Uremic pruritus

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Uremic pruritus
Other namesUraemic pruritus, renal pruritus, [1] chronic kidney disease-associated pruritus (CKD-aP), kidney itch
Specialty Dermatology   OOjs UI icon edit-ltr-progressive.svg

Uremic pruritus is caused by chronic kidney failure and is the most common internal systemic cause of itching. [2] : 52–3 

Contents

Nalfurafine, an orally administered, centrally acting κ-opioid receptor agonist, is approved to treat the condition in Japan. [3]

Signs and symptoms

The signs and symptoms of uremic pruritus can vary. The intensity ranges from mildly uncomfortable to highly upsetting and causing agitation. [4] The distribution is more prevalent on the back, face, and shunt arm and is typically symmetric and generalized, though it can also be localized. [5] Dryness, heat, cold, stress, and showering all exacerbate pruritus. Patients with this condition frequently have skin devoid of noticeable lesions. But in addition to xerosis, skin lesions like excoriation, crusts, impetigo, and prurigo nodularis may also develop as a result of repeated scratching. [4]

Causes

There are several potential causes of uremic pruritus, including immune dysregulation, uremic toxins, neuropathy, and opioid imbalance. [4]

Mechanism

Vitamin A, [6] parathyroid hormone, [7] calcium, phosphate, magnesium, [8] histamine, [9] and phosphate [8]  are the most researched potential pruritogens in the pathophysiology of uremic pruritus. [4]

The etiology of uremic pruritus may involve the immune system as well. Research comparing hemodialysis patients with and without uremic pruritus revealed that those with the condition had noticeably higher levels of T helper 1 cells [10] as well as serum interleukin (IL)-6, IL-2, [11] and IL-31. [12] [13]

In uremic pruritus, both peripheral and central neuropathy are thought to be involved. [4]

Diagnosis

Uremic pruritus is defined as itching that is directly caused by chronic kidney disease, with no other explainable conditions. [14] Uremic pruritus cannot be diagnosed with laboratory tests or established criteria because of its variability and lack of specific skin lesions. Comprehensive consideration of the diagnosis is necessary, encompassing neuropathic, psychogenic, renal, dermatologic, endocrine, hepatobiliary, hematologic, rheumatologic, oncologic, and endocrine causes. [4]

Treatment

The pathophysiology of uremic pruritus is still poorly understood, which contributes to the difficulty of current treatments. [4] Prior to the approval of difelikefalin in the US in 2021, there was no FDA-approved treatment for uremic pruritus. [15] Emollients, topical medications, antihistamines, phototherapy, dialysis modification, and serotonin receptor antagonists are examples of conventional treatments. More data from recent studies indicates that biologics, gabapentin, pregabalin, and opioid receptor agonists and antagonists may be involved in treating uremic pruritus. [4]

Xerosis is a contributing factor to pruritus and is present in 50–85% of patients with uremic pruritus. [16] Many studies have shown that emollients such as glycerol and paraffin, [17] physiological lipids, [18] 10% urea and dexpanthenol, [19] and baby oil [20] can reduce xerosis and pruritus in patients with uremic pruritus. For patients with uremic pruritus, especially in cases of milder severity, emollient is recommended as the initial line of treatment. [14]

Pregabalin and gabapentin are analogues of gamma-aminobutyric acid that modulate neurotransmitters, possibly through reducing the release of neurotransmitters. [21] Numerous pruritic disorders, including brachioradial pruritus and pruritus in patients with diabetic neuropathic pain, have been linked to the neuropathic role in their pathogenesis. [22] Pregabalin and gabapentin have been shown in multiple clinical trials to be statistically significant in reducing the intensity of pruritus in patients with uremic pruritus. [23] [24]

It has been demonstrated that mast cell stabilizers, which stop mast cells from releasing inflammatory mediators, are useful in treating uremic pruritus. These stabilizers include zinc sulfate, [25] ketotifen, [26] oral cromolyn sodium, [27] and topical cromolyn sodium. [28]

