Donald W. Kennerley
The child who presents in a clinic with an itchy rash is usually miserable and the parents are anxious for a quick fix to the problem. The dilemma for the healthcare provider is to quickly identify the problem and find a treatment plan that provides immediate relief as well as a long-term cure, or amelioration in the chronic case that won’t be cured. The source of the problem may be an infection, infestation, environmental toxin/irritant, or allergy/immunologic problem. This scenario will help the clinician sort through those issues.
1. Develop a multimodal approach for the treatment of atopic dermatitis.
2. Understand the complex role that the environment and aeroallergens have in the development of atopic dermatitis.
3. Review and understand new therapies for compromised barrier function.
4. Understand the effects that atopic dermatitis has on the social, financial, and psychological well-being of a family with a child affected with this disorder.
Case Presentation and Discussion
Anna Logan is a 3-year-old white female who comes into the office accompanied by her mother. She has come today because of a persisting rash that the mother indicates comes and goes and was first noted when her daughter was 1 year old. Though the rash does at times get better, it has never left her daughter. In fact, as her daughter gets older the intensity of the rash worsens and is spreading to other areas of her body. Originally the rash started on Anna’s face but is now on her neck, arms, and legs. Mrs. Logan indicates that her daughter is scratching more now than in the past and is often awake at night due to the scratching. Further questioning of the mother reveals that, apart from the rash, her daughter also has trouble with chronic sneezing and a constant running nose. The child does not have a history of asthma. The mother is concerned about the spreading rash and is worried about the possibility of her daughter causing further damage to her skin as a result of her constant scratching. The mother comes with her daughter to find out what the rash is and how to get rid of it.
Upon general physical examination you notice that Anna appears healthy with a slight paleness in her color and darkness beneath her eyes. She scratches during the entire examination. She has a red, dry, inflamed rash on her face, neck, wrists, and antecubital and popliteal fossae. Some of the areas show scratch marks and are lichenified. There are no areas of weeping. She has signs of chronic rhinitis with redness of the nasal turbinates. The rest of her physical examination is unremarkable.
What questions do you feel would help you to make a diagnosis?
Before proceeding with those questions, let us now look at atopic dermatitis in more detail.
Atopic dermatitis (AD) is a common skin condition in children, often beginning in early childhood. Its presentation can be quite severe. Approximately 15–20% of school-age children are affected, with 1–2% having severe involvement. About 1–3% of adults are affected by this condition (Barclay, 2008; Krakowski, Eichenfield, & Dohil, 2008). Approximately 60–65% of patients with atopic dermatitis develop their disease before age 1 year, and by age 5 years, 85–90% of patients have developed signs of their disease (Krakowski et al., 2008; Lewin Group, 2005). The prevalence of atopic dermatitis, asthma, and allergic rhinitis has been rising in industrialized countries (Spergel & Paller, 2003).
Atopic dermatitis is a chronic and relapsing disease and persists from an average of 4.4 years in children to 18.2 years in adults (Lewin Group, 2005). Most forms of this childhood disease improve with the onset of puberty, but up to 40% of cases do not and can recur even into adulthood. AD is often associated with other atopic predispositions; many patients suffering with atopic dermatitis will go on to develop asthma or allergic rhinitis in what is known as the “atopic march” (Spergel & Paller, 2003). Up to 30–60% of patients with atopic dermatitis will go on to develop asthma and 35–66% will go on to develop allergic rhinitis (Lewin Group).
This condition has a significant impact on the quality of life of the individual and his or her family. Cost estimates for the United States range from $364 million to $3.8 billion annually, depending upon the study parameters (Carroll et al., 2005; Mancini, Kaulback, & Chamlin, 2008). The condition accounts for an estimated 7.4 million office visits in the United States alone (Krakowski et al., 2008). Studies have shown that AD can affect sleep, negatively affect school performance, cause low self-esteem, decrease participation in sports and other social activities, and induce stress and anxiety (Krakowski et al.).
