eMedicine Specialties > Pediatrics: General Medicine > Allergy & Immunology
Delayed-type Hypersensitivity: Treatment & Medication
Updated: Jun 2, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Medical Care
Delayed-type hypersensitivity (DTH) skin testing requires the use of antigen doses as defined under Lab Studies. See Lab Studies for a more complete discussion of the interpretation of delayed-type hypersensitivity reactions.
- Delayed-type hypersensitivity responses represent cellular immune responses to recall antigens to which the subject has been introduced at least 4-6 weeks previously. The reaction occurs 48-72 hours after exposure and induces induration of 5 mm or more.
- The inflammatory reaction may be sufficient to induce pain at the local site. Topical steroids and diphenhydramine have been used to decrease an unusually severe reaction. If an excessive reaction is anticipated, such as in caseating tuberculosis, decrease the amount of antigen; for M tuberculosis, for example, decrease the strength of the purified protein derivative (PPD) from the customary 5 units to 1 unit.
- Negative reactions to a recall antigen to which the patient is known to have adequate exposure require investigation for an underlying illness or a T-cell deficiency.
- Positive delayed-type hypersensitivity reactions do not indicate protection against the recall antigen that is tested. Antibody responses to the specific antigen usually reveal better correlation with immune protection.
- In patients with mutations in the interferon (IFN)-γ/interleukin (IL)-12/IL-23 signaling pathways, medical care includes consideration of hematopoietic stem cell transplantation in patients with severe deficiencies and consideration of exogenous IFN-γ therapy in patients with partial deficiencies with milder clinical features. In the presence of nontuberculosis mycobacteria (NTM) infection, patients require treatment with an aggressive regimen of antimycobacterial drugs.
Consultations
- In a context in which a T-cell disorder is likely, a clinical immunologist should manage the diagnostic workup in order to obtain informative cell-mediated immunologic testing and appropriate mutational analysis.
- Both types of evaluations for rare T-cell disorders are commonly available only in laboratories of specific investigators.
Diet
- Resolution of protein-energy malnutrition induces an intact delayed-type hypersensitivity response.
Medication
Purified protein derivative (PPD), used to evaluate exposure to M tuberculosis, and Candida antigen are the only currently available US Food and Drug Administration (FDA)-approved antigens for delayed-type hypersensitivity (DTH) skin testing. The most clinically informative antigens used for delayed-type hypersensitivity reactivity are Candida and tetanus antigens because most individuals are exposed to these antigens as infants. By age 9-12 months, more than 80% of immunocompetent children mount positive responses to these antigens.
Previously available delayed-type hypersensitivity antigens withdrawn from clinical use include the Cell-mediated immunity (CMI) multitest, coccidioidin, mumps, and histoplasmin. Mumps antigen is a relatively poor antigen in eliciting a positive delayed-type hypersensitivity skin test reactivity. Studies have shown only 60% of previously infected adults to have a positive test reactivity. An even lower response is predicted when the only exposure to mumps is by measles, mumps, and rubella (MMR) immunization.
Tuberculin tests
These agents are used to detect infection with M tuberculosis.
Tuberculin, purified protein derivative (PPD Mantoux test, Aplisol, Tubersol)
The standard skin test uses 5 U of PPD in a volume of 0.1 mL. A lower concentration of 1 U/0.1 mL is used when a high exposure to antigen, as in caseating tuberculosis, is suspected; 250 U can be used if standard test result is negative and person is known to be immunocompromised. A negative DTH reaction does not rule out infection but may indicate disseminated infection as in miliary tuberculosis.
Adult
0.1 mL, containing 5 U PPD, injected ID into volar surface of the forearm; test read at 48 and 72 h; induration measured at >5 mm, 10 mm, or 15 mm considered a positive result depending on patient age, immunologic status, and membership in at-risk population (see Clinical above)
Pediatric
Administer as in adults
Malnutrition, steroid therapy, sarcoidosis, Hodgkin lymphoma, other malignancies, and a number of other infections may cause anergy in the presence of active infection; the most likely infections to cause anergy are HIV, measles, and mumps; severe influenza, infectious mononucleosis, or the MMR vaccine may cause negative DTH
None reported; anaphylaxis is not reported; sterile abscesses that can occur with vaccines or antibiotics are rarely reported
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Know tuberculin positive reactors (higher degree of ulceration or necrosis at site of injection); extensive painful reaction can be treated with topical steroid creams, diphenhydramine, or, possibly, ibuprofen; avoid SC injection; reading test at 24 h and measuring erythema and induration distinguishes immediate IgE-mediated reaction at 24-48 h from DTH
Tetanus antigens
These are used to assess cellular immune responses following the primary series of diphtheria-tetanus-pertussis vaccine (3 doses). Conventionally used as a control for tuberculin testing in patients who are immunocompromised or suspected to have disseminated tuberculosis.
