Pruritus in diabetes mellitus (DM) and its pathophysiology-based treatment

https://doi.org/10.19106/JMedSci005401202210

Lorettha Wijaya(1*), Audrey Melanie(2), Veronica Veronica(3), Gabriela Christy(4)

(1) Department of Dermatology and Venereology, School of Medicine and Health Sciences, Atma Jaya Catholic University of Indonesia, Jakarta, Indonesia
(2) Department of Dermatology and Venereology, School of Medicine and Health Sciences, Atma Jaya Catholic University of Indonesia, Jakarta, Indonesia
(3) Department of Dermatology and Venereology, School of Medicine and Health Sciences, Atma Jaya Catholic University of Indonesia, Jakarta, Indonesia
(4) Department of Dermatology and Venereology, School of Medicine and Health Sciences, Atma Jaya Catholic University of Indonesia, Jakarta, Indonesia
(*) Corresponding Author

Abstract


Pruritus is a common complaint of diabetic patients with a substantial impact on financial and health status, but the pathophysiology is unclear and treatment with antihistamines has mostly been unsuccessful. To date, we still do not have guidelines to help us treat pruritus in diabetes mellitus, so we felt the need to review the existing literature to explore possible ways to treat these patients. We collected 85 pieces of literature from various sources such as PubMed and Google Scholar, and independently extracted these data to make this review. While the pathophysiology behind pruritus in diabetes mellitus remains largely unknown, some trials have found a few pharmacological treatments to be effective in alleviating itch in these patients.

Keywords


skin barrier disruption; diabetic neuropathy; oxidative stress; chronic kidney disease-associated pruritus; second line treatment

