Histamine Determination, Whole Blood

Whole blood, frozen

2 mL

1 mL (Note: This volume does not allow for repeat testing.)

Green-top (heparin) tube required. (Do not use EDTA.)

This test is used for the measurement of histamine in whole blood.

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)

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.