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Management of Itch in Atopic Dermatitis

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Abstract

Atopic dermatitis (AD) is the most common itchy dermatosis that affects millions of children and adults worldwide. Chronic itch in this condition has significant impact on measures of quality of life, such as sleep. Treating itch in AD has been challenging for decades, but new drugs have emerged in the last year with significant anti-pruritic effect. The optimal treatment regimen for atopic itch addresses barrier dysfunction, inflammation, neural hypersensitivity, and the itch–scratch cycle. Topical moisturizers remain the foundation of treatment and should be used by all patients with AD-associated pruritus. Step-wise therapy, from topical anti-inflammatory creams to systemic monoclonal antibodies and immunosuppressants, is recommended. There are multiple adjuvant therapies that can be used, especially to target itch in the setting of minimal skin inflammation. Finally, patient education, sleep management, and stress relief are important components to optimize outcomes. This review assesses the latest advances and treatment recommendations for pruritus in AD. Finally, suggested therapeutic ladders and emerging treatments are discussed.

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References

  1. Boguniewicz M. Atopic dermatitis: beyond the itch that rashes. Immunol Allergy Clin N Am. 2005;25(2):333–51.

    Article  Google Scholar 

  2. Dawn A, Papoiu AD, Chan YH, Rapp SR, Rassette N, Yosipovitch G. Itch characteristics in atopic dermatitis: results of a web-based questionnaire. Br J Dermatol. 2009;160(3):642–4.

    Article  CAS  PubMed  Google Scholar 

  3. Blome C, Radtke MA, Eissing L, Augustin M. Quality of life in patients with atopic dermatitis: disease burden, measurement, and treatment benefit. Am J Clin Dermatol. 2016;17(2):163–9.

    Article  PubMed  Google Scholar 

  4. Yosipovitch G, Papoiu AD. What causes itch in atopic dermatitis? Curr Allergy Asthma Rep. 2008;8(4):306–11.

    Article  CAS  PubMed  Google Scholar 

  5. Lifschitz C. The impact of atopic dermatitis on quality of life. Ann Nutr Metab. 2015;66(Suppl 1):34–40.

    Article  CAS  PubMed  Google Scholar 

  6. Bieber T. Atopic dermatitis. Ann Dermatol. 2010;22(2):125–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Thyssen JP, Kezic S. Causes of epidermal filaggrin reduction and their role in the pathogenesis of atopic dermatitis. J Allergy Clin Immunol. 2014;134(4):792–9.

    Article  CAS  PubMed  Google Scholar 

  8. Yamamoto A, Serizawa S, Ito M, Sato Y. Stratum corneum lipid abnormalities in atopic dermatitis. Arch Dermatol Res. 1991;283(4):219–23.

    Article  CAS  PubMed  Google Scholar 

  9. Eberlein-Konig B, Schafer T, Huss-Marp J, Darsow U, Mohrenschlager M, Herbert O, et al. Skin surface pH, stratum corneum hydration, trans-epidermal water loss and skin roughness related to atopic eczema and skin dryness in a population of primary school children. Acta Dermatol Venereol. 2000;80(3):188–91.

    Article  CAS  Google Scholar 

  10. Palmer CN, Irvine AD, Terron-Kwiatkowski A, Zhao Y, Liao H, Lee SP, et al. Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis. Nat Genet. 2006;38(4):441–6.

    Article  CAS  PubMed  Google Scholar 

  11. Yosipovitch G, Fleischer A. Itch associated with skin disease: advances in pathophysiology and emerging therapies. Am J Clin Dermatol. 2003;4(9):617–22.

    Article  PubMed  Google Scholar 

  12. Ikoma A, Steinhoff M, Stander S, Yosipovitch G, Schmelz M. The neurobiology of itch. Nat Rev Neurosci. 2006;7(7):535–47.

    Article  CAS  PubMed  Google Scholar 

  13. Schmelz M. Itch and pain. Neurosci Biobehav Rev. 2010;34(2):171–6.

    Article  CAS  PubMed  Google Scholar 

  14. Andersen HH, Elberling J, Solvsten H, Yosipovitch G, Arendt-Nielsen L. Non-histaminergic and mechanical itch sensitization in atopic dermatitis. Pain. 2017;158(9):1780-91.

    Article  CAS  PubMed  Google Scholar 

  15. Davidson S, Zhang X, Yoon CH, Khasabov SG, Simone DA, Giesler GJ Jr. The itch-producing agents histamine and cowhage activate separate populations of primate spinothalamic tract neurons. J Neurosci. 2007;27(37):10007–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Namer B, Carr R, Johanek LM, Schmelz M, Handwerker HO, Ringkamp M. Separate peripheral pathways for pruritus in man. J Neurophysiol. 2008;100(4):2062–9.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Reddy VB, Iuga AO, Shimada SG, LaMotte RH, Lerner EA. Cowhage-evoked itch is mediated by a novel cysteine protease: a ligand of protease-activated receptors. J Neurosci. 2008;28(17):4331–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Carstens E, Akiyama T. Central mechanisms of itch. Curr Probl Dermatol. 2016;50:11–7.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Han L, Dong X. Itch mechanisms and circuits. Annu Rev Biophys. 2014;43:331–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Papoiu AD, Coghill RC, Kraft RA, Wang H, Yosipovitch G. A tale of two itches. Common features and notable differences in brain activation evoked by cowhage and histamine induced itch. Neuroimage. 2012;59(4):3611–23.

