Irritant Contact Dermatitis

Irritant contact dermatitis (ICD) is the clinical result of sufficient inflammation arising from the release of proinflammatory cytokines from skin cells (principally keratinocytes), usually in response to chemical stimuli. ICD arises as a result of activated innate immunity without prior sensitization, which differentiates it from allergic contact dermatitis. Different clinical forms may arise. The three main pathophysiologic changes are skin barrier disruption, epidermal cellular changes, and cytokine release. ^[4]

With sufficient concentration or duration of exposures, a wide range of chemicals can act as cutaneous irritants. Common cutaneous irritants include solvents, microtrauma, and mechanical irritants.

Cumulative ICD from repeated mild skin irritation from soap and water is common. For example, a hand-washing frequency that exceeds 35 times per shift has been associated strongly with occupational hand dermatitis in intensive care unit (ICU) workers (odds ratio, 4.13). ^[5] Similarly, most cases of "homemaker's" eczema are ICD resulting from repeated skin exposure to low-grade cutaneous irritants, particularly soaps, water, and detergents.

Solvents cause cutaneous irritation because they remove essential fats and oils from the skin, which increases transepidermal water loss and renders the skin susceptible to the increased direct toxic effects of other previously well-tolerated cutaneous exposures. The alcohol propanol is less irritating to the skin than the detergent sodium lauryl sulfate.

pK_a, an acid dissociation constant, is a quantitative measure of the strength of an acid in solution. pK_a has been shown to be highly predictive of acute skin irritation for acids and bases: acids with a pK_a lower than 4 and bases with a pK_a higher than 8 are highly irritative. ^[6]

Microtrauma may produce skin irritation. A common example is fiberglass, which may produce pruritus with minimal visible inflammation in susceptible individuals. Many plant leaves and stems bear small spicules and barbs that produce direct skin trauma.

Physical irritants (eg, friction, abrasive grains, or occlusion) and detergents such as sodium lauryl sulfate produce more ICD in combination than singly. ^[7] Propanol and sodium lauryl sulfate are not additive irritants, however.

Skin irritation predisposes the skin to develop sensitization to topical agents. Skin irritation by both nonallergenic and allergenic compounds induces Langerhans cell migration and maturation. ^[8] An exacerbation of ICD may reflect development of allergic contact dermatitis to topical creams, medications, or rubber gloves.

The pathogenesis of ICD involves resident epidermal cells, dermal fibroblasts, endothelial cells, and various leukocytes interacting with each other under the control of a network of cytokines and lipid mediators. Keratinocytes play an important role in the initiation and perpetuation of skin inflammatory reactions through the release of and responses to cytokines. Resting keratinocytes produce some cytokines constitutively.

A variety of environmental stimuli (eg, ultraviolet light, chemical agents) can induce epidermal keratinocytes to release the following cytokines ^[4] :

• Inflammatory cytokines (interleukin [IL]-1, tumor necrosis factor [TBF]-α)
• Chemotactic cytokines (IL-8, IL-10)
• Growth-promoting cytokines (IL-6, IL-7, IL-15, granulocyte-macrophage colony-stimulating factor [GM-CSF], transforming growth factor [TGF]-α)
• Cytokines regulating humoral versus cellular immunity (IL-10, IL-12, IL-18)

Intercellular adhesion molecule 1 promotes the infiltration of leukocytes into the epidermis in cutaneous inflammatory reactions, including ICD.

Significantly increased numbers of dividing keratinocytes are present 48 and 96 hours after exposure to the anionic emulsifying agent sodium lauryl sulfate (used in shampoos, skin cleansers, acne treatments, and toothpastes and in laboratories as an experimental irritant). However, Heinemann et al found that repeated occlusive application of 0.5% sodium lauryl sulfate over 3 weeks often resulted in adaptation (the so-called hardening phenomenon), with an increase in ceramide 1 in the lipid composition of the stratum corneum. ^[9]

All irritants provoke a similar pattern of cellular infiltration in the dermis; the densities of most of the cell types rise in proportion to the intensity of inflammation. Within the epidermis, marked differences exist in the patterns of cellular infiltration among different irritants.

