2.2. Psoriasis

Psoriasis can affect patients of any age with no apparent gender bias. The peak age of onset appears to be adolescence/early adulthood [10,11], although psoriasis may be under-recognized in infants and children. Psoriasis vulgaris, or plaque psoriasis, is the most common form of psoriasis and is characterized by sharply circumscribed, persistent erythematous, indurated plaques with silvery-white, adherent scale and a predilection for extensor surfaces of the elbows or knees, or for the thumb in infants who suck their thumb (“thumb sign”) via the Köebner phenomenon (localization to areas of micro-trauma; Figure 3). However, other presentations are not uncommon and include acute widespread guttate, flexural (“inverse”), annular, palmoplantar, pustular, and scalp (pityriasis amiantacea, often accompanied by alopecia) psoriasis as well as psoriasis-eczema overlap (see Section 2.7) [12].

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Figure 3

Psoriasis.

In infants and children, psoriasis may be misdiagnosed as AD because scaling is often less prominent and the distribution of lesions more often includes the face. Unlike AD, psoriasis is frequently encountered in the diaper area. Nail involvement (fine pits) is a subtle feature that can help differentiate psoriasis or coexisting psoriasis from AD in infants and children. Family history is often used as supporting evidence for diagnosis; however, only about one-third of patients have a family history of psoriasis, which suggests that it may be underdiagnosed.

Although Streptococcal pharyngitis or pharyngeal colonization is a well-recognized psoriasis trigger, impetigo, or other skin infections are rare [11].

TCS are often used as first-line treatment [12], but long-term TCS monotherapy can be associated with suboptimal response and rebound. In these cases, addition of a topical steroid-sparing medication (e.g., vitamin D analog [13], salicylic acid [14] or TCI [15]) may improve efficacy and increase the chances of remission.

2.3. Nummular Dermatitis

Nummular dermatitis (ND) is characterized by round or oval (i.e., nummular), well-demarcated lesions that are sometimes itchy. Lesions are usually asymmetrically distributed on the limbs, rarely on the face, but the rash may affect any area. Unlike AD, ND is unusual before age 5 [16].

The cause of ND is unknown, but because many cases are associated with localized microtrauma (e.g., insect bite, scratching), some consider this condition to be a form of psoriasis. Other suspected factors include Staphylococcus aureus colonization, contact allergens or irritants, xerosis, or stasis dermatitis.

2.4. Contact Dermatitis

Contact dermatitis (CD) is the most common form of dermatitis and like all dermatitis, acute CD is characterized by cutaneous erythema and edema. CD can be acute, chronic, persistent, or relapsing and it has been classically categorized as either irritant or allergic, but both types can coexist. In infants and children, allergic CD often occurs in the same distribution as irritant CD and may be underappreciated.

Allergic CD is a delayed-type hypersensitivity reaction, with onset after several hours to days after allergen exposure. The distribution is classically geographic and often asymmetric. Irritant CD is a more rapid response to physical barrier microtrauma, typically occurring within minutes, and is often less itchy, less geographic, and more symmetric (except in instances when allergen exposure is bilateral such as footwear or gloves) than allergic CD. Recognition of isolated CD relies on temporal pattern, as well as suggestive distribution (Figure 4).

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Figure 4

Contact dermatitis.

CD commonly complicates other skin disease, including AD. Impaired skin barrier function has been a suspected risk factor but results of studies have been conflicting and risk may be allergen-specific [17,18,19,20]. Recognition of CD in the setting of coexisting skin disease requires a high index of suspicion based on personal/family history, presence of xerosis, and, if necessary, results of “patch testing” (although the sensitivity of patch testing is less than 70%). Diagnostic skill is also important for recognition of a less common manifestation of allergic CD called autoeczematization or “id” reaction, characterized by appearance of widespread, symmetrically distributed ectopic lesions [21,22].

