medalphabetМедицинский алфавитMedical alphabet2078-56312949-2807ООО «Альфмед»10.33667/2078-5631-2026-3-8-13medalphabet-4940Research ArticleСтатьиИммунопатогенетические основы кожных парадоксальных реакций при лечении ингибиторами ФНО-αImmunopathogenetic basis of paradoxical cutaneous reactions during treatment with TNF-α inhibitorshttps://orcid.org/0009-0001-4973-9098ЧуркинаД. Б.ChurkinaD. B.

Чуркина Дарья Борисовна, аспирант кафедры дерматовенерологии и косметологии

Москва

Churkina Daria B., postgraduate student at Det of Dermatovenereology and Cosmetology

Moscow 

dchursina3@gmail.comhttps://orcid.org/0000-0002-0238-6563ШатохинаЕ. А.ShatokhinaE. A.

Шатохина Евгения Афанасьевна, д.м.н., профессор кафедры дерматовенерологии и косметологии, ведущий научный сотудник. отдела внутренних болезней

Москва

Shatokhina Evgeniya A., Dr Med Sci (habil.), professor at Dept of Dermatovenereology and Cosmetology, leading researcher at Dept of Internal Medicine

Moscow 

e.a.shatokhina@gmail.comhttps://orcid.org/0000-0002-3818-6205КаграмановаА. В.KagramanovaA. V.

Каграманова Анна Валерьевна, д.м.н., старший научный сотрудник. отделения воспалительных заболеваний кишечника, ведущий специалист отд. по колопроктологии

Москва

Kagramanova Anna V., Dr Med Sci (habil.), senior researcher at Dept of Inflammatory Bowel Diseases, leading specialist at Dept of Proctology

Moscow 

kagramanova@me.comhttps://orcid.org/0000-0002-5044-5265КругловаЛ. С.KruglovaL. S.

Круглова Лариса Сергеевна, д.м.н., профессор, зав. кафедрой дерматовенерологии и косметологии

Москва

Kruglova Larisa S., Dr Med Sci (habil.), professor, head of Dept of Dermatovenereology and Cosmetology

Moscow 

kruglovals@mail.ruФГБУ ДПО «Центральная государственная медицинская академия» Управления делами Президента Российской ФедерацииРоссияCentral State Medical Academy of the Administrative Department of the President of the Russian FederationRussian FederationФГБУ ДПО «Центральная государственная медицинская академия» Управления делами Президента Российской Федерации ; Научно-образовательный институт ФГБОУ ВО «Московский государственный университет имени М.В. Ломоносова»РоссияCentral State Medical Academy of the Administrative Department of the President of the Russian Federation ; Research and Educational Institute of Lomonosov Moscow State UniversityRussian FederationГБУЗ «Московский клинический научно-практический центр им. А.С. Логинова» Департамента здравоохранения г. Москвы ; ГБУ «Научно-исследовательский институт организации здравоохранения и медицинского менеджмента» Департамента здравоохранения г. МосквыРоссияA.S. Loginov Moscow Clinical Scientific and Practical Center of the Moscow Department of Healthcare ; Research Institute for Healthcare Organization and Medical Management of the Moscow Department of HealthcareRussian Federation20261404202603Дерматология (1)813Copyright © Чуркина Д.Б., Шатохина Е.А., Каграманова А.В., Круглова Л.С., 20262026Чуркина Д.Б., Шатохина Е.А., Каграманова А.В., Круглова Л.С.Churkina D.B., Shatokhina E.A., Kagramanova A.V., Kruglova L.S.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-alphabet.com/jour/article/view/4940

Длительная терапия генно-инженерными препаратами из группы ингибиторов фактора некроза опухоли-α (иФНО-α), являющаяся стандартом лечения тяжелых иммуновоспалительных заболеваний, может индуцировать развитие парадоксальных реакций (ПР) – возникновение или обострение иммуноопосредованных дерматозов, патогенетически родственных тем, для лечения которых применяется препарат. В основе патогенеза ПР лежит нарушение системного иммунного гомеостаза вследствие блокады цитокина, обладающего широким спектром функций, что приводит к дисрегуляции цитокинового баланса, изменению доминирующего типа иммунного ответа и гиперактивации альтернативных провоспалительных путей. Клинические проявления ПР многообразны и включают псориазиформные, экзематозные, лихеноидные, гранулематозные реакции, а также парадоксальные формы нейтрофильных дерматозов, каждая из которых обладает уникальными эпидемиологическими и клинико-морфологическими особенностями. Развитие ПР детерминировано взаимодействием фармакологического вмешательства с индивидуальным генетическим фоном пациента. Изучение ПР представляет значительный интерес не только в контексте фармакологической безопасности, но и как уникальная модель для исследования иммунного гомеостаза человека in vivo, демонстрирующая высокую степень компенсации и нелинейность цитокиновых коллатералей.

