When topical therapy of atopic dermatitis fails: a guide for the clinician

References

• Weidinger S, Beck LA, Bieber T, et al. Atopic dermatitis. Nat Rev Dis Primers. 2018 Jun 21;4(1):1.
   PubMed Web of Science ®Google Scholar
• Dawn A, Papoiu ADP, Chan YH, et al. Itch characteristics in atopic dermatitis: results of a web-based questionnaire. Br J Dermatol (1951). 2009;160(3):642–644.
   PubMed Web of Science ®Google Scholar
• Kamata Y, Tominaga M, Takamori K. Itch in atopic dermatitis management. Itch Manage Clin Pract. 2016;50:86–93.
   Google Scholar
• Nakahara T, Kido-Nakahara M, and Tsuji G, et al. Basics and recent advances in the pathophysiology of atopic dermatitis. J Dermatol. 2020 48 2 130–139 .
   PubMed Web of Science ®Google Scholar
• Mollanazar NK, Smith PK, Yosipovitch G. Mediators of chronic pruritus in atopic dermatitis: getting the itch out? Clin Rev Allergy Immunol. 2016 Dec;51(3):263–292.
   PubMed Web of Science ®Google Scholar
• Ingrasci G, Lipman ZM, Hawash AA, et al. The pruritogenic role of the type 2 immune response in diseases associated with chronic itch. Exp Dermatol. 2021 May 25;30(9):1208–1217.
   PubMed Web of Science ®Google Scholar
• Chopra R, Vakharia PP, Sacotte R, et al. Efficacy of bleach baths in reducing severity of atopic dermatitis: a systematic review and meta-analysis. Ann Allergy Asthma Immunol. 2017;119(5):435–440.
   PubMed Web of Science ®Google Scholar
• Brooks G, Idson B. Skin lipids. Int J Cosmet Sci. 1991;13(2):103–113.
   PubMed Web of Science ®Google Scholar
• Pavlis J, Yosipovitch G. Management of itch in atopic dermatitis. Am J Clin Dermatol. 2018;19(3):319–332.
   PubMed Web of Science ®Google Scholar
• Kaufmann R, Bieber T, Helgesen A, et al. Onset of pruritus relief with pimecrolimus cream 1% in adult patients with atopic dermatitis: a randomized trial. Allergy. 2006;61(3):375–381.
   PubMed Web of Science ®Google Scholar
• Nakagawa H, Nemoto O, Igarashi A, et al. Delgocitinib ointment, a topical Janus kinase inhibitor, in adult patients with moderate to severe atopic dermatitis: a phase 3, randomized, double-blind, vehicle-controlled study and an open-label, long-term extension study. J Am Acad Dermatol. 2020;82(4):823–831.
   PubMed Web of Science ®Google Scholar
• Tom WL, Van Syoc M, Chanda S, et al. Pharmacokinetic profile, safety, and tolerability of crisaborole topical ointment, 2% in adolescents with atopic dermatitis: an open‐label phase 2a study. Pediatr Dermatol. 2016;33(2):150–159.
   PubMed Web of Science ®Google Scholar
• Lee HG, Grossman SK, Valdes-Rodriguez R, et al. Topical ketamine-amitriptyline-lidocaine for chronic pruritus: a retrospective study assessing efficacy and tolerability. J Am Acad Dermatol. 2017;76(4):760–761.
   PubMed Web of Science ®Google Scholar
• Diaz A, Guttman-Yassky E. Topical agents for the treatment of atopic dermatitis. Expert Rev Clin Immunol. 2019 Apr;15(4):369–382.
   PubMed Web of Science ®Google Scholar
• Megna M, Napolitano M, Patruno C, et al. Systemic treatment of adult atopic dermatitis: a review. Dermatol Ther (Heidelb). 2017 Mar;7(1):1–23.
   PubMed Web of Science ®Google Scholar
• Kalamaha K, Reis E, Newton S, et al. Atopic dermatitis: a review of evolving targeted therapies. Expert Rev Clin Immunol. 2019 Mar;15(3):275–288.
   PubMed Web of Science ®Google Scholar
• Cianferoni A, Spergel J. The importance of TSLP in allergic disease and its role as a potential therapeutic target. Expert Rev Clin Immunol. 2014 Nov;10(11):1463–1474.
   PubMed Web of Science ®Google Scholar
• Yosipovitch G, Berger T, Fassett MS. Neuroimmune interactions in chronic itch of atopic dermatitis. J Eur Acad Dermatol Venereol. 2020;34(2):239–250.
