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Can Atopic Dermatitis and Allergic Contact Dermatitis Coexist?
Author(s)
Hadley Johnson, BS
Danielle E. Novack, BA
Brandon L. Adler, MD
Jiade Yu, MD

Atopic dermatitis (AD) and allergic contact dermatitis (ACD) are 2 common inflammatory skin conditions that may have similar clinical presentations. Historically, it was thought that these conditions could not be diagnosed simultaneously due to their differing immune mechanisms; however, this belief has been challenged by recent evidence suggesting a more nuanced relationship between the 2 disease processes. In this review, we examine the complex interplay between AD and ACD and explain how shifts in conventional understanding of the 2 conditions shaped our evolving recognition of their ability to coexist.

Epidemiology of AD and ACD

Atopic dermatitis is the most common inflammatory skin disease in children and adolescents, with an estimated prevalence reaching 21%.1 In 60% of cases, onset of AD will occur within the first year of life, and 90% of cases begin within the first 5 years.2 Resolution may occur by adulthood; however, AD may continue to impact up to 8% to 9% of adults, with an increased prevalence in those older than 75 years.1 This may represent an underestimation of the burden of adult AD; one systematic review of 17 studies found that the pooled proportion of adult-onset AD was greater than 25%.3

In contrast, ACD previously was assumed to be a disease that more commonly impacted adults and only rarely children, primarily due to an early misconception that children were not frequently exposed to contact allergens and their immune systems were too immature to react to them even if exposed.4,5 However, it is now known that children do have risk factors for development of ACD, including a thinner stratum corneum and potentially a more absorbent skin surface.4 In addition, a 2022 study by the North American Contact Dermatitis Group (NACDG) found similar rates of ACD in children (n=1871) and adults (n=41,699) referred for patch testing (55.2% and 57.3%, respectively) as well as similar rates of having at least 1 relevant positive patch test (49.2% and 52.2%).6

In opposition to traditional beliefs, these findings highlight that AD and ACD can occur across age groups.

Immune Mechanism

The pathogenesis of AD represents a multifactorial process involving the immune system, cutaneous flora, genetic predisposition, and surrounding environment. Immunologically, acute AD is driven by a predominantly TH2 helper T-cell response with high levels of IL-4, IL-5, and IL-137; TH22, TH17, and TH1 also have been implicated.8 Notably, TH17 is found in high levels during the acute eczema phase, while TH1 and TH22are associated with the chronic phase.7

The pathophysiology of ACD is not completely understood. The classic paradigm involves 2 phases: sensitization and elicitation. Sensitization involves antigen-presenting cells that take up allergens absorbed by the skin to present them in regional lymph nodes where antigen-specific T lymphocytes are generated. Elicitation occurs upon re-exposure to the allergen, at which time the primed T lymphocytes are recruited to the skin, causing inflammation.9 Allergic contact dermatitis initially was thought to be driven by TH1 cytokines and IL-17 but now is understood to be more complex.10 Studies have revealed immune polarization of contact allergens, demonstrating that nickel primarily induces a TH1/TH17 response, whereas fragrance and rubber accelerators skew to TH2; TH9 and TH22 also may be involved depending on the causative allergen.11,12

Of note, the immunologic differences between AD and ACD led early investigators to believe that patients with AD were relatively protected from ACD.13 However, as previously described, there are several overlapping cytokines between AD and ACD. Furthermore, research has revealed that risk of contact sensitization might be increased in the chronic eczema phase due to the shared TH1 pathway.14 Barrier-disrupted skin (such as that in AD) also may increase the cytokine response and the density of antigen-presenting cells, leading to a proallergic state.15 This suggests that the immunologic pathways of AD and ACD are more intertwined than was previously understood.

 

 

Underlying Risk Factors

Skin barrier dysfunction is a key step in the pathogenesis of AD. Patients with AD commonly have loss-of-function mutations in the filaggrin gene, a protein that is key to the function of the stratum corneum. Loss of this protein may not only impact the immune response as previously noted but also may lead to increased transepidermal water loss and bacterial colonization.16 Interestingly, a 2014 review examined how this mutation could lead to an increased risk of sensitization to bivalent metal ions via an impaired chelating ability of the skin.17 Furthermore, a 2016 study conducted in Dutch construction workers revealed an increased risk for contact dermatitis (irritant and allergic) for those with a loss-of-function filaggrin mutation.18

Importantly, this same mutation may explain why patients with AD tend to have increased skin colonization by Staphylococcus aureus. The abundance of S aureus and the relative decrease in the diversity of other microorganisms on the skin may be associated with increased AD severity.19 Likewise, S aureus may play a role in the pathogenesis of ACD via production of its exotoxin directed at the T-cell receptor V beta 17 region. In particular, this receptor has been associated with nickel sensitization.17

Another risk factor to consider is increased exposure to contact sensitizers when treating AD. For instance, management often includes use of over-the-counter emollients, natural or botanical remedies with purported benefits for AD, cleansers, and detergents. However, these products can contain some of the most prevalent contact allergens seen in those with AD, including methyl-isothiazolinone, formaldehyde releasers, and fragrance.20 Topical corticosteroids also are frequently used, and ACD to steroid molecules can occur, particularly to tixocortol-21-pivalate (a marker for class A corticosteroids) and budesonide (a marker for class B corticosteroids).21 Other allergens (eg, benzyl alcohol, propylene glycol) also may be found as inactive ingredients of topical corticosteroids.22 These exposures may place AD patients at risk for ACD.

The Coexistence of AD and ACD

Given the overlapping epidemiology, immunology, and potentially increased risk for the development of ACD in patients with AD, it would be reasonable to assume that the 2 diagnoses could coexist; however, is there clinical data to support this idea? Based on recent database reviews, the answer appears to be yes.20,23-26 An analysis from the Pediatric Contact Dermatitis Registry revealed that 30% of 1142 pediatric patch test cases analyzed were diagnosed as AD and ACD simultaneously.24 The NACDG found similar results in its 2021 review, as 29.5% of children (n=1648) and 20.7% of adults (n=36,834) had a concurrent diagnosis of AD and ACD.20 Notably, older results from these databases also demonstrated an association between the 2 conditions.23,25,26

It remains unclear whether the prevalence of ACD is higher in those with or without AD. A comprehensive systematic review conducted in 2017 examined this topic through analysis of 74 studies. The results demonstrated a similar prevalence of contact sensitization in individuals with and without AD.27 Another systematic review of 31 studies conducted in 2017 found a higher prevalence for ACD in children without AD; however, the authors noted that the included studies were too variable (eg, size, design, allergens tested) to draw definitive conclusions.28

Even though there is no clear overall increased risk for ACD in patients with AD, research has suggested that certain allergens may be more prevalent in the setting of AD. An NACDG study found that adults with AD had increased odds of reacting to 10 of the top 25 NACDG screening allergens compared to those without AD.20 Other studies have found that AD patients may be more likely to become sensitized to certain allergens, such as fragrance and lanolin.14

Considerations for Management

Diagnosis of ACD in patients with AD can be challenging because these conditions may present similarly with chronic, pruritic, inflammatory patches and plaques. Chronic ACD may be misdiagnosed as AD if patch testing is not performed.29 Given the prevalence of ACD in the setting of AD, there should be a low threshold to pursue patch testing, especially when dermatitis is recalcitrant to standard therapies or presents in an atypical distribution (ie, perioral, predominantly head/neck, hand and foot, isolated eyelid involvement, buttocks).4,30 Various allergen series are available for patch testing adults and children including the NACDG Standard Series, American Contact Dermatitis Society Core Allergen Series, or the Pediatric Baseline Series.31-33

