G Lorenz1, L Schul1, F Schraml1, K M Riedhammer1, H Einwächter2, M Verbeek3, J Slotta-Huspenina4, C Schmaderer1, C Küchle1, U Heemann1, P Moog1. 1. Department of Nephrology, Klinikum rechts der Isar, Technical University Munich, Munich, Germany. 2. II Medizinische Klinik, Klinikum rechts der Isar, Technical University Munich, Munich, Germany. 3. III Medizinische Klinik, Klinikum rechts der Isar, Technical University Munich, Munich, Germany. 4. Institute of Pathology, Klinikum rechts der Isar, Technical University Munich, Munich, Germany.
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.
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.