Exploring itch in hidradenitis suppurativa with lessons from atopic dermatitis and psoriasis
Nicole Trupiano
Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
Search for more papers by this authorKelly Young
University of Michigan Medical School, Ann Arbor, Michigan, USA
Search for more papers by this authorHarika Echuri
Emory University Department of Dermatology, Atlanta, Georgia, USA
Search for more papers by this authorJalal Maghfour
Henry Ford Health Department of Dermatology, Detroit, Michigan, USA
Search for more papers by this authorCorresponding Author
Lauren A. V. Orenstein
Emory University Department of Dermatology, Atlanta, Georgia, USA
Correspondence
Lauren A. V. Orenstein, Emory University School of Medicine, 1525 Clifton Road NE, Suite 100, Atlanta, GA 30322, USA.
Email: [email protected]
Search for more papers by this authorIltefat Hamzavi
Henry Ford Health Department of Dermatology, Detroit, Michigan, USA
Search for more papers by this authorNicole Trupiano
Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
Search for more papers by this authorKelly Young
University of Michigan Medical School, Ann Arbor, Michigan, USA
Search for more papers by this authorHarika Echuri
Emory University Department of Dermatology, Atlanta, Georgia, USA
Search for more papers by this authorJalal Maghfour
Henry Ford Health Department of Dermatology, Detroit, Michigan, USA
Search for more papers by this authorCorresponding Author
Lauren A. V. Orenstein
Emory University Department of Dermatology, Atlanta, Georgia, USA
Correspondence
Lauren A. V. Orenstein, Emory University School of Medicine, 1525 Clifton Road NE, Suite 100, Atlanta, GA 30322, USA.
Email: [email protected]
Search for more papers by this authorIltefat Hamzavi
Henry Ford Health Department of Dermatology, Detroit, Michigan, USA
Search for more papers by this authorAbstract
Itch is a prominent symptom in many cutaneous disorders, including atopic dermatitis (AD), prurigo nodularis, and psoriasis. Itch is also a common but overlooked concern in patients with hidradenitis suppurativa (HS). Currently, the mechanisms underlying itch in HS remain unclear. To gain a better understanding, we reviewed the literature on pruritus in HS and other itch-predominant disorders, AD, and psoriasis. In HS, psoriasis, and AD, we found that itch often co-localized with pain and occurred more frequently at night. Furthermore, itch was found to negatively affect sleep and increase the risk for comorbid psychiatric disorders in HS, psoriasis, and AD. However, HS-, psoriasis-, and AD-related itch differ in temporality. Itch in AD is often described as chronic, while itch in HS and psoriasis is often described as episodic. HS-associated itch is likely multifactorial, and several mechanisms have been proposed including peripheral sensitization, central sensitization, and neuroinflammation. Prior studies in HS highlight enhanced IgE production and a dense infiltration of mast cells, along with a variety of cytokines and chemokines. Furthermore, alterations in the skin microbiome may contribute to itch in HS. To date, few therapies have been studied to treat itch in HS. Given the efficacy of several biologics and small molecules in treating itch in AD and psoriasis, similar agents may be explored in future HS studies. Alternative therapies to target neurological and psychiatric contributions to itch may include anticonvulsants, cannabinoids, and nonpharmacological treatments. In conclusion, pathomechanisms of itch in HS remain to be fully elucidated. However, we can draw on lessons from other pruritic disorders to begin addressing the symptom of it and identify important questions for future study.
CONFLICT OF INTEREST STATEMENT
Dr Orenstein has participated on advisory boards for Novartis and UCB, was a consultant and investigator for Chemocentryx, and received research grants from Pfizer. Dr Hamzavi has served as a consultant to Abbvie, Pfizer, Incyte, UCB, Boerhinger Ingelheim, Sonoma, Union therapeutics, Novartis, Jansen, Avita, Galderma, Vimela, and Almirall. He has also served as an investigator for Lenicura, Pfizer, Incyte, Avita, Loreal/Laroche Posay, and ITN. He is a board member and past-president of the HS Foundation and Global Vitiligo Foundation. The other authors have no conflicts of interest.
REFERENCES
- 1Green D, Dong X. The cell biology of acute itch. J Cell Biol. 2016; 213: 155–161.
- 2Thorlacius L, Ingram JR, Villumsen B, Esmann S, Kirby JS, Gottlieb AB, et al. A core domain set for hidradenitis suppurativa trial outcomes: an international Delphi process. Br J Dermatol. 2018; 179: 642–650.
