Tacrolimus-associated Kaposi's Sarcoma in a Patient with Refractory Generalized Myasthenia Gravis: A Case Report

Tacrolimus-associated Kaposi's Sarcoma in a Patient with Refractory Generalized Myasthenia Gravis: 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 Case Report Tacrolimus-associated Kaposi's Sarcoma in a Patient with Refractory Generalized Myasthenia Gravis: A Case Report mingjia lu, Maynur Mamat, Hongyan Li This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9008553/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 7 You are reading this latest preprint version Abstract Kaposi’s sarcoma (KS) is an endothelial cell neoplasm that is rarely observed in patients with myasthenia gravis (MG). A 71-year-old Uyghur male diagnosed with myasthenia gravis type IVb was evaluated. In 2023, the patient experienced an exacerbation of muscle weakness and dyspnea secondary to an infection. Prior to this episode, he was treated with oral pyridostigmine bromide 90 mg four times daily and prednisone acetate 30 mg once daily. Subsequently, his regimen was adjusted to include tacrolimus capsules administered at 2 mg in the morning and 1 mg in the evening. In July 2023, he experienced another myasthenic crisis and received corticosteroid pulse therapy combined with a subcutaneous injection of Telitacicept, after which intermittent edema developed in both lower limbs. Since January 2024, the patient has experienced persistent, asymmetrical lower limb edema that has interfered with ambulation. Additionally, a localized non-blanchable red pigmented area was observed on the anterior tibia of the left lower limb. Serologic tests for HIV and syphilis were negative, and dermoscopic examination revealed multiple purple-red lacunae, irregular vascular structures, crust formation, and rainbow patterns on a blue-red background;—the biopsy reveal the basal layer of the epidermis shows increased pigmentation. In the dermis, there is a nodular infiltration of numerous spindle-shaped cells, with vascular-like clefts visible among them. Some of these clefts contain red blood cells, and a small amount of hemosiderin deposition is observed. Immunohistochemistry (IHC): CD34 positive, HHV-8 positive. In combination with the clinical presentation,findings suggestive of KS. Currently, with the discontinuation of tacrolimus, a slight improvement in skin pigmentation has been observed. In conclusion, KS is a rare complication arising during immunosuppressive therapy in patients with MG, and timely detection with regular screening is essential for optimizing patient outcomes. Kaposi’s sarcoma myasthenia gravis Kaposi’s sarcoma-associated herpesvirus (KSHV) immunosuppressive therapy Figures Figure 1 Figure 2 Figure 3 Introduction Myasthenia gravis (MG) is an autoimmune disorder of the neuromuscular junction mediated by autoantibodies that impair neuromuscular transmission. The therapeutic strategies for MG include cholinesterase inhibitors, glucocorticoids, immunosuppressants, intravenous immunoglobulins (IVIG), plasma exchange (PE), and thymectomy. Kaposi’s sarcoma (KS) is a multicentric sarcoma of endothelial origin that primarily affects the skin, yet it can also involve mucosal surfaces, lymph nodes, and visceral organs. KS is currently recognized in four different clinical types: classical, endemic in Africa, epidemic associated with Acquired Immune Deficiency Syndrome, and iatrogenic. KS is etiologically linked to human herpesvirus-8 (HHV-8)[ 1 ], also known as Kaposi’s sarcoma-associated herpesvirus (KSHV). Although KS is relatively uncommon in China, the seropositivity rate for KSHV in Xinjiang is significantly higher than in other regions, which may predispose this population to an increased risk of iatrogenic KS[ 2 ]. Typically emerging in the context of immunosuppressive therapy[ 3 ], iatrogenic KS is frequently observed in patients undergoing treatment for organ transplantation[ 4 ] or autoimmune conditions. Herein, we report a rare case of KS in a patient with refractory generalized MG from Xinjiang who was receiving tacrolimus therapy. Case report A 71-year-old Uyghur male with a diagnosis of myasthenia gravis type IVb was admitted with a history of slurred speech, dyspnea persisting for over ten years, and lower limb edema lasting more than six months. His initial symptoms emerged in 2014 with slurred speech, dyspnea, and post-activity fatigue, and in January 2015 he was diagnosed with acute severe MG and myasthenic crisis, for which he received immunoglobulin therapy, non-invasive ventilation, and methylprednisolone pulse therapy, resulting in clinical improvement. Post-discharge, he was maintained on