If potentially relevant allergens are uncovered by patch testing, patients should be counseled on avoidance strategies. However, allergen avoidance may not always lead to complete symptom resolution, especially if AD is present concomitantly with ACD. Therefore, use of topical or systemic therapies still may be required. Topical corticosteroids can be used when dermatitis is acute and localized. Systemic corticosteroids are utilized for both diagnoses when cases are more severe or extensive, but their adverse-effect profile limits long-term use. Other systemic treatments, including conventional agents (ie, azathioprine, cyclosporine, methotrexate, mycophenolate mofetil), biologics, and small molecule inhibitors also may be considered for severe cases.34,35 Dupilumab, a monoclonal antibody targeting IL-4/IL-13, is approved for use in moderate to severe AD in patients 6 months and older. Recent evidence has suggested that dupilumab also may be an effective off-label treatment choice for ACD when allergen avoidance alone is insufficient.36 Studies have been conducted on secukinumab, a monoclonal antibody against IL-17; however, it has not been shown to be effective in either AD or ACD.37,38 This indicates that targeted biologics may not always be successful in treating these diagnoses, likely due to their complex immune pathways. Finally, there is an emerging role for JAK inhibitors. Three are approved for AD: topical ruxolitinib, oral abrocitinib, and oral upadacitinib.39 Further investigation is needed to determine the efficacy of JAK inhibitors in ACD.

Final Interpretation

Evolving evidence shows that AD and ACD can occur at the same time despite the historical perspective that their immune pathways were too polarized for this to happen. Atopic dermatitis may be an important risk factor for subsequent development of ACD. Management should include a low threshold to perform patch testing, while pharmacotherapies utilized in the treatment of both conditions should be considered.

References
  1. Chan LN, Magyari A, Ye M, et al. The epidemiology of atopic dermatitis in older adults: a population-based study in the United Kingdom. PLoS One. 2021;16:E0258219. doi:10.1371/journal.pone.0258219
  2. Eichenfield LF, Tom WL, Chamlin SL, et al. Guidelines of care for the management of atopic dermatitis: section 1. diagnosis and assessment of atopic dermatitis [published online November 27, 2013]. J Am Acad Dermatol. 2014;70:338-351. doi:10.1016/j.jaad.2013.10.010
  3. Lee HH, Patel KR, Singam V, et al. A systematic review and meta-analysis of the prevalence and phenotype of adult-onset atopic dermatitis [published online June 2, 2018]. J Am Acad Dermatol. 2019;80:1526-1532.e7. doi:10.1016/j.jaad.2018.05.1241
  4. Borok J, Matiz C, Goldenberg A, et al. Contact dermatitis in atopic dermatitis children—past, present, and future. Clin Rev Allergy Immunol. 2019;56:86-98. doi:10.1007/s12016-018-8711-2
  5. Goldenberg A, Silverberg N, Silverberg JI, et al. Pediatric allergic contact dermatitis: lessons for better care. J Allergy Clin Immunol Pract. 2015;3:661-667; quiz 668. doi:10.1016/j.jaip.2015.02.007
  6. Silverberg JI, Hou A, Warshaw EM, et al. Age-related differences in patch testing results among children: analysis of North American Contact Dermatitis Group data, 2001-2018 [published online July 24, 2021]. J Am Acad Dermatol. 2022;86:818-826. doi:10.1016/j.jaad.2021.07.030
  7. Tokura Y, Phadungsaksawasdi P, Ito T. Atopic dermatitis as Th2 disease revisited. J Cutan Immunol Allergy. 2018;1:158-164. doi:10.1002/cia2.12033
  8. Brunner PM, Guttman-Yassky E, Leung DY. The immunology of atopic dermatitis and its reversibility with broad-spectrum and targeted therapies. J Allergy Clin Immunol. 2017;139(suppl 4):S65-S76. doi:10.1016/j.jaci.2017.01.011
  9. Murphy PB, Atwater AR, Mueller M. Allergic Contact Dermatitis. StatPearls Publishing; 2021. https://www.ncbi.nlm.nih.gov/books/NBK532866/
  10. He D, Wu L, Kim HK, et al. IL-17 and IFN-gamma mediate the elicitation of contact hypersensitivity responses by different mechanisms and both are required for optimal responses [published online June 24, 2009]. J Immunol. 2009;183:1463-1470. doi:10.4049/jimmunol.0804108.
  11. Dhingra N, Shemer A, Correa da Rosa J, et al. Molecular profiling of contact dermatitis skin identifies allergen-dependent differences in immune response [published April 25, 2014]. J Allergy Clin Immunol. 2014;134:362-372. doi:10.1016/j.jaci.2014.03.009
  12. Owen JL, Vakharia PP, Silverberg JI. The role and diagnosis of allergic contact dermatitis in patients with atopic dermatitis. Am J Clin Dermatol. 2018;19:293-302. doi:10.1007/s40257-017-0340-7
  13. Uehara M, Sawai T. A longitudinal study of contact sensitivity in patients with atopic dermatitis. Arch Dermatol. 1989;125:366-368.
  14. Yüksel YT, Nørreslet LB, Thyssen JP. Allergic contact dermatitis in patients with atopic dermatitis. Curr Derm Rep. 2021;10:67-76.
  15. Gittler JK, Krueger JG, Guttman-Yassky E. Atopic dermatitis results in intrinsic barrier and immune abnormalities: implications for contact dermatitis [published online August 28, 2012]. J Allergy Clin Immunol. 2013;131:300-313. doi:10.1016/j.jaci.2012.06.048
  16. Drislane C, Irvine AD. The role of filaggrin in atopic dermatitis and allergic disease [published online October 14, 2019]. Ann Allergy Asthma Immunol. 2020;124:36-43. doi:10.1016/j.anai.2019.10.008
  17. Thyssen JP, McFadden JP, Kimber I. The multiple factors affectingthe association between atopic dermatitis and contact sensitization [published online December 26, 2013]. Allergy. 2014;69:28-36. doi:10.1111/all.12358
  18. Timmerman JG, Heederik D, Spee T, et al. Contact dermatitis in the construction industry: the role of filaggrin loss-of-function mutations [published online December 12, 2015]. Br J Dermatol. 2016;174:348-355. doi:10.1111/bjd.14215
  19. Edslev SM, Agner T, Andersen PS. Skin microbiome in atopic dermatitis. Acta Derm Venereol. 2020;100:adv00164. doi:10.2340/00015555-3514
  20. Silverberg JI, Hou A, Warshaw EM, et al. Prevalence and trend of allergen sensitization in adults and children with atopic dermatitis referred for patch testing, North American Contact Dermatitis Group data, 2001-2016 [published online March 27, 2021]. J Allergy Clin Immunol Pract. 2021;9:2853-2866.e14. doi:10.1016/j.jaip.2021.03.028
  21. Pratt MD, Mufti A, Lipson J, et al. Patch test reactions to corticosteroids: retrospective analysis from the North American Contact Dermatitis Group 2007-2014. Dermatitis. 2017;28:58-63. doi:10.1097/DER.0000000000000251
  22. Xiong M, Peterson MY, Hylwa S. Allergic contact dermatitis from benzyl alcohol in hydrocortisone cream [published online January 14, 2022]. Contact Dermatitis. 2022;86:424-425. doi:10.1111/cod.14042
  23. Goldenberg A, Mousdicas N, Silverberg N, et al. Pediatric Contact Dermatitis Registry inaugural case data. Dermatitis. 2016;27:293-302. doi:10.1097/DER.0000000000000214
  24. Jacob SE, McGowan M, Silverberg NB, et al. Pediatric Contact Dermatitis Registry data on contact allergy in children with atopic dermatitis. JAMA Dermatol. 2017;153:765-770. doi:10.1001/jamadermatol.2016.6136
  25. Zug KA, McGinley-Smith D, Warshaw EM, et al. Contact allergy in children referred for patch testing: North American Contact Dermatitis Group data, 2001-2004. Arch Dermatol. 2008;144:1329-1336. doi:10.1001/archderm.144.10.1329
  26. Zug KA, Pham AK, Belsito DV, et al. Patch testing in children from 2005 to 2012: results from the North American contact dermatitis group. Dermatitis. 2014;25:345-355. doi:10.1097/DER.0000000000000083
  27. Hamann CR, Hamann D, Egeberg A, et al. Association between atopic dermatitis and contact sensitization: a systematic review and meta-analysis [published online April 6, 2017]. J Am Acad Dermatol. 2017;77:70-78. doi:10.1016/j.jaad.2017.02.001
  28. Simonsen AB, Johansen JD, Deleuran M, et al. Contact allergy in children with atopic dermatitis: a systematic review [published online June 12, 2017]. Br J Dermatol. 2017;177:395-405. doi:10.1111/bjd.15628
  29. Chen R, Raffi J, Murase JE. Tocopherol allergic dermatitis masquerading as lifelong atopic dermatitis. Dermatitis. 2020;31:E3-E4. doi:10.1097/DER.0000000000000543
  30. Tam I, Yu J. Pediatric contact dermatitis: what’s new. Curr Opin Pediatr. 2020;32:524-530. doi:10.1097/MOP.0000000000000919
  31. Cohen DE, Rao S, Brancaccio RR. Use of the North American Contact Dermatitis Group Standard 65-allergen series alone in the evaluation of allergic contact dermatitis: a series of 794 patients. Dermatitis. 2008;19:137-141.
  32. Schalock PC, Dunnick CA, Nedorost S, et al. American Contact Dermatitis Society Core Allergen Series: 2020 update. Dermatitis. 2020;31:279-282. doi:10.1097/DER.0000000000000621
  33. Yu J, Atwater AR, Brod B, et al. Pediatric baseline patch test series: Pediatric Contact Dermatitis Workgroup. Dermatitis. 2018;29:206-212. doi:10.1097/DER.0000000000000385
  34. Bußmann C, Novak N. Systemic therapy of atopic dermatitis. Allergol Select. 2017;1:1-8. doi:10.5414/ALX01285E
  35. Sung CT, McGowan MA, Machler BC, et al. Systemic treatments for allergic contact dermatitis. Dermatitis. 2019;30:46-53. doi:10.1097/DER.0000000000000435
  36. Johnson H, Adler BL, Yu J. Dupilumab for allergic contact dermatitis: an overview of its use and impact on patch testing. Cutis. 2022;109:265-267, E4-E5. doi:10.12788/cutis.0519
  37. Todberg T, Zachariae C, Krustrup D, et al. The effect of treatment with anti-interleukin-17 in patients with allergic contact dermatitis. Contact Dermatitis. 2018;78:431-432. doi:10.1111/cod.12988
  38. Ungar B, Pavel AB, Li R, et al. Phase 2 randomized, double-blind study of IL-17 targeting with secukinumab in atopic dermatitis [published online May 16, 2020]. J Allergy Clin Immunol. 2021;147:394-397. doi:10.1016/j.jaci.2020.04.055
  39. Perche PO, Cook MK, Feldman SR. Abrocitinib: a new FDA-approved drug for moderate-to-severe atopic dermatitis [published online May 19, 2022]. Ann Pharmacother. doi:10.1177/10600280221096713
Article PDF
CT110003139.pdf
Author and Disclosure Information

