Immunopathogenesis of itching in Hodgkin’s lymphoma: current status

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Resumo

Itching is a frequent and debilitating symptom of Hodgkin’s lymphoma (HL), significantly reducing the quality of life of patients. This review is devoted to current understanding of the mechanisms of itching in this disease to deepen our understanding of the pathogenesis of this symptom and search for new therapeutic strategies aimed at improving the quality of life of patients.

The role of various factors, including cytokines, histamine and neurotransmitters, in its development is analyzed. Particular attention is paid to the interaction of these mechanisms and their impact on the intensity and duration of itching. Promising research areas that contribute to a deeper understanding of the pathogenesis of this symptom and the development of new therapeutic strategies are also analyzed. The need for an interdisciplinary approach to early diagnostics of Hodgkin’s lymphoma, taking into account itching as one of the possible clinical manifestations, and the importance of timely treatment are emphasized.

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Sobre autores

Anna Popova

Penza Institute for Advanced Medical Training – Branch Campus of the Russian Medical Academy of Continuous Professional Education

Autor responsável pela correspondência
Email: annapopova3107@gmail.com
ORCID ID: 0009-0006-4847-1735

Postgraduate Student, Department of Allergology and Immunology with a Course in Dermatovenereology and Cosmetology

Rússia, Penza

Ekaterina Orlova

Penza Institute for Advanced Medical Training – Branch Campus of the Russian Medical Academy of Continuous Professional Education

Email: lisaorl@yandex.ru
ORCID ID: 0000-0002-3902-2018

Dr. Sci. (Med.), Associate Professor, Head of the Department of Allergology and Immunology with a Course in Dermatovenereology and Cosmetology

Rússia, Penza

Elena Kostina

Penza Institute for Advanced Medical Training – Branch Campus of the Russian Medical Academy of Continuous Professional Education

Email: elmihkostina@yandex.ru
ORCID ID: 0000-0003-1797-8040

Dr. Sci. (Med.), Associate Professor, Professor at the Department of Allergology and Immunology with the Course of Dermatovenereology and Cosmetology

Rússia, Penza

Olga Nikolashina

Penza State University

Email: nikolashina515@mail.ru
ORCID ID: 0009-0001-6903-2356

Cand. Sci. (Med.), Associate Professor, Department of Microbiology, Epidemiology and Infectious Diseases

