Clinical Presentation

Introduction

The clinical presentation of Atopic Dermatitis (AD) is heterogenous. Acute AD presents with erythema, edema, scaling and excoriations. In more severe case, vesicles/papules are present, with crusting and serious drainage. Dyspigmentation and lichenification (skin thickening and accentuation of skin lines) are symptoms of chronic lesions, and are more prominent in darker skin. Pruritus is the hallmark symptom and is responsible for much of the disease burden. The itch-scratch cycle contributes to barrier dysfunction and facilitates secondary infections, both cutaneous and extra-cutaneous. Clinical findings vary by patient age and chronicity, which can range from mild, intermittent disease to severe, persistent disease. Diagnosis of AD is based on clinical findings, including history, morphology and distribution of lesions and associated signs and symptoms. Diagnostic criteria have been developed to aid in diagnosis. This module will review the clinical features of AD, highlighting differences between childhood and adult-onset AD. Differential diagnosis of AD will also be discussed, since accurate diagnosis is critical to optimal patient care.

Diagnostic Features of AD

Hanifin and Rajka Criteria

The Hanifin and Rajka criteria are recognized as the earliest diagnostic criteria for AD (Table 5-1). To meet these criteria, patients must have three of four major features and three of 23 minor features. Although these criteria have been streamlined by several groups, including the American Academy of Dermatology (AAD), they are still the most commonly used criteria in clinical trials. The following section will discuss the major and minor features of the Hanifin and Rajka criteria.

Major Hanifin and Rajka features (patients must have at least three of four):

• Pruritus: The hallmark symptom; active AD cannot be diagnosed without a history of itching. Skin lesions are typically diffuse and very pruritic.
• Typical morphology and distribution: Facial and extensor involvement in infants and children; flexural erythema and/or lichenification at all ages. The axillary folds are commonly involved and part of the flexural distribution; however, the axillary vault is typically spared. The diaper area and groin are typically spared.
• Chronic or chronically-relapsing dermatitis: AD is characterized by flares, often without obvious triggers. Flares and relapses can occur as often as weekly during active disease, or years after seemingly complete remission.
• Personal or family history of atopy (asthma, allergic rhinitis, AD): Allergic respiratory disease is present in up to 50% of patients, and approximately 70% of patients with AD have a family member with one or more manifestations of atopy.

Minor Hanifin and Rajka features (patients must at least have three of 23). These are less specific or relatively rare:

• Xerosis: The presence of generalized dry skin, which tends to fluctuate with disease severity.
• Ichthyosis/palmar hyperlinearity/keratosis pilaris: Ichthyosis vulgaris is a distinct dermatologic disease that causes extremely dry, thick and scaly skin. Hyperlinear palms and soles are a clinical feature of ichthyosis vulgaris. Up to 37% of patients with AD have evidence of ichthyosis vulgaris. AD and ichthyosis vulgaris are closely associated because loss-of-function mutations in the filaggrin gene play important roles in both conditions. Keratosis pilaris is a separate entity characterized by hyperkeratosis and erythema around the follicles, typically affecting the cheeks, anterior thighs and extensor upper arms.
• Immediate (type I) skin test reactivity: Approximately 80% of patients with AD manifest Type I responses to skin test antigens.
• Elevated serum lgE: Immunoglobulin E (IgE) plays an essential role in other allergic disorders (eg, asthma, hay fever, food allergy), but its importance in AD is unclear: 20% to 50% of patients with AD have normal total and allergen-specific IgE levels.
• Early age of onset: AD onset is seen in most patients before the age of 5.
• Tendency toward cutaneous infections: Patients with AD are at greater risk of infection, especially Staphylococcus aureus and Herpes simplex. S aureus can be cultured from >90% of patients with AD compared with approximately 5% of the general population. In addition, AD patients were found to have higher odds of extra-cutaneous, multi-organ and systemic infections with bacteria, mycobacteria, viruses and fungi.
• Tendency toward nonspecific hand or foot dermatitis: Hand eczema occurs in approximately 70% of patients with AD, with the disease starting on the hands in one third of cases.
• Nipple eczema: Not common, but the presence of chronic, lichenified, fissured, or weeping dermatitis on one or both nipples is fairly specific to AD.
• Cheilitis: Inflammation of the lips. Chronic desquamation of the upper lip is fairly specific to AD; both lips and perioral area are involved in many patients.
• Recurrent conjunctivitis: Commonly coexists with allergic rhinitis but may exist independently. Considerable conjunctival involvement may progress to severe ectropion.
• Dennie-Morgan infraorbital fold: Double skin-fold beneath the lower eyelids that is indicative of respiratory atopy and not specific to AD. A double-fold is present in approximately 30% of patients with AD. and should prompt evaluation for airborne allergies.
• Keratoconus: Progressive eye disease that is very infrequently seen in AD patients.
• Anterior subcapsular cataracts: Spontaneous development of bilateral cataracts in the anterior lens is quite specific for AD. Affects up to 16% of patients, most often with severe disease.
• Orbital darkening: Discoloration and swelling around the eyes. Referred to as “allergic shiners” and is indicative of respiratory atopy. Present in many patients with AD.
• Facial pallor/facial erythema: Both may be present simultaneously.
• Pityriasis alba: Post-inflammatory asymptomatic hypopigmentation occurring primarily on sun-exposed areas of patients with darker skin. The pigmentation changes are temporary but may persist for months to years.
• Anterior neck folds: Horizontal neck creases are present in most patients with AD.
• Itch when sweating: An almost universal symptom of AD, triggered by exertion, sweating, or occlusion.
• Intolerance to wool and lipid solvents: Likely due to a decreased itch threshold to irritants.
• Perifollicular accentuation: A pebbled appearance of the skin, most prominent in patients of African and Asian descent.
• Food intolerance: Cutaneous reactions to food. These reactions subside during childhood, but some adults retain this food sensitivity.
• Course influenced by environmental/emotional factors: AD is highly associated with stresses and environmental changes.
• White dermographism/delayed blanch: Stroking AD skin will produce a white line instead of the normal triple response of Lewis.

Enlarge 

Other Diagnostic Criteria

Although the Hanifin and Rajka criteria are extensive, several other clinical features can be present in AD patients. The allergic salute, a linear nasal crease resulting from repeated rubbing of the nasal tip, is common among patients who suffer from allergic rhinitis and can also be observed in AD patients. Eruption-type reactions, resulting from photosensitivity to UBA and/or UVB, have been observed in up to 3% of patients with AD in some studies. In addition to hypopigmentation, some individuals may experience post-inflammatory hyperpigmentation, which can also last for months to years following disease clearance or cause permanent loss of pigment at healed sites of previous deeper erosions or ulcers.

In the context of clinical trials, the Hanifin and Rajka criteria remain the most widely used criteria worldwide and in the US. However, the comprehensiveness of the Hanifin and Rajka criteria makes them difficult to implement in clinical practice, and more streamlined diagnostic criteria have been developed by several national and international professional organizations and working groups, including the American Academy of Dermatology (AAD). The AAD criteria were developed specifically to be applicable in the clinical setting and in all age groups affected by AD. In the AAD criteria (Table 5-3), features that inform a diagnosis of AD include:

1. Essential features, which must be present in all cases of AD (pruritus, eczema);
2. Important features, which are present in most cases of AD (early age of onset, atopy, xerosis); and
3. Several associated features, which may be present in a clinical setting but are too non-specific for use in clinical trials.

The AAD criteria also list several exclusionary conditions (e.g., scabies, contact dermatitis, psoriasis and others listed in Table 5-3) which must be ruled out before a diagnosis of AD is made.

Enlarge 

Comorbidities

AD commonly presents with comorbidities, some of which are not restricted to the skin. These include other atopic diseases, neuropsychiatric disorders, autoimmune diseases, infections, cancer and obesity and cardiovascular disease.

