Pediatric allergic contact dermatitis (ACD) has become a much more frequently recognized entity in the United States recently, accounting for an estimated 20% of all cases of dermatitis in this subgroup. It is important to recognize, however, that this type of dermatitis may be overlooked, especially in the very young and when it is a contributing factor in atopic dermatitis (AD; Militello, Jacob, & Crawford, 2006; Nijhawen, Matiz, & Jacob, 2009). It was not until 2008 that the first reported patch test studies in U.S.-based populations were reported, confirming that contact dermatitis was equally prevalent in U.S. children as it was in the adult population and that patch testing was safe and efficacious (Jacob, Brod, & Crawford, 2008; Zug et al., 2008). Although this was the case in the United States, a significant number of children were patch tested over the last decade at many international centers and were found to have ACD related to nickel-containing piercings, cosmetics, fragrances, and preservatives (Hogeling & Pratt, 2008; Jacob & Breithaupt, 2009; Militello et al., 2006).
THE CONTACT DERMATITIS DERMATOSES
Contact dermatitis refers to dermatoses that are related to an external agent. The two main types are irritant contact dermatitis (ICD) and ACD, which make up over 95% of the cases. Immune contact urticaria, nonimmune contact urticaria, and protein contact are further diagnoses that are much less common. Irritant contact dermatitis is by far the most common. It occurs when the skin is in contact with a substance that is caustic to the skin. It is not an immunologic reaction, usually occurring within 48 hours and resolving within 96 hours (Nijhawen et al., 2009).
Classic examples of ICD include saliva in lip-licking dermatitis, soap in hand dermatitis, and urine in diaper dermatitis; however, even mildly caustic substances could potentially be irritants if in contact with sensitive skin for a long enough time. In general, the severity of an irritant reaction will be directly proportional to the concentration and time of exposure to the inciting agent (Nijhawen et al., 2009). Moreover, it is easier for patients to avoid exposure to these agents, because they are usually able to make the association between the exposure and the distribution of the dermatitis. The shorter time frame from contact with the chemical to the reaction also facilitates making the connection and the diagnosis.
The second most common form of contact dermatitis, ACD, is characterized by a complex immunologic event. Clinically, it presents as a delayed Type IV hypersensitivity reaction, generally with a 48- to 96-hour latency period between contact with the substance and a reactivity state in the skin. Furthermore, it can then take weeks to resolve, as well (Militello et al., 2006; Nijhawen et al., 2009).
ACD can be thought of as occurring in two main stages: the first and rate-limiting step being sensitization and the second being elicitation. Sensitization involves the entry of allergens into the epidermis, where they bond to keratinocytes, and are recognized by the antigen-presenting cells. These cells then process these antigens and present them to naive T cells, resulting in memory T-cell clonal expansion (Militello et al., 2006; Nijhawen et al., 2009). Because of greater contact with an increasing number of chemicals in the environment from jewelry, cosmetics, and personal hygiene products to sporting gear and toys, rates of sensitization in the pediatric population may be on the rise (Hogeling & Pratt, 2008). Furthermore, an impaired skin barrier, such as that seen in AD, may facilitate the entrance of allergens into the skin.
The second phase of ACD, elicitation, occurs after repeated exposure to an environmental allergen. When recognition of the allergen occurs, there is cloning of memory T cells and release of inflammatory cytokines. This results in the appearance of the dermatitis at the site of contact with the allergen and potentially at prior sites of reactivity (Militello et al., 2006).
An important clinical clue to the diagnosis of ACD and a diagnostic conundrum is that it may take several days after contact with the instigating substance to develop the hypersensitivity response. Because of this, the patient may not be able to identify a temporal association with a source. Furthermore, the allergen may be something that the patient has been in contact with or has used repeatedly for years without a problem. This can lead the patient to doubt the association. Explaining the concept of threshold, the point at which the skin's ability to "tolerate" the chemical has been surpassed, becomes imperative both for the patient's understanding and for the treatment. When the threshold is reached through repeated exposures (elicitation) in a sensitized individual, the dermatitis reaction occurs. In the clinic, we give examples of how keys, jean snaps, spinach, and chocolate all contain one common ingredient, namely nickel. Each exposure is additive, making avoidance necessary to get beneath the threshold and into the "rash-free zone."
