Allergic Contact Dermatitis in AD

Atopic dermatitis (AD) is a chronic skin disorder with a complex etiology and presentation. Characteristic features of AD include immune dysregulation and skin barrier dysfunction.1,2 These features lead to pruritic and erythematous lesions in the acute phase, and xerotic lichenified lesions in the late stages.3

Figure 1. Female with allergy to numerous essential oils. Oil use was stopped and her dermatitis was treated. Hersymptoms resolved and did not return.

The prevalence of AD has been increasing worldwide,4 with cases documented in the United States in up to 20% of children and up to 10% of adults.5,6 AD has traditionally been considered a disease mostly limited to childhood with studies noting persistence into adulthood in only 1% to 3%.6 Recently, however, data from a large AD patient registry of 7157 patients showed that more than 80% of AD patients aged 2 to 26 years had symptoms of AD and were using medication to treat it. By age 20, about 50% of these patients had  attained only one 6-month period with no symptoms.7 In cases of recalcitrant AD, allergic contact dermatitis (ACD) is often an underrecognized problem and should be considered in all patients with a chronic dermatitis even when confirmed AD exists.

One important entity that can worsen and complicate the course of AD is ACD, which is a delayed (type IV) T-cell mediated hypersensitivity reaction that develops following cutaneous re-exposure to a culprit allergen in sensitized individuals. Contact dermatitis is an important disease estimated to notably affect more than 72 million Americans each year.8 The economic impact of this disease is high in regards to patient morbidity and quality of life, missed work days and loss of income, not to mention significant expenditures for visits to health care providers and for medications. Correctly diagnosing ACD results in improvement, prevention, or “cure” of the dermatitis and decreases overall costs to the health care system.9 Once patch testing is performed and a culprit has been identified, education becomes the critical intervention to ensure adherence to an avoidance regimen.

With allergen avoidance, remission of the dermatitis ensues. If patients are unable to comply with the avoidance regimen, they become at risk for recurrent or sustained dermatitis or progression to a systematized presentation.10 The evaluation of ACD fits well with theranostic theory, individualized therapy combining diagnostics and therapeutic intervention, as the patch test evaluation is used to dictate a personalized avoidance strategy for the management of each patient. Although ACD is not “curable,” many individuals will achieve complete remission with meticulous avoidance. This article highlights ACD in AD patients and explores top relevant allergens, pathophysiological factors, as well as clinical tips and pearls for diagnosis and treatment. ACD should be considered in any patient with chronic recalcitrant dermatitis.

Inflammatory Pathways Associated with AD and ACD

AD is a chronic condition that arises as a result of chronic immune dysregulation, skin barrier dysfunction, and susceptibility to infection or colonization with bacteria such as Staphylococcus aureus.1,2 The inflammation of AD is characterized primarily by the T-helper (Th) 2 cell phenotype, although there are also contributions from Th1, Th22, and Th17 cells.1,2

With ACD the initial sensitization occurs when small haptens penetrate the skin and are processed by Langerhans cells or dermal dendritic-antigen presenting cells. Subsequently, they are presented to naive T cells in the lymph nodes which in turn induce clonal expansion of the memory T cell.11 Upon re-exposure to the allergen, the primed T cells mount an immunologic response, eliciting the clinical picture of ACD that include edema, erythema, and vesiculation. The inflammation of ACD is primarily characterized by a T cytotoxic (Tc)1/Th1 phenotype, although Th2, Th17, and Th22 cells may be activated as well.1,2,12

Figure 2. Nine-year-old girl with lifelong history of atopic dermatitis and ichthyiosis vulgaris had been using bacitracin on all of the open sores of her eczema. Patch testing showed she is allergic to bacitracin. With avoidance of the bacitracin and a compounded formulation of fluocinonide in TrueLipids base her dermatitis improved. She was able to cease all steroids and maintain clearance with emollient care.


Figures 3 and 4. Eyelid dermatitis due to methychloroisothiazolinone. (Figure 3). The reaction resolved with avoidance of MI and treatment with TrueLipids 1% hydrocortisone cream for 2 weeks. (Figure 4).


Several inflammatory mechanisms may predispose AD patients to ACD. Irritant contact dermatitis (ICD) may induce an innate immune cascade that predisposes to ACD.2 In addition, AD in the chronic phase partially shifts to a more Th1 phenotype.2 Finally, the presence of bacteria, common in AD, has been suggested to promote ACD, possibly through the upregulation of similar inflammatory mediators to ACD, such as toll-like receptors and T-cell receptor Vbeta 17 region expansion.1 A recent study also linked nickel allergy and S aureus infection specifically in AD. These investigators reported an elevated secretion of IL-2 under nickel sulfate stimulation in vitro exclusively in atopic patients with nickel allergy infected by S aureus.13 IL-2, in addition to its role in promoting the differentiation of T cells following antigen stimulation (geared to aid in fighting off infections), also plays a pivotal role in the development of contact sensitization.