pyridostigmine bromide 90 mg four times daily and azathioprine 25 mg twice daily; however, due to persistent leukopenia, his regimen was modified to mycophenolate mofetil 1 g twice daily. The patient experienced recurrent exacerbations related to infections in 2017, 2019, and 2021, necessitating repeated immunoglobulin infusions. In 2023, following another infectious episode, his treatment was adjusted to include tacrolimus capsules (2 mg in the morning and 1 mg in the evening) alongside pyridostigmine bromide and prednisone acetate 30 mg daily. In July 2023, he suffered another myasthenic crisis, leading to intensive care admission where corticosteroid pulse therapy and a subcutaneous injection of Telitacicept were administered; therapeutic tacrolimus levels were confirmed by monitoring. Intermittent edema of the lower limbs was first noted in July 2023, and two months prior to the current admission, persistent and asymmetrical edema developed, impairing his ambulation. A localized non-blanchable red pigmented area was observed on the anterior tibia of the left lower limb (Fig. 1 ). Serologic testing for HIV and syphilis was negative, and dermoscopic evaluation revealed multiple purple-red lacunae, irregular vascular structures, crust formation, and rainbow patterns on a blue-red background, findings consistent with a diagnosis of iatrogenic KS. Owing to significant edema and high skin tension, a skin biopsy was deferred. Following the cessation of tacrolimus, the patient demonstrated a slight improvement in skin pigmentation (Fig. 2 ) and continues to be closely monitored.Histologic examination of the skin lesion on the left lower leg (Fig. 3 ) showed the basal layer of the epidermis shows increased pigmentation. In the dermis, there is a nodular infiltration of numerous spindle-shaped cells, with vascular-like clefts visible among them. Some of these clefts contain red blood cells, and a small amount of hemosiderin deposition is observed. Immunohistochemistry (IHC): CD34 positive, HHV-8 positive. In combination with the clinical presentation, it is consistent with Kaposi's sarcoma. Discussion Kaposi’s sarcoma (KS) is a multicentric sarcoma of endothelial origin that predominantly manifests in the skin but may also involve mucosal surfaces, lymph nodes, and visceral organs. Iatrogenic KS, frequently observed in the context of immunosuppressive therapy[ 3 ]—such as that administered to organ transplant recipients and patients with autoimmune conditions like myasthenia gravis (MG)—is considered to have an autoimmune component. Immunosuppressants, including glucocorticoids[ 5 ] and non-steroidal agents such as azathioprine[ 6 ], tacrolimus[ 7 ], mycophenolate mofetil, cyclosporine, methotrexate, and cyclophosphamide, play a crucial role in preventing MG relapses; notably, tacrolimus is widely used in clinical practice due to its rapid onset of action, typically within approximately one month[ 7 ].Human herpesvirus-8 (HHV-8), or Kaposi’s sarcoma-associated herpesvirus (KSHV), has been confirmed as the etiological agent of all KS variants, although its origins remain elusive. KSHV exhibits a distinct geographical distribution, with seroprevalence rates estimated to exceed 50% in the general populations of sub-Saharan Africa, approximately 20–80% in Mediterranean regions[8; 9], and less than 10% in North America, Northern Europe, and most parts of Asia[ 10 ]. Xinjiang, a northwestern Chinese autonomous region bordered by Russia, Kazakhstan, Kyrgyzstan, Tajikistan, Pakistan, Mongolia, Afghanistan, and India, is characterized by a diverse ethnic composition—including Uyghurs, Han, Kazakhs, and Hui—which, coupled with its historical significance along the ancient Silk Road, contributes to a markedly higher KSHV seroprevalence[ 11 ]. While most provinces in China report KSHV seropositivity below 8%, studies indicate that in Xinjiang, particularly among Uyghur and Kazakh populations, this rate can be as high as 19.3% to 46.6%[ 12 ]. Some research even suggests that the dominant KSHV genotypes in Xinjiang may trace back to the ancient Silk Road period[ 13 ], although further evidence is required to substantiate this hypothesis. In the present case, an elderly Uyghur male from Kashgar,Xinjiang, who had been on long-term tacrolimus therapy, developed pronounced asymmetrical lower limb edema and cutaneous lesions. A biopsy confirmed the diagnosis of KS. The underlying mechanism may involve tacrolimus-induced immunosuppression, which compromises immunosurveillance and potentially reactivates latent KSHV infection[ 14 ], thereby promoting the proliferation and differentiation of infected endothelial cells. Consistent with