- 3Vossen ARJV, Schoenmakers A, van Straalen KR, Prens EP, van der Zee HH. Assessing pruritus in hidradenitis Suppurativa: a cross-sectional study. Am J Clin Dermatol. 2017; 18: 687–695.
- 4Agarwal P, Lunge SB, Shetty NS, Karagaiah P, Daveluy S, Ortega-Loayza AG, et al. Itch in hidradenitis Suppurativa/acne Inversa: a systematic review. J Clin Med Res. 2022; 11:3813.
- 5Legat FJ. Itch in atopic dermatitis–what is new? Front Med. 2021; 7:644760.
10.3389/fmed.2021.644760 Google Scholar
- 6Garcovich S, Muratori S, Moltrasio C, Buscemi AA, Giovanardi G, Malvaso D, et al. Prevalence of neuropathic pain and related characteristics in hidradenitis Suppurativa: a cross-sectional study. J Clin Med Res. 2020; 9(12):4046. https://doi.org/10.3390/jcm9124046
- 7Nielsen RM, Lindsø Andersen P, Sigsgaard V, Theut Riis P, Jemec GB. Pain perception in patients with hidradenitis suppurativa. Br J Dermatol. 2020; 182: 166–174.
- 8Fernandez JM, Rizvi OH, Marr KD, Price KN, Hendricks AJ, Hsiao JL, et al. Itch and pain by lesion morphology in hidradenitis suppurativa patients. Int J Dermatol. 2021; 60: e56–e59.
- 9Kaaz K, Szepietowski JC, Matusiak Ł. Influence of itch and pain on sleep quality in patients with hidradenitis Suppurativa. Acta Derm Venereol. 2018; 98: 757–761.
- 10Matusiak Ł, Szczęch J, Kaaz K, Lelonek E, Szepietowski JC. Clinical characteristics of pruritus and pain in patients with hidradenitis Suppurativa. Acta Derm Venereol. 2018; 98: 191–194.
- 11Li Y, Speck P, Viera E, Siira M, Orenstein LAV. The influence of pain on reduced quality of life in patients with hidradenitis Suppurativa: a single-center retrospective study. Dermatology. 2023; 239: 1007–1012.
- 12Silverberg JI, Gelfand JM, Margolis DJ, Boguniewicz M, Fonacier L, Grayson MH, et al. Patient burden and quality of life in atopic dermatitis in US adults: a population-based cross-sectional study. Ann Allergy Asthma Immunol. 2018; 121: 340–347.
- 13Dawn A, Papoiu ADP, Chan YH, Rapp SR, Rassette N, Yosipovitch G. Itch characteristics in atopic dermatitis: results of a web-based questionnaire. Br J Dermatol. 2009; 160: 642–644.
- 14Elewski B, Alexis AF, Lebwohl M, Stein Gold L, Pariser D, Del Rosso J, et al. Itch: an under-recognized problem in psoriasis. J Eur Acad Dermatol Venereol. 2019; 33: 1465–1476.
- 15Yosipovitch G, Goon A, Wee J, Chan YH, Goh CL. The prevalence and clinical characteristics of pruritus among patients with extensive psoriasis. Br J Dermatol. 2000; 143: 969–973.
- 16 View of clinical characteristics of pruritus and pain in patients with hidradenitis suppurativa. 2024 https://medicaljournalssweden.se/actadv/article/view/2831/4409
- 17Wongvibulsin S, Khanna R, Kwatra SG. Anatomic localization and quantitative analysis of the burden of itch in the United States. J Am Acad Dermatol. 2020; 82: 234–236.
- 18O'Neill JL, Chan YH, Rapp SR, Yosipovitch G. Differences in itch characteristics between psoriasis and atopic dermatitis patients: results of a web-based questionnaire. Acta Derm Venereol. 2011; 91: 537–540.
- 19Ring HC, Theut Riis P, Zarchi K, Miller IM, Saunte DM, Jemec GB. Prodromal symptoms in hidradenitis suppurativa. Clin Exp Dermatol. 2017; 42: 261–265.
- 20Orenstein LAV, Salame N, Siira MR, Urbanski M, Flowers NI, Echuri H, et al. Pain experiences among those living with hidradenitis suppurativa: a qualitative study. Br J Dermatol. 2023; 188: 41–51.
- 21Simpson EL, Bieber T, Eckert L, Wu R, Ardeleanu M, Graham NMH, et al. Patient burden of moderate to severe atopic dermatitis (AD): insights from a phase 2b clinical trial of dupilumab in adults. J Am Acad Dermatol. 2016; 74: 491–498.