Rússia, Penza

Bibliografia

  1. Rowe B., Yosipovitch G. Malignancy-associated pruritus. Eur J Pain (London, England). 2016;20(1):19–23. https://dx.doi.org/10.1002/ejp.760
  2. McCormick B.J., Zieman D., Sluzevich J.C., et al. Clinical features of cutaneous paraneoplastic syndromes in Hodgkin Lymphoma. J Investig Med High Impact Case Rep. 2024;12:23247096241255840. https://dx.doi.org/10.1177/23247096241255840
  3. Ferretti E., Hohaus S., Di Napoli A., et al. Interleukin-31 and thymic stromal lymphopoietin expression in plasma and lymph nodes of Hodgkin lymphoma patients. Oncotarget. 2017;8(49):85263–85275. https://dx.doi.org/10.18632/oncotarget.19665
  4. Greaves P., Clear A., Owen A., et al. Defining characteristics of classical Hodgkin lymphoma microenvironment T-helper cells. Blood. 2013;122(16):2856–2863. https://dx.doi.org/10.1182/blood-2013-06-508044
  5. Weisshaar E., Szepietowski J.C., Dalgard F.J., et al. European S2k Guideline on chronic pruritus. Acta Derm Venereol. 2019;99(5):469–506. https://dx.doi.org/10.2340/00015555-3164
  6. Yosipovitch G. Chronic pruritus: a paraneoplastic sign. Dermatol Ther. 2010;23(6):590-596. https://dx.doi.org/10.1111/j.1529–8019.2010.01366.x
  7. Wang H., Yosipovitch G. New insights into the pathophysiology and treatment of chronic itch in patients with end-stage renal disease, chronic liver diseases, and lymphoma. Int J Dermatol. 2010;49(1):1–11. https://dx.doi.org/10.1111/j.1365-4632.2009.04249.x
  8. Рукавицын А.О., Ламоткин И.А., Рукавицын О.А. и др. Неспецифические поражения кожи при злокачественных лимфомах. Вестник дерматологии и венерологии. 2020;4:76–80. [Rukavitsyn A.O., Lamotkin I.A., Rukavitsyn O.A., Lamotkin A.I. Nonspecific skin lesions in malignant lymphomas. Vestnik Dermatologii i Venerologii. 2020;4:76–80. (In Russ.)]. https://dx.doi.org/10.34215/1609-1175-2020-4-76-80
  9. Rubenstein M., Duvic M. Cutaneous manifestations of Hodgkin’s disease. Int J Dermatol. 2006;45(3):251-256. https://dx.doi.org/10.1111/j.1365-4632.2006.02675.x
  10. Hiramanek N. Itch: a symptom of occult disease. Aust Fam Physician. 2004;33(7):495–499.
  11. Gobbi P.G., Attardo-Parrinello G., Lattancio G., et al. Severe pruritus should be a B symptom in Hodgkin’s disease. Cancer. 1983;51(10):1934–1936. https://dx.doi.org/10.1002/1097-0142(19830515)51:10<1934::aid-cncr2820511030>3.0.co;2-r
  12. Anderson A.C., Joller N., Kuchroo V.K. Lag-3, Tim-3, and TIGIT: co-inhibitory receptors with specialized functions in immune regulation. Immunity. 2016;44(5):989–1004.
  13. Ko Y.W., Jeon Y.K., Yoon D.H., et al. Programmed cell death 1 protein expression in the peritumoral microenvironment is associated with worse prognosis in classical Hodgkin lymphoma. Tumour Biol. 2016;37(6):7507–7514. https://dx.doi.org/10.1007/s13277-015-4622-5
  14. Greaves P., Clear A., Owen A., et al. Defining characteristics of classical Hodgkin lymphoma microenvironment T-helper cells. Blood. 2013;122(16):2856–2863. https://dx.doi.org/10.1182/blood-2013-06-508044
  15. Steidl C., Bertucci F., Finetti P., et al. Molecular profiling of classical Hodgkin lymphoma tissues identifies variations in the tumor microenvironment and correlations with EBV infection and outcome. Blood. 2009;113(12):2765–2775. https://dx.doi.org/10.1182/blood-2008-07-168096
  16. Churchill H.R., Roncador G., Warnke R.A., et al. Programmed death-1 ligand 1 expression in various histologic patterns of nodular lymphocyte predominant Hodgkin lymphoma: comparison with CD57 and lymphoma in the differential diagnosis. Hum Pathol. 2010;41(12):1726–1734. https://dx.doi.org/10.1016/j.humpath.2010.05.010
  17. Muenst S., Hoeller S., Dirnhof S., et al. Increased programmed death-1 receptor+ tumor-infiltrating lymphocytes in classical Hodgkin lymphoma is associated with decreased overall survival. Hum Pathol. 2009;40(12):1715–1722. https://dx.doi.org/10.1016/j.humpath.2009.03.025
  18. Hu M., Scheffel J., Elieh-Ali-Komi D., et al. Recent insights into itch mechanisms and potential treatment in primary cutaneous T-cell lymphoma. Clin Exp Dermatol. 2023;23(8):4177–4197. https://dx.doi.org/10.1007/s10238-023-01141-x
  19. Hu M., Scheffel J., Frischbutter S., et al. Characterization of itch-associated cells and mediators in primary cutaneous T-cell lymphomas. Clin Exp Dermatol. 2024;24(1):171. https://dx.doi.org/10.1007/s10238-024-01407-y
  20. Wen X., Yu H., Zhang L., et al. Correlation and clinical significance of serum cytokine expression levels and skin pruritus in patients with Hodgkin lymphoma and angioimmunoblastic T-cell lymphoma. Int Immunopharmacol. 2024;131:111777. https://dx.doi.org/10.1016/j.intimp.2024.111777
