What type of hypersensitivity reaction is a Mantoux (tuberculin skin) test?

From the Guidelines

A Mantoux test is a Type IV delayed hypersensitivity reaction. This test involves the intradermal injection of purified protein derivative (PPD) from Mycobacterium tuberculosis into the forearm. In individuals previously exposed to tuberculosis, sensitized T lymphocytes recognize the antigen and initiate a cell-mediated immune response that develops over 48-72 hours 1. The reaction manifests as induration (hardening) and erythema (redness) at the injection site, which is measured in millimeters to determine if the test is positive.

Key Characteristics of the Reaction

• The reaction is a delayed-type hypersensitivity reaction, which means it takes time to develop after the injection of the antigen
• The reaction is mediated by T cells, which recognize the antigen and initiate an immune response
• The reaction manifests as induration and erythema at the injection site, which is measured in millimeters to determine if the test is positive

Comparison to Other Hypersensitivity Reactions

Unlike immediate hypersensitivity reactions (Types I, II, and III) which involve antibodies and occur within minutes to hours, the Type IV reaction depends on T cells and takes days to develop 1. This delayed response reflects the time needed for T cells to migrate to the site, recognize the antigen, and orchestrate the inflammatory response through cytokine release and recruitment of other immune cells.

Clinical Significance

The Mantoux test is used to diagnose latent tuberculosis infection and to identify individuals who are at risk of developing active tuberculosis disease 1. The test is interpreted based on the size of the induration, with larger reactions indicating a greater likelihood of infection. However, the test is not 100% sensitive or specific, and false-positive and false-negative results can occur 1.

Factors Affecting the Reaction

Several factors can affect the reaction, including the dose and type of antigen used, the method of administration, and the individual's immune status 1. Additionally, cross-reactions with other mycobacteria can occur, which can affect the specificity of the test 1.

Overall, the Mantoux test is a useful tool for diagnosing latent tuberculosis infection, but it must be interpreted in the context of the individual's clinical history and risk factors. The test should be used in conjunction with other diagnostic tests and clinical evaluation to confirm the diagnosis of tuberculosis.

From the FDA Drug Label

The sensitization following infection with mycobacteria occurs primarily in the regional lymph nodes. Small lymphocytes (T lymphocytes) proliferate in response to the antigenic stimulus to give rise to specifically sensitized lymphocytes. After 3-8 weeks, these lymphocytes enter the blood stream and circulate for years (7) Subsequent restimulation of these sensitized lymphocytes with the same or a similar antigen, such as the intradermal injection of TUBERSOL, evokes a local reaction mediated by these cells. (8) Characteristically, delayed hypersentitivity reactions to tuberculin begin at 5 to 6 hours, are maximal at 48 to 72 hours and subside over a period of days A delayed hypersensitivity reaction is the type of hypersensitivity reaction that a Mantoux test is, which is mediated by T lymphocytes 2.

• The reaction is characterized by:
  • Induration due to cell infiltration
  • Occasionally vesiculation and necrosis
  • Begins at 5 to 6 hours, maximal at 48 to 72 hours, and subsides over a period of days

From the Research

Hypersensitivity Reaction Type

• The Mantoux test is a type of delayed-type hypersensitivity (DTH) reaction, which is a cell-mediated immune response 3.
• This reaction occurs in response to the intradermal injection of tuberculin purified protein derivative (PPD) and represents a cutaneous T cell mediated memory recall immune response 3.

Characteristics of the Reaction

• The Mantoux test is typically used to determine immunity to tuberculosis in humans and positive reactions develop in individuals previously exposed to Mycobacterium tuberculosis, and those immunised with the Bacillus of Calmette and Guérin (BCG) vaccine 3.
• The reaction is characterised by significant cellular proliferation and clonal expansion at the site of antigen deposition in the skin, as well as accelerated differentiation of cells undergoing proliferation 3.

Comparison with Other Tests

• The Mantoux test has been compared to other tests for latent tuberculosis infection, such as interferon-gamma tests, which have been found to be more sensitive and specific 4.
• However, the Mantoux test is still widely used due to its simplicity and low cost, despite its limitations 5.

Clinical Utility

• The Mantoux test has been found to be of low accuracy in the diagnosis of doubtful cases of cutaneous tuberculosis, with a sensitivity and specificity of 58.97% and 62.50%, respectively 6.
• Other studies have investigated the use of alternative antigens for delayed-type hypersensitivity skin testing, such as Candida albicans, tetanus toxoid, and purified protein derivative (PPD) 7.