Biomarkers

Numerous biomarkers have been evaluated for utility in diagnosing and/or treating AD. However, there are currently no biomarkers that accurately reflect the severity of AD or its symptoms, or distinguish AD from other diseases. As such, the diagnosis and severity assessment of AD remains entirely clinical.

Patient History

The most common age of onset occurs during infancy, typically younger than 6 months. However, numerous studies showed high rates of adolescent- and/or adult-onset AD. A systematic review and meta-analysis of 25 studies found that approximately one in four (26.1%) adult AD patients report adult-onset disease. Dry and sensitive skin may be present since birth and typically precede the onset of dermatitis per se. The active dermatitis may be persistent or wax and wane for months. Parents of the infant may also report a history of poor sleep and irritability, resulting from nighttime scratching. Older children and adults relate a history of pruritus, often described as a spreading itch. Clinicians should inquire about a family history of atopy, since approximately 70% of patients with AD have a positive family history of atopic disease. Children having one parent with atopic disease are at 2- to 3-fold higher risk of developing AD; this increases to 3- to 5- fold if both parents have atopic disease. However, personal and/or family history of atopic disease are less common in patients with adult-onset AD. A meta-analysis of 66 studies showed that parental history of allergic rhinitis and asthma were also associated with risk of AD in children, although parental history of AD was associated with the highest risk of their children developing AD. In a study of urban children from 20 US cities, persistent AD was associated with higher odds of ever having asthma. These findings suggest that AD and other atopic diseases have common underlying mechanisms. In some patients, atopic diseases manifest in an “atopic march”, a characteristic sequence which starts with AD and progresses to food allergies, asthma and finally allergic rhinitis.

The longitudinal course of AD lesional extent and severity in clinical practice is poorly understood. A prospective study in pediatric and adult patients with a 2-year observational period found that the majority of patients had fluctuating AD severity, with a smaller proportion showing persistent disease severity or improvement. A history of xerosis or food allergy was identified as a predictor of persistent moderate-to-severe disease.

History of atopic comorbidities is associated with more severe AD and a higher probability of itch triggers in AD. In a study of adult AD patients, hay fever was associated with a higher probability of sweat, stress, heat, hot temperature and weather change as triggers, while asthma or food allergy were associated with a higher probability of all triggers.

Clinical Presentation

AD is characterized by pruritus and xerosis, serosanguinous discharge, erythematous plaques, with lichenification following chronic rubbing and scratching. Pruritus is the most prominent feature of AD and can be severe, causing flares, exacerbations and chronic excoriations of the skin. For this reason, AD is referred to as the “itch that rashes.” Itching and scratching lead to secondary skin changes, which contribute to disruption of the epidermal barrier, perpetuating the disease and ultimately worsening the “itch-scratch cycle.” In severe cases of the disorder, especially in those whose disease persists into adulthood, disease may even progress to generalized erythroderma.

AD can be divided into three subsets, based on age of onset: infantile, occurring from infancy to age 2; childhood/adolescent, from 2 years old to puberty; and adult, occurring after puberty. Affected areas common to all age groups are shown in Figure 4-1. Approximately 60% of childhood cases appear during the first year of life and about 85% begin in the first 5 years of life. Many cases of childhood AD improve, with 80% of children achieving an observed period of disease clearanceand 40% of children achieving remission before reaching adulthood.

In infantile AD, onset typically occurs within 6 months following birth. Infantile AD is generally characterized by acute skin lesions with erythematous and edematous papules and plaques, accompanied by oozing, vesicles and crusts (Figure 4-2). There may also be subacute lesions, which are erythematous with fine scaling and less oozing and crusting. The lesions typically appear on the cheeks, neck, scalp, trunk and extensor surfaces of the infant, usually sparing the diaper area, which can help differentiate it from allergic or contact dermatitis. Many infants initially present with flexural or generalized dermatitis, in the absence of facial dermatitis.

