 2016 updated WHO classification and novel emerging treatment conceptsBlood2017129111420142828031180

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CastellsMCHornickJLAkinCAnaphylaxis after hymenoptera sting: is it venom allergy, a clonal disorder, or both?J Allergy Clin Immunol Pract20153335035525858055

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Prieto-GarciaASloaneDEGargiuloARFeldwegAMCastellsMAutoimmune progesterone dermatitis: clinical presentation and management with progesterone desensitization for successful in vitro fertilizationFertil Steril20119531121e9e13

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