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Current Topical and Systemic Therapies for Itch

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Pharmacology of Itch

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 226))

Abstract

Itch is a common distressing symptom which may be caused by multifactorial aetiologies including inflammatory skin diseases, systemic diseases, neuropathic conditions and psychogenic disorders. Itch is a term used synonymously with pruritus and is defined as acute if it lasts less than 6 weeks or chronic if it persists for more than 6 weeks. It can have the same impact on the quality of life as chronic pain and shares many of the same pathophysiological pathways. Depending on the aetiology of the itch, different pathogenic mechanisms have been postulated with a number of mediators identified. These include histamine, leukotrienes, proteases, neuropeptides, cytokines and opioids, which may activate peripheral itch-mediating C-fibres via receptors on the nerve terminals and central neuronal pathways. Therefore, there is no single universally effective anti-itch treatment available. First-line treatments for itch include topical therapies, such as emollients, mild cleansers (low pH), topical anaesthetics, steroids, calcineurin inhibitors and coolants (menthol). Treatment with systemic therapies can vary according to the aetiology of the chronic itch. Non-sedating antihistamines are helpful in conditions such as urticaria where the itch is primarily histamine mediated. Although the itch of eczema is not mediated by histamine, sedating antihistamines at night are helpful to break the itch-scratch cycle. Chronic itch may also be treated with other systemic therapies, such as anticonvulsants, antidepressants as well as mu-opioid antagonists, kappa-opioid agonists and phototherapy, depending on the cause of the itch. This article summarises the topical and systemic therapies available with our current understanding of the pathophysiology of itch.

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References

  • Akiyama T, Carstens E (2014) Spinal coding of itch and pain. In: Carsterns E, Akiyama T (eds) Itch: mechanisms and treatment. CRC, Boca Raton, FL, pp 319–338

    Chapter  Google Scholar 

  • Asero R, Tedeschi A, Cugno M (2013) Treatment of refractory chronic urticaria: current and future therapeutic options. Am J Clin Dermatol 14:481–488

    Article  PubMed  Google Scholar 

  • Daly BM, Shuster S (2000) Antipruritic action of thalidomide. Acta Derm Venereol 80:24–25

    Article  CAS  PubMed  Google Scholar 

  • Davidson S, Giesler GJ (2010) The multiple pathways for itch and their interactions with pain. Trends Neurosci 33:550–558

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Dawn AG, Yosipovitch G (2006) Butorphanol for treatment of intractable pruritus. J Am Acad Dermatol 54:527–531

    Article  PubMed  Google Scholar 

  • Drake LA, Fallon JD, Sober A (1994) The Doxepin Study Group. Relief of pruritus in patients with atopic dermatitis after treatment with topical doxepin cream. J Am Acad Dermatol 31:613–616

    Article  CAS  PubMed  Google Scholar 

  • Ehrchen J, Ständer S (2008) Pregabalin in the treatment of chronic pruritus. J Am Acad Dermatol 58(Suppl):S36–S37

    Article  PubMed  Google Scholar 

  • Elmariah SB, Lerner EA (2011) Topical therapies for pruritus. Semin Cutan Med Surg 30:118–126

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Engin B, Ozdemir M (2008) Prospective randomized non-blinded clinical trial on the use of dapsone plus antihistamine vs. antihistamine in patients with chronic idiopathic urticaria. J Eur Acad Dermatol Venereol 22:481–486

    Article  CAS  PubMed  Google Scholar 

  • Eschler DC, Klein PA (2010) An evidence-based review of the efficacy of topical antihistamines in the relief of pruritus. J Drugs Dermatol 9:992–997

    PubMed  Google Scholar 

  • Freitag G, Hoppner T (1997) Results of a postmarketing drug monitoring survey with a polidocanol-urea preparation for dry, itching skin. Curr Med Res Opin 13:529–537

    Article  CAS  PubMed  Google Scholar 

  • Gottlieb A, Feng JY, Harrison DJ, Globe D (2010) Validation and response to treatment of a pruritus self-assessment tool in patients with moderate to severe psoriasis. J Am Acad Dermatol 63:580–586

    Article  PubMed  Google Scholar 

  • Hundey JL, Yosipovitch G (2004) Mirtazapine for reducing nocturnal itch in patients with chronic pruritus: a pilot study. J Am Acad Dermatol 50:889–891

    Article  Google Scholar 

  • Imamachi N, Park GH, Leeh H et al (2009) TRPV1-expressing primary afferents generate behavioral responses to pruritogens via multiple mechanisms. Proc Natl Acad Sci U S A 106:11330–11335

