The criteria consists of 1 mandatory criterion—pruritis—plus ≥3 of the following 5 major criteria: history of flexural involvement, history of dry skin, onset of AD <2 years of age, history of any other atopic condition (eg, asthma), and visible flexural dermatitis.12 Validation of the criteria in dermatology patients provided a sensitivity and specificity of up to 85% and 96%, respectively.14 A more recent systematic review of 19 studies, however, has reported that while specificity was similarly high, sensitivity varied widely—between 10% and 100%.9
The Millennium criteria were first introduced in 1998 by Bos and colleagues, who sought to further distill and condense the Hanifin–Rajka and the UK Working Party criteria into a set that would identify and diagnose patients with true AD.15 It was the first criteria to include the presence of allergen-specific IgE as a diagnostic feature.
Further refined and validated by Schram and colleagues in 2011,16 the Millennium criteria mandate that ≥5 criteria are necessary to accurately identify AD patients: typical morphology, early age of onset, Dennie–Morgan infra-orbital skin fold, history of flexural involvement, and visible flexural eczema. The authors compared their refined criteria with the Hanifin–Rajka and UK Working Party criteria in a cohort of 210 outpatients for whom a diagnosis of AD was considered in the differential diagnosis. The Millennium criteria showed a sensitivity of 81.8% and a specificity of 98.8% compared with 100% and 48.8% for the Hanifin–Rajka criteria and 97.7% and 72.9% for the UK criteria, respectively.16
American Academy of Dermatology (AAD) Guidelines
In 2014, the AAD, the leading resource for dermatologists in the US, in conjunction with well-renowned experts in the field of AD, produced guidelines for AD diagnosis and assessment.5 The guidelines describe the clinical features that should be considered when making a diagnosis and are classified into essential, important, and associated features (Table 1).
Essential features in the AAD guidelines are those that must be present for an AD diagnosis to be made, and include: pruritis, eczema, timeline of disease, morphology, and disease pattern/ history (chronic or relapsing). Important features are those observed in most cases, lending support to the diagnosis. These include early age of AD onset, a personal/family history of atopy and/or IgE reactivity, and xerosis. Associated features are those suggestive of disease but are considered too non-specific. The AAD consensus criteria also recommend that physicians exclude conditions that mimic AD when making a diagnosis; these include scabies, irritant or allergic contact dermatitis, seborrheic dermatitis, cutaneous T-cell lymphoma, ichthyoses, psoriasis, photosensitive dermatoses, erythrodermas, and immunodeficiency disorders (Table 1).
Current Treatment Guidelines for AD
The current US recommendations for the treatment of AD, developed by the AAD were last updated in 2014.17,18 Topical agents form the basis of AD treatment. Non-pharmacologic approaches such as moisturizers, bathing practices, and wet wraps focus on moisturization and restoration of epidermal barrier function, with the aim of avoiding disease flares and the need for pharmacologic intervention.17 Pharmacologic topical therapies include corticosteroids, calcineurin inhibitors, phosphodiesterase inhibitors, antimicrobials, and antihistamines. Topical corticosteroids (TCS) are typically introduced after failure to respond to preventive measures and are often used alongside topical calcineurin/ phosphodiesterase inhibitors to maintain remission. Although the incidence is low, both topical and systemic side effects can occur with TCS and this should be considered, particularly when treating children. Topical calcineurin inhibitors are particularly useful at sensitive sites, such as the face and skin folds, where there is a greater adverse risk profile with TCS.17
Patients whose AD is refractory to topical agents require systemic treatments. According to the AAD, these are indicated “for the subset of adult and pediatric patients in whom optimized topical regimens and/or phototherapy do not adequately control the disease, or when quality of life is substantially impacted”.18 While phototherapy is still used in certain cases, the more prevalent treatment options are systemic immunomodulatory agents. The AAD guidelines suggest that cyclosporine (level of evidence: BI-II), methotrexate (BII), mycophenolate mofetil (CIII), and azathioprine (BII) are more widely used and more efficacious than IFN-g (BII) and oral calcineurin inhibitors.18 The AAD guidelines recommend avoiding systemic steroids for the treatment of AD, stating that their use should be restricted for acute severe exacerbations and as a bridge therapy to another systemic, steroid-sparing treatment.18
Despite the ongoing development of immunomodulatory biologic agents specifically targeting the type 2 inflammation common to AD, biologics are not mentioned as a systemic treatment option in US guidelines,19–21 though they are included in the most recent European guidelines.22 There is an urgent need for the AAD to address this omission.
In 2017, an expert panel from the International Eczema Council proposed in a consensus statement that the decision to start