See also

References

  1. ↑ Rapini RP, Bolognia JL, Jorizzo JL (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN   978-1-4160-2999-1.
  2. ↑ James WD, Berger T, Elston D (2006). Andrews' Diseases of the Skin: Clinical Dermatology (10th ed.). Philadelphia: Saunders Elsevier. ISBN   978-0-7216-2921-6.
  3. ↑ Inui S (2015). "Nalfurafine hydrochloride to treat pruritus: a review". Clinical, Cosmetic and Investigational Dermatology. 8: 249–255. doi: 10.2147/CCID.S55942 . PMC   4433050 . PMID   26005355.
  4. 1 2 3 4 5 6 7 8 Cheng, An-Yu; Wong, Lai-San (April 28, 2022). "Uremic Pruritus: From Diagnosis to Treatment". Diagnostics. 12 (5). MDPI AG: 1108. doi: 10.3390/diagnostics12051108 . ISSN   2075-4418. PMC   9140050 . PMID   35626264.
  5. ↑ Mettang, Thomas; Kremer, Andreas E. (2015). "Uremic pruritus". Kidney International. 87 (4). Elsevier BV: 685–691. doi: 10.1038/ki.2013.454 . ISSN   0085-2538. PMID   24402092.
  6. ↑ Yatzidis, H; Digenis, P; Fountas, P (August 9, 1975). "Hypervitaminosis A accompanying advanced chronic renal failure". BMJ. 3 (5979): 352–353. doi:10.1136/bmj.3.5979.352. ISSN   0959-8138. PMC   1673813 . PMID   1156752.
  7. ↑ STÅHLE-BÅCKDAHL, M.; HÄGERMARK, Ö.; LINS, L.-E.; TÖRRING, O.; HILLIGES, M.; JOHANSSON, O. (1989). "Experimental and immunohistochemical studies on the possible role of parathyroid hormone in uraemic pruritus". Journal of Internal Medicine. 225 (6). Wiley: 411–415. doi:10.1111/j.1365-2796.1989.tb00104.x. ISSN   0954-6820. PMID   2746157. S2CID   44406280.
  8. 1 2 Blachley, Jon D.; Blankenship, D. Michael; Menter, Alan; Parker, Tom F.; Knochel, James P. (1985). "Uremic Pruritus: Skin Divalent Ion Content and Response to Ultraviolet Phototherapy". American Journal of Kidney Diseases. 5 (5). Elsevier BV: 237–241. doi:10.1016/s0272-6386(85)80115-3. ISSN   0272-6386. PMID   4003393.
  9. ↑ Dugas-Breit, Susanne; Schöpf, Pia; Dugas, Martin; Schiffl, Helmut; Ruëff, Franziska; Przybilla, Bernhard (April 14, 2005). "Baseline serum levels of mast cell tryptase are raised in hemodialysis patients and associated with severity of pruritus". JDDG: Journal der Deutschen Dermatologischen Gesellschaft. 3 (5). Wiley: 343–347. doi:10.1111/j.1610-0387.2005.05706.x. ISSN   1610-0379. PMID   16372800. S2CID   22968227.
  10. ↑ Kimmel, Martin; Alscher, Dominik Mark; Dunst, Robert; Braun, Niko; Machleidt, Christoph; Kiefer, Thomas; Stülten, Christina; van der Kuip, Heiko; Pauli-Magnus, Christiane; Raub, Ulrich; Kuhlmann, Ulrich; Mettang, Thomas (October 25, 2005). "The role of micro-inflammation in the pathogenesis of uraemic pruritus in haemodialysis patients". Nephrology Dialysis Transplantation. 21 (3). Oxford University Press (OUP): 749–755. doi:10.1093/ndt/gfi204. ISSN   1460-2385. PMID   16249205.
  11. ↑ Fallahzadeh, M. K.; Roozbeh, J.; Geramizadeh, B.; Namazi, M. R. (March 3, 2011). "Interleukin-2 serum levels are elevated in patients with uremic pruritus: a novel finding with practical implications". Nephrology Dialysis Transplantation. 26 (10). Oxford University Press (OUP): 3338–3344. doi:10.1093/ndt/gfr053. ISSN   0931-0509. PMID   21372257.