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Jessell TM, Iversen LL, Cuello AC (1978) Capsaicin-induced depletion of substance P from primary sensory neurones. Brain Res 152:183–188

    Article  CAS  PubMed  Google Scholar 

  • Kanwar AJ, De D (2013) Methotrexate for treatment of lichen planus: old drug, new indication. J Eur Acad Dermatol Venereol 27:e410–e413

    Article  CAS  PubMed  Google Scholar 

  • Kaplan A, Ledford D, Ashby M et al (2013) Omalizumab in patients with symptomatic chronic idiopathic/spontaneous urticaria despite standard combination therapy. J Allergy Clin Immunol 132:101–109

    Article  CAS  PubMed  Google Scholar 

  • Kaufmann R, Bieber T, Helgesen AL et al (2006) Onset of pruritus relief with pimecrolimus cream 1 % in adult patients with atopic dermatitis: a randomized trial. Allergy 61:375–381

    Article  CAS  PubMed  Google Scholar 

  • Kemmler N, Peitsch WK, Glorer E, Goerdt S (2005) Hypereosinophilic dermatitis. An overlooked diagnosis? Hautarzt 56:1060–1067

    Article  CAS  PubMed  Google Scholar 

  • Ko M-J, Yang J-Y, Wu H-Y et al (2011) Narrowband ultraviolet B phototherapy for patients with refractory uraemic pruritus: a randomized controlled trial. Br J Dermatol 165:633–639

    Article  PubMed  Google Scholar 

  • Krueger GG, Langley RG, Finlay AY et al (2005) Patient-reported outcomes of psoriasis improvement with etanercept therapy: results of a randomized phase III trial. Br J Dermatol 153:1192–1199

    Article  CAS  PubMed  Google Scholar 

  • Kumagai H, Ebata T, Takamori K et al (2010) Effect of a novel kappa-receptor agonist, nalfurafine hydrochloride, on severe itch in 337 haemodialysis patients: a Phase III, randomized, double-blind, placebo-controlled study. Nephrol Dial Transplant 25:1251–1257

    Article  CAS  PubMed  Google Scholar 

  • Lawlor F (2014) Urticaria and angioedema in pregnancy and lactation. Immunol Allergy Clin North Am 34:149–156

    Article  PubMed  Google Scholar 

  • Leslie TA (2013) Itch. Medicine 41:367–371

    Article  Google Scholar 

  • Loosemore MP, Bordeaux JS, Bernhard JD (2007) Gabapentin treatment for notalgia paresthetica, a common isolated peripheral sensory neuropathy. J Eur Acad Dermatol Venereol 21:1440–1441

    Article  CAS  PubMed  Google Scholar 

  • Madan V, Griffiths CE (2007) Systemic ciclosporin and tacrolimus in dermatology. Dermatol Ther 20:239–250

    Article  CAS  PubMed  Google Scholar 

  • Maurer T, Poncelet A, Berger T (2004) Thalidomide treatment for prurigo nodularis in human immunodeficiency virus-infected subjects: efficacy and risk of neuropathy. Arch Dermatol 140:845–849

    Article  CAS  PubMed  Google Scholar 

  • Maurer M, Rosén K, Hsieh H-J et al (2013) Omalizumab for the treatment of chronic idiopathic or spontaneous urticaria. N Engl J Med 368:924–935

    Article  CAS  PubMed  Google Scholar 

  • McCollum AD, Paik A, Eichenfield LF (2010) The safety and efficacy of tacrolimus ointment in pediatric patients with atopic dermatitis. Pediatr Dermatol 27:425–436

    Article  PubMed  Google Scholar 

  • Metz M, Krause K, Maurer M, Magerl M (2011) Treatment of notalgia paraesthetica with an 8 % capsaicin patch. Br J Dermatol 165:1359–1361

    Article  CAS  PubMed  Google Scholar 

  • Mochizuki H, Papoiu ADP, Yosipovitch G (2014) Brain processing of itch and scratching. In: Carstens E, Akiyama T (eds) Itch: mechanisms and treatment. CRC Press, Boca Raton, FL, pp 391–407

    Chapter  Google Scholar 

  • Neuber K, Schwartz I, Itschert G, Dieck AT (2000) Treatment of atopic eczema with oral mycophenolate mofetil. Br J Dermatol 143:385–391

    Article  CAS  PubMed  Google Scholar 

  • O’Donaghue M, Tharp MD (2005) Antihistamines and their role as antipruritics. Dermatol Ther 18:333–340

