Atopic dermatitis (AD), or atopic eczema, is a common inflammatory skin disorder characterized by pruritus, a chronic and recurrent course, and a distinctive anatomic distribution and morphology. It is often accompanied by a personal or family history of other allergic disorders. Epidemiologic data indicate that AD has been increasing in prevalence, with rates as high as 18% in the United States.^1,2 Socioeconomic studies estimate that the annual financial impact of AD may be as high as $4400 per patient and $364 million to $3.8 billion per year in the United States.^3,4 Although most patients are treated in the outpatient setting, one third to one half of the yearly expenditures for AD are directly related to the costs of hospitalization.

Patients may require hospitalization because of the severity of their primary skin disease or as a result of secondary complications, predominantly bacterial or viral superinfections. Some patients presenting with an eczematous dermatitis along with other comorbidities may require inpatient evaluation for potential underlying causes, such as Wiskott-Aldrich syndrome, hyper-IgE syndrome, or a variety of metabolic disorders.

PATHOPHYSIOLOGY

AD appears to be a multifactorial disease that involves dysregulation of the immune response, with resulting alterations in skin barrier integrity and associated cutaneous hyperreactivity. Studies suggest that T cells, particularly those expressing markers for the Th2-response, are up-regulated in acute AD. The elaboration of Th2-related cytokines such as interleukin (IL)-4, IL-5, and IL-13 indirectly results in increased immunoglobulin E (IgE) production and eosinophilia. In the chronic phase of AD, there is a switch to the Th1-related cytokines IL-12 and interferon-γ. Other pathobiologic abnormalities noted in patients with AD include a genetic background of atopy, disturbed essential fatty acid metabolism, increased leukocyte phosphodiesterase activity, autonomic nervous system dysregulation, pruritus,^5-7 and a predisposition to infection.⁸

The specific genetic basis of the disease has yet to be elucidated. Studies of twins and families clearly indicate a familial predisposition in approximately two-thirds of patients. Twin studies suggest an 85% concordance among monozygotic twins, but only a 21% concordance among dizygotic twins and nontwin siblings.⁹ If one parent has AD, 59% of offspring will develop AD; if both parents have AD, 81% of offspring will develop the disease. It now appears unlikely that AD is the result of a single gene; rather, it appears to be the result of multiple genes interacting to produce the disorder. Recent research does, however, suggest that filaggrin mutations may play a central role in many patients with atopic dermatitis and indicates that filaggrin and other defects in barrier function, such as kallikrein 7 and cystatin A, are important in the pathogenesis of atopic dermatitis.¹⁰

Patients with AD have an increased propensity for other atopic diseases such as asthma and allergic rhinitis. Based on clinical observations, patients sometimes progress sequentially from AD to the development of asthma and allergic rhinitis in what has been referred to as the “atopic march.”¹¹

The threefold increase in the prevalence of AD over the past three decades has been attributed to the hygiene hypothesis, which suggests that reduced childhood exposure to microbial antigens that are thought to be mediated by Th1-related immune responses leads to an increased propensity for Th2-related diseases.^6,12,13

The diagnosis of AD involves the identification of characteristic clinical criteria. Although a broad spectrum of history and physical examination findings has been associated with AD, certain features have greater sensitivity and specificity. Diagnostic criteria described for the purposes of AD research have been difficult to apply in the clinical setting (Table 61-1).^14,15 A recent consensus conference on AD proposed a set of practical working guidelines for its diagnosis.¹⁶ These guidelines characterize AD on the basis of essential and supporting criteria. The presence of pruritus and a chronic and relapsing skin rash with a typical morphology and distribution are considered essential to the diagnosis of AD. Most cases are also associated with an early age of onset (typically younger than 2 years) and a personal or family history of atopy (e.g. asthma, allergic rhinitis, IgE reactivity). Supportive, but not entirely specific, findings can help confirm the diagnosis (Table 61-2). These guidelines emphasize that AD is principally a clinical diagnosis that generally does not require confirmatory laboratory testing or histopathologic analysis.

Pruritus is a hallmark feature of AD, and patients often complain of nighttime exacerbations. Exposed skin surfaces not covered by clothing are especially predisposed to itch, although certain rough fabrics, such as wool, may aggravate pruritus in atopic patients.

The skin in early atopic eczema may itch without obvious cutaneous findings. With continued scratching, the skin becomes erythematous, scaly, and excoriated. The term eczema has its origins in a Greek word meaning “boiling over,” and this accurately describes the morphology of an acute lesion of atopic eczema, with its exuberant oozing and crusting. Chronic excoriation may lead to thickening and altered pigmentation of the skin. Patients with significant involvement of the hands may also manifest nail pitting.

The distribution of AD lesions evolves with age. Infants generally show more widespread disease, with generalized involvement of the face, neck, extremities, and torso. Sparing of the nose, perinasal area, and diaper area is characteristic; this helps distinguish AD from seborrheic dermatitis and other skin disorders (Figure 61-1). Accentuation within the flexural creases—the wrist, antecubital, proximal posterior thigh, popliteal (Figure 61-2), and ankle (Figure 61-3) areas—may be evident in infancy but is more frequently observed in toddlers and older children. Children may also suffer from scalp pruritus, scaling, and lymphadenopathy, which may make it difficult to distinguish AD from other scalp dermatoses such as tinea capitis. The majority of affected adolescents and adults demonstrate only limited disease on the hands or face, including the eyelids. When the hands are affected, the eczema is often more pronounced on the dorsal aspect.

