Contact dermatitis

Contact dermatitis refers to the skin changes that occur as a result to exposure to allergenic or irritant substances. Phototoxic dermatitis results when either an allergen or an irritant is activated by sunlight. Most common allergic contact dermatitis is poison ivy dermatitis, inclusive of poison oak and sumac. Common causes of irritant contact dermatitis are harsh soaps, detergents, and cleaning products.

Introduction

The skin condition of eczema is more commonly associated with a surface inflammation of endogenous cause or origin. However, contact dermatitis is an eczematous reaction to an external stimulus, usually repeated in nature. With all types of contact dermatitis, it is only the superficial regions of the skin that are affected, and this is observed histopathologically with inflammation present in the outer dermis and epidermis (ESCD 2006). In the present review, the four types of contact dermatitis will be discussed.

These are irritant contact, allergic contact and photocontact dermatitis and contact urticaria. Photocontact dermatitis is divided into two catergories.

Irritant Contact Dermatitis (ICD)

This more common form of contact dermatitis, affecting around 1-2% of healthy Europeans (ESCD 2006), can be caused by either an acute or chronic exposure to a toxic insult. It is also referred to as non-allergic contact dermatitis (along with traumiterative or housewives eczema) referring to its non-immunological mechanism of toxicity. Mathias and Maibach (1978) refer to it as:

"a nonimmunologic local inflammatory reaction characterized by erythema, edema, or corrosion following single or repeated application of a chemical substance to an identical cutaneous site."

ICD can be caused either chemically or by physical irritants.

Chemical Irritant Contact Dermatitis (CICD) can be subdivided into acute and chronic ICD which are usually associated with strong and weak irritants respectively (HSE MS24). The mechanism of action varies between toxins, and can even involve chemical burns. Detergents, surfactants, extremes of pH and organic solvents all have the common effect of directly affecting the barrier properties of the epidermis. The fat emulsion can be removed, cellular damage can be inflicted on the epithelium or the transepidermal water loss can be increased due to damage to the horny layer water-binding mechanisms. This horny layer can be affected due to DNA damage by the chemical which causes the layer to thin. As suggested previously, strong concentrations of irritants cause an acute effect, but this is not as common as the accumulative, chronic effect of weaker irritants whose deleterious effects build up with subsequent doses (ESCD 2006).

Physcial irritant contact dermatitis (PICD) is a much less well researched form of ICD (Maurice-Jones et al). This is mainly because of its highly varied and numberous mechanisms of action and the lack of a test for its diagnosis. A complete Patient history in combination with negative allergic patch testing is usually necessary to arise at a correct diagnosis. The simplest form of PICD is that which arises as a consequence of prolonged rubbing by a substance, although the diversity of implicated irritants is far wider as indicated in Fig 1.

A variety of plants are known to cause ICD, and can act by either means of irritancy. Some plants inflict a physcial reaction by the action of their spines or irritant hairs, whereas some plants eg. the buttercup, spurge and daisy, act by chemical means. The sap of these plants contains a number of alkaloids, glycosides, saponins, anthroquinones, and in the case of plant bulbs, irritant calium oxalate crystals, all of which can cause CICD (Mantle and Lennard, 2001).

Allergic Contact Dermatitis (ACD)

This condition is the manifestation of an allergic response caused by contact with a substance. A list of common allergens is shown in Table 1 (Kucenic and Belsito, 2002). Although less common than ICD, it is accepted to be the most prevalent form of immunotoxicity found in humans (Kimber et al 2002). By its allergic nature, this form is a hypersensitive reaction which is atypical within the population. The mechanisms by which these reactions occur are complex, with many levels of fine control. Their immunology centres around the interaction of immunoregulatory cytokines and discrete subpopulations of T Lymphocytes.

ACD arises as a result of two essential stages - an induction phase which primes and sensitises the immune system for an allergic response, and an elicitation phase in which this response is triggered (Kimber et al 2002). As such, ACD is termed a Type 2 allergic response. Contact allergens are essentially soluble haptens (low in molecular weight) and, as such, have the physico-chemical properties that allow them to cross the stratum corneum of the skin. They can only cause their response as part of a complete antigen, involving their association with epidermal proteins forming hapten-protein conjugates. This in turn requires them to be protein-reactive.

The conjugate formed is then recognised as a foreign body by the Langerhans Cells (LC) (and in some cases Dentritic Cells (DC)), which then internalise the protein, transport it via the lymphatic system to the regional lymph nodes and present the antigen to T-lymphocytes. As mentioned earlier, this process is controlled by cytokines and chemokines, with tumour necrosis factor alpha (TNF?) and certain members of the interleukin family (1, 13 and 18) and their action serves either to promote or to inhibit the mobilisation and migration of these LCs. (Kimber et al 2002) As the Langerhans cells are transported to the lymph nodes, they become differentiated and transform into Dentric Cells which are immunostimulatory in nature. Once within the lymph glands, the differentiated DCs act to present the allergenic epitope associated with the allergen to T lymphocytes. As a result, these T cells divide and differentiate, clonally multiplying so that if the allergen is experienced again by the individual, these T cells will respond more quickly and more aggressively.

