Evaluation of pruritus

Pruritus is defined as an unpleasant sensation that causes a desire to scratch. The terms pruritus and itch are used synonymously. Pruritus is the most common subjective symptom in dermatology and may occur with or without visible skin lesions. It may be localized or generalized.

It is important to distinguish between acute and chronic pruritus. Pruritus lasting >6 weeks is defined as chronic pruritus.[1]Ständer S, Weisshaar E, Mettang T, et al. Clinical classification of itch: a position paper of the International Forum for the Study of Itch. Acta Derm Venereol. 2007;87:291-294. http://www.ncbi.nlm.nih.gov/pubmed/17598029?tool=bestpractice.com [2]Millington GWM, Collins A, Lovell CR, et al. British Association of Dermatologists' guidelines for the investigation and management of generalized pruritus in adults without an underlying dermatosis, 2018. Br J Dermatol. 2018 Jan;178(1):34-60. https://academic.oup.com/bjd/article/178/1/34/6668398?login=false http://www.ncbi.nlm.nih.gov/pubmed/29357600?tool=bestpractice.com [3]Ständer S, Zeidler C, Augustin M, et al. S2k guideline: diagnosis and treatment of chronic pruritus. J Dtsch Dermatol Ges. 2022 Oct;20(10):1387-402. https://onlinelibrary.wiley.com/doi/10.1111/ddg.14830 http://www.ncbi.nlm.nih.gov/pubmed/36252071?tool=bestpractice.com ​​​ Based on etiology, chronic pruritus may be classified as being of dermatologic, systemic, neurologic, psychogenic/psychosomatic, mixed, or unknown etiology. Chronic pruritus can be very distressing and refractory to treatment. Its intensity frequently correlates with degree of quality of life impairment, level of stigmatization, severity of depression, and emotional stress.

According to the currently accepted clinical classification, patients with pruritus may be characterized as those with itching on primarily diseased, inflamed skin; pruritus on primarily normal, noninflamed skin; and itchy skin with chronic secondary scratch lesions.[1]Ständer S, Weisshaar E, Mettang T, et al. Clinical classification of itch: a position paper of the International Forum for the Study of Itch. Acta Derm Venereol. 2007;87:291-294. http://www.ncbi.nlm.nih.gov/pubmed/17598029?tool=bestpractice.com

Epidemiology

Itching is a common ailment. European population-based studies report pruritus prevalence (acute and/or chronic [>6 weeks duration]) of between 7% and 17%.[4]Dalgard F, Svensson A, Holm JØ, et al. Self-reported skin morbidity in Oslo. Associations with sociodemographic factors among adults in a cross-sectional study. Br J Dermatol. 2004 Aug;151(2):452-7. http://www.ncbi.nlm.nih.gov/pubmed/15327554?tool=bestpractice.com [5]Ständer S, Schäfer I, Phan NQ, et al. Prevalence of chronic pruritus in Germany: results of a cross-sectional study in a sample working population of 11,730. Dermatology. 2010;221:229-35. http://www.ncbi.nlm.nih.gov/pubmed/20924157?tool=bestpractice.com [6]Dalgard F, Holm JO, Svensson A, et al. Self reported skin morbidity and ethnicity: a population-based study in a Western community. BMC Dermatol. 2007 Jun 29;7:4. http://bmcdermatol.biomedcentral.com/articles/10.1186/1471-5945-7-4 http://www.ncbi.nlm.nih.gov/pubmed/17603893?tool=bestpractice.com

Prevalence increases with age. One systematic review and meta-analysis reported an overall pooled prevalence of pruritus of 21% in older people (ages ≥60 years).[7]Chen S, Zhou F, Xiong Y. Prevalence and risk factors of senile pruritus: a systematic review and meta-analysis. BMJ Open. 2022 Feb 24;12(2):e051694. https://bmjopen.bmj.com/content/12/2/e051694.long http://www.ncbi.nlm.nih.gov/pubmed/35210338?tool=bestpractice.com ​​​ One large epidemiologic study conducted in Germany found an increase from 12.3% among young adults (16-30 years) to 20.3% among those aged 61-70 years.[5]Ständer S, Schäfer I, Phan NQ, et al. Prevalence of chronic pruritus in Germany: results of a cross-sectional study in a sample working population of 11,730. Dermatology. 2010;221:229-35. http://www.ncbi.nlm.nih.gov/pubmed/20924157?tool=bestpractice.com

