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SP0153 CALMING THE STORM IN ADULT MAS/HLH IN RHEUMATIC DISORDERS

Background: Hemofagocytic lymfohistiocytosis (HLH) is a rare and often overlooked clinical manifestation of an aberrant hyper inflammatory immune response leading to a fatal cytokine storm(1). Diagnostic criteria according to The HLH Study Group of the Histiocyte Society include fever, splenomegaly, bicytopenia, hypertriglyceridemia and/or hypofibrinogenemia, hyperferritinemia, low/or absent NK activity, increased soluble CD-25 levels and hemophagocytosis(2). Prompt recognition and differentiation from severe sepsis is essential to improve the outcome. HLH reflects a disbalanced immune system in response to infectious, malignancy, or autoinflammatory/autoimmune mediated triggers(1). The latter group of patients are regarded as having Macrophage Activation Syndrome (MAS-HLH)() In adults MAS-HLH comprises 12.5% of all HLH causing triggers(4). The most frequent immunological disorders associated with adult HLH-MAS are systemic lupus erythematosus and adult onset Still’s disease, but every other immunological disorder can be involved(4, 5). Treatment: Treatment of adults HLH patients requires swift recognition and an experienced team of specialists that are acquainted with the critical factors influencing the balance between co-morbidity, cytokine storm induced septic-like symptoms and toxicity of chemo-immunotherapy(6). In general, adult patients do not tolerate doses of etoposide that are given in (HLH-94 based) chemo-immunotherapy schedules that have been shown effective in children(7,8). Dose and frequency modifications of etoposide may avoid prolonged neutropenia, infectious complications or hepatic toxicity. The same precautions account for adults patients with MAS-HLH in which treatment differs from the HLH schedules. A step up approach depending on clinical features and severity is warranted(9, 10). High doses of corticosteroids are recognized as first-line treatment(9, 10). In patients with MAS-HLH and SLE steroids, cyclophosphamide or etoposide are given (10). Cyclosporine can be added in patients with insufficient immediate response(9). The cytokine blocking agent anakinra (anti-IL-1β) given in high doses is emerging as an alternative or additional treatment of adult MAS-HLH(11, 12, 13). Another promising cytokine blocker is anti-IL-6 (tocilizumab). Etoposide at a reduced dose can be initiated in patients with severe non-responsive and active disease or CNS-involvement(10). Conclusion: Awareness of the clinical emergency MAS-HLH in patients with autoinflammatory/autoimmune mediated disorders is essential for timely recognition and potential life-saving treatment. The management of MASH-HLH in adults requires a team of dedicated specialists with experience in the treatment of critically ill patients with immunological disorders and anticipation on its rapidly changing and deteriorating nature. References: [1] Janka GE. Familial and acquired hemophagocytic lymphohistiocytosis. Annu Rev Med. 2012;63:233-46 [2] Henter JI, Horne A, Arico M, et al. HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2007;48:124-131 [3] Carter SJ, Tattersall RS, Ramanan AV. Macrophage activation syndrome in adults: recent advances in pathophysiology, diagnosis and treatment. Rheumatology (Oxford). 2019;58(1):5-17. [4] Ramos-Casals M, Brito-Zerón P, López-Guillermo A, Khamashta MA, Bosch X. Adult haemophagocytic syndrome. Lancet. 2014;383:1503-1516 [5] 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: 1686–91 [6] Halyabar O, Chang MH, Schoettler ML, et al. Calm in the midst of cytokine storm: a collaborative approach to the diagnosis and treatment of hemophagocytic lymphohistiocytosis and macrophage activation syndrome. Pediatr Rheumatol Online J. 2019;17:7 [7] La Rosee P. Treatment of hemophagocytic lymphohistiocytosis in adults. Hematology Am Soc Hematol Educ Program. 2015;2015:190-196 [8] Ehl S, Astigarraga I, von Bahr Greenwood T, et al. Recommendations for the Use of Etoposide-Based Therapy and Bone Marrow Transplantation for the Treatment of HLH: Consensus Statements by the HLH Steering Committee of the Histiocyte Society. J Allergy Clin Immunol Pract. 2018;6:1508-1517 [9] Kumar B, Aleem S, Saleh H, Petts J, Ballas ZK. A Personalized Diagnostic and Treatment Approach for Macrophage Activation Syndrome and Secondary Hemophagocytic Lymphohistiocytosis in Adults. J Clin Immunol. 2017;37:638-643 [10] Gavand PE, Serio I, Arnaud L, et al. Clinical spectrum and therapeutic management of systemic lupus erythematosus-associated macrophage activation syndrome: A study of 103 episodes in 89 adult patients. Autoimmun Rev. 2017;16:743-749 [11] Wohlfarth P, Agis H, Gualdoni GA, et al. Interleukin 1 Receptor Antagonist Anakinra, Intravenous Immunoglobulin, and Corticosteroids in the Management of Critically Ill Adult Patients With Hemophagocytic Lymphohistiocytosis. J Intensive Care Med. 2017:885066617711386 [12] Schulert GS, Minoia F, Bohnsack J, et al. Effect of Biologic Therapy on Clinical and Laboratory Features of Macrophage Activation Syndrome Associated With Systemic Juvenile Idiopathic Arthritis. Arthritis Care Res (Hoboken). 2018;70:409-419 [13] Zhou S, Qiao J, Bai J, Wu Y, Fang H. Biological therapy of traditional therapy-resistant adult-onset Still”s disease: an evidence-based review. Ther Clin Risk Manag. 2018;14:167-171 Disclosure of Interests: None declared