What You Should Know About Atopic Dermatitis

     Atopic dermatitis (AD) has a multiplicity of clinical presentations and many authorities consider it to be a syndrome. It is a chronic inflammatory pruritic skin disease that is often associated with elevated serum IgE levels and a personal or family history of type 1 allergies, allergic rhinitis and asthma. This condition is made up of a group of specific signs and symptoms that characterize the dermatological expression of the atopic diathesis.

     Atopic dermatitis predominantly affects infants, children and young adults. Approximately 60 percent of the cases are diagnosed within the first year of life and 90 percent of all cases are diagnosed by the age of 5. Only 10 percent of AD cases are diagnosed over the age of 5 and it is rare for the condition not to be identified before a patient reaches his or her teens. The condition follows a relapsing course and most adults who suffer from AD have had it nearly all of their lives. However, a very small percentage of adults may first develop AD after the age of 18.

     Even though there are a few limitations in the clinical diagnosis of AD, the world literature continues to note AD as a common condition that is becoming more widespread. Some believe this increase of atopic disease in developed countries can be attributed to reduced microbial exposure in early life. Antiseptic soaps, skin cleansers, antibacterial household sprays, mouthwashes, floor cleaners and a large list of other “hygiene” products may have been the basis for this increasing occurrence of AD.

     In spite of the high prevalence of AD, there is still a lack of generalized consensus regarding the diagnosis, treatment and follow up of this condition. Unfortunately, since this problem is called, among other things, pediatric eczema, atopic eczema and atopic dermatitis, the diagnostic criteria and true prevalence of AD will [3] continue to remain inaccurate. The incidence of AD is further complicated by the common pattern of frequent remissions and changeable clinical courses, especially with the milder forms of AD.

A Few Thoughts On The Etiology And Pathophysiology Of AD

     There is no strong consensus on the etiology of AD but the greatest risk factor is a parental history of atopy or isolated eczema. The term atopy is generally and probably simplistically used to describe the clinical presentation of type I hypersensitivity, which one may see among patients with asthma, hay fever, eczema, urticaria and assorted allergies to food and/or wool products.

     Maternal atopy conveys a greater risk for offspring having atopic disorders than paternal atopy. Additionally, AD is inversely related to the number of siblings. In other words, the larger the family size, the less likely a child will have AD. As noted earlier, AD and atopy seem to be conditions of the advantaged classes in developed countries with a definite trend toward an increase of AD cases in these industrialized nations over the past few decades.

     Other than the genetic etiology, some still consider food and environmental antigens to be factors in the pathogenesis of AD. Atopic dermatitis is usually worse in extremes of climate. Generally, the condition poorly tolerates heat and extreme cold. A dry atmosphere in winter increases dry skin and exacerbates AD. On the [4] other hand, sun exposure improves the eczema but sweating increases the pruritus.

     Studies suggest there is an aberration of T helper 2 cells that results in an augmented production of interleukin-4 and increased IgE levels. This excess of interleukin-4 causes decreased interferon gamma levels. Tissue cells react with environmental antigens to produce increased levels of IgE. There are associated increases of serum and cellular histamine release and some believe these increases may be due to mast cell release from antigen-antibody reactions.

     Dry skin or xerosis is secondary to abnormalities of the stratum corneum lipids, which result in increased transepidermal moisture loss. Abnormalities of prostaglandin metabolism may also occur during this process. Additionally, the dry skin may allow antigens through the normal skin barrier, thereby setting up the abnormal interleukin response. These factors also predispose atopic patients to cutaneous viral and Staphylococcus aureus infections of the skin.

Essential Diagnostic Tips

     For most practitioners, it is not difficult to recognize AD in a newborn or infant with a very extensive eczematous rash. These patients may have an older sibling or other family member who has eczema, upper respiratory conditions, asthma or hay fever. However, when these conditions are not all present, when the patient [5] is older or the clinical signs and symptoms are somewhat altered, it may be more difficult to arrive at the diagnosis. In these cases, one diagnoses AD by exclusion. A clinically useful set of criteria for the diagnosis of AD includes atopy, pruritus, eczema and an altered vascular reactivity.

     One established guide lists major and minor features of AD (see “Assessing Major And Minor Diagnostic Criteria Of AD” on page 52). Using this guide, the patient should have a minimum of three features in the minor criteria and a minimum of three features in the major criteria in order to make the diagnosis.¹ In most individuals with AD, it is not difficult to find three items in each group that are positive.

