Dupilumab for the Treatment of Refractory Cutaneous Immune-Related Adverse Events: A Case Report

Dupilumab for the Treatment of Refractory Cutaneous Immune-Related Adverse Events: A Case Report | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Short Report Dupilumab for the Treatment of Refractory Cutaneous Immune-Related Adverse Events: A Case Report Zhenyu Luo, Jin Gong This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9460962/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Immune checkpoint inhibitors (ICIs) can induce immune-related adverse events (irAEs) affecting multiple organ systems. Cutaneous irAEs (cirAEs) are the most common among these, significantly impacting patients' quality of life and adherence to antitumor therapy. Conventional glucocorticoid treatment proves insufficient for some patients, and evidence regarding the use of biologics for cirAEs remains limited. We report a case of cutaneous adverse reactions associated with ICIs, in which the patient experienced recurrent symptoms following treatment with glucocorticoids, intravenous immunoglobulin, and immunosuppressants. After three doses of dupilumab, the patient's condition stabilized with no new rash development. Conclusion: Dupilumab may serve as an alternative therapeutic option for cirAEs refractory to glucocorticoids Immune checkpoint inhibitors Tislelizumab Cutaneous immune-related adverse events Dupilumab Refractory skin disease Elderly multiple malignancies Figures Figure 1 Introduction Immune checkpoint inhibitors (ICIs) have become established therapeutic strategies for various malignancies by activating the immune system against tumor cells. These agents include monoclonal antibodies targeting programmed cell death protein-1 (PD-1), programmed cell death ligand-1 (PD-L1), and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) 1 . Cutaneous immune-related adverse events (cirAEs) represent the most common toxicities associated with ICI treatment 2 . These reactions exhibit a broad spectrum of clinical manifestations, ranging from maculopapular rash, pruritus, psoriasis-like eruptions, and lichenoid dermatitis to severe cutaneous adverse reactions (SCARs) and bullous pemphigoid-like lesions. In severe instances, life-threatening conditions such as Stevens-Johnson syndrome may occur 3 . Additionally, rare yet potentially fatal variants have been reported, including neutrophilic drug eruptions such as cutaneous small-vessel vasculitis, pyoderma gangrenosum, and Sweet syndrome 4 .The pathogenesis of this condition is currently understood to involve dense immune cell infiltration, excessive immune activation, and genetic predisposition 5 , and glucocorticoids remain the first-line therapeutic option. However, a subset of patients with complex clinical backgrounds (e.g., multiple malignancies, elderly age) exhibit refractory cirAEs with recurrent symptoms after standard glucocorticoid-based therapy, and prolonged glucocorticoid use in oncologic populations may increase the risk of tumor recurrence 6 . Dupilumab, a fully human IgG4 monoclonal antibody targeting the interleukin-4 receptor alpha subunit (IL-4Rα), inhibits the IL-4/IL-13 axis and downregulates Th2-type inflammatory responses 7 , and has been reported to be effective in ICI-induced bullous pemphigoid 8 . Here, we report a case of tislelizumab-induced refractory cirAEs in a 72-year-old patient with three concurrent malignancies, who achieved sustained disease control after dupilumab treatment, expanding the clinical application of dupilumab in refractory cirAEs and providing a reference for clinical management of such special populations. Case Report A 72-year-old male was diagnosed with prostate, bladder, and lung cancer in July 2023. He underwent surgical resection for bladder cancer on November 6, 2023, followed by chemotherapy with gemcitabine plus nedaplatin (4 cycles, completed in January 2025). In February 2025, the patient initiated anti-PD-1 monoclonal antibody therapy with tislelizumab (200 mg intravenously every 3 weeks). After the third cycle of tislelizumab, the patient developed extensively distributed papules, papulopustules, and nodules on the scalp, bilateral upper limbs, back, and lower legs, accompanied by severe pruritus and exudation upon scratching (Fig. 1 a). Initial evaluation at another hospital led to a misdiagnosis of solar dermatitis, with treatment with loratadine tablets (10 mg orally once daily) and neomycin ointment (topically twice daily) yielding no clinical improvement. The patient was subsequently referred to our department, and a skin biopsy of a representative lesion on the right upper limb was performed. Histopathological examination (hematoxylin-eosin stain, original magnification ×40) revealed stratified squamous epithelium with basket-weave orthokeratosis, preserved epidermal thickness, focal vacuolar degeneration of basal cells, and mild lymphocytic infiltration and erythrocyte extravasation around superficial dermal vessels (Fig. 1 b). Baseline laboratory examinations were unremarkable: routine blood test, liver and kidney function, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) all within normal ranges. Based on the clinical presentation, histopathological findings, and ICI treatment history, a diagnosis of cirAEs secondary to tislelizumab therapy was established. The patient received sequential conventional anti-inflammatory and immunosuppressive therapy: compound glycyrrhizin (160 mg intravenously once daily for 10 days), methylprednisolone sodium succinate (60 mg, once daily for 3 days; due to suboptimal efficacy, dose was increased to 80 mg, once daily for 9 days; then gradually reduced to 60 mg, once daily for 6 days, followed by further gradual dose reduction.), intravenous immunoglobulin (12.5 g intravenously once daily for 3 days), and thalidomide 25 mg, twice daily, for 14 days). Initial mild improvement in rash and pruritus symptoms was observed, but complete remission was difficult to achieve. (Fig. 1 c). After obtaining written informed consent from the patient, dupilumab therapy was initiated: a loading dose of 600 mg subcutaneously, followed by 300 mg subcutaneously at weeks 2 and 5. At week 2 of dupilumab treatment, the rash had flattened with no new lesion development, and pruritus was markedly alleviated (Fig. 1 d). At week 5, cutaneous lesions showed further regression with complete resolution of exudation and pruritus (Fig. 1 e). A telephone follow-up at week 7 (2 weeks after the third dupilumab dose) confirmed near-complete resolution of all skin lesions, no pruritus, and no evidence of recurrence. Repeat laboratory examinations (routine blood test, liver/kidney function, CRP, ESR) remained within normal ranges, and no adverse events related to dupilumab were reported. The patient’s antitumor therapy was temporarily suspended during cirAE management, and the timing of ICI resumption was planned for individualized evaluation based on tumor status and long-term skin condition follow-up. Discussion ICIs are associated with a spectrum of irAEs affecting multiple organ systems, including dermatitis, hepatitis, and colitis 9 . Among these, cirAEs represent the most prevalent toxicity, with reported incidence rates ranging from 30% to 60% 5,6 . Glucocorticoids remain the first-line therapy, but a subset of patients, especially those with complex underlying conditions, exhibit refractory disease with recurrent symptoms after standard treatment 3 . Long-term use of glucocorticoids in cancer patients also carries risks of tumor recurrence and infection, highlighting the need for alternative biologic therapies 10 . Additionally, the patient was misdiagnosed as solar dermatitis initially, which reminds clinicians to improve the differential diagnosis awareness of cirAEs in patients receiving ICI therapy, especially those with multiple malignancies. A timely skin biopsy is critical for the definitive diagnosis of cirAEs, as histopathological features (e.g., basal cell vacuolar degeneration, dermal lymphocytic infiltration) can distinguish cirAEs from other cutaneous diseases such as solar dermatitis and allergic dermatitis 5 . Dupilumab, a human IgG4 monoclonal antibody targeting IL-4Rα, exerts its effect by inhibiting the IL-4/IL-13 axis and downregulating Th2-type inflammatory responses 7 , 11 . A scholar have reported a case of a melanoma patient who developed bullous pemphigoid following ICI therapy and was successfully treated with dupilumab 8 . Following resolution of bullous pemphigoid, the patient was able to resume ICI treatment. In a meta-analysis comprising 25 studies and 136 patients diagnosed with cutaneous immune-related adverse events (cirAEs), including clinical presentations such as bullous pemphigoid-like lesions, lichenoid eruptions, and maculopapular rash, dupilumab demonstrated marked efficacy. Notably, even among patients presenting with two distinct types of cirAEs, partial