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Dupilumab for Allergic Contact Dermatitis: An Overview of Its Use and Impact on Patch Testing
Author(s)
Hadley Johnson, BS
Brandon L. Adler, MD
Jiade Yu, MD

Dupilumab is a humanized monoclonal antibody approved by the US Food and Drug Administration (FDA) for the treatment of moderate to severe atopic dermatitis. Through inhibition of the IL-4R α subunit, it prevents activation of the IL-4/IL-13 signaling cascade. This dampens the T H 2 inflammatory response, thereby improving the symptoms associated with atopic dermatitis. 1,2 Recent literature suggests that dupilumab may be useful in the treatment of other chronic dermatologic conditions, including allergic contact dermatitis (ACD) refractory to allergen avoidance and other treatments. Herein, we provide an overview of ACD, the role that dupilumab may play in its management, and its impact on patch testing results.

Pathogenesis of ACD

Allergic contact dermatitis is a cell-mediated type IV hypersensitivity reaction that develops through 2 distinct stages. In the sensitization phase, an allergen penetrates the skin and subsequently is engulfed by a cutaneous antigen-presenting cell. The allergen is then combined with a peptide to form a complex that is presented to naïve T lymphocytes in regional lymph nodes. The result is clonal expansion of a T-cell population that recognizes the allergen. In the elicitation phase, repeat exposure to the allergen leads to the recruitment of primed T cells to the skin, followed by cytokine release, inflammation, and resultant dermatitis.3

Historically, ACD was thought to be primarily driven by the TH1 inflammatory response; however, it is now known that TH2, TH9, TH17, and TH22 also may play a role in its pathogenesis.4,5 Another key finding is that the immune response in ACD appears to be at least partially allergen specific. Molecular profiling has revealed that nickel primarily induces a TH1/TH17 response, while allergens such as fragrance and rubber primarily induce a TH2 response.4

Management of ACD

Allergen avoidance is the mainstay of ACD treatment; however, in some patients, this approach does not always improve symptoms. In addition, eliminating the source of the allergen may not be possible in those with certain occupational, environmental, or medical exposures.

There are no FDA-approved treatments for ACD. When allergen avoidance alone is insufficient, first-line pharmacologic therapy typically includes topical or oral corticosteroids, the choice of which depends on the extent and severity of the dermatitis; however, a steroid-sparing agent often is preferred to avoid the unfavorable effects of long-term steroid use. Other systemic treatments for ACD include methotrexate, cyclosporine, mycophenolate mofetil, and azathioprine.6 These agents are used for severe ACD and typically are chosen as a last resort due to their immunosuppressive activity.

Phototherapy is another option, often as an adjunct to other therapies. Narrowband UVB and psoralen plus UVA have both been used. Psoralen plus UVA tends to have more side effects; therefore, narrowband UVB often is preferred.7,8

Use of Dupilumab in ACD

Biologics are unique, as they can target a single step in the immune response to improve a wide variety of symptoms. Research investigating their role as a treatment modality for ACD is still evolving alongside our increasing knowledge of its pathophysiology.9 Of note, studies examining the anti–IL-17 biologic secukinumab revealed it to be ineffective against ACD,10,11 which suggests that targeting specific immune components may not always result in improvement of ACD symptoms, likely because its pathophysiology involves several pathways.

 

 

There have been multiple reports demonstrating the effectiveness of dupilumab in the treatment of ACD (eTable).12-20 The findings from these studies show that dupilumab can improve recalcitrant dermatitis caused by a broad range of contact allergens, including nickel. This highlights its ability to improve ACD caused by allergens with a TH1 bias, despite its primarily TH2-dampening effects. Notably, several studies have reported successful use of dupilumab for systemic ACD.12,18 In addition, dupilumab may be able to improve symptoms of ACD in as little as 1 to 4 weeks. Unlike some systemic therapies for ACD, dupilumab also benefits from its lack of notable immunosuppressive effects.9 A phase 4 clinical trial at Brigham and Women’s Hospital (Boston, Massachusetts) is recruiting participants, with a primary goal of investigating dupilumab’s impact on ACD in patients who have not improved despite allergen avoidance (ClinicalTrials.gov identifier NCT03935971).

Studies Demonstrating Improvement of ACD With Dupilumab Use

Studies Demonstrating Improvement of ACD With Dupilumab Use

There are a few potential disadvantages to dupilumab. Because it is not yet FDA approved for the treatment of ACD, insurance companies may deny coverage, making it likely to be unaffordable for most patients. Furthermore, the side-effect profile has not been fully characterized. In addition to ocular adverse effects, a growing number of studies have reported face and neck erythema after starting dupilumab. Although the cause is unclear, one theory is that the inhibition of IL-4/IL-13 leads to TH1/TH17 polarization, thereby worsening ACD caused by allergens that activate a TH1-predominant response.21 Finally, not all cases of ACD respond to dupilumab.22

Patch Testing While on Dupilumab

Diagnosing ACD is a challenging process. An accurate history and physical examination are critical, and patch testing remains the gold standard when it comes to identifying the source of the contact allergen(s).