    Article  Google Scholar 

  • Papoiu AD, Yosipovitch G (2010) Topical capsaicin. The fire of a ‘hot’ medicine is reignited. Expert Opin Pharmacother 11:1359–1371

    Article  CAS  PubMed  Google Scholar 

  • Papoiu ADP, Valdes-Rodriguez R, Nattkemper LA et al (2013) A novel topical formulation containing strontium chloride significantly reduces the intensity and duration of cowhage-induced itch. Acta Derm Venereol 93:520–526

    Article  PubMed  Google Scholar 

  • Patel T, Yosipovitch G (2010) Therapy of pruritus. Expert Opin Pharmacother 11:1673–1682

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Patel AN, Langan SM, Batchelor JM (2012) A randomized trial of methotrexate vs. azathioprine for severe atopic eczema: a critical appraisal. Br J Dermatol 166:701–714

    Article  CAS  PubMed  Google Scholar 

  • Pfeiffer C (2006) [Dermatitis herpetiformis. A clinical chameleon]. Hautarzt 57:1021–1028

    Article  CAS  PubMed  Google Scholar 

  • Phan NQ, Bernhard JD, Luger TA, Ständer S (2010) Antipruritic treatment with systemic μ-opioid receptor antagonists: a review. J Am Acad Dermatol 63:680–688

    Article  CAS  PubMed  Google Scholar 

  • Poterucha TJ, Murphy SL, Sandroni P et al (2013a) Topical amitriptyline combined with topical ketamine for the management of recalcitrant localized pruritus: a retrospective pilot study. J Am Acad Dermatol 69:320–321

    Article  CAS  PubMed  Google Scholar 

  • Poterucha TJ, Murphy SL, Davis MDP et al (2013b) Topical amitriptyline-ketamine for the treatment of brachioradial pruritus. JAMA Dermatol 149:148–150

    Article  PubMed  Google Scholar 

  • Raap U, Ständer S, Metz M (2011) Pathophysiology of itch and new treatments. Curr Opin Allergy Clin Immunol 11:420–427

    Article  CAS  PubMed  Google Scholar 

  • Ringkamp M, Schepers RJ, Shimada SG et al (2011) A role for nociceptive, myelinated nerve fibers in itch sensation. J Neurosci 31:14841–14849

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Rivard J, Lim HW (2005) Ultraviolet phototherapy for pruritus. Dermatol Ther 18:344–354

    Article  PubMed  Google Scholar 

  • Samrao A, Berry TM, Goreshi R, Simpson EL (2012) A pilot study of an oral phosphodiesterase inhibitor (apremilast) for atopic dermatitis in adults. Arch Dermatol 148:890–897

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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

    Article  PubMed Central  PubMed  Google Scholar 

  • Singer EM, Shin DB, Nattkemper LA et al (2013) IL-31 is produced by the malignant T-cell population in cutaneous T-cell lymphoma and correlates with CTCL pruritus. J Invest Dermatol 133:2783–2785

    Article  CAS  PubMed  Google Scholar 

  • Smith C, Barker J (2002) Methotrexate. In: Wakelin S (ed) Handbook of systemic drug treatment in dermatology. Manson, London, pp 172–181

    Google Scholar 

  • Sola-Ortigosa J, Sánchez-Regaña M, Umbert-Millet P (2012) Efficacy of adalimumab in the treatment of psoriasis: a retrospective study of 15 patients in daily practice. J Dermatol Treat 23:203–207

    Article  CAS  Google Scholar 

  • Ständer S, Reinhardt HW, Luger TA (2006a) Topical cannabinoid agonists. An effective new possibility for treating chronic pruritus. Hautarzt 57:801–807

    Article  PubMed  Google Scholar 

  • Ständer S, Schürmeyer-Horst F, Luger TA, Weisshaar E (2006b) Treatment of pruritic diseases with topical calcineurin inhibitors. Ther Clin Risk Manag 2:213–218

    Article  PubMed Central  PubMed  Google Scholar 

  • Ständer S, Böckenholt B, Schürmeyer-Horst F et al (2009) Treatment of chronic pruritus with the selective serotonin re-uptake inhibitors paroxetine and fluvoxamine: results of an open-labelled, two-arm proof-of-concept study. Acta Derm Venereol 89:45–51

    Article  PubMed  Google Scholar 

  • Ständer S, Siepmann D, Herrgott I et al (2010) Targeting the neurokinin receptor 1 with aprepitant: a novel antipruritic strategy. PLoS One 5(1–6):e10968

