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• W3140175551 abstract "To the Editor: Dupilumab facial redness (DFR) is a recently described adverse event of dupilumab use.1Waldman R.A. DeWane M.E. Sloan B. Grant-Kels J.M. Characterizing dupilumab facial redness: a multi-institution retrospective medical record review.J Am Acad Dermatol. 2020; 82: 230-232Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar Prior cases of its treatment with itraconazole have been reported.2Jaros J. Hendricks A.J. Shi V.Y. Lio P.A. A practical approach to recalcitrant face and neck dermatitis in atopic dermatitis.Dermatitis. 2020; 31: 169-177Crossref PubMed Scopus (13) Google Scholar In this retrospective study, we investigated the management of DFR using itraconazole or fluconazole. This study was approved by the Tufts Medical Center Institutional Review Board. Patients at Tufts Medical Center's Department of Dermatology who were on dupilumab for at least 16 weeks, were diagnosed with DFR, and had completed a course of at least 2 weeks of daily fluconazole or itraconazole (200 mg) were included. The data of an investigator global assessment before and after azole use, dupilumab-associated ocular surface disease (DOSD), and self-reported improvement (%), obtained from a routine phone call with a pharmacist 2 weeks after azole initiation, were recorded. DOSD was characterized by irritation, dryness, tearing, or conjunctivitis. Out of 413 patients prescribed dupilumab, 22 (5.3%) patients were diagnosed with DFR, with 8 (36%) also diagnosed with DOSD (Table I). The average time between the initiation of dupilumab and the onset of DFR was 8.5 months (range, 1-27 months). Fifteen patients completed a course of itraconazole, 3 of fluconazole, and 1 of fluconazole followed by itraconazole. All patients reviewed had completed at least a 2-week course of azoles.Table IDemographic information of patients reporting DFR, summary of dupilumab use, and summary of azole treatmentDemographicsItraconazolen = 16∗The patient who took both itraconazole and fluconazole was analyzed in both the itraconazole and fluconazole subgroups but was counted only once in the overall analysis.; n (%)Fluconazolen = 4∗The patient who took both itraconazole and fluconazole was analyzed in both the itraconazole and fluconazole subgroups but was counted only once in the overall analysis.; n (%)Overalln = 19∗The patient who took both itraconazole and fluconazole was analyzed in both the itraconazole and fluconazole subgroups but was counted only once in the overall analysis.; n (%)Sex Male11 (69%)2 (50%)12 (63%)Race White10 (63%)3 (75%)12 (63%) Black3 (19%)0 (0%)3 (16%) Asian3 (19%)1 (25%)4 (21%)Average age (years)334335.5Dosing frequency Every other week14 (88%)3 (75%)17 (89%) Weekly2 (13%)1 (25%)2 (11%)Dupilumab ocular surface disease6 (38%)3 (75%)8 (42%)Average time to onset between dupilumab initiation and DFR (months)8.98.38.5Number of patch tests performed before and after the diagnosis of DFR4 (25%), 1 (6%)0 (0%), 1 (25%)4 (21%), 2 (11%)Treatments tried after the diagnosis of DFR Topical steroid3 (19%)2 (50%)5 (26%) Topical calcineurin inhibitor8 (50%)1 (25%)8 (42%) Topical PDE-4 inhibitor2 (13%)1 (25%)2 (11%) Topical antibiotic1 (6%)2 (50%)2 (11%) Oral antibiotic2 (13%)0 (0%)2 (11%)DFR, Dupilumab facial redness; PDE-4, phosphodiesterase-4.∗ The patient who took both itraconazole and fluconazole was analyzed in both the itraconazole and fluconazole subgroups but was counted only once in the overall analysis. Open table in a new tab DFR, Dupilumab facial redness; PDE-4, phosphodiesterase-4. Of the patients treated with itraconazole, 11/16 (69%) had a post-treatment investigator global assessment result of clear or almost clear (0 or 1) 1-6 months later (Table II). The average self-reported improvement was 52%. Of the 4 patients treated with fluconazole, none (0%) had an investigator global assessment result of clear or almost clear, and the self-reported improvement was 0%. Of particular note is that the patient who utilized fluconazole followed by itraconazole did not improve with fluconazole but did improve with itraconazole. Four (80%) of 5 nonresponders to itraconazole failed to take at least 30 days of medication. Five (45%) of 11 responders to itraconazole remained on once-weekly dosing, and an additional 2 (18%) of 11 received further courses of daily itraconazole.Table IIClinical outcomes of patients with DFR treated with itraconazole or fluconazoleClinical outcomesItraconazolen = 16∗In the patient treated with both itraconazole and fluconazole, outcomes were analyzed separately for the itraconazole and fluconazole analyses.Fluconazolen = 4∗In the patient treated with both itraconazole and fluconazole, outcomes were analyzed separately for the itraconazole and fluconazole analyses.Self-reported improvement (%)52%0%IGA = 0 or 1 after treatment course, n (%)11 (69%)0 (0%)IGA, Investigator global assessment.