There is ongoing debate among contact dermatitis experts regarding the diagnostic accuracy of patch testing for those on immunomodulators or immunosuppressants, as these medications can dampen positive results and increase the risk for false-negative readings.23 Consequently, some have questioned whether patch testing on dupilumab is accurate or feasible.24 Contact dermatitis experts have examined patch testing results before and after initiation of dupilumab to further investigate. Puza and Atwater25 established that patients are able to mount a positive patch test reaction while on dupilumab. Moreover, a retrospective review by Raffi et al26 found that out of 125 before therapy/on therapy patch test pairs, only 13 were lost after administration of dupilumab. Although this would suggest that dupilumab has little impact on patch testing, Jo et al27 found in a systematic review that patch test reactions may remain positive, change to negative, or become newly positive after dupilumab initiation.

This inconsistency in results may relate to the allergen-specific pathogenesis of ACD—one allergen may have a different response to the mechanism of dupilumab than another.28,29 More recently, de Wijs et al30 reported a series of 20 patients in whom more than two-thirds of prior positive patch test reactions were lost after retesting on dupilumab; there were no clear trends according to the immune polarity of the allergens. This finding suggests that patient-specific factors also should be considered, as this too could have an impact on the reliability of patch test findings after starting dupilumab.29

Final Interpretation

Given its overall excellent safety profile, dupilumab may be a feasible off-label option for patients with ACD that does not respond to allergen avoidance or for those who experience adverse effects from traditional therapies; however, it remains difficult to obtain through insurance because it is not yet FDA approved for ACD. Likewise, its impact on the accuracy of patch testing is not yet well defined. Further investigations are needed to elucidate the pathophysiology of ACD and to guide further use of dupilumab in its treatment.

References
  1. Harb H, Chatila TA. Mechanisms of dupilumab. Clin Exp Allergy. 2020;50:5-14. doi:10.1111/cea.13491
  2. Gooderham MJ, Hong HC, Eshtiaghi P, et al. Dupilumab: a review of its use in the treatment of atopic dermatitis. J Am Acad Dermatol. 2018;78(3 suppl 1):S28-S36. doi:10.1016/j.jaad.2017.12.022
  3. Murphy PB, Atwater AR, Mueller M. Allergic Contact Dermatitis. StatPearls Publishing; 2022. https://www.ncbi.nlm.nih.gov/books/NBK532866/
  4. Dhingra N, Shemer A, Correa da Rosa J, et al. Molecular profiling of contact dermatitis skin identifies allergen-dependent differences in immune response. J Allergy Clin Immunol. 2014;134:362-372. doi:10.1016/j.jaci.2014.03.009
  5. 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
  6. Sung CT, McGowan MA, Machler BC, et al. Systemic treatments for allergic contact dermatitis. Dermatitis. 2019;30:46-53. doi:10.1097/DER.0000000000000435
  7. Chan CX, Zug KA. Diagnosis and management of dermatitis, including atopic, contact, and hand eczemas. Med Clin North Am. 2021;105:611-626. doi:10.1016/j.mcna.2021.04.003
  8. Simons JR, Bohnen IJ, van der Valk PG. A left-right comparison of UVB phototherapy and topical photochemotherapy in bilateral chronic hand dermatitis after 6 weeks’ treatment. Clin Exp Dermatol. 1997;22:7-10. doi:10.1046/j.1365-2230.1997.1640585.x
  9. Bhatia J, Sarin A, Wollina U, et al. Review of biologics in allergic contact dermatitis. Contact Dermatitis. 2020;83:179-181. doi:10.1111/cod.13584
  10. Todberg T, Zachariae C, Krustrup D, et al. The effect of anti-IL-17 treatment on the reaction to a nickel patch test in patients with allergic contact dermatitis. Int J Dermatol. 2019;58:E58-E61. doi:10.1111/ijd.14347
  11. 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
  12. Joshi SR, Khan DA. Effective use of dupilumab in managing systemic allergic contact dermatitis. Dermatitis. 2018;29:282-284. doi:10.1097/DER.0000000000000409
  13. Goldminz AM, Scheinman PL. A case series of dupilumab-treated allergic contact dermatitis patients. Dermatol Ther. 2018;31:E12701. doi:10.1111/dth.12701
  14. Chipalkatti N, Lee N, Zancanaro P, et al. Dupilumab as a treatment for allergic contact dermatitis. Dermatitis. 2018;29:347-348. doi:10.1097/DER.0000000000000414
  15. Zhu GA, Chen JK, Chiou A, et al. Repeat patch testing in a patient with allergic contact dermatitis improved on dupilumab. JAAD Case Rep. 2019;5:336-338. doi:10.1016/j.jdcr.2019.01.023
  16. Machler BC, Sung CT, Darwin E, et al. Dupilumab use in allergic contact dermatitis. J Am Acad Dermatol. 2019;80:280-281.e1. doi:10.1016/j.jaad.2018.07.043
  17. Chipalkatti N, Lee N, Zancanaro P, et al. A retrospective review of dupilumab for atopic dermatitis patients with allergic contact dermatitis. J Am Acad Dermatol. 2019;80:1166-1167. doi:10.1016/j.jaad.2018.12.048
  18. Jacob SE, Sung CT, Machler BC. Dupilumab for systemic allergy syndrome with dermatitis. Dermatitis. 2019;30:164-167. doi:10.1097/DER.0000000000000446
  19. Ruge IF, Skov L, Zachariae C, et al. Dupilumab treatment in two patients with severe allergic contact dermatitis caused by sesquiterpene lactones. Contact Dermatitis. 2020;83:137-139. doi:10.1111/cod.13545
  20. Wilson B, Balogh E, Rayhan D, et al. Chromate-induced allergic contact dermatitis treated with dupilumab. J Drugs Dermatol. 2021;20:1340-1342. doi:10.36849/jdd.6246
  21. Jo CE, Finstad A, Georgakopoulos JR, et al. Facial and neck erythema associated with dupilumab treatment: a systematic review. J Am Acad Dermatol. 2021;84:1339-1347. doi:10.1016/j.jaad.2021.01.012
  22. Koblinski JE, Hamann D. Mixed occupational and iatrogenic allergic contact dermatitis in a hairdresser. Occup Med (Lond). 2020;70:523-526. doi:10.1093/occmed/kqaa152
  23. Levian B, Chan J, DeLeo VA, et al. Patch testing and immunosuppression: a comprehensive review. Curr Derm Rep. 2021;10:128-139.
  24. Shah P, Milam EC, Lo Sicco KI, et al. Dupilumab for allergic contact dermatitis and implications for patch testing: irreconcilable differences. J Am Acad Dermatol. 2020;83:E215-E216. doi:10.1016/j.jaad.2020.05.036
  25. Puza CJ, Atwater AR. Positive patch test reaction in a patient taking dupilumab. Dermatitis. 2018;29:89. doi:10.1097/DER.0000000000000346
  26. Raffi J, Suresh R, Botto N, et al. The impact of dupilumab on patch testing and the prevalence of comorbid allergic contact dermatitis in recalcitrant atopic dermatitis: a retrospective chart review. J Am Acad Dermatol. 2020;82:132-138. doi:10.1016/j.jaad.2019.09.028
  27. Jo CE, Mufti A, Sachdeva M, et al. Effect of dupilumab on allergic contact dermatitis and patch testing. J Am Acad Dermatol. 2021;84:1772-1776. doi:10.1016/j.jaad.2021.02.044
  28. Raffi J, Botto N. Patch testing and allergen-specific inhibition in a patient taking dupilumab. JAMA Dermatol. 2019;155:120-121. doi:10.1001/jamadermatol.2018.4098
  29. Ludwig CM, Krase JM, Shi VY. T helper 2 inhibitors in allergic contact dermatitis. Dermatitis. 2021;32:15-18. doi: 10.1097/DER.0000000000000616
  30. de Wijs LEM, van der Waa JD, Nijsten T, et al. Effects of dupilumab treatment on patch test reactions: a retrospective evaluation. Clin Exp Allergy. 2021;51:959-967. doi:10.1111/cea.13892
Article PDF
CT109005265.PDF
Author and Disclosure Information