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References

  1. Kremer AE, Weisshaar E. Endocrine Diseases. In: Misery L, Ständer S, eds. Pruritus. 2nd ed. London: Springer. 2016; 267-70. https://doi.org/10.1007/978-3-319-33142-3
  2. Sabban ENC. Dermatoses most frequently related to diabetes mellitus. In: Sabban ENC, Puchulu FM, Cusi K, eds. Dermatology and diabetes. 1st ed. Cham: Springer International Publishing. 2018; 145-77. https://doi.org/10.1007/978-3-319-72475-1
  3. Weisshaar E. Epidemiology of itch. Curr Probl Dermatol 2016; 50:5-10. https://doi.org/10.1159/000446010
  4. Stefaniak AA, Chlebicka I, Szepietowski JC. Itch in diabetes: a common underestimated problem. Adv Dermatol Allergol 2021; XXXVIII(2):177-83. https://doi.org/10.5114/ada.2019.89712
  5. Kementerian Kesehatan RI. Infodatin hari diabetes sedunia tahun 2018. Direktorat Pencegahan dan Pengendali Penyakit Tidak Menular, Badan Litbangkes. 2019; 1-8. Available from: http://www.depkes.go.id/resources/download/pusdatin/infodatin/hari-diabetes-sedunia-2018.pdf
  6. Badan Pusat Statistik. Statistik Indonesia 2018. Jakarta: Badan Pusat Statistik; 2018. https://www.bps.go.id/publication/2018/07/03/5a963c1ea9b0fed6497d0845/statistik-indonesia-2018.html
  7. Al-Mutairi N, Zaki A, Sharma AK, Al-Sheltawi M. Cutaneous manifestations of diabetes mellitus: study from Farwaniya Hospital, Kuwait. Med Princ Pract 2006; 15(6):427-30. https://doi.org/10.1159/000095488
  8. Kini SP, DeLong LK, Veledar E, McKenzie-Brown AM, Schaufele M, Chen SC. The impact of pruritus on quality of life: the skin equivalent of pain. Arch Dermatol 2011; 147(10):1153-6. https://doi.org/10.1001/archdermatol.2011.178
  9. Erturk IE, Ozer A, Omurlu IK, Sut N. Effect of the pruritus on the quality of life: a preliminary study. Ann Dermatol 2012; 24(4):406-12. https://doi.org/10.5021/ad.2012.24.4.406
  10. Tripathi R, Knusel KD, Ezaldein HH, Bordeaux JS, Scott JF. The cost of an itch: a nationally representative retrospective cohort study of pruritus-associated health care expenditure in the United States. J Am Acad Dermatol 2019; 80(3):810-3. https://doi.org/10.1016/j.jaad.2018.10.025
  11. Alexiadou K, Doupis J. Management of diabetic foot ulcers. Diabetes Ther 2012; 3(1):4. https://doi.org/10.1007/s13300-012-0004-9
  12. Wijaya L, Budiyanto A, Astuti I, Mustofa. Pathogenesis, evaluation, and recent management of diabetic foot ulcer. Journal of the Medical Sciences. 2019; 51(1):82-97. https://doi.org/10.19106/JMedSci005101201910
  13. Medic G, Wille M, Hemels ME. Short- and long-term health consequences of sleep disruption. Nat Sci Sleep 2017; 9:151-61. https://doi.org/10.2147/NSS.S134864
  14. Song J, Xian D, Yang L, Xiong X, Lai R, Zhong J. Pruritus: progress toward pathogenesis and treatment. Biomed Res Int 2018: 2028:9625936. https://doi.org/10.1155/2018/9625936
  15. Lima AL, Illing T, Schliemann S, Elsner P. Cutaneous manifestations of diabetes mellitus: a review. Am J Clin Dermatol 2017; 18(4):541-53. https://doi.org/10.1007/s40257-017-0275-z
  16. Babakinejad P, Walton S. Diabetes and pruritus. Br J Diabetes 2016; 16(4):154-5. https://doi.org/10.15277/bjd.2016.095
  17. de Macedo GMC, Nunes S, Barreto T. Skin disorders in diabetes mellitus: an epidemiology and physiopathology review. Diabetol Metab Syndr. 2016; 8(1):63. https://doi.org/10.1186/s13098-016-0176-y
  18. Yamaoka H, Sasaki H, Yamasaki H, Ogawa K, Ohta T, Furuta H, et al. Truncal pruritus of unknown origin may be a symptom of diabetic polyneuropathy. Diabetes Care 2010; 33(1):150-5. https://doi.org/10.2337/dc09-0632
  19. Ko MJ, Chiu HC, Jee SH, Hu FC, Tseng CH. Postprandial blood glucose is associated with generalized pruritus in patients with type 2 diabetes. Eur J Dermatol 2013; 23(5):688-93. https://doi.org/10.1684/ejd.2013.2100
  20. Hillson RM, Hockaday TDR, Newton DJ, Pim B. Delayed diagnosis of non-insulin-dependent diabetes is associated with greater metabolic and clinical abnormality. Diabetic Med 1985; 2(5):383-6. https://doi.org/10.1111/j.1464-5491.1985.tb00657.x
  21. Neilly JB, Martin A, Simpson N, MacCuish AC. Pruritus in diabetes mellitus: investigation of prevalence and correlation with diabetes control. Diabetes Care 1986; 9(3):273-5. https://doi.org/10.2337/diacare.9.3.273