    Article  PubMed  Google Scholar 

  21. Davidson S, Zhang X, Khasabov SG, Simone DA, Giesler GJ Jr. Relief of itch by scratching: state-dependent inhibition of primate spinothalamic tract neurons. Nat Neurosci. 2009;12(5):544–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Ishiuji Y, Coghill RC, Patel TS, Oshiro Y, Kraft RA, Yosipovitch G. Distinct patterns of brain activity evoked by histamine-induced itch reveal an association with itch intensity and disease severity in atopic dermatitis. Br J Dermatol. 2009;161(5):1072–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Mollanazar NK, Smith PK, Yosipovitch G. Mediators of chronic pruritus in atopic dermatitis: getting the itch out? Clin Rev Allergy Immunol. 2016;51(3):263–92.

    Article  CAS  PubMed  Google Scholar 

  24. Zhu J. T helper 2 (Th2) cell differentiation, type 2 innate lymphoid cell (ILC2) development and regulation of interleukin-4 (IL-4) and IL-13 production. Cytokine. 2015;75(1):14–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Elbe-Burger A, Egyed A, Olt S, Klubal R, Mann U, Rappersberger K, et al. Overexpression of IL-4 alters the homeostasis in the skin. J Invest Dermatol. 2002;118(5):767–78.

    Article  CAS  PubMed  Google Scholar 

  26. Tazawa T, Sugiura H, Sugiura Y, Uehara M. Relative importance of IL-4 and IL-13 in lesional skin of atopic dermatitis. Arch Dermatol Res. 2004;295(11):459–64.

    Article  CAS  PubMed  Google Scholar 

  27. Simpson EL, Bieber T, Guttman-Yassky E, Beck LA, Blauvelt A, Cork MJ, et al. Two phase 3 trials of dupilumab versus placebo in atopic dermatitis. N Engl J Med. 2016;375(24):2335–48.

    Article  CAS  PubMed  Google Scholar 

  28. Furue M, Yamamura K, Kido-Nakahara M, Nakahara T, Fukui Y. Emerging role of interleukin-31 and interleukin-31 receptor in pruritus in atopic dermatitis. Allergy. 2017.

  29. Li C, Maillet I, Mackowiak C, Viala C, Di Padova F, Li M, et al. Experimental atopic dermatitis depends on IL-33R signaling via MyD88 in dendritic cells. Cell Death Dis. 2017;8(4):e2735.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Cevikbas F, Wang X, Akiyama T, Kempkes C, Savinko T, Antal A, et al. A sensory neuron-expressed IL-31 receptor mediates T helper cell-dependent itch: involvement of TRPV1 and TRPA1. J Allergy Clin Immunol. 2014;133(2):448–60.

    Article  CAS  PubMed  Google Scholar 

  31. Raap U, Weissmantel S, Gehring M, Eisenberg AM, Kapp A, Folster-Holst R. IL-31 significantly correlates with disease activity and Th2 cytokine levels in children with atopic dermatitis. Pediatr Allergy Immunol. 2012;23(3):285–8.

    Article  PubMed  Google Scholar 

  32. Savinko T, Matikainen S, Saarialho-Kere U, Lehto M, Wang G, Lehtimaki S, et al. IL-33 and ST2 in atopic dermatitis: expression profiles and modulation by triggering factors. J Invest Dermatol. 2012;132(5):1392–400.

    Article  CAS  PubMed  Google Scholar 

  33. Tamagawa-Mineoka R, Okuzawa Y, Masuda K, Katoh N. Increased serum levels of interleukin 33 in patients with atopic dermatitis. J Am Acad Dermatol. 2014;70(5):882–8.

    Article  CAS  PubMed  Google Scholar 

  34. Choi EH, Brown BE, Crumrine D, Chang S, Man MQ, Elias PM, et al. Mechanisms by which psychologic stress alters cutaneous permeability barrier homeostasis and stratum corneum integrity. J Invest Dermatol. 2005;124(3):587–95.

    Article  CAS  PubMed  Google Scholar 

  35. Jafferany M. Psychodermatology: a guide to understanding common psychocutaneous disorders. Prim Care Companion J Clin Psychiatry. 2007;9(3):203–13.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Amano H, Negishi I, Akiyama H, Ishikawa O. Psychological stress can trigger atopic dermatitis in NC/Nga mice: an inhibitory effect of corticotropin-releasing factor. Neuropsychopharmacology. 2008;33(3):566–73.

    Article  CAS  PubMed  Google Scholar 

  37. Held E, Sveinsdottir S, Agner T. Effect of long-term use of moisturizer on skin hydration, barrier function and susceptibility to irritants. Acta Derm Venereol. 1999;79(1):49–51.

    Article  CAS  PubMed  Google Scholar 

  38. Grimalt R, Mengeaud V, Cambazard F, Study Investigators G. The steroid-sparing effect of an emollient therapy in infants with atopic dermatitis: a randomized controlled study. Dermatology. 2007;214(1):61–7.