Ms. Johnson is from the University of Minnesota Medical School, Minneapolis. 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 and Dr. Yu report no conflict of interest. Dr. Adler has served as a research investigator and/or consultant for AbbVie and Skin Research Institute, LLC.

The eTable is available in the Appendix online at www.mdedge.com/dermatology.

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

Issue
Cutis - 109(5)
Publications
MDedge Dermatology
Cutis
Topics
Contact Dermatitis
Page Number
265-267,E4-E5
Sections
Contact Dermatitis
Author(s)
Hadley Johnson, BS
Brandon L. Adler, MD
Jiade Yu, MD
Author(s)
Hadley Johnson, BS
Brandon L. Adler, MD
Jiade Yu, MD
Author and Disclosure Information

Ms. Johnson is from the University of Minnesota Medical School, Minneapolis. 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 and Dr. Yu report no conflict of interest. Dr. Adler has served as a research investigator and/or consultant for AbbVie and Skin Research Institute, LLC.

The eTable is available in the Appendix online at www.mdedge.com/dermatology.

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

The eTable is available in the Appendix online at www.mdedge.com/dermatology.

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

Article PDF
CT109005265.PDF
Article PDF
CT109005265.PDF

Dupilumab is a humanized monoclonal antibody approved by the US Food and Drug Administration (FDA) for the treatment of moderate to severe atopic dermatitis. Through inhibition of the IL-4R α subunit, it prevents activation of the IL-4/IL-13 signaling cascade. This dampens the T H 2 inflammatory response, thereby improving the symptoms associated with atopic dermatitis. 1,2 Recent literature suggests that dupilumab may be useful in the treatment of other chronic dermatologic conditions, including allergic contact dermatitis (ACD) refractory to allergen avoidance and other treatments. Herein, we provide an overview of ACD, the role that dupilumab may play in its management, and its impact on patch testing results.