Childhood AD is usually characterized by subacute to chronic lesions. Chronic rubbing and scratching leads to lichenification. Affected areas classically include flexural areas of the body, such as the antecubital and popliteal fossae, neck, posterior auricular, wrists and ankles, as well as the face, hands and feet. Prurigo nodules can develop in some cases secondary to excessive picking of the skin. When the face is involved, it typically affects the perioral and periorbital areas rather than the cheeks, forehead and chin as seen in infantile AD. Nighttime scratching can lead to disrupted sleep and fatigue.

In adolescents and adults, AD predominantly affects flexural regions and the face, neck and extremities (Figure 4-3). A US population-based study identified five distinct phenotypes of AD lesional distribution in adults: 1) mild and less extensive disease; 2) anterior and posterior neck and trunk involvement; 3) antecubital fossa and upper extremity involvement; 4) arm, posterior hand, genital and buttock involvement, with a secondary face, palm and leg involvement; and 5) severe and more extensive disease. No sex differences in lesional distribution were found. The only significant racial/ethnic difference was a higher proportion of trunk lesions among Black and Hispanic adults. Adults over the age of 60 years had a significantly lower proportion of face, scalp and flexural lesions, and a significantly higher proportion of buttock or genital lesions.

Chronic lesions in all age groups are symmetric, dry, scaly papules and plaques. Lichenification and excoriations are common, whereas crusting and exudation are less frequently observed. Of note, crusting and exudation are features of AD per se, especially in younger children, even in the absence of frank infection. AD patients with crusting and exudation can be managed safely and effectively with topical corticosteroids and other anti-inflammatory agents. They do not warrant routine skin cultures or use of antibiotic therapy. Prurigo nodules are most commonly seen in adolescents and adults.

The clinical presentation of AD also varies by geographic region. A systematic review and meta-analysis of 101 studies identified several features that were common worldwide, including pruritus, xerosis, lichenification, flexural involvement and early disease onset. However, distinct regional characteristics in affected body areas and disease phenotypes were noted in every analyzed region, including the Americas, Europe, Australia, Africa, East Asia, Southeast Asia, India and Iran. Some examples include flexural lesions being most common in Australia and least common in the Middle East; head and neck involvement was most common in the Middle East and lowest in Southeast Asia; and papular lichenoid lesions were most common in Africa. These regional differences are likely multifactorial, secondary to differences of genetics, climate and other environmental factors. Regional and racial/ethnic differences in the characteristics of disease should be considered in the assessment of AD.

Atopic dermatitis has a substantial impact on the patient’s quality of life (QOL). A US population-based study found that increased severity of itch and other AD symptoms was associated with increased QOL impact, but that even mild AD impaired QOL. The most burdensome symptom of AD was itch (54.5%), followed by excessive skin dryness or scaling (19.6%) and skin redness/inflammation (7.2%). Over half (51.3%) of US adults with AD reported that these and other symptoms limited their lifestyle. Many adults, including those with mild AD, reported that AD impaired their activities and caused avoidance of social interaction because of appearance concerns. Another study, examining thirteen specific itch triggers in adult AD patients, found that many had multiple itch triggers, with stress, sweat, dry air and heat being the most common. About 1 in 3 patients had three or more itch triggers and the number of triggers was associated with more severe disease. Trigger avoidance is a core AD management strategy in all AD patients, regardless of their severity. These results underscore the difficulty of successfully avoiding all relevant itch triggers in AD patients.

Enlarge 

Enlarge 

Enlarge 

Adult-Onset Atopic Dermatitis

Silverberg and colleagues conducted a prospective study in 356 adults with AD to determine the associations and clinical characteristics of adult-onset AD. Using standardized questionnaires and examination, they found that adult-onset AD was associated with a distinct phenotype compared with childhood-onset AD. This included adult-onset AD being less frequently associated with a personal and/or family history of atopic disease, fewer signs and symptoms of AD, a higher probability of lesions affecting the head/neck and hands, and a lower probability of flexural lesions. In contrast with another study that found higher rates of scalp and posterior auricular involvement and follicular eczema, Silverberg and associates found lower rates of scalp and posterior auricular lesions in adult-onset AD, and no difference in rates of follicular eczema. Importantly, despite the phenotypical differences, no significant differences were observed between adult- and childhood-onset AD for severity, patient-reported intensity of itch or sleeplessness, disease activity as assessed by Patient Oriented Eczema Measure (POEM), or pruritus when sweating.