    Article  CAS  PubMed  Google Scholar 

  39. Lucky AW, Leach AD, Laskarzewski P, Wenck H. Use of an emollient as a steroid-sparing agent in the treatment of mild to moderate atopic dermatitis in children. Pediatr Dermatol. 1997;14(4):321–4.

    Article  CAS  PubMed  Google Scholar 

  40. Vilaplana J, Coll J, Trullas C, Azon A, Pelejero C. Clinical and non-invasive evaluation of 12% ammonium lactate emulsion for the treatment of dry skin in atopic and non-atopic subjects. Acta Derm Venereol. 1992;72(1):28–33.

    CAS  PubMed  Google Scholar 

  41. Msika P, De Belilovsky C, Piccardi N, Chebassier N, Baudouin C, Chadoutaud B. New emollient with topical corticosteroid-sparing effect in treatment of childhood atopic dermatitis: SCORAD and quality of life improvement. Pediatr Dermatol. 2008;25(6):606–12.

    Article  PubMed  Google Scholar 

  42. Yosipovitch G, Hundley JL. Practical guidelines for relief of itch. Dermatol Nurs. 2004;16(4):325–8 (quiz 9).

    PubMed  Google Scholar 

  43. Szczepanowska J, Reich A, Szepietowski JC. Emollients improve treatment results with topical corticosteroids in childhood atopic dermatitis: a randomized comparative study. Pediatr Allergy Immunol. 2008;19(7):614–8.

    Article  PubMed  Google Scholar 

  44. van Zuuren EJ, Fedorowicz Z, Arents BWM. Emollients and moisturisers for eczema: abridged Cochrane systematic review including GRADE assessments. Br J Dermatol. 2017.

  45. Wertz PW. Epidermal lipids. Semin Dermatol. 1992;11(2):106–13.

    CAS  PubMed  Google Scholar 

  46. Lynde CW, Andriessen A. A cohort study on a ceramide-containing cleanser and moisturizer used for atopic dermatitis. Cutis. 2014;93(4):207–13.

    PubMed  Google Scholar 

  47. Kurtz ES, Wallo W. Colloidal oatmeal: history, chemistry and clinical properties. J Drugs Dermatol. 2007;6(2):167–70.

    PubMed  Google Scholar 

  48. Fowler JF, Nebus J, Wallo W, Eichenfield LF. Colloidal oatmeal formulations as adjunct treatments in atopic dermatitis. J Drugs Dermatol. 2012;11(7):804–7.

    PubMed  Google Scholar 

  49. Lisante TA, Nunez C, Zhang P, Mathes BM. A 1% colloidal oatmeal cream alone is effective in reducing symptoms of mild to moderate atopic dermatitis: results from two clinical studies. J Drugs Dermatol. 2017;16(7):671–6.

    PubMed  Google Scholar 

  50. Fowler JF Jr. Colloidal oatmeal formulations and the treatment of atopic dermatitis. J Drugs Dermatol. 2014;13(10):1180–3 (quiz 4-5).

    CAS  PubMed  Google Scholar 

  51. Bratt K, Sunnerheim K, Bryngelsson S, Fagerlund A, Engman L, Andersson RE, et al. Avenanthramides in oats (Avena sativa L.) and structure-antioxidant activity relationships. J Agric Food Chem. 2003;51(3):594–600.

    Article  CAS  PubMed  Google Scholar 

  52. Schmid MH, Korting HC. The concept of the acid mantle of the skin: its relevance for the choice of skin cleansers. Dermatology. 1995;191(4):276–80.

    Article  CAS  PubMed  Google Scholar 

  53. Ali SM, Yosipovitch G. Skin pH: from basic science to basic skin care. Acta Derm Venereol. 2013;93(3):261–7.

    Article  PubMed  Google Scholar 

  54. Seidenari S, Giusti G. Objective assessment of the skin of children affected by atopic dermatitis: a study of pH, capacitance and TEWL in eczematous and clinically uninvolved skin. Acta Derm Venereol. 1995;75(6):429–33.

    CAS  PubMed  Google Scholar 

  55. Solodkin G, Chaudhari U, Subramanyan K, Johnson AW, Yan X, Gottlieb A. Benefits of mild cleansing: synthetic surfactant based (syndet) bars for patients with atopic dermatitis. Cutis. 2006;77(5):317–24.

    PubMed  Google Scholar 

  56. Hachem JP, Man MQ, Crumrine D, Uchida Y, Brown BE, Rogiers V, et al. Sustained serine proteases activity by prolonged increase in pH leads to degradation of lipid processing enzymes and profound alterations of barrier function and stratum corneum integrity. J Invest Dermatol. 2005;125(3):510–20.

    Article  CAS  PubMed  Google Scholar 

  57. Brazzini B, Pimpinelli N. New and established topical corticosteroids in dermatology: clinical pharmacology and therapeutic use. Am J Clin Dermatol. 2002;3(1):47–58.

    Article  PubMed  Google Scholar 

  58. Das A, Panda S. Use of topical corticosteroids in dermatology: an evidence-based approach. Indian J Dermatol. 2017;62(3):237–50.