Ms. Johnson is from the University of Minnesota Medical School, Minneapolis. Ms. Novack is from the Icahn School of Medicine at Mount Sinai, New York, New York. Dr. Adler is from the Department of Dermatology, Keck School of Medicine, University of Southern California, Los Angeles. Dr. Yu is from the Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston.

Ms. Johnson, Ms. Novack, and Dr. Yu report no conflict of interest. Dr. Adler has served as a consultant and/or research investigator for AbbVie and Skin Research Institute, LLC.

Correspondence: JiaDe Yu, MD, Department of Dermatology, Massachusetts General Hospital, 50 Staniford St, Ste 200, Boston, MA 02114 (Jiadeyu@mgh.harvard.edu).

Issue
Cutis - 110(3)
Publications
MDedge Dermatology
Cutis
Topics
Contact Dermatitis
Atopic Dermatitis
Page Number
139-142
Sections
Contact Dermatitis
Author(s)
Hadley Johnson, BS
Danielle E. Novack, BA
Brandon L. Adler, MD
Jiade Yu, MD
Author(s)
Hadley Johnson, BS
Danielle E. Novack, BA
Brandon L. Adler, MD
Jiade Yu, MD
Author and Disclosure Information

Ms. Johnson is from the University of Minnesota Medical School, Minneapolis. Ms. Novack is from the Icahn School of Medicine at Mount Sinai, New York, New York. Dr. Adler is from the Department of Dermatology, Keck School of Medicine, University of Southern California, Los Angeles. Dr. Yu is from the Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston.

Ms. Johnson, Ms. Novack, and Dr. Yu report no conflict of interest. Dr. Adler has served as a consultant and/or research investigator for AbbVie and Skin Research Institute, LLC.

Correspondence: JiaDe Yu, MD, Department of Dermatology, Massachusetts General Hospital, 50 Staniford St, Ste 200, Boston, MA 02114 (Jiadeyu@mgh.harvard.edu).

Author and Disclosure Information

Ms. Johnson is from the University of Minnesota Medical School, Minneapolis. Ms. Novack is from the Icahn School of Medicine at Mount Sinai, New York, New York. Dr. Adler is from the Department of Dermatology, Keck School of Medicine, University of Southern California, Los Angeles. Dr. Yu is from the Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston.

Ms. Johnson, Ms. Novack, and Dr. Yu report no conflict of interest. Dr. Adler has served as a consultant and/or research investigator for AbbVie and Skin Research Institute, LLC.

Correspondence: JiaDe Yu, MD, Department of Dermatology, Massachusetts General Hospital, 50 Staniford St, Ste 200, Boston, MA 02114 (Jiadeyu@mgh.harvard.edu).

Article PDF
CT110003139.pdf
Article PDF
CT110003139.pdf

Atopic dermatitis (AD) and allergic contact dermatitis (ACD) are 2 common inflammatory skin conditions that may have similar clinical presentations. Historically, it was thought that these conditions could not be diagnosed simultaneously due to their differing immune mechanisms; however, this belief has been challenged by recent evidence suggesting a more nuanced relationship between the 2 disease processes. In this review, we examine the complex interplay between AD and ACD and explain how shifts in conventional understanding of the 2 conditions shaped our evolving recognition of their ability to coexist.

