First Reported Case of Red Face Response to Tralokinumab in the United States

The chronic nature of atopic dermatitis (AD), which currently affects approximately 10.8% of children and 7.3% of adults in the United States,¹ makes long-term management challenging. Treatment has traditionally relied on hydration and emollients for managing mild disease. Due to a complex disease process, systemic medications have been developed to better treat the immune dysregulation present in moderate-to-severe AD. 

Pathogenesis

AD is driven by immune dysregulation, with increased levels of IL-4 and IL-13 contributing to systemic allergic conditions, such as allergic rhinitis, and asthma.² Elevated IL-4 levels are responsible for IgE production, enhancing skin inflammation, and mediating pruritus.³ IL-13 has been connected to skin barrier dysfunction via indirect filaggrin downregulation and inflammation, with concentration being directly related to AD severity.^4,5

It is this understanding that led to the development of biologic therapies targeting these cytokines, including dupilumab and tralokinumab. Dupilumab decreases the immune response broadly by targeting both IL-4 and IL-13; it received FDA approval in 2017.⁶ Tralokinumab was developed after dupilumab as a fully human monoclonal antibody inhibitor specifically targeting IL-13. Tralokinumab works by blocking its interaction with the IL-13Ra1/IL-4a receptor complex and the IL-4Ra2 receptor.⁷ Tralokinumab was subsequently approved in 2021 for the treatment of moderate to severe AD8 and has since become viewed as a useful alternative to dupilumab, with clinical trials demonstrating comparable efficacy.⁹

Clinical Report and Adverse Effects

Dupilumab has been associated with various side effects, including injection site reaction, conjunctivitis, and nasopharyngitis. Other adverse events reported include facial erythema and arthralgias.^10-13 The first case of facial redness with dupilumab was reported in 2018.¹⁴ Here, we present a case of a patient with moderate-to-severe AD who developed facial erythema following treatment with tralokinumab. A literature review revealed a single case of this adverse event associated with tralokinumab in a patient that resolved 3 weeks after discontinuing therapy.¹⁵ We believe this is the second reported case of facial redness with tralokinumab. Our patient was a 55-year-old white woman with a lifelong history of severe AD and asthma. The patient previously had been treated with dupilumab from 2015 to 2024 and switched from dupilumab to tralokinumab in January 2024 due to insurance issues. She remained clear of her AD until December 2024, when she noted that her face would become very red and hot to touch in the first 2 days following her injection. She contacted us in January 2025 and chose to discontinue the tralokinumab as the redness and discomfort became worse than her AD. The patient sent us photographs of her face showing the erythematous ill-defined patches (Figures 1 through 5).    

Figure 1. 

Figure 2.

Figure 3. 

Figure 4.

Figure 5.

Clinicians should be encouraged to report similar occurrences in patients receiving tralokinumab to further assess its safety profile. We do not know the cause of the reaction, but there has been speculation that facial erythema associated with dupilumab is multifactorial,¹⁶ and we would consider the same possibility here. Some believe there is a component of yeast overgrowth as well as contact dermatitis, but we patch tested this patient and she showed no new allergens. 

We are also unclear as to why this adverse event took 11 months to occur, but delayed adverse events have been seen with dupilumab.^17,18

After this patient chose to stop therapy with tralokinumab, her facial redness resolved completely within 4 weeks. There were no long-term sequelae or lingering effects. We have since started her on the IL-31 inhibitor nemolizumab, with the hope that a different mechanism of action will not cause facial erythema in this case. Her AD has been well-controlled to this point. 

Disclosures: The authors report no relevant financial disclosures. 

