Contents

Search

pruritus (itching)

Itching or pruritus is the unpleasant sensation associated with the urge to scratch. Classification: 1) pruritoceptive pruritus (primary skin disorder) 2) neurogenic pruritus (generalized itching without primary skin disorder) 3) neuropathic pruritus (localized itching without primary skin disorder) 4) psychogenic pruritus Etiology: === dermatologic causes (pruritoceptive) === 1) xerosis (dry skin), xerotic eczema, psoriasis, urticaria 2) infections, infestations a) dermatophytosis b) folliculitis c) Candida d) varicella e) HIV1 infection f) giardiasis g) parasites - scabies 3) physical causes a) sunburn b) fiberglass c) chemical irritants - topical agents d) too-frequent bathing e) pressure f) low-intensity electrical stimulation === systemic causes (neurogenic) === 1) uremia, chronic renal failure 2) obstructive biliary disease a) primary biliary cirrhosis b) primary sclerosing cholangitis c) hepatitis C 3) hematologic a) iron-deficiency anemia b) polycythemia vera c) systemic mastocytosis 4) endocrine a) hyperthyroidism b) hypothyroidism c) hypercalcemia d) carcinoid e) diabetes mellitus 5) pregnancy-related causes a) non-specific pruritus of pregnancy b) intrahepatic cholestasis of pregnancy c) pruritic urticarial papules & plaques of pregnancy (PUPPP) 6) malignancy a) Hodgkin's disease b) non-Hodgkin's lymphoma c) myeloid leukemia [22] d) multiple myeloma e) visceral malignancy 7) systemic medications a) allergy to drug b) idiosyncratic drug reaction c) pruritus-producing drugs - common, > 15% a] opiates b] statins c] BRAF inhibitors (vemurafenib) d] CTLA-4 inhibitors (ipilimumab) e] EGFR inhibitors (cetuximab) f] hydroxyethyl starch (> 15%) - others a] oral contraceptives b] barbiturates c] aspirin d] niacin e] phenothiazines f] tolbutamide g] quinidine h] diuretics (includin HCTZ) can worsen xerosis, pruritus i] NSAIDS j] calcium channel blockers d) immunostimulation - immunotherapy during treatment or 21-60 days after treatment - immunizations: Tdap, mRNA COVID-19 vaccine (within 1 week) [25] === neurologic (neuropathic) === 1) multiple sclerosis 2) stroke 3) brain tumor 4) brain abscess 5) postherpetic neuralgia 6) brachioradial pruritus 7) trigeminal trophic syndrome 8) notalgia paresthetica 9) peripheral neuropathy 7) 20% of pruritus of unknown etiology with systemic cause [9] === psychological cause (psychogenic) === 1) psychogenic itching 2) neurodermatitis - prurigo nodularis 3) stress 4) depression 5) negative emotions may increase itching & pain [4] Pathology: - B-type natriuretic peptide is a neurotransmitter for TRPV1-positive itch-specific neurons dorsal root ganglion cells - gastrin-releasing peptide-connected secondary & tertiary itch receptors in the spinal cord transmit the itch signal to the brain [5] - activation of mast cells & CD3+ T-cells to overproduce IL-31 (pruritic) - impaired release prostaglandin D2 (pruritus inhibitor) Clinical manifestations: 1) presence of a rash - preceeding or coincident with pruritus (scratching) 2) skin manifestations may not be seen [2] - scratching can damage skin (excoriation, lichenification) 3) pruritus exacerbated by bathing or exposure to water (aquagenic pruritus) suggests polycythemia vera [6] 4) medication-induced pruritus may occur after months or years on a drug [2] * images [18] Laboratory: pruritus without a rash 1) complete blood count (CBC) with differential - eosinophil count [24] 2) IgE in serum 3) thyroid function tests 4) serum iron, TIBC, serum ferritin 5) liver function tests a) serum AST, serum ALT b) serum alkaline phosphatase c) serum bilirubin d) serum GGT e) bile acids in serum 6) renal function tests a) serum creatinine b) serum urea nitrogen 7) serum glucose, hgbA1c [24] 8) cytokines (if severe & refractory) - serum IL-5, thymic stromal lymphopoietin [23] 8) consider age & gender-appropriate cancer screening as indicated by clinical presentation Radiology: - chest X-ray (neurogenic pruritus) Complications: - risk factor for hematologic malignancy & bile duct cancer but not other malignancies [11] Management: 1) general measures a) evaluation & management differ substantially depending upon the presence of a rash b) treatment of a rash generally resolves the itch c treatment of underlying disorder d) remove/discontinue offending agent 2) topical agents a) emollients (moisturizing agents) b) camphor/menthol/phenol soothe by counter irritation c) topical anesthetics [2] d) topical glucocorticoids e) topical calcineurin inhibitors - topical tacrolimus, topical picrolimus [2] 3) systemic agents a) systemic glucocorticoids for severe, intractable itching - glucocorticoids may not improve neurogenic pruritus or psychogenic pruritus [2] b) antihistamines - hydroxyzine (Atarax) - chlorpheniramine - diphenhydramine (Benadryl) - non-sedating antihistamines less effective - tricyclic antidepressants (doxepin) c) opioid receptor effectors - naltrexone, naloxone, butorphanol [2] d) NSAIDs may have a role e) biologic agents or methotrexate for severe refractory pruritus [23] - dupilumab, JAK inhibitors f) case report of 10-year history of chronic, severe recalcitrant pruritus due to primary sclerosing cholangitis with symptomatic resolution in 16 months with medical marijuana [21] 4) neuropathic pruritus a) gabapentin b) carbamazepine c) topical capsaisin 5) pruritus due to myeloproliferative disorders may respond to SSRIs, but not antihistamines or NSAIDs 6) mirtazapine may be useful for nocturnal pruritus, or pruritus due to renal disease, liver disease or lymphoma 7) naltrexone or butorphanol may useful for pruritus due to a) cholestasis b) end-stage renal disease 8) phototherapy for pruritus due to uremia, psoriasis or liver disease not responding to topical glucocorticoids [2] 13) screening for cancer as indicated