   PubMed Web of Science ®Google Scholar
• Simpson EL, Bieber T, Guttman-Yassky E, et al. Two phase 3 trials of dupilumab versus placebo in atopic dermatitis. N Engl J Med. 2016;375(24):2335–2348.
   PubMed Web of Science ®Google Scholar
• Blauvelt A, de Bruin-weller M, Gooderham M, et al. Long-term management of moderate-to-severe atopic dermatitis with dupilumab and concomitant topical corticosteroids (LIBERTY AD CHRONOS): a 1-year, randomised, double-blinded, placebo-controlled, phase 3 trial. Lancet. 2017;389(10086):2287–2303.
   PubMed Web of Science ®Google Scholar
• Cork MJ, Eckert L, and Simpson EL, et al. Dupilumab improves patient-reported symptoms of atopic dermatitis, symptoms of anxiety and depression, and health-related quality of life in moderate-to-severe atopic dermatitis: analysis of pooled data from the randomized trials SOLO 1 and SOLO 2. J Dermatolog Treat. 2019 31 ;1–9.
   PubMed Web of Science ®Google Scholar
• Fourzali K, Golpanian RS, Yosipovitch G. Dupilumab use in atopic dermatitis and beyond in skin diseases. Immunotherapy. 2020;12(17):1221–1235.
   PubMed Web of Science ®Google Scholar
• Silverberg JI, Yosipovitch G, Simpson EL, et al. Dupilumab treatment results in early and sustained improvements in itch in adolescents and adults with moderate to severe atopic dermatitis: analysis of the randomized phase 3 studies SOLO 1 and SOLO 2, AD ADOL, and CHRONOS. J Am Acad Dermatol. 2020;82(6):1328–1336.
   PubMed Web of Science ®Google Scholar
• Patruno C, Napolitano M, Argenziano G, et al. Dupilumab therapy of atopic dermatitis of the elderly: a multicentre, real-life study. J Eur Acad Dermatol Venereol. 2021;35(4):958–964.
   PubMed Web of Science ®Google Scholar
• Cork MJ, Thaçi D, Eichenfield LF, et al. Dupilumab in adolescents with uncontrolled moderate-to-severe atopic dermatitis: results from a phase IIa open-label trial and subsequent phase III open-label extension. Br J Dermatol. 2020 Jan;182(1):85–96.
   PubMed Web of Science ®Google Scholar
• Lee JK, Simpson RS. Dupilumab as a novel therapy for difficult to treat chronic spontaneous urticaria. J Allergy Clin Immunol: Pract (Cambridge, MA). 2019;7(5):1659–1661.e1.
   PubMed Web of Science ®Google Scholar
• Fourzali K, Yosipovitch G. Safety considerations when using drugs to treat pruritus. Expert Opin Drug Saf. 2020;19(4):467–477.
   PubMed Web of Science ®Google Scholar
• Kim HS, Yeung J. Psoriasis appearing after dupilumab therapy in atopic dermatitis: a case report. SAGE Open Med Case Rep. 2020;8:2050313.
   Web of Science ®Google Scholar
• Fowler E, Silverberg JI, Fox JD, et al. Psoriasiform dermatitis after initiation of treatment with dupilumab for atopic dermatitis. Dermatitis. 2019 May-Jun;30(3):234–236.
   PubMed Web of Science ®Google Scholar
• Varma A, Levitt J. Dupilumab-induced phenotype switching from atopic dermatitis to psoriasis. JAAD Case Rep. 2020;6(3):217–218.
   PubMedGoogle Scholar
• Oiwa T, Honda T, Otsuka A, et al. Three cases of facial erythema with dryness and pruritus in psoriasis patients during treatment with IL-17 inhibitors. J Eur Acad Dermatol Venereol. 2018 Apr;32(4):e122–e123.
   PubMed Web of Science ®Google Scholar
• Abe F, Mitsuyama S, Nagao E, et al. Atopic dermatitis-like eruption induced by two different biologics in a patient with psoriatic arthritis. Acta Derm Venereol. 2019 Dec 01;99(13):1291–1292.
   PubMed Web of Science ®Google Scholar
• Ishiuji Y, Umezawa Y, Asahina A, et al. Exacerbation of atopic dermatitis symptoms by ustekinumab in psoriatic patients with elevated serum immunoglobulin E levels: report of two cases. J Dermatol. 2018 Jun;45(6):732–734.