or complete response was achieved. Furthermore, the incidence of adverse events and tumor recurrence was low 12 . Our study further expands its application to non-bullous refractory cirAEs in elderly patients with multiple malignancies. Consistent with previous studies, our patient achieved rapid symptom control with dupilumab, with no adverse events or tumor recurrence observed during short-term follow-up, indicating the safety of dupilumab in this special population. The 600 mg loading dose plus 300 mg maintenance dose at weeks 2 and 5 showed a rapid onset of action, which may be related to the rapid inhibition of the overactivated IL-4/IL-13 inflammatory axis in cirAEs 5 , 9 , 13 . The clinical implications of this case are clear: for elderly patients with multiple malignancies who develop refractory cirAEs unresponsive to glucocorticoids, intravenous immunoglobulin, and immunosuppressants, dupilumab can be initiated early, and the 600 mg loading dose plus 300 mg maintenance dose at weeks 2 and 5 is a feasible regimen with rapid onset of action. Clinicians should monitor the patient's skin symptoms and immune status closely during treatment, and the timing of ICI resumption after cirAE remission requires individualized evaluation based on tumor status and skin condition. For patients with ICI therapy-induced skin lesions, early differential diagnosis and targeted treatment are critical to improve patient quality of life and avoid unnecessary discontinuation of antitumor therapy. Declarations Ethics Statement This case report describes the clinical course of a single patient. In accordance with local guidelines, retrospective analysis of patient data did not require ethical approval. Written informed consent for publication of this case report and accompanying images was obtained from the patient. The patient was fully informed of the content and purpose of the report and agreed to the disclosure of clinical data without revealing personal identifying information. Conflict of Interest The authors declare no conflicts of interest. Funding The authors received no external funding for this research. Author Contributions Jin Gong: data curation, formal analysis, investigation. Zhenyu Luo: writing original draft, writing review & editing. All authors have read and approved the final version of the manuscript. Data Availability Statement Data supporting the findings of this study are not publicly available to protect patient privacy but are available from the corresponding author upon reasonable request. References Arafat Hossain M (2024) A comprehensive review of immune checkpoint inhibitors for cancer treatment. International immunopharmacology Dec 25(Pt 2):113365. 10.1016/j.intimp.2024.113365 Jurlander RS, Guldbrandt LM, Holmstroem RB et al (2024) Immune-related adverse events in a nationwide cohort of real-world melanoma patients treated with adjuvant anti-PD1 - Seasonal variation and association with outcome. Eur J Cancer Nov 212:115053. 10.1016/j.ejca.2024.115053 [Chinese expert consensus on diagnosis (2024) and treatment of immune checkpoint inhibitor-related skin adverse reactions (2024 edition)]. Zhonghua yi xue za zhi . May 28(20):1790–1803. 10.3760/cma.j.cn112137-20240112-00091 Haanen J, Obeid M, Spain L et al (2022) Management of toxicities from immunotherapy: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Annals oncology: official J Eur Soc Med Oncology Dec 33(12):1217–1238. 10.1016/j.annonc.2022.10.001 Fattore D, Lauletta G, Pages C, Theret V, Sibaud V (2025) Update on dermatological toxicities of immune checkpoint inhibitors. Presse Med Nov 22(2):104330. 10.1016/j.lpm.2025.104330 Dougan M, Luoma AM, Dougan SK, Wucherpfennig KW (2021) Understanding and treating the inflammatory adverse events of cancer immunotherapy. Cell Mar 18(6):1575–1588. 10.1016/j.cell.2021.02.011 Harb H, Chatila TA (Jan 2020) Mechanisms of Dupilumab. Clinical and experimental allergy: journal of the British Society for Allergy and Clinical Immunology . 50(1):5–14. 10.1111/cea.13491 Grüninger J, Lehr S, Meiss F, Rafei D, Schauer F (2025) Case Report: Dupilumab therapy for immune checkpoint inhibitor-induced bullous pemphigoid enables dual immunotherapy initiation in progressive malignant melanoma. Front Oncol 15:1613552. 10.3389/fonc.2025.1613552 Weinmann SC, Pisetsky DS (2019) Mechanisms of immune-related adverse events during the treatment of cancer with immune checkpoint inhibitors. Rheumatology (Oxford) . Dec 1. ;58(Suppl 7):vii59-vii67. 