Цель обзора: систематизировать современные представления о патогенезе парадоксальных реакций (ПР), развивающихся на фоне генно-инженерной биологической терапии препаратами из группы ингибиторов ФНО-α.

Long-term therapy with tumor necrosis factor-alpha (TNF-α) inhibitors – a cornerstone in the treatment of severe immune-mediated inflammatory diseases – can induce paradoxical reactions (PR): the de novo onset or exacerbation of immune-mediated dermatoses that are pathogenetically related to the conditions for which the drug was prescribed. The pathogenesis of PR arises from a disruption of systemic immune homeostasis following blockade of TNF-α, a pleiotropic cytokine with diverse regulatory functions. This leads to cytokine imbalance, a shift in the dominant T-helper immune response, and hyperactivation of alternative pro-inflammatory pathways. Clinically, PR are highly heterogeneous, encompassing psoriasiform, eczematous, lichenoid, and granulomatous reactions, as well as paradoxical neutrophilic dermatoses – each characterized by distinct epidemiological and clinicomorphological features. The development of PR is determined by the interplay between pharmacological intervention and the patient’s individual genetic background. The study of PR is of considerable interest not only in the context of pharmacovigilance but also as a unique in vivo model for investigating human immune homeostasis, illustrating the high degree of compensatory capacity and nonlinearity inherent in cytokine networks.

Purpose of the review: to systematize current understanding of the pathogenesis of paradoxical reactions (PR) occurring during genetically engineered biological therapy with tumor necrosis factor-alpha (TNF-α) inhibitors.

