Table of Contents   This Chapter   All Chapters

ATOPIC DERMATITIS

Etiology and pathogenesis

Atopic dermatitis (AD) is an extremely common condition, especially during childhood. The prevalence of AD peaks in infancy and tapers gradually thereafter. Studies from the UK show that as many as 20% of infants have AD, while only 5–15% of prepubertal children are so affected. Patients with AD and their relatives are more likely to have asthma and/or allergic rhinitis (hay fever).

    Atopic dermatitis is caused by both a defective barrier function of the skin and by altered immune responses that include allergy to a variety of environmental and dietary allergens. IgE levels tend to be quite high. Treatment involves restoring the skin barrier function, reducing the exposure to allergens, and decreasing the patient’s immune response.

    Experimental work using an atopy patch test (APT), or aeroallergens dissolved in cream and applied for 48h, has demonstrated a type of epidermal immune reactivity different from that of allergic contact dermatitis. The APT is more likely to be positive if the patient’s eczematous lesions predominate on skin not covered by clothing (e.g. hands, forearms, head, neck, and ankles). In one study, the APT was positive for house dust mite (HDM) in 80% of patients, for grass pollen in 50%, and for cat dander in 3%, although there is wide variation: HDM gave positive results in only 36% and grass pollen in 16% in another study. In general, positive reactions to HDM are most frequent. The APT may correlate with antigen-specific IgE results by radio-allergo-sorbent test (RAST), but neither reliably correlates with patient history of HDM-related clinical problems.

    With regard to food allergy in children with AD, prick tests tend to correlate with acute skin reactions (e.g. pruritus, urticaria, and exanthema), whereas the patch test tends to correlate with delayed reactions (eczematous); this is as expected, as the former evaluate the more immediate IgE-mediated type I hypersensitivity.

Figure. 6.5  Atopic dermatitis, diffuse, with accentuation in the folds. Often there is accentuation of the flexures, as illustrated here.

Figure. 6.6  Atopic ‘dirty’ neck. The neck of an atopic may take on a brown, ‘dirty’ appearance.

Figure. 6.7  Atopic dermatitis of the lips.

Milk is more frequently a problem in children than in adults. Prick tests or RAST results to animal dander do not reliably correlate with patient’s experiences when in contact with animals.

    A further contributory factor is colonization of atopic skin with Staphylococcus aureus, and also increased nasal carriage. This can play a major part in exacerbations of the disease, as it produces superantigens that bypass the normal antigen-presenting mechanisms and directly activate T lymphocytes. Weeping of the skin and scratching allow increased staphylococcal colonization, hence more T-cell activation, and a vicious cycle is set up. Thus antibacterial measures may also be important in therapy.

    Environmental tobacco smoke aggravates AD. Parents of children with AD should be encouraged to stop smoking.

Clinical

Infants with AD may develop red, scaly lesions anywhere (Figs 6.1–6.3). In severe cases, the entire body may be affected (Fig.6.4). As the child ages, eczematous lesions gravitate toward the flexures (Fig.6.5), for example the antecubital fossa, the popliteal fossa, the neck (Fig.6.6), and the posterior gluteal cleft. In older children, wrists and ankles may be the most prominent

Figure. 6.9  Hyperlinear palms and lichenification. Atopic patients often develop accentuation of the palmar creases.

Figure. 6.13  Bacterial secondary infection in atopic dermatitis. Atopic skin often harbors significant numbers of bacteria. Overt infection is common and is manifested by areas of erosion, crusting, or oozing. Superinfection by Staphylococcus is most common. This patient developed a secondary infection by Streptococcus.

site of involvement. AD may persist into adulthood as frank, diffuse eczema. More often, however, the patient is affected by localized disease, for example lip (Fig.6.7), eyelid (Fig.6.8), retroauricular, facial, or hand dermatitis (Fig.6.9).

    Early lesions of AD are red and scaly. Chronic lesions that have been scratched may appear as lichenified plaques with excoriation (Figs 6.10 and 6.11); chronic scratching or rubbing, as well as the inflammation of the disease itself, may lead to pigmentary disturbance (Fig. 6.12). Secondary bacterial infection is a complicating factor (Fig.6.13), as discussed earlier. Chronic scratching precipitates and exacerbates both the dermatitis and the infection. Features of associated asthma or hay fever may be present (Fig.6.14), usually in slightly older children, and vascular hyperreactivity may occur (Fig. 6.15).

