A 3-year-old Child with a Rash
After reading this article and answering the review questions, the reader will be able to:
- Recognize atopic dermatitis and differentiate it from other skin lesions
- Describe how the pathophysiology of atopic dermatitis involves alterations in the natural skin barrier as well as immune dysregulation
- Explain the role of microbes in the propagation of the disease
- Be familiar with the evaluation and management, both medical and nonmedical, of atopic dermatitis patients
Addie is a 3-year-old girl who presents to your clinic with a chief complaint of “rash.” Her family has recently moved to the area from out-of-state and this is the first time you have seen the patient. Her parents report that Addie’s skin has always been very dry and that she has had similar appearing rashes before, albeit on different areas of the body. The parents have tried using baby lotion on the rash, but this has not helped significantly. They have tried application of an over-the-counter hydrocortisone product, though they are reluctant to use it regularly because they fear the side effects. Addie frequently complains that the rash is itchy. Occasionally, her parents note a crusted area overlying one of the lesions with a small amount of drainage.
Addie was a term newborn with no neonatal complications. She was breastfed for the first six months of life and then transitioned to a cow’s milk-based formula. She was seen in the emergency department at age two years with respiratory syncytial virus bronchiolitis. She is up-to-date on her immunizations. Her growth and development have been normal for her age. She lives in a new home in a suburban area with her parents and 7–year-old brother. They have two dogs in the home. Her mother and father both have seasonal allergies and her brother has a peanut allergy.
On physical exam, Addie is a pleasant, well-developed Caucasian girl. Her vital signs are within normal limits for age. Examination of the skin shows scattered clusters of erythematous papules with evidence of excoriation. The lesions are clustered on the cheeks, the abdomen, and the flexural folds of the upper and lower extremities. On closer examination of the antecubital fossae, the underlying skin is hyperpigmented with evidence of lichenification. On the right cheek, there is a crusted lesion with a small amount of serous drainage. The remainder of the physical exam is normal. Based on the history and physical exam findings, the most likely diagnosis is atopic dermatitis, a chronic or relapsing inflammatory skin disease that often precedes asthma and other allergic disorders.
Example of atopic dermatitis
Introduction to Atopic Dermatitis
Lifetime prevalence of atopic dermatitis (AD) in schoolchildren in the United States is reported to be up to 18%. Nearly 80% of children with AD show evidence of a genetic predisposition to produce specific IgE to environmental and food protein antigens. As many as 66% of children with AD will go on to develop asthma or other allergic problems by the age of three years, and this relationship is especially strong for infants with a more severe rash that is accompanied by allergies. Severe AD can have a significant impact on quality of life.
Pathophysiology of AD
The underlying pathology of AD involves two major defects. One is a defective skin barrier seen in both lesional and non-lesional skin. The second is the presence of immune dysregulation, which leads to acute and chronic inflammation. Both of these factors increase the risk of colonization and overt infection with Staphylococcus aureus and other microbes.
Disruption of the skin in AD is multifactorial. Skin in AD has a deficiency of ceramides, which are important water retaining molecules.3 Mutations in the FLG gene, which codes for a protein known as filaggrin have been strongly implicated in some patients with AD, especially those with severe AD that develops in infancy.1 Filaggrin plays an important role in the hydration of cells as well as the regulation of pH in the stratum corneum. Children with FLG gene mutations, and consequent decreases in filaggrin have a steeper water gradient across the stratum corneum, leading to water loss and skin dryness. Additionally, they have increased pH of the stratum corneum which serves to activate damaging proteases as well as make the skin environment more hospitable to colonizing microorganisms.1 AD patients also often have defective tight junctions in the stratum granulosum layer of the epidermis which leads to further water loss. These disruptions of the skin barrier are noted in both lesional and non-lesional skin.
