25 - IRRITANT DERMATITIS

Question 1

Define dermatitis

Answer 1

Dermatitis is an inflammatory disruption of the epidermis related to physical or immunologic provocation.

Dermatitis and eczema are often used interchangeably.1 Dermatitis appears as spongiosis histologically. There is impairment of the barrier functions of the skin, which results in increased transepidermal water loss.

Question 2

What causes irritant dermatitis?

Answer 2

As Fig. 25-1 illustrates, dermatitis is usually multifactorial. Irritant dermatitis results in barrier disruption which may predispose to higher concentrations of bacteria and yeast, and these microorganisms may stimulate immune response. 2-4 Immune signals from barrier disruption also predispose to allergic contact dermatitis to chemical antigens.

Irritant dermatitis begins with damage to keratinocytes, which then release danger signals that promote recruitment of inflammatory cells. In severe cases, necrotic keratinocytes are evident.

Irritant dermatitis is caused by physical damage to the epidermis and is temporally more immediate after provocation than the delayed hypersensitivity response leading to allergic contact dermatitis. Many variables influence expression of irritant dermatitis including climate and season, occlusion, frequency of exposure to the irritant, and concentration of the irritant.

Question 3

What causes Dermal injury producing scarring?

Answer 3

Dermal injury producing scarring can result from corrosive chemicals that coagulate protein and cause cutaneous scars. Corrosive chemicals are not further discussed in this chapter. Irritant chemicals by definition do not cause scarring when in contact with the skin for less than 4 hours. 6 Rarely, scarring can result from secondary infection of dermatitis, but not from uncomplicated dermatitis.

Question 4

common site for irritant contact dermatitis

Answer 4

Hand dermatitis

Repeated wetting and drying of the skin causes fissuring, especially if drying is rapid because of low ambient humidity.

Question 5

Define irritant hand dermatitis

Answer 5

Irritant hand dermatitis has been defined as “A documented exposure of the hands to an irritant, which is quantitatively likely to cause contact dermatitis. No relevant contact allergy (no current exposure to allergens to which the patient has reacted positive in patch test).”

Question 6

Differentiate irritant vs allergic contact dermatitis

Answer 6

Question 7

Irritants Encountered in Various Occupations

Answer 7

Question 8

common irritants encountered outside of work

Answer 8

Question 9

how does stasis dermatitis occur?

Answer 9

Stasis dermatitis occurs when swollen lower legs experience barrier disruption caused by stretching. Lymphatic obstruction accentuates inflammation in mice when challenged with the irritant croton oil. When challenged with the sensitizer dinitrofluorobenzene, mice with lymphatic obstruction had more swelling than those without, but also had lower levels of the inflammatory signals interferon-γ, tumor necrosis factor-α, and the chemokines CXCL9 and CXCL10 than did mice without lymphatic obstruction, suggesting that the increased swelling is a consequence of fluid retention rather than accentuated allergic contact dermatitis.

Question 10

Cutaneous findings of ICD

Answer 10

Epidermal disruption is the primary finding in irritant dermatitis, as opposed to allergic contact dermatitis which displays proportionately more dermal inflammatory infiltrate. Irritant contact dermatitis is characterized by redness, fissuring, oozing, and pain.

Question 11

Answer 11

chronic irritant contact dermatitis with epidermal thickening and pigment change.

Question 12

Answer 12

irritant patch test created by applying sodium lauryl sulfate 2.5% under occlusion. Note that there is scorched appearing skin surface without much induration. Irritant dermatitis, like this patch test, usually demonstrates more epidermal than dermal inflammation.

Question 13

Answer 13

severe acute irritant dermatitis can also produce blisters.

Question 14

Answer 14

Allergic contact dermatitis can occur with irritant dermatitis and is more likely to present with the symptoms of itch and more likely to demonstrate induration. Figure 25-5 shows an allergic patch test result. Note that there is more induration than epidermal change.

Question 15

Answer 15

Flexural accentuation is an important sign of irritant dermatitis. Common areas for irritant dermatitis are folds in the eyelid, neck, antecubital fossae, volar wrist, and intertriginous regions.

In the cases of irritant hand dermatitis and of diaper rash, irritant dermatitis is more apparent in finger webs and creases (Fig. 25-6) and intertriginous folds, respectively, where irritants concentrate, and is worsened by increased pH from soaps and feces, respectively. Irritant cleansers cause predominantly flexural dermatitis where the concentration of irritant is highest because of occlusion.

