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Published in: American Journal of Clinical Dermatology 3/2018

01-06-2018 | Review Article

Management of Itch in Atopic Dermatitis

Authors: Janelle Pavlis, Gil Yosipovitch

Published in: American Journal of Clinical Dermatology | Issue 3/2018

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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.
Literature
1.
go back to reference Boguniewicz M. Atopic dermatitis: beyond the itch that rashes. Immunol Allergy Clin N Am. 2005;25(2):333–51.CrossRef Boguniewicz M. Atopic dermatitis: beyond the itch that rashes. Immunol Allergy Clin N Am. 2005;25(2):333–51.CrossRef
2.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
3.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
4.
go back to reference Yosipovitch G, Papoiu AD. What causes itch in atopic dermatitis? Curr Allergy Asthma Rep. 2008;8(4):306–11.PubMedCrossRef Yosipovitch G, Papoiu AD. What causes itch in atopic dermatitis? Curr Allergy Asthma Rep. 2008;8(4):306–11.PubMedCrossRef
5.
go back to reference Lifschitz C. The impact of atopic dermatitis on quality of life. Ann Nutr Metab. 2015;66(Suppl 1):34–40.PubMedCrossRef Lifschitz C. The impact of atopic dermatitis on quality of life. Ann Nutr Metab. 2015;66(Suppl 1):34–40.PubMedCrossRef
7.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
8.
go back to reference Yamamoto A, Serizawa S, Ito M, Sato Y. Stratum corneum lipid abnormalities in atopic dermatitis. Arch Dermatol Res. 1991;283(4):219–23.PubMedCrossRef Yamamoto A, Serizawa S, Ito M, Sato Y. Stratum corneum lipid abnormalities in atopic dermatitis. Arch Dermatol Res. 1991;283(4):219–23.PubMedCrossRef
9.
go back to reference 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.CrossRef 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.CrossRef
10.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
11.
go back to reference Yosipovitch G, Fleischer A. Itch associated with skin disease: advances in pathophysiology and emerging therapies. Am J Clin Dermatol. 2003;4(9):617–22.PubMedCrossRef Yosipovitch G, Fleischer A. Itch associated with skin disease: advances in pathophysiology and emerging therapies. Am J Clin Dermatol. 2003;4(9):617–22.PubMedCrossRef
12.
go back to reference Ikoma A, Steinhoff M, Stander S, Yosipovitch G, Schmelz M. The neurobiology of itch. Nat Rev Neurosci. 2006;7(7):535–47.PubMedCrossRef Ikoma A, Steinhoff M, Stander S, Yosipovitch G, Schmelz M. The neurobiology of itch. Nat Rev Neurosci. 2006;7(7):535–47.PubMedCrossRef
14.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
15.
go back to reference 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.PubMedPubMedCentralCrossRef 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.PubMedPubMedCentralCrossRef
16.
go back to reference 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.PubMedPubMedCentralCrossRef 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.PubMedPubMedCentralCrossRef
17.
go back to reference 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.PubMedPubMedCentralCrossRef 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.PubMedPubMedCentralCrossRef
20.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
21.
go back to reference 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.PubMedPubMedCentralCrossRef 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.PubMedPubMedCentralCrossRef
22.
go back to reference 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.PubMedPubMedCentralCrossRef 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.PubMedPubMedCentralCrossRef
23.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
24.
go back to reference 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.PubMedPubMedCentralCrossRef 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.PubMedPubMedCentralCrossRef
25.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
26.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
27.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
28.
go back to reference 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. 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.
go back to reference 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.PubMedPubMedCentralCrossRef 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.PubMedPubMedCentralCrossRef
30.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
31.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
32.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
33.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
34.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
35.
36.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
37.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
38.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
39.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
40.
go back to reference 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.PubMed 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.PubMed
41.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
42.
go back to reference Yosipovitch G, Hundley JL. Practical guidelines for relief of itch. Dermatol Nurs. 2004;16(4):325–8 (quiz 9).PubMed Yosipovitch G, Hundley JL. Practical guidelines for relief of itch. Dermatol Nurs. 2004;16(4):325–8 (quiz 9).PubMed
43.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
44.
go back to reference van Zuuren EJ, Fedorowicz Z, Arents BWM. Emollients and moisturisers for eczema: abridged Cochrane systematic review including GRADE assessments. Br J Dermatol. 2017. van Zuuren EJ, Fedorowicz Z, Arents BWM. Emollients and moisturisers for eczema: abridged Cochrane systematic review including GRADE assessments. Br J Dermatol. 2017.
45.
46.
go back to reference 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 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
47.
go back to reference Kurtz ES, Wallo W. Colloidal oatmeal: history, chemistry and clinical properties. J Drugs Dermatol. 2007;6(2):167–70.PubMed Kurtz ES, Wallo W. Colloidal oatmeal: history, chemistry and clinical properties. J Drugs Dermatol. 2007;6(2):167–70.PubMed
48.
go back to reference 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 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
49.