  21. Cevikbas F., Wang X., Akiyama T., et al. IL-31 receptor-expressing sensory neurons mediate T helper cell-dependent itch: involvement of TRPV1 and TRPA1. J Allergy Clin Immunol. 2014;133(2):448–460. https://dx.doi.org/10.1016/j.jaci.2013.10.048
  22. Feld M., Garcia R., Buddenkotte J., et al. The itch-associated, TH2-derived cytokine IL-31 promotes sensory nerve growth. J Allergy Clin Immunol. 2016;138(2):500–508.e24. https://dx.doi.org/10.1016/j.jaci.2016.02.020
  23. Nakajima M., Watanabe M., Nakano K., et al. Differentiation of Hodgkin lymphoma cells induced by reactive oxygen species and regulated by heme oxygenase-1 via HIF-1α. Cancer Sci. 2021;112(6):2542–2555. https://dx.doi.org/10.1111/cas.14890
  24. Kim S.A., Jang J.H., Kim S., et al. Mitochondrial reactive oxygen species evoke acute and chronic itch via transient receptor potential canonical 3 activation in mice. Neurosci Bull. 2022;38(4):373–385. https://dx.doi.org/10.1007/s12264-022-00837-6
  25. Hsu S.M., Hsu P.L. Autocrine and paracrine functions of cytokines in malignant lymphomas. Biomed Pharmacother. 1994;48(10):433–444. https://dx.doi.org/10.1016/0753-3322(94)90004-3
  26. Chen Z.F. Neuropeptide coding of itch. Nat Rev Neurosci. 2021;22(12):758–776. https://dx.doi.org/10.1038/s41583-021-00526-9
  27. Datsi A., Steinhoff M., Ahmad F., et al. Interleukin-31: the «itchy» cytokine in inflammation and therapy. Allergy. 2021;76(10):2982–2997. https://dx.doi.org/10.1111/all.14791
  28. Di Salvo E., Allegra A., Casciaro M., Gangemi S. IL-31, itch, and hematological malignancies. Clin Mol Allergy. 2021;19(1):8. https://dx.doi.org/10.1186/s12948-021-00157-y
  29. Cevikbas F., Wang X., Akiyama T., et al. IL-31 receptor signaling mediates itch in atopic dermatitis. J Allergy Clin Immunol. 2014;133(2):448–460. https://dx.doi.org/10.1016/j.jaci.2013.10.048
  30. Di Salvo E., Casciaro M., Gangemi S. IL-33 genetics and epigenetics in immune-related diseases. Clin Mol Allergy. 2021;19(1):18. https://dx.doi.org/10.1186/s12948-021-00171-1
  31. Skinnider B.F., Mak T.W. The role of cytokines in classical Hodgkin lymphoma. Blood. 2002;99(12):4283–4297. https://dx.doi.org/10.1182/blood-2002-01-0099
  32. Benharroch D., Prinsloo J., Apte R.N., et al. Interleukin-1 and tumor necrosis factor-alpha in Reed-Sternberg cells of Hodgkin’s disease. Correlation with clinical and morphological «inflammatory» features. Cytokine Network. 1996;7(1):51–57
  33. Gorschlüter M., Bohlen H., Hasenclever D., et al. Serum cytokine levels correlate with clinical features in Hodgkin’s disease. Ann Oncol. 1995;6(5):477–482. https://dx.doi.org/10.1093/oxfordjournals.annonc.a059218
  34. Güler N., Yilmaz S., Ayaz S., et al. Platelet-derived growth factor (PDGF) levels in Hodgkin’s disease and non-Hodgkin’s lymphoma and its relationship with disease activation. Hematology. 2005;10(1):53–57. https://dx.doi.org/10.1080/10245330400020405
  35. Yosipovitch G., Rosen J.D., Hashimoto T. Itch: From mechanism to (novel) therapeutic approaches. J Allergy Clin Immunol. 2018;142(5):1375–1390. https://dx.doi.org/10.1016/j.jaci.2018.09.005
  36. Ellis A.K., Weatherman S. Hodgkin lymphoma presenting with markedly elevated IgE level: A case report. Allergy Asthma Clin Immunol. 2009;5(1):12. https://dx.doi.org/10.1186/1710-1492-5-12
  37. Wang F., Kim B.S. Itch: A Paradigm of neuroimmune crosstalk. Immunity. 2020;52(5):753–766. https://dx.doi.org/10.1016/j.immuni.2020.04.008
  38. Misery L., Pierre O., Le Gall-Ianotto C., et al. Major mechanisms of itch. J Allergy Clin Immunol. 2023;152(1):11–23. https://dx.doi.org/10.1016/j.jaci.2023.05.004
  39. Смирнова И.О., Петунова Я.Г., Шин Н.В. и др. Зуд, ассоциированный с ксерозом кожи: от патогенеза к терапии. Эффективная фармакотерапия. 2025;21(3):24–28. [Smirnova I.O., Petunova Y.G., Shin N.V., et al. Itch Associated with Xerosis Cutis: From Pathogenesis to Therapy. Effektivnaya Farmakoterapiya. 2025;21(3):24–28. (In Russ.)]. https://dx.doi.org/10.33978/2307-3586-2025-21-3-24-28
  40. Chen O., He Q., Han Q., et al. Mechanisms and treatment of neuropathic itch in a lymphoma mouse model. J Clin Invest. 2023;133(4):e160807. https://dx.doi.org/10.1172/JCI160807
  41. Demierre M.F., Taverna J. Mirtazapine and gabapentin for reducing pruritus in cutaneous T-cell lymphoma. J Am Acad Dermatol. 2006;55(3):543–544. https://dx.doi.org/10.1016/j.jaad.2006.04.025

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