An Italian study of adult AD patients likewise found a significantly lower prevalence of family history of AD among patients with adult-onset disease, but also reported lower disease severity and higher itch intensity in this group. This study identified no differences in either lesional morphology or regional involvement between the two age of onset groups. By contrast, another Italian study found a statistically lower incidence of lichenified/exudative flexural dermatitis with or without “portrait” dermatitis (affecting the head, neck and the upper torso) in adult-onset AD, and a statistically higher incidence of nummular eczema and prurigo nodules in this group.

A study of adult AD patients in Korea found significant differences in area of lesional involvement and treatment history between patients with childhood-onset and adult-onset AD. Adult-onset patients showed significantly lower initial arm and leg flexor surface involvement, but higher initial trunk involvement. They also received less frequent treatment compared to the childhood-onset patients.

The studies discussed above were performed on ambulatory patients, who typically have less severe disease than hospitalized patients. According to an Israeli study, hospitalized AD patients with adult-onset disease were significantly older than whose with childhood-onset AD and had a lower incidence of family history of AD. Compared to hospitalized patients with childhood-onset AD, those with adult-onset disease also exhibited different clinical and laboratory characteristics, including less frequent skin fold and eyelid involvement as well as lower IgE levels.

A systematic review and meta-analysis of adult-onset AD prevalence and phenotypes found that adult-onset disease was characterized by a lower incidence of facial dermatitis, conjunctivitis or eyelid dermatitis, cheilitis, pruritus after sweating, xeroderma or xerosis, hand and foot dermatitis, nipple dermatitis and Dennie-Morgan line, and a higher incidence of foot lesions and white dermatographism.

In conclusion, while childhood- and adult-onset AD have overall similar severity, morphology, symptomatology and quality of life impairment, clinicians should be aware of specific phenotypic differences between adult-onset and childhood-onset AD when evaluating adult patients with dermatitis.

Hand Eczema

Hand eczema is characterized by eczematous lesions occurring anywhere on the hand surface. It is closely associated with AD, with an estimated 60-70% of all AD patients exhibiting hand involvement. Although hand eczema is relatively common in the general population, patients with AD are at a 3-4 times higher risk of developing this condition. Several morphological subtypes can be distinguished, including hyperkeratotic, frictional, nummular, atopic and chronic vesicular. Atopic hand eczema most commonly presents with eczema on the dorsal hands and volar wrists. Like AD, moderate and severe chronic hand eczema is associated with a substantial impact on health-related quality of life, comparable to many other debilitating chronic diseases.

Nummular Eczema

Nummular eczema, also known as discoid eczema, is characterized by coin-like lesions (Figure 4-4). It most commonly occurs on extensor surfaces, and is associated with hyperpigmentation in skin of color. Two morphological subtypes can be distinguished: an acute, exudative (oozing) type and a subacute or chronic dry type. Nummular eczema lesions commonly occur in AD, particularly in adults, East Asian and Southeast Asian populations, and are more prevalent in adult-onset disease. Itch associated with nummular eczema has been shown to impair health-related QOL.

Enlarge 

Prurigo Nodules

Prurigo nodules are characterized by intensely pruritic, hyperkeratotic, firm, erosive nodules and papules (Figure 4-5). They can be widespread and are strongly associated with a personal history of atopic disease. They can also occur in patients with active AD, more commonly in adults, particularly adult-onset AD, and are more prevalent among AD patients from South-East Asia. In children with AD, prurigo nodules may manifest more commonly in African Americans. As with nummular eczema, the main factor contributing to reduced health-related QOL in patients with prurigo nodules is itch.