- 22Greenspan JD, Craft RM, LeResche L, Arendt-Nielsen L, Berkley KJ, Fillingim RB, et al. Studying sex and gender differences in pain and analgesia: a consensus report. Pain. 2007; 132(Suppl 1): S26–S45.
- 23Vossen ARJV, van der Zee HH, Tsoi LC, Xing X, Devalaraja M, Gudjonsson JE, et al. Novel cytokine and chemokine markers of hidradenitis suppurativa reflect chronic inflammation and itch. Allergy. 2019; 74: 631–634.
- 24Patel ZS, Hoffman LK, Sutton L, Cohen SR, Lowes MA, Seng EK. The patient experience of pain in hidradenitis suppurativa. Br J Dermatol. 2020; 183: 401–402.
- 25Reich A, Hrehorów E, Szepietowski JC. Pruritus is an important factor negatively influencing the well-being of psoriatic patients. Acta Derm Venereol. 2010; 90: 257–263.
- 26Gupta MA, Gupta AK, Schork NJ, Ellis CN. Depression modulates pruritus perception: a study of pruritus in psoriasis, atopic dermatitis, and chronic idiopathic urticaria. Psychosom Med. 1994; 56: 36–40.
- 27Chuquilin M, Alghalith Y, Fernandez KH. Neurocutaneous disease: cutaneous neuroanatomy and mechanisms of itch and pain. J Am Acad Dermatol. 2016; 74: 197–212.
- 28Glatte P, Buchmann SJ, Hijazi MM, Illigens BM-W, Siepmann T. Architecture of the cutaneous autonomic nervous system. Front Neurol. 2019; 10: 970.
- 29De Vita V, Matusiak Ł, Szepietowski JC. Comment on: “assessing pruritus in hidradenitis Suppurativa: a cross-sectional study”. Am J Clin Dermatol. 2017; 18: 707–708.
- 30van Straalen KR. Chronic pain in hidradenitis Suppurativa explained through the process of central sensitization. JAMA Dermatol. 2020; 156: 615–616.
- 31Ikoma A. Analysis of the mechanism for the development of allergic skin inflammation and the application for its treatment: mechanisms and management of itch in atopic dermatitis. J Pharmacol Sci. 2009; 110: 265–269.
- 32van der Zee HH, de Ruiter L, Boer J, van den Broecke DG, den Hollander JC, Laman JD, et al. Alterations in leucocyte subsets and histomorphology in normal-appearing perilesional skin and early and chronic hidradenitis suppurativa lesions. Br J Dermatol. 2012; 166: 98–106.
- 33Pascual JC, García-Martínez FJ, Martorell A, González I, Hispan P. Increased total serum IgE levels in moderate-to-severe hidradenitis suppurativa. Br J Dermatol. 2016; 175: 1101–1102.
- 34Ji R-R. Neuroimmune interactions in itch: do chronic itch, chronic pain, and chronic cough share similar mechanisms? Pulm Pharmacol Ther. 2015; 35: 81–86.
- 35Shi L, Liu C, Xiong H, Shi D. Elevation of IgE in patients with psoriasis: is it a paradoxical phenomenon? Front Med (Lausanne). 2022; 13:1007892.
10.3389/fmed.2022.1007892 Google Scholar
- 36Umehara Y, Kiatsurayanon C, Trujillo-Paez JV, Chieosilapatham P, Peng G, Yue H, et al. Intractable itch in atopic dermatitis: causes and treatments. Biomedicine. 2021; 9:229.
- 37List EK, Pascual JC, Zarchi K, Nürnberg BM, Jemec GBE. Mast cells in hidradenitis suppurativa: a clinicopathological study. Arch Dermatol Res. 2019; 311: 331–335.
- 38Fletcher JM, Moran B, Petrasca A, Smith CM. IL-17 in inflammatory skin diseases psoriasis and hidradenitis suppurativa. Clin Exp Immunol. 2020; 201: 121–134.
- 39Komiya E, Tominaga M, Kamata Y, Suga Y, Takamori K. Molecular and cellular mechanisms of itch in psoriasis. Int J Mol Sci. 2020; 21:8406.
- 40Kimball AB, Jemec GBE, Alavi A, Reguiai Z, Gottlieb AB, Bechara FG, et al. Secukinumab in moderate-to-severe hidradenitis suppurativa (SUNSHINE and SUNRISE): week 16 and week 52 results of two identical, multicentre, randomised, placebo-controlled, double-blind phase 3 trials. Lancet. 2023; 401: 747–761.
