巨噬細胞活化症候群住院病患之流行病學與預後分析：全國性回溯性研究

Epidemiology and Outcomes of Hospitalised Patients With Macrophage Activation Syndrome: A Nationwide Retrospective Study in Taiwan

背景：巨噬細胞活化症候群（Macrophage Activation Syndrome, MAS）為血球吞噬性淋巴組織細胞增生症（Hemophagocytic Lymphohistiocytosis, HLH）的一種繼發型態，是一種罕見但致命的高發炎性疾病，常與自體免疫疾病（如紅斑性狼瘡或成人型史迪爾氏病）相關。針對亞洲成人族群的流行病學資料仍相當有限。
目的：利用台灣全國健保資料庫，分析成人HLH/MAS之臨床特徵、流行病學、死亡率及治療趨勢。
方法：本研究為回溯性全國性世代研究，資料來源為2016至2018年間之台灣健保資料庫。依據ICD-10-CM診斷碼辨識HLH/MAS個案，分析其人口學特徵、共病、治療方式及臨床結果，並以Cox迴歸模型評估死亡風險。
結果：共納入651位HLH/MAS病患，中位年齡48歲，女性佔51.8%。2016至2018年之年盛行率分別為每10萬人0.99、0.92及0.96例，總死亡率為31.03%（95%信賴區間：27.5%–34.6%），且死亡率隨年齡增加。約34.9%的病患需入住加護病房。類固醇為最常使用之治療（78.5%），靜脈注射免疫球蛋白（IVIG）使用率為14.0%，但與較高的死亡率相關（aOR 5.45；95% CI, 2.95–10.06）。
結論：本研究顯示HLH/MAS於成人族群中具顯著的死亡負擔，且年齡與惡性腫瘤或感染相關之個案死亡風險更高。IVIG使用與死亡風險增加的關聯可能反映治療指標偏差。研究結果凸顯早期診斷與標準化治療指引之重要性，建議未來需進行前瞻性研究以優化成人MAS之管理策略。

Background: Macrophage activation syndrome (MAS), a secondary form of hemophagocytic lymphohistiocytosis (HLH), is a rare but life-threatening hyperinflammatory condition frequently associated with autoimmune diseases such as systemic lupus erythematosus and adult-onset Still’s disease. Notably, population-based data on adult MAS remain limited, particularly in Asian populations.
Objective: To describe the clinical characteristics, epidemiology, mortality, and treatment patterns of HLH/MAS in Taiwan by using a nationwide health database.
Methods: We conducted a retrospective cohort study by using data from Taiwan’s National Health Insurance Research Database from 2016 to 2018. Patients with HLH/MAS were identified using International Classification of Diseases, Tenth Revision, Clinical Modification codes. Demographic characteristics, comorbidities, treatments, and outcomes were analysed. Mortality and incidence rates were estimated using descriptive statistics and survival analyses.
Results: A total of 651 patients with HLH/MAS were included. The median age was 48 years, and 51.8% of the patients were women. The annual prevalence rates of HLH/MAS were 0.99, 0.92, and 0.96 per 100,000 persons in 2016, 2017, and 2018, respectively. The overall mortality rate was 31.03% (95% confidence interval [CI], 27.5%–34.6%), with mortality increasing with age. Intensive care was required in 34.9% of cases. Corticosteroids were administered in 78.5% of patients, whereas intravenous immunoglobulin (IVIG) was used in only 14%. IVIG use was associated with higher all-cause and in-hospital mortality.
Conclusion: This study highlights the substantial mortality burden of HLH/MAS in adults and suggests that IVIG treatment correlated with an increased rate of death, however, this finding likely reflects and indication bias. These findings underscore the need for early recognition, standardised treatment protocols, and further prospective studies in adult MAS populations.
Limitations: ICD-based coding precluded HLH-2004 or HScore application, preventing reliable distinction of MAS from other secondary HLH, while absence of key data, incomplete drug capture, and observational design further limited causal interpretation.