other reports of iatrogenic KS, most patients experience clinical improvement following a reduction or discontinuation of immunosuppressive agents; indeed, our patient demonstrated a slight amelioration of skin pigmentation after cessation of tacrolimus, though continued follow-up is warranted. Given the elevated seroprevalence of KSHV in Xinjiang, it is recommended that all patients undergoing long-term immunosuppressive therapy receive regular dermatological assessments to detect any suspicious cutaneous or mucosal lesions at an early stage. Moreover, pre-treatment screening for KSHV should be considered to mitigate the risk of iatrogenic KS. In summary, this case underscores the clinical importance of vigilant dermatological monitoring in patients receiving long-term immunosuppressive therapy, particularly in regions with elevated KSHV seroprevalence such as Xinjiang. Our findings highlight the need for routine screening and potential pre-treatment evaluation for KSHV to prevent the onset of iatrogenic KS. Such proactive measures could significantly enhance patient management and outcomes, marking an important step in the integration of virological screening into the care protocols for patients with autoimmune conditions. Declarations Author contributions Mingjia Lu：Writing – original draft, Methodology, Data curation,Conceptualization Maynur Mamat：review & editing, Supervision,Investigation, Conceptualization. Hongyan Li：Writing – review & editing,Visualization, Validation, Data curation, Conceptualization. Data availability statement The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation. Ethics statement The studies involving humans were approved by People's Hospital of Xinjiang Uygur Autonomous Region. The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study. Acknowledgments We thank all participants recruited in this study Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Funding Declaration T his work has been supported by Scientific Research Project of the Second Medical University of Xinjiang,ZR202415;Natural Science Foundation of Xinjinang Uygur Autonomous Region,2024D01D14 Ethics statement The studies involving human participants were reviewed and approved by the Ethical Review Committee of People’s Hospital of XinjiangUygur Autonomous Region (KY2025032701）.The patients provided their written informed consent to participate in the study. consent for publication We have already obtained the patient's handwritten informed consent for this article. References D.P. Dittmer, and B. Damania, Kaposi sarcoma associated herpesvirus pathogenesis (KSHV)—an update. Current Opinion in Virology 3 (2013) 238-244. X. Zhang, Q. Fang, S. Zhu, X. Wu, H. Yuan, Z. Liu, Y. Xu, T. Chen, Y. Zeng, and T. Zhang, Environmental risk factors and genetic markers of Kaposi's sarcoma‐associated herpesvirus infection among Uygur population in Xinjiang, China. Journal of Medical Virology 94 (2022) 2755-2765. E. Ruocco, V. Ruocco, M.L. Tornesello, A. Gambardella, R. Wolf, and F.M. Buonaguro, Kaposi’s sarcoma: Etiology and pathogenesis, inducing factors, causal associations, and treatments: Facts and controversies. Clinics in Dermatology 31 (2013) 413-422. Dariyush Raeisi, Mehrdad Payandeh, Seyed Hamid Madani. Kaposi’s Sarcoma after Kidney Transplantation: a 21-Years Experience. Int J Hematol Oncol Stem Cell Res . 2013;7(4):29-33. B. González-Sixto, A. Conde, E. Mayo, R. Pardavila, C. de la Torre, and M. Cruces, Kaposi Sarcoma Associated With Systemic Corticosteroid Therapy. Actas Dermo-Sifiliográficas (English Edition) 98 (2007) 553-555. A. van Kessel, and K.D. Quint, [Moritz Kaposi and his sarcoma]. Ned Tijdschr Geneeskd. 2011;155(45):A3879. T. Kanai, A. Uzawa, N. Kawaguchi, K. Himuro, F. Oda, Y. Ozawa, and S. Kuwabara, Adequate tacrolimus concentration for myasthenia gravis treatment. Eur J Neurol . 2017 Feb;24(2):270-275. M. Dedicoat, and R. Newton, Review of the distribution of Kaposi's sarcoma-associated herpesvirus (KSHV) in Africa in relation to the incidence of Kaposi's sarcoma. British Journal of Cancer 88 (2003) 1-3. S.J. Gao, M. Kingsley L Fau - Li, W. Li M Fau - Zheng, C. Zheng W Fau - Parravicini, J. Parravicini C Fau - Ziegler, R. Ziegler J Fau - Newton, C.R. Newton R Fau - Rinaldo, A. Rinaldo Cr Fau - Saah, J. Saah A Fau - Phair, R. Phair J Fau - Detels, Y. Detels R Fau - Chang, P.S. Chang Y Fau - Moore, and P.S. Moore, KSHV antibodies among Americans, Italians and Ugandans with and without Kaposi's sarcoma. Nat Med. 1996 Aug;2(8):925-8. Y. Chang, M.S. Cesarman E Fau - Pessin, F. Pessin Ms Fau - Lee, J. Lee F Fau - Culpepper, D.M. Culpepper J Fau - Knowles, P.S. Knowles Dm Fau - Moore, and P.S. Moore, Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi's sarcoma. Science. 