Eczematous Disorders, Atopic Dermatitis, and Ichthyoses Part 1

Eczematous Disorders

Eczematous dermatitis, or eczema, is a skin disease that is characterized by erythematous vesicular, weeping, and crusting patches. Although the term eczema is often used as a diagnosis, it can in fact be used appropriately to describe lesions seen in several diseases. Itching is a characteristic symptom, and epidermal intercellular edema (spongiosis) is a characteristic histopathologic finding of eczematous conditions. The term eczema is also commonly used to describe atopic dermatitis [see Atopic Dermatitis, below].

Contact dermatitis

Contact dermatitis, a paradigmatic example of an eczematous disorder, is common and well studied [see 2:V Contact Dermatitis and Related Disorders]. Contact dermatitis can be either allergic or irritant in etiology. Allergic contact dermatitis differs from other eczematous disorders in that determination of the offending contactant is an important part of the evaluation. If the patient’s history does not provide the answer, the body site of the lesion may (e.g., head involvement in allergy to paraphenylenedi-amine in hair dye). Patch testing may be required to confirm the diagnosis.1

The manifestations of irritant contact dermatitis are similar to those of allergic contact dermatitis2; in the irritant form, however, the mechanism is not immunologic. Given sufficient concentration and duration of contact, offending agents will induce irritation in anyone’s skin. Detergents, acids, alkalis, solvents, formaldehyde, and fiberglass are common causes.

Seborrheic dermatitis

Seborrheic dermatitis is another common eczematous condition [see 2:II Papulosquamous Disorders]. Clinically, seborrheic dermatitis may exist without vesicle formation. Lesional morphology is usually a greasy scale on erythematous patches; however, the scale may be dry and the patches may have an orange hue. Scalp, eyebrows, mustache area, nasolabial folds, and chest are typical areas of involvement. Psoriasis may be part of the differential diagnosis. Treatment is with shampoos containing selenium sulfide, zinc pyrithione, tar, or ketoconazole; emollients; and mild (nonfluorinated) topical steroids. Antimicrobial therapy directed at the commensal yeast Pityrosporum ovale can be effective, although a causative role of the organism remains unproved.

Other eczematous dermatitides

Two other eczematous dermatitides are nummular eczema and dyshidrotic eczema (pompholyx). Nummular eczema describes well-demarcated, coin-shaped eczematous patches that are usually 2 to 4 cm (rarely more than 10 cm) in diameter. The lesions are quite pruritic and require potent topical steroids, an-tihistamines, and, occasionally, intralesional or systemic corti-costeroids for treatment. Dyshidrotic eczema presents as a vesicular eruption of the hands and feet, accompanied on rare occasions by hyperhidrosis. Typically, 1 to 2 mm vesicles appear on the sides of fingers, although more extensive involvement can occur. Treatment is with compresses and soaks, antipruritics, topical steroids, and, in severe recalcitrant cases, systemic corti-costeroids. Photochemotherapy with topical psoralen and ultraviolet A irradiation (PUVA) may also be effective.

Atopic Dermatitis

Atopic dermatitis (AD) is a common chronic inflammatory dermatosis that generally begins in infancy. The term atopy was coined in the early 1920s to describe the associated triad of asthma, allergic rhinitis, and dermatitis.3 Children with AD are at increased high risk of developing asthma and allergic rhinitis, and the risk is further increased for patients with a family history of atopy.4 The role of reaginic antibodies and allergies in the etiology of AD is controversial; in 80% of patients with AD, however, serum immunoglobulin IgE is elevated, sometimes markedly.