Epidemiology of AD and ACD

Atopic dermatitis is the most common inflammatory skin disease in children and adolescents, with an estimated prevalence reaching 21%.1 In 60% of cases, onset of AD will occur within the first year of life, and 90% of cases begin within the first 5 years.2 Resolution may occur by adulthood; however, AD may continue to impact up to 8% to 9% of adults, with an increased prevalence in those older than 75 years.1 This may represent an underestimation of the burden of adult AD; one systematic review of 17 studies found that the pooled proportion of adult-onset AD was greater than 25%.3

In contrast, ACD previously was assumed to be a disease that more commonly impacted adults and only rarely children, primarily due to an early misconception that children were not frequently exposed to contact allergens and their immune systems were too immature to react to them even if exposed.4,5 However, it is now known that children do have risk factors for development of ACD, including a thinner stratum corneum and potentially a more absorbent skin surface.4 In addition, a 2022 study by the North American Contact Dermatitis Group (NACDG) found similar rates of ACD in children (n=1871) and adults (n=41,699) referred for patch testing (55.2% and 57.3%, respectively) as well as similar rates of having at least 1 relevant positive patch test (49.2% and 52.2%).6

In opposition to traditional beliefs, these findings highlight that AD and ACD can occur across age groups.

Immune Mechanism

The pathogenesis of AD represents a multifactorial process involving the immune system, cutaneous flora, genetic predisposition, and surrounding environment. Immunologically, acute AD is driven by a predominantly TH2 helper T-cell response with high levels of IL-4, IL-5, and IL-137; TH22, TH17, and TH1 also have been implicated.8 Notably, TH17 is found in high levels during the acute eczema phase, while TH1 and TH22are associated with the chronic phase.7

The pathophysiology of ACD is not completely understood. The classic paradigm involves 2 phases: sensitization and elicitation. Sensitization involves antigen-presenting cells that take up allergens absorbed by the skin to present them in regional lymph nodes where antigen-specific T lymphocytes are generated. Elicitation occurs upon re-exposure to the allergen, at which time the primed T lymphocytes are recruited to the skin, causing inflammation.9 Allergic contact dermatitis initially was thought to be driven by TH1 cytokines and IL-17 but now is understood to be more complex.10 Studies have revealed immune polarization of contact allergens, demonstrating that nickel primarily induces a TH1/TH17 response, whereas fragrance and rubber accelerators skew to TH2; TH9 and TH22 also may be involved depending on the causative allergen.11,12

Of note, the immunologic differences between AD and ACD led early investigators to believe that patients with AD were relatively protected from ACD.13 However, as previously described, there are several overlapping cytokines between AD and ACD. Furthermore, research has revealed that risk of contact sensitization might be increased in the chronic eczema phase due to the shared TH1 pathway.14 Barrier-disrupted skin (such as that in AD) also may increase the cytokine response and the density of antigen-presenting cells, leading to a proallergic state.15 This suggests that the immunologic pathways of AD and ACD are more intertwined than was previously understood.

 

 

Underlying Risk Factors

Skin barrier dysfunction is a key step in the pathogenesis of AD. Patients with AD commonly have loss-of-function mutations in the filaggrin gene, a protein that is key to the function of the stratum corneum. Loss of this protein may not only impact the immune response as previously noted but also may lead to increased transepidermal water loss and bacterial colonization.16 Interestingly, a 2014 review examined how this mutation could lead to an increased risk of sensitization to bivalent metal ions via an impaired chelating ability of the skin.17 Furthermore, a 2016 study conducted in Dutch construction workers revealed an increased risk for contact dermatitis (irritant and allergic) for those with a loss-of-function filaggrin mutation.18

Importantly, this same mutation may explain why patients with AD tend to have increased skin colonization by Staphylococcus aureus. The abundance of S aureus and the relative decrease in the diversity of other microorganisms on the skin may be associated with increased AD severity.19 Likewise, S aureus may play a role in the pathogenesis of ACD via production of its exotoxin directed at the T-cell receptor V beta 17 region. In particular, this receptor has been associated with nickel sensitization.17

Another risk factor to consider is increased exposure to contact sensitizers when treating AD. For instance, management often includes use of over-the-counter emollients, natural or botanical remedies with purported benefits for AD, cleansers, and detergents. However, these products can contain some of the most prevalent contact allergens seen in those with AD, including methyl-isothiazolinone, formaldehyde releasers, and fragrance.20 Topical corticosteroids also are frequently used, and ACD to steroid molecules can occur, particularly to tixocortol-21-pivalate (a marker for class A corticosteroids) and budesonide (a marker for class B corticosteroids).21 Other allergens (eg, benzyl alcohol, propylene glycol) also may be found as inactive ingredients of topical corticosteroids.22 These exposures may place AD patients at risk for ACD.

The Coexistence of AD and ACD

Given the overlapping epidemiology, immunology, and potentially increased risk for the development of ACD in patients with AD, it would be reasonable to assume that the 2 diagnoses could coexist; however, is there clinical data to support this idea? Based on recent database reviews, the answer appears to be yes.20,23-26 An analysis from the Pediatric Contact Dermatitis Registry revealed that 30% of 1142 pediatric patch test cases analyzed were diagnosed as AD and ACD simultaneously.24 The NACDG found similar results in its 2021 review, as 29.5% of children (n=1648) and 20.7% of adults (n=36,834) had a concurrent diagnosis of AD and ACD.20 Notably, older results from these databases also demonstrated an association between the 2 conditions.23,25,26

It remains unclear whether the prevalence of ACD is higher in those with or without AD. A comprehensive systematic review conducted in 2017 examined this topic through analysis of 74 studies. The results demonstrated a similar prevalence of contact sensitization in individuals with and without AD.27 Another systematic review of 31 studies conducted in 2017 found a higher prevalence for ACD in children without AD; however, the authors noted that the included studies were too variable (eg, size, design, allergens tested) to draw definitive conclusions.28

Even though there is no clear overall increased risk for ACD in patients with AD, research has suggested that certain allergens may be more prevalent in the setting of AD. An NACDG study found that adults with AD had increased odds of reacting to 10 of the top 25 NACDG screening allergens compared to those without AD.20 Other studies have found that AD patients may be more likely to become sensitized to certain allergens, such as fragrance and lanolin.14

Considerations for Management

Diagnosis of ACD in patients with AD can be challenging because these conditions may present similarly with chronic, pruritic, inflammatory patches and plaques. Chronic ACD may be misdiagnosed as AD if patch testing is not performed.29 Given the prevalence of ACD in the setting of AD, there should be a low threshold to pursue patch testing, especially when dermatitis is recalcitrant to standard therapies or presents in an atypical distribution (ie, perioral, predominantly head/neck, hand and foot, isolated eyelid involvement, buttocks).4,30 Various allergen series are available for patch testing adults and children including the NACDG Standard Series, American Contact Dermatitis Society Core Allergen Series, or the Pediatric Baseline Series.31-33

If potentially relevant allergens are uncovered by patch testing, patients should be counseled on avoidance strategies. However, allergen avoidance may not always lead to complete symptom resolution, especially if AD is present concomitantly with ACD. Therefore, use of topical or systemic therapies still may be required. Topical corticosteroids can be used when dermatitis is acute and localized. Systemic corticosteroids are utilized for both diagnoses when cases are more severe or extensive, but their adverse-effect profile limits long-term use. Other systemic treatments, including conventional agents (ie, azathioprine, cyclosporine, methotrexate, mycophenolate mofetil), biologics, and small molecule inhibitors also may be considered for severe cases.34,35 Dupilumab, a monoclonal antibody targeting IL-4/IL-13, is approved for use in moderate to severe AD in patients 6 months and older. Recent evidence has suggested that dupilumab also may be an effective off-label treatment choice for ACD when allergen avoidance alone is insufficient.36 Studies have been conducted on secukinumab, a monoclonal antibody against IL-17; however, it has not been shown to be effective in either AD or ACD.37,38 This indicates that targeted biologics may not always be successful in treating these diagnoses, likely due to their complex immune pathways. Finally, there is an emerging role for JAK inhibitors. Three are approved for AD: topical ruxolitinib, oral abrocitinib, and oral upadacitinib.39 Further investigation is needed to determine the efficacy of JAK inhibitors in ACD.

