PharmatecaPharmatecaФарматека2073-40342414-9128Bionika Media69124010.18565/pharmateca.2025.5.6-12ReviewsОбзорыReview ArticleImmunopathogenesis of itching in Hodgkin’s lymphoma: current statusИммунопатогенез зуда при лимфоме Ходжкина: современное состояние вопросаhttps://orcid.org/0009-0006-4847-1735PopovaAnna I.ПоповаАнна Ивановна
Russian Federation

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

аспирант кафедры аллергологии и иммунологии с курсом дерматовенерологии и косметологии

annapopova3107@gmail.comhttps://orcid.org/0000-0002-3902-2018OrlovaEkaterina A.ОрловаЕкатерина Александровна
Russian Federation

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

д.м.н., доцент, зав. кафедрой аллергологии и иммунологии с курсом дерматовенерологии и косметологии

lisaorl@yandex.ruhttps://orcid.org/0000-0003-1797-8040KostinaElena M.КостинаЕлена Михайловна
Russian Federation

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

д.м.н., доцент, профессор кафедры аллергологии и иммунологии с курсом дерматовенерологии и косметологии

elmihkostina@yandex.ruhttps://orcid.org/0009-0001-6903-2356NikolashinaOlga E.НиколашинаОльга Евгеньевна
Russian Federation

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

к.м.н., доцент кафедры микробиологии, эпидемиологии и инфекционных болезней

nikolashina515@mail.ruPenza Institute for Advanced Medical Training – Branch Campus of the Russian Medical Academy of Continuous Professional EducationПензенский институт усовершенствования врачей – филиал ФГБОУ ДПО РМАНПО Минздрава РоссииPenza State UniversityПензенский государственный университет240920253256122309202523092025Copyright ©; 2025, Bionika MediaCopyright ©; 2025, ООО «Бионика Медиа»2025Bionika MediaООО «Бионика Медиа»https://journals.eco-vector.com/2073-4034/article/view/691240

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.

Зуд – частый и изнурительный симптом лимфомы Ходжкина (ЛХ), существенно снижающий качество жизни пациентов. Данный обзор посвящен современным представлениям о механизмах зуда при этом заболевании для углубления понимания патогенеза этого симптома и поиска новых терапевтических стратегий, направленных на улучшение качества жизни пациентов.

Проанализирована роль различных факторов, включая цитокины, гистамин и нейромедиаторы, в его развитии. Особое внимание уделено взаимодействию этих механизмов и их влиянию на интенсивность и продолжительность зуда. Также анализируются перспективные направления исследований, способствующие более глубокому пониманию патогенеза этого симптома и разработке новых терапевтических стратегий. Подчеркивается необходимость междисциплинарного подхода к ранней диагностике ЛХ с учетом зуда как одного из возможных клинических проявлений и важность своевременного лечения.

Hodgkin’s lymphomaitchingpathogenesiscytokinesneuropeptidestreatmentлимфома ХоджкиназудпатогенезцитокинынейропептидылечениеRowe B., Yosipovitch G. Malignancy-associated pruritus. Eur J Pain (London, England). 2016;20(1):19–23. https://dx.doi.org/10.1002/ejp.760McCormick 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/10.1177/23247096241255840Ferretti 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.19665Greaves 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-2013-06-508044Weisshaar 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/10.2340/00015555-3164Yosipovitch G. Chronic pruritus: a paraneoplastic sign. Dermatol Ther. 2010;23(6):590-596. https://dx.doi.org/10.1111/j.1529–8019.2010.01366.xWang 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.xРукавицын 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/10.34215/1609-1175-2020-4-76-80Rubenstein 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.xHiramanek N. Itch: a symptom of occult disease. Aust Fam Physician. 2004;33(7):495–499.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-rAnderson 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.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/s13277-015-4622-5Greaves 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-2013-06-508044Steidl 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-2008-07-168096Churchill 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.2010.05.010Muenst 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.2009.03.025Hu 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-xHu 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-yWen 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.2024.111777Cevikbas 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.2013.10.048Feld 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.2016.02.020Nakajima 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.14890Kim 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/s12264-022-00837-6Hsu 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)90004-3Chen Z.F. Neuropeptide coding of itch. Nat Rev Neurosci. 2021;22(12):758–776. https://dx.doi.org/10.1038/s41583-021-00526-9Datsi 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.14791Di 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-yCevikbas 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.2013.10.048Di 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/s12948-021-00171-1Skinnider 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-2002-01-0099Benharroch 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):51–57Gorschlüter 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.a059218Güler 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/10.1080/10245330400020405Yosipovitch 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.2018.09.005Ellis 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/10.1186/1710-1492-5-12Wang F., Kim B.S. Itch: A Paradigm of neuroimmune crosstalk. Immunity. 2020;52(5):753–766. https://dx.doi.org/10.1016/j.immuni.2020.04.008Misery 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.2023.05.004Смирнова 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/10.33978/2307-3586-2025-21-3-24-28Chen 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/JCI160807Demierre 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