Etiology and pathogenesis

The expression of AD is a complex integration of environmental and genetic factors. The lifetime prevalence is estimated to be 30% of the population,5-7 possibly because of increasing contact with causative agents in the environment. Epidemiolog-ic data suggest a genetic influence—25% of dizygotic twins and 75% of monozygotic twins are concordant for AD.8 The condition develops in 60% of children who have one affected parent and in 80% of children with two affected parents.9 The defect is likely carried in the immune system, because both antigen-specific IgE reactivity and AD have been transplanted from an AD-affected bone marrow donor to a previously unaffected recipi-ent.10 Candidate genes continue to be investigated.11

AD can be quickly exacerbated by environmental trigger fac-tors.12 Wool, lanolin, and harsh detergents are particularly irritating. Emotional stress can also lead to flares, which are characterized by increased itch, erythema, vesiculation, and excoriation, as well as expanded area of involvement. The role of airborne and foodborne allergens is difficult to assess. Although patients with AD frequently have circulating dust mite antigen-specific IgE and Th2 CD4+ T cells,13 hyposensitization infrequently results in improvement. Contact urticaria to food occurs in AD,14 but generalized exacerbation after eating is rare. In the absence of a strong supporting history, elimination diets are rarely effective in treating AD. A role has been frequently suggested for cow’s milk in inducing AD; however, studies examining the association of AD and early feeding with cow’s milk have shown varying results.15,16 Meta-analyses indicate that exclusive breast-feeding during the first 3 months of life is associated with lower incidence rates of atopic dermatitis during childhood in children with a family history of atopy.17

Gut microflora may be a natural source of immune modulation that prevents atopic dermatitis. In a double-blind, randomized, placebo-controlled trial, a probiotic containing a strain of Lactobacillus was administered prenatally to mothers who had at least one first-degree relative with atopy and 6 months postna-tally to their infants; the frequency of AD in the group receiving Lactobacillus was half that of the placebo group.18 These findings suggest that impairment of the intestinal mucosal barrier may be involved in the pathogenesis of AD, and strengthening of the mucosal barrier with probiotic bacteria may help prevent AD in high-risk infants. Although intriguing, these results await confirmation.

Mechanisms have been proposed to explain a link between Staphylococcus aureus and exacerbations of AD,19 including effects of cell wall constituents to increase expression of IgE, IgE receptor, and enterotoxin B, a superantigen that activates T cells in an antigen-independent fashion.20

The apparent paradox of reduced cell-mediated immunity21,22 and hyperimmunoglobulinemia E seen in AD is addressed by the so-called Th1/Th2 model of helper T cells. In this model of the murine immune system, CD4+ T cells are divided into two mutually exclusive classes on the basis of cytokine secretion: Th1 cells, which secrete cytokines that promote cell-mediated immunity (e.g., interleukin-2 [IL-2], interferon gamma), and Th2 cells, which secrete cytokines that promote humoral immunity and eosinophil function (e.g., IL-4 and IL-5). Atopy, including AD, has been seen as the paradigmatic condition of a so-called Th1-deficient state. Refinements have shown a heterogeneity of responses within different AD lesions, however. The current model is that blood and acute lesions of AD patients are more often dominated by Th2 cells, whereas chronic lesions are more often dominated by Th1 cells.23

Table 1 Diagnostic Criteria for Atopic Dermatitis14

Major criteria

Personal or family history of atopy (atopic dermatitis, allergic rhinitis, allergic conjunctivitis, allergic blepharitis, or asthma)

Characteristic morphology and distribution of lesions


Chronic or chronically recurring dermatosis

Minor features

Hyperimmunoglobulinemia E

Food intolerance

Intolerance to wool and lipid solvents

Recurrent skin infections


Sweat-induced pruritus

White (not red) dermatographism


Chronically scaling scalp

Accentuation of hair follicles

Recurrent conjunctivitis

Anterior subcapsular cataracts and keratoconus

Morgan line, or Dennie sign (single or double creases in the lower eyelids)

Periorbital darkening (allergic shiner)

Pityriasis alba (hypopigmented, scaling patches, typically on the cheeks)


Anterior neck folds

Keratosis pilaris (perifollicular papules with keratotic plugs, typically on the arms and thighs)

Nipple eczema

Hyperlinear palms (increased folds, typically on the thenar or hypothenar eminence)