- 41Kimball AB, Jemec GBE, Sayed CJ, Kirby JS, Prens E, Ingram JR, et al. Efficacy and safety of bimekizumab in patients with moderate-to-severe hidradenitis suppurativa (BE HEARD I and BE HEARD II): two 48-week, randomised, double-blind, placebo-controlled, multicentre phase 3 trials. Lancet. 2024; 403: 2504–2519.
- 42Renert-Yuval Y, Gonzalez J, Garcet S, Williams SC, Moreno A, Krueger JG. Eosinophils in hidradenitis suppurativa patients exhibit pro-inflammatory traits, implicating a potential pathogenic role in the disease. Exp Dermatol. 2024; 33:e15129.
- 43Kagami S, Kakinuma T, Saeki H, Tsunemi Y, Fujita H, Nakamura K, et al. Significant elevation of serum levels of eotaxin-3/CCL26, but not of eotaxin-2/CCL24, in patients with atopic dermatitis: serum eotaxin-3/CCL26 levels reflect the disease activity of atopic dermatitis. Clin Exp Immunol. 2003; 134: 309–313.
- 44Li W, Yosipovitch G. The role of the microbiome and microbiome-derived metabolites in atopic dermatitis and non-histaminergic itch. Am J Clin Dermatol. 2020; 21(Suppl 1): 44–50.
- 45Celoria V, Rosset F, Pala V, Dapavo P, Ribero S, Quaglino P, et al. The skin microbiome and its role in psoriasis: a review. Psoriasis (Auckl). 2023; 26: 71–78.
- 46Hsu DK, Fung MA, Chen H-L. Role of skin and gut microbiota in the pathogenesis of psoriasis, an inflammatory skin disease. Med Microecol. 2020; 4:100016.
10.1016/j.medmic.2020.100016 Google Scholar
- 47Vossen ARJV, van der Zee HH, Prens EP. Hidradenitis suppurativa: a systematic review integrating inflammatory pathways into a cohesive pathogenic model. Front Immunol. 2018; 14: 2965.
- 48Ring HC, Thorsen J, Saunte DM, Lilje B, Bay L, Riis PT, et al. The follicular skin microbiome in patients with hidradenitis Suppurativa and healthy controls. JAMA Dermatol. 2017; 153: 897–905.
- 49Naik HB, Piguet V. Standardizing hidradenitis Suppurativa skin microbiome research: the methods matter. J Invest Dermatol. 2020; 140: 1688–1690.
- 50Riverain-Gillet É, Guet-Revillet H, Jais J-P, Ungeheuer M-N, Duchatelet S, Delage M, et al. The surface microbiome of clinically unaffected skinfolds in hidradenitis Suppurativa: a cross-sectional culture-based and 16S rRNA gene amplicon sequencing study in 60 patients. J Invest Dermatol. 2020; 140: 1847–1855.e6.
- 51Cusack NJ, Hourani SM, Loizou GD, Welford LA. Pharmacological effects of isopolar phosphonate analogues of ATP on P2-purinoceptors in Guinea-pig taenia coli and urinary bladder. Br J Pharmacol. 1987; 90: 791–795.
- 52Pascual JC, Alvarez P, Encabo B, González I, Hispán P, Poveda I, et al. Comment on: “assessing pruritus in hidradenitis Suppurativa: a cross-sectional study”. Am J Clin Dermatol. 2017; 18: 705–706.
- 53Kim SR, Choi Y-G, Jo SJ. Smoking cessation and risk of hidradenitis suppurativa development. JAMA Dermatol American Medical Association (AMA). 2024; 160: 1056–1065.
- 54Monfrecola G, Balato A, Caiazzo G, De Vita V, Di Caprio R, Donnarumma M, et al. Mammalian target of rapamycin, insulin resistance and hidradenitis suppurativa: a possible metabolic loop. J Eur Acad Dermatol Venereol. 2016; 30: 1631–1633.
- 55Obara I, Medrano MC, Signoret-Genest J, Jiménez-Díaz L, Géranton SM, Hunt SP. Inhibition of the mammalian target of rapamycin complex 1 signaling pathway reduces itch behaviour in mice. Pain. 2015; 156: 1519–1529.
- 56Xu H, Li H. Acne, the skin microbiome, and antibiotic treatment. Am J Clin Dermatol. 2019; 20: 335–344.