парадоксальные кожные реакцииингибиторы ФНО- αпсориазгангренозная пиодермияparadoxical skin reactionsTNFα-inhibitorspsoriasispyoderma gangrenosumReferencesBrown G., Wang E., Leon A., Huynh M., Wehner M. Tumor necrosis factor-α inhibitor-induced psoriasis: systematic review of clinical features, histopathological findings, and management experience. J Am Acad Dermatol. 2017; 76 (2): 334–341. https://doi.org/10.1016/j.jaad.2016.08.012Brown G., Wang E., Leon A., Huynh M., Wehner M. Tumor necrosis factor-α inhibitor-induced psoriasis: systematic review of clinical features, histopathological findings, and management experience. J Am Acad Dermatol. 2017; 76 (2): 334–341. https://doi.org/10.1016/j.jaad.2016.08.012Toussirot É., Aubin F. Paradoxical reactions under TNF-α blocking agents and other biological agents given for chronic immune-mediated diseases: an analytical and comprehensive overview. RMD Open. 2016; 2 (2): e000239. https://doi.org/10.1136/rmdopen-2015–000239Toussirot É., Aubin F. Paradoxical reactions under TNF-α blocking agents and other biological agents given for chronic immune-mediated diseases: an analytical and comprehensive overview. RMD Open. 2016; 2 (2): e000239. https://doi.org/10.1136/rmdopen-2015–000239Toussirot E., Pertuiset E. TNFα blocking agents and sarcoidosis: an update. Rev Med Interne. 2010; 31 (12): 828–37. https://doi.org/10.1016/j.revmed.2010.02.007Toussirot E., Pertuiset E. TNFα blocking agents and sarcoidosis: an update. Rev Med Interne. 2010; 31 (12): 828–37. https://doi.org/10.1016/j.revmed.2010.02.007Murphy M.J., Cohen J.M., Vesely M.D. Paradoxical eruptions to targeted therapies in dermatology: A systematic review and analysis. J Am Acad Der matol. 2022; 86 (5):1080–91. https://doi.org/10.1016/j.jaad.2020.12.010Murphy M.J., Cohen J.M., Vesely M.D. Paradoxical eruptions to targeted therapies in dermatology: A systematic review and analysis. J Am Acad Der matol. 2022; 86 (5):1080–91. https://doi.org/10.1016/j.jaad.2020.12.010Eyerich, K., Eyerich, S. Immune response patterns in non-communicable inflammatory skin diseases. J. Eur. Acad. Dermatol. Venereol. 2018; 32 (5): 692–703. https://doi.org/10.1111/jdv.14673Eyerich, K., Eyerich, S. Immune response patterns in non-communicable inflammatory skin diseases. J. Eur. Acad. Dermatol. Venereol. 2018; 32 (5): 692–703. https://doi.org/10.1111/jdv.14673Schett G., McInnes I.B., Neurath M.F. Reframing Immune-Mediated Inflammatory Diseases through Signature Cytokine Hubs. N. Engl. J. Med. 2021; 385 (7):628–639. https://doi.org/10.1056/NEJMra1909094Schett G., McInnes I.B., Neurath M.F. Reframing Immune-Mediated Inflammatory Diseases through Signature Cytokine Hubs. N. Engl. J. Med. 2021; 385 (7):628–639. https://doi.org/10.1056/NEJMra1909094Braegelmann C., Niebel D., Wenzel J. Targeted Therapies in Autoimmune Skin Diseases. J. Investig. Dermatol. 2022; 142 (3): 969–975.e7. https://doi.org/10.1016/j.jid.2021.08.439Braegelmann C., Niebel D., Wenzel J. Targeted Therapies in Autoimmune Skin Diseases. J. Investig. Dermatol. 2022; 142 (3): 969–975.e7. https://doi.org/10.1016/j.jid.2021.08.439Annunziato F., Romagnani C., Romagnani S. The 3 major types of innate and adaptive cell-mediated effector immunity. J. Allergy Clin. Immunol. 2015; 135 (3): 626–35. https://doi.org/10.1016/j.jaci.2014.11.001Annunziato F., Romagnani C., Romagnani S. The 3 major types of innate and adaptive cell-mediated effector immunity. J. Allergy Clin. Immunol. 2015; 135 (3): 626–35. https://doi.org/10.1016/j.jaci.2014.11.001Wenzel J., Tuting T. An IFN-associated cytotoxic cellular immune response against viral, self-, or tumor antigens is a common pathogenetic feature in “interface dermatitis”. J. Investig. Dermatol. 