Histamine Determination, Plasma

CPT: 83088
Print Share


  • Plasma Histamine

Special Instructions

This is not the Leukocyte Histamine Release Test (LHRT).

Expected Turnaround Time

2 - 4 days

Related Documents

Specimen Requirements


Plasma, frozen


2 mL

Minimum Volume

1 mL


Lavender-top (EDTA) tube


Separate plasma and transfer specimen to a plastic transport tube before freezing. To avoid delays in turnaround time when requesting multiple tests on frozen samples, please submit separate frozen specimens for each test requested.

Storage Instructions


Stability Requirements



Room temperature



14 days

Causes for Rejection

Gross lipemia; gross hemolysis; gross icterus

Test Details


This test is used for the measurement of histamine in plasma.


This test was developed and its performance characteristics determined by Labcorp. It has not been cleared or approved by the Food and Drug Administration.


Enzyme immunoassay (EIA)

Additional Information

Histamine is synthesized from the amino acid L-histidine through the action of the enzyme histidine decarboxylase.1 This small molecule is primarily produced by mast cells and basophils. These cells are morphologically characterized by numerous, electron dense cytoplasmic granules, which contain histamine and other compounds, enabling a massive acute release in response to immunologic and non-immunologic stimuli.2-10 Mast cells and basophils are critical effectors of local and systemic hypersensitivity reactions and other immediate or chronic inflammatory conditions.11-16 Histamine release can be triggered by allergic sensitization or by other stimuli, including cytokines, chemokines, complement components, IgG, microbes, drugs, and toxins through specific receptors expressed by these cells.11-13,16-18 In addition to mast cells and basophils, a number of cell types, including gastric enterochromaffin-like cells, histaminergic neurons, platelets, dendritic cells and T cells can produce histamine.1 These cells do not store histamine intracellularly but instead secrete it after synthesis.10,19-22

Histamine is a central mediator of allergic response. Exposure of sensitized individuals to allergens triggers histamine release by basophil and mast cells. Histamine binds to specific receptors on smooth muscle cells and provokes potent adverse effects. Histamine concentration in biological fluids is correlated with the severity of vascular and respiratory signs of anaphylaxis. Histamine quantification has been used to confirm that clinical signs result from the degranulation of mast cells and/or basophils.23-26 This confirmation can support further investigation in order to find the offending allergen against which the patient is sensitized, allowing there after the avoidance of a new anaphylaxis reaction by the specific eviction of the allergen, or aninduction of tolerance. Several other non-immunologic stimuli may also activate mast cells. These stimuli include neuropeptides and complement factors (i.e., C3a and C5a).27

Beyond its role in immediate type allergic reactions, histamine is involved in a number of physiological functions, including cell proliferation and differentiation, hematopoiesis, embryonic development, regeneration, and wound healing.6,7,28-30 Once released into the circulation, histamine produces many varied effects within the body, including the contraction of smooth muscle tissues of the lungs, uterus, and stomach; the dilation of blood vessels, which increases permeability and lowers blood pressure; the stimulation of gastric acid secretion in the stomach; and the acceleration of heart rate. Histamine also serves as a neurotransmitter, carrying chemical messages between nerve cells.

Mast cells have been implicated in the pathogenesis of a broad range of disorders and conditions related to mast cell activation.13,17,31 Severe forms of mast cell activation (anaphylaxis) are usually observed in patients with IgE-dependent allergies and those with clonal mast cell disorders.17,32,33 A number of predisposing genetic conditions, underlying allergic and other hypersensitivity states, and related comorbidities can contribute to the clinical manifestation of mast cell activation syndromes.31 The severity of mast cell activation symptoms depends on several factors, including the type of allergen, the route of exposure, augmenting factors, comorbid conditions, the presence of clonal mast cells, and genetic background. Histamine is released from mast cells during anaphylaxis and increased in biological fluids (plasma, urine) during and shortly after an anaphylactic episode.34 Compared to serum tryptase levels, histamine may sometimes be a more sensitive parameter (biomarkers) in allergic reactions and thus also detected as elevated in less severe or chronic forms of mast cell activation but are less specific for the mast cell lineage and less-well validated in mast cell activation contexts compared to tryptase.31,35

Histamine is endogenous in numerous foods and excessively high levels can be indicative of defective food processing, microbial activity, and general deterioration.36 On the other hand, the presence of histamine in processed foods, such as aged cheeses, is necessary to achieve characteristic flavors and textures. A number of alcoholic beverages contain a significant amount of histamine. In addition, fish can be a food source of histamine, depending on its exposure to microbial contamination or unfavorable storage conditions. Scombroid fish poisoning, also known as histamine fish poisoning, is an allergic-type reaction that occurs within a few hours of eating fish contaminated with high levels of histamine.37 When certain types of fish are not properly refrigerated, bacteria in the fish can multiply, break down the flesh of the fish, and produce high amounts of histamine. The most common sources of illness are finfish such as tuna, mackerel, amberjack and bonito. Other fish, such as mahi mahi, bluefish, marlin, and escolar, can also cause scombroid fish poisoning.

