Atopic dermatitis is a complex heterogeneous inflammatory disease with type I and IV allergies intertwined in a complicated manner, and the etiology may be multifactorial (genetic, immunologic, and environmental).¹⁴,¹⁵ There are two competing theories to explain the etiology. The most commonly accepted theory is that the disease occurs because of an intrinsic genetic defect in the epidermal barrier.² Filaggrin is a key protein that controls the terminal differentiation and formation of the epidermis, as well as maintenance of the skin barrier.² A genetic defect in this protein disrupts the epidermis, which allows allergens or irritants to penetrate the epidermal barrier easily.¹⁶ This event facilitates contact between immune cells in the dermis and antigens from the external environment, thus inducing a secondary immunologic reaction. This hypothesis is dubbed the outside-to-inside hypothesis and is the most accepted theory.¹,² Atopy leads to intense itching and scratching, which in turn can lead to further disruption and inflammation of the epidermal skin barrier. This results in a vicious cycle that has been dubbed the itch-scratch cycle.¹ That said, it should be noted that the genetic origin of atopic dermatitis is complex and poorly understood. Multiple alleles at several susceptibility loci, including 3q21, 1q21, 17q25, and others, have been proposed recently and are summarized elsewhere.¹⁷ Genetic defects in the filaggrin protein are also implicated in other forms of atopy like allergic rhinitis and asthma.¹⁶,¹⁸

An alternative theory that was more popular in the past is the so-called inside-to-outside hypothesis.²,¹⁹,²⁰ This theory postulates that cutaneous inflammation precedes barrier impairment and that immunological aberrations are a primary event in the initial development of atopic dermatitis. Regardless of the correct theory, the ultimate pathogenetic event is a leaky epidermal barrier or skin barrier insufficiency.¹⁶

It is difficult to attribute the global increase in the prevalence rates of atopic dermatitis to genetic or immunologic factors alone; in fact, both theories require a trigger factor.¹⁹ Environmental exposure to various agents may trigger initiation or flare-up of the disease in predisposed individuals.¹⁶,¹⁹ These factors may occur due to in utero or early life exposure to various environmental and climatic irritants or pollutants.¹⁹

The hallmark of the disease is early-onset, chronic relapsing pruritic dermatitis, with eczematous eruptions that are often accompanied by diffuse and symmetrical erythema.¹⁴,¹⁶ Atopic dermatitis is a common chronic disease affecting approximately 10% to 20% of the general population, and the prevalence is steadily increasing, at least in developing countries.² About 40% of patients have a history of other atopic diseases such as allergic rhinitis or asthma, and the disease is more frequent in females.⁴,²¹ Because of the strong genetic component, the onset of atopic dermatitis usually occurs within the first 2 years of life, and approximately 85% are
afflicted with the disease before the age of 5 years, although the incidence and prevalence increase with advancing age.¹²,¹⁶

A major obstacle in diagnosing atopic dermatitis is the clinical overlap with other dermatologic problems, as well as the lack of definitive biomarkers and histological findings for the disease. Therefore, the diagnosis has to be based on clinical findings, including the characteristic morphologies, age-dependent distribution, and associated clinical signs.³ The diagnostic criteria of atopic dermatitis have been laid out by Hanifin and Rajka in 1980 and included major and minor criteria.⁷,⁸ At least three of the major and minor criteria should be present to establish the diagnosis. Major criteria include (1) pruritus; (2) typical morphology and distribution of the lesions (facial and extensor involvement in infants and children or flexural lichenification in adults); (3) chronic or chronic relapsing dermatitis; or (4) personal or family history of other atopic diseases (asthma, allergic rhinitis).⁷,⁸ Minor criteria include cataracts, cheilitis, eczema, blepharoconjunctivitis, facial pallor or erythema, food intolerance, nonallergenic hand dermatitis, ichthyosis, elevated IgE, a predisposition to recurrent cutaneous infections (staphylococcal blepharitis, etc), Dennie-Morgan lines (prominent infraorbital lines, creases, or folds), itching when sweating, keratoconus, periorbital hyperpigmentation (allergic shiners), nipple dermatitis, palmar hyperlinearity, pityriasis alba (children), white dermographism, wool intolerance, or xerosis.⁷ A detailed discussion of alternative diagnostic standards including the criteria laid out by the American Academy of Dermatology and the Japanese Dermatological Association is beyond the scope of this chapter and is discussed elsewhere in the literature.¹⁴,²²

Eyelid changes may begin with spongiotic dermatitis consisting of red, pruritic, inflamed areas of cracked skin with fluid accumulation (Figure 52.1A) and then evolve to broad areas of erythematous, edematous, indurated, or weeping eczematous lesions (Figure 52.1B). Pruritus often leads to chronic rubbing, and as a result, the eyelid skin becomes violaceous early on (Figure 52.2), and with time, this violaceous hue evolves into periorbital hyperpigmentation, which is a common characteristic of the disease. Coalescent papules, fissures, and fine scaling may also be observed. As the condition progresses into chronicity, thickening and accentuation of normal skin lines (lichenification) are observed. This thickening occurs more frequently in the medial part of the upper or lower eyelids (Figure 52.3).¹³ Alternatively, periocular skin atrophy or hypopigmentation may be concomitantly observed if corticosteroid ointment was chronically applied in the past.¹³

Gradually, eversion or stenosis of the lacrimal puncta may occur, and frank ectropion may be seen in severe cases, as well as the loss of eyelashes. Infectious complications are common, and it has been shown that a significant proportion of patients with atopic dermatitis show bacterial colonization in the conjunctival sac and on the eyelid margins.²³ This secondary bacterial infection is commonly attributed to the colonization of the eczematous skin with Staphylococcus aureus and usually leads to chronic anterior blepharitis, which may make the diagnosis difficult. Also, bacterial infection may lead to skin ulceration with serous exudation.¹³

Patients with atopic dermatitis may have associated atopic keratoconjunctivitis, typically presenting with symptoms of chronic ocular irritation (burning, itching, and redness), which may be exacerbated during cold damp weather. These patients usually manifest with diffuse conjunctival injection and superficial punctate corneal epitheliopathy that may be attributed to chronic eye rubbing.¹³ Other clinical signs include chronic nonspecific papillary conjunctivitis, giant papillary conjunctivitis, symblepharon, corneal
vascularization, corneal pannus, stromal scarring, corneal opacification, keratoconus, or cataracts.⁶,¹³,²⁴,²⁵,²⁶,²⁷,²⁸,²⁹,³⁰,³¹ The prevalence of cataracts (particularly anterior or posterior subcapsular cataracts) in patients with atopic dermatitis is increased compared with the general population (8%-17%).²⁴,²⁵,²⁶,²⁷,²⁸,²⁹,³⁰,³¹ The mechanisms behind cataract formation remain elusive; however, a mechanical cause due to repetitive local rubbing and scratching or oxidative stress may be responsible.²⁷ Anterior subcapsular cataract appears to be more specific to the disease, but posterior subcapsular cataract is also very common.²⁷