   PubMed Web of Science ®Google Scholar
• Steck O, Bertschi NL, and Luther F, et al. Rapid and sustained control of itch and reduction in Th2 bias by dupilumab in a patient with Sezary syndrome. J Eur Acad Dermatol Venereol. 2020;35:1331–1337.
   PubMed Web of Science ®Google Scholar
• Espinosa ML, Nguyen MT, Aguirre AS, et al. Progression of cutaneous T-cell lymphoma after dupilumab: case review of 7 patients. J Am Acad Dermatol. 2020 Jul;83(1):197–199.
   PubMed Web of Science ®Google Scholar
• Lobo Y, Lee RC, Spelman L. Atopic dermatitis treated safely with dupilumab during pregnancy: a case report and review of the literature. Case Rep Dermatol. Copyright © 2021 by S. Karger AG, Basel. 2021;13(2):248–256.
   PubMed Web of Science ®Google Scholar
• Kage P, Simon JC, Treudler R. A case of atopic eczema treated safely with dupilumab during pregnancy and lactation. J Eur Acad Dermatol Venereol. 2020 Jun;34(6):e256–e257.
   PubMed Web of Science ®Google Scholar
• Mian M, Dunlap R, Simpson E. Dupilumab for the treatment of severe atopic dermatitis in a pregnant patient: a case report. JAAD Case Rep. 2020;6(10):1051–1052.
   PubMedGoogle Scholar
• Witzel SJ. Lactation and the use of biologic immunosuppressive medications. Breastfeed Med. 2014 Dec;9(10):543–546.
   PubMed Web of Science ®Google Scholar
• Wahlgren C, Scheynius A, Hägermark Ö. Antipruritic effect of oral cyclosporin A in atopic dermatitis. Acta Derm Venereol. 1990;70(4):323–329.
   PubMed Web of Science ®Google Scholar
• Roekevisch E, Spuls PI, Kuester D, et al. Efficacy and safety of systemic treatments for moderate-to-severe atopic dermatitis: a systematic review. J Allergy Clin Immunol. 2014;133(2):429–438.
   PubMed Web of Science ®Google Scholar
• Pacor M, Di Lorenzo G, Martinelli N, et al. Comparing tacrolimus ointment and oral cyclosporine in adult patients affected by atopic dermatitis: a randomized study. Clin Exp Allergy. 2004;34(4):639–645.
   PubMed Web of Science ®Google Scholar
• Harper J, Ahmed I, Barclay G, et al. Cyclosporin for severe childhood atopic dermatitis: short course versus continuous therapy. Br J Dermatol. 2000;142(1):52–58.
   PubMed Web of Science ®Google Scholar
• Spekhorst LS, Ariëns LF, van Der Schaft J, et al. Two‐year drug survival of dupilumab in a large cohort of difficult‐to‐treat adult atopic dermatitis patients compared to cyclosporine A and methotrexate: results from the BioDay registry. Allergy. 2020;75(9):2376.
   PubMed Web of Science ®Google Scholar
• Ariens LF, Gadkari A, Van Os-Medendorp H, et al. Dupilumab versus cyclosporine for the treatment of moderate-to-severe atopic dermatitis in adults: indirect comparison using the eczema area and severity index. Acta Derm Venereol. 2019;99(9–10):851–857.
   PubMed Web of Science ®Google Scholar
• Haw S, Shin MK, Haw CR. The efficacy and safety of long-term oral cyclosporine treatment for patients with atopic dermatitis. Ann Dermatol. 2010 Feb;22(1):9–15.
   PubMed Web of Science ®Google Scholar
• Davari DR, Nieman EL, McShane DB, et al. Current perspectives on the systemic management of atopic dermatitis. J Asthma Allergy. 2021;14:595–607.
   PubMed Web of Science ®Google Scholar
• Yosipovitch G, Rosen JD, Hashimoto T. Itch: from mechanism to (novel) therapeutic approaches. J Allergy Clin Immunol. 2018;142(5):1375–1391.
   PubMed Web of Science ®Google Scholar
• Babalola O, Strober BE. Treatment of atopic dermatitis in pregnancy. Dermatol Ther. 2013 Jul-Aug;26(4):293–301.
   PubMed Web of Science ®Google Scholar
• Ryan C, Amor KT, Menter A. The use of cyclosporine in dermatology: part II. J Am Acad Dermatol. 2010 Dec;63(6):949–972; quiz 973-4.
