Test Catalog

Test Id : RLTE4

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Leukotriene E4, Random, Urine

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Overview

Test Catalog

Useful For
Suggests clinical disorders or settings where the test may be helpful

Aiding in the evaluation of patients at-risk for mast cell activation syndrome (eg, systemic mastocytosis, IgE-mediated allergies, or aspirin-exacerbated respiratory disease) using random urine collections

Highlights

Quantitation of urinary metabolites of histamine, prostaglandin D2, and leukotriene E4 may provide significant clues for the diagnosis and management of symptomatic patients with both clonal and nonclonal mast cell activation syndromes. The presence of 1 or more elevated levels of these biomarkers in urine greatly narrows diagnostic possibilities for causes of symptoms; informs the practitioner what specific metabolic pathways are involved; and targets the treatment in a specific, personalized fashion.

Profile Information
A profile is a group of laboratory tests that are ordered and performed together under a single Mayo Test ID. Profile information lists the test performed, inclusive of the test fee, when a profile is ordered and includes reporting names and individual availability.

Test Id Reporting Name Available Separately Always Performed
LTE4R Leukotriene E4, Random, U No Yes
CRTFR Creatinine, Random, U No Yes

Method Name
A short description of the method used to perform the test

LTE4R: Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS)

CRTFR: Enzymatic Colorimetric Assay

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

Leukotriene E4, Random, U

Aliases
Lists additional common names for a test, as an aid in searching

Cysteinyl Leukotriene

LTE4

Mast Cell Activation Syndrome

Mastocytosis

Systemic Mast Cell Activation

Secondary MCAS

Aspirin-exacerbated respiratory disease (AERD)

Asthma

IgE-dependent and independent asthma

Idiopathic MCAS

Specimen Type
Describes the specimen type validated for testing

Urine

Ordering Guidance

Patients with mast cell activation syndrome may have chronically elevated leukotriene E4 (LTE4), however, in certain situations LTE4 can exhibit intermittent elevations. In these cases, a 24-hour urine collection is preferred. For 24-hour urine collection, order TLTE4 / Leukotriene E4, 24 Hour, Urine.

Additional Testing Requirements

For an optimal evaluation, testing for urinary leukotriene E4 should be accompanied with laboratory investigations for the presence of serum tryptase (TRYPT / Tryptase, Serum), urinary 2,3-dinor 11 beta-prostaglandin F2 alpha (23BPR / 2,3-Dinor 11 Beta-Prostaglandin F2 Alpha, Random, Urine) and urinary N-methylhistamine (NMHR / N-Methylhistamine, Random, Urine).

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

Supplies: Sarstedt Aliquot Tube, 5 mL (T914)

Container/Tube: Plastic vial

Specimen Volume: 5 mL

Collection Instructions:

1. Within a few hours of symptom onset, collect a random urine specimen.

2. No preservative

3. Aliquot urine into a plastic vial and send frozen.

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the testing laboratory. The minimum volume is sufficient for one attempt at testing.

2 mL

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

  All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
Urine Frozen (preferred) 28 days
Refrigerated 7 days
Ambient 24 hours

Useful For
Suggests clinical disorders or settings where the test may be helpful

Aiding in the evaluation of patients at-risk for mast cell activation syndrome (eg, systemic mastocytosis, IgE-mediated allergies, or aspirin-exacerbated respiratory disease) using random urine collections

Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Leukotrienes (LT) are eicosanoids generated from arachidonic acid via the 5-lipoxygenase pathway. Leukotriene E4 (LTE4) is the stable end product of this pathway and, therefore, regarded as a biomarker of total cysteinyl leukotriene production.(1-3) Assessment of LTE4 in urine allows for noninvasive specimen collection and avoids artifactual formation of LT during phlebotomy. Generation of LTE4 occurs nonspecifically from active mast cells (MC), basophils, eosinophils, and macrophages and is modulated through a variety of mechanisms.(1) Elevated concentrations of LTE4 are associated with both clonal (primary) and nonclonal (secondary and idiopathic) MC activation syndromes (MCAS).(1-3) MCAS have been defined as a group of disorders in which patients experience symptoms precipitated by MC proinflammatory and vasoactive mediator release.(1) Some of these MC mediators contribute to physiologic processes and maintenance of tissue homeostasis.