Older adults have both greater lifetime risk of repeated allergen exposure and reduced skin barrier repair mechanisms, and so may be especially prone to allergic CD [23]. However, CD can affect patients of any age including infants and children, contrary to what had been previously believed [21,24]. In pediatric patients, irritant CD is most common on the face, dorsal aspect of the hands, and “diaper area”, often triggered by frequent cycles of skin wetting and drying as well as exposure to endogenous (e.g., drool, lip-licking, urine, and feces) or exogenous (e.g., cleansing products, highly alkaline or acidic foods) irritants. In adults, irritant and allergic CD most often presents as “hand dermatitis” triggered by frequent hand washing in healthcare and food industry workers. Common topical allergens include emulsifiers, preservatives, and fragrances used in topical products (e.g., diaper wipes, hand sanitizers, emollient lotions, and creams). Recognition of these triggers may be especially difficult when the allergen is an ingredient contained in products that have been used as a treatment for dermatitis. In some cases, sensitization with one allergen contained in a complex topical product will enable cosensitization to another ingredient in the same product. Nickel is another common sensitizer. Nickel allergic CD is classically localized to the infraumbilical area (from jean snaps) or ear lobules. Ear piecing in infancy is an important risk factor for nickel allergy.

The most effective way to alleviate CD is with strict avoidance of likely triggers. When triggers cannot be identified/avoided or there is residual dermatitis after triggers have been removed, TCS [25,26] or TCIs [27,28,29] may reduce inflammation; however, chronic use of TCS should be avoided, especially on the face and diaper area. Long term and frequent (greater than once daily) application of TCS (especially higher potency preparations) is contraindicated, due to an increased risk of skin barrier compromise and systemic exposure.

2.5. Dermatographism

Dermatographism is an immunologic response to pressure applied the skin, characterized by local wheal-and-flare erythema followed by edema and itch (Figure 5). Alternately known as dermographism, dermatographic urticaria, or mechanical urticaria, signs and itch classically begin within 5 min of stimulation and persist for 15–30 min. Delayed-type dermatographism is much less common, presenting as an urticarial response 3–6 h after stimulation, and lasting for 24–48 h, not always preceded by an immediate wheal-and-flare. “White dermatographism” is a minor diagnostic criterion for AD and presents as pallor rather than erythema, with subsequent erythematous halo (Figure 6).

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Figure 5

Dermatographism.

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Figure 6

White dermatographism (typically observed in atopic dermatitis).

Patients of any age can be affected by dermatographism but it is most often diagnosed in young adults. Onset is generally gradual and resolution is often within five years [30]. Dermatographism can affect any region of the body including the palms and soles, but not usually the scalp or genitals. Tight clothing is a common trigger. Diagnosis is clinical and confirmed by the appearance of a wheal in response to mechanical stimulation. Although dermatographism is usually idiopathic, in some cases it is associated with drug reactions, scabies, stress/anxiety, or an underlying systemic disease (e.g., hyperthyroidism, type 2 diabetes mellitus). Trigger avoidance is the most effective way to control dermatographism.

2.6. Pityriasis Alba

Pityriasis alba (PA) is a common, idiopathic, generally asymptomatic condition, often noted as an incidental finding on skin exam. PA is associated with AD, as a minor diagnostic criterion. PA is most often found in school-age children with no gender bias [31].

PA appears as subtle, poorly circumscribed, hypopigmented patches with fine papular follicular accentuation, most often on the proximal upper extremities, although the face and trunk are sometimes involved (Figure 7). Patches become more prominent with increased summer sun exposure, as surrounding skin tans. In winter, hypopigmentation is less prominent, and the patches feature powdery, white scale. Some reports have suggested that PA is more common in patients with darker skin, but the condition is equiprevalent in all skin types, just more apparent on darker skin tones [31]. Severe cases of PA are clinically indistinguishable from hypopigmented mycosis fungoides (see Section 5.2).

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Figure 7

Pityriasis alba.

Emollients can minimize scaling but will not impact hypopigmentation, which may persist for months to years despite control of xerosis and inflammation. A few reports have documented efficacy of TCIs [32,33].

3.2. Viral Infections

3.2.1. Molluscum Dermatitis

In most patients, molluscum contagiosum (MC) causes a relatively benign infection characterized by scattered clusters of small, umbilicated, flesh-colored, pink, or “pearly” white papules. For some patients, diffuse or discoid dermatitis develops surrounding some of these MC papules (molluscum dermatitis; MD) often masking the papules altogether (Figure 12). Patients (with or without AD) that develop MD have a prolonged and/or more severe course [43,44] possibly due scratching and autoinoculation to other skins sites; however, in some patients the apparent “spread” of MC lesions may be due to autoeczematization [45]. Secondary infection is uncommon and characterized by acute onset of tenderness and drainage.