   PubMed Web of Science ®Google Scholar
• Armenti VT, Ahlswede KM, Ahlswede BA, et al. Variables affecting birthweight and graft survival in 197 pregnancies in cyclosporine-treated female kidney transplant recipients. Transplantation. 1995 Feb 27;59(4):476–479.
   PubMed Web of Science ®Google Scholar
• Bar Oz B, Hackman R, Einarson T, et al. Pregnancy outcome after cyclosporine therapy during pregnancy: a meta-analysis. Transplantation. 2001 Apr 27;71(8):1051–1055.
   PubMed Web of Science ®Google Scholar
• Stanley CW, Gottlieb R, Zager R, et al. Developmental well-being in offspring of women receiving cyclosporine post-renal transplant. Transplant Proc. 1999 Feb-Mar;31(1–2):241–242.
   PubMed Web of Science ®Google Scholar
• Schram M, Roekevisch E, Leeflang M, et al. A randomized trial of methotrexate and azathioprine for severe atopic dermatitis. Syst Treat Atopic Dermatitis. 2011;128(2):89.
   Google Scholar
• Kursewicz C, Valdes-Rodriguez R, Yosipovitch G. Methotrexate in the treatment of chronic itch in the geriatric population. Acta Derm Venereol. 2020;100(1–2):1–2.
   Web of Science ®Google Scholar
• Stull CM, Tey HL, Yosipovitch G. Methotrexate for the treatment of recalcitrant primary localized cutaneous amyloidosis: a case series. Acta Derm Venereol. 2018;98(9–10):900–901.
   PubMed Web of Science ®Google Scholar
• Sidbury R, Davis DM, Cohen DE, et al. Guidelines of care for the management of atopic dermatitis: section 3. Management and treatment with phototherapy and systemic agents. J Am Acad Dermatol. 2014 Aug;71(2):327–349.
   PubMed Web of Science ®Google Scholar
• Weatherhead SC, Wahie S, Reynolds NJ, et al. An open-label, dose-ranging study of methotrexate for moderate-to-severe adult atopic eczema. Br J Dermatol (1951). 2007;156(2):346–351.
   PubMed Web of Science ®Google Scholar
• El-Khalawany MA, Hassan H, Shaaban D, et al. Methotrexate versus cyclosporine in the treatment of severe atopic dermatitis in children: a multicenter experience from Egypt. Eur J Pediatr. 2013 Mar;172(3):351–356.
   PubMed Web of Science ®Google Scholar
• Neuber K, Schwartz I, Itschert G, et al. Treatment of atopic eczema with oral mycophenolate mofetil. Br J Dermatol. 2000;143(2):385–391.
   PubMed Web of Science ®Google Scholar
• Jackson JM, Fowler JF Jr, Callen JP, et al. Mycophenolate mofetil for the treatment of chronic dermatitis: an open-label study of 16 patients. J Drugs Dermatol. 2010;9(4):356–362.
   PubMed Web of Science ®Google Scholar
• Haeck IM, Knol MJ, Ten BO, et al. Enteric-coated mycophenolate sodium versus cyclosporin A as long-term treatment in adult patients with severe atopic dermatitis: a randomized controlled trial. J Am Acad Dermatol. 2011;64(6):1074–1084.
   PubMed Web of Science ®Google Scholar
• Berth-Jones J, Takwale A, Tan E, et al. Azathioprine in severe adult atopic dermatitis: a double-blind, placebo-controlled, crossover trial. Br J Dermatol. 2002 Aug;147(2):324–330.
   PubMed Web of Science ®Google Scholar
• Denby KS, Beck LA. Update on systemic therapies for atopic dermatitis. Curr Opin Allergy Clin Immunol. 2012;12(4):421–426.
   PubMed Web of Science ®Google Scholar
• Inman GJ, Wang J, Nagano A, et al. The genomic landscape of cutaneous SCC reveals drivers and a novel azathioprine associated mutational signature. Nat Commun. 2018 Sep 10;9(1):3667.
   PubMed Web of Science ®Google Scholar
• Levy LL, Urban J, King BA. Treatment of recalcitrant atopic dermatitis with the oral Janus kinase inhibitor tofacitinib citrate. J Am Acad Dermatol. 2015 Sep;73(3):395–399.
   PubMed Web of Science ®Google Scholar
• Okiyama N, Furumoto Y, Villarroel VA, et al. Reversal of CD8 T-cell-mediated mucocutaneous graft-versus-host-like disease by the JAK inhibitor tofacitinib. J Invest Dermatol. 2014 Apr;134(4):992–1000.
