Evaluation of pruritus

Summary

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] [2] [3] 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]

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] [5] [6]

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] 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]

In a self-reported morbidity study conducted in Norway, itch was the most frequently mentioned skin symptom (7%).[4] [6] Patients reporting itch were younger, predominantly female, and more distressed; they had lower income, poorer social support, and experienced more negative life events.[8] Itch was reported significantly more often by men from East Asia (18%) and the Middle East/North Africa (13%).[6]

Pruritus is a common symptom of many skin diseases.[2] [9] 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] Similarly, about 70% to 90% of patients with psoriasis have pruritus.[11] [12] [13] [14] Pruritus may also complicate other systemic diseases, such as chronic renal failure, blood malignancies, or liver disorders.[15] For instance, the frequency of chronic pruritus in hemodialysis patients has been estimated to be between 25% and 55%.[16] [17] [18]

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]

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] [21] [22]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] 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]

Library

Acute urticaria: typical wheals
Urticaria: wheals
Scabies
Scabies: typical lesions within interphalangeal areas
Plaque type psoriasis
Psoriasis: symmetric plaques on the back covered with thick scales
Solar urticaria: photoprovocation upon UVA exposure
Atopic dermatitis: erythema, excoriations, and lichenification in popliteal area
Lichenification due to chronic rubbing in a patient with atopic dermatitis
Prurigo nodularis: a disease with extensive scratch lesions
Prurigo nodularis: note sparing of upper part of back, which is difficult to access for scratching
Prurigo nodularis: secondary scratch lesions
Atopic dermatitis: white dermographism
Lichen planus: lacy network traversing the buccal mucosa
Lichen planus: flat, violaceous papules with visible Köbner phenomenon (arrow)
Dermatitis herpetiformis: typical lesions on extensor surface of forearm
Dermatitis herpetiformis: highly pruritic vesicles, small blisters, and erosions on extensor surfaces of extremities
Bullous pemphigoid: tense blisters and erosions on erythematous background

Citations

Key Articles

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.[Abstract]
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.[Abstract][Full Text]
Weisshaar E, Szepietowski JC, Dalgard FJ, et al. European S2k guideline on chronic pruritus. Acta Derm Venereol. 2019 Apr 1;99(5):469-506.[Abstract]
Ständer S, Pereira MP, Berger, T; et al. IFSI-guideline on chronic prurigo including prurigo nodularis. Itch. 2020;5:e42.
Eichenfield LF, Tom WL, Chamlin SL, et al; American Academy of Dermatology. Guidelines of care for the management of atopic dermatitis. Part 1: Diagnosis and assessment of atopic dermatitis. J Am Acad Dermatol. 2014;70:338-351.[Abstract][Full Text]