Histamine intolerance results from a disequilibrium between accumulated histamine and capacity for histamine degradation.38,39 Histamine occurs to various degrees in many foods. In healthy persons, dietary histamine can be rapidly detoxified by amine oxidases, whereas persons with low amine oxidase activity are at risk of histamine toxicity. The ingestion of histamine-rich food,alcohol or drugs that release histamine or block amine oxidase activity may provoke diarrhea,headache, rhinoconjunctival symptoms, asthma, hypotension, arrhythmia, urticaria, pruritus,flushing and other conditions in patients with histamine intolerance. Symptoms can be mitigated by a histamine-free diet and/or treatment with antihistamine drugs.


1. O'Mahony L, Akdis M, Akdis CA. Regulation of the immune response and inflammation by histamine and histamine receptors. J Allergy Clin Immunol. 2011 Dec;128(6):1153-1162.21824648
2. Moon TC, Befus AD, Kulka M. Mast cell mediators: their differential release and the secretory pathways involved. Front Immunol. 2014 Nov 14;5:569.25452755
3. He SH. Key role of mast cells and their major secretory products in inflammatory bowel disease. World J Gastroenterol. 2004 Feb 1;10:309-318.14760748
4. Beghdadi W, Porcherie A, Schneider BS, et al. Inhibition of histamine-mediated signaling confers significant protection against severe malaria in mouse models of disease. J Exp Med. 2008 Feb 18;205(2):395-408.18227221
5. Metz M, Doyle E, Bindslev-Jensen C, Watanabe T, Zuberbier T, Maurer M. Effects of antihistamines on innate immune responses to severe bacterial infection in mice. Int Arch Allergy Immunol. 2011;155(4):355-360.21346365
6. Akdis CA, Blaser K. Histamine in the immune regulation of allergic inflammation. J Allergy Clin Immunol. 2003 Jul;112(1):15-22.12847474
7. Jutel M, Watanabe T, Akdis M, Blaser K, Akdis CA. Immune regulation by histamine. Curr Opin Immunol. 2002 Dec;14(6):735-740.12413523
8. Jutel M, Watanabe T, Klunker S, et al. Histamine regulates T-cell and antibody responses by differential expression of H1 and H2 receptors. Nature. 2001 Sep 27;413(6854):420-425.11574888
9. Banu Y, Watanabe T. Augmentation of antigen receptor-mediated responses by histamine H1 receptor signaling. J Exp Med. 1999 Feb 15;189(4):673-682.9989982
10. Jutel M, Akdis M, Akdis CA. Histamine, histamine receptors and their role in immune pathology. Clin Exp Allergy. 2009 Dec;39(12):1786-1800.20085595
11. Schwartz LB. Mast cells and basophils. Clin Allergy Immunol. 2002;16:3-42.11577545
12. Galli SJ, Tsai M. Mast cells in allergy and infection: versatile effector and regulatory cells in innate and adaptive immunity. Eur J Immunol. 2010 Jul;40(7):1843-1851.20583030
13. Valent P, Akin C, Hartmann K, et al. Mast cells as a unique hematopoietic lineage and cell system: from Paul Ehrlich’s visions to precision medicine concepts. Theranostics. 2020 Aug 29;10(23):10743-10768.32929378
14. Metcalfe DD, Peavy RD, Gilfillan AM. Mechanisms of mast cell signaling in anaphylaxis. J Allergy Clin Immunol. 2009 Oct;124(4):639-646; quiz 647-648.19815110
15. Nadler MJ, Matthews SA, Turner H, Kinet JP. Signal transduction by the high-affinity immunoglobulin E receptor Fc epsilon RI: coupling form to function. Adv Immunol. 2000;76: 325-355.11079101
16. Gibbs BF. Human basophils as effectors and immunomodulators of allergic inflammation and innate immunity. Clin Exp Med. 2005 Jul;5(2):43-49.16096852
17. Theoharides TC, Valent P, Akin C. Mast cells, mastocytosis, and related disorders. N Engl J Med. 2015 Nov 5;373(19):1885-1886.26535528
18. Galli SJ, Gaudenzio N, Tsai M. Mast cells in inflammation and disease: recent progress and ongoing concerns. Annu Rev Immunol. 2020 Apr 26;38:49-77.32340580
19. Yoshimoto T, Tsutsui H, Tominaga K, et al. IL-18, although antiallergic when administered with IL-12, stimulates IL-4 and histamine release by basophils. Proc Natl Acad Sci U S A. 1999 Nov 23;96(24):13962-13966.10570181
20. Saxena SP, McNicol A, Brandes LJ, Becker AB, Gerrard JM. Histamine formed in stimulated human platelets is cytoplasmic. Biochem Biophys Res Commun. 1989 Oct 16;164(1):164-168.2803292
21. Kubo Y, Nakano K. Regulation of histamine synthesis in mouse CD41 and CD81 T lymphocytes. Inflamm Res. 1999 Mar;48(3):149-153.10219657