   PubMed Web of Science ®Google Scholar
• Clarysse K, Pfaff CM, Marquardt Y, et al. JAK1/3 inhibition preserves epidermal morphology in full‐thickness 3D skin models of atopic dermatitis and psoriasis. J Eur Acad Dermatol Venereol. 2019;33(2):367–375.
   PubMed Web of Science ®Google Scholar
• Vu M, Heyes C, Robertson SJ, et al. Oral tofacitinib: a promising treatment in atopic dermatitis, alopecia areata and vitiligo. Clin Exp Dermatol. 2017;42(8):942–944.
   PubMed Web of Science ®Google Scholar
• Smolen JS, Landewé RBM, Bijlsma JWJ, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update. Ann Rheum Dis. 2020 Jun;79(6):685–699.
   PubMed Web of Science ®Google Scholar
• Kader HA, Azeem M, Jwayed SA, et al. Current insights into immunology and novel therapeutics of atopic dermatitis. Cells. 2021 Jun 4;10(6):1392.
   PubMed Web of Science ®Google Scholar
• Samrao A, Berry TM, Goreshi R, et al. A pilot study of an oral phosphodiesterase inhibitor (apremilast) for atopic dermatitis in adults. Arch Dermatol. 2012 Aug;148(8):890–897.
   PubMedGoogle Scholar
• Volf EM, Au SC, Dumont N, et al. A phase 2, open-label, investigator-initiated study to evaluate the safety and efficacy of apremilast in subjects with recalcitrant allergic contact or atopic dermatitis. J Drugs Dermatol. 2012 Mar;11(3):341–346.
   PubMed Web of Science ®Google Scholar
• Drucker AM, Eyerich K, de Bruin-weller MS, et al. Use of systemic corticosteroids for atopic dermatitis: international Eczema Council consensus statement. Br J Dermatol. 2018 Mar;178(3):768–775.
   PubMed Web of Science ®Google Scholar
• Aljebab F, Choonara I, Conroy S. Systematic review of the toxicity of long-course oral corticosteroids in children. PLoS One. 2017;12(1):e0170259.
   PubMed Web of Science ®Google Scholar
• He A, Feldman SR, Fleischer AB Jr. An assessment of the use of antihistamines in the management of atopic dermatitis. J Am Acad Dermatol. 2018 Jul;79(1):92–96.
   PubMed Web of Science ®Google Scholar
• Yosipovitch G, Papoiu AD. What causes itch in atopic dermatitis? Curr Allergy Asthma Rep. 2008;8(4):306–311.
   PubMed Web of Science ®Google Scholar
• Matterne U, Böhmer MM, Weisshaar E, et al. Oral H1 antihistamines as ‘add-on’ therapy to topical treatment for eczema. Cochrane Database Syst Rev. 2019 Jan 22;1(1):Cd012167.
   PubMed Web of Science ®Google Scholar
• Kawashima M, Tango T, Noguchi T, et al. Addition of fexofenadine to a topical corticosteroid reduces the pruritus associated with atopic dermatitis in a 1-week randomized, multicentre, double-blind, placebo-controlled, parallel-group study. Br J Dermatol. 2003 Jun;148(6):1212–1221.
   PubMed Web of Science ®Google Scholar
• Werfel T, Layton G, Yeadon M, et al. Efficacy and safety of the histamine H-4 receptor antagonist ZPL-3893787 in patients with atopic dermatitis. J Allergy Clin Immunol. 2019;143(5):1830.
   PubMed Web of Science ®Google Scholar
• Davis MP, Frandsen JL, Walsh D, et al. Mirtazapine for pruritus. J Pain Symptom Manage. 2003;25(3):288–291.
   PubMed Web of Science ®Google Scholar
• Hundley JL, Yosipovitch G. Mirtazapine for reducing nocturnal itch in patients with chronic pruritus: a pilot study. J Am Acad Dermatol. 2004;50(6):889–891.
   PubMed Web of Science ®Google Scholar
• Demierre M-F, Taverna J. Mirtazapine and gabapentin for reducing pruritus in cutaneous T-cell lymphoma. J Am Acad Dermatol. 2006;55(3):543–544.
   PubMed Web of Science ®Google Scholar
• Ständer S, Weisshaar E, Luger TA. Neurophysiological and neurochemical basis of modern pruritus treatment. Exp Dermatol. 2008;17(3):161–169.
   PubMed Web of Science ®Google Scholar
• Matsuda KM, Sharma D, Schonfeld AR, et al. Gabapentin and pregabalin for the treatment of chronic pruritus. J Am Acad Dermatol. 2016 Sep;75(3):619–625.e6.