1994 Dec 16;266(5192):1865-9. P. Dilnur, Z.H. Katano H Fau - Wang, Y. Wang Zh Fau - Osakabe, M. Osakabe Y Fau - Kudo, T. Kudo M Fau - Sata, Y. Sata T Fau - Ebihara, and Y. Ebihara, Classic type of Kaposi's sarcoma and human herpesvirus 8 infection in Xinjiang, China. Pathol Int. 2001 Nov;51(11):845-52. Y. Fang, W. Li, Y. Zhang, C. Zhou, H. Wu, Y. Zhang, T. Dai, J. Wang, L. Wang, T. Chen, Y. Zhu, and L.A.-O. Wang, Seroprevalence of Kaposi's sarcoma-associated herpesvirus and risk factors in Jiuquan area, China. J Med Virol. 2022 Dec;94(12):6016-6022. Z. Liu, Q. Fang, J. Zuo, V. Minhas, C. Wood, N. He, and T. Zhang, Was Kaposi’s sarcoma-associated herpesvirus introduced into China via the ancient Silk Road? An evolutionary perspective. Archives of Virology 162 (2017) 3061-3068. L. Brambilla, A. Tourlaki, and G. Genovese, Iatrogenic Kaposi's Sarcoma: a Retrospective Cohort Study in an Italian Tertiary Care Centre. Clinical Oncology 29 (2017) e165-e171. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 03 Apr, 2026 Reviewers agreed at journal 31 Mar, 2026 Reviewers invited by journal 30 Mar, 2026 Editor invited by journal 20 Mar, 2026 Editor assigned by journal 20 Mar, 2026 Submission checks completed at journal 18 Mar, 2026 First submitted to journal 18 Mar, 2026 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-9008553","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":615390634,"identity":"8c95a70c-83b3-4553-8bed-ac566f39ca3e","order_by":0,"name":"mingjia lu","email":"","orcid":"","institution":"People's Hospital of Xinjiang Uygur Autonomous Region","correspondingAuthor":false,"prefix":"","firstName":"mingjia","middleName":"","lastName":"lu","suffix":""},{"id":615390635,"identity":"b53b5956-3602-42e6-b5dc-c1a68e0869fe","order_by":1,"name":"Maynur Mamat","email":"","orcid":"","institution":"People's Hospital of Xinjiang Uygur Autonomous Region","correspondingAuthor":false,"prefix":"","firstName":"Maynur","middleName":"","lastName":"Mamat","suffix":""},{"id":615390636,"identity":"6ff422d7-8df3-472f-9b02-bec4367e0886","order_by":2,"name":"Hongyan Li","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAzklEQVRIiWNgGAWjYBACAwkwZcPABiQPfPhBvJY0kBbGgzN7iNdyGEQwH+ZgI0aLdI+ZNG/b+cQ+6QagRh4GeX6xAwS0yJwxNpzZdjuxTeYAw+ECCwbDmbMTCDksx/DBx7bbxmwSCQyHZ/AwJBjcJqzF4EBi2zmIFh424rSAbDkgR4qWtGLDGeeS5dhkDjYAA1mCsF/sZyRvk+Yps+ORn918+MOHHzby/NIEtDAwcBgwMIKiQ4KxAUQSUg4C7A8YGP4Qq3gUjIJRMApGJAAAXVc/tySlXFIAAAAASUVORK5CYII=","orcid":"","institution":"People's Hospital of Xinjiang Uygur Autonomous Region","correspondingAuthor":true,"prefix":"","firstName":"Hongyan","middleName":"","lastName":"Li","suffix":""}],"badges":[],"createdAt":"2026-03-02 09:53:53","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9008553/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9008553/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":105923557,"identity":"6e3055b3-0eb5-47fc-a13e-b1ff2c6ec8d4","added_by":"auto","created_at":"2026-04-01 12:59:26","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":393716,"visible":true,"origin":"","legend":"\u003cp\u003e(a) Anterior tibial skin of the left lower limb; (b) Edematous appearance of the left lower limb; (c) Asymmetrical edema of both lower limbs.）\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-9008553/v1/5268dde31d7e5359e12c1675.png"},{"id":105923556,"identity":"41adb489-2ee9-42b8-8079-19ed5e6fb287","added_by":"auto","created_at":"2026-04-01 12:59:26","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":433026,"visible":true,"origin":"","legend":"\u003cp\u003eLower limb status observed three months after discontinuation of tacrolimus, demonstrating reduced edema, cutaneous lesions, and pigmentation.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-9008553/v1/346086a1aa2f1e6d88f21a0b.png"},{"id":105923558,"identity":"b18fc280-b71e-4b4a-a227-8c0ee2ee575f","added_by":"auto","created_at":"2026-04-01 12:59:26","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":1820603,"visible":true,"origin":"","legend":"\u003cp\u003eHistopathology/ Immunohistochemistry of a skin lesion on the left lower leg.(H\u0026amp;E,✖100)\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-9008553/v1/417bc5336103ccca2e765845.png"},{"id":106093323,"identity":"fa9b9e22-02d6-4709-b8e3-098512a54ec9","added_by":"auto","created_at":"2026-04-03 11:36:45","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3649885,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9008553/v1/a9925462-f369-4c79-b97a-6fe4de06d1bc.