In a self-reported morbidity study conducted in Norway, itch was the most frequently mentioned skin symptom (7%).[4]Dalgard F, Svensson A, Holm JØ, et al. Self-reported skin morbidity in Oslo. Associations with sociodemographic factors among adults in a cross-sectional study. Br J Dermatol. 2004 Aug;151(2):452-7. http://www.ncbi.nlm.nih.gov/pubmed/15327554?tool=bestpractice.com [6]Dalgard F, Holm JO, Svensson A, et al. Self reported skin morbidity and ethnicity: a population-based study in a Western community. BMC Dermatol. 2007 Jun 29;7:4. http://bmcdermatol.biomedcentral.com/articles/10.1186/1471-5945-7-4 http://www.ncbi.nlm.nih.gov/pubmed/17603893?tool=bestpractice.com ​​​ Patients reporting itch were younger, predominantly female, and more distressed; they had lower income, poorer social support, and experienced more negative life events.[8]Dalgard F, Lien L, Dalen I. Itch in the community: associations with psychosocial factors among adults. J Eur Acad Dermatol Venereol. 2007 Oct;21(9):1215-9. http://www.ncbi.nlm.nih.gov/pubmed/17894708?tool=bestpractice.com ​ Itch was reported significantly more often by men from East Asia (18%) and the Middle East/North Africa (13%).[6]Dalgard F, Holm JO, Svensson A, et al. Self reported skin morbidity and ethnicity: a population-based study in a Western community. BMC Dermatol. 2007 Jun 29;7:4. http://bmcdermatol.biomedcentral.com/articles/10.1186/1471-5945-7-4 http://www.ncbi.nlm.nih.gov/pubmed/17603893?tool=bestpractice.com

Pruritus is a common symptom of many skin diseases.[2]Millington GWM, Collins A, Lovell CR, et al. British Association of Dermatologists' guidelines for the investigation and management of generalized pruritus in adults without an underlying dermatosis, 2018. Br J Dermatol. 2018 Jan;178(1):34-60. https://academic.oup.com/bjd/article/178/1/34/6668398?login=false http://www.ncbi.nlm.nih.gov/pubmed/29357600?tool=bestpractice.com [9]Satoh T, Yokozeki H, Murota H, et al. 2020 guidelines for the diagnosis and treatment of cutaneous pruritus. J Dermatol. 2021 Sep;48(9):e399-413. https://onlinelibrary.wiley.com/doi/10.1111/1346-8138.16066 http://www.ncbi.nlm.nih.gov/pubmed/34288036?tool=bestpractice.com ​ For example, it is a cardinal symptom of atopic eczema, and all patients with this disease are believed to have pruritus at some point during their illness.[10]Ständer S, Streit M, Darsow U, et al. Diagnostic and therapeutic procedures in chronic pruritus [in German]. J Dtsch Dermatol Ges. 2006;4:350-370. http://www.ncbi.nlm.nih.gov/pubmed/16638066?tool=bestpractice.com Similarly, about 70% to 90% of patients with psoriasis have pruritus.​[11]Yosipovitch G, Goon A, Wee J, et al. The prevalence and clinical characteristics of pruritus among patients with extensive psoriasis. Br J Dermatol. 2000;143:969-973. http://www.ncbi.nlm.nih.gov/pubmed/11069504?tool=bestpractice.com [12]Szepietowski JC, Reich A, Wisnicka B. Itching in patients suffering from psoriasis. Acta Dermatovenerol Croat. 2002;10:221-226. http://www.ncbi.nlm.nih.gov/pubmed/12588672?tool=bestpractice.com [13]Szepietowski JC, Reich A. Pruritus in psoriasis: an update. Eur J Pain. 2016;20:41-46. http://www.ncbi.nlm.nih.gov/pubmed/26415584?tool=bestpractice.com [14]Jaworecka K, Kwiatkowska D, Marek-Józefowicz L, et al. Characteristics of pruritus in various clinical variants of psoriasis: final report of the binational, multicentre, cross-sectional study. J Eur Acad Dermatol Venereol. 2023 Apr;37(4):787-95. http://www.ncbi.nlm.nih.gov/pubmed/36606568?tool=bestpractice.com ​​​ Pruritus may also complicate other systemic diseases, such as chronic renal failure, blood malignancies, or liver disorders.[15]Manenti L, Tansinda P, Vaglio A. Uraemic pruritus: clinical characteristics, pathophysiology and treatment. Drugs. 2009;69:251-263. http://www.ncbi.nlm.nih.gov/pubmed/19275270?tool=bestpractice.com For instance, the frequency of chronic pruritus in hemodialysis patients has been estimated to be between 25% and 55%.[16]Weiss M, Mettang T, Tschulena U, et al. Prevalence of chronic itch and associated factors in haemodialysis patients: a representative cross-sectional study. Acta Derm Venereol. 2015;95:816-821. http://www.medicaljournals.se/acta/content/?doi=10.2340/00015555-2087&html=1 http://www.ncbi.nlm.nih.gov/pubmed/25740325?tool=bestpractice.com [17]Szepietowski JC, Sikora M, Kusztal M, et al. Uremic pruritus: a clinical study of maintenance hemodialysis patients. J Dermatol. 2002;29:621-627. http://www.ncbi.nlm.nih.gov/pubmed/12432992?tool=bestpractice.com [18]Hu X, Sang Y, Yang M, et al. Prevalence of chronic kidney disease-associated pruritus among adult dialysis patients: A meta-analysis of cross-sectional studies. Medicine (Baltimore). 2018 May;97(21):e10633. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6392722 http://www.ncbi.nlm.nih.gov/pubmed/29794739?tool=bestpractice.com