Final Interpretation

Evolving evidence shows that AD and ACD can occur at the same time despite the historical perspective that their immune pathways were too polarized for this to happen. Atopic dermatitis may be an important risk factor for subsequent development of ACD. Management should include a low threshold to perform patch testing, while pharmacotherapies utilized in the treatment of both conditions should be considered.

Atopic dermatitis (AD) and allergic contact dermatitis (ACD) are 2 common inflammatory skin conditions that may have similar clinical presentations. Historically, it was thought that these conditions could not be diagnosed simultaneously due to their differing immune mechanisms; however, this belief has been challenged by recent evidence suggesting a more nuanced relationship between the 2 disease processes. In this review, we examine the complex interplay between AD and ACD and explain how shifts in conventional understanding of the 2 conditions shaped our evolving recognition of their ability to coexist.

Epidemiology of AD and ACD

Atopic dermatitis is the most common inflammatory skin disease in children and adolescents, with an estimated prevalence reaching 21%.1 In 60% of cases, onset of AD will occur within the first year of life, and 90% of cases begin within the first 5 years.2 Resolution may occur by adulthood; however, AD may continue to impact up to 8% to 9% of adults, with an increased prevalence in those older than 75 years.1 This may represent an underestimation of the burden of adult AD; one systematic review of 17 studies found that the pooled proportion of adult-onset AD was greater than 25%.3

In contrast, ACD previously was assumed to be a disease that more commonly impacted adults and only rarely children, primarily due to an early misconception that children were not frequently exposed to contact allergens and their immune systems were too immature to react to them even if exposed.4,5 However, it is now known that children do have risk factors for development of ACD, including a thinner stratum corneum and potentially a more absorbent skin surface.4 In addition, a 2022 study by the North American Contact Dermatitis Group (NACDG) found similar rates of ACD in children (n=1871) and adults (n=41,699) referred for patch testing (55.2% and 57.3%, respectively) as well as similar rates of having at least 1 relevant positive patch test (49.2% and 52.2%).6

In opposition to traditional beliefs, these findings highlight that AD and ACD can occur across age groups.

Immune Mechanism

The pathogenesis of AD represents a multifactorial process involving the immune system, cutaneous flora, genetic predisposition, and surrounding environment. Immunologically, acute AD is driven by a predominantly TH2 helper T-cell response with high levels of IL-4, IL-5, and IL-137; TH22, TH17, and TH1 also have been implicated.8 Notably, TH17 is found in high levels during the acute eczema phase, while TH1 and TH22are associated with the chronic phase.7

The pathophysiology of ACD is not completely understood. The classic paradigm involves 2 phases: sensitization and elicitation. Sensitization involves antigen-presenting cells that take up allergens absorbed by the skin to present them in regional lymph nodes where antigen-specific T lymphocytes are generated. Elicitation occurs upon re-exposure to the allergen, at which time the primed T lymphocytes are recruited to the skin, causing inflammation.9 Allergic contact dermatitis initially was thought to be driven by TH1 cytokines and IL-17 but now is understood to be more complex.10 Studies have revealed immune polarization of contact allergens, demonstrating that nickel primarily induces a TH1/TH17 response, whereas fragrance and rubber accelerators skew to TH2; TH9 and TH22 also may be involved depending on the causative allergen.11,12

Of note, the immunologic differences between AD and ACD led early investigators to believe that patients with AD were relatively protected from ACD.13 However, as previously described, there are several overlapping cytokines between AD and ACD. Furthermore, research has revealed that risk of contact sensitization might be increased in the chronic eczema phase due to the shared TH1 pathway.14 Barrier-disrupted skin (such as that in AD) also may increase the cytokine response and the density of antigen-presenting cells, leading to a proallergic state.15 This suggests that the immunologic pathways of AD and ACD are more intertwined than was previously understood.

 

 

Underlying Risk Factors

Skin barrier dysfunction is a key step in the pathogenesis of AD. Patients with AD commonly have loss-of-function mutations in the filaggrin gene, a protein that is key to the function of the stratum corneum. Loss of this protein may not only impact the immune response as previously noted but also may lead to increased transepidermal water loss and bacterial colonization.16 Interestingly, a 2014 review examined how this mutation could lead to an increased risk of sensitization to bivalent metal ions via an impaired chelating ability of the skin.17 Furthermore, a 2016 study conducted in Dutch construction workers revealed an increased risk for contact dermatitis (irritant and allergic) for those with a loss-of-function filaggrin mutation.18

Importantly, this same mutation may explain why patients with AD tend to have increased skin colonization by Staphylococcus aureus. The abundance of S aureus and the relative decrease in the diversity of other microorganisms on the skin may be associated with increased AD severity.19 Likewise, S aureus may play a role in the pathogenesis of ACD via production of its exotoxin directed at the T-cell receptor V beta 17 region. In particular, this receptor has been associated with nickel sensitization.17

Another risk factor to consider is increased exposure to contact sensitizers when treating AD. For instance, management often includes use of over-the-counter emollients, natural or botanical remedies with purported benefits for AD, cleansers, and detergents. However, these products can contain some of the most prevalent contact allergens seen in those with AD, including methyl-isothiazolinone, formaldehyde releasers, and fragrance.20 Topical corticosteroids also are frequently used, and ACD to steroid molecules can occur, particularly to tixocortol-21-pivalate (a marker for class A corticosteroids) and budesonide (a marker for class B corticosteroids).21 Other allergens (eg, benzyl alcohol, propylene glycol) also may be found as inactive ingredients of topical corticosteroids.22 These exposures may place AD patients at risk for ACD.

The Coexistence of AD and ACD

Given the overlapping epidemiology, immunology, and potentially increased risk for the development of ACD in patients with AD, it would be reasonable to assume that the 2 diagnoses could coexist; however, is there clinical data to support this idea? Based on recent database reviews, the answer appears to be yes.20,23-26 An analysis from the Pediatric Contact Dermatitis Registry revealed that 30% of 1142 pediatric patch test cases analyzed were diagnosed as AD and ACD simultaneously.24 The NACDG found similar results in its 2021 review, as 29.5% of children (n=1648) and 20.7% of adults (n=36,834) had a concurrent diagnosis of AD and ACD.20 Notably, older results from these databases also demonstrated an association between the 2 conditions.23,25,26

It remains unclear whether the prevalence of ACD is higher in those with or without AD. A comprehensive systematic review conducted in 2017 examined this topic through analysis of 74 studies. The results demonstrated a similar prevalence of contact sensitization in individuals with and without AD.27 Another systematic review of 31 studies conducted in 2017 found a higher prevalence for ACD in children without AD; however, the authors noted that the included studies were too variable (eg, size, design, allergens tested) to draw definitive conclusions.28