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Tacrolimus-associated Kaposi's Sarcoma in a Patient with Refractory Generalized Myasthenia Gravis: A Case Report","fulltext":[{"header":"Introduction","content":"\u003cp\u003eMyasthenia gravis (MG) is an autoimmune disorder of the neuromuscular junction mediated by autoantibodies that impair neuromuscular transmission. The therapeutic strategies for MG include cholinesterase inhibitors, glucocorticoids, immunosuppressants, intravenous immunoglobulins (IVIG), plasma exchange (PE), and thymectomy. Kaposi\u0026rsquo;s sarcoma (KS) is a multicentric sarcoma of endothelial origin that primarily affects the skin, yet it can also involve mucosal surfaces, lymph nodes, and visceral organs. KS is currently recognized in four different clinical types: classical, endemic in Africa, epidemic associated with Acquired Immune Deficiency Syndrome, and iatrogenic. KS is etiologically linked to human herpesvirus-8 (HHV-8)[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e], also known as Kaposi\u0026rsquo;s sarcoma-associated herpesvirus (KSHV). Although KS is relatively uncommon in China, the seropositivity rate for KSHV in Xinjiang is significantly higher than in other regions, which may predispose this population to an increased risk of iatrogenic KS[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Typically emerging in the context of immunosuppressive therapy[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e], iatrogenic KS is frequently observed in patients undergoing treatment for organ transplantation[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e] or autoimmune conditions. Herein, we report a rare case of KS in a patient with refractory generalized MG from Xinjiang who was receiving tacrolimus therapy.\u003c/p\u003e"},{"header":"Case report","content":"\u003cp\u003eA 71-year-old Uyghur male with a diagnosis of myasthenia gravis type IVb was admitted with a history of slurred speech, dyspnea persisting for over ten years, and lower limb edema lasting more than six months. His initial symptoms emerged in 2014 with slurred speech, dyspnea, and post-activity fatigue, and in January 2015 he was diagnosed with acute severe MG and myasthenic crisis, for which he received immunoglobulin therapy, non-invasive ventilation, and methylprednisolone pulse therapy, resulting in clinical improvement. Post-discharge, he was maintained on pyridostigmine bromide 90 mg four times daily and azathioprine 25 mg twice daily; however, due to persistent leukopenia, his regimen was modified to mycophenolate mofetil 1 g twice daily. The patient experienced recurrent exacerbations related to infections in 2017, 2019, and 2021, necessitating repeated immunoglobulin infusions. In 2023, following another infectious episode, his treatment was adjusted to include tacrolimus capsules (2 mg in the morning and 1 mg in the evening) alongside pyridostigmine bromide and prednisone acetate 30 mg daily. In July 2023, he suffered another myasthenic crisis, leading to intensive care admission where corticosteroid pulse therapy and a subcutaneous injection of Telitacicept were administered; therapeutic tacrolimus levels were confirmed by monitoring. Intermittent edema of the lower limbs was first noted in July 2023, and two months prior to the current admission, persistent and asymmetrical edema developed, impairing his ambulation. A localized non-blanchable red pigmented area was observed on the anterior tibia of the left lower limb (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Serologic testing for HIV and syphilis was negative, and dermoscopic evaluation revealed multiple purple-red lacunae, irregular vascular structures, crust formation, and rainbow patterns on a blue-red background, findings consistent with a diagnosis of iatrogenic KS. Owing to significant edema and high skin tension, a skin biopsy was deferred. Following the cessation of tacrolimus, the patient demonstrated a slight improvement in skin pigmentation (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e) and continues to be closely monitored.Histologic examination of the skin lesion on the left lower leg (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e) showed the basal layer of the epidermis shows increased pigmentation. In the dermis, there is a nodular infiltration of numerous spindle-shaped cells, with vascular-like clefts visible among them. Some of these clefts contain red blood cells, and a small amount of hemosiderin deposition is observed. Immunohistochemistry (IHC): CD34 positive, HHV-8 positive. In combination with the clinical presentation, it is consistent with Kaposi's sarcoma.