Test Catalog

Test ID: LTE4    
Leukotriene E4, Urine

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

Evaluating patients suspected of having systemic mastocytosis


Identification of aspirin sensitivity in patient respiratory diagnoses

Testing Algorithm Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

When leukotriene E4 testing is performed, urine creatinine will always be performed at no additional charge.

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 (cys-LT) production. 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, basophils, eosinophils, and macrophages, and modulated through a variety of mechanisms. Elevated concentrations of LTE4 are associated with inflammatory and accelerated mast cell activation conditions, specifically in patients with systemic mast cell disease.(1)


Systemic mastocytosis (SM), or systemic mast cell disease, is a myeloproliferative neoplasm that has infiltrated extracutaneous organs. Release of mast cell inflammatory mediators leads to disease symptoms including those associated with allergic and anaphylactic reactions, while increased mast cell number leads to organ dysfunction. Consensus diagnostic criteria for SM include 1 major criterion: imaging of the multifocal infiltrates; and 4 minor criteria: 1) identifying morphological features of greater than 25% of mast cells from bone marrow biopsy, 2) detection of the point mutation at codon 816 in the KIT gene, 3) CD2 and/or CD25 expression in mast cells, and 4) persistently elevated serum tryptase. Diagnosis requires either 1 major plus 1 minor criterion or 3 minor criteria.(2)


Measurement of urinary mast cell activation biomarkers can aid in the initial evaluation of suspected cases of systemic mast cell disease, potentially avoiding the need for imaging and bone marrow examination. Patients with SM frequently have elevated urine concentrations of LTE4,(1) N-methylhistamine,(3,4) and 2,3-dinor 11 beta-prostaglandin F2 alpha.(4)


Urinary LTE4 has also demonstrated significant utility in patients with asthma and respiratory diseases. In a study of adults with mild to moderate asthma on 5-lipoxygenase inhibitors, urine LTE4 concentrations decreased approximately 40% compared with asthma control subjects, suggesting modest decreases in LTE4 production correlates with clinical improvements in asthma severity.

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.

< or =104 pg/mg creatinine

Interpretation Provides information to assist in interpretation of the test results

Elevated urinary leukotriene E4 (LTE4) concentrations above 104 pg/mg creatinine are consistent with the diagnosis of systemic mast cell disease when combined with clinical signs and symptoms. Pharmacological treatment with 5-lipoxygenase inhibitors or leukotriene receptor antagonists has been shown to decrease production of LTE4.


Urinary LTE4 may be used together with serum tryptase, urinary 2,3-dinor 11 beta-prostaglandin F2 alpha, and urinary N-methylhistamine.


LTE4 values of 166 pg/mg creatinine were 89% specific for aspirin sensitivity among patients with respiratory diagnoses.

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

Systemic mastocytosis is a heterogenous disease and lack of elevated LTE4 does not exclude the diagnosis of mast cell disease.


Increased excretion of LTE4 has also been reported in the following conditions: asthma, eosinophilic pneumonia, respiratory syncytial virus infection, atopic dermatitis, Crohn disease, and rheumatoid arthritis.


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

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

1. 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;4:665-670

2. Lueke AJ, Meeusen JW, Donato LJ, et al: Analytical and clinical validation of an LC-MS/MS method for urine leukotriene E4: A marker of systemic mastocytosis. Clin Biochem 2016 Sep;49(13-14):979-982

3. Gotlib J, Pardanani A, Akin C, et al: International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) and European Competence Network on Mastocytosis (ECNM) consensus response criteria in advanced systemic mastocytosis. Blood 2013 Mar 28;121(13):2393-2401

4. Heide R, Riezebos P, van Toorenbergen AW, et al: Predictive value of urinary N-methylhistamine for bone marrow involvement in mastocytosis. J Invest Dermatol 2000;115(3):587

5. Van Gysel D, Oranje AP, Vermeiden I, et al: Value of urinary N-methylhistamine measurements in childhood mastocytosis. J Am Acad Derm 1996;35(4):556-558

Special Instructions Library of PDFs including pertinent information and forms related to the test