The 2022 EULAR/ACR Points to Consider at the Early Stages of Diagnosis and Management of Suspected Haemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome (HLH/MAS)

Abstract

ObjectiveHaemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS) are life‐threatening systemic hyperinflammatory syndromes that can develop in most inflammatory contexts. They can progress rapidly, and early identification and management are critical for preventing organ failure and mortality. This effort aimed to develop evidence‐based and consensus‐based points to consider to assist clinicians in optimising decision‐making in the early stages of diagnosis, treatment and monitoring of HLH/MAS.MethodsA multinational, multidisciplinary task force of physician experts, including adult and paediatric rheumatologists, haematologist/oncologists, immunologists, infectious disease specialists, intensivists, allied healthcare professionals and patients/parents, formulated relevant research questions and conducted a systematic literature review (SLR). Delphi methodology, informed by SLR results and questionnaires of experts, was used to generate statements aimed at assisting early decision‐making and optimising the initial care of patients with HLH/MAS.ResultsThe task force developed 6 overarching statements and 24 specific points to consider relevant to early recognition of HLH/MAS, diagnostic approaches, initial management and monitoring of HLH/MAS. Major themes included the simultaneous need for prompt syndrome recognition, systematic evaluation of underlying contributors, early intervention targeting both hyperinflammation and likely contributors, careful monitoring for progression/complications and expert multidisciplinary assistance.ConclusionThese 2022 EULAR/American College of Rheumatology points to consider provide up‐to‐date guidance, based on the best available published data and expert opinion. They are meant to help guide the initial evaluation, management and monitoring of patients with HLH/MAS in order to halt disease progression and prevent life‐threatening immunopathology.

Comparison of plasma proteomic profiles of patients with Epstein‐Barr virus‐associated hemophagocytic lymphohistiocytosis and infectious mononucleosis

“…EBV DNA loads in four patients with EBV‐HLH (median; 93,556 IU/mL) were comparable to those of previous reports of EBV‐HLH 8,9 . Other conditions that can cause HLH, such as malignancies, rheumatic diseases, and immune deficiencies, were deemed unlikely from the laboratory data and clinical courses 10,11 …”

“…8,9 Other conditions that can cause HLH, such as malignancies, rheumatic diseases, and immune deficiencies, were deemed unlikely from the laboratory data and clinical courses. 10,11…”

Pathogenesis of Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome: A Case Report and Review of the Literature

“…In 2022, the European Alliance of Association for Rheumatology (EULAR) defined systemic hyperinflammation as a state of excessive immune activation that could lead to HLH/MAS. In addition, three categories of factors contributing to the development of HLH/MAS have been defined: (1) genetic causes, (2) predisposing conditions such as sJIA, lymphoma, and some metabolic diseases, and (3) triggering factors such as infections and immunotherapy [ 13 ].…”

Usefulness of interleukin-1 blockade in autoinflammatory diseases

“…A plethora of polygenic diseases appear to be mediated by IL-1 and respond to IL-1-targeted therapies also. These diseases include Still’s disease, macrophage activation syndrome (MAS), Schnitzler syndrome, gout, recurrent pericarditis, chronic recurrent multifocal osteomyelitis, hidradenitis suppurativa, pyoderma gangrenosum and acne, Kawasaki’s disease, Behçet’s disease and syndrome of periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) [ 4 , 5 ].…”