    A persistent red face pattern has been described in adult AD, and probably has various causes. In some this may represent HDM exposure (e.g. in pillows), in some it is probably due to Pityrosporum sensitivity or seborrheic dermatitis, in some it is at

Figure. 6.15  White dermatographism. There is a vascular reactivity in atopic patients that can create a white line on scratching. It may also occur in other erythrodermas.

least in part a corticosteroid-induced rosacea, and in others it may represent a contact allergy (e.g. due to topical corticosteroids that may have been applied long term).

    Various criteria for diagnosing AD have been proposed. One of the most recent is by the UK working party and is outlined in Table 6.1. Minor diagnostic criteria include nipple eczema (Fig. 6.16).

Trigger factors
House dust mite

There seems to be sufficient evidence now to implicate the HDM, Dermatophagoides pteronyssinus, as a trigger factor for AD. However, thorough avoidance of HDM is difficult, and there are conflicting results of trials of avoidance (especially in adults).

Food
Various foods can exacerbate AD, especially in children, the most common being eggs, peanuts, milk, fish, soybeans, and wheat. Adults may give a history of their disease being exacerbated by foods. In adults, milk-inducible eczema and casein-specific T cells are commonly found. Often, the flare is delayed—occurring 24 h after consumption of the offending food—and this should be distinguished from immediate urticarial reactions, which, while they may aggravate AD by leading to increased scratching, are not dermatitis and require oral antihistamine therapy rather than topical corticosteroids or other immunomodulators. Unfortunately, there is no reliable test to establish such a cause and effect role for dietary agents, short of a double-blind, placebo-controlled food challenge; RAST positivity, for example, does not always correlate with actual sensitivity (although prick tests or RAST are more reliable in the urticarial pattern of food reactions, as they measure type I hypersensitivity). Such tests are more valuable in excluding the presence of IgE-mediated food allergy than in proving a link with eczema or for predicting severity.

    It is clear that clinically relevant food-induced worsening of eczema is more likely in those with moderate or severe disease than in those with mild AD. If there is a clear history of reactions to specific foods, then there is evidence that avoidance may be helpful; however, undirected elimination diets should be avoided. It is also important to be aware of the effects of dietary restriction on nutritional status, and especially on growth in children. Usually, clinical testing and decisions about dietary intervention are made by the allergist, those who are most likely to benefit being children with moderate to severe AD that responds poorly to conventional therapy, or those with a clear history of dietary triggering.

    There is no unanimous evidence about the role of maternal avoidance of dietary agents or of aeroallergens during pregnancy or during breast-feeding, in terms of either the likelihood of the child having atopic eczema or of the severity if the child is affected. Prolonged breast-feeding may delay onset of clinical eczema, as may probiotic therapy with Lactobacillus, but probably have little protective effect on development of the disorder. The same uncertainty surrounds the role of supplements such as oil of evening primrose or its purified formulations.

Contact allergens
In an intriguing study, 25 of 39 children less than 2 years of age admitted to a hospital for AD tested positive for a contact allergen (standard allergic contact dermatitis allergens). Allergen avoidance was very helpful in the therapy of most of these children. However, this was probably a very selected group. In general, type IV contact hypersensitivity is unusual in children, especially if their clinical pattern is typical of AD for the age group, but those children not responding to standard therapy may benefit from patch testing.

Other factors that aggravate eczema
These include the following.

• Clothing—wool or other rough clothing may be irritating (Fig. 6.16); cotton clothing is better tolerated.
  
• Airborne irritants—exacerbation of eyelid involvement by chlorine or cigarette smoke has also been reported, although this pattern may also occur due to habitual rubbing (especially if there is associated watering of the eye due to allergic atopic conjunctivitis).
  
• Hormonal—premenstrual flaring is common, and pregnancy, parturition, or menopause may also be trigger factors.
  
  Stress—whether stress alone can cause a flare of AD is unclear.

• Sweating—in some patients, sweating can cause pruritus, scratching,
  and thus more eczema; in a recent study, activities that provoked sweating were viewed by patients as the most important factor in aggravation of their eczema. Most patients’ conditions are worse during dry, cold winters, but some may experience exacerbations during the summer.
  
• Others—the season of birth, animal exposure during the first few months of life, and exposure to viral infections have all been proposed to influence incidence or severity of AD.