Individuals with a history of atopic dermatitis are prone to develop ICD of the hands. Polymorphisms in the filaggrin (FLG) gene, which result in loss of filaggrin production, may alter the skin barrier and are a predisposing factor for atopic dermatitis. FLG null alleles are associated with increased susceptibility to chronic ICD. ^{[10, 11]}

Almost any material may be a cutaneous irritant, if the exposure is sufficiently prolonged and/or the concentration of the substance sufficiently high. The likelihood of developing ICD increases with the duration and intensity of exposure to the irritant. ^[2] Environmental factors may enhance the effect of other irritants. ^{[12, 13, 14]}

Dry air and temperature variation

Dry air renders the skin more susceptible to cutaneous irritants. Sufficiently dry air alone may provoke ICD. Most cases of winter itch are a result of dry skin from the drier air found during sustained periods of cold weather.

An increase in temperature (up to 43°C from 20°C) increases the cutaneous effect of an irritant. ^[15]

Water

Continual exposure to water may produce maceration, or repeated evaporation of water from the skin may produce cutaneous irritation through desiccation of the skin. Even distilled water experimentally provokes increased CD11c⁺ cells and neutrophils in the epidermis.

Solvents

Many individuals are exposed to solvents, particularly at work. Solvents such as alcohol or xylene remove lipids from the skin, producing direct ICD and rendering the skin more susceptible to other cutaneous irritants, such as soap and water.

ICD from alcohol most often is cumulative. Manual workers may wash their hands inappropriately with solvents to remove oil, grease, paints, or other materials and develop ICD as a consequence.

Inappropriate skin cleansing is a primary cause of ICD in the workplace. Washing facilities and methods must be inspected when investigating the workplace for one or more cases of occupational ICD. The irritating agents include aromatic, aliphatic, and chlorinated solvents, as well as solvents such as turpentine, alcohol, esters, and ketones. Some organic solvents produce an immediate erythematous reaction on the skin and remove lipids from the stratum corneum.

Metalworking fluids

Neat oils most commonly produce folliculitis and acne. They may cause ICD (as well as allergic dermatitis). Water-based metalworking fluids often cause ICD in exposed workers; surfactants in these fluids are the main culprit.

Cumulative irritant contact dermatitis

This is common in many "wet work" occupations. Healthcare workers wash their hands 20-40 times a day, producing cumulative ICD. Similar exposures occur among individuals who wash hair repeatedly or in cleaners or kitchen workers.

Multiple skin irritants may be additive or synergistic in their effects. Alcohol-based hand-cleansing gels cause less skin irritation than hand washing and therefore are preferred for hand hygiene from the dermatologic point of view. An alcohol-based hand-cleansing gel may even decrease, rather than increase, skin irritation after a hand wash, owing to a mechanical partial elimination of the detergent. ^[16]

Microtrauma

Fiberglass produces direct damage to the skin, usually manifested by pruritus that may result in excoriation and secondary skin damage. Cutaneous irritation primarily is caused by fiberglass with diameters exceeding 4.5 µm. Most workers with ICD resulting from fiberglass develop hardening, in which they tolerate further cutaneous exposure to fiberglass.

Many plant leaves and stems bear small spicules and barbs that produce direct skin trauma.

Mechanical trauma

Pressure produces callus formation. Pounding produces petechia or ecchymosis. Sudden trauma or friction produces blistering in the epidermis. Repeated rubbing or scratching produces lichenification. Sweating and friction appear to be the main cause of dermatitis that appears under soccer shin guards in children. ^[17]

Rubber gloves

Some rubber gloves may provoke direct cutaneous irritation. Many workers complain of irritation from the powder in rubber gloves.

It is important to remember that gloves compromised by a hole may allow an irritant to enter and that occlusion dramatically increases skin damage from the irritant. Occlusion accentuates the effects, good or bad, of topical agents. Kerosene may produce skin changes similar to those of toxic epidermal necrolysis following occluded cutaneous exposure. Excessive amounts of ethylene oxide in surgical sheets also may produce similar changes.

Sodium lauryl sulfate

This chemical is found in some topical medications, particularly acne medications, as well as a range of soaps and shampoos. It is also a classic experimental cutaneous irritant.

Hydrofluoric acid

A hydrofluoric acid burn is a medical emergency. It must be kept in mind that the onset of clinical manifestations may be delayed after the acute exposure (this is crucial to diagnosis). Unfortunately, hydrofluoric acid burns are most frequent on the digits, where the pain is most severe and management is most difficult (see Hydrofluoric Acid Burns).