   PubMed Web of Science ®Google Scholar
• Iannetti G, Zambreanu L, Wise RG, et al. From The Cover: pharmacological modulation of pain-related brain activity during normal and central sensitization states in humans. Proc Nat Acad Sci. 2005;102(50):18195–18200.
   PubMed Web of Science ®Google Scholar
• Ralvenius WT, Neumann E, Pagani M, et al. Itch suppression in mice and dogs by modulation of spinal α2 and α3GABA A receptors. Nat Commun. 2018;9(1):1–15.
   PubMed Web of Science ®Google Scholar
• Fowler E, Yosipovitch G. Chronic itch management: therapies beyond those targeting the immune system. Ann Allergy Asthma Immunol. 2019 2019/08/01/;123(2):158–165.
   PubMed Web of Science ®Google Scholar
• Fowler E, Yosipovitch G. A new generation of treatments for itch. Acta Dermato Venereologica. 2020;100(2):37–45.
   Web of Science ®Google Scholar
• Tominaga M, Takamori K. An update on peripheral mechanisms and treatments of itch. Biol Pharm Bull. 2013;36(8):1241–1247.
   PubMed Web of Science ®Google Scholar
• Tominaga M, Ogawa H, Takamori K. Possible roles of epidermal opioid systems in pruritus of atopic dermatitis. J Invest Dermatol. 2007;127(9):2228–2235.
   PubMed Web of Science ®Google Scholar
• Lipman ZM, Yosipovitch G. An evaluation of difelikefalin as a treatment option for moderate-to-severe pruritus in end stage renal disease. Expert Opin Pharmacother. 2020 Dec;14:1–7.
   Google Scholar
• Phan NQ, Bernhard JD, Luger TA, et al. Antipruritic treatment with systemic μ-opioid receptor antagonists: a review. J Am Acad Dermatol. 2010 Oct;63(4):680–688.
   PubMed Web of Science ®Google Scholar
• Phan N, Lotts T, Antal A, et al. Systemic kappa opioid receptor agonists in the treatment of chronic pruritus: a literature review. Acta Dermatol Venereologica. 2012;92(5):555–560.
   PubMed Web of Science ®Google Scholar
• Lipman ZM, Yosipovitch G. Substance use disorders and chronic itch. J Am Acad Dermatol. 2021 Jan;84(1):148–155.
   PubMed Web of Science ®Google Scholar
• Khanna R, Kwon CD, Patel SP, et al. Intranasal butorphanol rescue therapy for the treatment of intractable pruritus: a case series from the Johns Hopkins itch clinic. J Am Acad Dermatol. 2020;83(5):1529–1533.
   PubMed Web of Science ®Google Scholar
• Dawn AG, Yosipovitch G. Butorphanol for treatment of intractable pruritus. J Am Acad Dermatol. 2006 Mar;54(3):527–531.
   PubMed Web of Science ®Google Scholar
• Malekzad F, Arbabi M, Mohtasham N, et al. Efficacy of oral naltrexone on pruritus in atopic eczema: a double‐blind, placebo‐controlled study. J Eur Acad Dermatol Venereol. 2009;23(8):948–950.
   PubMed Web of Science ®Google Scholar
• Wallengren J, Sundler F. Phototherapy reduces the number of epidermal and CGRP-positive dermal nerve fibres. Acta Derm Venereol. 2004;84(2):111–115.
   PubMed Web of Science ®Google Scholar
• Kemény L, Varga E, Novak Z. Advances in phototherapy for psoriasis and atopic dermatitis. Expert Rev Clin Immunol. 2019 Nov;15(11):1205–1214.
   PubMed Web of Science ®Google Scholar
• Rivard J, Lim HW. Ultraviolet phototherapy for pruritus. Dermatol Ther. 2005;18(4):344–354.
   PubMedGoogle Scholar
• Reynolds NJ, Franklin V, Gray JC, et al. Narrow-band ultraviolet B and broad-band ultraviolet A phototherapy in adult atopic eczema: a randomised controlled trial. Lancet. 2001;357(9273):2012–2016.
   PubMed Web of Science ®Google Scholar
• Lam J, Polifka JE, Dohil MA. Safety of dermatologic drugs used in pregnant patients with psoriasis and other inflammatory skin diseases. J Am Acad Dermatol. 2008 Aug;59(2):295–315.
