Allergic contact dermatitis (ACD) in children is not uncommon and should be suspected in patients with chronic dermatitis.
Patch testing is the gold standard for the diagnosis of ACD even in children and should be considered for children with chronic or recurrent eczematous dermatitis including those with atopic dermatitis (AD) who fail to improve with standard treatment. The greatest abuse of patch testing is lack of use.
Counsel the patient and/or family by identifying and providing a list of the chemicals they are sensitive to and giving synonyms and sources.
Give patients a list of safe products to use, alternatives and substitutions if possible.
Patients with a suggestive history or physical findings but negative results on the thin-layer rapid-use epicutaneous test (T.R.U.E. TEST ® ) should be considered for further evaluation in a patch testing clinic.
Contact dermatitis (CD) is a spectrum of inflammatory skin reactions induced by exposure to external agents. Clinically, CD most commonly manifests as a dermatitis or eczema, but it can present as urticaria, erythroderma, phototoxic or photoallergic reactions, hypopigmentation or hyperpigmentation, and even as an acneiform eruption. The more common type of CD results from tissue damage caused by contact with irritants (irritant CD), whereas contact with allergens causes allergic contact dermatitis (ACD). The former is seen commonly in infants as diaper dermatitis, whereas nickel and poison ivy are more frequent causes of ACD in the pediatric population.
An estimated 85,000 chemicals exist in the world, and approximately 2,800 substances have been identified as contact allergens. The majority of these agents, when applied to the skin, can induce an irritant CD (ICD).
It was previously thought that ACD occurs less frequently in children, possibly because of reduced exposure to contact allergens or because the immune system in children may be less susceptible to contact allergens. However, subsequent studies found a sensitization rate of 20% to 24%. Two multicenter North American studies describing patch testing in pediatric patients with ACD found that allergen sensitivity rates were not different in children when compared to those of adults in the USA; however, the frequency of the relevant allergen reactions differed between the two populations. Another striking difference was the finding that the frequency of the concomitant diagnosis of atopic dermatitis (AD) was higher (34%) in children with a relevant positive patch test reaction compared to only 11.2% in adults.
ACD is considered rare in the first few months of life but has been reported as early as 1 week of age from a hospital ID bracelet. The prevalence rises with increasing age and by 10 years of age the incidence reaches that seen in adults. Subsequently, variations for some allergens depend on the patterns of exposure. With advancing age, ACD diminishes in severity and in the loss of allergic response in previously sensitized individuals.
In patients suspected of having ACD and referred for patch testing, the positive patch test rates ranged from 14% to 70%. Current relevance was reported at 56% to 93%. In a study by Seidenari et al in Italian children, the highest percentage of positive responses was found in children less than 3 years of age, suggesting a higher sensitization rate in young children. In a study designed to look specifically at infants and young children, Bruckner and colleagues found that 24.5% of asymptomatic children aged 6 months to 5 years were sensitized to one or more contact allergens. Approximately one half of the sensitized children were younger than 18 months. In the adolescent age group, females have significantly higher rates of ACD on the face, likely to be explained by increased exposure to nickel in piercing and to preservative and fragrance in cosmetic products. A USA-based study showed nickel, fragrance, cobalt, thimerosal, Balsam of Peru (BOP), potassium dichromate, neomycin, lanolin, thiuram mix and p -phenylenediamine (PPD) to be common allergens in children. Less common, but emerging allergens include cocamidopropyl betaine in ‘no tears’ shampoos, baby washes and cleansers and disperse dyes in clothing materials. A different study looking at age-related specific allergens showed that, with increasing age, nickel takes the place of mercurials as the principal allergen. With respect to race, in a large study of more than 9,000 individuals, De Leo and colleagues found no difference in the overall response rate to allergens on patch testing between white and black patients.
Irritant Contact Dermatitis
Irritant CD results from contact with agents that abrade or irritate the skin. Irritation is usually a cytotoxic event produced by a wide variety of chemicals, detergents, solvents, alcohol, creams, lotions, ointments and powders and by environmental factors such as wetting, drying, perspiration and temperature extremes. A major finding after exposure to skin irritants is perturbation of the skin barrier with an associated increase in transepidermal water loss. The mechanism associated with this barrier perturbation may include disorganization of the lipid bilayers in the epidermis. In addition, these changes can stimulate an array of proinflammatory cytokine production in the epidermis.
Although allergens are not implicated in ICD, the skin-associated immune system is clearly involved, and historically few differences were noted when ICD and ACD were compared immunohistopathologically. An important difference between the two forms of CD is that ICD does not require prior sensitization and immunologic memory is not involved in the clinical manifestation. The cellular infiltrate includes CD4 + T cells with a T helper cell type 1 (Th1)-type profile. A number of studies have identified the epidermal keratinocyte as a key effector cell in the initiation and propagation of contact irritancy. Keratinocytes can release both preformed and newly synthesized cytokines, as well as up-regulate major histocompatibility complex (MHC) class II molecules and induce adhesion molecules in response to irritants. These mediators can cause direct tissue damage, activating Langerhans cells, dermal dendritic cells and endothelial cells, which contribute to further cellular recruitment including neutrophils, lymphocytes and mast cells that also contribute to the inflammatory cascade. The ‘final’ cellular damage results from inflammatory mediators released by activated, nonsensitized T cells. The inflammatory response is dose and time dependent. Any impairment to the epidermal barrier layer (e.g. fissuring, overhydration) renders the skin more susceptible to an irritant effect. The clinical presentation of ICD is usually restricted to the skin site directly in contact with the offending agent, with little or no extension beyond the site of contact.