Although the pathogenesis of atopic dermatitis is not completely understood, in the simplest terms it is believed to be due to a combination of T-cell downregulation and skin barrier dysfunction (Gilliam & Frieden, 2006). The underlying immunologic abnormality for acute disease appears to be related to the overex-pression of T-helper-cell type 2 hypersensitivity, whereas chronic disease is related to augmented T-helper-cell type 1 activity (Novark, Bieber, & Leung, 2003). Genetic studies have found that AD has a complex genetic pattern. Some studies have shown that a primary defect in the skin barrier may be one central factor in the condition. Other factors are still being studied (Spergel, 2008).
The permeability barrier, which relies on the functional integrity of the stratum corneum, is altered in patients with atopic dermatitis, leading to accelerated transepidermal water loss and skin dryness. Improving that functional permeability barrier is a cornerstone of AD treatment.
The immune system response in atopic dermatitis involves both intrinsic (nonallergic) and extrinsic (allergic) components. Approximately 70–85% of cases of atopic dermatitis involve the extrinsic system whereas 15–30% of cases are intrinsic. Extrinsic atopic dermatitis is associated with high serum IgE levels and exhibits allergen-specific IgE to aeroallergens and foods, positive skin prick reactions, and a cytokine profile of high interleukin-4 (IL-4) and IL-13 levels (Bardana, 2004). Intrinsic atopic dermatitis is associated with normal IgE levels, negative skin prick reactions, and low IL-4 and IL-13 levels, and the individual does not have allergen-specific IgE to aeroallergens and foods (Bardana). Patients with intrinsic disease are characterized by an absence of other atopic diseases, asthma, and allergic rhinitis (Schmid-Grendelmeier, Simon, Simon, Akdis, & Wirthrich, 2001).
There are three distinct phases, related to stages of growth, in which atopic dermatitis can present. They include an infantile phase, a childhood phase, and an adult phase. In the infantile phase, which occurs from birth up to age 2, the disease presents with pruritic, erythematous papules, patches, and vesicles on cheeks and extensor surfaces of the extremities (Peterson & Chen, 2006). Other areas of involvement may include the scalp, forehead, chin, and trunk, but not in the diaper area in the majority of cases (Spergel & Paller, 2003). In the childhood phase, from age 2 to puberty, lichenification and scarring appear as a result of chronic rubbing and scratching. Distribution of the lesions changes to the flexor surfaces, particularly the antecubital and popliteal fossae as well as the neck, periorbital, perioral, hands, feet, wrists, and ankles (Spergel & Paller). The adult phase begins at puberty and may follow a continuous course. Areas of involvement include the flexor folds, face, hands, upper arms, back, wrists, and the dorsa of the hands, fingers, feet, and toes (Spergel & Paller). Large lichenified plaques; scaly, erythematous papules and plaques; and pruritic papules are featured in the adult phase (Leung & Bieber, 2003).
A diagnostic formula was established in 1996 to aid in the diagnosis of atopic dermatitis. A patient has to have a history of itchy skin and three or more of the following presentations: a history of rash in skin folds, a personal history of asthma or hay fever, a history of dry skin, onset before age 2 years, and visible flexural dermatitis (Williams et al., 1996).
Allergies play a major role in triggering atopic dermatitis. Approximately 20–40% of young children and infants with atopic dermatitis have clinically relevant food allergies that worsen their disease (Leung & Bieber, 2003). The most common food allergies include cow’s milk, eggs, fish, peanuts, soy, tree nuts, and wheat (Rudikoff & Lebwohl, 1998). Aeroallergens include animal dander, cockroaches, dust mites, human dander, molds, and pollens (Schmid-Grendelmeier et al., 2001). Tests for allergies are not necessary in most children with mild eczema. Radioallergosorbent/skin prick (RAST/SPT) testing has only a 20% positive predictive accuracy (Rowlands, Tofte, & Hanifin, 2006). A double blind placebo-controlled food challenge is considered the gold standard for diagnosing food allergies; however, if there is a history of anaphylaxis, a food challenge should be used with caution and only if the patient is closely monitored (Peterson & Chen, 2006).