Pathogenesis of ACD

Allergic contact dermatitis is a cell-mediated type IV hypersensitivity reaction that develops through 2 distinct stages. In the sensitization phase, an allergen penetrates the skin and subsequently is engulfed by a cutaneous antigen-presenting cell. The allergen is then combined with a peptide to form a complex that is presented to naïve T lymphocytes in regional lymph nodes. The result is clonal expansion of a T-cell population that recognizes the allergen. In the elicitation phase, repeat exposure to the allergen leads to the recruitment of primed T cells to the skin, followed by cytokine release, inflammation, and resultant dermatitis.3

Historically, ACD was thought to be primarily driven by the TH1 inflammatory response; however, it is now known that TH2, TH9, TH17, and TH22 also may play a role in its pathogenesis.4,5 Another key finding is that the immune response in ACD appears to be at least partially allergen specific. Molecular profiling has revealed that nickel primarily induces a TH1/TH17 response, while allergens such as fragrance and rubber primarily induce a TH2 response.4

Management of ACD

Allergen avoidance is the mainstay of ACD treatment; however, in some patients, this approach does not always improve symptoms. In addition, eliminating the source of the allergen may not be possible in those with certain occupational, environmental, or medical exposures.

There are no FDA-approved treatments for ACD. When allergen avoidance alone is insufficient, first-line pharmacologic therapy typically includes topical or oral corticosteroids, the choice of which depends on the extent and severity of the dermatitis; however, a steroid-sparing agent often is preferred to avoid the unfavorable effects of long-term steroid use. Other systemic treatments for ACD include methotrexate, cyclosporine, mycophenolate mofetil, and azathioprine.6 These agents are used for severe ACD and typically are chosen as a last resort due to their immunosuppressive activity.

Phototherapy is another option, often as an adjunct to other therapies. Narrowband UVB and psoralen plus UVA have both been used. Psoralen plus UVA tends to have more side effects; therefore, narrowband UVB often is preferred.7,8

Use of Dupilumab in ACD

Biologics are unique, as they can target a single step in the immune response to improve a wide variety of symptoms. Research investigating their role as a treatment modality for ACD is still evolving alongside our increasing knowledge of its pathophysiology.9 Of note, studies examining the anti–IL-17 biologic secukinumab revealed it to be ineffective against ACD,10,11 which suggests that targeting specific immune components may not always result in improvement of ACD symptoms, likely because its pathophysiology involves several pathways.

 

 

There have been multiple reports demonstrating the effectiveness of dupilumab in the treatment of ACD (eTable).12-20 The findings from these studies show that dupilumab can improve recalcitrant dermatitis caused by a broad range of contact allergens, including nickel. This highlights its ability to improve ACD caused by allergens with a TH1 bias, despite its primarily TH2-dampening effects. Notably, several studies have reported successful use of dupilumab for systemic ACD.12,18 In addition, dupilumab may be able to improve symptoms of ACD in as little as 1 to 4 weeks. Unlike some systemic therapies for ACD, dupilumab also benefits from its lack of notable immunosuppressive effects.9 A phase 4 clinical trial at Brigham and Women’s Hospital (Boston, Massachusetts) is recruiting participants, with a primary goal of investigating dupilumab’s impact on ACD in patients who have not improved despite allergen avoidance (ClinicalTrials.gov identifier NCT03935971).

Studies Demonstrating Improvement of ACD With Dupilumab Use

Studies Demonstrating Improvement of ACD With Dupilumab Use

There are a few potential disadvantages to dupilumab. Because it is not yet FDA approved for the treatment of ACD, insurance companies may deny coverage, making it likely to be unaffordable for most patients. Furthermore, the side-effect profile has not been fully characterized. In addition to ocular adverse effects, a growing number of studies have reported face and neck erythema after starting dupilumab. Although the cause is unclear, one theory is that the inhibition of IL-4/IL-13 leads to TH1/TH17 polarization, thereby worsening ACD caused by allergens that activate a TH1-predominant response.21 Finally, not all cases of ACD respond to dupilumab.22

Patch Testing While on Dupilumab

Diagnosing ACD is a challenging process. An accurate history and physical examination are critical, and patch testing remains the gold standard when it comes to identifying the source of the contact allergen(s).

There is ongoing debate among contact dermatitis experts regarding the diagnostic accuracy of patch testing for those on immunomodulators or immunosuppressants, as these medications can dampen positive results and increase the risk for false-negative readings.23 Consequently, some have questioned whether patch testing on dupilumab is accurate or feasible.24 Contact dermatitis experts have examined patch testing results before and after initiation of dupilumab to further investigate. Puza and Atwater25 established that patients are able to mount a positive patch test reaction while on dupilumab. Moreover, a retrospective review by Raffi et al26 found that out of 125 before therapy/on therapy patch test pairs, only 13 were lost after administration of dupilumab. Although this would suggest that dupilumab has little impact on patch testing, Jo et al27 found in a systematic review that patch test reactions may remain positive, change to negative, or become newly positive after dupilumab initiation.