Allergic Contact Dermatitis
Allergic CD is recognized as the prototypic cutaneous cell-mediated hypersensitivity reaction, in which the epidermal Langerhans cell plays a pivotal role. The offending agent, acting as an antigen, initiates the immunologic reaction at the site of contact with the skin. Most environmental allergens are haptens (>500 Da) that bind to carrier proteins to form complete antigens before they can cause sensitization. The thickness and integrity of the skin influence the allergic response. Thus thinner sites such as the eyelids, earlobes and genital skin are most vulnerable, whereas the thicker palms and soles are more resistant. Exposure patterns determine the clinical appearance and course of the dermatitis. An association of filaggrin gene ( FLG ) mutations with contact sensitization to nickel and contact sensitization to nickel combined with intolerance to fashion jewelry, but not with other contact allergens, has been demonstrated. Thus, FLG deficiency may represent a risk factor for contact sensitization to allergens.
The immune response of ACD requires completion of both an afferent and an efferent limb. The afferent limb consists of the hapten gaining entrance to the epidermis, activating keratinocytes to release inflammatory cytokines and chemokines including tumor necrosis factor (TNF)-α, GM-CSF, interleukin (IL)-1β, IL-10 and macrophage inflammatory protein (MIP)-2. The latter in turn activate Langerhans cells, other dendritic cells and endothelial cells, leading to an accumulation of even more dendritic cells at the site of antigen contact. In addition, the release of IL-1β by epidermal Langerhans cells promotes their egress from the epidermis. After the uptake of antigen, Langerhans cells process it while migrating to regional lymph nodes, where they present it to naïve T cells. Hapten-specific T cells have been shown to include Th1, Th2, Th17 and T regulatory subsets. An important property of Langerhans cells and dendritic cells is their ability to present exogenous antigens on both MHC class I and class II molecules. This cross-priming leads to the activation of both CD4 + and CD8 + hapten-specific T cells.
Although classic delayed-type hypersensitivity reactions are mediated primarily by CD4 + cells, CD to haptens is mediated primarily by CD8 + cells with a Th1-type cytokine profile.
On subsequent contact of the skin with a hapten, that is, during the elicitation phase of ACD, other antigen-presenting cells (APCs), including macrophages and dermal dendritic cells, may stimulate antigen-specific memory T cells and contribute to the initiation of the local inflammatory response (the dermatitis reaction). The sensitized T cells home in on the hapten-provoked skin site, releasing their inflammatory mediators, which results in epidermal spongiosis (‘eczema’). Secondary or subsequent hapten exposure shortens the period of latency from contact to appearance of the rash.
Innate Immune Recognition of Haptens
A recent review of early events in ACD described the earliest event in ACD as the formation of hapten-self complexes: pre-haptens oxidize before contact with the skin; pro-haptens such as urushiol are oxidized by the host after contact; complete haptens are directly active. Haptens induce the production of reactive oxygen species, which leads to release of ATP and other damage-associated molecular patterns (DAMPs), as well as to the generation of low-molecular-weight hyaluronic acid. The latter is sensed by neighboring cells via Toll-like receptor 2 (TLR2) and TLR4, resulting in increased expression of pro-IL-1β and pro-IL-18. Activation of the inflammasone by ATP with resultant caspase 1 activity generates active IL-1β and IL-18. Of interest, nickel has been found to directly bind histidine residues in the extracellular domain of TLR4, triggering the activation of this receptor.
Keratinocyte Apoptosis and Eczema
Spongiosis is a well-established histologic hallmark of the epidermis in eczema. It is characterized by the diminution and rounding of keratinocytes (condensation), and widening of intercellular spaces resulting in a spongelike appearance of the epidermis that can lead to formation of small intraepidermal vesicles. The function and integrity of the epidermis are dependent on specific cell surface adhesion molecules. Activated T cells infiltrating the skin in eczematous dermatosis induce keratinocyte apoptosis, resulting in spongiosis. Resolution of epidermal spongiosis and cellular infiltrate can be demonstrated when ACD is successfully treated.