Even though there is no clear overall increased risk for ACD in patients with AD, research has suggested that certain allergens may be more prevalent in the setting of AD. An NACDG study found that adults with AD had increased odds of reacting to 10 of the top 25 NACDG screening allergens compared to those without AD.20 Other studies have found that AD patients may be more likely to become sensitized to certain allergens, such as fragrance and lanolin.14

Considerations for Management

Diagnosis of ACD in patients with AD can be challenging because these conditions may present similarly with chronic, pruritic, inflammatory patches and plaques. Chronic ACD may be misdiagnosed as AD if patch testing is not performed.29 Given the prevalence of ACD in the setting of AD, there should be a low threshold to pursue patch testing, especially when dermatitis is recalcitrant to standard therapies or presents in an atypical distribution (ie, perioral, predominantly head/neck, hand and foot, isolated eyelid involvement, buttocks).4,30 Various allergen series are available for patch testing adults and children including the NACDG Standard Series, American Contact Dermatitis Society Core Allergen Series, or the Pediatric Baseline Series.31-33

If potentially relevant allergens are uncovered by patch testing, patients should be counseled on avoidance strategies. However, allergen avoidance may not always lead to complete symptom resolution, especially if AD is present concomitantly with ACD. Therefore, use of topical or systemic therapies still may be required. Topical corticosteroids can be used when dermatitis is acute and localized. Systemic corticosteroids are utilized for both diagnoses when cases are more severe or extensive, but their adverse-effect profile limits long-term use. Other systemic treatments, including conventional agents (ie, azathioprine, cyclosporine, methotrexate, mycophenolate mofetil), biologics, and small molecule inhibitors also may be considered for severe cases.34,35 Dupilumab, a monoclonal antibody targeting IL-4/IL-13, is approved for use in moderate to severe AD in patients 6 months and older. Recent evidence has suggested that dupilumab also may be an effective off-label treatment choice for ACD when allergen avoidance alone is insufficient.36 Studies have been conducted on secukinumab, a monoclonal antibody against IL-17; however, it has not been shown to be effective in either AD or ACD.37,38 This indicates that targeted biologics may not always be successful in treating these diagnoses, likely due to their complex immune pathways. Finally, there is an emerging role for JAK inhibitors. Three are approved for AD: topical ruxolitinib, oral abrocitinib, and oral upadacitinib.39 Further investigation is needed to determine the efficacy of JAK inhibitors in ACD.

Final Interpretation

Evolving evidence shows that AD and ACD can occur at the same time despite the historical perspective that their immune pathways were too polarized for this to happen. Atopic dermatitis may be an important risk factor for subsequent development of ACD. Management should include a low threshold to perform patch testing, while pharmacotherapies utilized in the treatment of both conditions should be considered.