Referenced Articles

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.[Abstract]
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.[Abstract][Full Text]
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.[Abstract][Full Text]
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.[Abstract]
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.[Abstract]
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.[Abstract][Full Text]
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.[Abstract][Full Text]
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.[Abstract]
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.[Abstract][Full Text]
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.[Abstract]
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.[Abstract]
12. Szepietowski JC, Reich A, Wisnicka B. Itching in patients suffering from psoriasis. Acta Dermatovenerol Croat. 2002;10:221-226.[Abstract]
13. Szepietowski JC, Reich A. Pruritus in psoriasis: an update. Eur J Pain. 2016;20:41-46.[Abstract]
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.[Abstract]
15. Manenti L, Tansinda P, Vaglio A. Uraemic pruritus: clinical characteristics, pathophysiology and treatment. Drugs. 2009;69:251-263.[Abstract]
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.[Abstract][Full Text]
17. Szepietowski JC, Sikora M, Kusztal M, et al. Uremic pruritus: a clinical study of maintenance hemodialysis patients. J Dermatol. 2002;29:621-627.[Abstract]
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.[Abstract][Full Text]
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.[Abstract][Full Text]
20. Sun YG, Zhao ZQ, Meng XL, et al. Cellular basis of itch sensation. Science. 2009;325:1531-1534.[Abstract][Full Text]
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.[Abstract]
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.[Abstract][Full Text]
23. Steinhoff M, Bienenstock J, Schmelz M, et al. Neurophysiological, neuroimmunological, and neuroendocrine basis of pruritus. J Invest Dermatol. 2006;126:1705-1718.[Abstract][Full Text]
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.[Abstract][Full Text]
25. Twycross R, Greaves MW, Handwerker H, et al. Itch: scratching more than the surface. QJM. 2003;96:7-26.[Abstract][Full Text]
26. Yosipovitch G, Greaves MW, Fleischer AB, et al. Itch: basic mechanisms and therapy. New York, Basel: Marcel Dekker; 2004.
27. Meyer N, Paul C, Misery L. Pruritus in cutaneous T-cell lymphomas: frequent, often severe and difficult to treat. Acta Derm Venereol. 2010;90:12-17.[Abstract]
28. Yosipovitch G, Samuel LS. Neuropathic and psychogenic itch. Dermatol Ther. 2008 Jan-Feb;21(1):32-41.[Abstract][Full Text]
29. Berny-Moreno J, Szepietowski JC. Neuropathic itch caused by nerve root compression: brachioradial pruritus and notalgia paresthetica. Serbian J Dermatol Venereol. 2009;2:68-72.
30. Steinhoff M, Oaklander AL, Szabó IL, et al. Neuropathic itch. Pain. 2019 May;160 Suppl 1:S11-S16.[Abstract]
31. Bell PL, Gabriel V. Evidence based review for the treatment of post-burn pruritus. J Burn Care Res. 2009;30:55-61.[Abstract]
32. Goutos I, Eldardiri M, Khan AA, et al. Comparative evaluation of antipruritic protocols in acute burns: the emerging value of gabapentin in the treatment of burns pruritus. J Burn Care Res. 2010;31:57-63.[Abstract]
33. Andreev VC, Petkov I. Skin manifestations associated with tumours of the brain. Br J Dermatol. 1975;92:675-678.[Abstract]
34. Summers CG, MacDonald JT. Paroxysmal facial itch: a presenting sign of childhood brainstem glioma. J Child Neurol. 1988;3:189-192.[Abstract]
35. Kimyai-Asadi A, Nousari HC, Kimyai-Asadi T, et al. Poststroke pruritus. Stroke. 1999;30:692-693.[Abstract][Full Text]
36. Massey EW. Unilateral neurogenic pruritus following stroke. Stroke. 1984;15:901-903.[Abstract][Full Text]
37. Shapiro PE, Braun CW. Unilateral pruritus after a stroke. Arch Dermatol. 1987;123:1527-1530.[Abstract]
38. King CA, Huff FJ, Jorizzo JL. Unilateral neurogenic pruritus: paroxysmal itching associated with central nervous system lesions. Ann Intern Med. 1982;97:222-223.[Abstract]
39. Weisshaar E, Szepietowski JC, Dalgard FJ, et al. European S2k guideline on chronic pruritus. Acta Derm Venereol. 2019 Apr 1;99(5):469-506.[Abstract]
40. Ständer S, Pereira MP, Berger, T; et al. IFSI-guideline on chronic prurigo including prurigo nodularis. Itch. 2020;5:e42.
41. Ständer S, Augustin M, Reich A, et al. Pruritus assessment in clinical trials: consensus recommendations from the International Forum for the Study of Itch (IFSI) Special Interest Group Scoring Itch in Clinical Trials. Acta Derm Venereol. 2013;93:509-514.[Abstract][Full Text]
42. Ständer S, Blome C, Breil B, et al. Assessment of pruritus - current standards and implications for clinical practice: consensus paper of the Action Group Pruritus Parameter of the International Working Group on Pruritus Research (AGP) [in German]. Hautarzt. 2012;63:521-522, 524-531.[Abstract]
43. Reich A, Heisig M, Phan NQ, et al. Visual analogue scale: evaluation of the instrument for the assessment of pruritus. Acta Derm Venereol. 2012;92:497-501.[Abstract][Full Text]
44. Furue M, Ebata T, Ikoma A, et al. Verbalizing extremes of the visual analogue scale for pruritus: a consensus statement. Acta Derm Venereol. 2013;93:214-215.[Abstract][Full Text]