Other triggers such as climate, irritants, and micro-organisms are also factors that have a pronounced effect on the severity of atopic dermatitis. Decreased humidity in winter allows the skin to dry out easier through increased transdermal water loss. Irritants such as hot water, soaps, cigarette smoke exposure, laundry detergents, household disinfectants, solvents, synthetic clothing fibers, and juice from fresh fruits are commonly implicated in atopic dermatitis (Abramovits, Goldstein, & Stevenson, 2003).
Bacteria, viruses, fungi, and yeast aggravate atopic dermatitis. Approximately 90% of atopic dermatitis lesions are colonized by Staphylococcus aureus, as opposed to only a 5% rate of colonization in skin of healthy controls (Abramovits, 2005; Chung, Jeon, Sung, Kim, & Hong, 2008). Community-acquired methicillin-resistant S. aureus (MRSA) accounted for 18.3% of those isolates in the Chung et al. study (2008).
Other information that should be ascertained includes the following:
• Does this child have food or other types of allergies?
• What type of clothing does the child wear?
• Is there a family history of asthma or hay fever?
• Has the rash ever been weeping or covered in an exudate?
• What type of soap is used in bathing and in laundry care?
• Has the mother been trying any home remedies on the rash?
• Has the child been seen by a physician in the past and treated for skin problems?
• How much sleep does the child get at night?
The mother responds that Anna is one of three children in the family. Her eldest daughter is on medication for asthma while the other child has intermittent seasonal allergies. Anna has had a history of some early childhood milk allergies that she seems to have outgrown. The mother indicates that she changed her daughter’s clothes from wool to cotton fiber when she discovered that her daughter’s scratching became worse in the wool clothing. During bathing, the mother uses Dove soap and has been applying Lubriderm cream after her daughter gets out of the bath. The rash persists despite the lotion treatment, and her daughter is getting only about 4–5 hours of sleep at night. The mother and her husband are getting less sleep also because they have to get up with their daughter in the night when she cannot sleep. This is beginning to cause some stress in the family. There have been no other medical visits or treatments.
Making the Diagnosis
The common conditions that should be considered in the differential diagnosis for atopic dermatitis are as follows:
• Classic atopic dermatitis
Infantile seborrheic dermatitis
Irritant or allergic contact dermatitis
Nutritional dermatitis; immunodeficiency
• Nummular dermatitis
Dry form: Tinea corporis, psoriasis, pityriasis rosea
Wet form: Impetigo, burns, allergic contact
• Dyshidrotic eczema
• Bullous impetigo
• Allergic bullous tinea
• Contact dermatitis
Reviewing the facts gained from the history and the correlating physical findings, you are assured that this child has atopic dermatitis. The patient has chronic scratching as well as a red erythematous rash on the flexor folds of her arms and knees with early lichenification. There is a history of asthma in the family and allergic rhinitis. The rash first appeared at age 1 year, and Anna has a mild to moderate case of atopic dermatitis.
Diagnostic tests are not indicated at this time because the child has mild involvement and the family is aware of the triggers for this disease and have already made changes to her clothing, bathing, and allergy exposure.
Management of atopic dermatitis in children should follow a stepped approach, with treatment steps tailored to the severity of the eczema. Even when the eczema clears, emollients should always be used and should form the basis of the management. Parents should be counseled on symptoms of atopic dermatitis flares, which include increased dryness, itching, redness, swelling, and general irritability, as well as how to treat the flares through a step-wise care plan (Barclay, 2008; Krakowski et al., 2008).
All patients with atopic dermatitis, including children, have hyper-irritable skin. It is important to avoid irritants such as soaps, cleaning agents, detergents, heat, and wool clothing. Over-the-counter preparations such as Aquaphor, CeraVe, Eucerin, or Vaseline are helpful. Newer prescription emollients such as Epiceram or Hylira are also available. Barrier repair formulations have recently come on the market and include ceramide-based creams such as TriCeram, Impruv, TriXera, Nouriva Repair, and Stelatopia. Their drawback is expense, particularly when the medication is used to cover large areas of the body. Emollients should be applied twice daily and immediately after bathing (Darsow et al., 2005).
