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MP 2.04.42 Leukocyte Histamine Release Test


Medical Policy    
Original Policy Date
Last Review Status/Date
Reviewed with literature search/4:2008
  Return to Medical Policy Index


Our medical policies are designed for informational purposes only and are not an authorization, or an explanation of benefits, or a contract.  Receipt of benefits is subject to satisfaction of all terms and conditions of the coverage.  Medical technology is constantly changing, and we reserve the right to review and update our policies periodically.




The leukocyte histamine release test (LHRT) is designed to provide an in vitro correlate to an in vivo allergic response (i.e., skin prick testing). An allergen is added to the peripheral blood leukocytes of the individual being tested and the in vitro release of histamine from basophils in response to exposure to the allergen is measured. Histamine is normally released as a consequence of the interaction of allergen with cell-bound IgE antibodies. In contrast, the RAST test (radioallergosorbent test) attempts to correlate the presence of allergy to serum levels of antigen-specific IgE as an index of allergic reactivity. Initially, measurements of histamine release required isolation of leukocytes from whole blood followed by the isolation of the released histamine; the laboratory techniques were difficult and time consuming and thus LHRT was primarily used as a research tool only. Recently, a special type of glass fiber has been developed that binds histamine with high affinity and selectivity. These glass fibers can be used as a "solid phase" to absorb the histamine that is released directly into the blood. The recent commercial availability of simplified and automated methods of laboratory analysis (i.e., both ELISA and radioimmunoassays) have renewed interest in the clinical applications of LHRT in the evaluation of food, inhalant, and drug allergies.




The leukocyte histamine release test (LHRT) is considered investigational as a technique for the diagnosis and management of allergic disorders.



Policy Guidelines

No applicable information



Benefit Application

BlueCard/National Account Issues

No applicable information




The published literature regarding LHRT is reviewed using the same criteria as used in the TEC Assessment of serial endpoint testing (See policy No. 2.01.23 ). For example, quality indicators for studies of diagnostic trials include:

  • Prospective enrollment
  • Representative patient population enrolled
  • Appropriate spectrum of patients
  • Unbiased enrollment (no referral bias)
  • Few patients not enrolled that are eligible
  • Appropriate accounting for all eligible patients
  • All eligible patients receive both tests
  • LHRT interpreted independently of alternative test (i.e., skin prick, RAST, or bronchial provocation test)
  • Alternative tests interpreted independently of LHRT.

In assessing the diagnostic accuracy, the comparative reproducibility, sensitivity, and specificity of LHRT are the primary outcomes to be considered. In the absence of an accepted gold standard for the diagnosis of allergy, it is difficult to ascertain the comparative performance characteristics of available diagnostic tests. For this reason, the concordance, or correlation, of results from different tests is typically reported for LHRT. The published literature regarding the commercially available LHRTs suffers from the fact that alternative tests have not been performed in a blinded manner, or studies did not indicate whether or not there were blinded interpretations of the tests. (1, 2) Some studies included patients with known allergies, and thus these highly selective populations do not represent the same population with equivocal allergy histories that would undergo testing. (2-6) In some situations, results were compared with bronchial provocation testing, considered the gold standard for inhalant allergies. However, bronchial provocation may only be performed on a subset of patients with a limited number of allergens. For example, bronchial provocation may only be performed when there are discordant results between RAST and skin prick testing. (7) Thus overall, these studies are potentially prone to spectrum bias, referral bias, and ascertainment bias, and are not sufficient to permit conclusions on the diagnostic accuracy of LHRT. It has been suggested that LHRT may be a valuable test in those patients with discordant results of skin prick testing and RAST testing, but studies focusing on this subgroup of patients were not identified in a literature search.

2005 Update

A search of the literature was performed for the period of 2003 through February 2005. No studies were identified that would prompt reconsideration of the policy statement, which remains unchanged.

2006 Update

A search of the MEDLINE database for the period of October 2004 through September 2006 found no studies that would prompt reconsideration of the policy statement; the policy is unchanged.

2007 Update
A search of the MEDLINE database for the period of October 2006 through January 2008 found no studies on the clinical use of the leukocyte histamine release test. The evidence is insufficient to permit conclusions concerning the effect of this test on health outcomes. Therefore, LHRT is considered investigational.


  1. Griese M, Kusenbach G, Reinhardt D. Histamine release test in comparison to standard tests in diagnosis of childhood allergic asthma. Ann Allergy 1990; 65(1):46-51.
  2. Skov PS, Mosbech M, Norn S et al. Sensitive glass microfibre-based histamine analysis for allergy testing in washed blood cells. Results compared with conventional leukocyte histamine release assay. Allergy 1985; 40(3):213-8.
  3. Ostergaard PA, Ebbensen F, Nolte H et al. Basophil histamine release in the diagnosis of house dust mite and dander allergy of asthmatic children. Comparison between prick test, RAST, basophil histamine release and bronchial provocation. Allergy 1990; 45(3):231-5.
  4. Kleine-Tebbe J, Werfel S, Roedsgaard D et al. Comparison of fiberglass-based histamine assay with a conventional automated fluorometric histamine assay, case history, skin prick test, and specific serum IgE in patients with milk and egg allergic reactions. Allergy 1993; 48(1):49-53.
  5. Kleine-Tebbe J, Galleani M, Jeep S et al. Basophil histamine release in patients with birch pollen hypersensitivity with and without allergic symptoms to fruits. Allergy 1992; 47(6):618-23.
  6. Paris-Kohler A, Demoly P, Persi L et al. In vitro diagnosis of cypress pollen allergy by using cytofluorimetric analysis of basophils (Bastotest). J Allergy Clin Immunol 2000; 105(2 pt 1):339-45.
  7. Nolte H, Storm K, Schiotz PO. Diagnostic value of a glass fibre-based histamine analysis for allergy testing in children. Allergy 1990; 45(3):213-23.







Leukocyte histamine release test 

ICD-9 Procedure 

No Codes 


ICD-9 Diagnosis 


Allergy to air-borne substance (specified allergen other than pollen, includes dust, mites, etc.) 



Allergy to air-borne substance (unspecified allergen, includes hay fever) 



Encounter for diagnostic skin and sensitization tests 


No Code 


Type of Service 


Place of Service 

Physician’s Office 




Leukocyte Histamine Release Test (LHRT)

Histamine Release Test
Histamine Release Assay




Policy History

Date Action Reason
06/27/05 Add policy New policy; leukocyte release test originally addressed in general policy on allergy testing (No. 2.01.23). Policy 2.01.23 now focused on serial endpoint testing, and leukocyte release test is now addressed in this separate policy. Policy statement unchanged; still considered investigational.
12/12/06 Replace policy Policy updated with literature search; no change in policy statement
04/09/08 Replace policy  Policy updated with literature search; no change in policy statement