Contact Dermatitis: Synopsis
Posted: August 2004
Contact dermatitis is characterized by redness, itching, vesiculation and in more chronic form, scaly desquamation, resulting from exposure to environmental substances. The site and morphological characteristics of the lesions are determined by the causative exposure.
Contact dermatitis is classified as:
Irritant Contact Dermatitis (ICD)
These skin lesions develop following prolonged and repeated exposure to irritants such as caustic agents or detergents. Although inflammatory cells have a role in the development of the dermatitis, allergen-specific immune lymphocytes are not involved in the pathogenesis and prior sensitization is not necessary. Susceptibility to irritants varies, but given sufficient exposure, nearly everyone would develop irritant contact dermatitis.
Phototoxic reactions are the direct result of photochemistry and do not depend on immune sensitization. The lesions resemble sunburn and all individuals with sufficient exposure to a photosensitizer (such as psoralen) together with ultraviolet light (UV) would develop erythematous skin reactions.
Allergic Contact Dermatitis (ACD)
These skin lesions result from inflammation caused by allergen-specific T lymphocytes. Prior sensitization is essential and rapid development of dermatitis occurs following re-exposure to low concentrations of allergen, which would not cause lesions in non-sensitized individuals.
Photoallergic reactions result from the photochemical reaction of UV with an allergenic hapten generated by a sensitizing agent. Once the allergenic photoproduct has been generated, the underlying mechanisms of photoallergic reactions are similar to that of allergic contact dermatitis.
85-95% of all occupational skin disease in the working population of industrialized countries is due to contact dermatitis. In these countries, hand dermatitis affects between 2% and 6% of the population.
The fundamental characteristic of contact dermatitis is the relationship to environmental exposure, which determines the site and shape of the skin lesions (click for picture).
Linearity, a sharp edge to an otherwise amorphous lesion or an abrupt cutoff, is a characteristic of contact dermatitis (click for picture).
Irritant contact dermatitis most frequently affects the hands (click for picture).
Phototoxic and photoallergic lesions due to systemically administered agents such as medications occur in skin exposed to sunlight. When the sensitizing agent is applied to the skin, for example fragrance, lesions occur at the site of application following exposure to sunlight.
Nickel allergy involves ears, skin under buckles and often the hands; accidental spread from the hands can affect the face.
Hair products - dyes and sprays - affect the face, neck and ears.
Dyes in socks and shoes affect the feet.
Medications for the treatment of leg ulcers can cause dermatitis of the legs (click for picture).
In sensitized individuals, an itchy, red rash develops at the site of re-exposure to the causative substance within 6 to 12 hours. The reaction peaks at 48 to 72 hours, and, if exposure continues, the skin becomes scaly, weepy and desquamates.
Strongly sensitized people require very little contact with the causative allergen for severe acute weeping eczematous reactions to occur.
Contact with the sensitizing allergen can occur even through several layers of clothing, for example nickel eluted from keys, money or studs by minimal perspiration.
The principle differential diagnosis is between ACD and ICD. This is of particular consequence in occupational dermatitis, since the correct diagnosis of an irritant cause may allow the patient to continue at work with appropriate skin protection. A detailed history of all domestic, occupational, sporting and leisure contactants together with the results of patch testing is required.
The differential diagnosis of contact dermatitis includes most inflammatory skin diseases. However the majority of skin diseases that are not related to contact have a symmetrical distribution, as is the case with the atopic eczema/dermatitis syndrome (AEDS), drug eruptions, psoriasis and connective tissue diseases.
Fixed drug eruptions can be single and round, and cutaneous T-cell lymphoma may be asymmetric. Both lesions can be diagnosed by histopathological examination.
Nickel is the most common cause of ACD in many countries. It is present in most metal alloys including 14-karat gold. Most nickel allergic patients can avoid problems by wearing 18-karat gold and testing other suspect alloys with a dimethylglyoxime test. The role of dietary nickel in skin eruptions is controversial.
Rubber Accelerators: Thiurams, Carbamates, Mercaptobenzothiazole
ACD to rubber usually results from sensitization to these compounds and occurs where rubber is worn next or close to the skin. Examples are elastic bands in underclothes, and rubber in gloves, shoes and barrier contraceptives (click for picture). Carbamates are found not only in rubber products but also in garden fungicides. Allergy to black rubber may also be the result of sensitization to paraphenylenediamine dye.
Latex rubber can also cause allergic contact urticaria which is an IgE-mediated reaction to protein allergens from the latex, and may also be a reaction to the accelerators used in rubber production. Patients with a history of contact urticaria should not undergo patch testing because of the risk of anaphylaxis.
Paraphenylenediamine is a black dye used in permanent oxidative hair dyes and with cross-linkers to produce all hair dye colors. It is a major cause of ACD in hairdressers. Paraphenylenediamine is also used as an antioxidant in oils and greases, as a component in color film developers and as a dye for leather and rubber, and so is an important cause of occupational dermatitis in a wide variety of trades.