 

Primary MCAS have clonal markers, such as the KIT Asp816Val variant or aberrant expression of CD25 or CD2 on MC. The 2 primary groups of MCAS are mastocytosis (cutaneous and systemic [SM]) and monoclonal MCAS. Patients with mastocytosis should fulfill the World Health Organization diagnostic criteria for this disorder. Diagnosis requires either the major plus one minor criterion or 3 minor criteria.(1,4,5)

The consensus diagnostic criteria for SM include:

Major criterion:

Imaging of the multifocal infiltrates

Minor criteria:

1. Identifying morphological features of above 25% of MC from bone marrow biopsy

2. Detection of the point alteration at codon 816 in the KIT gene

3. CD2, CD25, and/or CD30 expression in MC

4. Persistently elevated serum tryptase (>20 ng/mL)

 

The 2 main nonclonal MCAS categories include secondary MCAS, for which there is a known trigger for MC activation (IgE-dependent and independent allergic reactions, atopic disorders, autoimmune processes), and idiopathic, in which the etiology for MC activation is undefined.(1-3,5-7) Based on consensus criteria, the diagnosis of MCAS can be established when typical clinical symptoms arising from recurrent (episodic) acute systemic MC activation (typically in the form of recurrent anaphylaxis in at least 2 organ systems) have been documented; MC-derived mediators increase substantially in serum or urine over the individual’s baseline; and the symptoms respond to drugs blocking MC activation, MC mediators, mediator production, or mediator effects.(6)

 

A recently proposed diagnostic algorithm for the evaluation of patients with suspected MCAS considers 2 main diagnoses that may underlie severe forms of MC activation (anaphylaxis), namely, IgE-dependent allergies and clonal MC disorders.(1-3,5-7) A serum tryptase level, which has long been used in diagnosing these disorders, has several drawbacks, including the need to obtain acute and baseline specimens to fulfill diagnostic criteria. Furthermore, an increased baseline tryptase level has been reported in hereditary alpha tryptasemia, complicating the diagnostic possibilities.(1,3) In addition to the limitations of serum tryptase, there are reports of symptomatic patients with features of MC activation who do not meet all the criteria for MCAS but have elevated baseline mediator metabolites.(3,5,7) In these patients, there is evidence that their symptoms respond to drugs that target MC activation, the mediators released by MC, and/or the effects of these mediators. Based on these observations, validated biomarkers suggestive of MC activation, such as an increase in the histamine metabolite (N-methylhistamine) or the prostaglandin D2 metabolite (2,3-dinor 11 beta-prostaglandin F2 alpha), have been recommended for testing when tryptase is not available, or the result is inconclusive.(7)

 

With respect to urine LTE4, there is increasing clinical evidence for its use in patients at risk for aspirin intolerance in asthma (aspirin-exacerbated respiratory disease) and other forms of asthma.(8,9) For example, elevated LTE4 concentrations have been shown to correlate with traditional markers and represent a noninvasive approach to asthma phenotyping in patients with type 2 asthma mediated in part by MC and eosinophils.(9) In this study, increased urine LTE4 levels were associated with lower lung function and increased amounts of exhaled nitric oxide and eosinophil markers in blood, sputum, and urine in adult and adolescent patients with asthma. Based on these and other findings, there is interest for the use of therapeutics that target the production of inflammatory eicosanoids, such as LTE4, in the management of these diseases.(10-12)

Reference Values
Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

LEUKOTRIENE E4

< or =104 pg/mg creatinine

 

CREATININE

> or =18 years old: 16-326 mg/dL

Reference values have not been established for patients who are younger than 18 years of age.

Interpretation
Provides information to assist in interpretation of the test results

Elevated urinary leukotriene E4 concentrations above 104 pg/mg creatinine may be suggestive of mast cell activation syndrome if compatible features of disease are present.

Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Patients taking the 5-lipoxygenase inhibitor zileuton (Zyflo) may have decreased concentrations of leukotriene E4 (LTE4) if the dosage has not been discontinued for 48 hours.

 

Mast cell (MC) activation disorder is a heterogenous disease, and the absence of elevated LTE4 does not exclude the diagnosis of MC disease.

 

Increased excretion of LTE4 is nonspecific and should not be used alone to make a clinical diagnosis of a MC activation disease.

 

This assay measures both LTE4 and the 11-trans-LTE4 as markers of MC release.

