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Delayed Hypersensitivity Reactions Workup

  • Author: Stuart L Abramson, MD, PhD; Chief Editor: Michael A Kaliner, MD  more...
Updated: Dec 23, 2015

Laboratory Studies

Contact dermatitis

No specific laboratory tests are needed unless the diagnosis is uncertain. Contact dermatitis is a clinical diagnosis. A skin biopsy can be performed if the diagnosis is in question, and the results of patch tests are often helpful to determine the specific contactant.

Tuberculin hypersensitivity skin reaction

No laboratory tests are needed. This is a specific local reaction to an administered Mantoux test.

Granulomatous diseases

Diagnostic testing differs depending on the disease suggested.

If TB is considered, a Mantoux test and a chest radiograph should be performed.[5, 6]

If sarcoidosis is suggested, a chest radiograph and, if indicated, a biopsy, should be performed. An elevated serum angiotensin-converting enzyme level is not diagnostic.

If cutaneous lesions are possibly related to a granulomatous disease, then a skin biopsy can be performed.

Possible cell-mediated immunity

If a deficiency in cell-mediated immunity is suggested, an anergy battery of skin tests can be performed.[7] Typically, the antigens used are candidin, trichophytin, mumps skin test antigen, and tetanus toxoid. If fewer than 4 recall antigens are used, the likelihood of a false-negative result is increased.

The concentrations used are candidin at 1:100 (vol:vol), trichophytin at 1:30 or 1:100 (vol:vol), mumps skin test antigen at 40 colony-forming units/mL, and tetanus toxoid at 0.2 Loeffler units/0.1 mL in 1:100 (vol:vol). The test volume is 0.1 mL placed intradermally. The maximum perpendicular diameters of induration are determined at 24, 48, and 72 hours. An immediate (20 min) wheal and flare at the injection site during a DTH skin test may result in a false-negative DTH reaction.

The term anergy is now expanded to imply an absence of the capacity to express DTH skin test reactivity to the antigens usually encountered (so-called recall antigens). The presence of anergy depends on the number and type of antigens used in the skin test evaluation, the smallest reaction considered to be positive, and other technical factors.

Most investigators use a panel of 4-5 antigens to which more than 90% of healthy adults exhibit at least one positive reaction. This percentage of reactors is understandably lower in healthy children because of a reduced opportunity for prior exposure to the microorganisms that normally result in such DTH reactivity.

Generally, the highest prevalence of reactions occurs against mumps, candidal, and tetanus antigens.[8] Relative deficits are understandably more difficult to evaluate, but they are probably more common than absolute anergy in the biologic processes and clinical disorders described.

In some clinical situations, individuals may exhibit a deficit in expressing DTH reactions to particular antigens previously encountered, while other recall DTH responses are normal. Some controversy exists regarding whether the absence of reactivity to a tuberculin DTH skin test and normal responses to other recall antigens exclude previous or current infection with M tuberculosis. Reactivity to newly encountered antigens may not develop, but recall DTH reactivity is normal.

In more recent studies, investigators have focused on the cellular basis of anergy. With the aid of in vitro technology, abnormalities involving multiple components of the DTH apparatus have been described. The expression of DTH skin test reactivity requires the capacity to mount a cellular inflammatory reaction, a response frequently impaired nonspecifically in persons with chronic debilitating diseases. Moreover, other T-cell–dependent functions apparently are frequently impaired. Such deficits may either play an important role in the pathogenesis of a particular disease or occur as a consequence of that disease.

Laboratory correlate of the DTH skin test

Reactions include lymphocyte thymidine incorporation (ie, lymphocyte proliferation or blast transformation) following nonspecific stimulation with mitogens (eg, phytohemagglutinin, concanavalin A) or antigen stimulation. The mixed lymphocyte reaction is a thymidine incorporation T-cell reaction to cell surface antigens. Cytokine production from stimulated lymphocytes also may be measured.


Imaging Studies

If TB or sarcoidosis is suggested, chest radiographs and CT scans may be indicated.


Other Tests

Patch tests can be used for contact dermatitis in order to help determine the contactant.



Skin biopsy may be indicated.


Histologic Findings

The cellular events that result in delayed hypersensitivity reactions primarily involve T cells and macrophages. First, local immune and inflammatory responses at the site of foreign antigen up-regulate endothelial cell adhesion molecule expression, promoting the accumulation of leukocytes at the tissue site. The antigen is engulfed by macrophages and monocytes and is processed and presented to a T cell that has a specific receptor for that processed antigen. Macrophages secrete IL-1, IL-2, IL-6, and other lymphokines. Cytotoxic T cells can also be activated. The recruited macrophages can form giant cells. The characteristic histologic appearance of the macrophage–T-cell infiltrate is a granuloma. This type of infiltrate in the tissue is called granulomatous inflammation.

Contributor Information and Disclosures

Stuart L Abramson, MD, PhD Associate Professor of Pediatrics, Baylor College of Medicine; Consulting Staff, Allergy/Immunology Section, Texas Children's Hospital

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Michael R Simon, MD, MA Clinical Professor Emeritus, Departments of Internal Medicine and Pediatrics, Wayne State University School of Medicine; Professor, Department of Internal Medicine, Oakland University William Beaumont University School of Medicine; Adjunct Staff, Division of Allergy and Immunology, Department of Internal Medicine, William Beaumont Hospital

Michael R Simon, MD, MA is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American College of Allergy, Asthma and Immunology, Michigan State Medical Society, Michigan Allergy and Asthma Society, American College of Physicians, American Federation for Medical Research, Royal College of Physicians and Surgeons of Canada, Society for Experimental Biology and Medicine

Disclosure: Received ownership interest from Secretory IgA, Inc. for management position; Received ownership interest from siRNAx, Inc. for management position.

Chief Editor

Michael A Kaliner, MD Clinical Professor of Medicine, George Washington University School of Medicine; Medical Director, Institute for Asthma and Allergy

Michael A Kaliner, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Association of Immunologists, American College of Allergy, Asthma and Immunology, American Society for Clinical Investigation, American Thoracic Society, Association of American Physicians

Disclosure: Nothing to disclose.

Additional Contributors

Melvin Berger, MD, PhD Adjunct Professor of Pediatrics and Pathology, Case Western Reserve University; Senior Medical Director, Clinical Research and Development, CSL Behring, LLC

Melvin Berger, MD, PhD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Allergy Asthma and Immunology, American Academy of Pediatrics, American Association of Immunologists, American Pediatric Society, American Society for Clinical Investigation, Clinical Immunology Society

Disclosure: Received salary from CSL Behring for employment; Received ownership interest from CSL Behring for employment; Received consulting fee from America''s Health insurance plans for subject matter expert for clinical immunization safety assessment network acvtivity of cdc.


The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous authors Walter Duane Hinshaw, DO; Gregory Paul Neyman, MD; and Stephen Mark Olmstead, DO; to the development and writing of this article.

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