This inconsistency in results may relate to the allergen-specific pathogenesis of ACD—one allergen may have a different response to the mechanism of dupilumab than another.28,29 More recently, de Wijs et al30 reported a series of 20 patients in whom more than two-thirds of prior positive patch test reactions were lost after retesting on dupilumab; there were no clear trends according to the immune polarity of the allergens. This finding suggests that patient-specific factors also should be considered, as this too could have an impact on the reliability of patch test findings after starting dupilumab.29

Final Interpretation

Given its overall excellent safety profile, dupilumab may be a feasible off-label option for patients with ACD that does not respond to allergen avoidance or for those who experience adverse effects from traditional therapies; however, it remains difficult to obtain through insurance because it is not yet FDA approved for ACD. Likewise, its impact on the accuracy of patch testing is not yet well defined. Further investigations are needed to elucidate the pathophysiology of ACD and to guide further use of dupilumab in its treatment.

Dupilumab is a humanized monoclonal antibody approved by the US Food and Drug Administration (FDA) for the treatment of moderate to severe atopic dermatitis. Through inhibition of the IL-4R α subunit, it prevents activation of the IL-4/IL-13 signaling cascade. This dampens the T H 2 inflammatory response, thereby improving the symptoms associated with atopic dermatitis. 1,2 Recent literature suggests that dupilumab may be useful in the treatment of other chronic dermatologic conditions, including allergic contact dermatitis (ACD) refractory to allergen avoidance and other treatments. Herein, we provide an overview of ACD, the role that dupilumab may play in its management, and its impact on patch testing results.

Pathogenesis of ACD

Allergic contact dermatitis is a cell-mediated type IV hypersensitivity reaction that develops through 2 distinct stages. In the sensitization phase, an allergen penetrates the skin and subsequently is engulfed by a cutaneous antigen-presenting cell. The allergen is then combined with a peptide to form a complex that is presented to naïve T lymphocytes in regional lymph nodes. The result is clonal expansion of a T-cell population that recognizes the allergen. In the elicitation phase, repeat exposure to the allergen leads to the recruitment of primed T cells to the skin, followed by cytokine release, inflammation, and resultant dermatitis.3

Historically, ACD was thought to be primarily driven by the TH1 inflammatory response; however, it is now known that TH2, TH9, TH17, and TH22 also may play a role in its pathogenesis.4,5 Another key finding is that the immune response in ACD appears to be at least partially allergen specific. Molecular profiling has revealed that nickel primarily induces a TH1/TH17 response, while allergens such as fragrance and rubber primarily induce a TH2 response.4

Management of ACD

Allergen avoidance is the mainstay of ACD treatment; however, in some patients, this approach does not always improve symptoms. In addition, eliminating the source of the allergen may not be possible in those with certain occupational, environmental, or medical exposures.

There are no FDA-approved treatments for ACD. When allergen avoidance alone is insufficient, first-line pharmacologic therapy typically includes topical or oral corticosteroids, the choice of which depends on the extent and severity of the dermatitis; however, a steroid-sparing agent often is preferred to avoid the unfavorable effects of long-term steroid use. Other systemic treatments for ACD include methotrexate, cyclosporine, mycophenolate mofetil, and azathioprine.6 These agents are used for severe ACD and typically are chosen as a last resort due to their immunosuppressive activity.

Phototherapy is another option, often as an adjunct to other therapies. Narrowband UVB and psoralen plus UVA have both been used. Psoralen plus UVA tends to have more side effects; therefore, narrowband UVB often is preferred.7,8

Use of Dupilumab in ACD

Biologics are unique, as they can target a single step in the immune response to improve a wide variety of symptoms. Research investigating their role as a treatment modality for ACD is still evolving alongside our increasing knowledge of its pathophysiology.9 Of note, studies examining the anti–IL-17 biologic secukinumab revealed it to be ineffective against ACD,10,11 which suggests that targeting specific immune components may not always result in improvement of ACD symptoms, likely because its pathophysiology involves several pathways.

 

 

There have been multiple reports demonstrating the effectiveness of dupilumab in the treatment of ACD (eTable).12-20 The findings from these studies show that dupilumab can improve recalcitrant dermatitis caused by a broad range of contact allergens, including nickel. This highlights its ability to improve ACD caused by allergens with a TH1 bias, despite its primarily TH2-dampening effects. Notably, several studies have reported successful use of dupilumab for systemic ACD.12,18 In addition, dupilumab may be able to improve symptoms of ACD in as little as 1 to 4 weeks. Unlike some systemic therapies for ACD, dupilumab also benefits from its lack of notable immunosuppressive effects.9 A phase 4 clinical trial at Brigham and Women’s Hospital (Boston, Massachusetts) is recruiting participants, with a primary goal of investigating dupilumab’s impact on ACD in patients who have not improved despite allergen avoidance (ClinicalTrials.gov identifier NCT03935971).

Studies Demonstrating Improvement of ACD With Dupilumab Use

Studies Demonstrating Improvement of ACD With Dupilumab Use

There are a few potential disadvantages to dupilumab. Because it is not yet FDA approved for the treatment of ACD, insurance companies may deny coverage, making it likely to be unaffordable for most patients. Furthermore, the side-effect profile has not been fully characterized. In addition to ocular adverse effects, a growing number of studies have reported face and neck erythema after starting dupilumab. Although the cause is unclear, one theory is that the inhibition of IL-4/IL-13 leads to TH1/TH17 polarization, thereby worsening ACD caused by allergens that activate a TH1-predominant response.21 Finally, not all cases of ACD respond to dupilumab.22

Patch Testing While on Dupilumab

Diagnosing ACD is a challenging process. An accurate history and physical examination are critical, and patch testing remains the gold standard when it comes to identifying the source of the contact allergen(s).