  22. Afsar B, Elsurer Afsar R. HbA1c is related with uremic pruritus in diabetic and nondiabetic hemodialysis patients. Ren Fail 2012; 34(10):1264-9. https://doi.org/10.3109/0886022X.2011.560401
  23. Cevikbas F, Lerner EA. Physiology and pathophysiology of itch. Physiol Rev 2020; 100(3):945-82. https://doi.org/10.1152/physrev.00017.2019
  24. Dong X, Dong X. Peripheral and central mechanisms of itch. Neuron 2018; 98(3):482-94. https://doi.org/10.1016/j.neuron.2018.03.023
  25. Schmelz M. Itch processing in the skin. Front Med (Lausanne) 2019; 6:167. https://doi.org/10.3389/fmed.2019.00167
  26. Meixiong J, Dong X, Weng HJ. Neuropathic itch. Cells 2020; 9(10):2263. https://doi,org/10.3390/cells9102263
  27. Verduzco HA, Shirazian S. CKD-associated pruritus: new insights into diagnosis, pathogenesis, and management. Kidney Int Rep 2020; 5(9):1387-402. https://doi: 10.1016/j.ekir.2020.04.027
  28. Langedijk JAGM, Beuers UH, Oude Elferink RPJ. Cholestasis-associated pruritus and its pruritogens. Front Med (Lausanne) 2021; 8:639674. https://doi.org/10.3389/fmed.2021.639674
  29. Moniaga CS, Tominaga M, Takamori K. Mechanisms and management of itch in dry skin. Acta Derm Venereol 2020; 100(2):adv00024. https://doi.org/10.2340/00015555-3344
  30. Ullah A, Khan A, Khan I. Diabetes mellitus and oxidative stress—a concise review. Saudi Pharm J 2016; 24(5):547-53. https://doi.org/10.1016/j.jsps.2015.03.013
  31. Kanwar A. Skin barrier function. Indian J Med Res 2018; 147(1):117-8. https://doi.org/10.4103/0971-5916.232013
  32. Matsui T, Amagai M. Dissecting the formation, structure and barrier function of the stratum corneum. Int Immunol 2015; 27(6):269-80. https://doi.org/10.1093/intimm/dxv013
  33. Ibuki A, Kuriyama S, Toyosaki Y, Aiba M, Hidaka M, Horie Y, et al. Aging-like physiological changes in the skin of Japanese obese diabetic patients. SAGE Open Medicine 2018; 6:2050312118756662. https://doi.org/10.1177/2050312118756662
  34. Seité S, Khemis A, Rougier A, Ortonne JP. Importance of treatment of skin xerosis in diabetes. J Eur Acad Dermatology Venereol 2011; 25(5):607-9. https://doi.org/10.1111/j.1468-3083.2010.03807.x
  35. Kim JH, Yoon NY, Kim DH, Jung M, Jun M, Park HY, et al. Impaired permeability and antimicrobial barriers in type 2 diabetes skin are linked to increased serum levels of advanced glycation end-product. Exp Dermatol 2018; 27(8):815-23. https://doi.org/10.1111/exd.13466
  36. Cui L, Jia Y, Cheng ZW, Gao Y, Zhang GL, Li JY, et al. Advancements in the maintenance of skin barrier/skin lipid composition and the involvement of metabolic enzymes. J Cosmet Dermatol 2016; 15(4):549-58. https://doi.org/10.1111/jocd.12245
  37. Lechner A, Akdeniz M, Tomova-Simitchieva T, Bobbert T, Moga A, Lachmann N, et al. Comparing skin characteristics and molecular markers of xerotic foot skin between diabetic and non-diabetic subjects: an exploratory study. J Tissue Viability 2019; 28(4):200-9. https://doi.org/10.1016/j.jtv.2019.09.004
  38. Okano J, Kojima H, Katagi M, Nakagawa T, Nakae Y, Terashima T, et al. Hyperglycemia induces skin barrier dysfunctions with impairment of epidermal integrity in non-wounded skin of type 1 diabetic mice. PLoS One. 2016; 11(11):e0166215. https://doi.org/10.1371/journal.pone.0166215
  39. Kühbacher A, Burger-Kentischer A, Rupp S. Interaction of candida species with the skin. Microorganisms 2017; 5(2):32. https://doi.org/10.3390/microorganisms5020032
  40. Yosipovitch G, Misery L, Proksch E, Metz M, Ständer S, Schmelz M. Skin barrier damage and itch: review of mechanisms, topical management and future directions. Acta Derm Venereol 2019; 99(13):1201-9. https://doi.org/10.2340/00015555-3296
  41. Hu L, Mauro TM, Dang E, Man G, Zhang J, Lee D, et al. Epidermal dysfunction leads to an age-associated increase in levels of serum inflammatory cytokines. J Invest Dermatol 2017; 137(6):1277-85. https://doi.org/10.1016/j.jid.2017.01.007
  42. Pop-Busui R, Boulton AJM, Feldman EL, Bril V, Freeman R, Malik RA, et al. Diabetic neuropathy: a position statement by the American Diabetes Association. Diabetes Care 2017; 40(1):136-54. https://doi.org/10.2337/dc16-2042