Fragrances: Balsam of Peru and Cinnamic Aldehyde
Fragrances containing balsam of Peru and cinnamic aldehyde are present in many topical preparations, cosmetics, soaps, perfumes and toothpastes. Sensitized patients must use "fragrance free" products - "unscented" products are not suitable since they may contain masking fragrances.
Adhesives and Varnishes
P-Tertiary-butylphenol formaldehyde resin (PTBP) is a phenolic contact adhesive used in the manufacture of plastics, plywood, cardboard boxes, varnish, rubber cements, leather products and lacquers. PTBT is a factor in shoe dermatitis and in ACD to plastic products and oils.
Epoxy resins are widely used as adhesives in electronics, the construction industry, and in marine paints and varnishes and are an important cause of ACD.
Formaldehyde and Formaldehyde Releasers
Formaldehyde is one of the most widespread allergens in the environment, being present in fixatives, adhesives, preservatives and disinfectants. Many cosmetics and disinfectants contain either formaldehyde or the formaldehyde releasers imidazolidinyl urea and quaternium-15 (click for picture). Formaldehyde is also used as a fabric treatment particularly in the "care- free" type of garments, which retain their shape. Many formaldehyde sensitized patients can, however, tolerate garments that have been washed many times.
Exposure to potassium chromate is common in tanning of leather and in the construction industry due to cement (click for picture). ACD to chromate in leather shoes may be seasonal, as a result of the allergen being leached out by perspiration during warm weather.
Benzocaine is a sensitizer and is present in many nonprescription medications such as preparations for the treatment of hemorrhoids and burns and as a topical anesthetic. Cross-reactions with procaine occur.
The antibacterial agent neomycin is a common cause of ACD. Bacitracin may also cause sensitization.
Contact dermatitis is characterized by inflammation in the epidermis and superficial dermis. Acutely there is superficial perivascular infiltration with lymphocytes, monocytes and a small number of eosinophils. Edema in the epidermis is seen as increased intercellular spaces between keratinocytes (spongiosis). This may progress to vesicles and blisters (click for picture). Chronic contact dermatitis results in thickening of the epidermis, irregular elongation of the rete ridges and vertical thickening of the collagen of the papillary dermis - the changes of lichen simplex chronicus.
Contact allergens are small molecules, known as haptens, that must bind to macromolecules to become immunogenic. Many allergens, such as dinitrochlorobenzene, are chemically reactive and can covalently conjugate proteins. Others such as nickel, form non-covalent complexes with proteins. A third class of allergens, which includes urushiol, the allergenic component of poison ivy, are pro-haptens (click for picture). These compounds must be activated to a chemically reactive intermediate before they can conjugate proteins.
The Role of the Keratinocyte
Keratinocytes play a key role in the development of both ACD and ICD. These cells synthesize and release pro-inflammatory cytokines, in particular interleukins (IL-s) 1, 6 and 8, tumor necrosis factor α (TNF-α) and granulocyte monocyte colony-stimulating factor (GM-CSF). These cytokines play an important part in the recruitment and homing of inflammatory cells and can be induced and released from keratinocytes by both irritants and allergens.
Antigen presentation: The Role of the Langerhans Cell
Langerhans cells are the primary antigen presenting cells (APCs) of the epidermis. They are characterized by the cell surface expression of CD1a and the presence of intracytoplasmic Birbeck granules, which on electron microscopy have a tennis-racket shape. These cells process protein antigens by cleaving them into peptides and presenting these fragments in the peptide-binding groove of their surface located major histocompatibility complex molecules (MHC class II). Hapten-conjugated Langerhans cells migrate to the local lymph nodes where they present the allergen to T lymphocytes. The T lymphocytes must then home to the inflamed skin (see below).
Homing of T Lymphocytes
Homing is the process whereby circulating cells migrate to relevant sites. The number of T lymphocytes in the skin lesions in ACD is increased several times compared to that in circulating blood. This process relies on the linkage between adhesion molecules expressed on endothelial cells and their ligands expressed on lymphocytes. There is a homing receptor on T lymphocytes probably the "cutaneous lymphocyte antigen" (CLA), which is a ligand for E-selectin, an adhesion molecule expressed on dermal endothelial cells. Additional adhesion molecule pairs are essential for lymphocyte homing. These are endothelial intercellular adhesion molecule (ICAM-1) which interacts with lymphocyte function antigen (LFA-1) and endothelial vascular adhesion molecule (VCAM-1), which interacts with lymphocyte very late activation antigen (VLA-4): Both LFA-1 And VLA-4 are integrins.
Induction of Inflammation
T lymphocytes have a number of potent mechanisms for the induction of inflammation: These include:
- Cell mediated toxicity
- Recruitment of additional inflammatory cells
- The direct effect of released cytokines
It is known that TNF-α has an important role in the pathogenesis of allergic contact dermatitis, since in mice, these skin lesions can be blocked by the administration of antibody against TNF-α. The role of other cytokines in the development of allergic contact dermatitis remains to be evaluated.