Enlarge 

Lichenoid papules

Lichenoid papules are a common manifestation of adult AD, and are particularly prevalent in skin of color (Figure 4-6). Lichenoid papules were found in more than half of AD patients in a Nigerian study, and are more prevalent in Africa compared to other regions, according to a meta-analysis of regional and age-related differences in AD features.

Enlarge 

Differential Diagnosis

Due to the range of clinical manifestations of AD, differential diagnosis is broad and includes inflammatory, infectious, malignant, genetic, immunologic and nutritional disorders, among others. In infants, exudative lesions may appear similar to those caused by infectious conditions, such as scabies or impetigo. Seborrheic dermatitis can have a similar distribution as AD or occur concurrently. Other inflammatory dermatoses that can mimic AD include psoriasis, nummular dermatitis, irritant and allergic contact dermatitis, dermatographism and pityriasis alba. Immunodeficiency syndromes, genetic disorders that cause barrier dysfunction and metabolic disorders should also be considered in infants under 3 months of age who present with AD symptoms. The following section discusses selected conditions that mimic, overlap, or potentially complicate AD (Table 4-1).

Enlarge 

Seborrheic Dermatitis (SD)

SD is a common inflammatory skin condition, affecting the sebum-rich skin. Lesions often appear as pink patches with thick or greasy, whitish or yellow scales. In patients with darker skin types, lesions may be hypopigmented. SD is the most common differential diagnosis in infants and may be difficult to distinguish from AD. In infancy, SD has a predilection for the face. While children with AD may develop diaper rash secondary to irritant contact dermatitis, AD per se usually spares the groin and axillary regions. In contrast, SD and inverse or napkin psoriasis do not. In adolescents and adults, AD typically involves the scalp and alar and mesiolabial folds. Since SD is usually not pruritic, it can typically be differentiated from AD by lack of excoriations and sleep impairment secondary to itching. However, although SD and psoriasis are usually not pruritic, some can experience substantial pruritus. Both AD and SD can occur together, which can lead to confusion. In older AD patients with scalp dermatitis, it is important to distinguish between SD (more greasy scale) and atopic scalp (more dry particulate scale), as the management of these entities differ.

Irritant or Allergic Contact Dermatitis (CD)

Acute CD is characterized by erythema and edema (Figure 4-7). Two types of CD are recognized: irritant and allergic. Allergic CD has a delayed reaction, with onset occurring hours to days following allergen exposure. Irritant CD has a more rapid onset, typically minutes, following disruption of the skin barrier. The distribution of allergic CD is often asymmetrical (unless allergen exposure is bilateral), whereas irritant CD is more symmetrical and less itchy. Distinguishing an isolated case of CD from AD relies on identifying the trigger-reaction temporal relationship and recognizing a suggestive distribution pattern.

In infants, irritant CD most commonly affects the dorsal aspect of the hands, face and diaper area, the latter being triggered by irritants (eg, diaper wipes) and repeated wet-dry cycles. In adults, CD most commonly affects the hands of those who repeatedly wash/sanitize their hands as part of their employment, such as those in the healthcare or food industries. These reactions are triggered by the allergens (eg, fragrances, preservatives) present in hand sanitizers, lotions, creams and other cleansing products. Sensitization may occur after infrequent exposure to strong allergens or frequent exposure to milder allergens. Once sensitization occurs, even minimal exposures can be provocative. A reaction to one allergen in a topical product may sensitize the user to other ingredients in the same product.