    PubMed  PubMed Central  Google Scholar 

  59. Eichenfield LF, Tom WL, Berger TG, Krol A, Paller AS, Schwarzenberger K, et al. Guidelines of care for the management of atopic dermatitis: section 2. Management and treatment of atopic dermatitis with topical therapies. J Am Acad Dermatol. 2014;71(1):116–32.

    Article  PubMed  PubMed Central  Google Scholar 

  60. Polano MK. The topical use of corticosteroids in dermatology. Ned Tijdschr Geneeskd. 1965;109:180–5.

    CAS  PubMed  Google Scholar 

  61. Yarbrough KB, Neuhaus KJ, Simpson EL. The effects of treatment on itch in atopic dermatitis. Dermatol Ther. 2013;26(2):110–9.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Roth HL, Brown EP. Hydrocortisone valerate. Double-blind comparison with two other topical steroids. Cutis. 1978;21(5):695–8.

    CAS  PubMed  Google Scholar 

  63. Bolognia JL JJ, Schaffer JV. Glucocorticosteroids. Dermatology. 2012. 2075–88.

  64. Lio PA, Lee M, LeBovidge J, Timmons KG, Schneider L. Clinical management of atopic dermatitis: practical highlights and updates from the atopic dermatitis practice parameter 2012. J Allergy Clin Immunol Pract. 2014;2(4):361–9.

    Article  PubMed  Google Scholar 

  65. Stander S, Schurmeyer-Horst F, Luger TA, Weisshaar E. Treatment of pruritic diseases with topical calcineurin inhibitors. Ther Clin Risk Manag. 2006;2(2):213–8.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Luger T, Van Leent EJ, Graeber M, Hedgecock S, Thurston M, Kandra A, et al. SDZ ASM 981: an emerging safe and effective treatment for atopic dermatitis. Br J Dermatol. 2001;144(4):788–94.

    Article  CAS  PubMed  Google Scholar 

  67. Wellington K, Spencer CM. Sdz asm 981. BioDrugs. 2000;14(6):409–16.

    Article  CAS  PubMed  Google Scholar 

  68. Senba E, Katanosaka K, Yajima H, Mizumura K. The immunosuppressant FK506 activates capsaicin- and bradykinin-sensitive DRG neurons and cutaneous C-fibers. Neurosci Res. 2004;50(3):257–62.

    Article  CAS  PubMed  Google Scholar 

  69. McKenna SP, Whalley D, de Prost Y, Staab D, Huels J, Paul CF, et al. Treatment of paediatric atopic dermatitis with pimecrolimus (Elidel, SDZ ASM 981): impact on quality of life and health-related quality of life. J Eur Acad Dermatol Venereol. 2006;20(3):248–54.

    Article  CAS  PubMed  Google Scholar 

  70. Leung DY, Nicklas RA, Li JT, Bernstein IL, Blessing-Moore J, Boguniewicz M, et al. Disease management of atopic dermatitis: an updated practice parameter. Joint Task Force on Practice Parameters. Ann Allergy Asthma Immunol. 2004;93(3 Suppl 2):S1–21.

    Article  PubMed  Google Scholar 

  71. Kaufmann R, Bieber T, Helgesen AL, Andersen BL, Luger T, Poulin Y, et al. Onset of pruritus relief with pimecrolimus cream 1% in adult patients with atopic dermatitis: a randomized trial. Allergy. 2006;61(3):375–81.

    Article  CAS  PubMed  Google Scholar 

  72. Langley RG, Eichenfield LF, Lucky AW, Boguniewicz M, Barbier N, Cherill R. Sustained efficacy and safety of pimecrolimus cream 1% when used long-term (up to 26 weeks) to treat children with atopic dermatitis. Pediatr Dermatol. 2008;25(3):301–7.

    Article  PubMed  Google Scholar 

  73. Pereira U, Boulais N, Lebonvallet N, Pennec JP, Dorange G, Misery L. Mechanisms of the sensory effects of tacrolimus on the skin. Br J Dermatol. 2010;163(1):70–7.

    CAS  PubMed  Google Scholar 

  74. Siegfried EC, Jaworski JC, Hebert AA. Topical calcineurin inhibitors and lymphoma risk: evidence update with implications for daily practice. Am J Clin Dermatol. 2013;14(3):163–78.

    Article  PubMed  PubMed Central  Google Scholar 

  75. Remitz A, Harper J, Rustin M, Goldschmidt WF, Palatsi R, van der Valk PG, et al. Long-term safety and efficacy of tacrolimus ointment for the treatment of atopic dermatitis in children. Acta Derm Venereol. 2007;87(1):54–61.

    Article  CAS  PubMed  Google Scholar 

  76. Tom WL, Van Syoc M, Chanda S, Zane LT. 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):150–9.

    Article  PubMed  Google Scholar 

  77. Nazarian R, Weinberg JM. AN-2728, a PDE4 inhibitor for the potential topical treatment of psoriasis and atopic dermatitis. Curr Opin Investig Drugs. 2009;10(11):1236–42.

    CAS  PubMed  Google Scholar 

  78. Murrell DF, Gebauer K, Spelman L, Zane LT. Crisaborole topical ointment, 2% in adults with atopic dermatitis: a phase 2a, vehicle-controlled, proof-of-concept study. J Drugs Dermatol. 2015;14(10):1108–12.