  12. ↑ Oweis, Ashraf O.; AL-Qarqaz, Firas; Bodoor, Khaldon; Heis, Leen; Alfaqih, Mahmoud A.; Almomani, Rowida; Obeidat, Motaz A.; Alshelleh, Sameeha A. (2021). "Elevated interleukin 31 serum levels in hemodialysis patients are associated with uremic pruritus". Cytokine. 138 155369. Elsevier BV. doi:10.1016/j.cyto.2020.155369. ISSN   1043-4666. PMID   33221158. S2CID   227132161.
  13. ↑ Ko, Mei-Ju; Peng, Yu-Sen; Chen, Hung-Yuan; Hsu, Shih-Ping; Pai, Mei-Fen; Yang, Ju-Yeh; Wen, Su-Ying; Jee, Shiou-Hwa; Wu, Hon-Yen; Chiu, Hsien-Ching (2014). "Interleukin-31 is associated with uremic pruritus in patients receiving hemodialysis". Journal of the American Academy of Dermatology. 71 (6). Elsevier BV: 1151–1159.e1. doi:10.1016/j.jaad.2014.08.004. ISSN   0190-9622. PMID   25270263.
  14. 1 2 Verduzco, Hector Alvarado; Shirazian, Shayan (2020). "CKD-Associated Pruritus: New Insights Into Diagnosis, Pathogenesis, and Management". Kidney International Reports. 5 (9). Elsevier BV: 1387–1402. doi:10.1016/j.ekir.2020.04.027. ISSN   2468-0249. PMC   7486142 . PMID   32954065.
  15. ↑ Deeks, Emma D. (October 21, 2021). "Difelikefalin: First Approval". Drugs. 81 (16). Springer Science and Business Media LLC: 1937–1944. doi:10.1007/s40265-021-01619-6. ISSN   0012-6667. PMID   34674115. S2CID   239042330.
  16. ↑ Szepietowski, J. C. (September 22, 2004). "Uraemic xerosis". Nephrology Dialysis Transplantation. 19 (11). Oxford University Press (OUP): 2709–2712. doi:10.1093/ndt/gfh480. ISSN   1460-2385. PMID   15328388.
  17. ↑ Balaskas, Elias; Szepietowski, Jacek C.; Bessis, Didier; Ioannides, Dimitrios; Ponticelli, Claudio; Ghienne, Corinne; Taberly, Alain; Dupuy, Patrick (2011). "Randomized, Double-blind Study with Glycerol and Paraffin in Uremic Xerosis". Clinical Journal of the American Society of Nephrology. 6 (4). Ovid Technologies (Wolters Kluwer Health): 748–752. doi:10.2215/cjn.05490610. ISSN   1555-9041. PMC   3069365 . PMID   21258039.
  18. ↑ Szepietowski, Jacek C; Szepietowski, Tomasz; Reich, Adam (2005). "Efficacy and tolerance of the cream containing structured physiological lipids with endocannabinoids in the treatment of uremic pruritus: a preliminary study". Acta Dermatovenerologica Croatica. 13 (2): 97–103. PMID   16324422.
  19. ↑ Okada, Kazuyoshi; Matsumoto, Koichi (2004). "Effect of Skin Care With an Emollient Containing a High Water Content on Mild Uremic Pruritus". Therapeutic Apheresis and Dialysis. 8 (5). Wiley: 419–422. doi:10.1111/j.1526-0968.2004.00175.x. ISSN   1744-9979. PMID   15663539. S2CID   2690300.
  20. ↑ Singh, VimalaSuryanarayan; Vinayadev, V (2021). "Effectiveness of Baby Oil Therapy for Uremic Pruritus in Hemodialysis Patients". Saudi Journal of Kidney Diseases and Transplantation. 32 (1). Medknow: 163–169. doi: 10.4103/1319-2442.318518 . ISSN   1319-2442. PMID   34145126.