As mentioned briefly, the immunological reaction involved in ACD is highly complex with many levels of fine control. Kimber et al (2002) explore these complexities in short. It appears that there are two major phenotypes of cytokine production (although there exists a gradient of subsets in between), and these are termed T-helper 1 and 2 (Th1 and Th2). Although these cells initially differentiate from a common stem cell, they develop with time as the immune system matures. Th1 phenotypes are characterised by their focus on Interleukin and Interferon, while Th2 cells action is centred more around the regulation of IgE by cytokines. The CD4 and CD8 T lymphocyte subsets also have been found to contribute to differential cytokine regulation, with CD4 having been shown to produce high levels of IL-4 and IL10 while solely CD8 cells are associated with low levels of IFN?. These two cell subtypes are also closely associated with the cell matrix interactions essential for the pathogenesis of ACD.

It has been suggested (White et al 1986) that there appears to be a threshold to the mechanisms of allergic sensitisation by ACD-associated allergens. This is thought to be linked to the level at which the toxin induces the upregulation of the required mandatory cytokines and chemokines. It has also been proposed that the vehicle in which the allergen reaches the skin could take some responsibility in the sensitisation of the epidermis by both assisting the percutaneous penetration and causing some form of trauma and mobilisation of cytokines itself.

Photocontact Dermatitis (PCD)

Sometimes termed "photoaggrevated"(Bourke et al 2001), and divided into two categories, phototoxic and photoallergic, PCD is the eczematous condition which is triggered by an interaction between an otherwise unharmful or less harmful substance on the skin and ultraviolet light (320-400nm UVA) (ESCD 2006), therefore manifesting itself only in regions where the sufferer has been exposed to such rays. Without the presence of these rays, the photosensitiser is not harmful. For this reason, this form of contact dermatitis is usually associated only with areas of skin which are left uncovered by clothing. The mechanism of action varies from toxin to toxin, but is usually due to the production of a photoproduct. Toxins which are associated with PCD include the psoralens. Psoralens are in fact used therapeutically for the treatment of psoriasis, eczema and vitiligo.

Photocontact dermatitis is another condition where the distinction between forms of contact dermatitis is not clear cut. Immunological mechanisms can also play a part, causing a response similar to ACD.

Contact Urticaria

Contact urticaria is another form of allergic reaction. Its mechanism is classified as Type I allergy, and is different in nature to ACD in the toxins responsible, the toxicolgical mechanism and, more importantly, the time scale overwhich the reaction occurs. As mentioned previously, ACD requires both sensitisation and elicitation, whereas Type I reactions only require a single exposure to the allergen. Contact urticaria manifests itself as small itching wheals (ESCD 2006) which disappear soon after appearing. It has been shown that natural rubber along with other animal proteins trigger this form of contact dermatitis. The molecules associated with this condition are large molecular weight antigens and must therefore usually be aided by some form of previous skin irritation or damage to traverse the skin barrier.

As with other forms of contact dermatitis, the reactions occur at the site of contact with the chemical, and in this way differentiate themselves from other forms of eczema. However, unlike with some other forms of contact dermatitis, urticaria appears to have a genetic aspect to it, with atopic individuals being more susceptible due to their raised allergen-specific IgE plasma levels.

Summary

The distinction between the various types of contact dermatitis is based on a number of factors. The morphology of the tissues, the histology, and immunologic findings are all used in diagnosis of the form of the condition. However, as suggested previously, there is some confusion in the distinction of the different forms of contact dermatitis (Reitschel 1997). Using histology on its own is insufficient, as these findings have been acknowledged not to distinguish (Rietschel, 1997), and even positive patch testing does not rule out the existence of an irritant form of dermatitis as well as an immunological one. It is important to remember, therefore, that the distinction between the types of contact dermatitis is often blurred, with, for example, certain immunological mechanisms also being involved in a case of irritant contact dermatitis.

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References

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ESDC. What is contact dermatitis. European Society of Contact Dermatitis, http://orgs.dermis.net

HSE Guidance Notes. Guidance Note MS 24 - Health Surveillance of occupational skin disease. http://www.hse.gov.uk/pubns/ms24.pdf

Kimber I, Basketter DA, Gerberick GF, Dearman RJ. Allergic contact dermatitis. Int Immunopharmacol. 2002 Feb;2(2-3):201-11. Review.

Kimber I, Gerberick GF. Toxicological aspects of allergic contact dermatitis: report on selected proceedings of the society of toxicology meeting, New Orleans, LA, USA, March 14-18, 1999. Am J Contact Dermat. 1999 Dec;10(4):245-8.

Kucenic MJ, Belsito DV.Occupational allergic contact dermatitis is more prevalent than irritant contact dermatitis: a 5-year study. J Am Acad Dermatol. 2002 May;46(5):695-9.

Mantle D, Lennard TWJ. Plants and the skin. Brit J Derm Nurs. 2001 (Summer).

Mathias CG, Maibach HI. Dermatotoxicology monographs I. Cutaneous irritation: factors influencing the response to irritants. Clin Toxicol. 1978;13(3):333-46. Review. No abstract available.

Morris-Jones R, Robertson SJ, Ross JS, White IR, McFadden JP, Rycroft RJ. Dermatitis caused by physical irritants. Br J Dermatol. 2002 Aug;147(2):270- 5. Review.

Rietschel RL. Mechanisms in irritant contact dermatitis. Clin Dermatol. 1997 Jul-Aug;15(4):557-9.