References
  1. Chan LN, Magyari A, Ye M, et al. The epidemiology of atopic dermatitis in older adults: a population-based study in the United Kingdom. PLoS One. 2021;16:E0258219. doi:10.1371/journal.pone.0258219
  2. Eichenfield LF, Tom WL, Chamlin SL, et al. Guidelines of care for the management of atopic dermatitis: section 1. diagnosis and assessment of atopic dermatitis [published online November 27, 2013]. J Am Acad Dermatol. 2014;70:338-351. doi:10.1016/j.jaad.2013.10.010
  3. Lee HH, Patel KR, Singam V, et al. A systematic review and meta-analysis of the prevalence and phenotype of adult-onset atopic dermatitis [published online June 2, 2018]. J Am Acad Dermatol. 2019;80:1526-1532.e7. doi:10.1016/j.jaad.2018.05.1241
  4. Borok J, Matiz C, Goldenberg A, et al. Contact dermatitis in atopic dermatitis children—past, present, and future. Clin Rev Allergy Immunol. 2019;56:86-98. doi:10.1007/s12016-018-8711-2
  5. Goldenberg A, Silverberg N, Silverberg JI, et al. Pediatric allergic contact dermatitis: lessons for better care. J Allergy Clin Immunol Pract. 2015;3:661-667; quiz 668. doi:10.1016/j.jaip.2015.02.007
  6. Silverberg JI, Hou A, Warshaw EM, et al. Age-related differences in patch testing results among children: analysis of North American Contact Dermatitis Group data, 2001-2018 [published online July 24, 2021]. J Am Acad Dermatol. 2022;86:818-826. doi:10.1016/j.jaad.2021.07.030
  7. Tokura Y, Phadungsaksawasdi P, Ito T. Atopic dermatitis as Th2 disease revisited. J Cutan Immunol Allergy. 2018;1:158-164. doi:10.1002/cia2.12033
  8. Brunner PM, Guttman-Yassky E, Leung DY. The immunology of atopic dermatitis and its reversibility with broad-spectrum and targeted therapies. J Allergy Clin Immunol. 2017;139(suppl 4):S65-S76. doi:10.1016/j.jaci.2017.01.011
  9. Murphy PB, Atwater AR, Mueller M. Allergic Contact Dermatitis. StatPearls Publishing; 2021. https://www.ncbi.nlm.nih.gov/books/NBK532866/
  10. He D, Wu L, Kim HK, et al. IL-17 and IFN-gamma mediate the elicitation of contact hypersensitivity responses by different mechanisms and both are required for optimal responses [published online June 24, 2009]. J Immunol. 2009;183:1463-1470. doi:10.4049/jimmunol.0804108.
  11. Dhingra N, Shemer A, Correa da Rosa J, et al. Molecular profiling of contact dermatitis skin identifies allergen-dependent differences in immune response [published April 25, 2014]. J Allergy Clin Immunol. 2014;134:362-372. doi:10.1016/j.jaci.2014.03.009
  12. Owen JL, Vakharia PP, Silverberg JI. The role and diagnosis of allergic contact dermatitis in patients with atopic dermatitis. Am J Clin Dermatol. 2018;19:293-302. doi:10.1007/s40257-017-0340-7
  13. Uehara M, Sawai T. A longitudinal study of contact sensitivity in patients with atopic dermatitis. Arch Dermatol. 1989;125:366-368.
  14. Yüksel YT, Nørreslet LB, Thyssen JP. Allergic contact dermatitis in patients with atopic dermatitis. Curr Derm Rep. 2021;10:67-76.
  15. Gittler JK, Krueger JG, Guttman-Yassky E. Atopic dermatitis results in intrinsic barrier and immune abnormalities: implications for contact dermatitis [published online August 28, 2012]. J Allergy Clin Immunol. 2013;131:300-313. doi:10.1016/j.jaci.2012.06.048
  16. Drislane C, Irvine AD. The role of filaggrin in atopic dermatitis and allergic disease [published online October 14, 2019]. Ann Allergy Asthma Immunol. 2020;124:36-43. doi:10.1016/j.anai.2019.10.008
  17. Thyssen JP, McFadden JP, Kimber I. The multiple factors affectingthe association between atopic dermatitis and contact sensitization [published online December 26, 2013]. Allergy. 2014;69:28-36. doi:10.1111/all.12358
  18. Timmerman JG, Heederik D, Spee T, et al. Contact dermatitis in the construction industry: the role of filaggrin loss-of-function mutations [published online December 12, 2015]. Br J Dermatol. 2016;174:348-355. doi:10.1111/bjd.14215
  19. Edslev SM, Agner T, Andersen PS. Skin microbiome in atopic dermatitis. Acta Derm Venereol. 2020;100:adv00164. doi:10.2340/00015555-3514
  20. Silverberg JI, Hou A, Warshaw EM, et al. Prevalence and trend of allergen sensitization in adults and children with atopic dermatitis referred for patch testing, North American Contact Dermatitis Group data, 2001-2016 [published online March 27, 2021]. J Allergy Clin Immunol Pract. 2021;9:2853-2866.e14. doi:10.1016/j.jaip.2021.03.028
  21. Pratt MD, Mufti A, Lipson J, et al. Patch test reactions to corticosteroids: retrospective analysis from the North American Contact Dermatitis Group 2007-2014. Dermatitis. 2017;28:58-63. doi:10.1097/DER.0000000000000251
  22. Xiong M, Peterson MY, Hylwa S. Allergic contact dermatitis from benzyl alcohol in hydrocortisone cream [published online January 14, 2022]. Contact Dermatitis. 2022;86:424-425. doi:10.1111/cod.14042
  23. Goldenberg A, Mousdicas N, Silverberg N, et al. Pediatric Contact Dermatitis Registry inaugural case data. Dermatitis. 2016;27:293-302. doi:10.1097/DER.0000000000000214
  24. Jacob SE, McGowan M, Silverberg NB, et al. Pediatric Contact Dermatitis Registry data on contact allergy in children with atopic dermatitis. JAMA Dermatol. 2017;153:765-770. doi:10.1001/jamadermatol.2016.6136
  25. Zug KA, McGinley-Smith D, Warshaw EM, et al. Contact allergy in children referred for patch testing: North American Contact Dermatitis Group data, 2001-2004. Arch Dermatol. 2008;144:1329-1336. doi:10.1001/archderm.144.10.1329
  26. Zug KA, Pham AK, Belsito DV, et al. Patch testing in children from 2005 to 2012: results from the North American contact dermatitis group. Dermatitis. 2014;25:345-355. doi:10.1097/DER.0000000000000083
  27. Hamann CR, Hamann D, Egeberg A, et al. Association between atopic dermatitis and contact sensitization: a systematic review and meta-analysis [published online April 6, 2017]. J Am Acad Dermatol. 2017;77:70-78. doi:10.1016/j.jaad.2017.02.001
  28. Simonsen AB, Johansen JD, Deleuran M, et al. Contact allergy in children with atopic dermatitis: a systematic review [published online June 12, 2017]. Br J Dermatol. 2017;177:395-405. doi:10.1111/bjd.15628
  29. Chen R, Raffi J, Murase JE. Tocopherol allergic dermatitis masquerading as lifelong atopic dermatitis. Dermatitis. 2020;31:E3-E4. doi:10.1097/DER.0000000000000543
  30. Tam I, Yu J. Pediatric contact dermatitis: what’s new. Curr Opin Pediatr. 2020;32:524-530. doi:10.1097/MOP.0000000000000919
  31. Cohen DE, Rao S, Brancaccio RR. Use of the North American Contact Dermatitis Group Standard 65-allergen series alone in the evaluation of allergic contact dermatitis: a series of 794 patients. Dermatitis. 2008;19:137-141.
  32. Schalock PC, Dunnick CA, Nedorost S, et al. American Contact Dermatitis Society Core Allergen Series: 2020 update. Dermatitis. 2020;31:279-282. doi:10.1097/DER.0000000000000621
  33. Yu J, Atwater AR, Brod B, et al. Pediatric baseline patch test series: Pediatric Contact Dermatitis Workgroup. Dermatitis. 2018;29:206-212. doi:10.1097/DER.0000000000000385
  34. Bußmann C, Novak N. Systemic therapy of atopic dermatitis. Allergol Select. 2017;1:1-8. doi:10.5414/ALX01285E
  35. Sung CT, McGowan MA, Machler BC, et al. Systemic treatments for allergic contact dermatitis. Dermatitis. 2019;30:46-53. doi:10.1097/DER.0000000000000435
  36. Johnson H, Adler BL, Yu J. Dupilumab for allergic contact dermatitis: an overview of its use and impact on patch testing. Cutis. 2022;109:265-267, E4-E5. doi:10.12788/cutis.0519
  37. Todberg T, Zachariae C, Krustrup D, et al. The effect of treatment with anti-interleukin-17 in patients with allergic contact dermatitis. Contact Dermatitis. 2018;78:431-432. doi:10.1111/cod.12988
  38. Ungar B, Pavel AB, Li R, et al. Phase 2 randomized, double-blind study of IL-17 targeting with secukinumab in atopic dermatitis [published online May 16, 2020]. J Allergy Clin Immunol. 2021;147:394-397. doi:10.1016/j.jaci.2020.04.055
  39. Perche PO, Cook MK, Feldman SR. Abrocitinib: a new FDA-approved drug for moderate-to-severe atopic dermatitis [published online May 19, 2022]. Ann Pharmacother. doi:10.1177/10600280221096713
References
  1. Chan LN, Magyari A, Ye M, et al. The epidemiology of atopic dermatitis in older adults: a population-based study in the United Kingdom. PLoS One. 2021;16:E0258219. doi:10.1371/journal.pone.0258219
  2. Eichenfield LF, Tom WL, Chamlin SL, et al. Guidelines of care for the management of atopic dermatitis: section 1. diagnosis and assessment of atopic dermatitis [published online November 27, 2013]. J Am Acad Dermatol. 2014;70:338-351. doi:10.1016/j.jaad.2013.10.010