2008; 128 (10): 2392–2402. https://doi.org/10.1038/jid.2008.96Wenzel J., Tuting T. An IFN-associated cytotoxic cellular immune response against viral, self-, or tumor antigens is a common pathogenetic feature in “interface dermatitis”. J. Investig. Dermatol. 2008; 128 (10): 2392–2402. https://doi.org/10.1038/jid.2008.96Jutel M., Agache I., Zemelka-Wiacek M. Nomenclature of allergic diseases and hypersensitivity reactions: Adapted to modern needs: An EAACI position paper. Allergy. 2023; 78 (11): 2851–2874. https://doi.org/10.1111/all.15889Jutel M., Agache I., Zemelka-Wiacek M. Nomenclature of allergic diseases and hypersensitivity reactions: Adapted to modern needs: An EAACI position paper. Allergy. 2023; 78 (11): 2851–2874. https://doi.org/10.1111/all.15889Rappl G., Pabst S., Riemann D. Regulatory T cells with reduced repressor capacities are extensively amplified in pulmonary sarcoid lesions and sustain granuloma formation. Clin Immunol. 2011; 140 (1): 71–83. https://doi.org/10.1016/j.clim.2011.03.015Rappl G., Pabst S., Riemann D. Regulatory T cells with reduced repressor capacities are extensively amplified in pulmonary sarcoid lesions and sustain granuloma formation. Clin Immunol. 2011; 140 (1): 71–83. https://doi.org/10.1016/j.clim.2011.03.015Cilfone N.A., Perry C.R., Kirschner D.E. Multi-scale modeling predicts a balance of tumor necrosis factor-alpha and interleukin-10 controls the granuloma environment during Mycobacterium tuberculosis infection. PLoS One. 2013; 8 (7): e68680. https://doi.org/10.1371/journal.pone.0068680Cilfone N.A., Perry C.R., Kirschner D.E. Multi-scale modeling predicts a balance of tumor necrosis factor-alpha and interleukin-10 controls the granuloma environment during Mycobacterium tuberculosis infection. PLoS One. 2013; 8 (7): e68680. https://doi.org/10.1371/journal.pone.0068680Eyerich K., Eyerich S. Immune response patterns in non-communicable inflammatory skin diseases. J Eur Acad Dermatol Venereol. 2018; 32(5): 692–703. https://doi.org/10.1111/jdv.14673.Eyerich K., Eyerich S. Immune response patterns in non-communicable inflammatory skin diseases. J Eur Acad Dermatol Venereol. 2018; 32(5): 692–703. https://doi.org/10.1111/jdv.14673.Gonzalez Caldito N. Role of tumor necrosis factor-alpha in the central nervous system: a focus on autoimmune disorders. Front Immunol. 2023; 14: 1213448. https://doi.org/10.3389/fimmu.2023.1213448Gonzalez Caldito N. Role of tumor necrosis factor-alpha in the central nervous system: a focus on autoimmune disorders. Front Immunol. 2023; 14: 1213448. https://doi.org/10.3389/fimmu.2023.1213448Молочкова Ю.В., Хлебникова А.Н. Клинико-патоморфологические ассоциации красного плоского лишая. Российский журнал кожных и венерических болезней. 2016; 19 (5): 286–290. https://doi.org/10.18821/1560-9588-2016-19-5-286-290Molochkova Yu.V., Khlebnikova A.N. Clinical and pathological red flat depriving association. Russian Journal of Skin and Venereal Diseases. 2016; 19 (5): 286–290. (In Russ.). http://dx.doi.org/10.18821/1560-9588-2016-19-5-286-290Galli S.J. The mast cell-IgE paradox: from homeostasis to anaphylaxis. Am J Pathol. 2016; 186 (2): 212–224. https://doi.org/10.1016/j.ajpath.2015.07.025Galli S.J. The mast cell-IgE paradox: from homeostasis to anaphylaxis. Am J Pathol. 2016; 186 (2): 212–224. https://doi.org/10.1016/j.ajpath.2015.07.025Howell M.D., Kim B.E., Gao P. Cytokine modulation of atopic dermatitis filaggrin skin expression. J Allergy Clin Immunol. 2009; 124 (3): R7-R12. https://doi.org/10.1016/j.jaci.2009.07.012Howell M.D., Kim B.E., Gao P. Cytokine modulation of atopic dermatitis filaggrin skin expression. J Allergy Clin Immunol. 2009; 124 (3): R7-R12. https://doi.org/10.1016/j.jaci.2009.07.012Сапунцова С.Г., Лебедько О.