T Cell Recruitment in Allergic Contact Dermatitis
The recruitment of T cells into the skin is regulated by the expression of the specific skin-homing receptor, cutaneous lymphocyte-associated antigen (CLA), which mediates rolling of T cells over activated endothelial cells expressing E-selectin. In addition, chemokine receptors have been proposed as important regulators of the tissue targeting of T cells. In this respect, CLA + T cells co-express the chemokine receptor CCR4, the ligand for thymus and activation-regulated chemokine TARC (CCL17) and macrophage-derived chemokine (CCL22). CCR4 triggered by TARC exposed on the endothelial cell surface during inflammatory skin disorders is thought to augment integrin-dependent firm adhesion of T cells to endothelial intercellular adhesion molecule (ICAM)-1. T cell migration into peripheral tissues mostly depends on their chemokine receptor profiles. Th1-type cells express high levels of CCR5 and CXCR3, interacting with MIP-1β (CCL4) and interferon gamma (IFN-γ)-inducible protein 10 (CXCL10), respectively, whereas Th2-type cells express primarily CCR3, CCR4 and CCR8 and interact with eotaxin (CCL11), TARC and MDC, and I-309 (CCL1).
Epidermal keratinocytes have been shown to be an important source of inflammatory mediators for the initiation and amplification of skin immune responses. Treatment with IFN-γ or IFN-γ plus TNF-α induces keratinocytes to express ICAM-1 and MHC class II molecules and to release a number of chemokines and cytokines, including IL-1, TNF-α and GM-CSF. IL-17 modulates many of the effects induced by IFN-γ. Of note, IL-4, a Th2 cytokine, acts synergistically with the Th1 cytokine IFN-γ to enhance keratinocyte ICAM-1 expression and release of the CXCR3 agonistic chemokines, IP-10, monokines induced by IFN-γ (Mig; CXCL9), and IFN-inducible T cell α-chemoattractant (I-TAC; CXCL11), thus augmenting both recruitment and retention of Th1-type cells in lesional skin.
Effector T Cells in Allergic Contact Dermatitis
Both CD4 and CD8 T cells participate in ACD, with CD8 T cells predominating in effector mechanisms of tissue damage. Budinger and colleagues demonstrated that nickel-responsive peripheral T cells from patients with nickel-induced CD showed a significant overexpression of T cell receptor (TCR)-Vβ17, and the frequency of TCR-Vβ17 + T cells correlated significantly with the in vitro reactivity of peripheral blood mononuclear cells to nickel. In addition, the cutaneous infiltrate of nickel-induced patch test reactions consisted primarily of Vβ17 + T cells, suggesting that T cells with a restricted TCR-Vβ repertoire predominate in nickel-induced CD and may be crucial in the effector phase of nickel hypersensitivity. Of note, these nickel-specific T cells produced IL-5 but not IFN-γ, consistent with a Th2-type cytokine profile. Other studies have shown nickel-specific T cells with a Th1-type profile; in addition, nickel-specific CD4 + Th1-type cells have been shown to be cytotoxic (along with CD8 + T cells) against keratinocytes, whereas Th2-type nickel-reactive T cells were not. More recently, IL-17-producing TH17 cells have been shown to play a role in the immunopathology of ACD, including in both innate and adaptive immune responses to nickel.
Regulatory T Cells in Allergic Contact Dermatitis
Cavani and colleagues described nickel-specific CD4 + T cells from nickel-allergic subjects that secrete predominantly IL-10, which blocks the maturation of dendritic cells including IL-12 release, thus impairing their capacity to activate specific T effector lymphocytes. Thus regulatory T cells may limit excessive tissue damage and participate in the resolution of ACD.
Evaluation and Management
A number of both eczematous and noneczematous dermatoses should be considered in the evaluation of a child with suspected CD. Eczematous dermatoses such as seborrheic and atopic dermatitis occur commonly, whereas psoriasis and zinc deficiency are less common. Nummular eczema, neurodermatitis (lichen simplex chronicus) and adverse drug reaction should also be considered. Noneczematous dermatoses such as dermatophytosis, bullous impetigo, vesicular viral eruptions, urticarial vasculitis, mycosis fungoides and Sézary syndrome may mimic CD.
Spectrum of Contact Dermatitis
Contact dermatitis is traditionally divided into ICD, accounting for 80%, and ACD, accounting for 20% of these reactions. However, there are other diseases that are caused by an external inciting factor such as contact urticaria (CU) and protein contact dermatitis (PCD).
The innate allergenicity or irritancy of the allergen, the site of contact, the degree of contact, the exposure time to contactants, the thickness and integrity of the skin involved, the environmental conditions, the immunocompetency of the patient and genetics affect the type, severity and location of the CD. However, there is frequent overlap between ACD and ICD because many allergens at high enough concentrations can also act as irritants. Impairment to the epidermal barrier layer such as fissuring may increase allergen entry into the epidermis.
CU, a type I immediate hypersensitivity reaction, manifests as pruritic wheals after contact with the triggering substance. CU can be nonimmunologic or immunologic; the latter requires a prior sensitization phase and can spread beyond the localized contact point.
Protein CD manifests as chronic or recurrent eczematous dermatitis (rather than urticaria) upon exposure to specific proteins such as shrimp, fish, meat or latex and is thought to be caused by a combination of type I and type IV reactions. Both CU and PCD can be caused by contact to external allergens and can respond to antihistamines and topical corticosteroids.