- 57Blauvelt A, Teixeira HD, Simpson EL, Costanzo A, De Bruin-Weller M, Barbarot S, et al. Efficacy and safety of Upadacitinib vs Dupilumab in adults with moderate-to-severe atopic dermatitis: a randomized clinical trial. JAMA Dermatol. 2021; 157: 1047–1055.
- 58Reich K, Teixeira HD, de Bruin-Weller M, Bieber T, Soong W, Kabashima K, et al. Safety and efficacy of upadacitinib in combination with topical corticosteroids in adolescents and adults with moderate-to-severe atopic dermatitis (AD up): results from a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2021; 397: 2169–2181.
- 59Bieber T, Simpson EL, Silverberg JI, Thaçi D, Paul C, Pink AE, et al. Abrocitinib versus placebo or Dupilumab for atopic dermatitis. N Engl J Med. 2021; 384: 1101–1112.
- 60Simpson EL, Sinclair R, Forman S, Wollenberg A, Aschoff R, Cork M, et al. Efficacy and safety of abrocitinib in adults and adolescents with moderate-to-severe atopic dermatitis (JADE MONO-1): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial. Lancet. 2020; 396: 255–266.
- 61Simpson EL, Lacour J-P, Spelman L, Galimberti R, Eichenfield LF, Bissonnette R, et al. Baricitinib in patients with moderate-to-severe atopic dermatitis and inadequate response to topical corticosteroids: results from two randomized monotherapy phase III trials. Br J Dermatol. 2020; 183: 242–255.
- 62Bissonnette R, Papp KA, Poulin Y, Gooderham M, Raman M, Mallbris L, et al. Topical tofacitinib for atopic dermatitis: a phase IIa randomized trial. Br J Dermatol. 2016; 175: 902–911.
- 63Papp K, Szepietowski JC, Kircik L, Toth D, Eichenfield LF, Leung DYM, et al. Efficacy and safety of ruxolitinib cream for the treatment of atopic dermatitis: results from 2 phase 3, randomized, double-blind studies. J Am Acad Dermatol. 2021; 85: 863–872.
- 64Kirby JS, Okun MM, Alavi A, Bechara FG, Zouboulis CC, Brown K, et al. Efficacy and safety of the oral Janus kinase 1 inhibitor povorcitinib (INCB054707) in patients with hidradenitis suppurativa in a phase 2, randomized, double-blind, dose-ranging, placebo-controlled study. J Am Acad Dermatol. 2024; 90: 521–529.
- 65Silfvast-Kaiser A, Paek SY, Menter A. Anti-IL17 therapies for psoriasis. Expert Opin Biol Ther. 2019; 19: 45–54.
- 66Glatt S, Jemec GBE, Forman S, Sayed C, Schmieder G, Weisman J, et al. Efficacy and safety of Bimekizumab in moderate to severe hidradenitis Suppurativa: a phase 2, double-blind, placebo-controlled randomized clinical trial. JAMA Dermatol. 2021; 157: 1279–1288.
- 67Frew JW, Navrazhina K, Grand D, Sullivan-Whalen M, Gilleaudeau P, Garcet S, et al. The effect of subcutaneous brodalumab on clinical disease activity in hidradenitis suppurativa: an open-label cohort study. J Am Acad Dermatol. 2020; 83: 1341–1348.
- 68Orfali RL, Aoki V. Blockage of the IL-31 pathway as a potential target therapy for atopic dermatitis. Pharmaceutics. 2023; 15:577.
- 69Kabashima K, Furue M, Hanifin JM, Pulka G, Wollenberg A, Galus R, et al. Nemolizumab in patients with moderate-to-severe atopic dermatitis: randomized, phase II, long-term extension study. J Allergy Clin Immunol. 2018; 142: 1121–1130.e7.
- 70Ruzicka 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: 826–835.
- 71Silverberg JI, Pinter A, Pulka G, Poulin Y, Bouaziz J-D, Wollenberg A, et al. Phase 2B randomized study of nemolizumab in adults with moderate-to-severe atopic dermatitis and severe pruritus. J Allergy Clin Immunol. 2020; 145: 173–182.
- 72Sidbury R, Alpizar S, Laquer V, Dhawan S, Abramovits W, Loprete L, et al. Pharmacokinetics, safety, efficacy, and biomarker profiles during nemolizumab treatment of atopic dermatitis in adolescents. Dermatol Ther (Heidelb). 2022; 12: 631–642.