     Another recently developed criteria for the diagnosis of AD offers a modified variation of the aforementioned guide.2 Under the proposed guidelines by Williams, patients must have an itchy skin condition or a parent reports that his or her child is scratching or rubbing an itchy area. The guidelines also note that patients must have three or more of the following:

     • a history of involvement of the skin creases or folds (i.e., at the elbows, behind the knees, the front of the ankle or the neck);
     • a personal history of asthma or hay fever or a history of atopic disease in a first-degree relative in patients younger than 4 years of age;
     • a history of generally dry skin in the last year;
     • visible flexural dermatitis or dermatitis involving the cheeks or forehead, and the outer limbs in children younger than 4 years of age; and/or
     • an onset of the condition in patients younger than the age of 2.2

A Review Of Characteristic Presentations By Age

     The distribution of the eczema of AD is variable and age-related. Since AD causes the skin to itch, the primary reaction of the skin appears when it is rubbed or scratched. This irritation subsequently causes the skin to erupt and the eczema to present. Accordingly, the distribution corresponds to the areas of the body that are accessible to scratching and rubbing.

     In infants, the dermatitis is characterized by symmetric lesions on the ankles, feet, flexor areas of the extremities, cheeks, forehead and the scalp. Along with facial erythema, there may be perioral pallor that makes the erythema seem prominent. It is fascinating, though, that the diaper region and the nose are typically spared from eczematous changes. The skin may show an increase in skin lines and creases, and the palms frequently exhibit prominent hyperlinear creases.

     In young children, the dermatitis is characterized by generalized xerosis. There are eczematous and exudative lesions involving the flexural creases of the extremities. The feet and hands are frequently involved as is the face in most children with AD. Interestingly, young patients who are placed into below-the-knee casts [6] following surgery or injury do not develop eczema under the cast. However, there may be toe involvement and nail changes that are easily misdiagnosed as tinea pedis and onychomycosis. In these patients, one may often see striking infraorbital folds (Dennie-Morgan lines) and allergic shiners.

     In adolescents and adults, the dermatitis becomes more diffuse with an erythematous base. The face is commonly involved as are the flexural areas of the arms and legs. Generalized skin dryness is often prominent with accentuated skin lines and nail involvement. Ichthyosis vulgaris is present in over 30 percent of the patients with hyperlinear palmar creases and polygonal dry skin scales, especially on the legs. Hand and foot dermatitis may be the only manifestations of AD in this age group. Fissuring of the palms or soles (especially around the heels) may be apparent.

     Keratosis pilaris is characterized by asymptomatic horny folliculitis of the extensor surfaces of the arms, buttocks and anterior thighs. Pityriasis alba, hypopigmented asymptomatic macular areas on the face, neck, arms and trunk, may become more noticeable after sun exposure. Mycological evaluation is occasionally necessary to rule out tinea versicolor or a dermatophyte infection. Pityriasis alba generally is self-limiting and the lesions typically resolve by adulthood.

Understanding The Impact Of Pruritus And Xerosis

     When I was a resident on a dermatology rotation, the chief of dermatology told me AD is “an itch that rashes, not a rash that itches.” That statement is still relatively true today even though many experts think this is too simplified of a statement. Essentially, AD starts with itching due to abnormally dry skin and a lowered threshold for itching. It is the scratching or chronic rubbing that creates most of the characteristic patterns of the eczematous dermatitis.

     Older patients with AD make a concerted effort to decrease the amount of scratching during the day but they may lose this self-control while sleeping. In children, the itch-scratch cycle is established early and the act of scratching becomes [7] habitual, allowing the disease to progress. Chronic itching makes it difficult to concentrate, interferes with normal sleep patterns and causes irritability, anxiety, anger, stress and generally disrupts family life.

     A majority of patients with AD report their pruritus as very bothersome and at times, intolerable. It is the symptom that most affects their health-related quality of life and causes most to seek treatment. The most common triggers of itch in AD patients are heat and perspiration (96 percent), wool (91 percent), emotional stress (81 percent), vasodilatory foods (49 percent), alcohol ingestion (44 percent), upper respiratory infections (36 percent) and house dust mites (35 percent).