go back to reference 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 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
50.
go back to reference Fowler JF Jr. Colloidal oatmeal formulations and the treatment of atopic dermatitis. J Drugs Dermatol. 2014;13(10):1180–3 (quiz 4-5).PubMed Fowler JF Jr. Colloidal oatmeal formulations and the treatment of atopic dermatitis. J Drugs Dermatol. 2014;13(10):1180–3 (quiz 4-5).PubMed
51.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
52.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
53.
go back to reference Ali SM, Yosipovitch G. Skin pH: from basic science to basic skin care. Acta Derm Venereol. 2013;93(3):261–7.PubMedCrossRef Ali SM, Yosipovitch G. Skin pH: from basic science to basic skin care. Acta Derm Venereol. 2013;93(3):261–7.PubMedCrossRef
54.
go back to reference 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.PubMed 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.PubMed
55.
go back to reference 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 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
56.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
57.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
58.
go back to reference Das A, Panda S. Use of topical corticosteroids in dermatology: an evidence-based approach. Indian J Dermatol. 2017;62(3):237–50.PubMedPubMedCentral Das A, Panda S. Use of topical corticosteroids in dermatology: an evidence-based approach. Indian J Dermatol. 2017;62(3):237–50.PubMedPubMedCentral
59.
go back to reference 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.PubMedPubMedCentralCrossRef 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.PubMedPubMedCentralCrossRef
60.
go back to reference Polano MK. The topical use of corticosteroids in dermatology. Ned Tijdschr Geneeskd. 1965;109:180–5.PubMed Polano MK. The topical use of corticosteroids in dermatology. Ned Tijdschr Geneeskd. 1965;109:180–5.PubMed
62.
go back to reference Roth HL, Brown EP. Hydrocortisone valerate. Double-blind comparison with two other topical steroids. Cutis. 1978;21(5):695–8.PubMed Roth HL, Brown EP. Hydrocortisone valerate. Double-blind comparison with two other topical steroids. Cutis. 1978;21(5):695–8.PubMed
63.
go back to reference Bolognia JL JJ, Schaffer JV. Glucocorticosteroids. Dermatology. 2012. 2075–88. Bolognia JL JJ, Schaffer JV. Glucocorticosteroids. Dermatology. 2012. 2075–88.
64.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
65.
go back to reference 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.PubMedPubMedCentralCrossRef 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.PubMedPubMedCentralCrossRef
66.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
68.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
69.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
70.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
71.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
72.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
73.
go back to reference 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.PubMed 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.PubMed
74.
go back to reference 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.PubMedPubMedCentralCrossRef 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.PubMedPubMedCentralCrossRef
75.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
76.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
77.
go back to reference 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.PubMed 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.PubMed
78.
go back to reference 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.PubMed 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.PubMed
79.
go back to reference 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.PubMed 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.PubMed
80.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
81.
go back to reference 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.PubMedPubMedCentralCrossRef 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.PubMedPubMedCentralCrossRef
82.
go back to reference 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.PubMedPubMedCentralCrossRef 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.PubMedPubMedCentralCrossRef
83.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
84.
go back to reference Reimann S, Luger T, Metze D. Topical administration of capsaicin in dermatology for treatment of itching and pain. Hautarzt. 2000;51(3):164–72.PubMedCrossRef Reimann S, Luger T, Metze D. Topical administration of capsaicin in dermatology for treatment of itching and pain. Hautarzt. 2000;51(3):164–72.PubMedCrossRef
85.
go back to reference Dray A. Neuropharmacological mechanisms of capsaicin and related substances. Biochem Pharmacol. 1992;44(4):611–5.PubMedCrossRef Dray A. Neuropharmacological mechanisms of capsaicin and related substances. Biochem Pharmacol. 1992;44(4):611–5.PubMedCrossRef
86.
go back to reference Papoiu AD, Yosipovitch G. Topical capsaicin. The fire of a ‘hot’ medicine is reignited. Expert Opin Pharmacother. 2010;11(8):1359–71.PubMedCrossRef Papoiu AD, Yosipovitch G. Topical capsaicin. The fire of a ‘hot’ medicine is reignited. Expert Opin Pharmacother. 2010;11(8):1359–71.PubMedCrossRef
87.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
88.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
89.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
90.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
91.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
92.
go back to reference 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 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
93.
go back to reference 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.PubMed 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.PubMed
94.
go back to reference Stander S, Reinhardt HW, Luger TA. Topical cannabinoid agonists. An effective new possibility for treating chronic pruritus. Hautarzt. 2006;57(9):801–7.PubMedCrossRef Stander S, Reinhardt HW, Luger TA. Topical cannabinoid agonists. An effective new possibility for treating chronic pruritus. Hautarzt. 2006;57(9):801–7.PubMedCrossRef
95.
go back to reference 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. 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.