∗ In the patient treated with both itraconazole and fluconazole, outcomes were analyzed separately for the itraconazole and fluconazole analyses. Open table in a new tab IGA, Investigator global assessment. Itraconazole did not improve DOSD in any of the patients. The average age, sex, and time of onset of DFR were not statistically significant between the responders and nonresponders. Although DFR has been reported in the literature as a fairly common adverse event, occurring in 10% of patients using dupilumab, a smaller number of patients with DFR were assessed in our cohort.1Waldman R.A. DeWane M.E. Sloan B. Grant-Kels J.M. Characterizing dupilumab facial redness: a multi-institution retrospective medical record review.J Am Acad Dermatol. 2020; 82: 230-232Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar The other etiologies of facial dermatitis in atopic dermatitis include allergic contact dermatitis, rosacea, and periorificial dermatitis.2Jaros J. Hendricks A.J. Shi V.Y. Lio P.A. A practical approach to recalcitrant face and neck dermatitis in atopic dermatitis.Dermatitis. 2020; 31: 169-177Crossref PubMed Scopus (13) Google Scholar The treatment mechanism of azoles for DFR is unknown. The benefit from itraconazole may be due to its anti-inflammatory effects, such as IL-8 inhibition and proinflammatory metabolite production.3V'lckova-Laskoska M.T. Caca-Biljanovska N.G. Laskoski D.S. Kamberova S.J. Palmoplantar pustulosis treated with itraconazole: a single, active-arm pilot study.Dermatol Ther. 2009; 22: 85-89Crossref PubMed Scopus (20) Google Scholar It has been noted that itraconazole has a greater anti-inflammatory activity than fluconazole, which may make it a superior option if that is the pertinent mechanism of action for efficacy.4Steel H.C. Tintinger G.R. Anderson R. Comparison of the anti-inflammatory activities of imidazole antimycotics in relation to molecular structure.Chem Biol Drug Des. 2008; 72: 225-228Crossref PubMed Scopus (30) Google Scholar Additionally, the lipophilicity of Malassezia and itraconazole may explain the role of itraconazole in DFR treatment.2Jaros J. Hendricks A.J. Shi V.Y. Lio P.A. A practical approach to recalcitrant face and neck dermatitis in atopic dermatitis.Dermatitis. 2020; 31: 169-177Crossref PubMed Scopus (13) Google Scholar,5Kaffenberger B.H. Mathis J. Zirwas M.J. A retrospective descriptive study of oral azole antifungal agents in patients with patch test-negative head and neck predominant atopic dermatitis.J Am Acad Dermatol. 2014; 71: 480-483Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar The study's limitations include its retrospective nature, small number of patients, and subjective reporting of improvement by the patients. DFR incidence may have been underestimated because of under-reporting. Larger, multi-institutional studies are needed to characterize the true efficacy of itraconazole and/or fluconazole in treating DFR. Dr Rosmarin has received honoraria as a consultant for AbbVie, Boehringer-Ingelheim, Bristol Meyers Squibb, Celgene, Concert, Dermavant, Dermira, Incyte, Janssen, Kyowa Kirin, Lilly, Novartis, Pfizer, Regeneron, Sanofi, Sun Pharmaceuticals, UCB, and VielaBio; received research support from AbbVie , Amgen , Bristol Meyers Squibb, Celgene , Dermira , Galderma , Incyte, Janssen, Lilly , Merck , Novartis , Pfizer , and Regeneron Pharmaceuticals Inc; and served as a paid speaker for AbbVie , Amgen , Celgene , Janssen, Lilly , Novartis , Pfizer , Regeneron Pharmaceuticals Inc, and Sanofi . Authors Gao, Song, Kahn, and Dumont and Drs Cohen and Fiumara have no conflicts of interest to declare." @default.
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• W3140175551 title "Treatment of patients experiencing dupilumab facial redness with itraconazole and fluconazole: A single-institutional, retrospective medical record review" @default.
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