     There is a diffuse spectrum when it comes to triggers of itch in AD. Beltrani and Boguneiwicz noted the potential triggers of irritants, listing soaps, detergents, disinfectants such as chlorine, materials such as wool and nylon, contact with juices and occupational chemicals, fumes and dust.³ The authors also cited contact aeroallergens (such as house dust mites, pets, seasonal pollens, molds and dandruff) and microbial causes (such as Staph aureus infections, viral infections and mycologic infections caused by pityrosporum, Candida or dermatophytes). Other possible contributory factors included temperature/climate, foods, stress and hormones.³

     However, keep in mind that not all patients with AD will react to each stimulus. Some AD patients will experience severe exacerbations of their condition by some triggers and not by others.

     Xerosis or dry skin is considered to be the most common disorder of AD. This condition ranges from simple dry skin to ichthyosis and it can continue for life, independent of the range of atopic symptoms. About 75 percent of all AD patients report seasonal variations in the xerosis, with improvement for the duration of more humid, warmer weather and aggravation of the condition during the dry, colder winter months.

Exploring The Various Treatment Options

     In recent years, the treatment of AD has evolved from using a topical corticosteroid-based monotherapy to more of a broad-based and multifaceted approach. This new expanded treatment program now includes the avoidance of potential [8] trigger factors and the use of emollients, antibiotics, phototherapy, antihistamines, topical corticosteroids and most recently, topical calcineurin inhibitors.

     Emollients. Using emollients is considered standard therapy in treating patients with AD. They are steroid-sparing and useful for both prevention and maintenance therapy of xerosis. Most treatment plans include the use of emollients but take care to avoid creams and lotions with sensitizing ingredients such as fragrances, preservatives and stabilizers. Bland emollients are generally better accepted as are ointments.

     Antibiotics. Due to the fact that Staph aureus is isolated on the skin of approximately 90 percent of all patients with AD, the use of topical or oral antibiotics may be necessary in some cases. Assume the likelihood of bacterial overgrowth in an AD patient whose dermatitis has been under control but suddenly experiences an acute exacerbation. Given the increasing incidence of community-acquired methicillin-resistant S. aureus (MRSA), it is imperative to culture patients suspected of having this infection.

     Phototherapy. In a few cases, ultraviolet therapy may prove helpful in managing the chronic AD patient who has had a poor response to a well-designed topical regimen. Ultraviolet phototherapy, including photochemotherapy using methoxypsoralen (PUVA therapy), has been shown to provide substantial improvement in symptoms. Additionally, one may significantly reduce the use of topical corticosteroids after the patient has undergone UV or PUVA therapy. It is best to synchronize such therapy with a dermatologist.

     Antihistamines. Oral antihistamines also are often useful. The nonsedating antihistamines are safe and not associated with significant adverse effects even in very young patients. Keep in mind that many patients with AD also have accompanying urticaria, dermatographism and allergic rhinoconjunctivitis so they may benefit from the use of antihistamines. The soporific H1 blockers (sedating) antihistamines may indeed be useful in helping the AD patient sleep at night.

     Corticosteroids. Topical corticosteroids have been the mainstay of therapy for AD for many years. However, one needs to consider the potency of the steroid, its vehicle, the patient’s age, the location and thickness of the dermatitis, the season of the year and the presence or absence of infection. Since no firm guidelines exist, it is prudent to use the least potent corticosteroid that will deliver the maximum effect because skin atrophy, telangiectasia and hypopigmentation are potential side effects. When treating mild to moderate conditions in the dorsum of the foot and intertriginous spaces, less potent (class 7 or 6) corticosteroids are indicated and are usually effective.

     More potent agents may be necessary for the extremities, depending on lesion thickness. At this time, long-term intermittent topical steroid application with mid-potency fluticasone propionate (Cutivate®, 0.05% cream, 0.005% ointment, GlaxoSmithKline) is indicated for atopic eczema. Due to the vehicle, fluticasone ointment (Class 3) is more potent than fluticasone cream (Class 5). Fluticasone propionate, the first carbothiate corticosteroid, has high topical antiinflammatory effects and a lower potential to cause adverse effects. One should apply corticosteroids to the problem areas first and then apply the emollient to the entire area, including noninvolved skin.