А., Обухова Г.Г. Влияние гептапептида Семакс на содержание фактора некроза опухолей-альфа и биогенез свободных радикалов при атопическом дерматите. Дальневосточный медицинский журнал. 2015. (2): 61–64.Sapuntsova S.G., Lebed’ko O.A., Obuchova G.G. Effect of heptapeptide Semax on the level of tumor necrosis factor-alpha and biogenesis of free radicals in patients with atopic dermatitis. Far Eastern Medical Journal .2015. (2): 61–64. (In Russ.).Zhestkov A.V., Pobezhimova O.O. The main aspects of the immunopathogenesis of atopic dermatitis in children. Allergology and Immunology in Pediatrics. 2021; 3 (66): 27–34. (In Russ.). https://doi.org/10.53529/2500-1175-2021-3-27-34Zhestkov A.V., Pobezhimova O.O. The main aspects of the immunopathogenesis of atopic dermatitis in children. Allergology and Immunology in Pediatrics. 2021; 3 (66): 27–34. (In Russ.). https://doi.org/10.53529/2500-1175-2021-3-27-34Huang I.H., Chung W.H., Wu P.C., Chen C.B. JAK-STAT signaling pathway in the pathogenesis of atopic dermatitis: An updated review. Front Immunol. 2022; 13: 1068260. https://doi.org/10.3389/fimmu.2022.1068260Huang I.H., Chung W.H., Wu P.C., Chen C.B. JAK-STAT signaling pathway in the pathogenesis of atopic dermatitis: An updated review. Front Immunol. 2022; 13: 1068260. https://doi.org/10.3389/fimmu.2022.1068260Eyerich S., Eyerich K., Cavani A., Schmidt-Weber C. IL-17 and IL-22: siblings, not twins. Trends Immunol. 2010; 31 (9): 354–61. https://doi.org/10.1016/j.it.2010.06.004Eyerich S., Eyerich K., Cavani A., Schmidt-Weber C. IL-17 and IL-22: siblings, not twins. Trends Immunol. 2010; 31 (9): 354–61. https://doi.org/10.1016/j.it.2010.06.004Caruso R., Botti E., Sarra M. Involvement of interleukin-21 in the epidermal hyperplasia of psoriasis. Nat Med. 2009; 15 (9): 1013–5. https://doi.org/10.1038/nm.1995Caruso R., Botti E., Sarra M. Involvement of interleukin-21 in the epidermal hyperplasia of psoriasis. Nat Med. 2009; 15 (9): 1013–5. https://doi.org/10.1038/nm.1995Zheng Y., Danilenko D.M., Valdez P. Interleukin-22, a T(H)17 cytokine, mediates IL-23-induced dermal inflammation and acanthosis. Nature. 2007; 445 (7128): 648–51. https://doi.org/10.1038/nature05505Zheng Y., Danilenko D.M., Valdez P. Interleukin-22, a T(H)17 cytokine, mediates IL-23-induced dermal inflammation and acanthosis. Nature. 2007; 445 (7128): 648–51. https://doi.org/10.1038/nature05505Wolk K., Haugen H.S., Xu W. IL-22 and IL-20 are key mediators of the epidermal alterations in psoriasis while IL-17 and IFN-gamma are not. J Mol Med. 2009; 87 (5): 523–36. https://doi.org/10.1007/s00109-009-0457-0Wolk K., Haugen H.S., Xu W. IL-22 and IL-20 are key mediators of the epidermal alterations in psoriasis while IL-17 and IFN-gamma are not. J Mol Med. 2009; 87 (5): 523–36. https://doi.org/10.1007/s00109-009-0457-0Donetti E., Cornaghi L., Arnaboldi F. Epidermal barrier reaction to an in vitro psoriatic microenvironment. Exp Cell Res. 2017; 360 (2): 180–188. https://doi.org/10.1016/j.yexcr.2017.09.004Donetti E., Cornaghi L., Arnaboldi F. Epidermal barrier reaction to an in vitro psoriatic microenvironment. Exp Cell Res. 2017; 360 (2): 180–188. https://doi.org/10.1016/j.yexcr.2017.09.004Терещенко И.В., Каюшев П.Е. Фактор некроза опухоли α и его роль в патологии. РМЖ. Медицинское обозрение. 2022; 6 (9): 523–527. https://doi.org/10.32364/2587-6821-2022-6-9-523-527Tereshchenko I.V., Kayushev P. E. Tumor necrosis factor α and its role in pathologies. Russian Medical Inquiry. 2022; 6(9): 523–527 (In Russ.). https://doi.org/10.32364/2587-6821-2022-6-9-523-527Kumagai N., Fukuda K., Fujitsu Y., Nishida T. Expression of functional ICAM-1 on cultured human keratocytes induced by tumor necrosis factor-alpha. Jpn J Ophthalmol. 