Bathing remains somewhat controversial. On the one hand, bathing promotes skin hydration, cleansing, and absorption of topical therapies. On the other hand, bathing can dry the skin and disrupt the stratum corneum barrier during evaporation if emollients are not immediately used to maximize moisture retention (Krakowski et al., 2008). Soaps such as Eucerin, Dove, Aveeno, and Alpha Keri may provide benefit.
Treatment of the pruritis in children is also extremely important because sleep deprivation becomes a factor parents have to deal with frequently. General measures may include cooling the skin with cool wraps or cool baths. Moisturizing and minimizing itching are essential. Oral antihistamines have not been shown to be very effective at reducing itch, but sedating antihistamines may promote night-time sleep.
Topical corticosteroids are divided into classes based on their potency. Class 1 is the most potent of steroids whereas class 7 is the least potent (Table 30-1). Class 1–5 steroids are not to be used in areas of thinner skin including the eyelids, face, mucous membranes, genitalia, and intertriginous areas because those areas have increased likelihood of transepidermal corticosteroid absorption (Leung et al., 2004). Higher potency steroids should be avoided in children (Paller et al., 2005).
Topical steroids should be used for only a few weeks in a continuous fashion and then tapered as soon as symptoms improve. It is preferable to use low-potency steroids for maintenance therapy and mid- to high-potency steroids for flares (Leung et al., 2004). Traditional vehicle choices are ointments for dry skin, creams or lotions for moist skin, lotions or foams for hair-bearing areas, and lotions for facial skin in teens. Local side effects of steroids include striae, telangiectiasis, skin atrophy, dyspigmentation, and acneiform eruptions.
Table 30–1 Common Topical Corticosteroids by Potency
Topical Calcineurin Inhibitor (TCIs)
This class of medications exhibits a potent anti-inflammatory effect without the immune suppression caused by corticosteroids. Pimecrolimus (Elidel) and tacrolimus (Protopic) are safe products in children after the age of 2 years. Pimecrolimus is effective in treating mild to moderate atopic dermatitis whereas tacrolimus is more often used to treat moderate to severe atopic dermatitis. Both are applied two times a day and can be used concomitantly with topical steroids. In addition, both can be used in areas of thinner skin without the risk of skin atrophy and striae (Peterson & Chen, 2006). These agents inhibit the phosphatase activity of calcineurin, thereby preventing the expression of a number of proinflammatory cytokines (interleukin [IL]-2, IL-3, IL-4, IL-5, granulocyte-macrophage colony-stimulating factor, tumor necrosis factor-alpha, and interferon-gamma), which play significant roles in the pathophysiology of atopic dermatitis (Nghiem, Peterson, & Langley, 2002). These agents have decided advantages over topical corticosteroids because they can be used safely on the face and in intertriginous areas without causing skin atrophy, striae, hypopigmentation, or hypothalamic-pituitary-adrenal (HPA) axis suppression.
Topical calcineurin inhibitors can be used safely around the eyes of atopic dermatitis patients without concern for increasing intraocular pressure or contributing to cataract formation (Tharp, 2005).
Systemic steroids may be employed for a short period of time to treat severe atopic dermatitis. However, concerns over side effects and a rebound effect that may occur after discontinuation limit their use (Abramovits, 2005). In severe recalcitrant atopic dermatitis immunomodulators (cyclosporine, azathioprine, mycophenolate mofetil) may also be needed, but it is imperative that these patients be followed closely to detect any side effects. These types of medications should not be used long term (Paller et al., 2005).
Some other treatments that may be used include:
• Ultraviolet (UV) light therapy: Psoralen plus ultraviolet A light (PUVA) therapy should only be used in patients with severe, widespread, recalcitrant atopic dermatitis (Leung & Bieber, 2003). Referral to a dermatologist would be indicated for such a condition.
• Antibiotics: These are recommended for patients with an active infection or heavy colonization of S. aureus (Darsow et al., 2005). If a flare-up of atopic dermatitis occurs with evidence of skin infection, a course of oral antibiotics is recommended.
• Antivirals: Acyclovir should be used in herpeticum eczema because this infection can be life threatening in patients with atopic dermatitis.