- 73Yamanaka-Takaichi M, Demer AM, Baum CL, Theoharides TC, Alavi A. The role of mast cells and related molecules in itch of hidradenitis suppurativa. Exp Dermatol. 2024; 33:e15061.
- 74Kim S-W, Kang H-J, Jhon M, Kim J-W, Lee J-Y, Walker AJ, et al. Statins and inflammation: new therapeutic opportunities in psychiatry. Front Psychiatry. 2019; 5: 103.
10.3389/fpsyt.2019.00103 Google Scholar
- 75Diamantis E, Kyriakos G, Quiles-Sanchez LV, Farmaki P, Troupis T. The anti-inflammatory effects of statins on coronary artery disease: an updated review of the literature. Curr Cardiol Rev. 2017; 13: 209–216.
- 76Molina-Leyva A, Cuenca-Barrales C. Pruritus and malodour in patients with hidradenitis Suppurativa: impact on quality of life and clinical features associated with symptom severity. Dermatology. 2020; 236: 59–65.
- 77Gunal AI, Ozalp G, Yoldas TK, Gunal SY, Kirciman E, Celiker H. Gabapentin therapy for pruritus in haemodialysis patients: a randomized, placebo-controlled, double-blind trial. Nephrol Dial Transplant. 2004; 19: 3137–3139.
- 78Matsuda KM, Sharma D, Schonfeld AR, Kwatra SG. Gabapentin and pregabalin for the treatment of chronic pruritus. J Am Acad Dermatol. 2016; 75: 619–625.e6.
- 79Avila C, Massick S, Kaffenberger BH, Kwatra SG, Bechtel M. Cannabinoids for the treatment of chronic pruritus: a review. J Am Acad Dermatol. 2020; 82: 1205–1212.
- 80Shojaei D, Zabihi H, Maida V, Kirchhof MG, Alavi A. Evaluation of cannabis-related product use among patients with hidradenitis suppurativa: a narrative review. J Cutan Med Surg. 2024; 31:12034754241266124.
- 81Nickles MA, Lio PA. Cannabinoids in dermatology: Hope or hype? Cannabis Cannabinoid Res. 2020; 5: 279–282.
- 82Eagleston LRM, Kalani NK, Patel RR, Flaten HK, Dunnick CA, Dellavalle RP. Cannabinoids in dermatology: a scoping review. Dermatol Online J. 2018; 24(6):13030/qt7pn8c0sb. https://www.ncbi.nlm.nih.gov/pubmed/30142706
10.5070/D3246040706 Google Scholar
- 83Liu X, Li L, Jiang J, Ge W, Huang Y, Jin Z, et al. Role of type I cannabinoid receptor in sensory neurons in Psoriasiform skin inflammation and pruritus. J Invest Dermatol. 2023; 143: 812–821.e3.
- 84Pulvirenti N, Nasca MR, Micali G. Topical adelmidrol 2% emulsion, a novel aliamide, in the treatment of mild atopic dermatitis in pediatric subjects: a pilot study. Acta Dermatovenerol Croat. 2007; 15: 80–83.
- 85Eberlein B, Eicke C, Reinhardt H-W, Ring J. Adjuvant treatment of atopic eczema: assessment of an emollient containing N-palmitoylethanolamine (ATOPA study). J Eur Acad Dermatol Venereol. 2008; 22: 73–82.
- 86Bigliardi PL, Stammer H, Jost G, Rufli T, Büchner S, Bigliardi-Qi M. Treatment of pruritus with topically applied opiate receptor antagonist. J Am Acad Dermatol. 2007; 56: 979–988.
- 87Yatsuzuka R, Inoue T, Jiang S, Nakano Y, Kamei C. Development of new atopic dermatitis models characterized by not only itching but also inflammatory skin in mice. Eur J Pharmacol. 2007; 565: 225–231.
- 88Ständer S, Steinhoff M. Pathophysiology of pruritus in atopic dermatitis: an overview. Exp Dermatol. 2002; 11: 12–24.
- 89Jafferany M, Davari ME. Itch and psyche: psychiatric aspects of pruritus. Int J Dermatol. 2019; 58: 3–23.
- 90Hong J, Buddenkotte J, Berger TG, Steinhoff M. Management of itch in atopic dermatitis. Semin Cutan Med Surg. 2011; 30: 71–86.
- 91Habib S, Morrissey S. Stress management for atopic dermatitis. Behav Chang. 1999; 16: 226–236.