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eKaposi\u0026rsquo;s sarcoma (KS) is a multicentric sarcoma of endothelial origin that predominantly manifests in the skin but may also involve mucosal surfaces, lymph nodes, and visceral organs. Iatrogenic KS, frequently observed in the context of immunosuppressive therapy[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u0026mdash;such as that administered to organ transplant recipients and patients with autoimmune conditions like myasthenia gravis (MG)\u0026mdash;is considered to have an autoimmune component. Immunosuppressants, including glucocorticoids[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] and non-steroidal agents such as azathioprine[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e], tacrolimus[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], mycophenolate mofetil, cyclosporine, methotrexate, and cyclophosphamide, play a crucial role in preventing MG relapses; notably, tacrolimus is widely used in clinical practice due to its rapid onset of action, typically within approximately one month[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].Human herpesvirus-8 (HHV-8), or Kaposi\u0026rsquo;s sarcoma-associated herpesvirus (KSHV), has been confirmed as the etiological agent of all KS variants, although its origins remain elusive. KSHV exhibits a distinct geographical distribution, with seroprevalence rates estimated to exceed 50% in the general populations of sub-Saharan Africa, approximately 20\u0026ndash;80% in Mediterranean regions[8; 9], and less than 10% in North America, Northern Europe, and most parts of Asia[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Xinjiang, a northwestern Chinese autonomous region bordered by Russia, Kazakhstan, Kyrgyzstan, Tajikistan, Pakistan, Mongolia, Afghanistan, and India, is characterized by a diverse ethnic composition\u0026mdash;including Uyghurs, Han, Kazakhs, and Hui\u0026mdash;which, coupled with its historical significance along the ancient Silk Road, contributes to a markedly higher KSHV seroprevalence[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. While most provinces in China report KSHV seropositivity below 8%, studies indicate that in Xinjiang, particularly among Uyghur and Kazakh populations, this rate can be as high as 19.3% to 46.6%[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Some research even suggests that the dominant KSHV genotypes in Xinjiang may trace back to the ancient Silk Road period[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e], although further evidence is required to substantiate this hypothesis.\u003c/p\u003e \u003cp\u003eIn the present case, an elderly Uyghur male from Kashgar,Xinjiang, who had been on long-term tacrolimus therapy, developed pronounced asymmetrical lower limb edema and cutaneous lesions. A biopsy confirmed the diagnosis of KS. The underlying mechanism may involve tacrolimus-induced immunosuppression, which compromises immunosurveillance and potentially reactivates latent KSHV infection[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e], thereby promoting the proliferation and differentiation of infected endothelial cells. Consistent with other reports of iatrogenic KS, most patients experience clinical improvement following a reduction or discontinuation of immunosuppressive agents; indeed, our patient demonstrated a slight amelioration of skin pigmentation after cessation of tacrolimus, though continued follow-up is warranted. Given the elevated seroprevalence of KSHV in Xinjiang, it is recommended that all patients undergoing long-term immunosuppressive therapy receive regular dermatological assessments to detect any suspicious cutaneous or mucosal lesions at an early stage. Moreover, pre-treatment screening for KSHV should be considered to mitigate the risk of iatrogenic KS.\u003c/p\u003e \u003cp\u003eIn summary, this case underscores the clinical importance of vigilant dermatological monitoring in patients receiving long-term immunosuppressive therapy, particularly in regions with elevated KSHV seroprevalence such as Xinjiang. Our findings highlight the need for routine screening and potential pre-treatment evaluation for KSHV to prevent the onset of iatrogenic KS. Such proactive measures could significantly enhance patient management and outcomes, marking an important step in the integration of virological screening into the care protocols for patients with autoimmune conditions.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMingjia Lu：Writing\u0026nbsp;\u0026ndash;\u0026nbsp;original draft, Methodology, Data curation,Conceptualization\u003c/p\u003e\n\u003cp\u003eMaynur Mamat：review \u0026amp; editing, Supervision,Investigation, Conceptualization.