Dupilumab Treatment in Severe Allergic Contact Dermatitis Due to Sesquiterpene Lactones

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• The authors report 2 cases of patients with allergic contact dermatitis (ACD) due to sesquiterpene lactones (commonly found in plants) who were inadequately controlled on multiple prior therapies including azathioprine, topical corticosteroids, cyclosporine, methotrexate, ustekinumab, and others. Both patients responded well to dupilumab at standard dosing throughout the spring and summer. Dupilumab therapy was held during winter when ACD from sesquiterpene lactones was quiescent.

• Dupilumab targets IL-4 and IL-13, part of the Th2 pathway, while ACD is traditionally considered a Th1 process. More studies are needed to investigate the effect of dupilumab on ACD and other Th1 processes.

– Caitlyn T. Reed, MD

Written by

 

 

Thy N Huynh MD

Written by

 

 

Stephen E Helms MD

There has been a great deal of interest in determining whether dupilumab (DPM) could play a role in the treatment of allergic contact dermatitis.1 Several experts have suggested that DPM does not "significantly" affect patch testing results. On the other hand, other leaders in the field have heralded DPN as "effective" in treating or preventing allergic contact dermatitis! This controversy persists even after assessing the mechanism of action of the subtypes of CD4 cells (Th1 and Th2) and the particular cytokines they secrete.1-2 For years, allergic contact dermatitis was thought to be a Th1-related disease in association with a Th17 and Th22 polarized response. In contrast, atopic dermatitis was considered to be a Th2-related condition, with new studies demonstrating some Th1 and Th17 response.3

DPM targets Th2 cells and has received FDA approval for the treatment of atopic dermatitis. It was not expected to be an effective treatment for diseases in which Th1 cells are the primary inflammatory effector cells. However, evidence has been building that Th2 may play a significant role in allergic dermatitis. Studies have revealed that some allergens, particularly nickel, may be mediated by Th1/Th17 response. Other allergens, however, including rubber and fragrances, induce immune responses via the Th2/Th22 pathway.3A number of case reports and case series have shown similar findings and suggest DPM as an effective treatment for allergens such as fragrance mixes 1 and 2, rubber, balsam of Peru, carba mix, cobalt, cocamidopropyl betaine, colophonium, formaldehyde, mercapto mix, methylchloroisothiazolinone, mixed dialkyl thiourea, nickel, oleamidopropyl dimethylamine, propylene glycol, and textile dyes.1,4

Obviously, the best treatment for allergic contact dermatitis is to avoid any and all responsible allergens. However, as demonstrated in the two cases presented in this article, some allergens such as sesquiterpene lactones may be difficult to avoid. Unfortunately, there were a number of confounding variables that make this study difficult to interpret. Both patients had a number of positive contact allergens, some of which have been demonstrated to be TH2-mediated and would, therefore, be expected to possibly respond to DPM. The extent of exposure to sesquiterpene lactones at the time the DPM therapy is unclear. The first patient still had evidence of a significant unexplained active rash during treatment with DPM. Therefore, we cannot definitely conclude that the DPM was the sole factor leading to the improvement experienced by these patients.

We agree with the authors' support for further studies to elucidate this perplexing conundrum. Characterizing the Th1 vs Th2 immune response of each specific allergen would enhance our understanding of treatment options, including dupilumab and other biologics, both those available today and new agents that will be introduced in the future.

References

1. Derosier A, Huynh T, Helms S, Brodell R. The role of dupilumab in managing allergic contact dermatitis. Skin. 2019;3(4):234-238. https://jofskin.org/index.php/skin/article/view/601
2. Li L, Sad S, Kagi D, Mosmann TR. CD8 Tc1 and Tc2 cells secrete distinct cytokine patterns in vitro and in vivo but insuce similar inflammatory reactions. J Immunol. 1997;158(9):4152-4161. https://www.jimmunol.org/content/158/9/4152.long
3. Correa da Rosa J, Malajian D, Shemer A, et al. Patients with atopic dermatitis have attenuated and distinct contact hypersensitivity responses to common allergens in skin. J Allergy Clin Immunol. 2015;135(3):712-720. https://www.jacionline.org/article/S0091-6749(14)01671-6/fulltext
4. Huynh T, Hadi S, Tan K, Guttman-Yassky E. Dupilumab therapy for chronic refractory hand dermatitis [abstract]. Exp Dermatol. 2018;27(S2):33. https://onlinelibrary.wiley.com/doi/full/10.1111/exd.13795

Abstract

Sesquiterpene lactones (SLs) are a group of allergenic secondary plant metabolites represented in about 10% of all flowers 1,2. SLs are abundant in the sunflower family, but also exist in vegetables, cosmetics and herbal medicine3. Airborne spread of SLs typically causes allergic contact dermatitis in exposed skin areas including face, V-line of the neck, hands and forearms and with a distinct seasonal variation (i.e. dermatitis worsens in the plant-growing season)4. Affected patients develop severe and widespread, often treatment resistant eczema, that can severely affect their daily lives with need of systemic treatment 2. Even though allergic contact dermatitis predominately is a TH1-cell mediated process, certain allergens activate the TH2-pathway.5 Dupilumab; a monoclonal antibody binds to the interleukin (IL)-4 receptor alpha and inhibits IL-4 and IL-13 signaling and thus the TH2-mediated pathway. Dupilumab has been approved for the treatment of atopic dermatitis in adolescents and adults6. Further, studies indicate a potential effect in allergic contact dermatitis7,8. We report the treatment outcome with dupilumab in two patients with SL induced allergic contact dermatitis.

Contact Dermatitis

Dupilumab Treatment in Two Patients With Severe Allergic Contact Dermatitis Caused by Sesquiterpene Lactones

Contact Derm 2020 Apr 03;[EPub Ahead of Print], IF Ruge, L Skov, C Zachariae, JP Thyssen 

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Benjamin Hidalgo-Matlock
Skin Care Physicians of Costa Rica

Clinica Victoria en San Pedro: 4000-1054
Momentum Escazu: 2101-9574

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