Background: Adult-onset Still’s disease (AOSD) is associated with the development of macrophage activation syndrome (MAS) [1], sometimes termed secondary haemophagocytic lymphohistiocytosis (sHLH), a severe hyperinflammatory state with high mortality. Successful management of AOSD and MAS is contingent on early identification and treatment of the syndromes and any triggers, with aggressive immunosuppression in acutely unwell patients [2].

Objectives: To describe the case of a patient with newly diagnosed AOSD who developed severe MAS requiring ICU admission and immunosuppression with high-dose glucocorticoids, tocilizumab and anakinra.

Methods: Case report

Results: A 24-year-old woman attended hospital with a 4 month history of fever, arthralgia, rash and later dry cough. She became hypoxic and was admitted to the ICU for ventilation and vasopressor support. Imaging revealed splenomegaly, pleural effusions and lung consolidation but there was no response to antibiotics and no clear evidence of infection. Cytomegalovirus (CMV) DNA was initially absent, with IgG avidity indicating prior exposure. Bloods confirmed significant inflammation (CRP 107 mg/L, ferritin 6154 μg/L, ESR 47mm/hr) without disordered haematopoiesis. A bone marrow aspirate showed no haemophagocytosis. After extensive investigation a diagnosis of AOSD was made given the fulfilment of the Yamaguchi criteria and absence of evidence of an alternative driver of inflammation.

The patient deteriorated further, with deranged liver chemistry, rising CRP, triglycerides and ferritin (>100,000 μg /L), and trilineage cytopenia raising concern for MAS. This was managed by treating the presumed trigger (AOSD) with intravenous methylprednisolone (IVMP, 3x 500mg then 32mg daily) and anakinra (100mg twice daily). She developed a CMV viraemia that progressed despite aciclovir and later valganciclovir, which was switched to foscarnet and CMV immunoglobulin. The viraemia then stabilised and improved.

Due to persistent pyrexia, tachycardia, and elevated inflammatory markers, further IVMP (3x250mg), increased anakinra doses (100mg IV TDS) and intravenous immunoglobulin (2x60g) were given. A repeat bone marrow biopsy was consistent with MAS and testing for HLH-associated genes was negative.

The patient became increasingly hypoalbuminaemic and oedematous, developing acute kidney injury requiring continuous haemodiafiltration in the ICU. Anakinra was increased to 500mg daily in divided doses. The blood counts improved transiently, before the ferritin rose sharply again, with fevers and broad-spectrum antimicrobials continuing. Cytokine profile testing at this point revealed significant elevation in IL-1b and IL-6. Tocilizumab 8mg/kg fortnightly was added to existing therapy.

After tocilizumab initiation the inflammatory markers, blood counts and clinical state improved, though the patient remained hypertensive despite numerous antihypertensives. She left the ICU ten weeks after initial presentation. Corticosteroids and anakinra were weaned and she was discharged on tocilizumab monotherapy. Renal function did not return, and she continues outpatient haemodialysis.

Conclusion: The evidence base for effective therapies in MAS is poor. Reports exist of the use of either anakinra or tocilizumab [3] but not both agents in combination. In this case, cytokine blockade with both agents produced significant clinical improvement in a critically unwell patient.

REFERENCES:

[1]Carter, J et al. “Macrophage activation syndrome in adults: recent advances in pathophysiology, diagnosis and treatment.” Rheumatology (Oxford, England ) vol. 58,1 (2019): 5-17.

[2]Buyse, S et al. “Critical care management of patients with hemophagocytic lymphohistiocytosis.” Intensive care medicine vol. 36,10 (2010): 1695-702.

[3]Gilboa, M et al. “Macrophage activation syndrome complicating rheumatic diseases in adults: case-based review.” Rheumatology international vol. 40,4 (2020): 663-669.

Acknowledgements: We acknowledge the kind permission of the patient for her case to be used for educational purposes, and to all those involved in her care during the acute admission

Disclosure of Interests: None declared