  3. Lee HH, Patel KR, Singam V, et al. A systematic review and meta-analysis of the prevalence and phenotype of adult-onset atopic dermatitis [published online June 2, 2018]. J Am Acad Dermatol. 2019;80:1526-1532.e7. doi:10.1016/j.jaad.2018.05.1241
  4. Borok J, Matiz C, Goldenberg A, et al. Contact dermatitis in atopic dermatitis children—past, present, and future. Clin Rev Allergy Immunol. 2019;56:86-98. doi:10.1007/s12016-018-8711-2
  5. Goldenberg A, Silverberg N, Silverberg JI, et al. Pediatric allergic contact dermatitis: lessons for better care. J Allergy Clin Immunol Pract. 2015;3:661-667; quiz 668. doi:10.1016/j.jaip.2015.02.007
  6. Silverberg JI, Hou A, Warshaw EM, et al. Age-related differences in patch testing results among children: analysis of North American Contact Dermatitis Group data, 2001-2018 [published online July 24, 2021]. J Am Acad Dermatol. 2022;86:818-826. doi:10.1016/j.jaad.2021.07.030
  7. Tokura Y, Phadungsaksawasdi P, Ito T. Atopic dermatitis as Th2 disease revisited. J Cutan Immunol Allergy. 2018;1:158-164. doi:10.1002/cia2.12033
  8. Brunner PM, Guttman-Yassky E, Leung DY. The immunology of atopic dermatitis and its reversibility with broad-spectrum and targeted therapies. J Allergy Clin Immunol. 2017;139(suppl 4):S65-S76. doi:10.1016/j.jaci.2017.01.011
  9. Murphy PB, Atwater AR, Mueller M. Allergic Contact Dermatitis. StatPearls Publishing; 2021. https://www.ncbi.nlm.nih.gov/books/NBK532866/
  10. He D, Wu L, Kim HK, et al. IL-17 and IFN-gamma mediate the elicitation of contact hypersensitivity responses by different mechanisms and both are required for optimal responses [published online June 24, 2009]. J Immunol. 2009;183:1463-1470. doi:10.4049/jimmunol.0804108.
  11. Dhingra N, Shemer A, Correa da Rosa J, et al. Molecular profiling of contact dermatitis skin identifies allergen-dependent differences in immune response [published April 25, 2014]. J Allergy Clin Immunol. 2014;134:362-372. doi:10.1016/j.jaci.2014.03.009
  12. Owen JL, Vakharia PP, Silverberg JI. The role and diagnosis of allergic contact dermatitis in patients with atopic dermatitis. Am J Clin Dermatol. 2018;19:293-302. doi:10.1007/s40257-017-0340-7
  13. Uehara M, Sawai T. A longitudinal study of contact sensitivity in patients with atopic dermatitis. Arch Dermatol. 1989;125:366-368.
  14. Yüksel YT, Nørreslet LB, Thyssen JP. Allergic contact dermatitis in patients with atopic dermatitis. Curr Derm Rep. 2021;10:67-76.
  15. Gittler JK, Krueger JG, Guttman-Yassky E. Atopic dermatitis results in intrinsic barrier and immune abnormalities: implications for contact dermatitis [published online August 28, 2012]. J Allergy Clin Immunol. 2013;131:300-313. doi:10.1016/j.jaci.2012.06.048
  16. Drislane C, Irvine AD. The role of filaggrin in atopic dermatitis and allergic disease [published online October 14, 2019]. Ann Allergy Asthma Immunol. 2020;124:36-43. doi:10.1016/j.anai.2019.10.008
  17. Thyssen JP, McFadden JP, Kimber I. The multiple factors affectingthe association between atopic dermatitis and contact sensitization [published online December 26, 2013]. Allergy. 2014;69:28-36. doi:10.1111/all.12358
  18. Timmerman JG, Heederik D, Spee T, et al. Contact dermatitis in the construction industry: the role of filaggrin loss-of-function mutations [published online December 12, 2015]. Br J Dermatol. 2016;174:348-355. doi:10.1111/bjd.14215
  19. Edslev SM, Agner T, Andersen PS. Skin microbiome in atopic dermatitis. Acta Derm Venereol. 2020;100:adv00164. doi:10.2340/00015555-3514
  20. Silverberg JI, Hou A, Warshaw EM, et al. Prevalence and trend of allergen sensitization in adults and children with atopic dermatitis referred for patch testing, North American Contact Dermatitis Group data, 2001-2016 [published online March 27, 2021]. J Allergy Clin Immunol Pract. 2021;9:2853-2866.e14. doi:10.1016/j.jaip.2021.03.028
  21. Pratt MD, Mufti A, Lipson J, et al. Patch test reactions to corticosteroids: retrospective analysis from the North American Contact Dermatitis Group 2007-2014. Dermatitis. 2017;28:58-63. doi:10.1097/DER.0000000000000251
  22. Xiong M, Peterson MY, Hylwa S. Allergic contact dermatitis from benzyl alcohol in hydrocortisone cream [published online January 14, 2022]. Contact Dermatitis. 2022;86:424-425. doi:10.1111/cod.14042
  23. Goldenberg A, Mousdicas N, Silverberg N, et al. Pediatric Contact Dermatitis Registry inaugural case data. Dermatitis. 2016;27:293-302. doi:10.1097/DER.0000000000000214
  24. Jacob SE, McGowan M, Silverberg NB, et al. Pediatric Contact Dermatitis Registry data on contact allergy in children with atopic dermatitis. JAMA Dermatol. 2017;153:765-770. doi:10.1001/jamadermatol.2016.6136
  25. Zug KA, McGinley-Smith D, Warshaw EM, et al. Contact allergy in children referred for patch testing: North American Contact Dermatitis Group data, 2001-2004. Arch Dermatol. 2008;144:1329-1336. doi:10.1001/archderm.144.10.1329
  26. Zug KA, Pham AK, Belsito DV, et al. Patch testing in children from 2005 to 2012: results from the North American contact dermatitis group. Dermatitis. 2014;25:345-355. doi:10.1097/DER.0000000000000083
  27. Hamann CR, Hamann D, Egeberg A, et al. Association between atopic dermatitis and contact sensitization: a systematic review and meta-analysis [published online April 6, 2017]. J Am Acad Dermatol. 2017;77:70-78. doi:10.1016/j.jaad.2017.02.001
  28. Simonsen AB, Johansen JD, Deleuran M, et al. Contact allergy in children with atopic dermatitis: a systematic review [published online June 12, 2017]. Br J Dermatol. 2017;177:395-405. doi:10.1111/bjd.15628
  29. Chen R, Raffi J, Murase JE. Tocopherol allergic dermatitis masquerading as lifelong atopic dermatitis. Dermatitis. 2020;31:E3-E4. doi:10.1097/DER.0000000000000543
  30. Tam I, Yu J. Pediatric contact dermatitis: what’s new. Curr Opin Pediatr. 2020;32:524-530. doi:10.1097/MOP.0000000000000919
  31. Cohen DE, Rao S, Brancaccio RR. Use of the North American Contact Dermatitis Group Standard 65-allergen series alone in the evaluation of allergic contact dermatitis: a series of 794 patients. Dermatitis. 2008;19:137-141.
  32. Schalock PC, Dunnick CA, Nedorost S, et al. American Contact Dermatitis Society Core Allergen Series: 2020 update. Dermatitis. 2020;31:279-282. doi:10.1097/DER.0000000000000621
  33. Yu J, Atwater AR, Brod B, et al. Pediatric baseline patch test series: Pediatric Contact Dermatitis Workgroup. Dermatitis. 2018;29:206-212. doi:10.1097/DER.0000000000000385
  34. Bußmann C, Novak N. Systemic therapy of atopic dermatitis. Allergol Select. 2017;1:1-8. doi:10.5414/ALX01285E
  35. Sung CT, McGowan MA, Machler BC, et al. Systemic treatments for allergic contact dermatitis. Dermatitis. 2019;30:46-53. doi:10.1097/DER.0000000000000435
  36. Johnson H, Adler BL, Yu J. Dupilumab for allergic contact dermatitis: an overview of its use and impact on patch testing. Cutis. 2022;109:265-267, E4-E5. doi:10.12788/cutis.0519
  37. Todberg T, Zachariae C, Krustrup D, et al. The effect of treatment with anti-interleukin-17 in patients with allergic contact dermatitis. Contact Dermatitis. 2018;78:431-432. doi:10.1111/cod.12988
  38. Ungar B, Pavel AB, Li R, et al. Phase 2 randomized, double-blind study of IL-17 targeting with secukinumab in atopic dermatitis [published online May 16, 2020]. J Allergy Clin Immunol. 2021;147:394-397. doi:10.1016/j.jaci.2020.04.055
  39. Perche PO, Cook MK, Feldman SR. Abrocitinib: a new FDA-approved drug for moderate-to-severe atopic dermatitis [published online May 19, 2022]. Ann Pharmacother. doi:10.1177/10600280221096713
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Can Atopic Dermatitis and Allergic Contact Dermatitis Coexist?
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Can Atopic Dermatitis and Allergic Contact Dermatitis Coexist?
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Practice Points

  • Although it previously was thought that atopic dermatitis (AD) and allergic contact dermatitis (ACD) could not coexist due to their polarized immune pathways, current evidence suggests otherwise.
  • When both diagnoses are suspected, patch testing should be considered as well as therapeutic strategies that can treat both AD and ACD simultaneously.
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