of ceramide elongation, directly promoting skin barrier function. Studies have shown that prolonged remission of AD after the cessation of dupilumab is possible.28,29 After proper restoration of the skin's epidermal barrier and normalization of the microbiome found on the skin surface, patients treated with dupilumab have visible skin clearance at week 16 with sustained results after one year.1 For individuals who decide to stop the medication completely, their AD comes back more slowly compared with traditional systemic medications.28 We hypothesize that the relatively prolonged remissions reported after dupilumab discontinuation are due to the time it takes for the filaggrin and ceramides to be metabolized away and for the microbiome to return to being Staph dominant after antimicrobial peptide production declines.
5. The IL-4 Overproduction Associated With Atopic Dermatitis is Protective Against Psoriasis, Inflammatory Arthritis and Seborrheic Dermatitis
There have been numerous cases of new onset psoriasis, inflammatory arthritis, or seborrheic dermatitis (Ps, IA, SD) in patients treated with dupilumab.30-32 All of these effects are hypothesized to be triggered by the elimination of IL-4 induced inhibition of the Th1 and Th17 pathways. Thus, in individuals who are predisposed to a Th1 or Th17 skin or joint disease, the IL-4 over-expression induced by AD was protective against expression of that predisposition.
5. The IL-4 Overproduction Associated With Atopic Dermatitis is Protective Against Psoriasis, Inflammatory Arthritis and Seborrheic Dermatitis
There have been numerous cases of new onset psoriasis, inflammatory arthritis, or seborrheic dermatitis (Ps, IA, SD) in patients treated with dupilumab.30-32 All of these effects are hypothesized to be triggered by the elimination of IL-4 induced inhibition of the Th1 and Th17 pathways. Thus, in individuals who are predisposed to a Th1 or Th17 skin or joint disease, the IL-4 over-expression induced by AD was protective against expression of that predisposition.
DISCLOSURES
Dr. Zirwas has received compensation from the following companies for speaking, consulting, and/or being an investigator: Abbvie, All Free Clear / Sun, Amgen, Anaptys Bio, Arcutis, AsepticMD, Biocon, Cara, Concert, Dermavant, Edessa Biotech, EPI Health, Evelo, Fit Bit, Galderma, Genench / Novartis, Incyte, L'Oreal, Leo, Level-Ex, Lilly, LUUM, Oculus, Peloton, Pfizer, Regeneron / Sanofi, Trevi, UCB, Vial
REFERENCES
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2. Nusbaum KB, Kaffenberger BH, Paradiso Bs MM, et al. Dupilumab for treatment of atopic dermatitis in patients living with HIV: a case series. Int J Dermatol. 2021;60(9):e344-e346. doi:10.1111/ijd.15471.
3. Alawadhi A, Karibayeva D, Gottlieb AB. Dupilumab in HIV-positive patients: A case series report of 4 patients. JAAD Case Rep. 2020;6(12):1356-1359. doi:10.1016/j.jdcr.2020.09.023.
4. Mollanazar NK, Qiu CC, Aldrich JL, et al. Use of dupilumab in patients who are HIV-positive: report of four cases. Br J Dermatol. 2019;181(6):1311-1312. doi:10.1111/bjd.18222.
5. Jin A, Pousti BT, Savage KT, Mollanazar NK, Lee JB, Hsu S. Eosinophilic dermatosis of hematologic malignancy responding to dupilumab in a patient with chronic lymphocytic leukemia. JAAD Case Rep. 2019;5(9):815-817. doi:10.1016/j.jdcr.2019.07.026.
6. Goyal A, Lofgreen S, Mariash E, Bershow A, Gaddis KJ. Targeted inhibition of IL-4/13 with dupilumab is an effective treatment for eosinophilic dermatosis of hematologic malignancy. Dermatol Ther. 2020;33(4):e13725. doi:10.1111/dth.13725.
7. Fowler E, Rosen J, Lev-Tov H, Yosipovitch G. Two cancer patients receiving dupilumab for treatment of atopic dermatitis. Acta Derm Venereol. 2019;99(10):899-900. doi:10.2340/00015555-3201.
8. Braddock M, Hanania NA, Sharafkhaneh A, Colice G, Carlsson M. Potential risks related to modulating interleukin-13 and interleukin-4 signalling: a systematic review. Drug Saf. 2018;41(5):489-509. doi:10.1007/s40264-017-0636-9.
9. Storan ER, Woolf RT, Smith CH, Pink AE. Clearance of molluscum contagiosum virus infection in patients with atopic eczema treated with dupilumab. Br J Dermatol. 2019;181(2):385-386. doi:10.1111/bjd.17712.
10. Di Lernia V, Casanova DM, Simonetti V. Dupilumab may facilitate the clearance of molluscum contagiosum in atopic dermatitis patients. J Dtsch Dermatol Ges. 2020;18(9):1016-1018. doi:10.1111/ddg.14257.
