Adult macrophage activation syndrome-haemophagocytic lymphohistiocytosis: 'of plasma exchange and immunosuppressive escalation strategies' - a single centre reflection.

Abstract

OBJECTIVE:

In the context of systemic autoimmunity, that is systemic lupus erythematosus (SLE) or adult-onset Still's disease (AOSD), secondary haemophagocytic lymphohistiocytosis (HLH; also referred to as macrophage activation syndrome (MAS) or more recently MAS-HLH) is a rare and potentially life-threatening complication. Pathophysiological hallmarks are aberrant macrophage and T cell hyperactivation and a systemic cytokine flare, which generate a sepsis-like, tissue-damaging, cytopenic phenotype. Unfortunately, for adult MAS-HLH we lack standardized treatment protocols that go beyond high-dose corticosteroids. Consequently, outcome data are scarce on steroid refractory cases. Aside from protocols based on treatment with calcineurin inhibitors, etoposide, cyclophosphamide and anti-IL-1, favourable outcomes have been reported with the use of intravenous immunoglobulin (IvIG) and plasma exchange (PE).

METHODS:

Here we report a retrospective series of steroid refractory MAS-HLH, the associated therapeutic regimes and outcomes.

RESULTS:

In this single-centre experience, 6/8 steroid refractory patients survived (median follow-up: 54.4 (interquartile range: 23.3-113.3) weeks). All were initially treated with PE, which induced partial response in 5/8 patients. Yet, all patients required escalation of immunosuppressive therapies. One case of MAS-HLH in new-onset AOSD had to be escalated to etoposide, whereas most SLE-associated MAS-HLH patients responded well to cyclophosphamide. Relapses occurred in 2/8 cases.

CONCLUSION:

Together, early use of PE is at most a supportive measure, not a promising monotherapy of adult MAS-HLH. In refractory cases, conventional cytoreductive therapies (i.e. cyclophosphamide and etoposide) constitute potent and reliable rescue approaches, whereas IvIG, anti-thymoglobulin, and biologic agents appear to be less effective.

• Authors: G Lorenz, L Schul, F Schraml, K M Riedhammer, H Einwächter, M Verbeek, J Slotta-Huspenina, C Schmaderer, C Küchle, U Heemann, P Moog
• Journal: Lupus (Lupus) Vol. 29 Issue 3 Pg. 324-333 (Mar 2020) ISSN: 1477-0962 [Electronic] England
• PMID: 32013725 (Publication Type: Journal Article)

Chemical References

• Adrenal Cortex Hormones
• Cytokines
• Immunoglobulins, Intravenous
• Immunosuppressive Agents
• Cyclosporine

Topics

• Adrenal Cortex Hormones (therapeutic use)
• Adult
• Aged
• Cyclosporine (therapeutic use)
• Cytokines (metabolism)
• Female
• Humans
• Immunoglobulins, Intravenous (therapeutic use)
• Immunosuppressive Agents (therapeutic use)
• Lupus Erythematosus, Systemic (complications, therapy)
• Lymphohistiocytosis, Hemophagocytic (etiology, therapy)
• Macrophage Activation Syndrome (etiology, therapy)
• Male
• Middle Aged
• Plasma Exchange (methods)
• Retrospective Studies
• Sepsis (etiology, therapy)
• Still's Disease, Adult-Onset (complications, therapy)
• Young Adult