Tetanus toxoid USP, fluid (8 LFU/mL, NDC#49281-0812-84)
The standard TD vaccine is diluted to 1:100 or 1:10. A positive DTH reaction indicates recognition by cell-mediated immunity; protection correlates with antibody responses.
Adult
Injected ID in a volume of 0.1 mL into volar surface of forearm; lower concentration of 1:100 dilution used for DTH testing because most adults have had several TD boosters since childhood; test read at 24, 48, and 72 h; induration > 5 mm positive at 48-72 h
Pediatric
<2 years: 1:10 dilution ID
>2 years: 1:100 dilution ID initially; if no response consider retesting with higher concentration
Malnutrition, steroid therapy, sarcoidosis, Hodgkin lymphoma, other malignancies, and a number of other infections may cause anergy in presence of active infection; the most likely infections to cause anergy are HIV, measles, and mumps; severe influenza, infectious mononucleosis, or the MMR vaccine may cause negative DTH
None reported
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Painful reaction can be treated with topical steroids, diphenhydramine, or ibuprofen; reading the test at 24 h and measuring erythema and induration distinguishes the immediate IgE-mediated reaction at 24-48 h from DTH
Candida antigens
Most infants have been exposed to Candida antigen even without clinical thrush or Candida diaper dermatitis. Japanese studies showed that 80% of children had positive delayed-type hypersensitivity responses by age 1 year; therefore, Candida is a conventional antigen used as a positive control for tuberculin testing in individuals who are immunocompromised or when disseminated tuberculosis is suspected.
Candida skin test antigen (Candin, NDC#38697-200-1; Allermed)
Also known as Dermatophytin. It is diluted 1:10 or 1:100 with sterile water.
Adult
0.1 mL injected ID into the volar surface of the forearm; initial skin test dilution is 1:100 ID; induration > 5 mm at 48-72 h read as positive result
Pediatric
<2 years: 1:10 dilution in a volume of 0.1 mL ID
>2 years: Administer as in adults
Extensive active
Candida infection: 1:100 dilution in a volume of 0.1 mL ID initially
Malnutrition, steroid therapy, sarcoidosis, Hodgkin lymphoma, other malignancies, and a number of other infections may cause anergy in the presence of active infection; the most likely infections to cause anergy are HIV, measles, and mumps; severe influenza, infectious mononucleosis, or the MMR vaccine may cause negative DTH
None reported
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Painful reaction can be treated with topical steroid cream, diphenhydramine, or ibuprofen; reactions to Candida antigen seem to be more common than to other recall antigens; reading test at 24 h and measuring erythema and induration distinguishes the immediate IgE-mediated reaction at 24-48 h from DTH
More on Delayed-type Hypersensitivity |
| Overview: Delayed-type Hypersensitivity |
| Differential Diagnoses & Workup: Delayed-type Hypersensitivity |
 Treatment & Medication: Delayed-type Hypersensitivity |
| Follow-up: Delayed-type Hypersensitivity |
| References |
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Further Reading
Keywords
delayed-type hypersensitivity, DTH, DTH reaction, DTH response, delayed-type hypersensitivity reaction, delayed type hypersensitivity, delayed hypersensitivity, hypersensitive response, hypersensitive reaction, cell mediated immunity, CMI, antigen-presenting cells, APCs, cell-mediated immunity to recall antigens, anergy, anergic reaction, T cell, T-cell receptor, Candida antigen, Candida infection, DTH skin test, T-cell disorder, T-cell defect, bone marrow transplantation, BMT
Mycobacterium tuberculosis, tetanus, Candida, Trichophyton, mumps, contact hypersensitivity, nickel, dinitrochlorobenzene, DNCB, picryl chloride, leprosy, poison ivy, Listeria monocytogenes, Legionella pneumophila, Toxoplasma gondii, Leishmania, lymphocytic choriomeningitis virus, mouse hepatitis virus, herpes simplex virus, HSV, malnutrition, atopic dermatitis, MMR vaccine, sarcoidosis, mononucleosis, HIV, influenza, malignant lymphomas, severe combined immunodeficiency, SCID, cytomegalovirus, CMV, Hodgkin lymphoma, asthma, atopy, glomerulonephritis, treatment, diagnosis