Differential diagnosis
A list of differential diagnoses is given in Table 6.2.
    A red, scaly, itchy rash in an infant is most commonly AD, but infantile seborrheic dermatitis should be considered if the rash predominates in the scalp, axillae, and groin, or if the appearance of the rash is florid while the degree of itch is less prominent. Scabies should always be considered and the presence of burrows excluded.
    In a child, except for scabies, the differential possibilities are few. Rarely, pityriasis rubra pilaris, psoriasis, and cutaneous T-cell lymphoma (CTCL) will present in a similar fashion.
    When an adult presents with the recent onset of an eczematous rash, one should exclude scabies and contact dermatitis. Patch testing is usually necessary. Excessive water contact may precipitate asteatotic eczema. Occasionally, drugs will cause a drug eruption with an eczematous morphology. Tinea corporis may be suggested by annular, raised edges.

Treatment
An overview of treatment is provided in Table 6.3.

Basic skin care and approach to therapy
The singular admonition to not scratch is of paramount importance and should be reinforced during every visit. When the child is very young, such intervention is unrewarding; only older children may follow such direction. Daily bathing is useful, but patients should avoid baths or showers lasting longer than 5 min, avoid unduly hot water, and pat dry. A mild soap (e.g. non-deodorized and uncolored) or a soap substitute should be used to avoid the irritant effects of soaps and detergents; patients should avoid harsh shampoos or any use of bubble bath products. Topical emollients and medicines should be applied to the skin within minutes of the bath or shower to lock in the moisture, for example an emolliating cream or ointment to the non-inflamed skin plus either a topical immunomodulator or steroid to the active, eczematous areas. Because of their high water content, lotions are less effective. Bath emollients, with or without an antiseptic as determined by the clinical picture, appear to be helpful in some instances but generally have limited emollient effect.

Topical steroids
Topical steroids have been the mainstay of therapy for decades. They should be used when emollients are not sufficient. However, it is important that patients or parents do not use them for the emollient effect of the base. A useful rule is to use emollients for dry skin but steroids for red skin. Often, steroids are needed for thicker-skinned areas such as the trunk and extremities of adults, and some patients need to use different potencies for different sites, or different frequency of application for different sites. In general, studies suggest that once-daily application is as effective as more frequent use, with emollients at other times. Medium-potency topical steroids such as triamcinolone are appropriate for mild to moderate disease, with higher-strength steroids reserved for severe disease.
    As discussed in Chapter 3, there are several potential local side effects of steroids, and even the potential for systemic absorption and hypothalamic–pituitary axis suppression. However, such effects in normal use are very uncommon; some relate mainly to the enthusiasm that followed introduction of high-potency fluorinated steroids. The greatest risk of systemic problems is in young children with severe eczema, but it should be noted that AD in itself may lead to growth retardation. The best way to avoid excessive use of steroids is by experience of judging eczema severity combined with elimination of triggers (food allergy and secondary infection); use of adjunctive therapy (emollients, topical immunomodulators, bandaging, appropriate clothing, oral antihistamines, etc.); and adequate time, explanation, and demonstration of treatment application by a dermatology-trained nurse.

Topical immunomodulators
Topical pimecrolimus and tacrolimus have made a dramatic impact on the therapy of AD. They both appear to be safe and effective, and most significantly lack the potential for cutaneous atrophy inherent with topical steroids. Pimecrolimus and 0.03% tacrolimus equate to hydrocortisone potency, and 0.1% tacrolimus to moderate steroid potency, in terms of clinical effectiveness. They are particularly helpful for eczema of the face and neck in both adults and children, and should probably be used as the foundation of therapy for active eczema of the face, neck, and flexures. However, they are contraindicated in the presence of infection, may cause initial burning or stinging, are much more expensive than equivalent-potency steroids, and their longer-term skin cancer risks are unknown (they are similar to drugs used for systemic immunosuppressive therapy, in which skin tumor risk is significant).

Other therapies
The primary method for decreasing the itch of eczema is to decrease the eczema. Scratching, of course, makes the eczema worse, but some patients seem unable to stop scratching and need more intervention than just topical steroids. Hydroxyzine is a time-honored intervention. When given routinely (e.g. 2mg/kg per day every 6h while awake and before sleeping), it can help decrease the itch. It should be noted that antihistamines are not thought to improve the rash directly, but they merely decrease scratching. Much of the evidence suggests that they do this through sedation, and are thus especially indicated for patients with nighttime itch. Bandaging, either with tar- or emollient-impregnated bandages, or with wet wraps, may be useful, especially for acute flares of AD or to occlude lichenified areas where scratching has become habitual. Mittens, especially in bed at night (even sewn to pajamas) may be helpful to reduce scratching.
    Topical doxepin is very helpful for reducing the itch in localized areas. If applied over a large area, sedation may result. The use of special silk fabric improved AD compared with use of cotton clothing in one study of 46 children.
Many other therapies have been suggested but have limited or conflicting evidence; some are listed in Table 6.3.

