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.