2003; 47 (2): 134–41. https://doi.org/10.1016/s0021–5155(02)00686-xKumagai N., Fukuda K., Fujitsu Y., Nishida T. Expression of functional ICAM-1 on cultured human keratocytes induced by tumor necrosis factor-alpha. Jpn J Ophthalmol. 2003; 47 (2): 134–41. https://doi.org/10.1016/s0021–5155(02)00686-xRendon A., Schäkel K. Psoriasis Pathogenesis and Treatment. Int J Mol Sci. 2019; 20(6):1475. https://doi.org/10.3390/ijms20061475Rendon A., Schäkel K. Psoriasis Pathogenesis and Treatment. Int J Mol Sci. 2019; 20(6):1475. https://doi.org/10.3390/ijms20061475Sabat R., Alavi A., Wolk K. Hidradenitis suppurativa. Lancet. 2025; 405 (10476): 420–438. https://doi.org/10.1016/S0140–6736 (24) 02475-9Sabat R., Alavi A., Wolk K. Hidradenitis suppurativa. Lancet. 2025; 405 (10476): 420–438. https://doi.org/10.1016/S0140–6736 (24) 02475-9Maverakis E., Marzano A.V., Le S.T. Pyoderma gangrenosum. Nat Rev Dis Primers. 2020; 6 (1): 81. https://doi.org/10.1038/s41572–020–0213-xMaverakis E., Marzano A.V., Le S.T. Pyoderma gangrenosum. Nat Rev Dis Primers. 2020; 6 (1): 81. https://doi.org/10.1038/s41572–020–0213-xGunes P., Goktay F., Mansur A.T., Koker F., Erfan G. Collagen-elastic tissue changes and vascular involvement in granuloma annulare: a review of 35 cases. J Cutan Pathol. 2009; 36 (8): 838–44. https://doi.org/10.1111/j.1600–0560.2008.01169.xGunes P., Goktay F., Mansur A.T., Koker F., Erfan G. Collagen-elastic tissue changes and vascular involvement in granuloma annulare: a review of 35 cases. J Cutan Pathol. 2009; 36 (8): 838–44. https://doi.org/10.1111/j.1600–0560.2008.01169.xVerwoerd A., Hijdra D., Vorselaars A.D. Infliximab therapy balances regulatory T cells, tumour necrosis factor receptor 2 (TNFR2) expression and soluble TNFR2 in sarcoidosis. Clin Exp Immunol. 2016; 185 (2): 263–70. https://doi.org/10.1111/cei.12808Verwoerd A., Hijdra D., Vorselaars A.D. Infliximab therapy balances regulatory T cells, tumour necrosis factor receptor 2 (TNFR2) expression and soluble TNFR2 in sarcoidosis. Clin Exp Immunol. 2016; 185 (2): 263–70. https://doi.org/10.1111/cei.12808Cantaert T., Baeten D., Tak P.P. Type I IFN and TNFA cross-regulation in immune-mediated inflam matory disease: Basic concepts and clinical relevance. Arthritis Res Ther. 2010; 12 (5). https://doi.org/10.1186/ar3150Cantaert T., Baeten D., Tak P.P. Type I IFN and TNFA cross-regulation in immune-mediated inflam matory disease: Basic concepts and clinical relevance. Arthritis Res Ther. 2010; 12 (5). https://doi.org/10.1186/ar3150Palucka A.K., Blanck J.P., Bennett L. Cross-regulation of TNF and IFN-a in autoimmune diseases. Proc Natl Acad Sci U S A. 2005; 102 (9): 3372–7. https://doi.org/10.1073/pnas.0408506102Palucka A.K., Blanck J.P., Bennett L. Cross-regulation of TNF and IFN-a in autoimmune diseases. Proc Natl Acad Sci U S A. 2005; 102 (9): 3372–7. https://doi.org/10.1073/pnas.0408506102Круглова Л.С., Щукина О.Б. Парадоксальная псориазиформная воспалительная реакция на фоне применения блокаторов фактора некроза опухоли-альфа у пациентов с болезнью Крона. Альманах клинической медицины. 2018; 46 (5): 522–530. https://doi.org/10.18786/20720505-2018-46-5-522-530Kruglova LS, Shchukina OB. Paradoxical psoriasiform inflammatory reaction during the use of tumor necrosis factor-alpha inhibitors in patients with Crohn’s disease. Almanac of Clinical Medicine. 2018; 46 (5): 522–30. (In Russ.). https://doi.org/10.18786/2072-0505-2018-465-522-530DeGannes G.C., Ghoreishi M., Pope J. Psoriasis and pustular dermatitis triggered by TNF-{alpha} inhibitors in patients with rheumatologic conditions. Arch Dermatol. 2007; 143 (2): 223–31. https://doi.org/10.1001/archdermDeGannes G.C., Ghoreishi M., Pope J. Psoriasis and pustular dermatitis triggered by TNF-{alpha} inhibitors in patients with rheumatologic conditions. Arch Dermatol. 