    CAS  PubMed  Google Scholar 

  79. Draelos ZD, Stein Gold LF, Murrell DF, Hughes MH, Zane LT. Post hoc analyses of the effect of crisaborole topical ointment, 2% on atopic dermatitis: associated pruritus from phase 1 and 2 clinical studies. J Drugs Dermatol. 2016;15(2):172–6.

    CAS  PubMed  Google Scholar 

  80. Paller AS, Tom WL, Lebwohl MG, Blumenthal RL, Boguniewicz M, Call RS, et al. Efficacy and safety of crisaborole ointment, a novel, nonsteroidal phosphodiesterase 4 (PDE4) inhibitor for the topical treatment of atopic dermatitis (AD) in children and adults. J Am Acad Dermatol. 2016;75(3):494–503.

    Article  CAS  PubMed  Google Scholar 

  81. Zane LT, Kircik L, Call R, Tschen E, Draelos ZD, Chanda S, et al. Crisaborole topical ointment, 2% in patients ages 2 to 17 years with atopic dermatitis: a phase 1b, open-label, maximal-use systemic exposure study. Pediatr Dermatol. 2016;33(4):380–7.

    Article  PubMed  PubMed Central  Google Scholar 

  82. Jancso N, Jancso-Gabor A, Szolcsanyi J. Direct evidence for neurogenic inflammation and its prevention by denervation and by pretreatment with capsaicin. Br J Pharmacol Chemother. 1967;31(1):138–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Wallengren J, Klinker M. Successful treatment of notalgia paresthetica with topical capsaicin: vehicle-controlled, double-blind, crossover study. J Am Acad Dermatol. 1995;32(2 Pt 1):287–9.

    Article  CAS  PubMed  Google Scholar 

  84. Reimann S, Luger T, Metze D. Topical administration of capsaicin in dermatology for treatment of itching and pain. Hautarzt. 2000;51(3):164–72.

    Article  CAS  PubMed  Google Scholar 

  85. Dray A. Neuropharmacological mechanisms of capsaicin and related substances. Biochem Pharmacol. 1992;44(4):611–5.

    Article  CAS  PubMed  Google Scholar 

  86. Papoiu AD, Yosipovitch G. Topical capsaicin. The fire of a ‘hot’ medicine is reignited. Expert Opin Pharmacother. 2010;11(8):1359–71.

    Article  CAS  PubMed  Google Scholar 

  87. Yosipovitch G, Maibach HI, Rowbotham MC. Effect of EMLA pre-treatment on capsaicin-induced burning and hyperalgesia. Acta Derm Venereol. 1999;79(2):118–21.

    Article  CAS  PubMed  Google Scholar 

  88. Lee HG, Grossman SK, Valdes-Rodriguez R, Berenato F, Korbutov J, Chan YH, et al. Topical ketamine-amitriptyline-lidocaine for chronic pruritus: a retrospective study assessing efficacy and tolerability. J Am Acad Dermatol. 2017;76(4):760–1.

    Article  PubMed  Google Scholar 

  89. Freitag G, Hoppner T. Results of a postmarketing drug monitoring survey with a polidocanol-urea preparation for dry, itching skin. Curr Med Res Opin. 1997;13(9):529–37.

    Article  CAS  PubMed  Google Scholar 

  90. Yosipovitch G, Maibach HI. Effect of topical pramoxine on experimentally induced pruritus in humans. J Am Acad Dermatol. 1997;37(2 Pt 1):278–80.

    Article  CAS  PubMed  Google Scholar 

  91. Shuttleworth D, Hill S, Marks R, Connelly DM. Relief of experimentally induced pruritus with a novel eutectic mixture of local anaesthetic agents. Br J Dermatol. 1988;119(4):535–40.

    Article  CAS  PubMed  Google Scholar 

  92. Szepietowski JC, Szepietowski T, Reich A. Efficacy and tolerance of the cream containing structured physiological lipids with endocannabinoids in the treatment of uremic pruritus: a preliminary study. Acta Dermatovenerol Croat. 2005;13(2):97–103.

    PubMed  Google Scholar 

  93. Eberlein B, Eicke C, Reinhardt HW, Ring J. Adjuvant treatment of atopic eczema: assessment of an emollient containing N-palmitoylethanolamine (ATOPA study). J Eur Acad Dermatol Venereol. 2008;22(1):73–82.

    CAS  PubMed  Google Scholar 

  94. Stander S, Reinhardt HW, Luger TA. Topical cannabinoid agonists. An effective new possibility for treating chronic pruritus. Hautarzt. 2006;57(9):801–7.

    Article  CAS  PubMed  Google Scholar 

  95. Sherkheli MA, Gisselmann G, Vogt-Eisele AK, Doerner JF, Hatt H. Menthol derivative WS-12 selectively activates transient receptor potential melastatin-8 (TRPM8) ion channels. Pak J Pharm Sci. 2008;21(4):370–8.

    CAS  Google Scholar 

  96. Yosipovitch G, Szolar C, Hui XY, Maibach H. Effect of topically applied menthol on thermal, pain and itch sensations and biophysical properties of the skin. Arch Dermatol Res. 1996;288(5–6):245–8.