Figure. 6.17  Atopic infant. The infant with atopic dermatitis is often quite unhappy, the skin is very itchy, and sleeping is difficult.

Sleep difficulties
One study found that children with AD who have sleep difficulties usually experience them during AD flares and may keep their parents up for 2–3 h a night on average. Those strategies rated by the parents as most successful were putting creams on the child, using cotton clothes, keeping the room cool, using wet wraps, putting very few blankets over the child, and cuddling the child. Bringing the child into the parents’ bed seemed only to prolong the problem (Fig. 6.17).

Treatment for severe atopic dermatitis in a child
For children with moderate to severe AD, unresponsive to topical therapies, the following may be considered.

Treatment for severe atopic dermatitis in an adult
All the above measures for children should be considered. Systemic therapies and phototherapy are more likely to be tried in adults, due to disease chronicity and the fact that adult AD often affects the whole body. Measures listed in Table 6.3, such as consideration of patch testing, are also important, particularly if there has been a change in clinical pattern.
    Treatments that may be considered in adults include the following (see Table 6.3 for a fuller list).

Role of the dermatology nurse
Anecdotally, for many years, dermatologists have utilized the skills and knowledge of their nursing staff to help in management of AD and other eczemas. The benefits of this approach are now supported by scientific study. There is a huge amount of information for patients and parents to assimilate regarding causation and treatment, and many of these issues relate to practicalities regarding bathing, how and when to use treatment, strengths of treatment, how to apply bandages, how to cope with itch or flares, etc. This cannot be taken in at a single clinic visit, no matter how prolonged. Using a nurse to reinforce the discussion and to demonstrate treatment and bandage application is immensely useful. In the UK, many nurses in hospital departments have extended this educational role and now run eczema clinics, are trained to prescribe, and can take on treatment of many children with AD. A similar process in primary care is entirely feasible, particularly with good links with the local hospital for shared care, but is rather more limited to enthusiasts rather than being the accepted norm.

Prognosis

Generally, it has been thought that most infants or young children with AD outgrow it over several years. However, one recent study found that, after 20 years, 72% of patients were still affected by micromanifestations (e.g. perlèche, eyelid dermatitis, retroauricular dermatitis, and dry, cracked fingertips). Nummular

Figure. 6.18  Eczema herpeticum in a child. A periorbital distribution is not infrequent.

Figure 6.19  Eczema herpeticum in a child.

dermatitis was not seen in this population. Thus parents should be told that their child’s skin disease will most likely improve, but that he or she may always have a tendency toward dry skin and eczema. In particular, older children need advice about occupations that might cause aggravation or recurrence of their eczema; hairdressing is the notable culprit but any irritant exposure may be relevant. Armed forces may not accept applicants with atopic disease.

PRACTICE POINTS

•	Always consider secondary infection as a reason for a flare of atopic dermatitis (AD), especially infections due to Staphylococcus aureus (or less commonly, see below, herpes simplex).
•	For the adult who presents with ‘new onset’ eczema, inquire about any eczema as a child, as adults with a history of AD may have experienced a recurrence in cold weather, when water exposure is high (e.g. when taking a water aerobics class or showering multiple times per day), or if exposed to an offending allergen (e.g. from dog or cat)
•	In adults with known AD but with a change of pattern or severity, consider the possibility of a contact allergy (always include treatment agents in the test series).
•	Patients with AD (and their parents) need ample discussion of bathing, soaps, emollients, itching, sleep time, clothing, pets, etc. A trained nurse who can provide this care is a major asset

Figure. 6.20  The face of a patient with eczema herpeticum. The patient with atopic dermatitis is predisposed to infection not only by Staphylococcus aureus but also by herpes simplex. Rapidly progressive, widespread, crusted papules, vesicles, and erosions are characteristic of this viral infection.

Figure 6.21  Close-up view of eczema herpeticum. Crusted lesions in the atopic patient may represent bacterial or viral infection. At times, only culture will distinguish between the two.

Figure. 6.22  Close-up view of eczema herpeticum, showing classic umbilicated vesicles.

White/Cox: Diseases of the Skin, 2ed.(c) 2006, Elsevier Inc. All rights reserved.