A clinical analysis of hemophagocytic syndrome secondary to autoimmune diseases

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 1^st, 2011, and April 1^st, 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.