The majority of patients with AD manifest features of the disease within the first 2 years of life, and 80% show signs of AD by age 5 years. Fortunately, most children who develop AD improve with age. Remission rates as high as 92% by age 10 years have been reported; 10-year clearance rates appear to be closer to 50% to 70% for those who develop signs of AD during childhood. Approximately 84% of children diagnosed with AD have mild to moderate disease, and 16% have more severe disease.¹⁷ Those suffering from severe disease also have a lower rate of spontaneous remission than do those with milder disease.

The findings of xerosis, ichthyosis, keratosis pilaris, pityriasis alba, pruritus with sweating, perifollicular accentuation, orbital darkening, hand and foot dermatitis, conjunctivitis, white dermatographism, and nipple eczema are all associated with AD.¹⁴ Although these findings have low individual sensitivity and specificity, the presence of multiple corroborating features can be helpful in confirming the diagnosis of AD when the presentation is atypical.

The signs and symptoms of AD can be a major burden for patients and their families. Children may suffer bouts of itching and scratching that are hard to control, and sleep may be disturbed for both the child and the family. Children may have difficulty in school because they are distracted by their disease or fatigued due to poor sleep at night, or they may have secondary complications necessitating hospitalization. The treatments for AD are often both time and labor intensive. The psychosocial and socioeconomic costs of this disease are significant and should not be underestimated.

SUPERINFECTION

Patients with AD have a predilection for colonization and infection by both bacterial and viral organisms, especially Staphylococcus aureus, herpes simplex virus (HSV), and molluscum contagiosum virus. The propensity for microbial colonization in AD patients is likely multifactorial—a combination of impaired skin integrity permitting a favorable environment for adherence of the organism and a disease-associated decrease in antimicrobial skin properties. Naturally occurring peptides known as cathelicidins and defensins possess antimicrobial activity against organisms such as Staphylococcus species as well as viruses and fungi, and recent data suggest that patients with AD produce less of these peptides on the skin compared with controls.⁸ These factors predispose AD patients to staphylococcal superinfection, Kaposi varicelliform eruption (or, more specifically, eczema herpeticum), and extensive outbreaks of molluscum contagiosum and coxsackie. This has led to speculation that because certain bacterial superantigens are known to bind glucocorticoid receptors, patients with significant bacterial colonization may show apparent steroid resistance¹⁸ or apparent tachyphylaxis.

Bacterial Superinfection

Although patients with AD are nearly universally colonized by S. aureus, approximately half go on to develop frank signs and symptoms of infection at some point in their disease (Figure 61-4). Patients who show evidence of fever with cellulitis may require hospitalization for intravenous antibiotic therapy and appropriate skin care. Severe AD flares with impetiginization may require hospitalization for more potent topical therapy as well as antibiotic therapy to reduce cutaneous bacterial populations. Studies suggest that patients with AD clear faster with oral antistaphylococcal antibiotic therapy, so judicious use of these drugs is reasonable. Superinfection limited to small areas may be treated with topical mupirocin. Larger areas may require systemic antibiotics. However, this approach needs to be balanced against the increased potential for the development of antibiotic resistance. At present, it is unclear whether the high prevalence of methicillin resistance among hospitalized patients affects those with AD to the same degree, but studies suggest that the rate of methicillin-resistant S. aureus may approach 15%.^19,20

When AD patients present with invasive infections such as cellulitis or furuncles (Figure 61-5), treatment with penicillinase-resistant penicillins or first-generation cephalosporins is indicated, but due consideration should be given to the potential for antibiotic resistance. With severe infections such as bacteremia or sepsis, empirical therapy with clindamycin, trimethoprim-sulfamethoxazole, or vancomycin should be considered. It should be noted that with increased use of these antibiotics, resistance may emerge as well.²¹

Patients who have staphylococcal carriage in reservoir areas such as the nares, fingertips, or perianal area may benefit from treatment with mupirocin applied to these reservoir areas to reduce the carrier state.

Kaposi Varicelliform Eruption

Patients with AD may suffer acute superimposed eruptions of umbilicated vesicular or pustular lesions due to superinfection by HSV, coxsackievirus, vaccinia virus, and variola virus. The phenomenon has been referred to as Kaposi varicelliform eruption because of its resemblance to severe varicella infection. When the causative agent is HSV, the condition is specifically called eczema herpeticum; when it is vaccinia, the term eczema vaccinatum is used. The risk of eczema vaccinatum is one of the primary reasons that smallpox vaccination is contraindicated in patients with AD. As individual lesions of HSV evolve, they become hemorrhagic and then develop a more typical “punched-out” appearance (Figure 61-6). Often, clusters of vesicles and pustules localize to facial or flexural areas and may be superimposed on areas of existing AD. Children may have fever, lymphadenopathy, and poor oral intake, especially if there is an associated gingivostomatitis.

Diagnostic workup of Kaposi varicelliform eruption includes swabs of the affected area for fluorescent antibody testing (HSV) and polymerase chain reaction (HSV, coxsackie, vaccinia) and viral culture (HSV); for more atypical cases, skin biopsy for histology and electron microscopy (variola) may be warranted. All patients require close follow-up of hydration status and nutrition, as well as management of any primary viral and secondary bacterial infections with appropriate antivirals (e.g. acyclovir) and antibiotics. Tap water or saline soaks of affected skin areas two to four times daily may help reduce crusting.