There is ongoing debate among contact dermatitis experts regarding the diagnostic accuracy of patch testing for those on immunomodulators or immunosuppressants, as these medications can dampen positive results and increase the risk for false-negative readings.23 Consequently, some have questioned whether patch testing on dupilumab is accurate or feasible.24 Contact dermatitis experts have examined patch testing results before and after initiation of dupilumab to further investigate. Puza and Atwater25 established that patients are able to mount a positive patch test reaction while on dupilumab. Moreover, a retrospective review by Raffi et al26 found that out of 125 before therapy/on therapy patch test pairs, only 13 were lost after administration of dupilumab. Although this would suggest that dupilumab has little impact on patch testing, Jo et al27 found in a systematic review that patch test reactions may remain positive, change to negative, or become newly positive after dupilumab initiation.

This inconsistency in results may relate to the allergen-specific pathogenesis of ACD—one allergen may have a different response to the mechanism of dupilumab than another.28,29 More recently, de Wijs et al30 reported a series of 20 patients in whom more than two-thirds of prior positive patch test reactions were lost after retesting on dupilumab; there were no clear trends according to the immune polarity of the allergens. This finding suggests that patient-specific factors also should be considered, as this too could have an impact on the reliability of patch test findings after starting dupilumab.29

Final Interpretation

Given its overall excellent safety profile, dupilumab may be a feasible off-label option for patients with ACD that does not respond to allergen avoidance or for those who experience adverse effects from traditional therapies; however, it remains difficult to obtain through insurance because it is not yet FDA approved for ACD. Likewise, its impact on the accuracy of patch testing is not yet well defined. Further investigations are needed to elucidate the pathophysiology of ACD and to guide further use of dupilumab in its treatment.