   PubMed Web of Science ®Google Scholar
• Park KK. Narrowband UV-B phototherapy during pregnancy and folic acid depletion. Arch Dermatol. United States. 2012;148(1):132–133.
   PubMedGoogle Scholar
• Crowley EL, Nezamololama N, Papp K, et al. Abrocitinib for the treatment of atopic dermatitis. Expert Rev Clin Immunol. 2020 Oct;16(10):955–962.
   PubMed Web of Science ®Google Scholar
• Silverberg JI, Simpson EL, Thyssen JP, et al. Efficacy and safety of abrocitinib in patients with moderate-to-severe atopic dermatitis: a randomized clinical trial. JAMA Dermatol. 2020;156(8):863–873.
   PubMed Web of Science ®Google Scholar
• Simpson EL, Sinclair R, Forman S, et al. Efficacy and safety of abrocitinib in adults and adolescents with moderate-to-severe atopic dermatitis (JADE MONO-1): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial. Lancet. 2020;396(10246):255–266.
   PubMed Web of Science ®Google Scholar
• Yosipovitch G, Bieber T, Gold LS, et al. 15517 Eczema area and severity index 90 (EASI-90) responder rates with abrocitinib and relationship with quality of life (QoL) and itch in patients with moderate to severe atopic dermatitis: results from a randomized phase 3 clinical trial. J Am Acad Dermatol. 2020;83(6):AB41–AB41.
   Web of Science ®Google Scholar
• Guttman-Yassky E, Thaçi D, Pangan AL, et al. Upadacitinib in adults with moderate to severe atopic dermatitis: 16-week results from a randomized, placebo-controlled trial. J Allergy Clin Immunol. 2020;145(3):877–884.
   PubMed Web of Science ®Google Scholar
• Simpson E, Lacour JP, Spelman L, et al. Baricitinib in patients with moderate‐to‐severe atopic dermatitis and inadequate response to topical corticosteroids: results from two randomized monotherapy phase III trials. Br J Dermatol. 2020;183(2):242–255.
   PubMed Web of Science ®Google Scholar
• Damsky W, Peterson D, Ramseier J, et al. The emerging role of Janus kinase inhibitors in the treatment of autoimmune and inflammatory diseases. J Allergy Clin Immunol. 2021;147(3):814–826.
   PubMed Web of Science ®Google Scholar
• Dubin C, Del Duca E, Guttman-Yassky E. The IL-4, IL-13 and IL-31 pathways in atopic dermatitis. Expert Rev Clin Immunol. 2021 Aug;17(8):835–852.
   PubMed Web of Science ®Google Scholar
• Tubau C, Puig L. Therapeutic targeting of the IL-13 pathway in skin inflammation. Expert Rev Clin Immunol. 2021 Jan;17(1):15–25.
   PubMed Web of Science ®Google Scholar
• Morra DE, and Drucker AM. Tralokinumab for atopic dermatitis: a promising new therapy. Br J Dermatol (1951). 2020;184:386–387.
   PubMed Web of Science ®Google Scholar
• Guttman-Yassky E, Blauvelt A, Eichenfield LF, et al. Efficacy and safety of lebrikizumab, a high-affinity interleukin 13 inhibitor, in adults with moderate to severe atopic dermatitis: a phase 2b randomized clinical trial. JAMA Dermatol. 2020;156(4):411–420.
   PubMed Web of Science ®Google Scholar
• Kabashima K, Matsumura T, Komazaki H, et al. Trial of nemolizumab and topical agents for atopic dermatitis with pruritus. N Engl J Med. 2020;383(2):141–150.
   PubMed Web of Science ®Google Scholar
• Shea P, Presnell SR, Foster D, et al. Interleukin 31, a cytokine produced by activated T cells, induces dermatitis in mice. Nat Immunol. 2004;5(7):752–760.
   PubMed Web of Science ®Google Scholar
• Cevikbas FP, Wang XP, Akiyama TP, et al. A sensory neuron–expressed IL-31 receptor mediates T helper cell–dependent itch: involvement of TRPV1 and TRPA1. J Allergy Clin Immunol. 2013;133(2):448–460.e7.
   PubMed Web of Science ®Google Scholar
• Feld M, Garcia R, Buddenkotte J, et al. The pruritus- and TH2-associated cytokine IL-31 promotes growth of sensory nerves. J Allergy Clin Immunol. 2016;138(2):500–508.e24.
   PubMed Web of Science ®Google Scholar
• Yang X, Kambe N, Takimoto-Ito R, et al. Advances in the pathophysiology of atopic dermatitis revealed by novel therapeutics and clinical trials. Pharmacol Ther. 2021;224:107830.
