Delayed-type Allergy (Type IV Allergy)
Type IV allergy is the most common allergic condition of the delayed type. These reactions typically present as contact allergies (contact dermatitis), allergic reactions to dental materials (e.g. dentures, filling materials), or drug hypersensitivity. The typical symptoms do not appear until 24 to 72 hours after contact with the triggering allergen. The main effector cells of Type IV allergy are T lymphocytes. Upon first exposure to the allergen, specific T cells are activated and long-lived, potentially reactive memory T cells are formed, which remain in the body. This process, known as sensitisation, proceeds without any noticeable symptoms. If the allergen enters the body again, the memory T cells are reactivated and differentiate into effector T cells, which then trigger an inflammatory response at the site of allergen contact.
Contact Allergy
Contact allergy is the most common delayed-type hypersensitivity reaction. Between 15 and 28% of the general population are sensitised to at least one contact allergen. Around 7% develop allergic contact dermatitis, the most common clinical manifestation of a delayed-type allergic reaction, at least once per year. This usually presents as a localised skin inflammation with itchy or oozing redness or swelling. If the triggering allergen is removed, the allergic reaction typically subsides within a few days, and the affected skin heals completely. However, constant exposure to the allergen may lead to chronic eczema, which is marked by inflamed thickening and scaling of the skin (allergic contact eczema). Continued skin damage impairs the skin's barrier function, thereby allowing other allergens and bacteria to penetrate more easily. This potentially results in further, more extensive skin reactions.
Allergy to Dental Materials
In dentistry, there has been a noticeable increase in sensitisation to dental materials used in crowns, bridges, or braces. Type IV allergies are often triggered by metal alloys used as filling materials. Sensitivities can also be caused by composite cements or denture plastics, particularly acrylates. Clinical symptoms range from localised reactions such as tooth or jaw pain, periodontitis, or inflammation of the oral mucosa, to non-specific, systemic complaints including headaches, muscle pain, fatigue, or depression.
Drug Allergy
Reactions to drugs frequently present as Type IV allergies. Apart from direct skin contact (e.g. with ointments), drugs typically enter the body through mucous membranes, or systemically via the bloodstream — especially when the allergen is a metabolite of the drug. Therefore, the clinical presentation of drug-induced Type IV allergy is often non-specific and highly variable. The skin is commonly affected by rashes (exanthema) or urticaria.
Diagnosing a Type IV Allergy
Potential sensitisation to metals, dental materials or drugs can be assessed in vitro using the Lymphocyte Transformation Test (LTT, 3HT-Memory-Spot®). The strength of T-cell proliferation induced by the test depends on whether prior immune exposure to the antigen/allergen has occurred – i.e. whether sensitisation exists. The 3HT-Memory-Spot® test allows in vitro evaluation of antigen-specific cellular memory responses.
The standardised 3HT-Memory-Spot® test provides a reliable alternative to the epicutaneous (patch) test in terms of specificity and sensitivity. Unlike the patch test, the 3HT-Memory-Spot® can also be used to assess symptoms that do not affect the skin, but appear in other organs or present as non-specific health complaints.