Recurrent hand and foot dermatitis

Exacerbation of symptoms by environmental or emotional factors

Hyperstimulatory dendritic antigen-presenting cells (Langer-hans cells) are present in patients with AD.24 One proposed mechanism for the augmented function of Langerhans cells in AD is the binding of antigen-specific IgE and antigen to the IgE receptors on Langerhans cells as a means of antigen focusing.25 Another antigen-presenting cell, the monocyte, also manifests altered function in AD. Cyclic adenosine monophosphate (cAMP) phosphodiesterase has increased activity in monocytes of patients with AD—leading to hyperproduction of prosta-glandin E2, among other effects. Increased cAMP phosphodi-esterase in AD may explain aberrant adrenergic responses, and the increased prostaglandin E2 leads to diminished interferon-gamma production. Additionally, monocytes secrete IL-10 in AD, which further augments the so-called Th2 responses.26 Altered cyclic nucleotide metabolism leads to excessive release of histamine by basophils and, potentially, to mast cell degranula-tion. High levels of cAMP phosphodiesterase are found in the umbilical cord blood of infants of AD-affected parents.27 This finding may indicate an early, if not primary, defect in the disease that may become the basis of a diagnostic laboratory test.

Because IL-5 is a critical eosinophil growth factor and activating cytokine, blood eosinophilia may be expected to occur in a Th2 disease such as AD28; tissue eosinophilia, however, is variable. Cutaneous endothelial cells are also activated in AD, leading to increased expression of adhesion molecules and recruitment of leukocytes into the skin (i.e., dermatitis).


AD remains a clinical diagnosis. Major diagnostic criteria are (1) personal or family history of atopy (AD, allergic rhinitis, allergic conjunctivitis, allergic blepharitis, or asthma); (2) characteristic morphology and distribution of lesions; (3) pruritus; and (4) chronic or chronically recurring dermatosis. Several minor features can be added [see Table 1].14 Pruritus is a consistent feature of AD. The lack of itching or of another major diagnostic criterion should prompt consideration of alternative diagnoses [see Differential Diagnosis, below]. Cutaneous signs can vary, depending on the age of the lesions.

Acute lesions of AD are eczematous—erythematous, scaling, and papulovesicular. Weeping and crusted lesions may develop [see Figure 1]. Scratching results acutely in linear excoriations, presenting as erosions or a hemorrhagic crust. In extremely severe cases, exfoliative dermatitis (erythroderma) may occur, with generalized redness, scaling, weeping, and crusting. There may be accompanying systemic toxicity, sepsis, lymphadenopa-thy, altered thermoregulation (either hyperthermia or hypothermia), and high-output cardiac failure. Erythroderma is a potentially life-threatening condition.

Chronic lesions tend not to be eczematous (thus, atopic eczema is not an ideal synonym for AD). Instead, lichenified plaques [see Figure 2] or nodules predominate. Lichenification denotes areas of thickened skin divided by deep linear furrows. Lichenified plaques result from repeated rubbing or scratching and thus often occur in areas of predilection, such as the popliteal and antecubital fossae. As is typical of lesions in AD, lichenification is poorly demarcated. There may be accompanying acute signs. Lichenified lesions are very difficult to treat; once established, they may persist for months even with adequate therapy and avoidance of rubbing or scratching.

Clinical expression of AD also varies with the age of the patient. The infantile stage of AD occurs up to approximately 2 years of age. Of all cases of AD, approximately 90% arise before the fifth year and 60% in the first year of life; onset before 2 months of age is unusual, however.8 During infancy, ill-defined, erythematous scaling patches and confluent, edematous papules and vesicles are typical. These lesions may become crusted and exudative. Intense pruritus leads to scratching, which induces linear excoriations and, with time, lichenification. Before the infant begins to crawl, the scalp and face are most often involved [see Figure 3], although lesions may be seen anywhere. After the child begins crawling, the extensor surfaces—particu-larly the knees—become involved. Involvement of fingers can be severe if the child sucks them frequently. Intense pruritus can lead to sleep disturbances of child and parents. Other features may arise [see Table 1]. Perifollicular accentuation and papules are commonly seen at any point in the life of an atopic patient, particularly in persons of Asian or African ancestry.