Impact of a Defective Skin Barrier

The skin of AD patients notably shows increased transepidermal water loss, with decreased production of terminal differentiation proteins such as filaggrin, aberrations in skin lipid concentrations and ratios, and increased pH.1,14 Additionally, defective skin barrier acidification has been shown to lead to a myriad of other problems including decreased skin barrier lipid production, diminished production and secretion of cutaneous antimicrobial peptides, defective cellular differentiation, excessive inflammation, and the initiation of contact sensitization.15 Several studies have suggested that skin barrier acidification may be the missing link and the “master switch” in AD.16,17 Immune abnormalities may also contribute to the barrier dysfunction of AD. For example, the Th2 cytokines IL-4 and IL-13 have been shown to downregulate ceramides and the expression of epidermal differentiation complex genes.2

ACD Should Be Considered in AD Patients

Strong evidence exists that the Th2 bias in AD may lower the risk of contact sensitization compared with healthy controls.1 However, AD patients appear to be at similar or even increased risk of ACD compared with the general population for several reasons.

First, the dysfunctional skin barrier in AD patients allows for increased penetration of chemicals, which may increase the risk for sensitization and ACD.1 Of note, this barrier defect also results in increased rates of ICD, which further compromises the skin barrier and magnifies this issue.

In addition, the mainstay of therapy in AD patients includes chronic emollients and topical anti-inflammatory therapy for treatment and maintenance, which may result in children with AD becoming sensitized to allergens found in their topical products.1,18 For example, many so-called hypoallergenic pediatric cosmetic products for sale in the United States contain potent contact allergens such as fragrances and preservatives.19 It has been suggested that skin barrier repair medicaments that do not contain any of the common allergens seen in AD may be helpful, although further research is required.14

Clinical studies show that AD patients are as much at risk for ACD as the general population. One study found that 89% of AD patients and 66% of non-AD patients with suspected ACD and chronic eczema were patch test positive.20 In another study, Czarnobilska and colleagues21 found that 44% of 7-year-old children and 53% of 16 year-olds with a history of chronic eczema were patch test positive. When the study was repeated in atopic children only, 67% of 7 to 8 year olds and 58% of 16 to 17 year olds were patch test positive.22 Common allergens in these age groups included nickel (35.9% and 19.4%, respectively), propolis (16.5% and 5.4%, respectively), cobalt (9.7% and 6.5%, respectively), fragrance mix I (6.8% and 3.2%, respectively), chromium (6.8% and 3.2%, respectively), and fragrance mix II (5.8% and 2.2%, respectively).22

While there has been a heightened awareness of ACD in the last decade, the true prevalence is likely grossly underestimated as it is often overlooked, especially in very young patients. ACD has been reported to occur even in those who are as young as 6 months.11

Many studies show rates of ACD in AD are lower during flares and higher during periods of disease quiescence.23 In a dinitrochlorobenzene sensitization study, 33% of severe, 95% of moderate, and 100% of mild atopics could be sensitized.23 When nonresponders were rechallenged at a time of disease quiescence, almost all demonstrated an ACD response.

In another study, when adolescent and adult AD patients were patch tested during a period of quiescence, 48% of patients had an allergic reaction to at least 1 European Standard Series allergen, and 12.8% of patients had an allergic reaction to at least 1 corticosteroid.24 This finding underscores the importance of concomitant therapies aimed at barrier repair in the atopic patient, which ultimately decreases the utilization of topical therapies and associated risk of sensitization. Notably, the most common allergens in this study were nickel sulfate (28.2%), potassium dichromate (20.5%), cobalt chloride (12.8%), and phenylenediamine, budesonide, betamethasone, clobetasol, and dexamethasone (7.7% each).

ACD can be localized or distant from the site of exposure and may also predominantly involve the flexures, due to exposure patterns or local factors such as friction, occlusion, and maceration.25 This is often confused for a flare of AD. Various factors may affect the thresholds for sensitization among individuals including age, type of allergen, degree of skin barrier dysfunction, and frequency and duration of exposure.1 Some patients require repeated exposure to the allergen to develop ACD while other more potent allergens may elicit earlier and more intense reactions.

As it may be difficult to differentiate ACD from AD, minimization of allergens that have been shown to be statistically significantly more common in AD (Table) may be prudent in all children who have any form of chronic eczema.26-28


Figure 5. Thirteen-year-old girl with 3-year history of dermaitis that began on her leg and then spread to her face. She was treated with 2.5% hydrocortison butyrate, which would improve and then exacerbate the dermatitis. Patch testing revealed she was allergic to tixocortol pivalate, nickel sulfate, neomycin sulfate, and thimerosal. All hydrocortisone was removed from her treatment plan and she was treated with TrueLipids emollient for 3 weeks. She recovered completely.

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