Clinically, because ACD often appears as pruritic, eczematous plaques, it can be difficult to distinguish from ICD or AD (Militello et al., 2006). As mentioned above, acute ICD and acute ACD can often be distinguished by clinical time course. This is also true of these reactions during patch testing; although ICD reactions generally resolve by 72-96 hours, ACD may just be peaking in intensity at that time. In addition, ICD is usually confined to areas of contact exposure, will appear as a well-demarcated erythematous and sometimes follicular reaction, and tends to burn, whereas ACD often expands beyond the area of contact, is marked by induration and/or papulovesicular eruptions, and tends to itch (Jacob, Steele, & Brod, 2008; Militello et al., 2006). Chronic ICD and chronic ACD, however, can be extremely difficult to distinguish from each other as the inflammatory areas become poorly demarcated and lichenified, and here the patch test becomes a highly useful tool.
On a final note, immune contact urticaria and protein contact, both IgE-mediated Type I immunologic reactions, as well as nonimmune urticaria are beyond the scope of this article. Most often, these diagnoses are investigated by the allergist. Radioallergosorbent testing, prick testing, and protein and atopy patch testing can be useful diagnostic tests in these conditions (Militello et al., 2006).
As mentioned above, for the most part, ACD occurs in the area of contact with an allergen. That being said, there are instances when the location of the dermatitis is not directly related to the site of contact exposure with the allergen. This makes the diagnosis difficult. For example, ectopic ACD refers to the transfer of the allergen into an area where it otherwise would not be found, such as the scratching of atopic sites with nail polish causing a flare (Jacob & Stechschulte, 2008) or a cashier who rubs her eyelids after handling metal money. Furthermore, idiopathic reactions may also be seen, in which there are nonspecific widespread eruptions when the patient comes in contact with his or her allergen (Militello et al., 2006; Nijhawen et al., 2009).
Along these same lines, distinguishing between ACD and AD can be challenging because of their similar morphologic presentation. The National Institute of Arthritis and Musculoskeletal and Skin Diseases estimates that 10%-20% of all children experience AD (National Institute of Arthritis and Musculoskeletal Diseases, 2009), which is likely an underestimate, as milder cases may go unrecognized or unreported because they may not seek medical care (Jacob, Burk, & Connelly, 2008). Furthermore, most children are not evaluated with patch testing and, thus, could potentially be classified as AD when they may have ACD or an overlap of both disorders. In fact, some studies have shown that children affected by AD are at higher risk for developing ACD because of a defective skin barrier, allowing for allergens to more easily penetrate the skin (Giordano et al., 1999; Jacob, Burk, et al., 2008; Jacob & Stechschulte, 2008; Lammintausta, Kamino, & Fagerlund, 1992). In addition, it is possible that atopic patients' prolonged use of topical medicaments can increase their sensitization to antibiotics (Lammintausta et al., 1992) as well as corticosteroids, especially if they no longer respond to treatment (Gonul & Gul, 2005). Just as epicutaneous patch testing can aid in distinguishing between ACD and ICD (based on timeline), it is also of high utility in the evaluation of atopic patients (Jacob, Steele, et al., 2008; Militello et al., 2006; Nijhawen et al., 2009). That being said, an investigative history and diagnostic clues, such as a new onset and/or a progressing or deteriorating dermatitis that is recalcitrant to standard therapies, can also help guide a clinician to diagnosing ACD and proceeding to refer for patch testing (Zug et al., 2008).
Unfortunately, there is very limited access to comprehensive patch testing, despite a high prevalence of dermatitis in pediatric populations. Therefore, the patients most likely to be referred and to receive the benefits of patch testing are those with a minimum of 2 months of uncontrollable or worsening dermatitis and those who have failed standard treatments and not improved on super sensitive skin regimens (Jacob, Burk, et al., 2008). One significant limitation in pediatric patch testing in younger children is the relatively small surface area on the patients' backs available for patch testing, even more so if the skin area is at all affected. This further increases the need for an even higher selectivity when choosing which allergens to evaluate the patient with for patch testing. Whereas, ideally, patients would discontinue their systemic immunosuppressives prior to and during testing, there are some patients who may be so extensively affected that there is too limited an area to test without them and, thus, patch testing is performed on the lowest possible dose of the immunosuppressant.
