10.5826/dpc.1204a184
text/xml
2160-9381
2229
en
Daniel Morgado-Carrasco
https://creativecommons.org/licenses/by-nc/4.0
Dermatology Practical & Conceptual
ivermectin
Dupilumab-associated facial erythema successfully treated with oral ivermectin
Text.Serial.Journal
https://dpcj.org/index.php/dpc
Research Letter
2022-10-31
2021-12-08
2022-10-31
2022-12-02
e2022184
Dermatol Pract Concept
Daniel Morgado-Carrasco
2022/10/31
10.5826/dpc.1204a184
e2022184
Dermatology Department, Hospital Clínic de Barcelona, Universitat de Barcelona, Spain
2160-9381
ivermectin
en
e2022184
Gao DX, Song S, Kahn JS, et al. Treatment of patients experiencing dupilumab facial redness with itraconazole and fluconazole: A single-institutional, retrospective medical record review. J Am Acad Dermatol 2021; :S0190-9622(21)00627-7.
Dupilumab-associated facial erythema successfully treated with oral ivermectin
https://dpcj.org/index.php/dpc/article/download/2229/1782
Dupilumab-associated Facial Erythema Successfully
          Treated With Oral Ivermectin
                                    Javier Gil Liane1, Daniel Morgado-Carrasco1


1 Department of Dermatology, University of Barcelona, Hospital Clinic Barcelona, Spain



Key words: dupilumab, facial dermatitis, atopic dermatitis, ivermectin
Citation: Gil-Lianes J, Morgado-Carrasco D. Dupilumab-associated facial erythema successfully treated with oral ivermectin. Dermatol
Pract Concept. 2022;12(4):e2022184. DOI: https://doi.org/10.5826/dpc.1204a184
Accepted: January 19, 2022; Published: October 2022
Copyright: ©2022 Gil-Lianes et al. This is an open-access article distributed under the terms of the Creative Commons Attribution-
NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use,
distribution, and reproduction in any medium, provided the original authors and source are credited.
Funding: None.
Competing interests: None.
Authorship: All authors have contributed significantly to this publication.
Corresponding author: Daniel Morgado-Carrasco, MD, Dermatology Department, Hospital Clínic de Barcelona, Barcelona. C/ Villarroel,
170, 08036 Barcelona, Spain. Phone: (+34) 93 227 54 00, Fax: (+34) 932275438, E-mail: morgadodaniel8@gmail.com




Introduction                                                             corticosteroids or tacrolimus with local adverse e­ ffects (AE),
                                                                         nor to oral itraconazole and topical ketoconazole. Since small
Dupilumab, a monoclonal antibody which inhibits IL-4 and                 pustules were present on dermoscopy, dupilumab-associated
IL-13 signaling, has revolutionized atopic dermatitis (AD)               rosacea was suspected. To avoid local AE, a single dose of
treatment. Dupilumab-associated facial erythema (DFE) has                oral ivermectin 200 mcg/kg (12 mg) was prescribed. The
been described in 10% of patients and can lead to dupilumab              patient presented a complete resolution of facial erythema
discontinuation [1]. Etiology remains unclear and treatment              in 3 weeks, which has been maintained after 14 months of
is challenging [1-3]. Here we present a patient with DFE suc-            follow-up (Figure 2).
cessfully treated with oral ivermectin.

                                                                         Conclusions
Case Presentation
                                                                         Face and neck dermatitis (FND) in atopic dermatitis is a di-
A 20-year-old woman with severe AD, refractory to cyc-                   agnostic challenge in which dupilumab adds a new grade of
losporine, started dupilumab. After 6 weeks, although AD                 complexity [2]. In a recent systematic review of 101 patients
lesions had resolved, she manifested itching and facial er-              with DFE, 45% of patients reported different cutaneous
ythema which were not previously present. On physical                    symptoms from preexisting atopic dermatitis [3]. Diverse
examination, scaly ill-defined erythematous plaques were                 etiologies for DFE have been proposed, including worsen-
observed on the forehead and cheeks. Dermoscopy showed                   ing of AD, allergic contact dermatitis (ACD), rosacea, top-
small pustules (Figure 1 A and B). DFE was diagnosed. No                 ical corticoids withdrawal (TCW), Malassezia furfur (MF)
patch tests were performed. There was no response to topical             hypersensitivity and alcohol-induced facial flushing [2-4].



