系统性红斑狼疮合并巨噬细胞活化综合征的诊治进展
Advances in the Diagnosis and Treatment of Systemic Lupus Erythematosus Complicated with Macrophage Activation Syndrome
摘要: 巨噬细胞活化综合征(MAS)是一种继发于风湿免疫疾病的噬血细胞性淋巴组织细胞增多症(HLH)，是一种罕见的、危及生命的过度炎症性疾病。巨噬细胞活化综合征的典型临床症状包括持续高热、皮疹以及肝和脾的肿大，实验室的检测结果显示患者的血细胞数量减少，伴有高甘油三酯或低纤维蛋白原、高铁蛋白血症和转氨酶水平上升等现象。在全身性幼年特发性关节炎(sJIA)和成人发病斯蒂尔氏病(AOSD)中，巨噬细胞活化综合征的发病率较高，但目前有越来越多的学者对系统性红斑狼疮患者发生巨噬细胞活化综合征进行了报道。巨噬细胞活化综合征病情复杂，进展凶险，若误诊或延误治疗时机，可能造成无法挽回的不良结果，所以早期识别巨噬细胞活化综合征并进行诊治就显得十分必要。本文通过检索Pubmed数据库，对系统性红斑狼疮合并巨噬细胞活化综合征的诊治进展做一综述。
Abstract: Macrophage activation syndrome (MAS), a hemophagocytic lymphohistiocytosis (HLH) secondary to rheumatic immune disease, is a rare, life-threatening hyperinflammatory disease. Typical clinical symptoms of macrophage activation syndrome include persistent high fever, rash, and enlargement of the liver and spleen, and laboratory tests show a decrease in the number of blood cells in the patient, with high triglycerides or low fibrinogen, ferritinemia, and elevated aminotransferase levels. The incidence of macrophage activation syndrome is high in systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still’s disease (AOSD), but more and more scholars have reported the occurrence of macrophage activation syndrome in patients with systemic lupus erythematosus. Macrophage activation syndrome is complex and progresses dangerously, and if it is misdiagnosed or delayed, it may cause irreversible adverse results, so it is necessary to identify and treat macrophage activation syndrome early. This article reviews the progress in the diagnosis and treatment of systemic lupus erythematosus complicated with macrophage activation syndrome by searching the Pubmed database.
文章引用：龚蕾, 唐琳. 系统性红斑狼疮合并巨噬细胞活化综合征的诊治进展[J]. 临床医学进展, 2025, 15(2): 1989-1995. https://doi.org/10.12677/acm.2025.152561

参考文献

[1] Clementi, R., Emmi, L., Maccario, R., Liotta, F., Moretta, L., Danesino, C., et al. (2002) Adult Onset and Atypical Presentation of Hemophagocytic Lymphohistiocytosis in Siblings Carrying PRF1 Mutations. Blood, 100, 2266-2266. [Google Scholar] [CrossRef] [PubMed]
[2] Griffin, G., Shenoi, S. and Hughes, G.C. (2020) Hemophagocytic Lymphohistiocytosis: An Update on Pathogenesis, Diagnosis, and Therapy. Best Practice & Research Clinical Rheumatology, 34, Article ID: 101515. [Google Scholar] [CrossRef] [PubMed]
[3] Wu, Y., Sun, X., Kang, K., Yang, Y., Li, H., Zhao, A., et al. (2024) Hemophagocytic Lymphohistiocytosis: Current Treatment Advances, Emerging Targeted Therapy and Underlying Mechanisms. Journal of Hematology & Oncology, 17, Article No. 106. [Google Scholar] [CrossRef] [PubMed]
[4] Wafa, A., Hicham, H., Naoufal, R., Hajar, K., Rachid, R., Souad, B., et al. (2022) Clinical Spectrum and Therapeutic Management of Systemic Lupus Erythematosus-Associated Macrophage Activation Syndrome: A Study of 20 Moroccan Adult Patients. Clinical Rheumatology, 41, 2021-2033. [Google Scholar] [CrossRef] [PubMed]
[5] Shakoory, B., Geerlinks, A., Wilejto, M., Kernan, K., Hines, M., Romano, M., et al. (2023) The 2022 EULAR/ACR Points to Consider at the Early Stages of Diagnosis and Management of Suspected Haemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome (HLH/MAS). Annals of the Rheumatic Diseases, 82, 1271-1285. [Google Scholar] [CrossRef] [PubMed]
[6] Gioia, C., Paroli, M., Izzo, R., Di Sanzo, L., Rossi, E., Pignatelli, P., et al. (2024) Pathogenesis of Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome: A Case Report and Review of the Literature. International Journal of Molecular Sciences, 25, Article 5921. [Google Scholar] [CrossRef] [PubMed]
[7] Andersson, U. (2021) Hyperinflammation: On the Pathogenesis and Treatment of Macrophage Activation Syndrome. Acta Paediatrica, 110, 2717-2722. [Google Scholar] [CrossRef] [PubMed]
[8] Crayne, C.B., Albeituni, S., Nichols, K.E. and Cron, R.Q. (2019) The Immunology of Macrophage Activation Syndrome. Frontiers in Immunology, 10, Article 119. [Google Scholar] [CrossRef] [PubMed]
[9] Aringer, M., Costenbader, K., Daikh, D., Brinks, R., Mosca, M., Ramsey-Goldman, R., et al. (2019) 2019 European League against Rheumatism/American College of Rheumatology Classification Criteria for Systemic Lupus Erythematosus. Arthritis & Rheumatology, 71, 1400-1412.