Question 16

Answer 16

Figure 25-7 shows flexural accentuation of acute dermatitis in a patient who inadvertently applied a cleanser, mistaking it for an emollient, to the entire surface of both legs.

Question 17

Answer 17

Retinoid dermatitis also preferentially involves folds such as the nasolabial fold. This is often noted several days after starting cutaneous application, as retinoids produce a delayed irritant reaction. 26 Figure 25-8 shows irritant dermatitis on the neck in a patient who began applying tretinoin daily to the neck after tolerating long-term use on the face.

Question 18

Answer 18

Glove use can protect skin from water and detergents, but perspiration or leakage of moisture around the cuff can occlude moisture under the glove causing maceration from perspiration. Rapid drying of the retained moisture when the glove is removed causes even more damage to the epidermis. Figure 25-9 shows a patient with underlying hand dermatitis who aggravated the dermatitis by wearing occlusive gloves.

Question 19

Pathogenesis of ICD

Answer 19

STEP 1: EPIDERMAL INSULT

The barrier function of the epidermis can be diminished by solvents that remove lipids from the upper epidermal layers, or by desiccation of the stratum corneum from repeated rapid drying. Genetic factors, such as filaggrin mutations, lower the threshold for epidermal damage to include even minor friction.

STEP 2: DANGER SIGNALS

Damaged keratinocytes release danger signals termed alarmins that are analogous to pathogen associated molecular patterns that defend against infections. Examples of candidate alarmins include defensins and uric acid, which may be operative in psoriasis and other inflammatory skin diseases in addition to dermatitis. In fact, the signals from epidermal trauma that drive koebnerization in psoriasis may be different than those in dermatitis and may explain the differences in downstream cytokines that explain the inverse relationship between psoriasis and autoimmune disease and allergic dermatitis.34

These danger signals can bind toll-like receptors and promote inflammatory pathways such as nuclear factor-κB that link to the adaptive immune response leading to allergic dermatitis.35

STEP 3: POTENTIAL FOR ALLERGIC SENSITIZATION

Chemical allergens and microorganisms stimulate the innate immune system, and toll-like receptors play an important role in mediating both irritant and subsequent allergic contact dermatitis.

Irritant dermatitis predisposes to allergic sensitization to antigens that would not normally cause allergic contact dermatitis on noninflamed skin.

Potent sensitizers that can cause allergy on previously noninflamed skin are dependent on their inherent irritant properties. Athymic mice, as an example of intact innate response without adaptive response, mount a neutrophil response and some diminished T-helper (Th)1/Th2 cell response to the sensitizer oxazolone, while FcγR knockout mice, as an example of intact adaptive response without innate response, have a greatly diminished response when sensitized and rechallenged with oxazolone.

Question 20

Answer 20

Childhood-onset dermatitis, also known as atopic dermatitis, is associated with inflammatory responses to common organisms such as Staphylococcus aureus, Malassezia sympodialis, and Alternaria. These organisms may exist as part of a biofilm that concentrates microorganisms and their antigens and may lead to an allergiclike immunologic response to these organisms.38 Figure 25-10 shows a positive patch test to M. sympodialis yeast in a patient with adult-onset dermatitis of the neck and upper torso (Fig. 25-11).

The immune response to microbial allergens is distinct from allergic contact dermatitis to potent

conventional sensitizers that function as their own irritants on normal-appearing skin. Weakly potent antigens such as propylene glycol, defined as negative in the guinea pig local lymph node assay, 39 are more likely to cause contact allergy in patients with barrier disruption triggering “danger signals.” In general, patients with ongoing innate immune signals from either genetic barrier dysfunction or wet work become sensitized to less potent allergens as measured by the local lymph node assay.40

Patients without preexisting irritant dermatitis are more likely to become sensitized to potent antigens that likely create their own innate signal, such as poison ivy. Innate signal from disrupted skin barrier, together with the irritant signal of a potent antigen, may drive dendritic cells into the dermis and promote immunologic tolerance. 41 This is consistent with the observation that patients with atopic dermatitis are less likely to exhibit dermatitis to the potent allergen in poison ivy that is also a strong irritant.

Question 21

Answer 21

Infants with irritant dermatitis around the mouth from drooling are at risk for allergic contact sensitization from food contact with the inflamed skin. Foods are generally weak allergens and do not sensitize noninflamed skin. If initial food exposure is on mucosa, tolerance develops. 42 This likely explains the higher incidence of peanut allergy in the Unites States where initial peanut exposure is often by self-feeding peanut butter as opposed to the 10-fold lower incidence Israel where initial exposure is to soft baked peanut bambas, which are placed into the mouth directly.