Eliciting a thorough history from the patient and his or her family to determine which allergens have the greatest potential to be culprits is the first step in evaluation. This includes information about the patient's medical history, personal hygiene, and home environment (Jacob, Burk, et al., 2008). A review of their caregiver's environment is also necessary, as patients may develop a connubial dermatitis from transfer from a caregiver, either directly or indirectly (Nijhawen et al., 2009). The geographic locations of the reaction can also provide clues regarding allergens to which the patient may be reacting. Furthermore, examining and reviewing the products used by patients and their habits can help determine the allergens that may be repeating in the patients' environment, often from seemingly unrelated sources.
There is a commercially available prepackaged allergen panel kit available for screening purposes, the Thin Rapid Use Epicutaneous Test (T.R.U.E. Test, Mekos Laboratories A/S, Hillerod, Denmark), but it is currently only approved by the Food and Drug Administration for use in patients of greater than 18 years of age (T.R.U.E. Test website). Despite this, in a data analysis from the North American Contact Dermatitis Group 2001-2004, it was found that of the 200 children (ages 0-18 years) with relevant, positive patch tests when testing with the North American Contact Dermatitis Group series allergens, 123 (61.5%) would have had all of their relevant, positive patch test reactions detected if only the T.R.U.E. Test (Panels 1.1 and 2.1) had been used (Zug et al., 2008).
Comprehensive patch testing or custom-tailored individual allergen panels have the highest efficacy in determining the cause of a patient's ACD, because the allergens are selected specifically based on the patient's environmental exposures. The allergens are placed onto individual chambers that are then applied to unaffected regions of the child's back in linear configurations under occlusion (Figure 1) and secured with Hypafix tape (Smith & Nephew, London, United Kingdom). After 24-48 hours, these chambers should be removed to reduce irritant reactions (Jacob, Burk, et al., 2008; Worm et al., 2007). The initial reading is performed at this time, noting any erythema, induration, papules, or blistering. The patient then returns for a 72- to 120-hour delayed read (Militello et al., 2006). Again, this reading also helps to distinguish between allergic and irritant contact reactions, because ICD reactions are typically seen early and are usually in the healing resolution phase by 72-96 hours (Nijhawen et al., 2009). ACD reactions, on the other hand, continue to worsen over the duration of the patch test procedure.
A second retrospective history is obtained after the final patch test reading to further delineate the clinical relevance of the positive reactions and to investigate for potential exposure sources. This is crucial to avoid unnecessarily restricting the patients' daily routine, as all positive patch test results may not be relevant to the patient's current dermatitis presentation (Jacob, Brod et al., 2008; Table 1).
Once clinical relevance is determined, the patients and their families are provided with comprehensive education regarding which chemicals and products to avoid. In our clinic, the families are given both literature on these specific chemicals and a list of alternative products derived from the American Contact Dermatitis Society Contact Allergen Management Program (CAMP) or from the Mayo Clinic Contact Allergen Replacement Database (CARD; Jacob, Brod, et al., 2008). It is important to instruct families on how to perform a provocative use test on the patient, as products on the Contact Allergen Replacement Database list may contain chemicals that have not been tested. This involves applying a small amount of the product twice a day for 7 days to a 2.5-cm circle drawn on the inner arm, proximal to the antecubital fossa. If burning, redness, or irritation develops, the patient should discontinue use; furthermore, if any reaction occurs, the patient should return to their physician for evaluation of the application site at the end of the test period (Jacob, Brod, et al., 2008).
Avoidance of the relevant chemicals to which the patient has reacted on patch testing is the mainstay of treatment for ACD (Jacob, Brod, et al., 2008; Jacob & Castanedo-Tardan, 2007). There are instances, however, when pharmacotherapy needs to be used, as an allergen may not be identified or avoidance may not be possible; in this case, a treatment algorithm is advised. (Table 2). In addition to focusing on diagnosis and treatment of ACD, one must take into account the psychological toll that it takes on the patients and their families. Many people experience depression and anxiety; therefore, counseling and support may be helpful (Jacob & Castanedo-Tardan, 2007). Moreover, without proper recognition of ACD as a potential cause of moderate to severe or recalcitrant dermatitis, preventative measures cannot be attempted. Thus, it is vital that providers become educated on the diagnostic clues, so that, with avoidance, the morbidity of childhood dermatoses can decrease.
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