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Figure 12

Molluscum dermatitis.

Children are primarily affected with no apparent gender bias. Approximately one-quarter of patients with MC develop MD [44,46] while half of patients with AD do so [44]. There is some speculation that patients with AD may also be more susceptible to MC, but data are not conclusive [44,46,47,48].

Uncomplicated MC does not usually require treatment; however, for MD, short-course TCS may help control the dermatitis and prevent spread [44]. Data are conflicting as to the effect of TCS on recurrence rate [44,46].

3.2.2. Eczema Herpeticum

Eczema herpeticum (EH), is an acute-onset, potentially life-threatening viral infection caused by herpes simplex virus occurring almost exclusively in patients with a history of chronic skin disease, especially AD. Patients present with widespread tender “punched out” erosions with a predilection for the face and areas of chronic dermatitis (Figure 13). Regional lymphadenopathy is often present.

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Figure 13

Eczema herpeticum.

EH may be easily mistaken for impetigo (see Section 3.3.1.), especially for recurrent EH in patients with severe AD (“EH incognito”). Positive skin surface bacterial culture for with Staphylococcal or Streptococcal bacteria is common, and does not exclude EH. Diagnosis can be confirmed by skin scraping for Tzanck smear, viral culture, PCR, or immunofluorescence, but sensitivity is low for all these techniques, so a high index of suspicion is important. Empiric antiviral treatment is often indicated; however, acyclovir resistance is emerging [49]. Continued monitoring after clearance is recommended because EH recurs in about half of patients [50].

EH can affect patients of any age, but it is most common in infants and children. Approximately 10%–20% of patients with AD develop EH and those that do typically have more severe/earlier onset AD, higher prevalence of atopic comorbidities, and are more likely to have a history of S. aureus or MC infection [50,51]. Previous TCS use has been cited as a possible risk factor for EH [52]. Thus far, data are not sufficient to determine the effect of TCIs on EH risk [52,53,54].

3.2.4. Eczema Coxsackium

Initially reported in 2013, a new variant of Kaposi’s varicelliform eruption (eczema coxsackium (EC)), attributable to coxsackievirus A6 (CSVA6), is being increasingly recognized. EC is related to the well-described hand, foot, and mouth disease (HFMD), which is most often caused by CSVA16. Over half of CSVA6-related HFMD manifests as EC [55].

In contrast to the oral erosions and gray-white, oval vesicles on the hands, feet, and buttocks typically associated with HFMD, EC manifests as EH-like lesions with a predilection for hemorrhagic vesicles within dermatitic skin (Figure 14). While the cutaneous findings of EC are the most dramatic presenting sign, children with AD typically have associated fever and constitutional symptoms as well as subsequent onychomadesis.

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Figure 14

Eczema coxsackium.

A majority of patients with EC have a history skin disease, most often AD, and patients with a history of AD are significantly more likely to manifest EC [55]. A diagnosis of EC is most reliably confirmed by serum PCR for coxsackievirus. Treatment is supportive, with antipyretics and bland skin care.

3.2.5. Viral Exanthem

Viral exanthems (VE) are a heterogeneous group of skin findings associated with a wide variety of systemic viral infections. The most common VE is acute onset of generalized morbilliform eruption, featuring widespread, fine, pink macules and/or papules that may be confused with AD (Figure 15). Other VEs include more pathognomonic features: unilateral laterothoracic exanthem (asymmetric periflexural exanthem of childhood), purpuric socks and gloves syndrome, infantile popular acrodermatitis (Gianotti-Crosti syndrome), and fifth disease [56]. VEs are generally self-limited and treatment is supportive.

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Figure 15

Viral exanthem.

7.2. HIV/AIDS-Related Skin Changes

As of 2011, 57 different cutaneous skin disorders have been linked to HIV/AIDS and nearly every patient with HIV/AIDS will experience some cutaneous changes, many of which mimic AD [68]. These HIV/AIDS-related cutaneous changes are more often than not secondary to immunosuppression (i.e., opportunistic infections or increased susceptibility to malignancy); however, a significant number of inflammatory dermatoses are directly related to HIV infection. The mechanisms by which HIV infection effects these changes has not been completely elucidated but there is evidence to suggest that they may be related to changes in sweat/oil production, depletion of Langerhans cells, decreased CD4+ T cell function, and/or shifts in cytokine profile.