    Article  CAS  PubMed  Google Scholar 

  97. Peier AM, Moqrich A, Hergarden AC, Reeve AJ, Andersson DA, Story GM, et al. A TRP channel that senses cold stimuli and menthol. Cell. 2002;108(5):705–15.

    Article  CAS  PubMed  Google Scholar 

  98. Devillers AC, de Waard-van der Spek FB, Mulder PG, Oranje AP. Treatment of refractory atopic dermatitis using ‘wet-wrap’ dressings and diluted corticosteroids: results of standardized treatment in both children and adults. Dermatology. 2002;204(1):50–5.

    Article  CAS  PubMed  Google Scholar 

  99. Oranje AP, Devillers AC, Kunz B, Jones SL, DeRaeve L, Van Gysel D, et al. Treatment of patients with atopic dermatitis using wet-wrap dressings with diluted steroids and/or emollients. An expert panel’s opinion and review of the literature. J Eur Acad Dermatol Venereol. 2006;20(10):1277–86.

    Article  CAS  PubMed  Google Scholar 

  100. Devillers AC, Oranje AP. Efficacy and safety of ‘wet-wrap’ dressings as an intervention treatment in children with severe and/or refractory atopic dermatitis: a critical review of the literature. Br J Dermatol. 2006;154(4):579–85.

    Article  CAS  PubMed  Google Scholar 

  101. Hauser C, Wuethrich B, Matter L, Wilhelm JA, Sonnabend W, Schopfer K. Staphylococcus aureus skin colonization in atopic dermatitis patients. Dermatologica. 1985;170(1):35–9.

    Article  CAS  PubMed  Google Scholar 

  102. Ryan C, Shaw RE, Cockerell CJ, Hand S, Ghali FE. Novel sodium hypochlorite cleanser shows clinical response and excellent acceptability in the treatment of atopic dermatitis. Pediatr Dermatol. 2013;30(3):308–15.

    Article  PubMed  PubMed Central  Google Scholar 

  103. Wong SM, Ng TG, Baba R. Efficacy and safety of sodium hypochlorite (bleach) baths in patients with moderate to severe atopic dermatitis in Malaysia. J Dermatol. 2013;40(11):874–80.

    Article  CAS  PubMed  Google Scholar 

  104. Reynolds NJ, Franklin V, Gray JC, Diffey BL, Farr PM. Narrow-band ultraviolet B and broad-band ultraviolet a phototherapy in adult atopic eczema: a randomised controlled trial. Lancet. 2001;357(9273):2012–6.

    Article  CAS  PubMed  Google Scholar 

  105. Wallengren J, Sundler F. Phototherapy reduces the number of epidermal and CGRP-positive dermal nerve fibres. Acta Derm Venereol. 2004;84(2):111–5.

    Article  CAS  PubMed  Google Scholar 

  106. Rivard J, Lim HW. Ultraviolet phototherapy for pruritus. Dermatol Ther. 2005;18(4):344–54.

    Article  PubMed  Google Scholar 

  107. Wahlgren CF, Scheynius A, Hagermark O. Antipruritic effect of oral cyclosporin A in atopic dermatitis. Acta Derm Venereol. 1990;70(4):323–9.

    CAS  PubMed  Google Scholar 

  108. Roekevisch E, Spuls PI, Kuester D, Limpens J, Schmitt J. Efficacy and safety of systemic treatments for moderate-to-severe atopic dermatitis: a systematic review. J Allergy Clin Immunol. 2014;133(2):429–38.

    Article  CAS  PubMed  Google Scholar 

  109. Pacor ML, Di Lorenzo G, Martinelli N, Mansueto P, Rini GB, Corrocher R. Comparing tacrolimus ointment and oral cyclosporine in adult patients affected by atopic dermatitis: a randomized study. Clin Exp Allergy. 2004;34(4):639–45.

    Article  CAS  PubMed  Google Scholar 

  110. Harper JI, Ahmed I, Barclay G, Lacour M, Hoeger P, Cork MJ, et al. Cyclosporin for severe childhood atopic dermatitis: short course versus continuous therapy. Br J Dermatol. 2000;142(1):52–8.

    Article  CAS  PubMed  Google Scholar 

  111. Allison AC, Eugui EM. Purine metabolism and immunosuppressive effects of mycophenolate mofetil (MMF). Clin Transplant. 1996;10(1 Pt 2):77–84.

    CAS  PubMed  Google Scholar 

  112. Neuber K, Schwartz I, Itschert G, Dieck AT. Treatment of atopic eczema with oral mycophenolate mofetil. Br J Dermatol. 2000;143(2):385–91.

    Article  CAS  PubMed  Google Scholar 

  113. Jackson JM, Fowler JF Jr, Callen JP, Lorenz DJ. Mycophenolate mofetil for the treatment of chronic dermatitis: an open-label study of 16 patients. J Drugs Dermatol. 2010;9(4):356–62.

    PubMed  Google Scholar 

  114. Haeck IM, Knol MJ, Ten Berge O, van Velsen SG, de Bruin-Weller MS, Bruijnzeel-Koomen CA. 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):1074–84.