During childhood, the clinical features evolve into those seen in adults. Lesions tend to become less eczematous and drier, with increasing flexural and neck involvement. Scaling, fissured, and crusted hands may become especially troublesome. Infraor-bital folds (sometimes called Morgan lines or the Dennie sign) and pityriasis alba can appear. Chronic or chronically relapsing pruritic, erythematous, papulovesicular eruptions that progress to scaling, lichenified dermatitis in a flexural distribution typify adult AD. Extensive areas of skin may be involved, including the face, chest, neck, flanks, and hands. Areas of dyspigmenta-tion may result from repeated skin trauma. Approximately 10% to 15% of childhood AD persists after puberty.8

AD that begins after 20 years of age has been termed adult-onset atopic dermatitis.29 This condition should be considered in patients with characteristic features of AD.

There are many associated features of AD. Asthma and allergic rhinitis, the major and minor criteria, respectively, have already been mentioned. Another important association, cutaneous infection, is related to diminished cutaneous cell-mediated immunity and defective chemotaxis. S. aureus is usually found on AD skin, and its density correlates with lesion severi-ty.30 Although such observations have implicated S. aureus as a cause of AD,19,31 it is also clear that reduction in AD lesions reduces bacterial colonization.32 Regardless, the high bacterial counts in lesional skin and the relative ease of their reduction suggest the desirability of extra efforts (e.g., use of topical steroids) to reduce the presence of S. aureus before elective procedures are performed through involved skin. Frank infection also occurs more commonly in AD, which results in pustules and oozing, crusted lesions.

Cutaneous fungal and viral infections also occur frequently and with increased severity in patients with AD. Eczema her-peticum, an extensive eruption of 2 to 3 mm vesicles, pustules, and punched-out erosions caused by herpes simplex virus, may coalesce into extensive areas of eroded skin. Frequently, the condition is most severe on the face (where it often arises from a her-petic lesion) and diminishes as it progresses to the trunk and extremities. Secondary bacterial infection is common. Lym-phadenopathy, fever, and malaise may develop. Antiviral and antibiotic therapy can be lifesaving and should be started empirically upon presentation. Tzanck test, viral culture, and direct fluorescent antibody detection of viral antigens can confirm the diagnosis.

Molluscum contagiosum and common warts are also problematic in patients with AD, as are dermatophyte infections. Because of similar appearance, foot eczema must be distinguished from tinea pedis by potassium hydroxide preparation or fungal culture.

Extensive, severe, weeping, crusted acute eczematous patches on the face of this infant are characteristic of patients in this age group.

Figure 1 Extensive, severe, weeping, crusted acute eczematous patches on the face of this infant are characteristic of patients in this age group.

Lichenified patches appear after chronic rubbing of eczematous patches. These lesions are characteristic of chronic allergic contact dermatitis and atopic dermatitis.

Figure 2 Lichenified patches appear after chronic rubbing of eczematous patches. These lesions are characteristic of chronic allergic contact dermatitis and atopic dermatitis.

Numerous ocular complications of AD exist.33 These include anterior subcapsular cataracts, retinal detachment, keratoconus, blepharitis, conjunctivitis, and iritis.

Differential diagnosis

The differential diagnosis of AD includes the eczematous conditions and ichthyoses described in this topic and other immunologic, metabolic, neoplastic, and rheumatologic disorders [see Table 2]. Because 80% to 85% of patients with occupational hand dermatitis have AD, the possibility of coexisting AD and contact dermatitis needs to be considered. Another important element of the differential diagnosis is cutaneous T cell lymphoma. Cutaneous T cell lymphoma can arise clinically as scaling, erythematous patches or exfoliative erythroder-ma. The classic distribution—near axillae, buttocks, and groin—is distinct from that of AD, and patches are frequently well demarcated. There is often sufficient clinical overlap between the two conditions, however, to necessitate further investigation, including histology, immunophenotyping, and gene-rearrangement analysis of T cell receptors. Cutaneous T cell lymphoma can arise in patients with AD, and the lack of conclusive clinical or laboratory tests for either disease can make distinction difficult. Reassessment from time to time in such cases is recommended.

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