Contact hypersensitivity

Toxicology and Ecotoxicology in Chemical Safety Assessment.” Blackwell Publishing Ltd 2005 by Laura Robinson and edited by Dr. Ian Thorn.

1.4.2 Chemical hypersensitivity
An allergy is an adverse reaction caused by an over-stimulation of the immune system in response to a specific allergen that is otherwise harmless and would normally be tolerated by the majority of those who come into contact with it. It is the clinical manifestation of hypersensitivity.

Many of us have probably had a form of allergy at some time or another in our lives, hay fever (pollen allergy) is a very common example. Different types of allergies will give rise to different symptoms depending on the tissues of the body involved.  These symptoms can include sneezing, runny nose and eyes, coughing and skin rashes.

A word commonly seen in print is allergen. This is simply a foreign substance (an antigen) that causes an allergic reaction in a hypersensitive person. Typical allergens are proteins such as pollen, peanuts, shellfish, etc.

Allergens are either:

• Whole allergens — allergens able to elicit an immune response themselves. Complex biological substances such as pollen typically act as whole allergens.

• Haptens – these allergens themselves do not trigger an immune response. Instead, they combine with and modify the body’s own proteins to form complete antigens. It is this combination that the body sees as ‘foreign’. Many chemicals, and in particular those which are of a low molecular weight, will act as haptens. How does an allergic reaction occur?
An allergy is an adverse effect resulting from specific immunological responses and it has two stages.

• Sensitisation (or induction) phase — during the first encounter with the allergen, the individual becomes sensitised as a result of changes in the immune system which involve the lymphocytes.

• Elicitation phase — subsequent exposure to the same allergen, which can be at much lower concentrations than experienced in the sensitisation phase, can lead to the development of allergic symptoms.

In a cell-mediated response, there is generally a delay of between 24 and 48 hours following exposure before symptoms develop in a sensitised individual. This is often why it is called a delayed response. An example of this is contact hypersensitivity, which could be caused, for example, by formaldehyde. However, with an antibody- mediated response the symptoms are seen within minutes of exposure (again in a sensitised individual), which is why it is often called an immediate response. Occupational asthma is an example of this.

1.4.3 Contact hypersensitivity (allergic contact dermatitis) What is allergic contact dermatitis?
Allergic contact dermatitis (another name for skin sensitisation) arises as a result of the skin becoming sensitised to a specific allergen. Subsequent exposure to that same allergen results in an inflammatory reaction.

Of particular interest to us is the handling of chemicals used during the pulp and paper-making process. As may be recalled, most chemicals, and especially those that are of a low molecular weight, are unable to provoke an immune response on their own. This is because they are too small to be recognised by the immune s – Instead, they act as haptens. Common contact allergens include formaldehyde, epoxy resin and nickel. What is the mechanism of allergic contact dermatitis?
As is the case with allergy, there are two stages in the development of allergic contact dermatitis.

(1) Induction/sensitisation. The chemical substance penetrates the skin where it combines with natural proteins in the epidermis thereby forming a complete antigen. This is subsequently transported to the local draining lymph nodes where an immune response is stimulated. The whole process usually takes at least 10 days, after which time the individual is sensitised (allergic). During this induction/sensitisation stage there are no indications of skin damage.

(2) Elicitation. Subsequent contact elicits an immune reaction with the outbreak of dermatitis usually within 48 hours. The symptoms are that of an allergic reaction, i.e. itching, redness, pain, rash, etc. What factors dictate whether or not allergic contact dermatitis will develop?

Although there is no way to predict who will develop allergic contact dermatitis there are some factors which can play a role. These include the following.

(1) Any predisposing skin condition such as irritant contact dermatitis or simply skin abrasions or cuts will increase the possibility of developing allergic contact dermatitis. This is because any skin damage makes it much easier for chemicals to enter the skin layers thus allowing sensitisation to occur more readily.

(2) As with irritant contact dermatitis, the working environment will be of importance and the same principles will apply (sweating, friction, etc.).

(3) The ability of the chemical to penetrate the upper layers of the skin is an important factor and its allergenic ability will depend upon this. Thus, if it cannot penetrate the upper layers of the skin, then it will not be able to invoke an immune response, and therefore, there will be no allergic reaction. The duration and frequency of exposure together with the concentration and amount of chemical allergen involved will also play a role. A weak allergen would require more frequent contact compared to a strong allergen before any sensitisation effects were induced.

(4) Genetic predisposition (atopy) will also be a factor.
However, not all the workers who handle a chemical that has potentially allergenic properties will develop this disease. In some cases, workers could have worked with such a substance for many years before any symptoms occur. For others, it could develop much more rapidly. Similarly, although it is possible to become sensitised to a particular allergen, it is not always the case that an outbreak of dermatitis will occur upon subsequent exposures. What are the consequences of developing allergic contact dermatitis?

The problem with allergic contact dermatitis is that it can persist for many years and, once sensitised, the only way to avoid the outbreak of the symptoms (dermatitis) is to avoid all contact with that specific allergen. However, even if all efforts are made to avoid contact with that specific chemical, it is possible to get cross-sensitivity reactions.

As with other forms of hypersensitivity, allergic contact dermatitis is a very important issue in the workplace because normal handling and protective precautions are often ineffective. Even if a particular chemical has an occupational exposure limit and attempts are made to keep the levels well below this, the breakout of symptoms associated with that particular allergy in sensitised individuals may still occur. This is because the levels needed to trigger an outbreak of symptoms are very low and often well below that specified by an occupational hygiene limit.