What happens in the skin?

Many substances can trigger wheals and itchiness. Many of these substances are produced by the body itself and act on the skin “from inside”. However, there are numerous substances in our environment that cause our skin to itch and wheal. A common characteristic of most of these substances is that they release the messenger histamine, believed to play a key role in triggering wheals, itching and angioedema. This itch-triggering effect of histamine is very clearly evident after an insect bite for example, or after contact with stinging nettles. Beyond substances that release the body’s supply of histamine, the venom of many insects and pruritic (itch-inducing) plants contains histamine that penetrates and stimulates the skin. The stimulant is sensed by specialised nerves (one might also say the “itch nerves”). A message is sent to the brain, the neural circuitry of the brain: something is itching here! This is often quite a good thing. In the case of insect bites or following contact with pruritic plants, itchiness induces us to scratch the skin, cool it under cold water (and thereby eliminate the trigger) or rub it (whereby more blood reaches the spot of the reaction allowing the itch stimulants or venoms to be transported away more quickly with the bloodstream). Almost all of the histamine is stored in a specific kind of cell, the so-called mast cells. When these cells are activated, i.e. if they are “nettled” by a stimulant (and there are a number of stimulants that do so), the mast cells release their histamine into the skin tissue resulting in whealing and itching.

Illustration 4: Mast cells (dark blue) – the cells which trigger urticaria symptoms. (Source: Allergy Centre Charité)

One process is common to all forms of urticaria. Histamine (Ill. 4) and many other inflammation triggers, e.g. leukotrienes or the platelet activating factor (PAF) is released by activating mast cells in the skin.

These factors then lead to the dilation of the blood vessels in the skin followed by swelling and itching. Mast cells are actually the “firefighters” or the “border patrol” of the human body. They are most commonly found in the parts of the body where we have direct contract with our environment: in the skin, in the mucous membranes of the gastrointestinal tract and in the respiratory tract. They fulfil crucial life functions for the body: dangerous assailants like bacteria or parasites are identified and neutralised – be it because the mast cells block the path of the intruders into the body, neutralise their venom, because they kill or eat them, or because they alarm the cells of the immune system (our body’s defence system) and direct them to the spot of the incidence.

The prevalence of mast cells in the skin and in the mucous membranes of the human body explains why urticaria is particularly noticeable in those spots. The activation of the mast cells in the upper (outermost) dermal and mucous membrane layers leads to wheals, while the activation in the lower (deeper) dermal layers leads to deeper swelling (angioedema). An activation of the mast cells in the mucous membranes of the pharynx and of the respiratory tract can lead to difficulty in swallowing and create respiratory distress; an activation of the mucous membranes of the gastrointestinal tract leads to stomach aches, nausea and diarrhoea.

Wheals and angioedema develop by the smallest skin vessels “leaking” in the area in which the skin is affected. The space between the cells that form the walls of the blood vessels increases, allowing blood plasma and other blood cells to escape from the interior of the blood vessels into the surrounding tissues. Apart from histamine, leukotrienes, PAF and other mast cell products increase the permeability of blood vessels. The fact that antipruritic substances are, in many cases, effective in connection with urticaria may be explained by the fact that these drugs directly block the impact of histamine. These drugs are therefore also called antihistaminic drugs. Antihistaminic drugs have been tested and proven for decades. They are generally tolerated very well; serious side effects are extremely rare. Formerly antihistaminic drugs often made the patient very tired. In the modern antihistaminic drugs of the 2nd generation this adverse effect has been more or less “eliminated”. When “antihistaminic drugs” are spoken of in the following text, the modern antihistaminic drugs of the 2nd generation which do not cause drowsiness are meant. The fact that antihistaminic drugs are not always effective for all cases of urticaria indicates that histamine is not the only substance which triggers itchiness and wheals.

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