Immune dysregulation in AD patients is present at both systemic and local levels. Most AD patients have increased concentrations of serum IgE, increased allergen sensitization, increased numbers of T lymphocytes expressing skin-homing receptors, and increased expression of the high-affinity IgE receptor (FcεRI) on Langerhans and dendritic cells.1 At the local level, there is a strong Th2 influence with increased local production of Th2 cytokines such as IL-4 and IL-13 in T cells of the skin.2 T regulatory cells (Tregs), which serve to mitigate both Th1 and Th2 responses, while increased systemically in AD patients, are absent in biopsies from skin lesions.1 This leads to a state of unchecked Th2-driven inflammation at lesional sites. Increased expression of chemokines such as CCL-4, eotaxin, and RANTES increase migration of macrophages, eosinophils, and T-cells into skin lesions.2 Pruritis in AD patients is mediated to some extent by increased histamine release, although the lack of response to antihistamine medications suggests other factors mediate this major AD symptom. Increased levels of IL-31 correlate with increased disease activity in AD patients and this pathway may be a potential target for relieving some of the discomfort associated with AD.1
Patients with AD have an increased prevalence of colonization with a variety of microorganisms. S. aureus can be cultured from up to 90% of skin lesions in patients with AD, as well as from non-lesional skin.4 Secondary skin infection with S. aureus is the most common complication in children with AD. S. aureus binding is enhanced in the skin of AD patients. AD patients have a Th2-driven decrease in production of endogenous antimicrobial peptides, such as HBD-2, at the lesional level, thus increasing the susceptibility to infection.1 Staphylococcal toxins serve as superantigens, increasing activation of T lymphocytes and macrophages and thus increasing local inflammation.2 Many AD patients also make specific IgE to these toxins, which further propagates the inflammatory response.2 Other infectious agents, most notably herpes simplex virus, can also be contributing factors in the propagation of AD.2
The relationship between the severity of AD and IgE-mediated sensitization to food proteins has been established, mostly in infants.2 However, while 40-90% of children with severe AD will have a positive skin prick test to common food allergens (milk, egg, peanut, etc.), many of those same children (up to 70%) will pass an oral-graded food challenge to the same allergen without an immediate hypersensitivity reaction.5 Food allergy should be suspected in children with more severe AD who do not respond to standard clinical care plans. Some children will experience a delayed eczematous reaction upon eating the food to which they are sensitized.5 The relationship between AD and food allergy has created two competing hypotheses regarding their chronologic relationship. The “inside-out” hypothesis claims that AD is an outward manifestation of an underlying atopic state and that sensitivity to food allergens is manifested cutaneously by AD. The “outside-in” hypothesis claims that sensitivity to food allergens occurs epicutaneously through the defective skin barrier seen in AD. Most likely, an interplay of the two exists.
Evaluation of a Child with AD
AD is one of the most frequently encountered dermatoses in the general pediatrician’s office.3 A well-defined evaluation and management strategy is important to consider when treating AD patients. The first step in the evaluation is to ensure that the diagnosis of AD is correct. Other diseases, including scabies infection, contact dermatitis, and psoriasis can mimic AD. The diagnosis is made on clinical grounds, with skin biopsy required only in the event that an alternative diagnosis seems more likely.
Once the diagnosis is made, severity should be determined, considering the physical signs (erythema, exudation, excoriation, dryness, cracking and lichenification), and degree of functional impairment related to itching and discomfort.2,3 After assessing the severity of the disease, a decision should be made on whether to commence treatment or consider referral to an allergist or dermatologist. In most cases, it is reasonable to start treatment, assess responsiveness, and reserve specialist referral for those patients who fail to respond to appropriate therapy. While evaluating for food protein specific IgE and aeroallergen specific IgE may be important diagnostic tools in AD, the substantial false positive rates of IgE tests as well as their complex relationship to allergy and AD makes it most prudent to consult an allergist.
Treatment of AD
Successful treatment of AD requires addressing both major components of the disease: the altered skin barrier and the immune dysregulation.
Skin hydration is of utmost importance in managing both lesional and non-lesional skin in AD. We prefer the use of a non-irritating emollient cream such as Eucerin®, Vanicream®, or Cetaphil®. Ointments can be used for extremely dry skin or in winter, although some children can experience increased pruritis due to occlusion of sweat glands.3 In general, lotions contain a higher percentage of water than creams and can lead to water loss through evaporation.3 We recommend application of moisturizers at least twice daily. Application of moisturizers after bathing is especially important to maintain skin hydration and increase barrier function.
Management of inflammation is another critical component of the care of AD. Topical corticosteroids have long been the mainstay of AD therapy. There are many different acceptable topical corticosteroids and many reasonable regimens for their application. Our preferred method is to use a 1:1 mixture of 2.5% hydrocortisone cream and an emollient cream. This mixture, which can be dispensed in a 1 pound jar if the eczema is extensive, can then be applied to the skin (including the face) one to two times daily. For more problematic areas on the body, we will generally prescribe a medium potency topical corticosteroid cream, such as 0.025% triamcinolone or 0.05% fluticasone. The higher potency corticosteroids should not be used on the face, axillae, or groin as the skin in those areas is more prone to thinning and discoloration. The other class of immunomodulatory medications used in AD is the topical calcineurin inhibitors. Two of these medications, tacrolimus (Protopic®) and pimecrolimus (Elidel®), have been approved for use in AD in children two years of age and older. Studies have shown these medications to be even more effective than the lower potency topical corticosteroids, and have the advantage of not inhibiting collagen synthesis, a principal side effect of more potent corticosteroid preparations. However, in 2005, the Food and Drug Adminstration issued a black box warning for the topical calcineurin inhibitors because of the potential risk of malignancy associated with their use. Post-marketing studies are in progress, and parents can be reassured that so far there is no evidence that children using these medications have increased rates of cancer. The topical calcineurin inhibitors are generally considered as second-line therapy.