\u003c/p\u003e\n\u003cp\u003eHongyan Li：Writing\u0026nbsp;\u0026ndash;\u0026nbsp;review \u0026amp; editing,Visualization, Validation, Data curation, Conceptualization.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe studies involving humans were approved by People\u0026apos;s Hospital of Xinjiang Uygur Autonomous Region. The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank all participants recruited in this study\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding Declaration\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eT\u003c/strong\u003ehis work has been supported by Scientific Research Project of the Second Medical University of Xinjiang,ZR202415;Natural Science Foundation of Xinjinang Uygur Autonomous Region,2024D01D14\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics statement\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe studies involving human participants were reviewed and approved by the Ethical Review Committee of People\u0026rsquo;s Hospital of XinjiangUygur Autonomous Region\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e(KY2025032701）.The patients provided their written informed consent to participate in the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003econsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe have already obtained the patient\u0026apos;s handwritten informed consent for this article.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eD.P. Dittmer, and B. Damania, Kaposi sarcoma associated herpesvirus pathogenesis (KSHV)\u0026mdash;an update. Current Opinion in Virology 3 (2013) 238-244.\u003c/li\u003e\n\u003cli\u003eX. Zhang, Q. Fang, S. Zhu, X. Wu, H. Yuan, Z. Liu, Y. Xu, T. Chen, Y. Zeng, and T. Zhang, Environmental risk factors and genetic markers of Kaposi\u0026apos;s sarcoma‐associated herpesvirus infection among Uygur population in Xinjiang, China. Journal of Medical Virology 94 (2022) 2755-2765.\u003c/li\u003e\n\u003cli\u003eE. Ruocco, V. Ruocco, M.L. Tornesello, A. Gambardella, R. Wolf, and F.M. Buonaguro, Kaposi\u0026rsquo;s sarcoma: Etiology and pathogenesis, inducing factors, causal associations, and treatments: Facts and controversies. Clinics in Dermatology 31 (2013) 413-422.\u003c/li\u003e\n\u003cli\u003eDariyush Raeisi, Mehrdad Payandeh, Seyed Hamid Madani. Kaposi\u0026rsquo;s Sarcoma after Kidney Transplantation: a 21-Years Experience. Int J Hematol Oncol Stem Cell Res . 2013;7(4):29-33.\u003c/li\u003e\n\u003cli\u003eB. Gonz\u0026aacute;lez-Sixto, A. Conde, E. Mayo, R. Pardavila, C. de la Torre, and M. Cruces, Kaposi Sarcoma Associated With Systemic Corticosteroid Therapy. Actas Dermo-Sifiliogr\u0026aacute;ficas (English Edition) 98 (2007) 553-555.\u003c/li\u003e\n\u003cli\u003eA. van Kessel, and K.D. Quint, [Moritz Kaposi and his sarcoma]. Ned Tijdschr Geneeskd. 2011;155(45):A3879.\u003c/li\u003e\n\u003cli\u003eT. Kanai, A. Uzawa, N. Kawaguchi, K. Himuro, F. Oda, Y. Ozawa, and S. Kuwabara, Adequate tacrolimus concentration for myasthenia gravis treatment. Eur J Neurol . 2017 Feb;24(2):270-275.\u003c/li\u003e\n\u003cli\u003eM. Dedicoat, and R. Newton, Review of the distribution of Kaposi\u0026apos;s sarcoma-associated herpesvirus (KSHV) in Africa in relation to the incidence of Kaposi\u0026apos;s sarcoma. British Journal of Cancer 88 (2003) 1-3.\u003c/li\u003e\n\u003cli\u003eS.J. Gao, M. Kingsley L Fau - Li, W. Li M Fau - Zheng, C. Zheng W Fau - Parravicini, J. Parravicini C Fau - Ziegler, R. Ziegler J Fau - Newton, C.R. Newton R Fau - Rinaldo, A. Rinaldo Cr Fau - Saah, J. Saah A Fau - Phair, R. Phair J Fau - Detels, Y. Detels R Fau - Chang, P.S. Chang Y Fau - Moore, and P.S. Moore, KSHV antibodies among Americans, Italians and Ugandans with and without Kaposi\u0026apos;s sarcoma. Nat Med. 1996 Aug;2(8):925-8.\u003c/li\u003e\n\u003cli\u003eY. Chang, M.S. Cesarman E Fau - Pessin, F. Pessin Ms Fau - Lee, J. Lee F Fau - Culpepper, D.M. Culpepper J Fau - Knowles, P.S. Knowles Dm Fau - Moore, and P.S. Moore, Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi\u0026apos;s sarcoma. Science. 1994 Dec 16;266(5192):1865-9.\u003c/li\u003e\n\u003cli\u003eP. Dilnur, Z.H. Katano H Fau - Wang, Y. Wang Zh Fau - Osakabe, M. Osakabe Y Fau - Kudo, T. Kudo M Fau - Sata, Y. Sata T Fau - Ebihara, and Y. Ebihara, Classic type of Kaposi\u0026apos;s sarcoma and human herpesvirus 8 infection in Xinjiang, China. Pathol Int. 2001 Nov;51(11):845-52.\u003c/li\u003e\n\u003cli\u003eY. Fang, W. Li, Y. Zhang, C. Zhou, H. Wu, Y. Zhang, T. Dai, J. Wang, L. Wang, T. Chen, Y. Zhu, and L.A.-O. Wang, Seroprevalence of Kaposi\u0026apos;s sarcoma-associated herpesvirus and risk factors in Jiuquan area, China. J Med Virol. 2022 Dec;94(12):6016-6022.