Background/Purpose: Macrophage activation syndrome (MAS), a life-threatening condition resulting from aberrant immune activation, is a form of hemophagocytic lymphohistiocytosis (HLH) that develops in patients with an underlying rheumatologic disease, classically juvenile idiopathic arthritis. Patients may or may not have an established rheumatologic diagnosis at the onset of MAS, making the identification of an underlying trigger challenging. Moreover, the commonly used diagnostic tools, such as the H-score, were developed from an adult population with a paucity of autoimmune disease. We aim to identify clinical features that may distinguish MAS cases from malignancy-associated HLH.

Methods: We identified adult HLH patients using ICD9/10 coding for HLH at an academic center from 2004 to 2020. A diagnosis of HLH required fulfillment of the 2004 HLH diagnostic criteria and/or clinical diagnosis by an expert. We included HLH cases that were secondary to either a rheumatologic disease (MAS) or a hematologic malignancy. MAS cases were compared to malignancy-associated HLH using STATA®.

Results: Of the 162 patients identified, 34 fulfilled inclusion criteria: 18 patients with MAS and 16 patients with hematologic malignancy-associated HLH. As expected, rheumatologic patients were younger (39.7 years vs. 62.3 years, p< 0.001) and more likely to be female (78% vs. 44%, p=0.042). MAS patients were less likely to have hepatomegaly (0% vs. 25%, p< 0.024), and developed milder cytopenias (Neutrophils: 3.7 vs. 1.2 K/μL, p=0.012; hemoglobin: 9.1 vs. 7.2 g/dL, p=0.004, platelets: 59.7vs. 30.9 K/μL, p=0.005) than malignancy-associated HLH patients. Soluble IL-2 receptor serum concentration was higher in malignancy patients but the difference did not reach statistical significance (5797.5 vs. 81786.4 pg/mL, p=0.11). MAS and HLH patients did not differ in the initial need for ICU levels of care but those with malignancy had a more prolonged hospital stay and a non-statistically significant increased mortality (Table 1). MAS patients were exclusively treated with immunosuppressives including pulse corticosteroids, while HLH patients were treated with chemotherapy or etoposide-based protocols.

Conclusion: MAS patients had overall better outcomes including shorter hospital stays than malignancy-associated HLH patients. While there were numerically fewer deaths in the MAS versus the malignancy-associated HLH cohort, one in five patients died from MAS during their initial hospitalization. Some notable differences in disease characteristics between the two groups include organomegaly and severity of cytopenias, which could be helpful in differentiating malignancy from rheumatologic etiologies of hemophagocytic syndromes.

Table 1: hospital course and outcomes of MAS vs. malignancy-associated HLH (n=number of patients; MAS=macrophage activation syndrome; HLH=hemophagocytic lymphohistiocytosis; SLE=systemic lupus erythematosus; AOSD=adult onset Still’s disease; DLBCL=diffuse large B-cell lymphoma).

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-spectrum-of-hemophagocytic-lymphohistiocytosis-autoimmunity-vs-malignancy/