Enlarge 

Cutaneous T-Cell Lymphoma (CTCL)

Early CTCL presents as either quickly progressing erythema (Sézary syndrome) or slowly progressing plaques/patches (mycosis fungoides [MF]). Tumors and pruritus typically present at later stages. MF is the most common form of CTCL and may resemble AD in both children and adults at early stages, when it has a “smudgy” thumbprint shape (Figure 4-8). A hypopigmented clinical variant of MF can occur, most frequently in children with darker skin, which resembles pityriasis alba. In adults, classical MF presents as eczematous patches and plaques on the trunk, buttocks and extremities. The onset of CTCL typically occurs after the age of 50. However, the incidence of CTCL in children has increased over the past 10 years. CTCL should be considered when AD is recalcitrant to therapy or when symptoms present later in life. Adult onset, lack of atopy and symptoms of weight loss and/or malaise are crucial to differential diagnosis.

Enlarge 

Psoriasis

Psoriasis (Figure 4-9) affects patients of any age but has a peak onset of adolescence/early adulthood. The most common form of psoriasis, plaque psoriasis, is characterized by sharply defined, raised erythematous plaques covered by silvery-white scales. It most commonly affects the elbows, knees, or thumbs of infants who suck their thumb. Other presentations can occur and include scalp, pustula, palmoplantar, flexural (rare), guttate and annular psoriasis. Psoriasis may be difficult to distinguish from AD and rarely can even overlap with AD. Psoriasis is more likely to be misdiagnosed in infants and children, when distribution can affect the face and scaling is less prominent. However, psoriasis frequently affects the diaper area, whereas AD typically does not. Nail involvement in psoriasis may also help distinguish the conditions.

Enlarge 

Dermatitis Herpetiformis (DH)

DH typically presents as circular groupings of polymorphic erythemic papulovesicles. Intense pruritus may lead to excoriations and crusting. Lichenification and hypopigmentation may develop in chronic lesions. DH typically affects the extensor surfaces of limbs, back, buttocks, but face and scalp may also be affected. DH is directly related to gluten-sensitive enteropathy, but disease severity does not correlate with degree of intestinal inflammation and does not necessarily present with gastrointestinal symptoms. Diagnosis is confirmed by laboratory detection of immunoglobulin A (IgA) deposits along the dermal-epidermal border by immunofluorescence.

Eczematous Drug Eruptions

Eczematous drug eruptions have been described, particularly to calcium channel blockers and possibly other antihypertensives. These can be very difficult to distinguish from mature onset AD (Figure 4-10). Eczematous drug eruption should be considered in all patients with adult-onset dermatitis, especially when there is no prior history of skin disease. However, a definitive diagnosis of eczematous drug eruption can be challenging to make. Biopsies are not particularly helpful, since eczematous drug eruptions have similar histological features as other eczematous eruptions, including AD. The diagnosis is made clinically and empiric class switch of antihypertensives and/or other medications with monitoring of clinical response may be required for confirmation. Other drug eruptions rarely may be confused with AD.

Enlarge 

Hyper-IgE Syndromes (HIES)

HIES are rare immunodeficiencies inherited through a dominant mutation in the signal transducer and activator of transcription 3 (STAT3) gene or a recessive mutation in the dedicator of cytokinesis 8 protein gene (DOCK8). HIES are associated with very high serum IgE, severe AD and recurrent S aureus abscesses and pneumonia. Autosomal recessive HIES is associated with recurrent infections and sinopulmonary disease. Patients with autosomal dominant HIES have more serious complications, including abscesses of internal organs, severe infections, bone fractures, scoliosis and others.

Scabies

Scabies is a skin infestation by the scabies mite (Sarcoptes scabiei). An allergic reaction, which presents as small red papulovesicles or dermatitic lesions, is triggered by the eggs and feces of the female mite. Burrows may sometimes be visible in the skin. In infants, scabies most frequently affects the palms, soles, face and scalp. In adults, wrists, finger webs, genitals and areolar areas are most commonly affected. Pruritus can be intense, especially at night, but may not be present in all patients. Scabies is infectious and not limited to any age or socioeconomic group, although young children and young adults are most commonly affected. Lack of xerosis, and other family members being affected are key to differential diagnosis. Confirmation of scabies depends on positive scrapings for mites and/or their feces/eggs or visualization of their burrows. The skin barrier and immunologic changes present in AD patients make them prone to more severe reactions to scabies infestation. It is always important to consider scabies in the differential diagnosis. However, patients with chronic dermatitis and lack of friends or family with similar dermatitis are less likely to have scabies. Of note, topical permethrin may have anti-itch properties, even in those without scabies. Thus, improved symptoms after empiric treatment with topical permethrin is not a confirmation of the diagnosis.

