Hemophagocytic lymphohistiocytosis (HLH) is a well-recognised complication of systemic lupus erythematosus (SLE). In one small case series, HLH was noted in approximately 5% of patients with lupus.¹ Differentiating lupus flare from HLH can be challenging, since both can cause fever and cytopenia. A recent review of published literature included studies that combined information about a total of 249 patients with lupus and HLH.² HLH episodes were described concomitant with first lupus presentation, at the time of subsequent lupus flare and associated with a secondary triggering infection. Other recognized HLH drivers in people with SLE include drugs, malignancy and pregnancy. Mortality is quoted to be up to 19%.²

Epidemiological studies show that the number of people diagnosed with HLH of all causes has increased significantly over the last 20 years.³ This rise is likely multifactorial in origin, in part due to increased recognition and in part due to complications of newer therapies including chimeric antigen receptor (CAR)-T cell therapy, and novel infections such as COVID-19. The risk of HLH in patients with lupus treated with CAR-T cell therapy is not yet known.

In recent years there has been the development of international guidelines for the identification, diagnosis and initial management of HLH.^{4 5} These guidelines describe a framework to approach any patient unwell with HLH, which include the work-up and rapid diagnosis of lupus as a possible HLH driver. There is a clear focus on the need for cross-speciality working, which is associated with improved outcomes.

Managing the patient with HLH complicating lupus involves managing the lupus, any additional trigger, and controlling the secondary HLH related hyperinflammation. This will sometimes require using multiple immunosuppressive therapies in parallel. From the HLH perspective, this may include anakinra, intravenous immunoglobulin, ciclosporin, and in the most unwell patients, etoposide. Prospective trials of managing HLH in patients with SLE are lacking.

References

1. Fukaya S, Yasuda S, Hashimoto T, et al. Clinical features of haemophagocytic syndrome in patients with systemic autoimmune diseases: Analysis of 30 cases. Rheumatology (Oxford). 2008;47(11):1686–91. doi: 10.1093/rheumatology/ken342.

2. Aziz A, Castaneda EE, Ahmad N, et al. Exploring macrophage activation syndrome secondary to systemic lupus erythematosus in adults: A systematic review of the literature. Cureus. 2021;13(10):e18822. doi: 10.7759/cureus.18822.

3. West J, Stilwell P, Liu H, et al. Temporal trends in the incidence of hemophagocytic lymphohistiocytosis: A nationwide cohort study from England 2003–2018. Hemasphere. 2022;6(11):e797. doi: 10.1097/HS9.0000000000000797.

4. Cox MF, Mackenzie S, Low R, et al. Diagnosis and investigation of suspected haemophagocytic lymphohistiocytosis in adults: 2023 hyperinflammation and HLH across speciality collaboration (HiHASC) consensus guideline. Lancet Rheumatol. 2024;6(1):e51-e62. doi: 10.1016/S2665-9913(23)00273-4.

5. Shakoory B, Geerlinks A, Wilejto M, et al. The 2022 EULAR/ACR points to consider at the early stages of diagnosis and management of suspected haemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS). Arthritis Rheumatol. 2023;75(10):1714–32. doi: 10.1002/art.42636.

Learning Objectives At the end of this presentation participants will be able to:

• Describe the approach to a patient who presents with HLH and unknown drivers

• Describe which patients with lupus are most at risk of HLH and explain how to recognise the condition early

• Discuss how a patient with lupus and HLH should be treated

• Describe the role of cross-speciality working for all patients with HLH