10.1093/rheumatology/kez308 Ramos-Casals M, Brahmer JR, Callahan MK et al (2020) Immune-related adverse events of checkpoint inhibitors. Nature reviews Disease primers May 7(1):38. 10.1038/s41572-020-0160-6 Del Rosso JQ, MONOCLONAL ANTIBODY THERAPIES for Atopic Dermatitis (2019) Where Are We Now in the Spectrum of Disease Management? The Journal of clinical and aesthetic dermatology . Feb 12(2):39–41 Koumprentziotis IA, Niforou A, Tsimpidakis A, Nikolaou C, Stratigos A, Nikolaou V (2025) Dupilumab for the Treatment of Cutaneous Immune-Related Adverse Events: A Systematic Review. International J dermatology Oct 64(10):1825–1832. 10.1111/ijd.17850 Powers CM, Kim M, Chang A et al (2025) Tape Strip Profiling of Checkpoint Inhibitor-Associated Dermatitis Highlights Pan-T-Cell Activation: A Pilot Study. JID Innov Jul 5(4):100375. 10.1016/j.xjidi.2025.100375 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9460962","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Short Report","associatedPublications":[],"authors":[{"id":626193452,"identity":"bda78350-540e-41eb-861b-6c73a715bc90","order_by":0,"name":"Zhenyu Luo","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA3klEQVRIie3QsQrCMBCA4UggLmddr1iij6AUxMFH8CEShE4VHDuIFCrtoL6Lo6Nd4hKdHfUN6qaLWHFU2ro55J/zcXchxGT6w1g92t8zQGCUpmcRzMqJBUq00Blwqx6Pu2etygnHUQdhGLgcdN++LGiFxRBIF32UMXpeIENGmslSFJPWeiem+kXG6iS3DkF92BQT5yh29uo95SQ1y2dOSgj6vbDxeBG/P5UxrURcAoAuy88n1QgojyIgZ/kno9AKSm9pJ5GqZTCHdkTT6y2Y8WayLiYfwW/PTSaTyfS1J6wVQ7Hel27EAAAAAElFTkSuQmCC","orcid":"","institution":"The First Affiliated Hospital of Yangtze University","correspondingAuthor":true,"prefix":"","firstName":"Zhenyu","middleName":"","lastName":"Luo","suffix":""},{"id":626193455,"identity":"46c5909b-8aa9-4e81-9d96-328f8ff6cef2","order_by":1,"name":"Jin Gong","email":"","orcid":"","institution":"The First Affiliated Hospital of Yangtze University","correspondingAuthor":false,"prefix":"","firstName":"Jin","middleName":"","lastName":"Gong","suffix":""}],"badges":[],"createdAt":"2026-04-19 09:38:44","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9460962/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9460962/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":108102110,"identity":"cb9884d1-6f16-45c4-aae7-9d8aaf7d5aee","added_by":"auto","created_at":"2026-04-29 11:03:43","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":131668,"visible":true,"origin":"","legend":"\u003cp\u003e(a) Extensive papules, papulopustules, and nodules on the patient’s scalp, bilateral upper limbs, and back on admission, with visible exudation from scratched lesions; (b) Histopathological findings of neck lesion (hematoxylin-eosin stain, original magnification ×40) showing squamous epithelium with rete ridge orthokeratosis and an epidermis of approximately normal thickness. Focal vacolar degeneration of basal cells is observed, along with mild perivascular lymphocytic infiltration and extravasated erythrocytes in the superficial dermis; (c) Rash after conventional treatment; (d)Two weeks after initiating dupilumab therapy, the patient's rash showed significant improvement, with lesions flattening and no new eruptions appearing; (e) After 5 weeks of dupilumab treatment initiation, the patient's rash almost completely resolved, leaving only mild hyperpigmentation.\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-9460962/v1/00b729e232811bfa12415327.jpg"},{"id":108181848,"identity":"ad55a308-8e09-429e-ae2f-5af12deaf195","added_by":"auto","created_at":"2026-04-30 08:58:58","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":259689,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9460962/v1/7150ba0e-735d-42db-9dd2-30bed1808aff.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Dupilumab for the Treatment of Refractory Cutaneous Immune-Related Adverse Events: A Case Report","fulltext":[{"header":"Introduction","content":"\u003cp\u003eImmune checkpoint inhibitors (ICIs) have become established therapeutic strategies for various malignancies by activating the immune system against tumor cells. These agents include monoclonal antibodies targeting programmed cell death protein-1 (PD-1), programmed cell death ligand-1 (PD-L1), and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4)\u003csup\u003e1\u003c/sup\u003e. Cutaneous immune-related adverse events (cirAEs) represent the most common toxicities associated with ICI treatment\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. These