Allergic Contact Dermatitis and Atopic Dermatitis
The relationship between ACD and AD is complex and controversial. Earlier literature suggested that patients with AD, especially severe AD, had a depressed Th1 immune system and therefore were less likely to become sensitized to allergens and develop ACD. However, more recent literature suggests that development of ACD may be enhanced in patients with chronic moderate to severe AD. Two later studies showed that the rates of ACD in patients are similar regardless of whether they have AD or not, the frequencies of positive patch test reactions in patients with AD being 63% to 74% and without AD 61.3% to 67%. In 2010, Jacob et al reported that 95.6% of 69 children with suspected ACD had at least one positive patch test reaction, and of these, 76.7% had a history of AD. Although many of the common allergens seen in AD, such as fragrances and lanolin, are similar to those seen in the general population there are certain topical agents that are especially relevant in AD such as topical antibiotics (neomycin and bacitracin) and topical corticosteroids. Interestingly, bacitracin is also reported to cause contact urticaria and anaphylactic reactions. Allergic reactions to topical steroids, the mainstay of treatment of AD, have been reported not only to components of the vehicle (e.g. preservative, fragrance, emulsifier) but to the actual corticosteroid itself. Thus, although the incidence of ACD in patients with AD remains unknown, newer recommendations include the consideration of patch testing in patients with AD who are refractory to standard therapies.
Diagnosis of Contact Dermatitis
A careful, thorough and comprehensive, age-appropriate history should include possible contact exposure of the child such as diapers, hygiene products, perfume-containing products, moisturizers, cosmetics, sun blocks, tattoos, body piercing, textiles with dyes and fire retardant, medications, pets and pet products, school projects, recreational exposure, sports, work, etc. ICD may be the cause of the dermatitis or an aggravating factor. Frequent handwashing, use of water and soaps, detergents and cleansers should be noted. The evolution of the skin reaction is influenced by many factors, including the patient’s skin, age, color, ambient conditions, the use of topical or other oral medication and response to all prior treatment. Because the majority of contact reactions present as eczematous eruptions, it is essential to note clinical evolution from acute vesiculation to chronic lichenification.
Unfortunately, although history can strongly suggest the cause of CD, relying solely on the history, other than with obvious nickel reactions and a few other allergens, may confirm sensitization in only 10% to 20% of patients with ACD. CD must be considered in patients with AD because they have an impaired epidermal barrier layer and use multiple medications, creams and other topical products that subject them to a greater risk for both allergic sensitization and irritation. Also, atopy amplifies the effects of contact irritants and allergens on the skin, and contact sensitization is an aggravating factor in AD.
The diagnosis of ACD is suspected from the clinical presentation of the rash and the possible exposure to a contact allergen. CD can be described as acute, subacute or chronic. Acute dermatitis can present with erythematous papules, vesicles and even bullae. Chronic CD is generally pruritic, erythematous and may be associated with crusting, scaling, fissuring, excoriations and lichenification. ICD usually presents as well-demarcated, erythematous macules, papules and plaques confined to the area of the skin in direct contact with the offending agents, with little or no extension beyond the site of contact ( Figure 53-1 ). ICD generally spares ‘protected’ areas such as the inguinal folds in diaper dermatitis. In ACD, the dermatitis can spread beyond the areas of contact and can even cause an activation of dermatitis at distant sites of prior dermatitis as in systemic CD.
Although geographic location of dermatitis can aid in the determination of the suspected allergen, other factors may influence the location of the dermatitis. In connubial dermatitis, the product may be transferred to the child by the parent/caregiver or to the patient by a partner. Clinically, it is difficult to differentiate CD from AD, especially in the common areas of involvement such as the eyelids, lips, hands, flexural areas of the neck, and even dermatitis with scattered generalized distribution.
A broader spectrum of ICD, including acute, acute delayed, cumulative, traumatic and subjective, has been described.
Regional Considerations in Children
Hand dermatitis in children is extremely common.Its differential diagnosis can be challenging and it is not often studied with patch testing. Hand dermatitis may be due to ICD or ACD, AD, dyshidrosis or psoriasis. Because the skin on the palm is much thicker than that on the dorsum of the hands, ACD rarely involves the palms, occurring most often on the thinner skin between the fingers and the dorsum of the hands ( Figure 53-2 ). However, because of significant overlap, it may be difficult to distinguish the etiology of hand dermatitis. In a study by Toledo et al, 36% of the children with hand eczema had ACD, supporting the recommendation of patch testing of children with chronic hand eczema, independently of age, sex, personal history of atopic dermatitis or distribution of the eczema.
Patch tests in patients with hand eczema showed that relevant allergens included nickel sulfate (17.6%), potassium dichromate (7.2%), rubber elements including thiuram mix, carba mix, p -phenylenediamine (PPD) and mercaptobenzothiazole (MBT) (19.6%) and cobalt chloride (6.4%). A Swedish study of 5,700 patients showed that patients whose entire hands were involved were more likely to react to thiuram mix, p -phenylenediamine, chromate and BOP, while those with involvement of the fingers and interdigital spaces or palm were more likely to react to nickel, cobalt and 5-chloro-2-methyl-4-isothiazolin-3-one/2-methyl-4-isothiazolin-3-one.