Related

xerosis (dry skin)

Specific

anal pruritus aquagenic pruritus inguinal pruritus neurogenic pruritus neuropathic pruritus pruritoceptive pruritus psychogenic pruritus vulvar pruritus

General

sign/symptom

References

  1. Saunders Manual of Medical Practice, Rakel (ed), WB Saunders, Philadelphia, 1996, pg 908
  2. Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 15, 16, 17, 18. American College of Physicians, Philadelphia 1998, 2006, 2009, 2012, 2015, 2018
  3. Takahashi S, In: Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 29-Oct 2, 2004
  4. van Laarhoven AIM et al Role of induced negative and positive emotions in sensitivity to itch and pain in women. Br J Dermatol 2012 Aug; 167:262 PMID: 22404598
  5. Mishra SK, Hoon MA. The cells and circuitry for itch responses in mice. Science 2013 May 24; 340:968 PMID: 23704570
  6. Siegel FP et al. Aquagenic pruritus in polycythemia vera: Characteristics and influence on quality of life in 441 patients. Am J Hematol 2013 Aug; 88:665 PMID: 23657863
  7. Greaves MW. Recent advances in pathophysiology and current management of itch. Ann Acad Med Singapore. 2007 Sep;36(9):788-92. PMID: 17925991
  8. O'Donoghue M, Tharp MD. Antihistamines and their role as antipruritics. Dermatol Ther. 2005 Jul-Aug;18(4):333-40. PMID: 16297006
  9. Zirwas MJ, Seraly MP Pruritus of unknown origin: a retrospective study. J Am Acad Dermatol. 2001 Dec;45(6):892-6. PMID: 11712035
  10. Berger TG, Shive M, Harper GM. Pruritus in the older patient: a clinical review. JAMA. 2013;310(22):24432450 PMID: 24327039
  11. Fett N, Haynes K, Propert KJ, Margolis DJ. Five-year malignancy incidence in patients with chronic pruritus: a population-based cohort study aimed at limiting unnecessary screening practices. J Am Acad Dermatol. 2014 Apr;70(4):651-8. PMID: 24485529
  12. Cassano N, Tessari G, Vena GA, Girolomoni G Chronic pruritus in the absence of specific skin disease: an update on pathophysiology, diagnosis, and therapy. Am J Clin Dermatol. 2010 Dec 1;11(6):399-411 PMID: 20866115
  13. Reamy BV, Bunt CW, Fletcher S. A diagnostic approach to pruritus. Am Fam Physician. 2011 Jul 15;84(2):195-202. PMID: 21766769
  14. Stander 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(4):291-4. PMID: 17598029
  15. Yosipovitch G, Bernhard JD Clinical practice. Chronic pruritus. N Engl J Med. 2013 Apr 25;368(17):1625-34 PMID: 23614588
  16. Patel T, Yosipovitch G. The management of chronic pruritus in the elderly. Skin Therapy Lett. 2010 Sep;15(8):5-9. PMID: 20844849
  17. Butler DF, James WD Medscape: Pruritus and Systemic Disease http://emedicine.medscape.com/article/1098029-overview
  18. DermNet NZ. Itch, pruritus (images) http://www.dermnetnz.org/systemic/itch.html
  19. Lambert J. Pruritus in female patients. Biomed Res Int. 2014;2014:541867. Review. PMID: 24711996 Free PMC Article
  20. Silverberg JI. Practice Gaps in Pruritus. Dermatol Clin. 2016 Jul;34(3):257-61. Review. PMID: 27363881 Free PMC Article
  21. Roh YS, Sutaria N, Biles NF et al Treatment of Chronic Pruritus With Medical Marijuana. JAMA Dermatol. Published online April 9, 2021 PMID: 33835147 https://jamanetwork.com/journals/jamadermatology/fullarticle/2778442
  22. Deng J et al. Risk of hematologic cancer in patient with undifferentiated pruritis. JAMA Dermatol 2022 Jul; 158:791. PMID: 35612839 PMCID: PMC9134041 (available on 2023-05-25) https://jamanetwork.com/journals/jamadermatology/fullarticle/2792454
  23. Kilgore C Chronic Itch in Older Adults: Workup and Management Advice. Medscape. August 07, 2024 https://www.medscape.com/viewarticle/chronic-itch-older-adults-workup-and-management-advice-2024a1000eih
  24. Roh YS, Choi J, Sutaria N, Kwatra SG. Itch: Epidemiology, clinical presentation, and diagnostic workup. J Am Acad Dermatol. 2022 Jan;86(1):1-14. PMID: 34428534 PMCID: PMC8678917 Free PMC article. Review.
  25. Manjunath J, Liao V, Kambala A et al Immune stimulus exposure as a trigger for the development of chronic pruritus and circulating blood type 2 inflammation. JAAD Int. 2024 Apr 7;16:97-102. PMID: 38868400 PMCID: PMC11166869 Free PMC article.