Clinical Reference
Recommendations for in-depth reading of a clinical nature

1. Weiler CR. Mast cell activation syndrome: Tools for diagnosis and differential diagnosis. J Allergy Clin Immunol Pract. 2020;8(2):498-506

2. Gulen T, Akin C, Bonadonna P, et al. Selecting the right criteria and proper classification to diagnose mast cell activation syndromes: A critical review. J Allergy Clin Immunol Pract. 2021;9(11):3918-3928

3. Butterfield JH. Nontryptase urinary and hematologic biomarkers of mast cell expansion and mast cell activation: Status 2022. J Allergy Clin Immunol Pract. 2022;10(8):1974-1984

4. Valent P, Akin C, Metcalfe DD. Mastocytosis: 2016 updated WHO classification and novel emerging treatment concepts. Blood. 2017;129(11):1420-1427

5. Valent, P, Akin, C, Hartmann, K., et.al. Updated diagnostic criteria and classification of mast cell disorders: A consensus proposal. Hemasphere. 2021;5(11): e646

6. Divekar R, Hagan J, Rank M, et al. Diagnostic utility of urinary LTE4 in asthma, allergic rhinitis, chronic rhinosinusitis, nasal polyps, and aspirin sensitivity. J Allergy Clin Immunol Pract. 2016;4(4):665-670

7. Valent P, Hartmann K, Bonadonna P, et al. Global classification of mast cell activation disorders: An ICD-10-CM-adjusted proposal of the ECNM-AIM Consortium. J Allergy Clin Immunol Pract. 2022;10(8):1941-1950

8. Kolmert J, Gomez C, Balgoma D, et al. Urinary leukotriene E(4) and prostaglandin D(2) metabolites increase in adult and childhood severe asthma characterized by type 2 inflammation. A clinical observational study. Am J Respir Crit Care Med. 2021;203(1):37-53

9. Hagan JB, Laidlaw TM, Divekar R, et al: Urinary leukotriene E4 to determine aspirin intolerance in asthma: A systematic review and meta-analysis. J Allergy Clin Immunol Pract. 2017;5(4):990-997.e1. doi:10.1016/j.jaip.2016.11.004

10. Hayashi H, Fukutomi Y, Mitsui C, et al. Omalizumab for aspirin hypersensitivity and leukotriene overproduction in aspirin-exacerbated respiratory disease. A randomized controlled trial. Am J Respir Crit Care Med. 2020;201(12):1488-1498

11. Buchheit KM, Lewis E, Gakpo D, et al: Mepolizumab targets multiple immune cells in aspirin-exacerbated respiratory disease. J Allergy Clin Immunol. 2021;148(2):574-584

12. Buchheit KM, Sohail A, Hacker J, et al: Rapid and sustained effect of dupilumab on clinical and mechanistic outcomes in aspirin-exacerbated respiratory disease. J Allergy Clin Immunol. 2022;150(2):415-424

Method Description
Describes how the test is performed and provides a method-specific reference

Leukotriene E4:

The specimen and an internal standard are assayed by liquid chromatography tandem mass spectrometry(LC-MS/MS). The analyte is detected by multiple-reaction monitoring.(Lueke AJ, Meeusen JW, Donato LJ, Gray AV, Butterfield JH, Saenger AK: Analytical and clinical validation of an LC-MS/MS method for urine leukotriene E4: A marker of systemic mastocytosis. Clin Biochem. 2016;49[13-14]:979-982)

 

Creatinine:

This enzymatic method is based on the determination of sarcosine from creatinine with the aid of creatininase, creatinase, and sarcosine oxidase. The liberated hydrogen peroxide is measured via a modified Trinder reaction using a colorimetric indicator. Optimization of the buffer system and the colorimetric indicator enables the creatinine concentration to be quantified both precisely and specifically.(Package insert: Creatinine plus ver 2. Roche Diagnostics; V15.0, 03/2019)

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Monday, Tuesday, Thursday

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

2 to 9 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

14 days

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees :
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Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.

CPT Code Information
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

82542

82570

LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.

Test Id Test Order Name Order LOINC Value
RLTE4 Leukotriene E4, Random, U 33343-5
Result Id Test Result Name Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
603457 Leukotriene E4, Random, U 33343-5
CRTFR Creatinine, Random, U 2161-8

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Pdf

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports

Test Update Resources

Change Type Effective Date
File Definition - Algorithm 2023-03-21