A Patient With Extensive AD Unresponsive to Topical Treatment
A 34-year-old Filipino woman presented with a lifelong history of extensive atopic dermatitis (AD). Antecubital fossae involvement with lichenification and dyspigmentation is evident (Figure).
Other areas affected include her face, neck, trunk, and limbs. The patient reported that treatment with topical corticosteroid (betamethasone valerate) cream was ineffective at managing acute flares. The remainder of the physical exam was unremarkable.
Overview and Categorization
AD is a chronic, inflammatory skin condition that affects up to 20% of children and 1% to 3% of adults.1,2 It tends to present in individuals prior to 5 years of age and clears in many cases by adolescence. Pruritus is the hallmark of the condition. AD is often referred to as the “the itch that rashes” due to its cyclical “itch-scratch” nature.
The clinical presentation is variable dependent on disease activity. Acutely, it tends to present as erythematous papules and/or vesicles, often with exudation, crusting, and weepy patches. Chronically, it can present as dry, scaly erythematous papules or plaques, frequently with excoriation and lichenification.3
Left untreated, AD can affect quality of life, family dynamics, and sleep.4 AD frequently presents alongside asthma and allergic rhinitis in an atopic march, a triad with a strong familial component.5
AD is a clinical diagnosis based on history, morphology, skin lesion distribution, and clinical signs and symptoms. Infants tend to present with red, dry, scaly, and crusty areas on extensor surfaces, cheeks, and scalp.6 In older children, the rash presents most commonly in a flexural distribution.6 In adults, AD tends to be more localized to flexural surfaces, hands, eyelids or nipples, and the chronicity causes skin to be drier and lichenified.6 Despite these patterns, with severe disease, any body area can be affected at any age.
While comprehensive, the extensive 1980 Hanifin and Rajka criteria can be difficult to apply in clinical practice as many of the specifications are nonspecific and uncommon. The United Kingdom Working Party tapered the Hanifin and Rajka criteria.7-9 It requires patients to have a history of itchy skin and at least 3 of the following: history of a flexural involvement, visible flexural dermatitis, personal history of asthma or hay fever (or history of atopic disease in parents or siblings if the patient is younger than 4 years), history of generally dry skin in the last 12 months, and onset younger than age 2.
The American Academy of Dermatology also streamlined the Hanifin and Rajka criteria into a set applicable to patients of all ages10 (Table).
The pathogenesis of AD is multifactorial, involving genetic mutations, skin barrier dysfunction, impaired immune response, and environmental factors. The most common genetic basis lies in the filaggrin gene (FLG) that encodes profilaggrin.11 Profilaggrin gets cleaved into filaggrin, a protein that breaks down into the components of the natural moisturizer factor which maintains skin hydration and promotes water retention.
Loss-of-function mutations impair the skin’s barrier function and cause excess transepidermal water loss, leading to prolonged dryness.12 Disproportionate activity between stratum corneum proteases (ie, kallikrein) and protease inhibitors (ie, LEKTI) as well as abnormalities in tight junction proteins also contribute to skin barrier dysfunction.13 Decreased toll-like receptor (TLR) 2 and TLR9 function cause a defect in the immune-mediated skin barrier function.14,15 An excess of T-helper (Th) 2 cells and their associated cytokines augments the skin barrier dysfunction and allows for enhanced allergen and irritant penetration.16
In AD, the Langerhans cells have an exaggerated response to these antigens and cause an excessive Th2 cell response, worsening the skin barrier and perpetuating the cycle. This results in a reduction of ceramide, filaggrin, and antimicrobial peptides.17 The skin is also hyperreactive to environmental stimuli, such as food and inhalant allergens, irritants, humidity, and stress. The components of the skin microbiome have also been causatively implicated.18,19
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