reactions exhibit a broad spectrum of clinical manifestations, ranging from maculopapular rash, pruritus, psoriasis-like eruptions, and lichenoid dermatitis to severe cutaneous adverse reactions (SCARs) and bullous pemphigoid-like lesions. In severe instances, life-threatening conditions such as Stevens-Johnson syndrome may occur\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. Additionally, rare yet potentially fatal variants have been reported, including neutrophilic drug eruptions such as cutaneous small-vessel vasculitis, pyoderma gangrenosum, and Sweet syndrome\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e.The pathogenesis of this condition is currently understood to involve dense immune cell infiltration, excessive immune activation, and genetic predisposition\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e, and glucocorticoids remain the first-line therapeutic option.\u003c/p\u003e \u003cp\u003eHowever, a subset of patients with complex clinical backgrounds (e.g., multiple malignancies, elderly age) exhibit refractory cirAEs with recurrent symptoms after standard glucocorticoid-based therapy, and prolonged glucocorticoid use in oncologic populations may increase the risk of tumor recurrence\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e. Dupilumab, a fully human IgG4 monoclonal antibody targeting the interleukin-4 receptor alpha subunit (IL-4Rα), inhibits the IL-4/IL-13 axis and downregulates Th2-type inflammatory responses\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e, and has been reported to be effective in ICI-induced bullous pemphigoid\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e. Here, we report a case of tislelizumab-induced refractory cirAEs in a 72-year-old patient with three concurrent malignancies, who achieved sustained disease control after dupilumab treatment, expanding the clinical application of dupilumab in refractory cirAEs and providing a reference for clinical management of such special populations.\u003c/p\u003e"},{"header":"Case Report","content":"\u003cp\u003eA 72-year-old male was diagnosed with prostate, bladder, and lung cancer in July 2023. He underwent surgical resection for bladder cancer on November 6, 2023, followed by chemotherapy with gemcitabine plus nedaplatin (4 cycles, completed in January 2025). In February 2025, the patient initiated anti-PD-1 monoclonal antibody therapy with tislelizumab (200 mg intravenously every 3 weeks). After the third cycle of tislelizumab, the patient developed extensively distributed papules, papulopustules, and nodules on the scalp, bilateral upper limbs, back, and lower legs, accompanied by severe pruritus and exudation upon scratching (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003ea).\u003c/p\u003e\u003cp\u003eInitial evaluation at another hospital led to a misdiagnosis of solar dermatitis, with treatment with loratadine tablets (10 mg orally once daily) and neomycin ointment (topically twice daily) yielding no clinical improvement. The patient was subsequently referred to our department, and a skin biopsy of a representative lesion on the right upper limb was performed. Histopathological examination (hematoxylin-eosin stain, original magnification ×40) revealed stratified squamous epithelium with basket-weave orthokeratosis, preserved epidermal thickness, focal vacuolar degeneration of basal cells, and mild lymphocytic infiltration and erythrocyte extravasation around superficial dermal vessels (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003eb). Baseline laboratory examinations were unremarkable: routine blood test, liver and kidney function, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) all within normal ranges.\u003c/p\u003e\u003cp\u003eBased on the clinical presentation, histopathological findings, and ICI treatment history, a diagnosis of cirAEs secondary to tislelizumab therapy was established. The patient received sequential conventional anti-inflammatory and immunosuppressive therapy: compound glycyrrhizin (160 mg intravenously once daily for 10 days), methylprednisolone sodium succinate (60 mg, once daily for 3 days; due to suboptimal efficacy, dose was increased to 80 mg, once daily for 9 days; then gradually reduced to 60 mg, once daily for 6 days, followed by further gradual dose reduction.), intravenous immunoglobulin (12.5 g intravenously once daily for 3 days), and thalidomide 25 mg, twice daily, for 14 days). Initial mild improvement in rash and pruritus symptoms was observed, but complete remission was difficult to achieve. (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003ec).