[10] Kiriakidou, M. and Ching, C.L. (2020) Systemic Lupus Erythematosus. Annals of Internal Medicine, 172, ITC81-ITC96. [Google Scholar] [CrossRef] [PubMed]
[11] Allen, C.E., Yu, X., Kozinetz, C.A. and McClain, K.L. (2007) Highly Elevated Ferritin Levels and the Diagnosis of Hemophagocytic Lymphohistiocytosis. Pediatric Blood & Cancer, 50, 1227-1235. [Google Scholar] [CrossRef] [PubMed]
[12] La Rosée, P., Horne, A., Hines, M., von Bahr Greenwood, T., Machowicz, R., Berliner, N., et al. (2019) Recommendations for the Management of Hemophagocytic Lymphohistiocytosis in Adults. Blood, 133, 2465-2477. [Google Scholar] [CrossRef] [PubMed]
[13] Zhao, Y., Zhang, Q., Li, Z., Zhang, L., Lian, H., Ma, H., et al. (2018) Central Nervous System Involvement in 179 Chinese Children with Hemophagocytic Lymphohistiocytosis. Chinese Medical Journal, 131, 1786-1792. [Google Scholar] [CrossRef] [PubMed]
[14] Henter, J., Horne, A., Aricó, M., Egeler, R.M., Filipovich, A.H., Imashuku, S., et al. (2006) HLH‐2004: Diagnostic and Therapeutic Guidelines for Hemophagocytic Lymphohistiocytosis. Pediatric Blood & Cancer, 48, 124-131. [Google Scholar] [CrossRef] [PubMed]
[15] Henter, J.I., Elinder, G. and Ost, A. (1991) Diagnostic Guidelines for Hemophagocytic Lymphohistiocytosis. The FHL Study Group of the Histiocyte Society. Seminars in Oncology, 18, 29-33.
[16] Seo, J.J. (2015) Hematopoietic Cell Transplantation for Hemophagocytic Lymphohistiocytosis: Recent Advances and Controversies. Blood Research, 50, 131-139. [Google Scholar] [CrossRef] [PubMed]
[17] Filipovich, A.H. (2009) Hemophagocytic Lymphohistiocytosis (HLH) and Related Disorders. Hematology, 2009, 127-131. [Google Scholar] [CrossRef] [PubMed]
[18] Fardet, L., Galicier, L., Lambotte, O., Marzac, C., Aumont, C., Chahwan, D., et al. (2014) Development and Validation of the HScore, a Score for the Diagnosis of Reactive Hemophagocytic Syndrome. Arthritis & Rheumatology, 66, 2613-2620. [Google Scholar] [CrossRef] [PubMed]
[19] Knaak, C., Nyvlt, P., Schuster, F.S., Spies, C., Heeren, P., Schenk, T., et al. (2020) Hemophagocytic Lymphohistiocytosis in Critically Ill Patients: Diagnostic Reliability of HLH-2004 Criteria and HScore. Critical Care, 24, Article No. 244. [Google Scholar] [CrossRef] [PubMed]
[20] Ramos-Casals, M., Brito-Zerón, P., López-Guillermo, A., Khamashta, M.A. and Bosch, X. (2014) Adult Haemophagocytic Syndrome. The Lancet, 383, 1503-1516. [Google Scholar] [CrossRef] [PubMed]
[21] Gavand, P., Serio, I., Arnaud, L., Costedoat-Chalumeau, N., Carvelli, J., Dossier, A., et al. (2017) Clinical Spectrum and Therapeutic Management of Systemic Lupus Erythematosus-Associated Macrophage Activation Syndrome: A Study of 103 Episodes in 89 Adult Patients. Autoimmunity Reviews, 16, 743-749. [Google Scholar] [CrossRef] [PubMed]
[22] De Benedetti, F., Grom, A.A., Brogan, P.A., Bracaglia, C., Pardeo, M., Marucci, G., et al. (2023) Efficacy and Safety of Emapalumab in Macrophage Activation Syndrome. Annals of the Rheumatic Diseases, 82, 857-865. [Google Scholar] [CrossRef] [PubMed]
[23] Galea, J., Ogungbenro, K., Hulme, S., Greenhalgh, A., Aarons, L., Scarth, S., et al. (2010) Intravenous Anakinra Can Achieve Experimentally Effective Concentrations in the Central Nervous System within a Therapeutic Time Window: Results of a Dose-Ranging Study. Journal of Cerebral Blood Flow & Metabolism, 31, 439-447. [Google Scholar] [CrossRef] [PubMed]
[24] Mehta, P., Cron, R.Q., Hartwell, J., Manson, J.J. and Tattersall, R.S. (2020) Silencing the Cytokine Storm: The Use of Intravenous Anakinra in Haemophagocytic Lymphohistiocytosis or Macrophage Activation Syndrome. The Lancet Rheumatology, 2, e358-e367. [Google Scholar] [CrossRef] [PubMed]