11. Kawano N, Shiratori T, Kawada A. Case of molluscum contagiosum of an aged female in association with the use of upadacitinib. J Dermatol. 2022;49(5):e171-e172. doi:10.1111/1346- 8138.16307.
12. Ferrucci S, Tavecchio S, Veraldi S, Berti E, Benzecry V. Transitory Dissemination of molluscum contagiosum in a patient treated with dupilumab for atopic dermatitis. Acta Derm Venereol. 2020;100(14):adv00207. doi:10.2340/00015555-3565.
13. Narla S, Silverberg JI. Association between atopic dermatitis and serious cutaneous, multiorgan, and systemic infections in US adults. Ann Allergy Asthma Immunol. 2018;120(1):66-72.e11. doi:10.1016/j.anai.2017.10.019.
14. Fleming P, Drucker AM. Risk of infection in patients with atopic dermatitis treated with dupilumab: A meta-analysis of randomized controlled trials. J Am Acad Dermatol. 2018;78(1):62-69.e1. doi:10.1016/j.jaad.2017.09.052.
15. Droitcourt C, Vittrup I, Kerbrat S, Egeberg A, Thyssen JP. Risk of systemic infections in adults with atopic dermatitis: A nationwide cohort study. J Am Acad Dermatol. 2021;84(2):290-299. doi:10.1016/j.jaad.2020.07.111.
16. Aliyu S, Cohen B, Liu J, Larson E. Prevalence and risk factors for bloodstream infection present on hospital admission. J Infect Prev. 2018;19(1):37-42. doi:10.1177/1757177417720998.
17. Callewaert C, Nakatsuji T, Knight R, et al. IL-4Rα Blockade by dupilumab decreases staphylococcus aureus colonization and increases microbial diversity in atopic dermatitis. J Invest Dermatol. 2020;140(1):191-202.e7. doi:10.1016/j.jid.2019.05.024.
18. Olesen CM, Ingham AC, Thomsen SF, et al. Changes in skin and nasal microbiome and staphylococcal species following treatment of atopic dermatitis with dupilumab. Microorganisms. 2021;9(7):1487. doi:10.3390/microorganisms9071487.
19. Lee SJ, Kim SE, Shin KO, Park K, Lee SE. Dupilumab Therapy Improves Stratum Corneum Hydration and Skin Dysbiosis in Patients With Atopic Dermatitis. Allergy Asthma Immunol Res. 2021;13(5):762-775. doi:10.4168/aair.2021.13.5.762.
20. Ou Z, Chen C, Chen A, Yang Y, Zhou W. Adverse events of Dupilumab in adults with moderate-to-severe atopic dermatitis: A meta-analysis. Int Immunopharmacol. 2018;54:303- 310. doi:10.1016/j.intimp.2017.11.031.
21. Oetjen LK, Mack MR, Feng J, et al. Sensory neurons co-opt classical immune signaling pathways to mediate chronic itch. Cell. 2017;171(1):217-228.e13. doi:10.1016/j. cell.2017.08.006.
22. Hashimoto T, Okuno S, Okuzawa M, Satoh T. Dupilumab improves both histaminergic and touch-evoked itch sensitization (hyperkinesis) in atopic dermatitis: a pilot study. J Eur Acad Dermatol Venereol. 2022;36(11):e911-e912. doi:10.1111/jdv.18356.
23. Stanger R, Rivera-Oyola R, Lebwohl M. Dupilumab as a treatment for generalized idiopathic pruritus: a report of two cases. Br J Dermatol. 2020;182(6):1494-1495. doi:10.1111/bjd.18852.
24. Danso M, Boiten W, van Drongelen V, et al. Altered expression of epidermal lipid biosynthesis enzymes in atopic dermatitis skin is accompanied by changes in stratum corneum lipid composition. J Dermatol Sci. 2017;88(1):57-66. doi:10.1016/j.jdermsci.2017.05.005.
25. van Smeden J, Janssens M, Kaye EC, et al. The importance of free fatty acid chain length for the skin barrier function in atopic eczema patients. Exp Dermatol. 2014;23(1):45-52. doi:10.1111/exd.12293.
26. Berdyshev E, Goleva E, Bronova I, et al. Lipid abnormalities in atopic skin are driven by type 2 cytokines. JCI Insight. 2018;3(4):e98006. doi:10.1172/jci.insight.98006\.
27. Berdyshev E, Goleva E, Bronova I, et al. Lipid abnormalities in atopic skin are driven by type 2 cytokines. JCI Insight. 2018;3(4):e98006. doi:10.1172/jci.insight.98006.