Patients with atopic dermatitis often, but not always, have only a transient Th1 response to cutaneous contact sensitization. This might explain the tendency for atopic dermatitis to improve as children get older. These patients also develop a more persistent Th2 skewed response 43 that might contribute to the atopic march. Figure 25-12 shows the typical perioral inflammation seen with infantile dermatitis that can be complicated by contact sensitization and food allergy with delayed and immediate type hypersensitivity (the atopic march).

Although there is no prospective study to confirm the recommendation, new foods should logically be introduced when there is no perioral irritant dermatitis and fed with an infant feeding spoon directly into the mouth rather than being self-fed, which results in substantially more skin contact.

Question 22

measure of the ability of the skin to maintain homeostasis of fluids in the body

Answer 22

Transepidermal water loss (TEWL)

In addition to the stratum corneum, tight junctions between living keratinocytes contribute to skin barrier function and provide defense between microbial pathogens and their ligands including tolllike receptors. 44 TEWL is a measure of barrier function and increased TEWL indicates increased permeability to antigens. 45 TEWL is not routinely tested in clinical practice but is used in research studies of irritant contact dermatitis.

Question 23

histopathologic findings of ICD

Answer 23

All forms of dermatitis show intercellular edema, or spongiosis, of the epidermis. In the acute phase, there is more fluid which correlates with the clinical presence of vesicles, bullae, and crusting. With chronicity, the stratum corneum exhibits hyperkeratosis, and there is less spongiosis. Figure 25-13 shows the features of subacute dermatitis. In very chronic dermatitis, there is even less spongiosis, no crusting, and elongation of the rete ridges in the epidermis and dermal fibrosis.

Question 24

DIAGNOSTIC ALGORITHM for ICD

Answer 24

Diagnosis of irritant dermatitis begins with a detailed history of potential irritants, temporal course of symptoms, and examination for evidence of flexural accentuation. In patients with severe inflammation and itch, allergic contact dermatitis needs to be investigated with appropriate testing.

An example is shown in Table 25-4 for a patient with complaint of itching and redness of the hands after wearing rubber gloves for wet work where irritant contact dermatitis, contact urticaria, and allergic contact dermatitis are considered. Contact urticaria to latex is an example of a contact allergen that is more common in atopic patients and where the allergic contact sensitization has a more persistent Th2 than Th1 response.

Question 25

Examples of Allergens Speculated to Be Most Likely to Cause Sensitization Based on the Type and Severity of Preexisting Irritant Contact Dermatitis

Answer 25

Question 26

Irritant dermatitis often resolves despite continued exposure to the irritant; this is known as _________

Answer 26

HARDENING

The process is incompletely understood, which makes it difficult to know which patients will go on to develop chronic irritant hand dermatitis. 51 In a prospective experiment, participants challenged with repeated higher concentrations of sodium lauryl sulfate were more likely to harden than those challenged with lower concentrations or distilled water. Only about half of all participants hardened. Those who hardened and those who did not had similar measurements of hyperkeratosis and ceramide content of the stratum corneum.52

This area represents a tremendous knowledge gap. Hardening is the ideal response to unavoidable chronic irritant exposure. Understanding how to promote hardening could reduce the impact of allergic complications of irritant dermatitis including allergic contact dermatitis and atopic diseases.

Question 27

TOPICAL PREWORK PRODUCTS for ICD

Answer 27

British standards for occupational contact dermatitis suggest that the term prework cream replace barrier cream to avoid the suggestion that creams can replace more effective barrier equipment such as protective gloves. 53 These creams, designed for application prior to irritant exposure, may be modestly effective in some circumstances. A systematic review of barrier creams revealed considerable variation in methodology. The reviewers point out that participants were often tested on the forearm or back, rather than the hand, which is the most frequently affected site. Friction and multiple flexures on the hands may increase the risk of irritation at this site. 54 Barrier creams may not be applied in the same quantity in the workplace as in the studies. Barrier creams were more effective for preventing irritation from the detergent sodium lauryl sulfate and the alkaline sodium hydroxide than against the solvent toluene.

Question 28

MEDICATIONS

Answer 28

Given the weak evidence for the most commonly used treatments, avoidance of irritants is the best treatment option.