2007; 143 (2): 223–31. https://doi.org/10.1001/archdermConrad C., Di Domizio J., Mylonas A. TNF blockade induces a dysregulated type I interferon response without autoimmunity in paradoxical psoriasis. Nat Commun. 2018; 9 (1): 25. https://doi.org/10.1038/s41467-017-02466-4Conrad C., Di Domizio J., Mylonas A. TNF blockade induces a dysregulated type I interferon response without autoimmunity in paradoxical psoriasis. Nat Commun. 2018; 9 (1): 25. https://doi.org/10.1038/s41467-017-02466-4Fania L., Morelli M., Scarponi C. Paradoxical psoriasis induced by TNF-α blockade shows immunological features typical of the early phase of psoriasis development. J Pathol Clin Res. 2020; 6 (1): 55–68. https://doi.org/10.1002/cjp2.147Fania L., Morelli M., Scarponi C. Paradoxical psoriasis induced by TNF-α blockade shows immunological features typical of the early phase of psoriasis development. J Pathol Clin Res. 2020; 6 (1): 55–68. https://doi.org/10.1002/cjp2.147Collamer A.N., Guerrero K.T., Henning J.S., Battafarano D.F. Psoriatic skin lesions induced by tumor necrosis factor antagonist therapy: a literature review and potential mechanisms of action. Arthritis Rheum. 2008; 59 (7): 996-1001. https://doi.org/10.1002/art.23835.PMID: 18576309.Collamer A.N., Guerrero K.T., Henning J.S., Battafarano D.F. Psoriatic skin lesions induced by tumor necrosis factor antagonist therapy: a literature review and potential mechanisms of action. Arthritis Rheum. 2008; 59 (7): 996-1001. https://doi.org/10.1002/art.23835.PMID: 18576309.Ursini F., Naty S., Bruno C. CD4+ T-cells lymphocytosis and reduction of neutrophils during treatment with adalimumab: Challenge and dechallenge study. Clin Immunol. 2010; 135 (3): 499–500. https://doi.org/10.1016/j.clim.2010.02.004Ursini F., Naty S., Bruno C. CD4+ T-cells lymphocytosis and reduction of neutrophils during treatment with adalimumab: Challenge and dechallenge study. Clin Immunol. 2010; 135 (3): 499–500. https://doi.org/10.1016/j.clim.2010.02.004Frew J. W., Vekic D. A., Woods J. A., Cains G. D. Drug-associated hidradenitis suppurativa: A systematic review of case reports. J Am Acad Dermatol. 2018; 78 (1): 217–219.e2. https://doi.org/10.1016/j.jaad.2017.08.046Frew J. W., Vekic D. A., Woods J. A., Cains G. D. Drug-associated hidradenitis suppurativa: A systematic review of case reports. J Am Acad Dermatol. 2018; 78 (1): 217–219.e2. https://doi.org/10.1016/j.jaad.2017.08.046Ghoreschi K., Thomas P., Breit S. Interleukin-4 therapy of psoriasis induces Th2 responses and improves human autoimmune disease. Nat Med. 2003; 9 (1): 40–6. https://doi.org/10.1038/nm804Ghoreschi K., Thomas P., Breit S. Interleukin-4 therapy of psoriasis induces Th2 responses and improves human autoimmune disease. Nat Med. 2003; 9 (1): 40–6. https://doi.org/10.1038/nm804Zaba L.C., Cardinale I., Gilleaudeau P. Amelioration of epidermal hyperplasia by TNF inhibition is associated with reduced Th17 responses. J Exp Med. 2007; 204 (13): 3183–94. https://doi.org/10.1084/jem.20071094Zaba L.C., Cardinale I., Gilleaudeau P. Amelioration of epidermal hyperplasia by TNF inhibition is associated with reduced Th17 responses. J Exp Med. 2007; 204 (13): 3183–94. https://doi.org/10.1084/jem.20071094Quaglino P., Bergallo M., Ponti R. Th1, Th2, Th17 and regulatory T cell pattern in psoriatic patients: modulation of cytokines and gene targets induced by etanercept treatment and correlation with clinical response. Dermatology. 2011; 223 (1): 57–67. https://doi.org/10.1159/000330330Quaglino P., Bergallo M., Ponti R. Th1, Th2, Th17 and regulatory T cell pattern in psoriatic patients: modulation of cytokines and gene targets induced by etanercept treatment and correlation with clinical response. Dermatology. 