\u003c/p\u003e\u003cp\u003eAfter obtaining written informed consent from the patient, dupilumab therapy was initiated: a loading dose of 600 mg subcutaneously, followed by 300 mg subcutaneously at weeks 2 and 5. At week 2 of dupilumab treatment, the rash had flattened with no new lesion development, and pruritus was markedly alleviated (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003ed). At week 5, cutaneous lesions showed further regression with complete resolution of exudation and pruritus (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003ee). A telephone follow-up at week 7 (2 weeks after the third dupilumab dose) confirmed near-complete resolution of all skin lesions, no pruritus, and no evidence of recurrence. Repeat laboratory examinations (routine blood test, liver/kidney function, CRP, ESR) remained within normal ranges, and no adverse events related to dupilumab were reported. The patient’s antitumor therapy was temporarily suspended during cirAE management, and the timing of ICI resumption was planned for individualized evaluation based on tumor status and long-term skin condition follow-up.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eICIs are associated with a spectrum of irAEs affecting multiple organ systems, including dermatitis, hepatitis, and colitis\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. Among these, cirAEs represent the most prevalent toxicity, with reported incidence rates ranging from 30% to 60%\u003csup\u003e5,6\u003c/sup\u003e. Glucocorticoids remain the first-line therapy, but a subset of patients, especially those with complex underlying conditions, exhibit refractory disease with recurrent symptoms after standard treatment\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. Long-term use of glucocorticoids in cancer patients also carries risks of tumor recurrence and infection, highlighting the need for alternative biologic therapies\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e. Additionally, the patient was misdiagnosed as solar dermatitis initially, which reminds clinicians to improve the differential diagnosis awareness of cirAEs in patients receiving ICI therapy, especially those with multiple malignancies. A timely skin biopsy is critical for the definitive diagnosis of cirAEs, as histopathological features (e.g., basal cell vacuolar degeneration, dermal lymphocytic infiltration) can distinguish cirAEs from other cutaneous diseases such as solar dermatitis and allergic dermatitis\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eDupilumab, a human IgG4 monoclonal antibody targeting IL-4Rα, exerts its effect by inhibiting the IL-4/IL-13 axis and downregulating Th2-type inflammatory responses\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e,\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e. A scholar have reported a case of a melanoma patient who developed bullous pemphigoid following ICI therapy and was successfully treated with dupilumab\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e. Following resolution of bullous pemphigoid, the patient was able to resume ICI treatment. In a meta-analysis comprising 25 studies and 136 patients diagnosed with cutaneous immune-related adverse events (cirAEs), including clinical presentations such as bullous pemphigoid-like lesions, lichenoid eruptions, and maculopapular rash, dupilumab demonstrated marked efficacy. Notably, even among patients presenting with two distinct types of cirAEs, partial or complete response was achieved. Furthermore, the incidence of adverse events and tumor recurrence was low\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e. Our study further expands its application to non-bullous refractory cirAEs in elderly patients with multiple malignancies. Consistent with previous studies, our patient achieved rapid symptom control with dupilumab, with no adverse events or tumor recurrence observed during short-term follow-up, indicating the safety of dupilumab in this special population. The 600 mg loading dose plus 300 mg maintenance dose at weeks 2 and 5 showed a rapid onset of action, which may be related to the rapid inhibition of the overactivated IL-4/IL-13 inflammatory axis in cirAEs\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e,\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e,\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe clinical implications of this case are clear: for elderly patients with multiple malignancies who develop refractory cirAEs unresponsive to glucocorticoids, intravenous immunoglobulin, and immunosuppressants, dupilumab can be initiated early, and the 600 mg loading dose plus 300 mg maintenance dose at weeks 2 and 5 is a feasible regimen with rapid onset of action. Clinicians should monitor the patient's skin symptoms and immune status closely during treatment, and the timing of ICI resumption after cirAE remission requires individualized evaluation based on tumor status and skin condition. For patients with ICI therapy-induced skin lesions, early differential diagnosis and targeted treatment are critical to improve patient quality of life and avoid unnecessary discontinuation of antitumor therapy.\u003c/p\u003e "},{"header":"Declarations","content":"\u003cp\u003eEthics Statement\u003c/p\u003e\n\u003cp\u003eThis case report describes the clinical course of a single patient. In accordance with local guidelines, retrospective analysis of patient data did not require ethical approval. Written informed consent for publication of this case report and accompanying images was obtained from the patient. The patient was fully informed of the content and purpose of the report and agreed to the disclosure of clinical data without revealing personal identifying information.\u003c/p\u003e\n\u003cp\u003eConflict of Interest\u003c/p\u003e\n\u003cp\u003eThe authors declare no conflicts of interest.\u003c/p\u003e\n\u003cp\u003eFunding\u003c/p\u003e\n\u003cp\u003eThe authors received no external funding for this research.\u003c/p\u003e\n\u003cp\u003eAuthor Contributions\u003c/p\u003e\n\u003cp\u003eJin Gong: data curation, formal analysis, investigation. Zhenyu Luo: writing \u0026nbsp;original draft, writing review \u0026amp; editing. All authors have read and approved the final version of the manuscript.\u003c/p\u003e\n\u003cp\u003eData Availability Statement\u003c/p\u003e\n\u003cp\u003eData supporting the findings of this study are not publicly available to protect patient privacy but are available from the corresponding author upon reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eArafat Hossain M (2024) A comprehensive review of immune checkpoint inhibitors for cancer treatment. 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JID Innov Jul 5(4):100375. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.xjidi.2025.100375\u003c/span\u003e\u003cspan address=\"10.1016/j.xjidi.2025.100375\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Immune checkpoint inhibitors, Tislelizumab, Cutaneous immune-related adverse events, Dupilumab, Refractory skin disease, Elderly multiple malignancies","lastPublishedDoi":"10.21203/rs.3.rs-9460962/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9460962/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eImmune checkpoint inhibitors (ICIs) can induce immune-related adverse events (irAEs) affecting multiple organ systems. Cutaneous irAEs (cirAEs) are the most common among these, significantly impacting patients' quality of life and adherence to antitumor therapy. Conventional glucocorticoid treatment proves insufficient for some patients, and evidence regarding the use of biologics for cirAEs remains limited. We report a case of cutaneous adverse reactions associated with ICIs, in which the patient experienced recurrent symptoms following treatment with glucocorticoids, intravenous immunoglobulin, and immunosuppressants. After three doses of dupilumab, the patient's condition stabilized with no new rash development. Conclusion: Dupilumab may serve as an alternative therapeutic option for cirAEs refractory to glucocorticoids\u003c/p\u003e","manuscriptTitle":"Dupilumab for the Treatment of Refractory Cutaneous Immune-Related Adverse Events: A Case Report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-29 11:03:40","doi":"10.21203/rs.3.rs-9460962/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"cd97f0af-daba-4c0c-aab5-5f2045fab150","owner":[],"postedDate":"April 29th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-04-29T11:03:40+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-29 11:03:40","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9460962","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9460962","identity":"rs-9460962","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}