Research Letter | Dermatol Pract Concept. 2022;12(4):e2022184                                                                          1
                Figure 1. Dupilumab-associated facial erythema. (A) New onset of scaly erythematous plaques on the
                forehead and cheeks, without affecting nasolabial folds or the palpebral region, 6 weeks after initiating
                dupilumab therapy. (B) Dermoscopy examination shows white scaling and a central pustule.




                                                                          Regarding DFE treatment, topical corticosteroids and
                                                                      calcineurin inhibitors are the most used, although with low
                                                                      response rates. However, management of DFE should start
                                                                      with a precise differential diagnosis, since ACD, rosacea,
                                                                      TCW and MF-dermatitis respond to different approaches
                                                                      [2, 5]. Thus, most treatment failures could be explained by
                                                                      DFE being erroneously thought of as a unique entity. Ev-
                                                                      idence on rosacea-like dermatitis treatment remains sparse
                                                                      [2]. Partial or complete response to acaricidal agents such as
                                                                      topical and oral metronidazole, topical ivermectin or doxy-
                                                                      cycline have been reported [2]. Topical ivermectin is a first-
                                                                      line therapy for papulopustular rosacea, although it requires
                                                                      prolonged treatment (up to 12 weeks). Oral ivermectin treat-
                                                                      ment for rosacea has been reported in isolated cases with
                                                                      satisfactory results. It has very low systemic AE (<1%) and
                                                                      two main advantages: single administration schedule and
                                                                      avoidance of local AE.
                                                                          In patients under treatment with dupilumab presenting
                                                                      with facial erythema, DFE should be considered. Rather
                                                                      than a unique entity, DFE should be considered as a com-
                                                                      pendium of differential diagnoses. If rosacea-like dermati-
                                                                      tis is suspected, oral ivermectin could represent a good and
                                                                      well-tolerated alternative.
Figure 2. Almost complete resolution after a single dose of oral
­ivermectin (200 mcg/kg).
                                                                      References
                                                                       1. Zhu GA, Chen JK, Chiou A, Ko J, Honari G. Assessment of the
In a retrospective study of 94 patients with dupilumab [4],               Development of New Regional Dermatoses in Patients Treated
6% presented rosacea-like folliculitis and increased demo-                for Atopic Dermatitis With Dupilumab. JAMA Dermatol.
dex count in reflectance confocal microscopy [1,4].                       2019;155(7):850-852. DOI: 10.1001/jamadermatol.2019.0109.
    Although DFE pathogenesis remains unclear, recent                     PMID: 31042259. PMCID: PMC6495362.
                                                                       2. Jaros J, Hendricks AJ, Shi VY, Lio PA. A Practical Approach
studies have hypothesized that IL-4 blockage shifts Th1/
                                                                          to Recalcitrant Face and Neck Dermatitis in Atopic Dermati-
Th2 balance towards Th1/Th17-mediated dermatoses [2].
                                                                          tis. Dermat Contact Atopic Occup Drug. 2020;31(3):169–717.
In rosacea, especially if papulopustular, the main factors are            DOI: 10.1097/DER.0000000000000590. PMID: 32355092.
induction of Demodex proliferation by Th2 blockade and                 3. Jo CE, Finstad A, Georgakopoulos JR, Piguet V, Yeung J,
Th17-infllamatory response [1].                                           Drucker AM. Facial and neck erythema associated with




2                                                                          Research Letter | Dermatol Pract Concept. 2022;12(4):e2022184
    dupilumab treatment: A systematic review. J Am Acad Derma-         5. Gao DX, Song S, Kahn JS, et al. Treatment of patients experienc-
    tol. 2021;84(5):1339-1347. DOI: 10.1016/j.jaad.2021.01.012.           ing dupilumab facial redness with itraconazole and fluconazole:
    PMID: 33428978.                                                       A single-institutional, retrospective medical record review.
 4. Okiyama N, Nakamura Y, Ishitsuka Y, et al. Successful topical         J Am Acad Dermatol. 2022;86(4):938-940. DOI: 10.1016/j.
    treatment with ketoconazole for facial rashes refractory to dup-      jaad.2021.03.070. PMID: 33775718.
    ilumab in patients with atopic dermatitis: case reports. J Eur
    Acad Dermatol Venereol. 2020;34(9):e474-e476. DOI: 10.1111/
    jdv.16383. PMID: 32215964.




Research Letter | Dermatol Pract Concept. 2022;12(4):e2022184                                                                           3