1. Centers for Disease Control and Prevention. More than a quarter of U.S. adults and children have at least one allergy. CDC. Published January 27, 2023. Accessed August 18, 2025. https://www.cdc.gov/nchs/pressroom/nchs_press_releases/2022/20220126.htm

2. 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(4)(suppl):S65-S76. https://doi.org/10.1016/j.jaci.2017.01.011

3. Chiricozzi A, Maurelli M, Peris K, Girolomoni G. Targeting IL-4 for the treatment of atopic dermatitis. Immunotargets Ther. 2020;9:151-156. https://doi.org/10.2147/ITT.S260370

4. Furue M. Regulation of filaggrin, loricrin, and involucrin by IL-4, IL-13, IL-17A, IL-22, AHR, and NRF2: pathogenic implications in atopic dermatitis. Int J Mol Sci. 2020;21(15):5382. https://doi.org/10.3390/ijms21155382

5. Napolitano M, di Vico F, Ruggiero A, Fabbrocini G, Patruno C. The hidden sentinel of the skin: an overview on the role of interleukin-13 in atopic dermatitis. Front Med (Lausanne). 2023;10:1165098. https://doi.org/10.3389/fmed.2023.1165098

6. Vangipuram R, Tyring SK. Dupilumab for moderate-to-severe atopic dermatitis. Skin Therapy Lett. 2017;22(6):1-4.

7. Tollenaere MAX, Mølck C, Henderson I, et al. Tralokinumab effectively disrupts the IL-13/IL-13Rα1/IL-4Rα signaling complex but not the IL-13/IL-13Rα2 complex. JID Innov. 2023;3(5):100214. https://doi.org/10.1016/j.xjidi.2023.100214

8. Center for Drug Evaluation and Research. Application number: 761180Orig1s000 labeling. U.S. Food and Drug Administration. Accessed August 18, 2025. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2022/761180Orig1s000lbl.pdf

9. Sedeh FB, Henning MAS, Jemec GBE, Ibler KS. Comparative efficacy and safety of monoclonal antibodies and Janus kinase inhibitors in moderate-to-severe atopic dermatitis: a systematic review and meta-analysis. Acta Derm Venereol. 2022;102:adv00764. https://doi.org/10.2340/actadv.v102.2075

10. Paller AS, Silverberg JI, Cork MJ, et al. Efficacy and safety of dupilumab in patients with erythrodermic atopic dermatitis: a post hoc analysis of 6 randomized clinical trials. JAMA Dermatol. 2023;159(3):255-266. https://doi.org/10.1001/jamadermatol.2022.6192

11. 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(5):1339-1347. https://doi.org/10.1016/j.jaad.2021.01.012

12. Simpson EL, Merola JF, Silverberg JI, et al. Safety of tralokinumab in adult patients with moderate-to-severe atopic dermatitis: pooled analysis of five randomized, double-blind, placebo-controlled phase II and phase III trials. Br J Dermatol. 2022;187(6):888-899. https://doi.org/10.1111/bjd.21867

13. de Wijs LEM, Nguyen NT, Kunkeler ACM, et al. Clinical and histopathological characterization of paradoxical head and neck erythema in patients with atopic dermatitis treated with dupilumab: a case series. Br J Dermatol. 2020;183(4):745-749. https://doi.org/10.1111/bjd.18730

14. Dalia Y, Johnson SM. First reported case of facial rash after dupilumab therapy. Pract Dermatol. 2018;Apr:25-26.

15. García-González S, Villagrasa-Boli P, Bularca E, et al. Tralokinumab-related facial redness: a therapeutic challenge. Int J Dermatol. 2024;63(11):1605-1606. https://doi.org/10.1111/ijd.17231

16. Liane JG, Morgado-Carrasco D. Dupilumab-associated facial erythema successfully treated with oral ivermectin. Dermatol Pract Concept. 2022;12(4):e2022184. https://doi.org/10.5826/dpc.1204a184

17. Xu J, Shih J, Kalangara M. Delayed onset localized urticarial reactions to dupilumab. J Allergy Clin Immunol. 2021;147(2):AB12.

18. Pacheco CS, White KM. Delayed hyperpigmented injection site reactions due to chronic dupilumab use. Cureus. 2023;15(4):e37441. https://doi.org/10.7759/cureus.37441

Evan Hicks

• Medical student
• University of Arkansas for Medical Sciences
  Little Rock, AR

Sandra Marchese Johnson, MD

• Dermatologist, Johnson Dermatology
  Fort Smith, AR