References
  1. Harb H, Chatila TA. Mechanisms of dupilumab. Clin Exp Allergy. 2020;50:5-14. doi:10.1111/cea.13491
  2. Gooderham MJ, Hong HC, Eshtiaghi P, et al. Dupilumab: a review of its use in the treatment of atopic dermatitis. J Am Acad Dermatol. 2018;78(3 suppl 1):S28-S36. doi:10.1016/j.jaad.2017.12.022
  3. Murphy PB, Atwater AR, Mueller M. Allergic Contact Dermatitis. StatPearls Publishing; 2022. https://www.ncbi.nlm.nih.gov/books/NBK532866/
  4. Dhingra N, Shemer A, Correa da Rosa J, et al. Molecular profiling of contact dermatitis skin identifies allergen-dependent differences in immune response. J Allergy Clin Immunol. 2014;134:362-372. doi:10.1016/j.jaci.2014.03.009
  5. 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
  6. Sung CT, McGowan MA, Machler BC, et al. Systemic treatments for allergic contact dermatitis. Dermatitis. 2019;30:46-53. doi:10.1097/DER.0000000000000435
  7. Chan CX, Zug KA. Diagnosis and management of dermatitis, including atopic, contact, and hand eczemas. Med Clin North Am. 2021;105:611-626. doi:10.1016/j.mcna.2021.04.003
  8. Simons JR, Bohnen IJ, van der Valk PG. A left-right comparison of UVB phototherapy and topical photochemotherapy in bilateral chronic hand dermatitis after 6 weeks’ treatment. Clin Exp Dermatol. 1997;22:7-10. doi:10.1046/j.1365-2230.1997.1640585.x
  9. Bhatia J, Sarin A, Wollina U, et al. Review of biologics in allergic contact dermatitis. Contact Dermatitis. 2020;83:179-181. doi:10.1111/cod.13584
  10. Todberg T, Zachariae C, Krustrup D, et al. The effect of anti-IL-17 treatment on the reaction to a nickel patch test in patients with allergic contact dermatitis. Int J Dermatol. 2019;58:E58-E61. doi:10.1111/ijd.14347
  11. 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
  12. Joshi SR, Khan DA. Effective use of dupilumab in managing systemic allergic contact dermatitis. Dermatitis. 2018;29:282-284. doi:10.1097/DER.0000000000000409
  13. Goldminz AM, Scheinman PL. A case series of dupilumab-treated allergic contact dermatitis patients. Dermatol Ther. 2018;31:E12701. doi:10.1111/dth.12701
  14. Chipalkatti N, Lee N, Zancanaro P, et al. Dupilumab as a treatment for allergic contact dermatitis. Dermatitis. 2018;29:347-348. doi:10.1097/DER.0000000000000414
  15. Zhu GA, Chen JK, Chiou A, et al. Repeat patch testing in a patient with allergic contact dermatitis improved on dupilumab. JAAD Case Rep. 2019;5:336-338. doi:10.1016/j.jdcr.2019.01.023
  16. Machler BC, Sung CT, Darwin E, et al. Dupilumab use in allergic contact dermatitis. J Am Acad Dermatol. 2019;80:280-281.e1. doi:10.1016/j.jaad.2018.07.043
  17. Chipalkatti N, Lee N, Zancanaro P, et al. A retrospective review of dupilumab for atopic dermatitis patients with allergic contact dermatitis. J Am Acad Dermatol. 2019;80:1166-1167. doi:10.1016/j.jaad.2018.12.048
  18. Jacob SE, Sung CT, Machler BC. Dupilumab for systemic allergy syndrome with dermatitis. Dermatitis. 2019;30:164-167. doi:10.1097/DER.0000000000000446
  19. Ruge IF, Skov L, Zachariae C, et al. Dupilumab treatment in two patients with severe allergic contact dermatitis caused by sesquiterpene lactones. Contact Dermatitis. 2020;83:137-139. doi:10.1111/cod.13545
  20. Wilson B, Balogh E, Rayhan D, et al. Chromate-induced allergic contact dermatitis treated with dupilumab. J Drugs Dermatol. 2021;20:1340-1342. doi:10.36849/jdd.6246
  21. Jo CE, Finstad A, Georgakopoulos JR, et al. Facial and neck erythema associated with dupilumab treatment: a systematic review. J Am Acad Dermatol. 2021;84:1339-1347. doi:10.1016/j.jaad.2021.01.012
  22. Koblinski JE, Hamann D. Mixed occupational and iatrogenic allergic contact dermatitis in a hairdresser. Occup Med (Lond). 2020;70:523-526. doi:10.1093/occmed/kqaa152
  23. Levian B, Chan J, DeLeo VA, et al. Patch testing and immunosuppression: a comprehensive review. Curr Derm Rep. 2021;10:128-139.
  24. Shah P, Milam EC, Lo Sicco KI, et al. Dupilumab for allergic contact dermatitis and implications for patch testing: irreconcilable differences. J Am Acad Dermatol. 2020;83:E215-E216. doi:10.1016/j.jaad.2020.05.036
  25. Puza CJ, Atwater AR. Positive patch test reaction in a patient taking dupilumab. Dermatitis. 2018;29:89. doi:10.1097/DER.0000000000000346
  26. Raffi J, Suresh R, Botto N, et al. The impact of dupilumab on patch testing and the prevalence of comorbid allergic contact dermatitis in recalcitrant atopic dermatitis: a retrospective chart review. J Am Acad Dermatol. 2020;82:132-138. doi:10.1016/j.jaad.2019.09.028
  27. Jo CE, Mufti A, Sachdeva M, et al. Effect of dupilumab on allergic contact dermatitis and patch testing. J Am Acad Dermatol. 2021;84:1772-1776. doi:10.1016/j.jaad.2021.02.044
  28. Raffi J, Botto N. Patch testing and allergen-specific inhibition in a patient taking dupilumab. JAMA Dermatol. 2019;155:120-121. doi:10.1001/jamadermatol.2018.4098
  29. Ludwig CM, Krase JM, Shi VY. T helper 2 inhibitors in allergic contact dermatitis. Dermatitis. 2021;32:15-18. doi: 10.1097/DER.0000000000000616
  30. de Wijs LEM, van der Waa JD, Nijsten T, et al. Effects of dupilumab treatment on patch test reactions: a retrospective evaluation. Clin Exp Allergy. 2021;51:959-967. doi:10.1111/cea.13892
References
  1. Harb H, Chatila TA. Mechanisms of dupilumab. Clin Exp Allergy. 2020;50:5-14. doi:10.1111/cea.13491
  2. Gooderham MJ, Hong HC, Eshtiaghi P, et al. Dupilumab: a review of its use in the treatment of atopic dermatitis. J Am Acad Dermatol. 2018;78(3 suppl 1):S28-S36. doi:10.1016/j.jaad.2017.12.022
  3. Murphy PB, Atwater AR, Mueller M. Allergic Contact Dermatitis. StatPearls Publishing; 2022. https://www.ncbi.nlm.nih.gov/books/NBK532866/