Although not clearly effective for prevention of hand dermatitis, use of emollients is recommended for treatment of hand dermatitis, even though some emollients appear to increase the penetration of allergen and irritants, and it is not clear which emollients are best in specific settings. 56 Only some emollients, usually with high lipid content, including petrolatum, accelerate barrier repair in experimentally induced irritant and allergic contact dermatitis.57

Topical corticosteroids are frequently used, but chronic use may impair barrier function by thinning the epidermis. 26 Topical immunomodulators may be of some benefit but are not consistently more effective than vehicle alone.26

Although rarely needed for purely irritant dermatitis, phototherapy and systemic immunosuppressive medications are often used for multifactorial dermatitis, such as hand dermatitis. Alitretinoin is considered second-line therapy for chronic hand dermatitis in Europe, 56 but is not available in the United States as of 2018.

Question 29

Answer 29

Avoidance of irritants, including use of water-resistant gloves for wet work, is the best strategy to prevent and treat irritant dermatitis. In people without other irritant factors, that is, no history of childhood onset dermatitis to suggest genetically impaired barrier function, no use of irritant chemicals at work, infrequent wet work, occlusive gloves are well tolerated. However, occlusion alone can cause inflammation in skin that is already irritated. 60 Figure 25-14 shows a patient with atopic dermatitis where polyethylene film alone applied to the skin for 24 hours caused visible inflammation as did the adjacent 3 patch tests to sodium lauryl sulfate.

Occlusive gloves should be used for wet work but only worn for the shortest time possible. In persons with preexisting irritant dermatitis, cotton gloves are recommended under occlusive gloves if the duration of glove usage is longer than 10 minutes.

People who itch with occlusion often also report itching with perspiration. The same factors that contribute to irritant dermatitis under gloves also cause irritation under bandages that mimic allergic contact dermatitis to adhesive.6

Patients who itch with occlusion generally prefer foam, lotion, or cream vehicles for topical products as they find ointments to cause itching.

Question 30

TREATMENT ALGORITHM

Answer 30

Dermatitis should be treated as soon as it is recognized, as chronic dermatitis has a worse prognosis than acute dermatitis. All irritants should be avoided for weeks beyond visual recovery. There was lowered irritancy threshold lasting longer than 10 weeks after visual recovery from experimentally induced dermatitis from sodium lauryl sulfate applied 15 times to forearm skin over 3 weeks.62

The British guidelines for occupational contact dermatitis suggest referral to a dermatologist knowledgeable about patch testing for occupational contact dermatitis if there is no improvement 3 months after initial evaluation for dermatitis and if there is suspicion for allergic contact dermatitis or changes to job duties are contemplated.

Question 31

PREVENTION OF IRRITANT DERMATITIS

Answer 31

A systematic review published in 2010 found no significant evidence to prove efficacy of gloves, barrier creams, emollients, or worker education programs in preventing occupational irritant hand dermatitis.

Barrier creams were discussed in the section “Topical Pre-Work Products” earlier. There are studies that show some emollients may provide some degree of prevention when used prior to developing dermatitis rather than as intervention for dermatitis. A study of normal volunteers who washed their hands 15 times daily with an antiseptic soap to mimic hand hygiene in health care workers found that 3 of 5 emollients decreased visible irritation and TEWL compared to no emollient.

Duration of application prior to exposure may influence the degree to which it provides protection from an irritant. An emollient applied 15 minutes prior to exposure to sodium lauryl sulfate (SLS) prevented irritation as measured by TEWL, but daily use of the same emollient increased irritation after sodium lauryl sulfate exposure. This suggests that hydrated skin may be more susceptible to irritants and that prolonged use of emollients may actually increase the risk of irritant contact dermatitis.

Question 32

PREVENTION OF COMPLICATIONS

Answer 32

In regard to prevention of atopic dermatitis as a complication of irritant dermatitis resulting from genetic barrier deficits, a randomized controlled trial of daily application of emollients in infants from 3 weeks to 6 months of age showed a significant benefit in favor or emollients compared to no emollients. Thirteen percent of the control group used emollients despite randomization to the nonemollient group, and the authors did not comment on seasonal comparability of the control groups during this year-long study in cities in Oregon and the United Kingdom. Cream-based emollients were favored by parents in this study over oil- and ointment-based emollients.66

Another study of daily versus occasional application of petroleum jelly to infants from birth to 32 weeks of age showed lower incidence of dermatitis in the daily application group, but no significant decrease in sensitization to egg white as measured by antigen-specific immunoglobulin E to egg at 32 weeks of life.

Prevention of both irritant contact dermatitis and its complications is understudied as discussed in the section “Clinical Course and Prognosis” on hardening. We do not know the components of emollients least likely to cause allergic contact dermatitis in various populations, the ideal pH of emollients, or the effect of various types of emollients on potentially inflammatory components of the microbiome.