In the skin, histamine, which is responsible for itching and hives, occurs practically only in mast cells. Wheals arise due to the fact that the skin vessels in the affected skin area begin to leak. Histamine makes the cells of blood vessels move away from each other by binding to specific structures (histamine receptors) on the vascular cells and thus indicating to vascular cells that they should move away from each other. This allows blood fluid and some blood cells to escape from the interior of the vessel into the surrounding tissue. In addition to histamine, mast cell products such as leukotrienes or other messengers (so-called cytokines) can increase the permeability of blood vessels. The effect of anti-itch drugs in cases of urticaria can be explained by the fact that these drugs specifically inhibit the binding of histamine to the histamine receptors. These drugs are therefore referred to as antihistamines. The fact that antihistamines do not help in all cases of urticaria indicates that histamine is not the only itch- and hives-inducing substance that is playing a role here.

How are mast cells activated in connection with the different types of urticaria?

This question can be answered most easily with regard to allergic urticaria, a rare subtype of chronic urticaria. The mast cell is the ultimate allergy cell and is involved in all allergies mediated by the protein immunoglobulin E (IgE) and thus responsible for the symptoms of asthma, hay fever, or eczema. The hives can cause allergic mast cell activation, that is, an activation by IgE and an allergen (a substance that can trigger an allergic reaction). In such a case, allergens enter the body along with food or air that is breathed in (e.g. tree pollen, grass pollen, house dust mite droppings) and then activate mast cells, which are loaded with corresponding IgE antibodies. Rarely, the absorption of cross-reacting foods can trigger urticaria even in cases of such an allergy.

Any person can become allergic in the course of her or his life. This occurs if we become sensitized against certain pollen such as birch pollen after contact with the pollen. Sensitization refers to the production of immunoglobulins (anti-proteins) against a particular substance, in our example against birch pollen. If we are sensitized, our bodies produce various immunoglobulins with different tasks. The type E immunoglobulins (IgEs) formed by the defense cells of the immune system, for example, get stuck at specially prepared sites on mast cells (IgE receptors) on their way through the human body. Now, when our bodies again come in contact with birch pollen, the IgEs that adhere to the IgE receptors on the mast cells recognize the birch pollen and collect them. The mast cell to which the IgE with the captive birch pollen is stuck is activated and discharges its histamine. An allergic reaction occurs. This best studied pathway of mast cell activation is found only in a small proportion of all urticaria patients.

Much more often the formation of antibodies (defense protein bodies) against the IgE receptor or IgE bound to it seems to be responsible for urticaria. In up to 30 percent of patients with chronic urticaria, such antibodies against the body’s own substances can be detected. In other words, the body reacts against itself. Therefore, one also speaks of autoantibodies and autoimmune urticaria. A simple test for the existence of such autoimmune urticaria is the injection of a patient’s own blood, or the liquid portion of the blood, into the skin of the forearm. In patients with antibodies against their own IgE receptor or IgE, this results in significant wheal formation.

The complement system is an essential component in the network of the body’s immune defense. Its main responsibilities include the direct destruction of cells and agents (such as bacteria or parasites) and the activation of the immune system. The activation of the complement system, e.g. in the context of bacterial infections, leads to the release of powerful mast-cell-activating substances. Not infrequently, chronic urticaria has been caused by a chronic infection (e.g. of the paranasal sinuses, the tonsils, the gastric mucosa, or the teeth): it is known that the removal of such a chronic focus of infection can lead to the healing of chronic urticaria. This is called urticaria due to infection.

The term intolerance urticaria is used in cases in which the body cannot tolerate a particular substance. Discomfort occurs due to intolerance reactions to substances such as medicines, preservatives, or dyes in food. Avoidance of the triggering substance, e.g. by means of a diet, can bring about the healing.