The prevalence of hand eczema in patients with AD is 2- to 10-fold higher than in nonatopics. Involvement of the dorsal aspect of the hand and fingers, combined with volar wrist involvement, suggests AD as a contributing etiologic factor. Irritant CD commonly presents as a localized dermatitis without vesicles over webs of fingers extending onto the dorsal and ventral surfaces (‘apron’ pattern), dorsum of the hands, palms and ball of the thumb. In contrast, ACD is often associated with vesicles and tends to favor the fingertips, nail folds and dorsum of the hands; less commonly it involves the palms. Since ICD of the hands can precede ACD, pattern changes such as increasing dermatitis from web spaces to fingertips or from palms to dorsal surfaces should prompt patch testing.
Face and Eyelid Dermatitis
Eyelid dermatitis may be due to ACD (55–63.5%), ICD (15%), AD (<10%) and seborrheic dermatitis (4%). The eyelid is susceptible to ACD because of higher exposure to allergens, greater sensitivity to allergens including aeroallergens, and easy accessibility to touch, facilitating the transfer of chemicals from other areas of the body (e.g. nails, scalp) to the eyelid. Although CD is considered to be the most common cause of eyelid dermatitis, it is believed that 25% of patients with AD may have chronic eyelid dermatitis.
Pure eyelid dermatitis may be distinct from dermatitis with other areas of involvement. Common allergens causing eyelid dermatitis are fragrances (facial tissues, cosmetics), preservatives, nickel (eyelash curlers), thiuram (rubber sponges, masks, balloons, toys), cocamidopropyl betaine and amidoamine (shampoos), tosylamide formaldehyde resin (nail polish) and gold. Facial tissues may contain fragrances, formaldehyde or benzalkonium chloride. PPD and ammonium persulfate can cause urticaria and/or eyelid edema.
Facial dermatitis may also occur secondary to allergens transferred to the face from other regions of the body. The cosmetic industry markets heavily to children, especially the adolescent population. Cosmetics and personal products such as moisturizers, sunscreens, foundations and powders can cause ACD which tends to be symmetrical but can be patchy. The products most likely to cause ACD in the peripheral face (pre-auricular, submental and jawline areas) are shampoos, conditioners and facial cleansers. In contrast, the products most likely to cause a central facial dermatitis (cheeks, forehead) are make-up and moisturizers. ACD that affects the lateral neck is most likely secondary to perfumes/colognes and nail cosmetics. Preservatives and fragrances are the most common allergens in patients with ACD of the face. Rubber-sensitive individuals may react to rubber sponges, masks, balloons, children’s toys and other products that are in contact with the face.
The scalp skin is relatively resistant to allergens in shampoos and hair dyes; shampoos, conditioners, hair sprays, gels and mousses may cause eyelid or facial dermatitis without causing scalp or forehead lesions. Severe burns of the scalp and hair can be caused by the misuse of hair straighteners and relaxers. The manufacturers of hair dyes recommend patch testing with the product before each application.
Oral Mucous Membranes, Perioral Dermatitis and Cheilitis
Perioral dermatitis and cheilitis are common in children and are associated with lip licking, lip chewing, thumb sucking or excessive drooling. Objectively, changes may be barely visible or may vary from a mild erythema to a fiery red color, with or without edema. Juices of foods and even chewing gum may contribute to skin irritation of these areas. Cinnamon flavorings and peppermint are the most common causes of allergic cheilitis from toothpastes.
Contact allergy of the mucous membrane is rare and use of patch testing to evaluate patients with mucosal involvement is controversial. In a series of 331 patients with different oral diseases (burning mouth syndrome, cheilitis, gingivitis, orofacial granulomatosis, perioral dermatitis, lichenoid tissue reaction and recurrent aphthous stomatitis), metals (nickel and gold) were most frequently positive on patch testing. Metals, including mercury, chromate, nickel, gold, cobalt, beryllium and palladium, have been used in orthodontic materials and are important allergens in patients with dental implants or orthodontic devices presenting with oral lichenoid lesions. Other allergens with a high percentage of positive reactions on patch testing include flavorings and preservatives. ‘Fragrances’ are used as flavoring in food products, skin care products and dentifrices. Balsam of Peru is found in dentifrice, mouthwash, lipstick and food. Dodecyl gallate is a preservative used to extend the shelf life of oil-based foods such as peanut butter, soups and pastries. Toothpaste, fluoride mouth washes, chewing gum and other foods may contain cinnamic aldehyde, flavorings and peppermint, which are common causes of allergic cheilitis. Thus, an oral antigen screening series in patients with cheilitis should include not only metals but also an even more comprehensive panel of flavorings, preservatives, medications and dental acrylates. The usefulness of patch testing in the evaluation of orofacial granulomatosis and recurrent aphthous stomatitis is questionable.