  21. ↑ Robertson, Kelvin; Marshman, Laurence A. G.; Plummer, David; Downs, Elena (January 1, 2019). "Effect of Gabapentin vs Pregabalin on Pain Intensity in Adults With Chronic Sciatica". JAMA Neurology. 76 (1). American Medical Association: 28–34. doi:10.1001/jamaneurol.2018.3077. ISSN   2168-6149. PMC   6439871 . PMID   30326006.
  22. ↑ Gunal, A. I.; Ozalp, G.; Yoldas, T. K.; Gunal, S. Y.; Kirciman, E.; Celiker, H. (December 1, 2004). "Gabapentin therapy for pruritus in haemodialysis patients: a randomized, placebo-controlled, double-blind trial". Nephrology Dialysis Transplantation. 19 (12). Oxford University Press (OUP): 3137–3139. doi:10.1093/ndt/gfh496. ISSN   0931-0509. PMID   15575002.
  23. ↑ Nofal, Eman; Farag, Fawzia; Nofal, Ahmad; Eldesouky, Fatma; Alkot, Reham; Abdelkhalik, Zeinab (April 4, 2016). "Gabapentin: A promising therapy for uremic pruritus in hemodialysis patients: A randomized-controlled trial and review of literature". Journal of Dermatological Treatment. 27 (6). Informa UK Limited: 515–519. doi:10.3109/09546634.2016.1161161. ISSN   0954-6634. PMID   27043168. S2CID   25857291.
  24. ↑ SOLAK, YALCIN; BIYIK, ZEYNEP; ATALAY, HUSEYIN; GAIPOV, ABDUZHAPPAR; GUNEY, FIGEN; TURK, SULEYMAN; COVIC, ADRIAN; GOLDSMITH, DAVID; KANBAY, MEHMET (October 29, 2012). "Pregabalin versus gabapentin in the treatment of neuropathic pruritus in maintenance haemodialysis patients: A prospective, crossover study". Nephrology. 17 (8). Wiley: 710–717. doi:10.1111/j.1440-1797.2012.01655.x. ISSN   1320-5358. PMID   22909343. S2CID   1870828.
  25. ↑ Najafabadi, Mojgan Mortazavi; Faghihi, Gita; Emami, Afsoon; Monghad, Maryam; Moeenzadeh, Firoozeh; Sharif, Nima; Davarpanah Jazi, Amir Hosein (January 5, 2012). "Zinc Sulfate for Relief of Pruritus in Patients on Maintenance Hemodialysis". Therapeutic Apheresis and Dialysis. 16 (2). Wiley: 142–145. doi:10.1111/j.1744-9987.2011.01032.x. ISSN   1744-9979. PMID   22458392. S2CID   205906092.
  26. ↑ Amirkhanlou, Saeid; Rashedi, Anna; Taherian, Jalal; Hafezi, Ali Akbar; Parsaei, Sahar (December 31, 1969). "Comparison of Gabapentin and Ketotifen in Treatment of Uremic Pruritus in Hemodialysis Patients". Pakistan Journal of Medical Sciences. 32 (1): 22–26. doi:10.12669/pjms.321.8547. ISSN   1681-715X. PMC   4795872 . PMID   27022338.
  27. ↑ ROSNER, Mitchell H. (March 28, 2006). "Cromolyn sodium: A potential therapy for uremic pruritus?". Hemodialysis International. 10 (2). Wiley: 189–192. doi:10.1111/j.1542-4758.2006.00093.x. ISSN   1492-7535. PMID   16623673. S2CID   34803063.
  28. ↑ Feily, Amir; Dormanesh, Benafshe; Ghorbani, Ali Reza; Moosavi, Zahra; Kouchak, Maryam; Cheraghian, Bahman; Mousavi, Seyed Seifollah Beladi; Mehrabian, Abolfath; Ranjbari, Nastaran (July 1, 2012). "Efficacy of topical cromolyn sodium 4% on pruritus in uremic nephrogenic patients: A randomized double-blind study in 60 patients". International Journal of Clinical Pharmacology and Therapeutics. 50 (7). Dustri-Verlgag Dr. Karl Feistle: 510–513. doi:10.5414/cp201629. ISSN   0946-1965. PMID   22732382.

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