Metals used in dentistry and orthopaedic surgery are frequently transition metals, and are capable of binding to proteins and enzymes in the body. This process may trigger an allergic reaction in some individuals. The reaction is identical to the well-known nickel-induced contact dermatitis. In addition to the skin, all organs in the body can be affected depending on where the metal is deposited.

MELISA is a non-invasive blood test for diagnosing metal allergies. It requires a blood sample to be sent to a licensed laboratory. Blood samples must arrive to the laboratory within 24 hours after the blood has been drawn, and at 48 hours latest. White blood cells (lymphocytes) are isolated and tested against allergens chosen according to the patient’s history and current and/or future exposure to metals. Some of the lymphocytes, so-called memory cells, remember past exposure to metal ions (and other allergens).

The blood is incubated for five days. Normally, memory cells are inactive as they circulate in the blood. If, however, the remembered foreign substance, or antigen, such as a metal ion, reappears in the blood, memory cells become active in an attempt to fight it; starting to divide and enlarge.
This lymphocyte reaction is measured by two separate technologies: one based on the uptake of radioisotope by dividing lymphocytes and the other evaluation by microscopy. The level of reactivity is measured as a Stimulation Index (SI).

If lymphocytes do not divide or enlarge when exposed to metal salts, then the test is negative. If an increased number of growing lymphocytes (lymphoblasts) appear, then the immune system is sensitized to the tested metal, and the results are positive.

A value over 3 generally indicates a positive reaction to a given allergen. The results are available within 10-14 days.

Metal-induced responses are strictly specific, meaning that patients with a positive reaction to inorganic mercury might test negative to other mercury compounds such as methyl mercury, phenyl mercury and ethyl mercury, or the other way around. 
Testing for Titanium Allergy

Traditional patch testing is not effective for indicating titanium allergy as  titanium is not soluble and the particles are too large to penetrate the skin.  With MELISA  titanium allergy testing, lymphocytes are exposed to different titanium salts, such as titanium dioxide, titanium sulphate and calcium titanate. However, it must be mentioned, that even very pure titanium dioxide salts might contain minute amounts of impurities of other metals such as manganese or nickel. The same is true for body implants, food and medical grade titanium dioxide, where impurities of other metals are often present. This is described in the article Hypersensitivity reactions to metallic implants - diagnostic algorithm and suggested patch test series for clinical use from 2012. Titanium-induced lymphocyte reaction is clinically relevant since patients with a positive reaction in MELISA test negative to titanium after the removal and replacement of titanium-containing implants (as published by Valentine-Thon 2006).


Titanium not only enters the body through the corrosion of implants but also through ingestion of food colouring, toothpaste and medicine, or through the skin via the nano particles contained in sunscreen and cosmetics.