28. Treister AD, Lio PA. Remittive effect of Dupilumab in atopic dermatitis. Dermatol Ther. 2018;31(6):e12711. doi:10.1111/dth.12711.
29. Worm M, Simpson EL, Thaçi D, et al. Efficacy and safety of multiple dupilumab dose regimens after initial successful treatment in patients with atopic dermatitis: a randomized clinical trial. JAMA Dermatol. 2020;156(2):131–143. doi:10.1001/jamadermatol.2019.3617
30. Tracey EH, Elston C, Feasel P, Piliang M, Michael M, Vij A. Erythrodermic presentation of psoriasis in a patient treated with dupilumab. JAAD Case Rep. 2018;4(7):708-710. Published 2018 Aug 15. doi:10.1016/j.jdcr.2018.05.014.
31. Fowler E, Silverberg JI, Fox JD, Yosipovitch G. Psoriasiform dermatitis after initiation of treatment with dupilumab for atopic dermatitis. Dermatitis. 2019;30(3):234-236. doi:10.1097/ DER.0000000000000481.
32. Brumfiel CM, Patel MH, Zirwas MJ. Development of psoriasis during treatment with dupilumab: A systematic review. J Am Acad Dermatol. 2022;86(3):708-709. doi:10.1016/j. jaad.2021.05.013.
2. Nusbaum KB, Kaffenberger BH, Paradiso Bs MM, et al. Dupilumab for treatment of atopic dermatitis in patients living with HIV: a case series. Int J Dermatol. 2021;60(9):e344-e346. doi:10.1111/ijd.15471.
3. Alawadhi A, Karibayeva D, Gottlieb AB. Dupilumab in HIV-positive patients: A case series report of 4 patients. JAAD Case Rep. 2020;6(12):1356-1359. doi:10.1016/j.jdcr.2020.09.023.
4. Mollanazar NK, Qiu CC, Aldrich JL, et al. Use of dupilumab in patients who are HIV-positive: report of four cases. Br J Dermatol. 2019;181(6):1311-1312. doi:10.1111/bjd.18222.
5. Jin A, Pousti BT, Savage KT, Mollanazar NK, Lee JB, Hsu S. Eosinophilic dermatosis of hematologic malignancy responding to dupilumab in a patient with chronic lymphocytic leukemia. JAAD Case Rep. 2019;5(9):815-817. doi:10.1016/j.jdcr.2019.07.026.
6. Goyal A, Lofgreen S, Mariash E, Bershow A, Gaddis KJ. Targeted inhibition of IL-4/13 with dupilumab is an effective treatment for eosinophilic dermatosis of hematologic malignancy. Dermatol Ther. 2020;33(4):e13725. doi:10.1111/dth.13725.
7. Fowler E, Rosen J, Lev-Tov H, Yosipovitch G. Two cancer patients receiving dupilumab for treatment of atopic dermatitis. Acta Derm Venereol. 2019;99(10):899-900. doi:10.2340/00015555-3201.
8. Braddock M, Hanania NA, Sharafkhaneh A, Colice G, Carlsson M. Potential risks related to modulating interleukin-13 and interleukin-4 signalling: a systematic review. Drug Saf. 2018;41(5):489-509. doi:10.1007/s40264-017-0636-9.
9. Storan ER, Woolf RT, Smith CH, Pink AE. Clearance of molluscum contagiosum virus infection in patients with atopic eczema treated with dupilumab. Br J Dermatol. 2019;181(2):385-386. doi:10.1111/bjd.17712.
10. Di Lernia V, Casanova DM, Simonetti V. Dupilumab may facilitate the clearance of molluscum contagiosum in atopic dermatitis patients. J Dtsch Dermatol Ges. 2020;18(9):1016-1018. doi:10.1111/ddg.14257.
11. Kawano N, Shiratori T, Kawada A. Case of molluscum contagiosum of an aged female in association with the use of upadacitinib. J Dermatol. 2022;49(5):e171-e172. doi:10.1111/1346- 8138.16307.
12. Ferrucci S, Tavecchio S, Veraldi S, Berti E, Benzecry V. Transitory Dissemination of molluscum contagiosum in a patient treated with dupilumab for atopic dermatitis. Acta Derm Venereol. 2020;100(14):adv00207. doi:10.2340/00015555-3565.
13. Narla S, Silverberg JI. Association between atopic dermatitis and serious cutaneous, multiorgan, and systemic infections in US adults. Ann Allergy Asthma Immunol. 2018;120(1):66-72.e11. doi:10.1016/j.anai.2017.10.019.
14. Fleming P, Drucker AM. Risk of infection in patients with atopic dermatitis treated with dupilumab: A meta-analysis of randomized controlled trials. J Am Acad Dermatol. 2018;78(1):62-69.e1. doi:10.1016/j.jaad.2017.09.052.