   PubMed Web of Science ®Google Scholar
• Guttman-Yassky E, Pavel AB, Zhou L, et al. GBR 830, an anti-OX40, improves skin gene signatures and clinical scores in patients with atopic dermatitis. J Allergy Clin Immunol. 2019 Aug;144(2):482–493.e7.
   PubMed Web of Science ®Google Scholar
• SA IS, S.A. GP. Phase 2b study to evaluate the efficacy and safety of ISB 830 in adults with moderate to severe atopic dermatitis. 2018. [cited 2021 May 10]. https://ClinicalTrials.gov/show/NCT03568162
   Google Scholar
• Kyowa Kirin I, and Kyowa Kirin Co L. Study of an anti-OX40 monoclonal antibody (KHK4083) in subjects with moderate to severe atopic dermatitis2018. [cited 2021 May 10]. https://ClinicalTrials.gov/show/NCT03703102
   Google Scholar
• Cara Therapeutics I. Study to evaluate the efficacy and safety of oral Difelikefalin (CR845) for moderate to severe pruritus in subjects with atopic dermatitis. 2019. [cited 2021 May 10]. https://ClinicalTrials.gov/show/NCT04018027
   Google Scholar
• Spinaci A, Buccioni M, Dal Ben D, et al. P2X3 receptor ligands: structural features and potential therapeutic applications. Front Pharmacol. 2021;12:653561.
   PubMed Web of Science ®Google Scholar
• Inc BH. A multiple-dose study of BLU-5937 in chronic pruritus associated with atopic dermatitis. 2020. [cited 2021 May 10]. https://ClinicalTrials.gov/show/NCT04693195
   Google Scholar
• Rajasimhan S, Pamuk O, Katz JD. Safety of Janus kinase inhibitors in older patients: a focus on the thromboembolic risk. Drugs Aging. 2020 Aug;37(8):551–558.
   PubMed Web of Science ®Google Scholar
• Mishra SK, Wheeler JJ, Pitake S, et al. Periostin activation of integrin receptors on sensory neurons induces allergic itch. Cell Rep (Cambridge). 2020;31(1):107472.
   PubMed Web of Science ®Google Scholar
• Hashimoto T, Nattkemper LA, Kim HS, et al. Dermal periostin: a new player in itch of prurigo nodularis. Acta Derm Venereol. 2021 Jan 20;101(1):adv00375.
   PubMed Web of Science ®Google Scholar
• Meixiong J, Anderson M, Limjunyawong N, et al. Activation of mast-cell-expressed mas-related G-protein-coupled receptors drives non-histaminergic itch. Immunity. 2019 May 21;50(5):1163–1171.e5.
   PubMed Web of Science ®Google Scholar
• Nattkemper LA, Tey HL, Valdes-Rodriguez R, et al. The genetics of chronic itch: gene expression in the skin of patients with atopic dermatitis and psoriasis with severe itch. J Invest Dermatol. 2018;138(6):1311–1317.
   PubMed Web of Science ®Google Scholar
• Ingrasci G, El-Kashlan N, Alexis A, et al. Chronic itch in African Americans: an unmet need. Arch Dermatol Res. 2021 Jun 15. DOI:https://doi.org/10.1007/s00403-021-02255-6.
   Google Scholar
• Kaufman BP, Guttman-Yassky E, Alexis AF. Atopic dermatitis in diverse racial and ethnic groups-Variations in epidemiology, genetics, clinical presentation and treatment. Exp Dermatol. 2018;27(4):340–357.
   PubMed Web of Science ®Google Scholar
• McEwen MW, Fite EM, Yosipovitch G, et al. Drugs on the horizon for chronic pruritus. Dermatol Clin. 2018 Jul;36(3):335–344.
   PubMed Web of Science ®Google Scholar
• Ständer S, Spellman MC, Kwon P, et al. The NK1 receptor antagonist serlopitant for treatment of chronic pruritus. Expert Opin Investig Drugs. 2019 Aug;28(8):659–666.
   PubMed Web of Science ®Google Scholar
• Welsh SE, Xiao C, Kaden AR, et al. Neurokinin-1 receptor antagonist tradipitant has mixed effects on itch in atopic dermatitis: results from EPIONE, a randomized clinical trial. J Eur Acad Dermatol Venereol. 2021;35(5):e338–e340.
   PubMed Web of Science ®Google Scholar