2011; 223 (1): 57–67. https://doi.org/10.1159/000330330Malisiewicz B., Murer C., Schmid J.P. Eosinophilia during psoriasis treatment with TNF antagonists. Dermatology. 2011; 223 (4): 311–5. https://doi.org/10.1159/000334805Malisiewicz B., Murer C., Schmid J.P. Eosinophilia during psoriasis treatment with TNF antagonists. Dermatology. 2011; 223 (4): 311–5. https://doi.org/10.1159/000334805Stoffel E., Maier H., Riedl E. Analysis of anti-tumour necrosis factor-induced skin lesions reveals strong T helper 1 activation with some distinct immunological characteristics. Br.J. Dermatol. 2018; 178 (5): 1151–1162. https://doi.org/10.1111/bjd.16126Stoffel E., Maier H., Riedl E. Analysis of anti-tumour necrosis factor-induced skin lesions reveals strong T helper 1 activation with some distinct immunological characteristics. Br.J. Dermatol. 2018; 178 (5): 1151–1162. https://doi.org/10.1111/bjd.16126Ariyasu T., Tanaka T., Fujioka N. Effects of interferon-alpha subtypes on the TH1/TH2 balance in peripheral blood mononuclear cells from patients with hepatitis virus infection-associated liver disorders. In Vitro Cell Dev Biol Anim. 2005; 41 (1): 50–56. https://doi.org/10.1290/0501008.1Ariyasu T., Tanaka T., Fujioka N. Effects of interferon-alpha subtypes on the TH1/TH2 balance in peripheral blood mononuclear cells from patients with hepatitis virus infection-associated liver disorders. In Vitro Cell Dev Biol Anim. 2005; 41 (1): 50–56. https://doi.org/10.1290/0501008.1Esmailzadeh A., Yousefi P., Farhi D. Predictive Factors of Eczema-Like Eruptions among Patients without Cutaneous Psoriasis Receiving Infliximab: A Cohort Study of 92 Patients. Dermatology. 2009; 219 (3): 263–267. https://doi.org/10.1159/000235582Esmailzadeh A., Yousefi P., Farhi D. Predictive Factors of Eczema-Like Eruptions among Patients without Cutaneous Psoriasis Receiving Infliximab: A Cohort Study of 92 Patients. Dermatology. 2009; 219 (3): 263–267. https://doi.org/10.1159/000235582De Vries H.J., van Marle J., Teunissen M.B. Lichen planus is associated with human herpesvirus type 7 replication and infiltration of plasmacytoid dendritic cells. Br J Dermatol. 2006; 154(2): 361–364. https://doi.org/10.1111/j.1365–2133.2005.06999.xDe Vries H.J., van Marle J., Teunissen M.B. Lichen planus is associated with human herpesvirus type 7 replication and infiltration of plasmacytoid dendritic cells. Br J Dermatol. 2006; 154(2): 361–364. https://doi.org/10.1111/j.1365–2133.2005.06999.xSantoro A., Majorana A., Roversi L. Recruitment of dendritic cells in oral lichen planus. J Pathol. 2005; 205 (4): 426–434. https://doi.org/10.1002/path.1699.Santoro A., Majorana A., Roversi L. Recruitment of dendritic cells in oral lichen planus. J Pathol. 2005; 205 (4): 426–434. https://doi.org/10.1002/path.1699.Wenzel J, Scheler M, Proelss J, et al. Type I interferon-associated cytotoxic inflammation in lichen planus. J Cutan Pathol. 2006; 33 (10): 672–678. https://doi.org/10.1111/j.1600–0560.2006.00527.xWenzel J, Scheler M, Proelss J, et al. Type I interferon-associated cytotoxic inflammation in lichen planus. J Cutan Pathol. 2006; 33 (10): 672–678. https://doi.org/10.1111/j.1600–0560.2006.00527.xKarnik P, Tekeste Z, McCormick TS, et al. Hair follicle stem cell-specific PPARγ deletion causes scarring alopecia. J Invest Dermatol. 2009; 129 (5): 1243–1257. https://doi.org/10.1038/jid.2008.369Karnik P, Tekeste Z, McCormick TS, et al. Hair follicle stem cell-specific PPARγ deletion causes scarring alopecia. J Invest Dermatol. 2009; 129 (5): 1243–1257. https://doi.org/10.1038/jid.2008.369

The authors declare that there are no conflicts of interest present.