\u003c/li\u003e\n\u003cli\u003eZ. Liu, Q. Fang, J. Zuo, V. Minhas, C. Wood, N. He, and T. Zhang, Was Kaposi\u0026rsquo;s sarcoma-associated herpesvirus introduced into China via the ancient Silk Road? An evolutionary perspective. Archives of Virology 162 (2017) 3061-3068.\u003c/li\u003e\n\u003cli\u003eL. Brambilla, A. Tourlaki, and G. Genovese, Iatrogenic Kaposi\u0026apos;s Sarcoma: a Retrospective Cohort Study in an Italian Tertiary Care Centre. Clinical Oncology 29 (2017) e165-e171.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"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":"bmc-neurology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"nurl","sideBox":"Learn more about [BMC Neurology](http://bmcneurol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/nurl","title":"BMC Neurology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Kaposi’s sarcoma, myasthenia gravis, Kaposi’s sarcoma-associated herpesvirus (KSHV), immunosuppressive therapy","lastPublishedDoi":"10.21203/rs.3.rs-9008553/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9008553/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eKaposi\u0026rsquo;s sarcoma (KS) is an endothelial cell neoplasm that is rarely observed in patients with myasthenia gravis (MG). A 71-year-old Uyghur male diagnosed with myasthenia gravis type IVb was evaluated. In 2023, the patient experienced an exacerbation of muscle weakness and dyspnea secondary to an infection. Prior to this episode, he was treated with oral pyridostigmine bromide 90 mg four times daily and prednisone acetate 30 mg once daily. Subsequently, his regimen was adjusted to include tacrolimus capsules administered at 2 mg in the morning and 1 mg in the evening. In July 2023, he experienced another myasthenic crisis and received corticosteroid pulse therapy combined with a subcutaneous injection of Telitacicept, after which intermittent edema developed in both lower limbs. Since January 2024, the patient has experienced persistent, asymmetrical lower limb edema that has interfered with ambulation. Additionally, a localized non-blanchable red pigmented area was observed on the anterior tibia of the left lower limb. Serologic tests for HIV and syphilis were negative, and dermoscopic examination revealed multiple purple-red lacunae, irregular vascular structures, crust formation, and rainbow patterns on a blue-red background;\u0026mdash;the biopsy reveal the basal layer of the epidermis shows increased pigmentation. In the dermis, there is a nodular infiltration of numerous spindle-shaped cells, with vascular-like clefts visible among them. Some of these clefts contain red blood cells, and a small amount of hemosiderin deposition is observed. Immunohistochemistry (IHC): CD34 positive, HHV-8 positive. In combination with the clinical presentation,findings suggestive of KS. Currently, with the discontinuation of tacrolimus, a slight improvement in skin pigmentation has been observed. In conclusion, KS is a rare complication arising during immunosuppressive therapy in patients with MG, and timely detection with regular screening is essential for optimizing patient outcomes.\u003c/p\u003e","manuscriptTitle":"Tacrolimus-associated Kaposi's Sarcoma in a Patient with Refractory Generalized Myasthenia Gravis: A Case Report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-01 12:59:21","doi":"10.21203/rs.3.rs-9008553/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-04-04T01:38:23+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"325553518394995872629135554981081870375","date":"2026-03-31T15:14:25+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-03-31T00:57:29+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-03-20T13:17:44+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-03-20T13:14:20+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-03-18T06:44:04+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Neurology","date":"2026-03-18T04:24:19+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-neurology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"nurl","sideBox":"Learn more about [BMC Neurology](http://bmcneurol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/nurl","title":"BMC Neurology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"686b3c2a-4b51-49bf-b744-1928885d59a1","owner":[],"postedDate":"April 1st, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-01T12:59:21+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-01 12:59:21","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9008553","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9008553","identity":"rs-9008553","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}