Pediatric Dermatology

A Practical Overview of Pediatric Atopic Dermatitis, Part 2: Triggers and Grading

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Genetics and AD

Of 762 infants in a birth cohort with a parent with atopy in Cincinnati, Ohio, 39% developed eczema by the age of 3 years. Single nucleotide polymorphisms of IL-4Rα 175 V and CD14-159 C/T were linked to greater eczema risk at 2 to 3 years of age.23 Monozygotic twins have a concordance rate of 0.72 to 0.86 versus 0.21 to 0.23 in dizygotic twins, demonstrating a strong genetic component in the development of AD.24 Linkage to AD has been positively made to the epidermal differentiation complex on human chromosome 1q21, which contains the genes for filaggrin and other proteins such as loricrin. Other genes linked to AD include the serine protease inhibitor SPINK5 (serine peptidase inhibitor, Kazal type 5) implicated in Netherton syndrome (triad of ichthyosis linearis circumflexa, bamboo hair, and atopic disorders); RANTES (regulated on activation, normal T-expressed, and secreted), which has been associated with severity of AD; IL-4; and IL-13.5,25,26

The Hygiene Hypothesis

Atopic dermatitis is more common in wealthy developed countries, leading some to believe that hygiene and relative reduction in illness via vaccination have contributed to the rise of AD prevalence in developed nations.13,27 There currently is evidence demonstrating that wild-type varicella infection confers long-standing protection against AD and mediates reduced total IgE and peripheral blood lymphocytes.27

Grading of AD

Grading of AD is a subject of controversy, as there currently are no uniform grading scales.28 A recent outcomes group attempted to determine the best scale for disease monitoring. Schmitt et al29 presented the Harmonizing Outcome Measures for Eczema (HOME) roadmap, which was intended to determine a core outcome set for eczema; however, because these outcome measurements have not yet been standardized, only the eczema assessment and severity index (EASI) scoring system meets criteria for standardization. In clinical practice, physicians often assign mild, moderate, or severe labeling based on their general sense of the disease extent using an investigator global assessment score.28

The EASI score is a well-validated composite score of AD severity based on 4 body regions: (1) head and neck, (2) trunk (including genital area), (3) upper limbs, and (4) lower limbs (including buttocks). The total area of involvement in each region is graded on a scale of 0 to 6, and AD severity is graded as a composite of 4 parameters (ranked on a scale of 0–3), including redness (erythema, inflammation), thickness (induration, papulation, swelling [acute eczema]), scratching (excoriation), and lichenification (prurigo nodules [chronic eczema]). The surface area of each region relative to body size is used as a multiplying factor, resulting in the following severity strata: 0=clear; 0.1–1.0=almost clear; 1.1–7.0=mild; 7.1–21.0=moderate; 21.1–50.0=severe; 50.1–72.0=very severe (κ=0.75).30-32 The six area, six sign AD (SASSAD) score32,33 is a similar score without adjustment for body surface area by region.34

An older, now less frequently used eczema score is the SCORAD, which addressed surface area by rule of nines and severity of 6 features—redness, swelling, oozing/crusting, scratch marks, skin thickening (lichenification), dryness (assessed in an area with no inflammation)—by region on a scale of 0 to 3. A subjective symptom parameter for itching and sleeplessness helped highlight that these comorbidities are important in gauging disease activity and impact on a child’s life.35

Natural History of AD

The clinical dogma has been that AD would improve with age, with reduction at grade school entry and perhaps full disappearance in adulthood; however, 3 recent surveys have suggested otherwise. The ISAAC group has found prevalence of AD in wealthy developed countries among children aged 6 to 7 years to be at a consistent increase.36 A US-based survey from the National Health Interview Survey showed a 1-year prevalence of 10.2% of active AD in adults and 9.8% when occupational dermatitis was excluded.37 Halvorsen et al38 demonstrated that eczema prevalence is 9.7% in individuals aged 18 to 19 years.

A prospective trial of eighth graders followed from 1995 to 2010 demonstrated that AD persisted in 50% at school age. Persistent eczema into adulthood was associated with early-onset childhood allergic rhinitis and hand eczema.39 In a cohort of hand eczema patients (N=368), 28% had AD and 39% had an atopic illness.40 An association with allergic contact dermatitis and increased IgE to Malassezia furfur was further associated.41


The role of triggers and allergens in disease activity in AD is an important consideration in children with AD and requires ongoing consideration with age and varied exposures. Understanding the grading of AD is important in evaluating clinical trial data. The natural history of AD has changed, which is important for the practitioner to note when counseling patients and guardians.


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