Pediatric Atopic Dermatitis Clinical Presentation

Diagnostic criteria for atopic dermatitis (AD) have been proposed by Hanifin and Rajka (1980) and largely adopted by the American Academy of Allergy, Asthma, and Immunology.^[8] Appropriate cases must have at least 3 major characteristics and at least 3 minor characteristics.

Major characteristics include the following:

• Pruritus
• Typical morphology and distribution (ie, flexural lichenification and linearity in adults, facial and extensor involvement in infants and young children)
• Chronic or chronically relapsing dermatitis
• Personal or family history of atopy (eg, asthma, allergic rhinoconjunctivitis, atopic dermatitis)

Minor characteristics are as follows:

• Xerosis (dry skin)
• Ichthyosis, palmar hyperlinearity, keratosis pilaris
• Hand dermatitis, foot dermatitis
• Cheilitis
• Nipple eczema
• Susceptibility to cutaneous infection (eg, with Staphylococcus aureus, herpes simplex virus [HSV], other viruses, warts, molluscum, dermatophytes)
• Erythroderma
• Perifollicular accentuation
• Pityriasis alba
• Early age of onset
• Impaired cell-mediated immunity
• Recurrent conjunctivitis
• Orbital darkening
• Infraorbital fold (eg, Dennie pleat, Morgan fold)
• Anterior neck folds
• Keratoconus
• Anterior subcapsular cataracts
• Sensitivity to emotional factors
• Food intolerance
• Pruritus with sweating
• Intolerance of wool
• White dermographism
• Immediate type I skin test response
• Elevated total serum immunoglobulin E (IgE)
• Peripheral blood eosinophilia

Most children with atopic dermatitis relate a history notable for intense pruritus and dry skin. The quality of the pruritus is referred to as a spreading itch. Affected children often have a lowered itch threshold, resulting in increased levels of cutaneous reactivity in response to stimuli. Patients may succumb to a vicious itch-scratch-itch cycle, in which pruritus stimulates a bout of scratching. This, in turn, increases skin inflammation and triggers a greater sensation of itching, thus exacerbating flares.

Altered cell-mediated immunity has been noted in patients with atopic dermatitis; these patients exhibit both impaired skin barrier function and defects in skin innate immunity.^[9] This is clinically observed as a history of repeated unusual cutaneous infections (eg, eczema herpeticum, warts, molluscum, dermatophytes).^{[10, 11]}

Three classes of skin lesions are recognized.

• Acute - Intensely pruritic erythematous papules and vesicles overlying erythematous skin; frequently associated with extensive excoriations and erosions accompanied by serous exudates
• Subacute - Erythema, excoriation, and scaling
• Chronic - Thickened plaques of skin, accentuated skin markings (lichenification), fibrotic papules (prurigo nodularis); possible coexistence of all 3 types of lesions in chronic atopic dermatitis

Typical locations of lesions by age

• Nonmobile infant - Face and scalp
• Crawling infant - Extensor surfaces of extremities, trunk, face, and neck
• Older child and adolescent - Wrists, ankles, antecubital fossae, popliteal fossae, and neck
• Adult - May be limited to hand and foot eczema

Associated findings

Associated findings in atopic dermatitis include keratosis pilaris; accentuated palmar creases; lichenification; atopic pleats; allergic shiners; transverse nasal crease; pallor around the nose, mouth, and ears; white dermographism; cataracts; and keratoconus.

Keratosis pilaris, or plucked-chicken skin, consists of large cornified plugs in the upper part of hair follicles and produces a stippled appearance of the skin on the outer aspects of the arms and legs and on the buttocks and trunk.

Hyperlinear palms are usually present at birth and persist throughout life. These consist of an increased number of fine lines and accentuated markings on the palms.

Lichenification of the wrists, ankles, popliteal fossae, or antecubital fossae is characteristic of chronic atopic dermatitis. It is observed as thickened, leathery, hyperpigmented patches of skin with a deepening of normal skin creases.

Atopic pleats (also referred to as Morgan-Dennie folds, Morgan folds, Dennie pleats, or mongolian lines) are skin folds observed just below the lower lid of both eyes and are retained throughout life.

Allergic shiners are violet-gray infraorbital discolorations caused by underlying vascular stasis. Increased pressure on nasal and paranasal venous plexuses causes edema in these areas, leading to development of atopic pleats and allergic shiners.

A prominent transverse nasal crease is a common sign of concurrent allergic rhinitis and, along with allergic shiners and atopic pleats, may be a clue to the diagnosis of an atopic diathesis.

Dermographism is a normal reaction in 5% of the population. After a firm pointed instrument is stroked against the skin, the path of the instrument is observed as a red line followed by an erythematous flare that ultimately develops into a wheal. This response occurs within 3 minutes of the insult. White dermographism is a paradoxical reaction wherein the initial red line is replaced within 10 seconds by a white line and an absence of a wheal. This reaction can be observed in atopic dermatitis and allergic contact dermatitis.

Atopic cataracts affect 4-12% of patients with AD and occur much earlier in life than senile cataracts. They typically are bilateral, central, and shield-shaped, and they mature rapidly. Because patients generally are asymptomatic, diagnosis is usually made by slit lamp examination. Incidence of cataracts in atopic patients appears to be unrelated to the use of topical steroids.

Keratoconus is an elongation of the corneal surface that is thought to be caused by long-term eye rubbing and may be a degenerative change in the cornea. Keratoconus affects approximately 1% of children with atopic dermatitis and can generally be alleviated with the use of contact lenses.