Nummular Dermatitis (ND)

ND presents as round/oval, well-demarcated lesions. Lesions can be itchy and are typically asymmetrically distributed on the limbs, but generally spare the face. The accompanying rash may affect any area. ND is rare before the age of 5. Nummular eczematous lesions commonly occur in AD patients (Figure 4-11), particularly in school-age children and adult-onset AD. Lesional morphology distribution and age of onset are therefore key to differential diagnosis.

Enlarge 

Clinical Presentation and Special Considerations for Skin of Color

The classic presentations of AD are essentially the same across various racial and ethnic groups. However, there are a number of distinguishing features that are more characteristic of skin of color and must be considered. First, erythema is not as pronounced on more darkly pigmented skin and can be difficult to visually appreciate (Figure 4-12). Second, erythema in skin of color often appears violaceous or purple. Third, many patients of Black, African and/or Afro-Caribbean descent have papular/follicular eczema and/or lichenoid lesions. Papular lichenoid lesions were found in 54.1% of patients with AD in a region of southeastern Nigeria. This can present an obstacle to a physician making the diagnosis and/or attempting to assess the severity of AD, as erythema is a characteristic that is included in a number of the popular scoring tools, including SCORAD (Scoring Atopic Dermatitis) and EASI (Eczema Area and Severity Index). This phenomenon could lead to a delay in diagnosis and treatment and, ultimately, more severe disease at presentation. When the lesions of AD resolve, they can cause persistent dyschromia or pigmentary alterations. These are almost always more pronounced in patients of racial and ethnic groups with darker skin. Post-inflammatory pigment alteration poses a challenge for the assessment of active dermatitis, as it can mask underlying erythema or be present even after the active dermatitis is resolved.

Papular eczema presents with a pattern of small, distinct papules, especially on the trunk, as opposed to the more conventional patches and plaques and can present with severe pruritus. This particular morphology has been observed to be more common in skin of color, as is a pattern of perifollicular accentuation (Figure 4-13). In the Nigerian study, 70.3% of patients had a scattered, often perifollicular, micropapular rash, on the extensor aspects of the joints. In a series of case reports, investigators identified three children with AD, two of which were African American, who developed prominent, pruritic, follicular papules in the periumbilical area as well as on the flexural areas of the arms and legs. Such a pattern should alert the physician to the diagnosis even if other signs have not yet made their appearance.

Asian patients may present with “sandpaper-like lesions” on their extensor surfaces, wrist dermatitis and hyperkeratotic papules as accompanying features. African-American children and adolescents often present with lesions on the extensor surfaces of the body as opposed to the more traditional presentation of flexural involvement in this age group. Dennie-Morgan lines are more commonly noted in patients of color, even in those without AD. Ichthyosis vulgaris has also been reported to be more common in patients of color.

Enlarge 

Enlarge 

Subsets of AD Patients

Less commonly, AD may present as localized disease or as distinct variants. That is, patients may experience mild flexural dermatitis with seasonal course or environmental influence. However, they may have more prominent and refractory dermatitis affecting localized body sites. For example, hand eczema is often the predominant finding in adults with AD. This variation of AD is worse during the winter months and triggered by hand washing and irritant exposure. Another variant form of AD, foot eczema, is usually worsened by heat and/or sweat and occlusive shoes. Other variants include nipple dermatitis, fingertip dermatitis, eyelid dermatitis, genital dermatitis and others. These may occur as the sole manifestation of AD in patients with previously well-established history of AD or may occur in addition to the more classic lesion distribution pattern. Morphological variants have also been reported, including nummular, papular-lichenoid, prurigo-like and follicular variants.