Yang Liu1,2, Qian Li3, Yazhen Su1,2, Guozhu Che1,2, Ying Liu1,2, Pengyan Qiao1,2, Sumiao Liu1,2, Ke Xu1,2

1Department of Rheumatology and Immunology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, China
2Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
3Department of Rheumatology and Immunology, Heping Hospital Affiliated to Changzhi Medical College, Changzhi, China

Keywords: Autoimmune diseases, hemophagocytic syndrome, macrophage activation syndrome.


Objectives: This study aimed to analyze the differences of etiologies and clinical features between patients with autoimmune-associated hemophagocytic syndrome (AAHS) and those with other underlying diseases of hemophagocytic syndrome (HPS).

Patients and methods: The retrospective study was performed with 130 HPS patients (70 males, 60 females; mean age: 50.4±18.1 years; range, 13 to 85 years) between January 1st, 2011, and April 1st, 2022. The patients fulfilled at least five of the eight criteria proposed by the Histiocytosis Society in 2004. The underlying diseases related to HPS were divided into four categories: autoimmune, infection, malignancy and idiopathic diseases. And the clinical manifestations, laboratory examinations, treatments, and prognosis were analyzed respectively.

Results: Nineteen (14.6%) patients had AAHS, 45 (34.6%) had infection-associated HPS, 57 (43.8%) had malignancy-associated HPS, and nine (6.9%) had idiopathic HPS. The most common symptoms of HPS were unremitting fever in 123 (94.6%) of 130 patients and splenomegaly in 92 (70.8%). All patients manifested a decline of at least two lineages of hematopoietic cells. The absolute values of T cells and B cells of AAHS were significantly higher than that of malignancy-associated HPS. The levels of soluble CD25 (interleukin-2 receptor) of AAHS were the lowest among all-cause HPS (p<0.05). The all-cause mortality rate of hospitalized patients with HPS was 46.2%. The patients with AAHS had a better prognosis compared to other etiologies (odds ratio [OR]=0.091, 95% confidence interval [CI]: 0.011-0.775, p=0.028). Epstein-Barr virus infection (OR=4.761, 95% CI: 1.619-14.004, p=0.005) and pulmonary involvement (OR=4.555 95% CI: 1.524-13.609, p=0.007) were independent predictors of poor outcome in HPS. Thrombocytopenia (OR=0.978, 95% CI: 0.968-0.999, p=0.040) had a boundary effect on prognosis.

Conclusion: Patients with HPS secondary to autoimmune disease have better outcomes compared to patients complicated with Epstein-Barr virus infection or pulmonary involvement.

Citation: Liu Y, Li Q, Su Y, Che G, Liu Y, Qiao P, et al. A clinical analysis of hemophagocytic syndrome secondary to autoimmune diseases. Arch Rheumatol 2023;38(3):406-418.

Ethics Committee Approval

The study protocol was approved by the Shanxi Bethune Hospital Ethics Committee (date 16.05.2022, no: YXLL-2022-056). The study was conducted in accordance with the principles of the Declaration of Helsinki.

Author Contributions

Study conception and design: Y.L.; Acquisition of data: Y.L., Q.L., Y.S.; Analysis and interpretation of data: Y.L.; Manuscript preparation: Y.L., Q.L., Y.S., G.C., Y.L., P.Q., S.L., K.X.; Statistical analysis: Y.L., Q.L., Y.S., G.C., Y.L., P.Q., S.L., K.X. All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors approved the final version to be submitted for publication,and took responsibility for the integrity of the data and the accuracy of the data analysis.

Conflict of Interest

The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.

Financial Disclosure

This work was supported by grants from the National Natural Science Foundation (81871292) and the Key Research and Development (R&D) Projects of Shanxi Province (201803D31136).

Data Sharing Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.