45. Phan NQ, Blome C, Fritz F, et al. Assessment of pruritus intensity: prospective study on validity and reliability of the visual analogue scale, numerical rating scale and verbal rating scale in 471 patients with chronic pruritus. Acta Derm Venereol. 2012 Sep;92(5):502-7.[Abstract]
46. Magerl M, Altrichter S, Borzova E, et al. The definition, diagnostic testing, and management of chronic inducible urticarias - The EAACI/GA(2) LEN/EDF/UNEV consensus recommendations 2016 update and revision. Allergy. 2016 Jun;71(6):780-802.[Abstract]
47. Sabroe RA, Lawlor F, Grattan CEH, et al. British Association of Dermatologists guidelines for the management of people with chronic urticaria 2021. Br J Dermatol. 2022 Mar;186(3):398-413.[Abstract][Full Text]
48. Mirzoyev SA, Davis MD. Brachioradial pruritus: Mayo Clinic experience over the past decade. Br J Dermatol. 2013;169:1007-1015.[Abstract]
49. Ellis C. Notalgia paresthetica: the unreachable itch. Dermatol Pract Concept. 2013;3:3-6.[Abstract][Full Text]
50. Eichenfield LF, Tom WL, Chamlin SL, et al; American Academy of Dermatology. Guidelines of care for the management of atopic dermatitis. Part 1: Diagnosis and assessment of atopic dermatitis. J Am Acad Dermatol. 2014;70:338-351.[Abstract][Full Text]
51. Hanifin JM, Rajka G. Diagnostic features of atopic dermatitis. Acta Derm Venereol. 1980;(suppl 92):44-47.
52. Johnson EE, Irons JS, Patterson R, et al. Serum IgE concentration in atopic dermatitis. Relationship to severity of disease and presence of atopic respiratory disease. J Allergy Clin Immunol. 1974 Aug;54(2):94-9.[Abstract]
53. Khalil HM, el Shimi S, Sarwat MA, et al. Recent study of Hymenolepis nana infection in Egyptian children. J Egypt Soc Parasitol. 1991;21:293-300.[Abstract]
54. Wittner M, Tanowitz HB, White AC. Taenia and other tapeworms. In: Guerrant RL, Walker DH, Weller PF, eds. Tropical infectious diseases: principles, pathogens & practice. 1st ed. Oxford, UK: Churchill Livingstone; 2005:1327-1340.
55. Di Lernia V, Ricci C, Albertini G. Skin eruption associated with Hymenolepis nana infection. Int J Dermatol. 2004;43:357-359.[Abstract]
56. Cuetter AC, Garcia-Bobadilla J, Guerra LG, et al. Neurocysticercosis: focus on intraventricular disease. Clin Infect Dis. 1997;24:157-164.[Abstract][Full Text]
57. Sunderkötter C, Mayser P, Folster-Holst R, et al. Scabies. J Dtsch Dermatol Ges. 2007;5:424-430.[Abstract]
58. Yancey KB, Egan CA. Pemphigoid: clinical, histologic, immunopathologic, and therapeutic considerations. JAMA. 2000;284:350-356.[Abstract]
59. Alonso-Llamazares J, Rogers RS 3rd, Oursler JR, et al. Bullous pemphigoid presenting as generalized pruritus: observations in six patients. Int J Dermatol. 1998;37:508-514.[Abstract]
60. Bakker CV, Terra JB, Pas HH, et al. Bullous pemphigoid as pruritus in the elderly: a common presentation. JAMA Dermatol. 2013;149:950-953.[Abstract]
61. Szepietowski JC, Reich A, Schwartz RA. Uraemic xerosis. Nephrol Dial Transplant. 2004;19:2709-2712.[Abstract][Full Text]
62. Cohen EP, Russell TJ, Garancis JC. Mast cells and calcium in severe uremic itching. Am J Med Sci. 1992;303:360-365.[Abstract]
63. Duque MI, Thevarajah S, Chan YH, et al. Uremic pruritus is associated with higher kt/V and serum calcium concentration. Clin Nephrol. 2006;66:184-191.[Abstract]
64. Diehn F, Tefferi A. Pruritus in polycythaemia vera: prevalence, laboratory correlates and management. Br J Haematol. 2001;115:619-621.[Abstract]
65. Gangat N, Strand JJ, Lasho TL, et al. Pruritus in polycythemia vera is associated with a lower risk of arterial thrombosis. Am J Hematol. 2008;83:451-453.[Abstract]
66. Saini KS, Patnaik MM, Tefferi A. Polycythemia vera-associated pruritus and its management. Eur J Clin Invest. 2010;40:828-834.[Abstract]
67. National Center for HIV/AIDS, Viral Hepatitis, and TB Prevention (U.S.). Division of HIV/AIDS Prevention; Association of Public Health Laboratories. 2018 Quick reference guide: recommended laboratory HIV testing algorithm for serum or plasma specimens. Jan 2018 [internet publication].[Full Text]
68. World Health Organization. Consolidated guidelines on HIV prevention, testing, treatment, service delivery and monitoring: recommendations for a public health approach. Jul 2021 [internet publication].[Full Text]
69. Caravati CM Jr, Richardson DR, Wood BT, et al. Cutaneous manifestations of hyperthyroidism. South Med J. 1969;62:1127-1130.[Abstract]
70. Weisshaar E, Weiss M, Mettang T, et al. Paraneoplastic itch: an expert position statement of the Special Interest Group (SIG) of the International Forum on the Study of Itch (IFSI). Acta Derm Venereol. 2015;95:261-265.[Abstract]
71. Oaklander AL, Bowsher D, Galer B, et al. Herpes zoster itch: preliminary epidemiologic data. J Pain. 2003;4:338-343.[Abstract]
72. Chabre O, Labat F, Pinel N, et al. Cutaneous lesion associated with multiple endocrine neoplasia type 2A: lichen amyloidosis or notalgia paresthetica? Henry Ford Hosp Med J. 1992;40:245-248.[Abstract]
73. Mazeh D, Melamed Y, Cholostoy A, et al. Itching in the psychiatric ward. Acta Derm Venereol. 2008;88:128-131.[Abstract]
74. Misery L, Alexandre S, Dutray S, et al. Functional itch disorder or psychogenic pruritus: suggested diagnosis criteria from the French Psychodermatology Group. Acta Derm Venereol. 2007;87:341-344.[Abstract]
75. Reich A, Kwiatkowska D, Pacan P. Delusions of Parasitosis: An Update. Dermatol Ther (Heidelb). 2019 Dec;9(4):631-638.[Abstract][Full Text]

Diseases