Patch testing requires three visits. On the first day, the allergens are applied to the back in a dermatitis-free area, usually in Finn chambers under Scanpore tape. Forty-eight hours later, the patches are removed and the skin is examined. The patient returns the following day for the final assessment of skin reactivity. Topical corticosteroids must not be applied to the test site, nor oral corticosteroids administered to the patient for at least 2 weeks prior to patch testing. It is important to use standardized allergens for occluded patch testing whenever possible, since these have been extensively tested and shown not to induce skin irritation or sensitization. It may be necessary on occasion to use non-standardized materials. Clippings of shoes and clothing can be applied as occluded patch tests along with a small volume of water. Non-standardized compounds that are generally safe for occluded patch testing are cosmetics, moisturizers and topical medications.
Interpretation of Patch Test Reactions
All patch tests must be interpreted in the light of the patient's clinical history and the morphology of the skin lesions. Positive patch tests may not be relevant to the patient's present clinical condition and may simply represent sensitization (click for picture). Sweat and moisture are important factors in the development of contact dermatitis, since they may be necessary to leach out allergen from the contact material. For this reason in some patients, skin lesions may only occur during hot weather.
Grading of Patch Tests
|+ / -||Mild erythema and no edema||
|1 +||Erythema, edema and induration||
|2 +||Erythema, edema and isolated vesicles||Positive|
|3 +||Erythema, edema and confluent vesicles||Positive|
Standardized Patch Test Allergen Series
The standardized patch test allergen series consists of 20 commonly encountered contact sensitizers. The frequency with which these or indeed other contact sensitizers are encountered will vary between countries worldwide.
|Adhesives||Epoxy resin 1%
p-Tertiary-butylphenol formaldehyde resin 1%
Rubber compounds in rubber adhesives
Imidazolidinyl urea 2%
Neomycin sulfate 20%
|Fragrances||Balsam of Peru 25%
Cinnamic aldehyde 1%
|Hair dye||Paraphenylenediamine 1%|
|Metals||Nickel sulphate 2.5%|
|Rubber compounds||Black rubber mix 0.6%
Mercapto mix 1%
Thiuram mix 1%
|Topical medicaments||Benzocaine 5%
Ethylenediamine dihydrochloride 1%
Lanolin alcohol 30%
(Neomycin sulfate 20%)
|Rosins, waxes, polishes||Colophony 20%|
|Cement and leather||Potassium dichromate 0.25%|
(….) Indicates allergens that are repeated in different groups.
False positive patch test reactions
The causes of false positive tests are:
The petrolatum vehicle may cause a mild folliculitis, some erythema and an occasional pustule, but this reaction is around hair follicles rather than being evenly distributed throughout the patch test area.
Allergic or irritant reactions to the tape are recognized by their relation to the site of the occlusive tape rather than the patch test.
3+ reactions may induce 1+ reaction at nearby test sites. If doubt exists the tests need to be repeated a greater distance apart.
Contact dermatitis resolves spontaneously when the causative agent is identified by clinical history, site, appearance and patch testing and removed.
Neither the itching nor the inflammation of contact dermatitis responds to antihistamine therapy. However, sedating antihistamines, such as diphenhydramine and hydroxyzine, are often administered at night to help sleep.
If allergen/irritant avoidance is not possible or on rare occasions not helpful, topical corticosteroids are the mainstay of therapy. The vehicle is an important consideration.
- Gels are drying and are preferred on acute vesicular dermatitis.
- Ointments are most effective on chronic lichenified dermatitis.
- Creams are often used when patients do not tolerate ointments for aesthetic reasons.
Potent corticosteroid preparations should not be used on the face since they can give rise to:
- Acne vulgaris
- Skin atrophy
Systemic Corticosteroid Treatment
The indication for this treatment in contact dermatitis is involvement of a large area of the body and interference with essential aspects of daily life. A sufficient dose must be prescribed - 1.0mg/kg of prednisolone or its equivalent in divided doses for 2 to 4 days followed by 0.66mg/kg for 10 to 12 days. The total duration of treatment is 14 days at which time the corticosteroids are discontinued without tapering.
Patients must be informed of the unwanted effects of systemic corticosteroid treatment, in particular possible infection of the skin lesions. Blood pressure and glucose levels should be monitored.
Classification of the Potency of Topical Corticosteroid Preparations
|1||Clobetasol propionate 0.05% cream or ointment
Dirlurasone diacetate 0.05% ointment
Betamethasone dipropionate 0.05% cream or ointment
Acute dermatitis responds best to Group 1 corticosteroids.
|2||Fluocinonide 0.05% cream or ointment||
|3||Triamcinolone 0.1% ointment
Amcinonide 0.1% ointment
Betamethasone valerate 0.1% ointment
|4||Triamcinolone 0.1% cream
Fluocinolone acetonide 0.025%
|Can be used on the face for one week only|
|5||Hydrocortisone valerate 0.2% cream||Can be used on the face for longer periods|
|6||Hydrocortisone 1% & 2.5% cream or ointment||Advised for treatment of contact dermatitis inchildren|