Alkalies

Skin surfaces normally have an acidic pH, and alkalies (eg, many soaps) produce more irritation than many acids. The "acid mantle" of the stratum corneum seems to be important for both permeability barrier formation and cutaneous antimicrobial defense. Use of skin cleansing agents, especially synthetic detergents with a pH of approximately 5.5 rather than alkaline pH, may help prevent skin disease. ^[18]

United States statistics

ICD is common in occupations that involve repeated hand washing or repeated exposure of the skin to water, food materials, and other irritants. High-risk occupations include cleaning, hospital care, food preparation, and hairdressing. ^{[19, 20]}

The prevalence of occupational hand dermatitis was found to be 55.6% in two ICUs and was 69.7% in the most highly exposed workers. ^[5] A hand-washing frequency greater than 35 times per shift was associated strongly with occupational hand dermatitis.

International statistics

In some European studies among employees in high-risk occupations (eg, hairdressing, healthcare, and metalworking) the 1-year prevalence was between 20% and 30%. ^[11] Specifically, in Denmark, cleaners comprise the greatest number of affected workers, but culinary workers have the highest incidence. A higher proportion of prolonged sick leave is seen among those in food-related occupations than among those in "wet work" occupations. ^[21]

The incidence figures reported for contact dermatitis in Germany were 4.5 cases per 10,000 workers for ICD, compared with 4.1 cases per 10,000 for allergic contact dermatitis. The annual incidence of ICD was found to be highest in hairdressers (46.9 cases per 10,000 workers per year), bakers (23.5 cases per 10,000 workers per year), and pastry cooks (16.9 cases per 10,000 workers per year). ^[22]

Age-related demographics

ICD may occur at any age. Many cases of diaper dermatitis are ICD resulting from direct skin irritants present in urine and, especially, feces. Older persons have drier and thinner skin that does not tolerate soaps and solvents as well as younger individuals. Occupational hand eczema often is associated with persistent dermatitis and prolonged sick leave, with substantially greater severity among those with occupational ICD and atopic dermatitis and those older than 50 years.

Sex-related demographics

ICD is significantly more common in women than in men. The higher frequency of hand eczema in women as compared with men is caused by environmental factors, not genetic factors. Occupational ICD affects women almost twice as often as men, in contrast to other occupational diseases that predominantly affect men. Women experience greater exposure to cutaneous irritants from their traditionally disproportionately greater role in housecleaning and the care of small children at home. In addition, women predominantly perform many occupations at high risk for ICD (eg, hairdressing and nursing).

For nonatopic individuals in whom ICD is diagnosed and managed promptly, the prognosis is good. Individuals with atopic dermatitis remain highly susceptible to ICD and may find that the tasks of many common occupations (eg, nursing and hairdressing) produce too much direct skin inflammation to allow them to continue with these careers.

Hardening may be specific to the irritant inducing the hardening phenomenon and does not occur in all persons with long-term exposure to an irritant. ^[6] Hardened skin may also have a thickened stratum granulosum, with changes in the expression of various inflammatory mediators and markers. ^[6] An induction of an increase in the stratum corneum lipid ceramide 1 may play a key role as a protection mechanism against irritation by repeated application of sodium lauryl sulfate. ^{[7, 9]}

Activities of daily living (ADLs) and work may be reduced by severe ICD.

Acute ICD reactions to potent irritants (eg, acids and alkaline solutions) are comparable to a chemical burn and can be graded similarly to a thermal burn (ie, as first-, second-, or third-degree). With appropriate symptomatic management, the prognosis for this type of ICD is usually good, and unless the dermis is damaged, no permanent scarring should occur. (See Chemical Burns for more information.)

Mortality

Hydrofluoric acid is a potent cutaneous irritant used in low-technology and high-technology industries and at home in rust removal. ^[23] Death from hypocalcemia may ensue if as little as 1% of the skin's surface area is exposed sufficiently to this strong inorganic acid and if complications are not managed optimally (see Hydrofluoric Acid Burns).

Individuals must be reminded to continue to avoid cutaneous irritants; they will redevelop or aggravate dermatitis if they continue to have the same skin care exposures that resulted in ICD. The possibility of secondary or complicating allergic contact dermatitis or impetigo must always be considered as well.

For patient education information, see the Skin Conditions & Beauty Center, as well as Contact Dermatitis.