[25] Phadke, O., Rouster-Stevens, K., Giannopoulos, H., Chandrakasan, S. and Prahalad, S. (2021) Intravenous Administration of Anakinra in Children with Macrophage Activation Syndrome. Pediatric Rheumatology, 19, Article No. 98. [Google Scholar] [CrossRef] [PubMed]
[26] Kübler, L., Bittmann, I. and Kuipers, J.G. (2020) Macrophage Activation Syndrome Triggered by Active Systemic Lupus Erythematosus: Successful Treatment by Interleukin-1 Inhibition (Anakinra). Zeitschrift für Rheumatologie, 79, 1040-1045. [Google Scholar] [CrossRef] [PubMed]
[27] Zhang, G., Liu, W., Zhang, X. and Liu, L. (2021) Rescued from Desperation: Adult-Onset Still’s Disease with Life-Threatening Interstitial Lung Disease and Macrophage Activation: Successful Treatment by Tocilizumab. Zeitschrift für Rheumatologie, 81, 335-338. [Google Scholar] [CrossRef] [PubMed]
[28] Wu, J., Sun, L., Tang, X., Zheng, Q., Guo, L., Xu, L., et al. (2021) Effective Therapy of Tocilizumab on Systemic Juvenile Idiopathic Arthritis-Associated Refractory Macrophage Activation Syndrome. Modern Rheumatology, 32, 1114-1121. [Google Scholar] [CrossRef] [PubMed]
[29] Yamabe, T., Ohmura, S., Uehara, K. and Naniwa, T. (2021) Macrophage Activation Syndrome in Patients with Adult-Onset Still’s Disease under Tocilizumab Treatment: A Single-Center Observational Study. Modern Rheumatology, 32, 169-176. [Google Scholar] [CrossRef] [PubMed]
[30] Novick, D., Kim, S., Fantuzzi, G., Reznikov, L.L., Dinarello, C.A. and Rubinstein, M. (1999) Interleukin-18 Binding Protein: A Novel Modulator of the Th1 Cytokine Response. Immunity, 10, 127-136. [Google Scholar] [CrossRef] [PubMed]
[31] Ahmed, A., Merrill, S.A., Alsawah, F., Bockenstedt, P., Campagnaro, E., Devata, S., et al. (2019) Ruxolitinib in Adult Patients with Secondary Haemophagocytic Lymphohistiocytosis: An Open-Label, Single-Centre, Pilot Trial. The Lancet Haematology, 6, e630-e637. [Google Scholar] [CrossRef] [PubMed]
[32] Jung, J.I., Kim, J.Y., Kim, M.H., Park, J.K., Lee, E.Y., Lee, E.B., et al. (2023) Successful Treatment of Hemophagocytic Lymphohistiocytosis in a Patient with Systemic Lupus Erythematosus with Ruxolitinib: A Case Report. Journal of Rheumatic Diseases, 31, 125-129. [Google Scholar] [CrossRef] [PubMed]
[33] Song, Z., Yao, H., Jin, Y., Li, X., Jia, Y., He, J., et al. (2024) Ruxolitinib as a Salvage Therapy in Adult-Onset Macrophage Activation Syndrome: Insights from Eight Cases. Annals of the Rheumatic Diseases, 83, 1798-1799. [Google Scholar] [CrossRef] [PubMed]
[34] Harnchoowong, S., Soponkanaporn, S., Vilaiyuk, S., Lerkvaleekul, B. and Pakakasama, S. (2022) Central Nervous System Involvement and Thrombocytopenia as Predictors of Mortality in Children with Hemophagocytic Lymphohistiocytosis. Frontiers in Pediatrics, 10, Article 941318. [Google Scholar] [CrossRef] [PubMed]
[35] Wang, J., Rong, W. and Yan, H. (2024) Eighty‐Six Cases of Clinical Characteristics and Outcomes of Systemic Lupus Erythematosus‐Associated Macrophage Activation Syndrome: A Meta‐Analysis Study. Immunity, Inflammation and Disease, 12, e1364. [Google Scholar] [CrossRef] [PubMed]
[36] Ahn, S.S., Yoo, B., Jung, S.M., Lee, S., Park, Y. and Song, J.J. (2017) In-Hospital Mortality in Febrile Lupus Patients Based on 2016 EULAR/ACR/PRINTO Classification Criteria for Macrophage Activation Syndrome. Seminars in Arthritis and Rheumatism, 47, 216-221. [Google Scholar] [CrossRef] [PubMed]

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