    Article  PubMed Central  PubMed  Google Scholar 

  • Steinhoff M, Cevikbas F, Ikoma A, Berger TG (2011) Pruritus: management algorithms and experimental therapies. Semin Cutan Med Surg 30:127–137

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Streit M, Von Felbert V, Braathen LR (2002) Pruritus sine materia. Pathophysiology, diagnostic assessment and therapy. Hautarzt 53:830–849

    Article  CAS  PubMed  Google Scholar 

  • Sur R, Nigam A, Grote D et al (2008) Avenanthramides, polyphenols from oats, exhibit anti-inflammatory and anti-itch activity. Arch Dermatol Res 300:569–574

    Article  CAS  PubMed  Google Scholar 

  • Szolcsányi J (2004) Forty years in capsaicin research for sensory pharmacology and physiology. Neuropeptides 38:377–384

    Article  PubMed  Google Scholar 

  • Tey HL, Yosipovitch G (2011) Targeted treatment of pruritus—a look into the future. Br J Dermatol 16:5–17

    Article  Google Scholar 

  • Weisshaar E, Szepietowski JC, Darsow U et al (2012) European guideline on chronic pruritus. Acta Derm Venereol 92:563–581

    Article  PubMed  Google Scholar 

  • Yosipovitch G, Bernhard JD (2013) Chronic pruritus. N Engl J Med 368:1625–1634

    Article  CAS  PubMed  Google Scholar 

  • Yosipovitch G, Sugeng MW, Chan YH et al (2001) The effect of topically applied aspirin on localized circumscribed neurodermatitis. J Am Acad Dermatol 45:910–913

    Article  CAS  PubMed  Google Scholar 

  • Yosipovitch G, Carstens E, McGlone F (2007) Chronic itch and chronic pain: analogous mechanisms. Pain 131:4–7

    Article  PubMed  Google Scholar 

  • Young TA, Patel TS, Camacho F et al (2009) A pramoxine-based anti-itch lotion is more effective than a control lotion for the treatment of uremic pruritus in adult hemodialysis patients. J Dermatolog Treat 20:76–81

    Article  CAS  PubMed  Google Scholar 

  • Zhai H, Frisch S, Pelosi A et al (2000a) Antipruritic and thermal sensation effects of hydrocortisone creams in human skin. Skin Pharmacol Appl Skin Physiol 13:352–357

    Article  CAS  PubMed  Google Scholar 

  • Zhai H, Hannon W, Hahn GS et al (2000b) Strontium nitrate decreased histamine-induced itch magnitude and duration in man. Dermatology 200:244–246

    Article  CAS  PubMed  Google Scholar 

  • Zimmermann AB, Berger EM, Elmariah SB, Soter NA (2012) The use of mycophenolate mofetil for the treatment of autoimmune and chronic idiopathic urticaria: experience in 19 patients. J Am Acad Dermatol 66:767–770

    Article  Google Scholar 

  • Zuberbier T et al (2014) The EAACI/GA(2) LEN/EDF/WAO Guideline for the definition, classification, diagnosis, and management of urticaria: the 2013 revision and update. Allergy 69(7):868–887

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Royal Free Hospital, London, UK

    Tabi Anika Leslie

  2. St John’s Institute of Dermatology, Guy’s and St Thomas’ Hospital, London, UK

    Tabi Anika Leslie

  3. Cutaneous Allergy Clinic, St Johns Institute of Dermatology, St Thomas’ Hospital, London, UK

    Malcolm W. Greaves

  4. Department of Dermatology, Temple University Medical Center, Philadelphia, PA, USA

    Gil Yosipovitch

  5. Itch Center, Temple University Medical Center, Philadelphia, PA, USA

    Gil Yosipovitch

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  1. Tabi Anika Leslie
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  2. Malcolm W. Greaves
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  3. Gil Yosipovitch
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Correspondence to Tabi Anika Leslie .

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Editors and Affiliations

  1. Department of Pharmacology Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, Pennsylvania, USA

    Alan Cowan

  2. Department of Dermatology, Temple University School of Medicine, Philadephia, Pennsylvania, USA

    Gil Yosipovitch

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Leslie, T.A., Greaves, M.W., Yosipovitch, G. (2015). Current Topical and Systemic Therapies for Itch. In: Cowan, A., Yosipovitch, G. (eds) Pharmacology of Itch. Handbook of Experimental Pharmacology, vol 226. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-44605-8_18

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