SD (see Section 2.1), psoriasis (see Section 2.2), eosinophilic folliculitis (erythematous urticarial vesiculopapular or pustular rash affecting the face, neck, and upper chest/back), primary HIV viremia (morbilliform eruption affecting the trunk and limbs), pruritic papular eruption of HIV (diffuse red rash affecting the trunk and face), xerosis, and AD have each been linked directly to HIV infection. AD is observed in ~30%–50% of HIV/AIDS patients, particularly AIDS patients [68]. Patients with HIV/AIDS also often report drug eruptions (DE; see Section 9.2) possibly related to HIV-related changes in immune function and/or metabolic dysfunction.

Treatment is often disappointing, as HIV-related cutaneous changes are particularly resistant to treatment and/or prone to recurrence. Highly active antiretroviral therapy has significantly reduced the incidence of opportunistic infections and Kaposi’s sarcoma, but it has had little effect on the incidence of inflammatory dermatoses. TCS have limited efficacy [68].

8.1. Cystic Fibrosis

In infants, the initial symptoms of CF may be CFNDD. This potentially life threatening nutritional deficiency presents as erythematous annular papules that are distributed periorally, periocularly, or in the “diaper area”. The eruption then spreads to the flexural surfaces of the extremities and takes on a “peeling paint” scaly appearance. In addition, patients demonstrate sparse brittle hair, periorbital and extremity edema, and failure to thrive. CFNDD generally presents during the first weeks to months of infancy and precedes pulmonary and gastrointestinal symptoms by a few months. Though this is an extremely rare presentation, these manifestations are associated with false-negative sweat test results [74], making diagnosis difficult.

CFNDD is related to malabsorption of nutrients either as a direct result of membrane dysfunction or indirectly via reduced digestive enzyme availability and pancreatic dysfunction due to abnormal ion transport [75]. With nutritional intervention, CFNDD should subside.

Although data are limited, CF does appear to be associated with atopy (but not AD) and increased risk of cutaneous drug reactions [75].

8.2. Phenylketonuria

After the first few months of birth, patients with PKU may present with severe acute dermatitis on most of the body. Individuals may also be photosensitive, hypopigmented relative to siblings and parents, and present with a “musty odor” in sweat and urine due to a buildup of phenylalanine metabolic byproducts [76]. The severities of other symptoms depend on age and generally include intellectual disability, microcephaly, seizures, and movement disorders.

8.3. Zinc Deficiency and Biotin Deficiency

Most cases of ZD occur in premature infants who are still breast feeding at three months of age when zinc levels in mother’s milk drop as the infant’s zinc requirements increase. Typical presentation includes a “horseshoe” pattern of facial dermatitis or crusty erosions on the cheeks and chin. “Diaper area” involvement typically features sharply demarcated plaques with peripheral scale that, unlike Candidiasis, classically spares the folds. In older children, lesions localize to the extensor surfaces of the elbows and knees. Paronychia, alopecia, diarrhea, and recurrent skin infections are also common. Children with ZD tend to be irritable although there is no xerosis or pruritus. Until solid food is introduced, zinc supplementation improves clinical signs.

BD, or multiple carboxylase deficiency, is a rare autosomal recessive trait based on reduced activity of any or all three associated biotin-dependent carboxylases. BD presents with alopecia and maculopapular erythemic rash around the eyes, nose, mouth, ears, and genitals. The eruption is often accompanied by vomiting, apnea, hypotonia, seizures, lethargy, recurrent infections, metabolic acidosis, organic aciduria, hyperammonemia, and difficulty feeding. Symptoms generally present within the first year of life. Family history of BD is an important risk factor. Biotin supplementation improves symptoms.

All manuscript content was developed independent of funding source. Jennifer Jaworski, a full-time employee of Prescott Medical Communications Group (Chicago, IL, USA) assisted with preparation of the manuscript at the direction of the authors with financial support from Valeant Pharmaceuticals North America LLC.