15. Droitcourt C, Vittrup I, Kerbrat S, Egeberg A, Thyssen JP. Risk of systemic infections in adults with atopic dermatitis: A nationwide cohort study. J Am Acad Dermatol. 2021;84(2):290-299. doi:10.1016/j.jaad.2020.07.111.
16. Aliyu S, Cohen B, Liu J, Larson E. Prevalence and risk factors for bloodstream infection present on hospital admission. J Infect Prev. 2018;19(1):37-42. doi:10.1177/1757177417720998.
17. Callewaert C, Nakatsuji T, Knight R, et al. IL-4Rα Blockade by dupilumab decreases staphylococcus aureus colonization and increases microbial diversity in atopic dermatitis. J Invest Dermatol. 2020;140(1):191-202.e7. doi:10.1016/j.jid.2019.05.024.
18. Olesen CM, Ingham AC, Thomsen SF, et al. Changes in skin and nasal microbiome and staphylococcal species following treatment of atopic dermatitis with dupilumab. Microorganisms. 2021;9(7):1487. doi:10.3390/microorganisms9071487.
19. Lee SJ, Kim SE, Shin KO, Park K, Lee SE. Dupilumab Therapy Improves Stratum Corneum Hydration and Skin Dysbiosis in Patients With Atopic Dermatitis. Allergy Asthma Immunol Res. 2021;13(5):762-775. doi:10.4168/aair.2021.13.5.762.
20. Ou Z, Chen C, Chen A, Yang Y, Zhou W. Adverse events of Dupilumab in adults with moderate-to-severe atopic dermatitis: A meta-analysis. Int Immunopharmacol. 2018;54:303- 310. doi:10.1016/j.intimp.2017.11.031.
21. Oetjen LK, Mack MR, Feng J, et al. Sensory neurons co-opt classical immune signaling pathways to mediate chronic itch. Cell. 2017;171(1):217-228.e13. doi:10.1016/j. cell.2017.08.006.
22. Hashimoto T, Okuno S, Okuzawa M, Satoh T. Dupilumab improves both histaminergic and touch-evoked itch sensitization (hyperkinesis) in atopic dermatitis: a pilot study. J Eur Acad Dermatol Venereol. 2022;36(11):e911-e912. doi:10.1111/jdv.18356.
23. Stanger R, Rivera-Oyola R, Lebwohl M. Dupilumab as a treatment for generalized idiopathic pruritus: a report of two cases. Br J Dermatol. 2020;182(6):1494-1495. doi:10.1111/bjd.18852.
24. Danso M, Boiten W, van Drongelen V, et al. Altered expression of epidermal lipid biosynthesis enzymes in atopic dermatitis skin is accompanied by changes in stratum corneum lipid composition. J Dermatol Sci. 2017;88(1):57-66. doi:10.1016/j.jdermsci.2017.05.005.
25. van Smeden J, Janssens M, Kaye EC, et al. The importance of free fatty acid chain length for the skin barrier function in atopic eczema patients. Exp Dermatol. 2014;23(1):45-52. doi:10.1111/exd.12293.
26. Berdyshev E, Goleva E, Bronova I, et al. Lipid abnormalities in atopic skin are driven by type 2 cytokines. JCI Insight. 2018;3(4):e98006. doi:10.1172/jci.insight.98006\.
27. Berdyshev E, Goleva E, Bronova I, et al. Lipid abnormalities in atopic skin are driven by type 2 cytokines. JCI Insight. 2018;3(4):e98006. doi:10.1172/jci.insight.98006.
28. Treister AD, Lio PA. Remittive effect of Dupilumab in atopic dermatitis. Dermatol Ther. 2018;31(6):e12711. doi:10.1111/dth.12711.
29. Worm M, Simpson EL, Thaçi D, et al. Efficacy and safety of multiple dupilumab dose regimens after initial successful treatment in patients with atopic dermatitis: a randomized clinical trial. JAMA Dermatol. 2020;156(2):131–143. doi:10.1001/jamadermatol.2019.3617
30. Tracey EH, Elston C, Feasel P, Piliang M, Michael M, Vij A. Erythrodermic presentation of psoriasis in a patient treated with dupilumab. JAAD Case Rep. 2018;4(7):708-710. Published 2018 Aug 15. doi:10.1016/j.jdcr.2018.05.014.
31. Fowler E, Silverberg JI, Fox JD, Yosipovitch G. Psoriasiform dermatitis after initiation of treatment with dupilumab for atopic dermatitis. Dermatitis. 2019;30(3):234-236. doi:10.1097/ DER.0000000000000481.
32. Brumfiel CM, Patel MH, Zirwas MJ. Development of psoriasis during treatment with dupilumab: A systematic review. J Am Acad Dermatol. 2022;86(3):708-709. doi:10.1016/j. jaad.2021.05.013.