    Article  CAS  PubMed  Google Scholar 

  115. Meggitt SJ, Gray JC, Reynolds NJ. Azathioprine dosed by thiopurine methyltransferase activity for moderate-to-severe atopic eczema: a double-blind, randomised controlled trial. Lancet. 2006;367(9513):839–46.

    Article  CAS  PubMed  Google Scholar 

  116. Schram ME, Roekevisch E, Leeflang MM, Bos JD, Schmitt J, Spuls PI. A randomized trial of methotrexate versus azathioprine for severe atopic eczema. J Allergy Clin Immunol. 2011;128(2):353–9.

    Article  CAS  PubMed  Google Scholar 

  117. Berth-Jones J, Takwale A, Tan E, Barclay G, Agarwal S, Ahmed I, et al. Azathioprine in severe adult atopic dermatitis: a double-blind, placebo-controlled, crossover trial. Br J Dermatol. 2002;147(2):324–30.

    Article  CAS  PubMed  Google Scholar 

  118. Vachiramon V, Tey HL, Thompson AE, Yosipovitch G. Atopic dermatitis in African American children: addressing unmet needs of a common disease. Pediatr Dermatol. 2012;29(4):395–402.

    Article  PubMed  Google Scholar 

  119. Schmitt J, Schakel K, Folster-Holst R, Bauer A, Oertel R, Augustin M, et al. Prednisolone vs. ciclosporin for severe adult eczema. An investigator-initiated double-blind placebo-controlled multicentre trial. Br J Dermatol. 2010;162(3):661–8.

    Article  CAS  PubMed  Google Scholar 

  120. Hannuksela M, Kalimo K, Lammintausta K, Mattila T, Turjanmaa K, Varjonen E, et al. Dose ranging study: cetirizine in the treatment of atopic dermatitis in adults. Ann Allergy. 1993;70(2):127–33.

    CAS  PubMed  Google Scholar 

  121. Diepgen TL, Early Treatment of the Atopic Child Study G. Long-term treatment with cetirizine of infants with atopic dermatitis: a multi-country, double-blind, randomized, placebo-controlled trial (the ETAC trial) over 18 months. Pediatr Allergy Immunol. 2002;13(4):278–86.

    Article  PubMed  Google Scholar 

  122. Hundley JL, Yosipovitch G. Mirtazapine for reducing nocturnal itch in patients with chronic pruritus: a pilot study. J Am Acad Dermatol. 2004;50(6):889–91.

    Article  PubMed  Google Scholar 

  123. Davis MP, Frandsen JL, Walsh D, Andresen S, Taylor S. Mirtazapine for pruritus. J Pain Sympt Manag. 2003;25(3):288–91.

    Article  Google Scholar 

  124. Rowe B, Yosipovitch G. Paraneoplastic itch management. Curr Probl Dermatol. 2016;50:149–54.

    Article  PubMed  Google Scholar 

  125. Dawn AG, Yosipovitch G. Butorphanol for treatment of intractable pruritus. J Am Acad Dermatol. 2006;54(3):527–31.

    Article  PubMed  Google Scholar 

  126. Ong PY. Emerging drugs for atopic dermatitis. Expert Opin Emerg Drugs. 2009;14(1):165–79.

    Article  CAS  PubMed  Google Scholar 

  127. Furue M, Onozuka D, Takeuchi S, Murota H, Sugaya M, Masuda K, et al. Poor adherence to oral and topical medication in 3096 dermatological patients as assessed by the Morisky Medication Adherence Scale-8. Br J Dermatol. 2015;172(1):272–5.

    Article  CAS  PubMed  Google Scholar 

  128. Balkrishnan R. The importance of medication adherence in improving chronic-disease related outcomes: what we know and what we need to further know. Med Care. 2005;43(6):517–20.

    Article  PubMed  Google Scholar 

  129. Fischer G. Compliance problems in paediatric atopic eczema. Australas J Dermatol. 1996;37(Suppl 1):S10–3.

    Article  PubMed  Google Scholar 

  130. Basak PY, Ozturk M, Baysal V. Assessment of information and education about topical corticosteroids in dermatology outpatient departments: experience from Turkey. J Eur Acad Dermatol Venereol. 2003;17(6):652–8.

    Article  CAS  PubMed  Google Scholar 

  131. LeBovidge J, Borok J, Udkoff J, Yosipovitch G, Eichenfield LF. Atopic dermatitis: therapeutic care delivery: therapeutic education, shared decision-making, and access to care. Semin Cutan Med Surg. 2017;36(3):131–6.

    Article  PubMed  Google Scholar 

  132. Staab D, Diepgen TL, Fartasch M, Kupfer J, Lob-Corzilius T, Ring J, et al. Age related, structured educational programmes for the management of atopic dermatitis in children and adolescents: multicentre, randomised controlled trial. BMJ. 2006;332(7547):933–8.

    Article  PubMed  PubMed Central  Google Scholar 

  133. Yosipovitch G, Kwatra SG. Living with Itch 2013. 2013.

  134. Hall JM, Cruser D, Podawiltz A, Mummert DI, Jones H, Mummert ME. Psychological stress and the cutaneous immune response: roles of the HPA axis and the sympathetic nervous system in atopic dermatitis and psoriasis. Dermatol Res Pract. 2012;2012:403908.