Flexural Areas of Neck and Axillary Dermatitis
The thin intertriginous skin of the neck is vulnerable to irritant reactions from ‘perms’, hair dyes, shampoos and conditioners. ‘Berloque’ dermatitis from certain perfumes or nail polish presents as localized areas of eczema. Nickel-sensitive individuals may react to wearing a necklace or to zippers.
ACD can be caused by deodorants but is rarely due to antiperspirants, the latter usually causing ICD. These agents generally cause a dermatitis involving the entire axillary vault, whereas textile ACD spares the apex of the vault. However, sweat and perspiration may cause increased deodorant allergen in the periphery, giving a dermatitis that is less intense in the apex of the axillae. ACD due to disperse dyes such as disperse Orange 1, disperse blue 106 and disperse blue 124 in clothing can elicit eczematous eruptions in the axillae, arms and groin.
Eruptions in the diaper area are the most common dermatologic disorder of infancy. Friction, occlusion, maceration and increased exposure to water, moisture, urine and feces contribute to ICD. The prevalence of diaper dermatitis, an ICD, in infants has been estimated to be 7% to 35% with a peak incidence between ages 9 and 12 months. However, a large-scale study in the UK demonstrated an incidence of 25% in the first 4 weeks of life alone.
Allergic CD to rubber chemicals (mercaptobenzothiazole, cyclohexyl thiophthalimide) or glues ( p -tertiary butylphenol-formaldehyde resin) has been called ‘Lucky Luke’ CD. The characteristic dermatitis is predominantly located on the outer buttocks and hips in toddlers (‘gun holster’ pattern) and is caused by the elastic bands that hold tightly on the thighs to prevent leaking. Treatment usually involves increasing the frequency of diaper changes, using superabsorbent disposable diapers and applying low-potency corticosteroids and barrier ointments or creams. A topical antifungal agent is beneficial in secondary Candida albicans infection. There has been a definite decrease in the incidence of diaper dermatitis due to the availability of newer and improved diapers, including those with superabsorbent gel.
Medication, douches, spermicides, sprays and cleaners can cause CD in the genital area. Fragrances found in liners, toilet paper, soap and bubble baths can cause a reaction in sensitized patients. Contraceptive devices can affect rubber- and latex-sensitive individuals. Ammonia and/or the acidity of urine may cause ICD, especially in incontinent patients. The ingestion of spices, antibiotics or laxatives may cause anal itching.
Leg and Foot Dermatitis
Shaving agents, moisturizers and rubber in the elastic of socks can cause allergic reactions in children. Romaguera and Vilaplana found that the foot was the most frequent localization of CD in children. Irritant dermatitis of the feet may occur in children because of excessive perspiration or the use of synthetic footwear. More commonly, children can develop ACD to rubber accelerators (MBT mix, thiuram mix, carba mix, and PPD mix), dichromates ( Figure 53-3 ) or glues used in the manufacture of shoes. Chrome used in the tanning and dyeing processes of leather, and colophony used in glues in soles and insoles, may be sensitizing. Other chemicals in footwear (e.g. leather, adhesives, glues and dyes) or in topical medications (e.g. creams, ointments and antiperspirants) can cause ACD. Reactions to nickel sulfate were also frequent with metal in footwear buckles, eyelets and ornaments. In ACD, the involvement of the dorsal aspect of the foot and toes, especially the hallux, and sparing of the interdigital areas is characteristic. Irritant dermatitis can involve either the dorsum or the sole. Patients with hyperhidrosis or ‘sweaty sock’ dermatitis should be encouraged to wear cotton socks and to change them frequently, along with wearing breathable footwear.
Dermatitis with scattered generalized distribution (SGD) is a difficult diagnostic and therapeutic challenge because it lacks the characteristic distribution that gives a clue as to the possible diagnosis of ACD. Interestingly, the most common body location of dermatitis for both children and adults reported by the NACD in 2013 was scattered/generalized pattern, followed by the hands and then the face. Zug and colleagues reported that approximately half (49%) of patients with SGD referred for patch testing had a positive patch test deemed at least possibly relevant to their dermatitis, the prevalence being higher in patients with a history of AD. The two allergens most commonly identified were nickel and BOP. Hjorth reported two children who were patch test positive to BOP whose eczema flared after oral intake of naturally occurring balsams. Other relevant positive patch test reactions included preservatives (formaldehyde, quaternium 15, methyldibromoglutaronitrile/phenoxyethanol, diazolidinyl urea, 2-bromo-2-nitropropane-1, 3-diol, imidazolidinyl urea, and DMDM hydantoin) and propylene glycol. Dyes such as disperse blue 106 in synthetic fibers in children’s garments have also been implicated.
Advising patients to use skin care products without the most frequent, relevant allergens (formaldehyde-releasing preservatives, fragrances and propylene glycol) is one strategy that may be helpful while awaiting definitive patch testing results. However, 8% to 10% of patients with SGD remain in the unclassified eczema category.