• Atopiclair: This is a new steroid-sparing prescription cream whose safety and efficacy have been previously demonstrated in adults with atopic dermatitis. It is also reported to be effective and safe in children and infants. The most frequent side effects are stinging, burning, fever, urinary tract infection, and the common cold (Louden, 2007). Its main drawback is its price. Again, a dermatologist probably should prescribe this medication if more common, less expensive medications are ineffective.
• MimyX: This product is indicated for relief of burning and itching associated with atopic dermatitis, allergic contact dermatitis, and radiation dermatitis. It contains olive and vegetable oils, glycerin, squalene, lecithin, and palmitoylethanolamide (PEA). PEA is thought to be missing in atopic skin. Its main action seems to be downregulating mast cell activation. When applied two times a day, studies have shown a decrease of 80% in itching, a 63% reduction in steroid use, and a 65% improvement in sleep quality in children (Smith, 2008).
How would you proceed to treat this patient with mild to moderate atopic dermatitis?
Parental education is key to the successful treatment of AD in a child. Bathing is first addressed by instructing the mother to use only tepid bath water and Dove soap. After patting her daughter dry, she is to apply Aquaphor cream two times a day. On the affected areas she is to apply triamcinolone 0.1% ointment three times a day for 4–5 days. At night the child is to be given Benadryl liquid to help her sleep until the eczema improves and the itching subsides. You ask the mother to follow this initial treatment plan for 5 days and then return for re-evaluation. You are expecting improvement in that time.
The child is rechecked in 5 days and the areas of involvement are already healing well. The mother is instructed to use a step-up/step-down approach to her daughter’s eczema, and hydrocortisone 2.5% ointment is prescribed for application to the affected areas until the inflammatory reaction has cleared. Once the inflammation has resolved, emollients alone are recommended for daily application to the skin of her body and face.
Patient and family education is an integral part of managing atopic dermatitis (Chisolm, Taylor, Balkrishnan, & Feldman, 2008). Education should include information on causes and triggers of atopic dermatitis, prognosis, treatment, and its prevention. Written instructions facilitate understanding and adherence (Chisolm et al., 2008). The healthcare provider must also address the patient’s quality of life. In this particular case, you instruct the mother to avoid the triggers that contributed to her daughter’s condition, especially clothing and bathing, and tell her that the routine use of emollients on a daily basis is foremost in the care of a child with atopic dermatitis. You may address food allergens later if Anna’s condition remains problematic after treatment is started.
The use of midpotency corticosteroids with emollients during periods of flare-up and how to taper to less potent steroids over the course of the treatment needs to be understood by the family. Educate that there will be flare-ups and exacerbations, but provide reassurance that with a step-up/step-down treatment approach by the family these conditions can be brought under quick control. A significant percentage of children will outgrow atopic dermatitis in time, so constant reassurance to the family is extremely important and helps the family to adjust to the difficult times they may often have.
When do you wish to see this patient again?
Anna and her mother were to follow up in 3 weeks to reassess the treatment program and address any new questions the family may have.
When the patient and her mother return in 3 weeks, you notice a happier child with improved color and no dark lines under her eyes. The mother says her daughter is sleeping much better and her scratching has almost cleared. Reexamination of the patient’s skin shows only a faint redness in the affected areas, and the lichenified areas are almost clear now. The mother is advised to continue with the emollients daily and to return if her daughter has a new flare-up that does not respond to step care by the family.
Key Points from the Case
1. Atopic dermatitis is treated through a multimodal approach.
2. In mild to moderate disease, the use of emollients and mild potency corticosteroids should be initiated.
3. In moderate to severe cases, the primary care provider may need to use emollients, moderate potency topical steroids, and topical calcineurin inhibitors in a step-wise approach.
4. In extreme cases, one would use all of the above as well as phototherapy and even systemic therapy. Care would be transferred to a dermatologist at this level.
5. Therapy for barrier dysfunction, inflammation, infection, and pruritus as well as the identification of possible trigger factors are all necessary in the management of atopic dermatitis.
6. Sometimes bacterial superinfection also needs to be treated.
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