    Article  PubMed  PubMed Central  Google Scholar 

  135. Schut C, Mollanazar NK, Kupfer J, Gieler U, Yosipovitch G. Psychological interventions in the treatment of chronic itch. Acta Derm Venereol. 2016;96(2):157–61.

    Article  PubMed  CAS  Google Scholar 

  136. Jacobson E. Entspannung Als Therapie (Relaxation as Therapy). Stuttgart: Klett-Cotta. 2011.

  137. Schut C, Weik U, Tews N, Gieler U, Deinzer R, Kupfer J. Psychophysiological effects of stress management in patients with atopic dermatitis: a randomized controlled trial. Acta Derm Venereol. 2013;93(1):57–61.

    Article  PubMed  Google Scholar 

  138. Belgrade MJ, Solomon LM, Lichter EA. Effect of acupuncture on experimentally induced itch. Acta Derm Venereol. 1984;64(2):129–33.

    CAS  PubMed  Google Scholar 

  139. Pfab F, Hammes M, Backer M, Huss-Marp J, Athanasiadis GI, Tolle TR, et al. Preventive effect of acupuncture on histamine-induced itch: a blinded, randomized, placebo-controlled, crossover trial. J Allergy Clin Immunol. 2005;116(6):1386–8.

    Article  CAS  PubMed  Google Scholar 

  140. Pfab F, Huss-Marp J, Gatti A, Fuqin J, Athanasiadis GI, Irnich D, et al. Influence of acupuncture on type I hypersensitivity itch and the wheal and flare response in adults with atopic eczema—a blinded, randomized, placebo-controlled, crossover trial. Allergy. 2010;65(7):903–10.

    Article  CAS  PubMed  Google Scholar 

  141. Lewis KE, Holdren MS, Maurer MF, Underwood S, Meengs B, Julien SH, et al. Interleukin (IL) 31 induces in cynomolgus monkeys a rapid and intense itch response that can be inhibited by an IL-31 neutralizing antibody. J Eur Acad Dermatol Venereol. 2017;31(1):142–50.

    Article  CAS  PubMed  Google Scholar 

  142. Ruzicka T, Hanifin JM, Furue M, Pulka G, Mlynarczyk I, Wollenberg A, et al. Anti-interleukin-31 receptor A antibody for atopic dermatitis. N Engl J Med. 2017;376(9):826–35.

    Article  CAS  PubMed  Google Scholar 

  143. McGuire D. Safety, pharmacokinetics and preliminary efficacy of asimadoline in pruritus associated with atopic dermatitis. https://ClinicalTrials.gov/show/NCT02475447.

  144. Hawi A, Alcorn H Jr, Berg J, Hines C, Hait H, Sciascia T. Pharmacokinetics of nalbuphine hydrochloride extended release tablets in hemodialysis patients with exploratory effect on pruritus. BMC Nephrol. 2015;16:47.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  145. Sciascia T. Study of nalbuphine HCl ER tablets in patients with prurigo nodularis. https://clinicaltrials.gov/show/NCT02174419. Accessed 25 May 2017.

  146. Results presented at the 2017 AAD: menlo therapeutics announces successful pruritus reduction results from phase 2 serlopitant trial (TCP-102) in 127 subjects with prurigo nodularis (press release). 2017.

  147. Ständer S PC, Heitman A, Xiao C, Polymeropoulos MH., editor An Investigational Study of Tradipitant for the Treatment of Chronic Pruritus in Patients with Atopic Dermatitis. In: 8th World Congress on Itch; 2015; Nara Kasugano International Forum IRAKA, Nara, Japan: Acta Derm Venereol.

  148. Murata Y, Song M, Kikuchi H, Hisamichi K, Xu XL, Greenspan A, et al. Phase 2a, randomized, double-blind, placebo-controlled, multicenter, parallel-group study of a H4 R-antagonist (JNJ-39758979) in Japanese adults with moderate atopic dermatitis. J Dermatol. 2015;42(2):129–39.

    Article  CAS  PubMed  Google Scholar 

  149. Werfel T, Lynch V, Asher A, et al. A phase 2a proof of concept clinical trial to evaluate ZPL-3893787 (ZPL-389), a potent, oral histamine H4 receptor antagonist for the treatment of moderate to severe atopic dermatitis (AD) in adults. Eur Acad Dermatol Venereol. 2016;71:95.

    Google Scholar 

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  1. Department of Dermatology and Itch Center, University of Miami Miller School of Medicine, Miami, FL, USA

    Janelle Pavlis & Gil Yosipovitch

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  1. Janelle Pavlis
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Correspondence to Gil Yosipovitch.

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No funding was received for the preparation of this review.

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Dr. Yosipovitch has been a consultant and investigator and advisory board member of Sanofi and Regeneron, Galderma, TREVI Menlo, TIOGA. He received royalties as the author of Living with Itch. Dr. Pavlis has no conflicts of interest to declare.

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Pavlis, J., Yosipovitch, G. Management of Itch in Atopic Dermatitis. Am J Clin Dermatol 19, 319–332 (2018). https://doi.org/10.1007/s40257-017-0335-4

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