22. Radvany Z, Darvas Z, Kerekes K, et al. H1 histamine receptor antagonist inhibits constitutive growth of Jurkat T cells and antigen-specific proliferation of ovalbumin-specific murine T cells. Semin Cancer Biol. 2000 Feb;10(1):41.10888270
23. Bosso JV, Schwartz LB, Stevenson DD. Tryptase and histamine release during aspirin-induced respiratory reactions. J Allergy Clin Immunol. 1991 Dec;88(6):830-837.
24. Halmerbauer G, Hauk P, Forster J, Urbanek R, Kaufmehl K, Koller DY. In vivo histamine release during the first minutes after deliberate sting challenges correlates with the severity of allergic symptoms. Pediatr Allergy Immunol. 1999 Feb;10(1):53-57.10410918
25. Lin RY, Schwartz LB, Curry A, et al. Histamine and tryptase levels in patients with acute allergic reactions: An emergency department-based study. J Allergy Clin Immunol. 2000 Jul;106(1 Pt 1):65-71.10887307
26. Laroche D, Gomis P, Gallimidi E, Malinovsky JM, Mertes PM. Diagnostic value of histamine and tryptase concentrations in severe anaphylaxis with shock or cardiac arrest during anesthesia. Anesthesiology. 2014 Aug;121(2):272-279.24787350
27. Vlieg-Boerstra BJ, van der Heide S, Oude Elberink JNG, Kluin-Nelemans JC, Dubois AEJ. Mastocytosis and adverse reactions to biogenic amines and histamine-releasing foods: what is the evidence? Neth J Med. 2005 Jul-Aug;63(7):244-249.16093574
28. Dy M, Schneider E. Histamine-cytokine connection in immunity and hematopoiesis. Cytokine Growth Factor Rev. 2004 Oct;15(5):393-410.15450254
29. Schneider E, Rolli-Derkinderen M, Arock M, Dy M. Trends in histamine research: new functions during immune responses and hematopoiesis. Trends Immunol. 2002 May;23(5):255-263.12102747
30. MacGlashan D Jr. Histamine: a mediator of inflammation. J Allergy Clin Immunol. 2003 Oct;112(suppl):S53-59.14530789
31. Valent P, Hartmann K, Bonadonna P et al. Mast Cell Activation Syndromes: Collegium Internationale Allergologicum Update 2022. Int Arch Allergy Immunol. 2022;183(7):693-705.35605594
32. Moneret-Vautrin DA, Morisset M, Flabbee J, Beaudouin E, Kanny G. Epidemiology of life-threatening and lethal anaphylaxis: a review. Allergy. 2005 Apr;60(4):443-451.15727574
33. Kumar A, Teuber SS, Gershwin ME. Why do people die of anaphylaxis? A clinical review. Clin Dev Immunol. 2005 Dec;12(4):281-287.16584114
34. Butterfield J, Weiler CR. The utility of measuring urinary metabolites of mast cell mediators in systemic mastocytosis and mast cell activation syndrome. J Allergy Clin Immunol Pract. 2020 Sep;8(8):2533-2541.32142966
35. Afrin LB, Ackerley MB, Bluestein LS, et al. Diagnosis of mast cell activation syndrome: a global "consensus-2". Diagnosis (Berl). 2020 Apr 22;8(2):137-152.32324159
36. Briguglio M, Dell'Osso B, Panzica G, et al. Dietary Neurotransmitters: A Narrative Review on Current Knowledge. Nutrients. 2018 May 10;10(5):591.29748506
37. Brock I, Eng N, Maitland A. Adult-onset mast cell activation syndrome following scombroid poisoning: a case report and review of the literature. J Med Case Rep. 2021 Dec 18;15(1):620.34920756
38. Maintz L, Novak N. Histamine and histamine intolerance. Am J Clin Nutr. 2007 May;85(5):1185-1196.17490952
39. Wöhrl S, Hemmer W, Focke M, Rappersberger K, Jarisch R. Histamine intolerance-like symptoms in healthy volunteers after oral provocation with liquid histamine. Allergy Asthma Proc. 2004 Sep-Oct;25(5):305-311.15603203


Order Code Order Code Name Order Loinc Result Code Result Code Name UofM Result LOINC
144600 Histamine, Plasma 2416-6 144601 Histamine, Plasma ng/mL 2416-6

For Providers

Please login to order a test

Order a Test

© 2021 Laboratory Corporation of America® Holdings and Lexi-Comp Inc. All Rights Reserved.

CPT Statement/Profile Statement

The LOINC® codes are copyright © 1994-2021, Regenstrief Institute, Inc. and the Logical Observation Identifiers Names and Codes (LOINC) Committee. Permission is granted in perpetuity, without payment of license fees or royalties, to use, copy, or distribute the LOINC® codes for any commercial or non-commercial purpose, subject to the terms under the license agreement found at https://loinc.org/license/. Additional information regarding LOINC® codes can be found at LOINC.org, including the LOINC Manual, which can be downloaded at LOINC.org/downloads/files/LOINCManual.pdf