Systemic CD should be considered as a possible cause of dermatitis with SGD. It manifests as a localized or generalized inflammatory skin disease that occurs in sensitized individuals when they are exposed to the specific allergen orally, transcutaneously, intravenously or by inhalation. There are a variety of manifestations of systemic CD reactions including a reactivation of a previous dermatitis, reactivation of a previously positive patch test (localized ‘recall reactions’), a systemic inflammatory skin disease such as the ‘baboon syndrome’ and/or oral lichenoid reactions. Patients allergic to ethylenediamine may react to systemic aminophylline and antihistamines of the piperazine or ethanolamine families. Similar reactions have been reported to glucocorticoids, diphenhydramine, neomycin, penicillin, sulfonamides, thiuram, colophony, BOP, fragrance mix and nickel ( Table 53-1 ).
|Contact Sensitizer||Systemic Reaction to|
|Benadryl cream ®||Oral diphenhydramine|
|Sulfonamide||Para-amino sulfonamide hypoglycemics (tolbutamide, chlorpropamide)|
|Colophony, Balsam of Peru, fragrance mix||Spices: clove, nutmeg, cinnamon, cayenne pepper |
Citrus fruits: oranges, lemon, tangerines
(alternative: oral theophylline, IV theophylline)
Piperazine and ethanolamine (Atarax ® , Antivert ® )
(alternatives: diphenhydramine, chlorpheniramine, fexofenadine)
|Nickel||Nickel in tap water, utensils and food high in nickel content such as soy, chocolate, lentils, cashews|
|Chromate||Inhaled chromium: oral potassium dichromate|
Unfortunately, even with an extensive history and physical exam, only about 10% to 20% of patients with ACD can be diagnosed accurately without patch testing. Patch testing is needed to identify the responsible allergens, is helpful in young children suspected of ACD and remains the gold standard for confirming ACD. Although the application of antigens for patch testing is rather simple, antigen selection and patch test interpretation require an experienced clinician ( Table 53-2 ).
|Grade||Patch Test Grading|
|(?+)||Doubtful reaction with faint erythema only|
|1+||Weak positive reaction with nonvesicular erythema, infiltration, possible papules|
|2+||Strong positive reaction with vesicular erythema, infiltration and papules|
|3+||Extreme positive reaction with intense erythema and infiltration coalescing vesicles, bullous reaction|
Selection of Appropriate Subjects to Test
The higher the index of suspicion, the more frequent the diagnosis of ACD. Patch testing should be considered for children with a chronic, pruritic or recurrent eczematous dermatitis, especially those with eyelid or hand involvement, those with uncontrollable or worsening chronic dermatitis of greater than 2 months duration and those who fail to improve following standard treatment protocols including a preliminary avoidance regimen of formaldehyde and fragrance. Indeed, the observation that the greatest abuse of patch testing is its lack of use holds true even for the pediatric population. Immunocompromised patients, including those on oral steroids or those on cancer chemotherapy or immunosuppressive drugs, are not appropriate candidates for patch testing. Ideally, the patient’s dermatitis should be quiescent because flare-up reactions may be elicited during patch testing. The patch test site should have had no potent topical immune modulators or steroid applied for 5 to 7 days before testing. Patients should avoid sun or ultraviolet light exposure for 96 hours. Systemic antihistamines have no effect on patch test results. However, not all children with suspected ACD can have patch testing. Given the smaller surface area for patch testing, especially in young children, if comprehensive patch testing cannot be done, a detailed exposure history may guide the choice of potential allergens to test based on the history of exposures and the patient’s own personal care products.
Sources of Allergens
Commercially available standardized patch testing allergens have been calibrated with respect to nonirritant concentrations and compatibility with the test vehicle. Test systems currently available in the USA are the T.R.U.E. TEST ® and the standardized allergens loaded in patch test chambers. Certain screening panels such as the NACD recommended series or the American Contact Dermatitis Society Core Allergen Series, with a range from 65 to 70 allergens are not approved by the US Food and Drug Administration (FDA) but conform to standards of care recommended by CD experts. Commercial sources of customized patch test materials include Smart Practice Canada (1.866.903.2671), SmartPractice Europe +49 (0)40 6701768 and Dormer Laboratories, Inc. (416-242 6167) (email@example.com).
The German Contact Dermatitis Group (GCDG) recommends that children under 6 should only be subjected to patch testing if there is a high degree of clinical suspicion and that only the suspected allergens should be used. Some authors suggest dose adjustment in younger children for allergens such as nickel, formaldehyde, formaldehyde releasers, mercaptobenzothiazole, thiuram and potassium dichromate to avoid irritant false-positive reactions. Jacob et al recommend a reduced concentration of nickel, formaldehyde and rubber additives in children under 5, especially in those who also have AD. Children over the age of 12 can be tested in the same manner as adults and most studies to date suggest that the same test concentrations as in adults can be used.
The ideal number of patch tests to be applied depends on the patient. The usefulness of patch testing is enhanced with the number of allergens tested. Allergens not found on commercially available screening series in the USA frequently give relevant reactions, and personal products are a useful supplement especially in facial or periorbital dermatitis.
