Clinical Challenge: Facial Erythema

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A 64-year-old woman with atopic dermatitis (AD) presents for evaluation and treatment of a rash on her face. The patient’s AD has been managed for decades with topical therapies, phototherapy, and intermittent courses of oral and intramuscular steroids. Her medical history is significant for osteopenia, which was diagnosed by DXA scan; when osteopenia was detected, oral cyclosporine was commenced. This therapy required downward titration due to the development of hypertension. In 2017, she was prescribed dupilumab and experienced marked clearing of AD along with greatly diminished pruritus.

Atopic dermatitis is a chronic inflammatory disorder characterized by marked pruritus, erythema, excoriation, and lichenification. The disorder affects up to 25% of children and approximately 2% to 3% of adults.1 The incidence of AD has been increasing over the past decade.2 Atopic...

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Atopic dermatitis is a chronic inflammatory disorder characterized by marked pruritus, erythema, excoriation, and lichenification. The disorder affects up to 25% of children and approximately 2% to 3% of adults.1 The incidence of AD has been increasing over the past decade.2 Atopic dermatitis has a negative impact on patient’s quality of life and comorbidities include depression and anxiety.3

The cause of AD is not completely understood and involves a complex interrelation between environmental factors, skin barrier disruption, genetic predisposition, and immunologic dysregulation. Type 2 cytokines that are increased in AD include interleukin (IL)-4, IL-13, and IL-31.4

Dupilumab, a fully human monoclonal antibody that inhibits IL-4 and IL-13, revolutionized the therapy of AD as the first biologic agent to target this condition.5 In phase 3 clinical studies of dupilumab, conjunctivitis and injection-site reactions were identified as more frequent in the dupilumab group than in the placebo group.6 After approval of this agent, facial erythema was identified as an adverse event in a minority of patients.7 The prescribing information for dupilumab notes hypersensitivity reactions, including urticaria, rash, and erythema nodosum.

The etiology of this rash is unclear. Researchers have postulated that the cause of the rash may be related to proliferation of Demodex folliculorum (mites) and allergic contact dermatitis.8

Stephen Schleicher, MD, is director of the DermDox Center for Dermatology in Pennsylvania, as well as associate professor of medicine at Commonwealth Medical College and clinical instructor of dermatology at Arcadia University and Kings College.   

References

1. Eichenfield LF, Tom WL, Chamlin SL, et al. Guidelines of care for the management of atopic dermatitis: section 1. Diagnosis and assessment of atopic dermatitisJ Am Acad Dermatol. 2014;70(2):338-351. doi:10.1016/j.jaad.2013.10.010

2. Williams H, Stewart A, von Mutius E, et al. Is eczema really on the increase worldwide? J Allergy Clin Immunol. 2008;121(4):947-54.e15. doi:10.1016/j.jaci.2007.11.004

3. Cheng BT, Silverberg JI. Depression and psychological distress in US adults with atopic dermatitisAnn Allergy Asthma Immunol. 2019;123(2):179-185. doi:10.1016/j.anai.2019.06.002

4. Kim J, Kim BE, Leung DYM. Pathophysiology of atopic dermatitis: clinical implicationsAllergy Asthma Proc. 2019;40(2):84-92. doi:10.2500/aap.2019.40.4202

5. D’Erme AM, Romanelli M, Chiricozzi A. Spotlight on dupilumab in the treatment of atopic dermatitis: design, development, and potential place in therapyDrug Des Devel Ther. 2017;11:1473-1480. doi:10.2147/DDDT.S113192

6. Simpson EL, Bieber T, Guttman-Yassky E, et al. Two phase 3 trials of dupilumab versus placebo in atopic dermatitisN Engl J Med. 2016;375(24):2335-2348. doi:10.1056/NEJMoa1610020

7. Waldman RA, DeWane ME, Sloan B, Grant-Kels JM. Characterizing dupilumab facial redness: a multi-institution retrospective medical record reviewJ Am Acad Dermatol. 2020;82(1): 230-232. doi:10.1016/j.jaad.2019.06.02

8. Jo CE. Finstad A, Georgakopoulos JR, Piguet V, Yeung J, Drucker AM. Facial and neck erythema associated with dupilumab treatment: a systematic review. J Am Acad Dermatol. 2021;84(5):1339-1347. doi:10.1016/j.jaad.2021.01.012