96.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
97.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
98.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
99.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
100.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
101.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
102.
go back to reference 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.PubMedPubMedCentralCrossRef 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.PubMedPubMedCentralCrossRef
103.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
104.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
105.
go back to reference Wallengren J, Sundler F. Phototherapy reduces the number of epidermal and CGRP-positive dermal nerve fibres. Acta Derm Venereol. 2004;84(2):111–5.PubMedCrossRef Wallengren J, Sundler F. Phototherapy reduces the number of epidermal and CGRP-positive dermal nerve fibres. Acta Derm Venereol. 2004;84(2):111–5.PubMedCrossRef
106.
107.
go back to reference Wahlgren CF, Scheynius A, Hagermark O. Antipruritic effect of oral cyclosporin A in atopic dermatitis. Acta Derm Venereol. 1990;70(4):323–9.PubMed Wahlgren CF, Scheynius A, Hagermark O. Antipruritic effect of oral cyclosporin A in atopic dermatitis. Acta Derm Venereol. 1990;70(4):323–9.PubMed
108.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
109.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
110.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
111.
go back to reference Allison AC, Eugui EM. Purine metabolism and immunosuppressive effects of mycophenolate mofetil (MMF). Clin Transplant. 1996;10(1 Pt 2):77–84.PubMed Allison AC, Eugui EM. Purine metabolism and immunosuppressive effects of mycophenolate mofetil (MMF). Clin Transplant. 1996;10(1 Pt 2):77–84.PubMed
112.
go back to reference Neuber K, Schwartz I, Itschert G, Dieck AT. Treatment of atopic eczema with oral mycophenolate mofetil. Br J Dermatol. 2000;143(2):385–91.PubMedCrossRef Neuber K, Schwartz I, Itschert G, Dieck AT. Treatment of atopic eczema with oral mycophenolate mofetil. Br J Dermatol. 2000;143(2):385–91.PubMedCrossRef
113.
go back to reference 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 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
114.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
115.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
116.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
117.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
118.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
119.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
120.
go back to reference 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.PubMed 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.PubMed
121.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
122.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
123.
go back to reference Davis MP, Frandsen JL, Walsh D, Andresen S, Taylor S. Mirtazapine for pruritus. J Pain Sympt Manag. 2003;25(3):288–91.CrossRef Davis MP, Frandsen JL, Walsh D, Andresen S, Taylor S. Mirtazapine for pruritus. J Pain Sympt Manag. 2003;25(3):288–91.CrossRef
124.
125.
go back to reference Dawn AG, Yosipovitch G. Butorphanol for treatment of intractable pruritus. J Am Acad Dermatol. 2006;54(3):527–31.PubMedCrossRef Dawn AG, Yosipovitch G. Butorphanol for treatment of intractable pruritus. J Am Acad Dermatol. 2006;54(3):527–31.PubMedCrossRef
126.
127.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
128.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
129.
go back to reference Fischer G. Compliance problems in paediatric atopic eczema. Australas J Dermatol. 1996;37(Suppl 1):S10–3.PubMedCrossRef Fischer G. Compliance problems in paediatric atopic eczema. Australas J Dermatol. 1996;37(Suppl 1):S10–3.PubMedCrossRef
130.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
131.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
132.
go back to reference 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.PubMedPubMedCentralCrossRef 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.PubMedPubMedCentralCrossRef
133.
go back to reference Yosipovitch G, Kwatra SG. Living with Itch 2013. 2013. Yosipovitch G, Kwatra SG. Living with Itch 2013. 2013.
134.
go back to reference 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.PubMedPubMedCentralCrossRef 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.PubMedPubMedCentralCrossRef
135.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
136.
go back to reference Jacobson E. Entspannung Als Therapie (Relaxation as Therapy). Stuttgart: Klett-Cotta. 2011. Jacobson E. Entspannung Als Therapie (Relaxation as Therapy). Stuttgart: Klett-Cotta. 2011.
137.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
138.
go back to reference Belgrade MJ, Solomon LM, Lichter EA. Effect of acupuncture on experimentally induced itch. Acta Derm Venereol. 1984;64(2):129–33.PubMed Belgrade MJ, Solomon LM, Lichter EA. Effect of acupuncture on experimentally induced itch. Acta Derm Venereol. 1984;64(2):129–33.PubMed
139.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
140.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
141.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
142.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
144.
go back to reference 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.PubMedPubMedCentralCrossRef 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.PubMedPubMedCentralCrossRef
146.
go back to reference 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. 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.
go back to reference 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. 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.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
149.
go back to reference 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. 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.
Metadata
Title
Management of Itch in Atopic Dermatitis
Authors
Janelle Pavlis
Gil Yosipovitch
Publication date
01-06-2018
Publisher
Springer International Publishing
Published in
American Journal of Clinical Dermatology / Issue 3/2018
Print ISSN: 1175-0561
Electronic ISSN: 1179-1888
DOI
https://doi.org/10.1007/s40257-017-0335-4

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