A 2011 Pediatric Research Equity Act (PREA)-1 found that the T.R.U.E. TEST ® test with 29 patches was efficacious and safe, in a study of 102 children aged 6 to 18 years . Since then seven more allergens have been added to the T.R.U.E. TEST ® , whose safety and efficacy in pediatric age groups are still being studied ( Table 53-3 ). Comparative results of the T.R.U.E. TEST ® and Finn Chamber method have shown a 64% to 98% concordance, depending on the allergen.
|Nickel sulfate||Snaps, jewelry, food|
|Wool alcohols (lanolin)||Cosmetics (lipstick, hair spray), skin care products (creams, ointments, lotions, moisturizer, baby oil, diaper lotion), personal hygiene items (soaps, cleansers, shampoos), facial masks, sunscreens, over-the-counter and prescription medications for skin rashes, pet grooming aids|
|Neomycin sulphate||Topical antibiotics|
|Potassium dichromate||Chrome-tanned leather products (shoes, boots, gloves), cement, pigments in inks and paints, make-up|
|Caine mix||Topical anesthetics|
|Fragrance mix||Fragrances, scented household products|
|Colophony||Cosmetics, sunscreens, adhesives, household products, diapers, feminine napkins, wax depilatories, match tips|
|Paraben mix||Preservative in topical formulations, cosmetics|
|Balsam of Peru||Cosmetics, fragrances, dental hygiene products, topical medications, food|
|Ethylenediamine dihydrochloride||Topical medications, piperazine-related antihistamines, aminophylline, hydroxyzine hydrochloride|
|Cobalt dichloride||Metal-plated objects (utensils, keys, magnets, clothing fasteners, jewelry), paints, cobalt-based pigments, vitamin B 12 supplements|
|p-tert -Butylphenol-formaldehyde resin||Fabrics, glued rubber (rubber-containing footwear, handbags, watchbands, belts, bras), sports gear, leather goods|
|Epoxy resin||Two-part adhesives and paints, art and sculpture materials, manufacture of tennis racquets, skis, circuit boards, lightweight equipment|
|Carba mix||Rubber products, shampoos, disinfectants|
|Black rubber mix||All black rubber products (tires, playgrounds), some hair dyes|
|CL+ ME– Isothiazolinone (MCI/MI)||Cosmetics (foundations, powders, blush, mascaras, eye shadows, eyeliners and pencils), skin care products (creams, lotions, moisturizers, soaps, cleaners, bubble baths, wipes), hair care products (conditioners, shampoos, coloring agents), laundry products (detergents, fabric softener)|
|Quaternium-15||Preservative in cosmetics and skin care products|
|Methyldibromo glutaronitrile||Skin care products such as body creams, facial/hand lotions, sun screens, and baby lotions |
Personal hygiene products such as moist toilet paper, shampoos, conditioners and shower gels
|p -Phenylenediamine||Permanent or semipermanent hair dyes, cosmetics, printing ink, black henna tattoo|
|Formaldehyde||Fabric finishes, cosmetics|
|Mercapto mix||Rubber products, glues for leather and plastics|
|Thimerosal||Preservative in contact lens solutions, cosmetics, injectable drugs|
|Thiuram mix||Rubber products, adhesives|
|Diazolidinyl urea||Products for personal care, hygiene and hair care; cosmetics; pet shampoos|
|Quinoline mix||Paste bandages; prescription and non-prescription topical antibiotics and antifungal creams, lotions, ointments; animal food|
|Gold sodium thiosulfate||Gold or gold-plated jewelry, dental restorations|
|Imidazolidinyl urea||Products for personal care, hygiene and hair care; cosmetics; liquid soaps; moisturizers|
|Budesonide||Corticosteroid creams, lotions and ointments, nasal corticosteroid spray; asthma controller medication in inhaler, nebulized suspension and dry powder forms|
|Mercaptobenzothiazole||Rubber products, nitrile or neoprene, such as rubber bands, ear- and headphones, masks, condoms and diaphragms, goggles, shoes, utility gloves, swimwear, toys, hoses, tubing and elastic |
Sports equipment made with natural rubber, butyl rubber, nitrile or neoprene such as shoes, wetsuits, boots, masks, racquet and club handles
|Bacitracin||Prescription and in over-the-counter preparations such as topical antibiotic creams, lotions, ointments, bandages, ophthalmic and otic products|
|Parthenolide||Plants and gardens, herbal teas containing sesquiterpenes, supplements, tablets or tinctures|
|Disperse blue 106||Synthetic fabrics such as polyester, acetate, nylon with black or navy blue color; dark-colored polyester velour and in children’s diapers and exercise garments; dyed fabrics such as bedding, clothing, nylon stockings, swimming suits, tights, velour, children’s diapers|
|2-Bromo-2-nitropropane-1,3-diol (Bronopol)||Topical antibiotic/antifungal creams/ointments, finger paints, kitty litter, detergents, toiletries and cleansers, cleansing lotions, creams, foundations, hair conditioners, mouthwash, shampoos|