  43. Hicks CW, Selvin E. Epidemiology of peripheral neuropathy and lower extremity disease in diabetes. Curr Diab Rep 2019; 19(10):86. https://doi.org/10.1007/s11892-019-1212-8
  44. Dogiparthi SN, Muralidhar K, Seshadri KG, Rangarajan S. Cutaneous manifestations of diabetic peripheral neuropathy. Dermatoendocrinol 2017; 9(1):e1395537. https://doi.org/10.1080/19381980.2017.1395537
  45. Román-Pintos LM, Villegas-Rivera G, Rodríguez-Carrizalez AD, Miranda-Díaz AG, Cardona-Muñoz EG. Diabetic polyneuropathy in type 2 diabetes mellitus: inflammation, oxidative stress, and mitochondrial function. J Diabetes Res 2016; 2016:3425617. https://doi.org/10.1155/2016/3425617
  46. Feldman EL, Callaghan BC, Pop-Busui R, Zochodne DW, Wright DE, Bennett DL, et al. Diabetic neuropathy. Nat Rev Dis Primers 2019; 5(1):41. https://doi.org/10.1038/s41572-019-0092-1
  47. Baum P, Toyka KV, Blüher M, Kosacka J, Nowicki M. Inflammatory mechanisms in the pathophysiology of diabetic peripheral neuropathy (DN)—new aspects. Int J Mol Sci 2021; 22(19):10835. https://doi.org/10.3390/ ijms221910835
  48. Zhang F, Hong S, Stone V, Smith PJW. Expression of cannabinoid CB1 receptors in models of diabetic neuropathy. J Pharmacol Exp Ther 2007; 323(2):508-15. https://doi.org/10.1124/jpet.107.128272
  49. Bodman MA, Varacallo M. Peripheral Diabetic Neuropathy. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan.Available from: https://www.ncbi.nlm.nih.gov/books/NBK442009/
  50. Luo KR, Chao CC, Hsieh PC, Lue JH, Hsieh ST. Effect of glycemic control on sudomotor denervation in type 2 diabetes. Diabetes Care 2012; 35(3):612-6. https://doi.org/10.2337/dc11-1607
  51. Vinik A, Casellini C, Nevoret ML. Diabetic Neuropathies. In: Feingold K, Anawalt B, Boyce A, eds. Endotext [Internet]. South Darmouth (MA): MDText.com,Inc. 2018. Available from: https://www.ncbi.nlm.nih.gov/books/NBK279175/
  52. Shiohara T, Sato Y, Komatsu Y, Ushigome Y, Mizukawa Y. Sweat as an efficient natural moisturizer. Curr Probl Dermatol 2016; 51:30-41. https://doi.org/10.1159/000446756
  53. Shiohara T, Mizukawa Y, Shimoda-Komatsu Y, Aoyama Y. Sweat is a most efficient natural moisturizer providing protective immunity at points of allergen entry. Allergol Int 2018; 67(4):442-7. https://doi.org/10.1016/j.alit.2018.07.010
  54. North RY, Lazaro TT, Dougherty PM. Ectopic spontaneous afferent activity and neuropathic pain. Neurosurgery 2018; 65(CN_suppl_1):49-54. https://doi.org/10.1093/neuros/nyy119
  55. Cheng RX, Feng Y, Liu D, Wang ZH, Zhang JT, Chen LH, et al. The role of Nav 1.7 and methylglyoxal-mediated activation of TRPA1 in itch and hypoalgesia in a murine model of type 1 diabetes. Theranostics 2019; 9(15):4287-307. https://doi.org/10.7150/thno.36077
  56. Kruk J, Duchnik E. Oxidative stress and skin diseases: possible role of physical activity. Asian Pac J Cancer Prev 2014; 15(2):561-8. https://doi.org/10.7314/apjcp.2014.15.2.561
  57. Giacco F, Brownlee M. Oxidative stress and diabetic complications. Circ Res 2010; 107(9):1058-70. https://doi.org/10.1161/CIRCRESAHA.110.223545
  58. Liu T, Ru-Rong J. Oxidative stress induces itch via activation of transient receptor potential subtype ankyrin 1 in mice. Neurosci Bull 2012; 28(2):145-54. https://doi.org/10.1007/s12264-012-1207-9
  59. Zhou F, Cheng RX, Wang S, Huang Y, Gao YJ, Zhou Y, et al. Antioxidants attenuate acute and chronic Itch: peripheral and central mechanisms of oxidative stress in pruritus. Neurosci Bull 2017; 33(4):423-35. https://doi.org/10.1007/s12264-016-0076-z
  60. Alicic RZ, Rooney MT, Tuttle KR. Diabetic kidney disease: challenges, progress, and possibilities. Clin J Am Soc Nephrol 2017; 12(12):2032-45. https://doi.org/10.2215/CJN.11491116
  61. Pecoits-Filho R, Abensur H, Betônico CCR, Machado AD, Parente EB, Queiroz M, et al. Interactions between kidney disease and diabetes: dangerous liaisons. Diabetol Metab Syndr 2016; 8:50. https://doi.org/10.1186/s13098-016-0159-z
  62. Tarikci N, Kocatürk E, Güngör Ş, Oğuz Topal I, Ülkümen Can P, Singer R. Pruritus in systemic diseases: a review of etiological factors and new treatment modalities. Sci World J 2015; 2015:803752. https://doi.org/10.1155/2015/803752
  63. Germain MJ. Uremic pruritus: an itch with ominous consequences. Am J Nephrol 2017; 46(6):448-9. https://doi.org/10.1159/000484572