For both emollients and topical corticosteroids, it is important to consider the amount required for therapy and ensure that a sufficient quantity has been prescribed. When applying topical medications, there is great variability among patients when determining how much is appropriate. We prefer the use of the fingertip unit (FTU) – the amount of a topical medication it takes to cover the palmar aspect of the index finger from the tip to the first knuckle.3 The approximate number of FTUs required to cover various areas of the body is shown in Table 1.3
Table 1: Approximate dose of topical medication required for coverage in fingertip units (FTU)
|Hand or groin||1 FTU|
|Face or foot||2 FTU|
Adapted From: Boguniewicz, Immunol Allergy Clin N Am 2005
In addition to medical management, several practical strategies can be employed to prevent skin irritation. These are summarized in Table 2. For more severe lesions, we advocate the use of wet wraps. After application of topical anti-inflammatory medications and topical emollients, strips of gauze or cloth are moistened and wrapped around problem areas. These are left in place for 15 minutes. If gauze is not available, strips from a clean cotton shirt may be used. Aggressive moisturization techniques such as this are often needed to facilitate healing of severe AD lesions.
Table 2: Practical strategies in AD patients
|Use cleansers with minimal defatting activity and neutral pH instead of soap|
|Bathe daily for 15-20 minutes|
|Pat dry and immediately apply topical anti-inflammatories and emollients|
|Avoid alcohol and astringents in skin care products|
|Wash new clothing to remove formaldehyde and other chemicals|
|Use liquid detergents which rinse more completely than powders|
|Use scent- and dye-free detergents|
|Add a second rinse cycle to remove additional detergent|
|Bathe immediately after swimming in pools to remove chlorine and/or bromine|
Adapted From: Boguniewicz, Immunol Allergy Clin N Am 2005
There has been considerable debate on the role of reducing the microbial colonization in children with AD. Huang, et al, published a paper in 2009 reporting benefits in patients who bathed in water containing 8 ounces (1/2 cup) of bleach twice weekly.4 These patients and their family members also applied mupirocin, intranasally, twice daily for five days at the beginning of each month.4 Both of these strategies are commonly used, though a recent Cochrane review did not find evidence of benefit in employing strategies that decreased the microbial burden in children with AD.1 We do not routinely recommend that all patients use “bleach baths” and intranasal mupirocin. However, in cases in which children have had recurrent secondary infection or recalcitrant disease, we have used both strategies with success.
Occasionally, AD lesions become secondarily infected, typically with S. aureus. In this situation, additional therapy is needed to resolve the infection. Use of topical antimicrobials such as bacitracin or mupirocin is generally sufficient for smaller lesions that are confined to one area of the body. Occasionally, more widespread lesions may require systemic antimicrobial therapy. We recommend obtaining a wound culture from the lesion before commencing antimicrobial therapy. If systemic antimicrobial therapy is used, it should be directed at S. aureus. If methicillin-resistant S. aureus (MRSA) is a concern, trimethoprim/sulfamethoxazole or clindamycin should be considered.
AD is a common, chronic, and often difficult to manage condition that is frequently encountered in the primary care setting. Its pathology is rooted in both a defective skin barrier and an altered immune response. Colonizing microorganisms, primarily S. aureus, propagate and often worsen the disease course, especially when secondary infection is encountered. The diagnosis is clinical and we do not recommend obtaining any laboratory studies (including serum specific IgE levels to food and aeroallergens) unless another diagnosis is strongly suspected. Management consists of effectively targeting both of the underlying defects, while being mindful of the microbial component as well. Effective moisturization with non-irritating topical emollients and effective anti-inflammatory therapy with either topical corticosteroids or topical calcineurin inhibitors are both of utmost importance. Nonmedical management, such as use of appropriate cleansers, avoidance of chemical irritants, and use of wet wraps when appropriate, can be effective in augmenting the effect of medications.
- Boguniewicz M, Leung DYM. Recent insights into atopic dermatitis and implications for management of infectious complications. J Allergy Clin Immunol 2010; 125(1):4-13.
- Akdis CA, Akdis M, Bieber T, et al. Diagnosis and treatment of atopic dermatitis in children and adults: European Academy of Allergology and Clinical Immunology/American Academy of Allergy, Asthma, and Immunology/PRACTALL Consensus Report. Allergy 2006; 61:969-987.
- Boguniewicz M. Atopic dermatitis: Beyond the itch that rashes. Immunol Allergy Clin N Am 2005; 25:333-351.
- Huang JT, Abrams M, Tlougan B, et al. Treatment of Staphylococcus aureus colonization in atopic dermatitis decreases disease severity. Pediatrics 2009; 123:e808-e814.
- Campbell DE. Role of food allergy in childhood atopic dermatitis. J Paed Chlld Health 2011; 47(12):1-7.