A Closer Look At Calcineurin Inhibitors

     Calcineurin inhibitors. Two topical calcineurin inhibitors approved for the treatment of AD are tacrolimus ointment (Protopic®, 0.03% and 0.1%, Fujisawa Healthcare) and pimecrolimus cream (Elidel®, 1%, Novartis Pharmaceuticals). Both of these immunomodulator drugs have proven to be more effective than the base vehicle alone in alleviating the signs and symptoms of AD without causing significant side effects. Some patients with very active dermatitis note stinging or burning when initially using these agents, although this problem usually goes away in a few days. Approximately 10 percent of atopic patients will complain of burning and stinging even with the application of bland placebo emollients.

     I used Protopic for several years with relatively good results. Once Elidel was available, I started using this compound on my pediatric patients. I noticed similar results to Protopic in the early part of treatment but I found that most patients complained less about stinging with Elidel and were more likely to continue using it for longer periods of time. Both of these agents are indicated for the short-term or intermittent, long-term treatment of mild-to-moderate and moderate-to-severe AD, respectively, in patients 2 years of age and older.

     These agents have decided advantages over topical corticosteroids because one may use them safely on thinner skin and in intertriginous areas without causing skin atrophy, telangiectasia or hypopigmentation. It is important to remember that these medications were developed for intermittent use and are most effective when one combines them with other treatment modalities. Regarding the general safety of the topical calcineurin inhibitors, the present weight of human evidence would suggest that Protopic and Elidel may be safer than topical corticosteroids in the long-term control of AD.

Emphasizing The Avoidance Of Triggering Agents

     The avoidance of potential trigger factors is very important in managing this condition. One should emphasize this to patients and urge them to be careful about contact with irritants and aeroallergens. Since most AD patients experience increased transepidermal water loss due to an altered stratum corneum, daily bathing and the extensive use of emollients after bathing are necessary treatment measures. Bathing helps hydrate the stratum corneum while simultaneously removing possible irritants and bacteria.

     In addition, advise patients to decrease stress whenever possible. They should also avoid fragrances and perfumes, minimize sweating and allow sun exposure in moderation. Patients should humidify the house in winter and cool the house in summer. They may wear thin white cotton gloves to bed to prevent scratching of the skin while sleeping.

In Conclusion

     Atopic dermatitis is a chronic disease of unknown etiology that starts in early infancy and is typified by pruritus, eczematous lichenified lesions and xerosis of the skin. It is also associated with other conditions (asthma, allergic rhinitis, urticaria) and increased immunoglobulin E (IgE) production. In treating an AD patient, the goal of the podiatric physician always should be to minimize dermatitis activity as quickly as possible and then maintain the skin with as little treatment as necessary, ideally using only effective bathing techniques and emollients. In most cases, referring the patient to a pediatric dermatologist is recommended.

Dr. Dockery is a Fellow of the American College of Foot and Ankle Surgeons and a Fellow of the American Society of Podiatric Dermatology. He is also a Fellow of the American College of Foot and Ankle Pediatrics. Dr. Dockery is the Chairman and Director of Scientific Affairs of the Northwest Podiatric Foundation for Education and Research in Seattle, Wash. He is the author of Cutaneous Disorders of the Lower Extremity.

References:

1. Hanifin JM, Rajka G: Diagnostic features of atopic dermatitis. Acta Derm Venereol Suppl (Stockh). 92:44-47, 1980
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4. Krafchik BR: Atopic dermatitis. eMedicine. Online Dermatology. 10:1-11, 2004.
Recommended Reading
1. Barclay L: Fluticasone reduces relapse in atopic dermatitis. Brit Med J. 326:1367-1370, 2003.
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3. Belsito DV: Management of atopic dermatitis in the adult patient. Medscape Dermatology. 6:1-10, 2005.
4. Beltrani VS, Boguneiwicz M: Atopic Dermatitis. Dermatology Online Journal 9 (2), 2003.
5. Berth-Jones J, Damstra RJ, Golsch S, Livden JK, et al: Twice weekly fluticasone propionate added to emollient maintenance treatment to reduce risk of relapse in atopic dermatitis: randomized, double blind, parallel group study. Brit Med J 326:1367-1370, 2003.
6. Boguniewicz, M: Atopic dermatitis: Beyond the itch that rashes. Immunol Allergy Clin North Am. 25:333-51, 2005.
7. Dockery GL: Eczematous dermatitis. In: Cutaneous Disorders of the Lower Extremity. WB Saunders, Chapter 10, pp. 134-159, 1997.
8. Dockery GL, Crawford ME: Eczema. In: Color Atlas of Foot & Ankle Dermatology. Lippincott-Raven, Chapter 2, pp. 11-28, 1999.
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