  64. Makar M, Smyth B, Brennan F. Chronic kidney disease-associated pruritus: a review. Kidney Blood Press Res 2021; 46(6):659-9. https://doi.org/10.1159/000518391
  65. Reich A, Ständer S, Szepietowski JC. Drug-induced pruritus: a review. Acta Derm Venereol 2009; 89(3):236-44. https://doi.org/10.2340/00015555-0650
  66. Imam MH, Gossard AA, Sinakos E, Lindor KD. Pathogenesis and management of pruritus in cholestatic liver disease. J Gastroenterol Hepatol 2012; 27(7):1150-8. https://doi.org/10.1111/j.1440-1746.2012.07109.x
  67. Bassari R, Koea JB. Jaundice associated pruritis: a review of pathophysiology and treatment. World J Gastroenterol 2015; 21(5):1404-13. https://doi.org/10.3748/wjg.v21.i5.1404
  68. Rayner H, Baharani J, Smith S, Suresh V, Dasgupta I. Uraemic pruritus: relief of itching by gabapentin and pregabalin. Nephron Clin Pract 2012; 122(3–4):75–9. https://doi.org/10.1159/000349943
  69. Tamez-Pérez HE, Quintanilla-Flores DL, Rodríguez-Gutiérrez R, González-González JG, Tamez-Peña AL. Steroid hyperglycemia: prevalence, early detection and therapeutic recommendations: a narrative review. World J Diabetes 2015; 6(8):1073-81. https://doi.org/10.4239/wjd.v6.i8.1073
  70. Nowak DA, Yeung J. Diagnosis and treatment of pruritus. Can Fam Physician 2017; 6312):918-24.
  71. American Diabetes Association. Skin complications [Accessed on 2021 Nov 1] Available from: https://www.diabetes.org/diabetes/complications/skin-complications..
  72. Bristow I. Emollients in the care of the diabetic foot. Diabetic Foot 2013; 16(2):63-6.
  73. Narbutt J, Bednarski IA, Lesiak A. The effect of an emollient with benfothiamine and Biolin prebiotic on the improvement of epidermal skin function. Postepy Dermatol Alergol 2016; 33(3):224-31. https://doi.org/10.5114/ada.2016.60616
  74. Ibrahim IM, Elsaie ML, Almohsen AM, Mohey-Eddin MH. Effectiveness of topical clove oil on symptomatic treatment of chronic pruritus. J Cosmet Dermatol 2017; 16(4):508-11. https://doi.org/10.1111/jocd.12342
  75. Şavk E. Neurologic itch management. Curr Prob Dermatol (Switzerland) 2016; 50:116-23. https://doi.org/10.1159/000446053
  76. Matsuda KM, Sharma D, Schonfeld AR, Kwatra SG. Gabapentin and pregabalin for the treatment of chronic pruritus. J Am Acad Dermatol 2016; 75(3):619-25.e6 https://doi.org/10.1016/j.jaad.2016.02.1237
  77. Bajaj S, Khan Afreen. Antioxidants and diabetes. Indian J Endocrinol Metab 2012; 16:S267-71. https://doi.10.4103/2230-8210.104057
  78. Rochette L, Zeller M, Cottin Y, Vergely C. Diabetes, oxidative stress and therapeutic strategies. Biochim Biophys Acta Gen Subj 2014; 1840(9):2709-29. https://doi.org/10.1016/j.bbagen.2014.05.017
  79. Hahm JR, Kim BJ, Kim KW. Clinical experience with thioctacid (thioctic acid) in the treatment of distal symmetric polyneuropathy in Korean diabetic patients. J Diabetes Complications 2004; 18(2):79-85. https://doi.org/10.1016/S1056-8727(03)00033-3
  80. Avila C, Massick S, Kaffenberger BH, Kwatra SG, Bechtel M. Cannabinoids for the treatment of chronic pruritus: a review. J Am Acad Dermatol 2020; 82(5):1205-12. https://doi.org/10.1016/j.jaad.2020.01.036
  81. Mounessa JS, Siegel JA, Dunnick CA, Dellavalle RP. The role of cannabinoids in dermatology. J Am Acad Dermatol 2017; 77(1):188-90. https://doi.org/10.1016/j.jaad.2017.02.056
  82. Xu DH, Cullen BD, Tang M, Fang Y. The effectiveness of topical cannabidiol oil in symptomatic relief of peripheral neuropathy of the lower extremities. Curr Pharm Biotechnol 2020; 21(5):390-402. https://doi.org/10.2174/1389201020666191202111534
  83. Kouwenhoven TA, van de Kerkhof PCM, Kamsteeg M. Use of oral antidepressants in patients with chronic pruritus: a systematic review. J Am Acad Dermatol 2017; 77(6):1068-73.37. https://doi.org/10.1016/j.jaad.2017.08.025
  84. Gooding SMD, Canter PH, Coelho HF, Boddy K, Ernst E. Systematic review of topical capsaicin in the treatment of pruritus. Int J Dermatol 2010; 49(8):858-65. https://doi.org/10.1111/j.1365-4632.2010.04537.x
  85. Gupta K, Harvima IT. Mast cell-neural interactions contribute to pain and itch. Immunol Rev 2018; 282(1):168-87. https://doi.org/10.1111/imr.12622



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