  4. Dhingra N, Shemer A, Correa da Rosa J, et al. Molecular profiling of contact dermatitis skin identifies allergen-dependent differences in immune response. J Allergy Clin Immunol. 2014;134:362-372. doi:10.1016/j.jaci.2014.03.009
  5. 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
  6. Sung CT, McGowan MA, Machler BC, et al. Systemic treatments for allergic contact dermatitis. Dermatitis. 2019;30:46-53. doi:10.1097/DER.0000000000000435
  7. Chan CX, Zug KA. Diagnosis and management of dermatitis, including atopic, contact, and hand eczemas. Med Clin North Am. 2021;105:611-626. doi:10.1016/j.mcna.2021.04.003
  8. Simons JR, Bohnen IJ, van der Valk PG. A left-right comparison of UVB phototherapy and topical photochemotherapy in bilateral chronic hand dermatitis after 6 weeks’ treatment. Clin Exp Dermatol. 1997;22:7-10. doi:10.1046/j.1365-2230.1997.1640585.x
  9. Bhatia J, Sarin A, Wollina U, et al. Review of biologics in allergic contact dermatitis. Contact Dermatitis. 2020;83:179-181. doi:10.1111/cod.13584
  10. Todberg T, Zachariae C, Krustrup D, et al. The effect of anti-IL-17 treatment on the reaction to a nickel patch test in patients with allergic contact dermatitis. Int J Dermatol. 2019;58:E58-E61. doi:10.1111/ijd.14347
  11. 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
  12. Joshi SR, Khan DA. Effective use of dupilumab in managing systemic allergic contact dermatitis. Dermatitis. 2018;29:282-284. doi:10.1097/DER.0000000000000409
  13. Goldminz AM, Scheinman PL. A case series of dupilumab-treated allergic contact dermatitis patients. Dermatol Ther. 2018;31:E12701. doi:10.1111/dth.12701
  14. Chipalkatti N, Lee N, Zancanaro P, et al. Dupilumab as a treatment for allergic contact dermatitis. Dermatitis. 2018;29:347-348. doi:10.1097/DER.0000000000000414
  15. Zhu GA, Chen JK, Chiou A, et al. Repeat patch testing in a patient with allergic contact dermatitis improved on dupilumab. JAAD Case Rep. 2019;5:336-338. doi:10.1016/j.jdcr.2019.01.023
  16. Machler BC, Sung CT, Darwin E, et al. Dupilumab use in allergic contact dermatitis. J Am Acad Dermatol. 2019;80:280-281.e1. doi:10.1016/j.jaad.2018.07.043
  17. Chipalkatti N, Lee N, Zancanaro P, et al. A retrospective review of dupilumab for atopic dermatitis patients with allergic contact dermatitis. J Am Acad Dermatol. 2019;80:1166-1167. doi:10.1016/j.jaad.2018.12.048
  18. Jacob SE, Sung CT, Machler BC. Dupilumab for systemic allergy syndrome with dermatitis. Dermatitis. 2019;30:164-167. doi:10.1097/DER.0000000000000446
  19. Ruge IF, Skov L, Zachariae C, et al. Dupilumab treatment in two patients with severe allergic contact dermatitis caused by sesquiterpene lactones. Contact Dermatitis. 2020;83:137-139. doi:10.1111/cod.13545
  20. Wilson B, Balogh E, Rayhan D, et al. Chromate-induced allergic contact dermatitis treated with dupilumab. J Drugs Dermatol. 2021;20:1340-1342. doi:10.36849/jdd.6246
  21. Jo CE, Finstad A, Georgakopoulos JR, et al. Facial and neck erythema associated with dupilumab treatment: a systematic review. J Am Acad Dermatol. 2021;84:1339-1347. doi:10.1016/j.jaad.2021.01.012
  22. Koblinski JE, Hamann D. Mixed occupational and iatrogenic allergic contact dermatitis in a hairdresser. Occup Med (Lond). 2020;70:523-526. doi:10.1093/occmed/kqaa152
  23. Levian B, Chan J, DeLeo VA, et al. Patch testing and immunosuppression: a comprehensive review. Curr Derm Rep. 2021;10:128-139.
  24. Shah P, Milam EC, Lo Sicco KI, et al. Dupilumab for allergic contact dermatitis and implications for patch testing: irreconcilable differences. J Am Acad Dermatol. 2020;83:E215-E216. doi:10.1016/j.jaad.2020.05.036
  25. Puza CJ, Atwater AR. Positive patch test reaction in a patient taking dupilumab. Dermatitis. 2018;29:89. doi:10.1097/DER.0000000000000346
  26. Raffi J, Suresh R, Botto N, et al. The impact of dupilumab on patch testing and the prevalence of comorbid allergic contact dermatitis in recalcitrant atopic dermatitis: a retrospective chart review. J Am Acad Dermatol. 2020;82:132-138. doi:10.1016/j.jaad.2019.09.028
  27. Jo CE, Mufti A, Sachdeva M, et al. Effect of dupilumab on allergic contact dermatitis and patch testing. J Am Acad Dermatol. 2021;84:1772-1776. doi:10.1016/j.jaad.2021.02.044
  28. Raffi J, Botto N. Patch testing and allergen-specific inhibition in a patient taking dupilumab. JAMA Dermatol. 2019;155:120-121. doi:10.1001/jamadermatol.2018.4098
  29. Ludwig CM, Krase JM, Shi VY. T helper 2 inhibitors in allergic contact dermatitis. Dermatitis. 2021;32:15-18. doi: 10.1097/DER.0000000000000616
  30. de Wijs LEM, van der Waa JD, Nijsten T, et al. Effects of dupilumab treatment on patch test reactions: a retrospective evaluation. Clin Exp Allergy. 2021;51:959-967. doi:10.1111/cea.13892
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Dupilumab for Allergic Contact Dermatitis: An Overview of Its Use and Impact on Patch Testing
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Dupilumab for Allergic Contact Dermatitis: An Overview of Its Use and Impact on Patch Testing
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Practice Points

  • Dupilumab is approved by the US Food and Drug Administration for the treatment of moderate to severe atopic dermatitis.
  • Multiple reports have suggested that dupilumab may be effective in the treatment of allergic contact dermatitis, and a phase 4 clinical trial is ongoing.
  • The accuracy of patch testing after dupilumab initiation is unclear, as reactions may remain positive, change to negative, or become newly positive after its administration.
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