Some advocate use a scoring system, the SCORAD (Index) is the best validated scoring system in atopic dermatitis.^[12] The extent of disease is measured by "the rule of nines," applied on a front/back drawing of the patient's inflammatory lesions. They are graded from 0-100 on 6 items, including erythema, edema/papulation, excoriations, lichenification, oozing/crusts, and dryness, with each item evaluated on a scale from 0-3.

The etiology of atopic dermatitis appears to be linked both to genetic causes and to environmental agents.

The prevalence of atopic dermatitis in children with one affected parent is 60% and rises to nearly 80% for children of two affected parents. Additionally, nearly 40% of patients with newly diagnosed cases report a positive family history for atopic dermatitis in at least one first-degree relative. Children of parents with atopic dermatitis have an increased risk of developing atopic dermatitis by age 3 years.^[13] Much higher concordance rates for atopic dermatitis are observed in monozygotic twins (77%) than in dizygotic twins (15%).^[2]

Recent evidence has demonstrated a strong genetic predisposition towards the development of atopic dermatitis in patients with loss-of-function mutations in the gene that encodes the epidermal structural protein filaggrin (FLG). Filaggrin deficiency causes a significant defect in the normal epidermal barrier that allows for enhanced allergen absorption through the skin, resulting in a higher incidence of dermatitis. FLG gene mutations have been associated with a more severe atopic dermatitis phenotype, earlier onset of atopic dermatitis, increased levels of systemic allergen sensitivity, and a higher proportion of patients with atopic dermatitis who eventually develop asthma.^[14]

In addition, the specific loss-of-function null mutation R501x in the filaggrin gene appears to confer a higher risk of developing eczema herpeticum, which is a rare but serious complication that requires treatment with antiviral medications.^[15]

Prenatal risk factors for atopic dermatitis are under investigation. Term infants of mothers who had gestational diabetes during pregnancy had an almost 8-fold increase in the prevalence of atopic dermatitis by age 6 years. Interestingly, this relationship did not occur in preterm infants of mothers with gestational diabetes. The reasons for this discrepancy are yet to be determined.^[16]

A retrospective study of 414 children and adolescents with atopic dermatitis suggested that prolonged obesity in early childhood may be a risk factor for atopic dermatitis; this advocated the concept that weight loss may facilitate prevention and treatment of childhood atopic dermatitis.^[17]

Environmental allergens repeatedly have been shown to trigger exacerbations of atopic dermatitis in susceptible individuals. Contact irritants, climate, sweating, aeroallergens, microbial organisms, and stress/psyche commonly trigger exacerbations.

Contact irritants (eg, soaps, solvents, wool clothing, mechanical irritants, detergents, preservatives, perfumes) compromise the integument, creating inflammation, irritation, and a portal of entry for further environmental insult. These surface irritants, along with the macerative effects of sweating and the drying effects of low humidity, lower the pruritic threshold. A vicious cycle of itching and scratching ensues, in which added cutaneous damage caused by scratching further lowers the pruritic threshold and subsequently causes increased itching.

Aeroallergens (eg, house dust mite, molds, pollen, dander) induce peripheral eosinophilia and elevate serum IgE levels. These early effects lead to increased histamine release from IgE-activated mast cells and elevated activity of the T-helper cell–mediated immune system. The increased release of vascular mediators (eg, bradykinin, histamine, slow-reacting substance of anaphylaxis [SRS-A]) induces vasodilation, edema, and urticaria, which in turn stimulate pruritus and inflammatory cutaneous changes.

Microbial agents (eg, S aureus, Pityrosporum yeasts, Candida organisms, Trichophyton dermatophytes) act in 2 different ways to promote the flares of atopic dermatitis. The microorganisms directly invade the skin, creating local injury and inflammation, and they induce a systemic allergic response to specific antigens, causing a rise in serum IgE and enhanced activity of the immune system.

Nearly all patients with atopic dermatitis are colonized by S aureus on lesional skin. More than half of patients with atopic dermatitis are colonized by S aureus strains capable of producing superantigens. These patients can develop superantigen-specific IgE antibodies that activate inflammatory cells in the skin. Staphylococcal enterotoxin B is a superantigen known to upregulate interleukin (IL)-31 expression in skin. IL-31 has been shown to induce pruritus and skin lesions resembling atopic dermatitis in mice.^[2]

Specific IgE levels to Malassezia furfur have been correlated with atopic dermatitis severity in a subgroup of patients. These Malassezia -specific IgE antibodies have been shown to crossreact with autoantigens in atopic dermatitis skin.^[2]

Food allergy is implicated as a cause in one third to one half of children with atopic dermatitis. Food allergens may be the initial trigger for IgE autoreactivity to epithelial autoantigens in young children with atopic dermatitis.^[2] The most common food allergens in children are egg, soy, milk, wheat, fish, shellfish, and peanut, which together account for 90% of food-induced cases of atopic dermatitis in double-blind, placebo-controlled food challenges. Fortunately, many clinically significant food allergies self-resolve within the first 5 years of life, eliminating the need for long-term restrictive diets.

Stress may trigger atopic dermatitis at the sites of activated cutaneous nerve endings, possibly by the actions of substance P, vasoactive intestinal peptide (VIP), or via the adenyl cyclase–cyclic adenosine monophosphate (cAMP) system.