Pathophysiology

Pathophysiology depends on the underlying disease. Itch may be induced or modulated by many different mediators, including histamine, acetylcholine, catecholamines, hemokinins, chemokines, cytokines (interleukin 2, interleukin 31), neuropeptides, endothelin, endovanilloids, endocannabinoids, hormones of the hypothalamus-pituitary axis, kallikreins, proteases, prostaglandins, leukotriene B4, neurotropic peptides, and opioids.[19]Paus R, Schmelz M, Biro T, et al. Frontiers in pruritus research: scratching the brain for more effective itch therapy. J Clin Invest. 2006;116:1174-1186. http://www.jci.org/articles/view/28553 http://www.ncbi.nlm.nih.gov/pubmed/16670758?tool=bestpractice.com

A specific neuronal pathway for itch has been identified. Pruritic stimuli are transmitted mainly by mechano-insensitive unmyelinated afferent C-fibers that have a particularly low conduction velocity, large innervation territories, and high transcutaneous electrical threshold.

In the spinal cord, the pruritic stimuli are transferred by specific pruriceptive neurons of dorsal horns to the posterior part of the ventromedial thalamic nucleus, which projects to the dorsal insular cortex. Itch pathway neurons have been identified in the spinal cord showing expression of gastrin-releasing peptide receptors.[20]Sun YG, Zhao ZQ, Meng XL, et al. Cellular basis of itch sensation. Science. 2009;325:1531-1534. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2786498 http://www.ncbi.nlm.nih.gov/pubmed/19661382?tool=bestpractice.com [21]Akiyama T, Tominaga M, Takamori K, et al. Roles of glutamate, substance P, and gastrin-releasing peptide as spinal neurotransmitters of histaminergic and nonhistaminergic itch. Pain. 2014;155:80-92. http://www.ncbi.nlm.nih.gov/pubmed/24041961?tool=bestpractice.com [22]Papoiu AD, Coghill RC, Kraft RA, et al. A tale of two itches. Common features and notable differences in brain activation evoked by cowhage and histamine induced itch. Neuroimage. 2012;59:3611-3623. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3288667 http://www.ncbi.nlm.nih.gov/pubmed/22100770?tool=bestpractice.com Induced itch stimuli coactivate the anterior cingulate cortex, supplementary motor area, and inferior parietal lobe predominantly in the left hemisphere.

Following itch induction, the multiple activated sites in the brain argue against the existence of a single itch center and reflect the multidimensionality of pruritus.[23]Steinhoff M, Bienenstock J, Schmelz M, et al. Neurophysiological, neuroimmunological, and neuroendocrine basis of pruritus. J Invest Dermatol. 2006;126:1705-1718. http://www.jidonline.org/article/S0022-202X(15)33013-X/fulltext http://www.ncbi.nlm.nih.gov/pubmed/16845410?tool=bestpractice.com Importantly, it has been demonstrated that the brain activity in patients suffering from chronic itch upon pruritic stimuli differs significantly from that observed in healthy subjects.[24]Ishiuji Y, Coghill RC, Patel TS, et al. 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;161:1072-1080. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2784001 http://www.ncbi.nlm.nih.gov/pubmed/19663870?tool=bestpractice.com