Macrophage activation syndrome: early diagnosis is key

Abstract

Macrophage activation syndrome (MAS) is a life-threatening condition, and it is a subset of hemophagocytic lymphohistiocytosis (HLH). The clinical features include a persistent high-grade fever, hepatosplenomegaly, lymphadenopathy, hemorrhagic manifestations, and a sepsis-like condition. From the clinical features, it is usually difficult to differentiate between a true sepsis, disease flare-ups, or MAS. Although the laboratory abnormalities are similar to those of a disseminated intravascular coagulation, which shows pancytopenia, coagulopathy, hypofibrinogenemia, and an elevated d-dimer test, it can also be a late stage of MAS. Currently, MAS is still underrecognized and usually results in delayed in diagnosis, which leads to high morbidity and mortality. This literature review was conducted in the context of the clinical manifestations and the laboratory abnormalities in MAS, which might provide some clues for an early diagnosis. The best ways for an early recognition and a satisfactory diagnosis were based on the relative changes in the overall parameters from the baseline, together with a thorough and continuous physical examination for these kinds of patients. At present, diagnostic criteria have been proposed for HLH, MAS-associated systemic juvenile idiopathic arthritis, and an MAS-associated systemic lupus erythematosus. Therefore, selecting the proper diagnostic criteria for use is essential because not all of the criteria are suitable for every autoimmune disease.

Continuous Intravenous Anakinra Infusion to Calm the Cytokine Storm in Macrophage Activation Syndrome

“…Although similar in their inflammatory pathophysiology, primary HLH, a familial or genetic syndrome, and secondary HLH (sHLH), usually triggered by infectious, rheumatologic, or hematologic/oncologic syndromes, are recognized as separate subsets of the disease spectrum (4‐6). Macrophage activation syndrome (MAS) is a subset of HLH often associated with rheumatologic diseases.…”

“…The diagnosis of MAS is often delayed because of the lack of widely accepted diagnostic criteria specific to this disease (12). In addition, the lack of a true guideline‐directed therapy for MAS results in high mortality (6). As such, early diagnosis and rapid initiation of therapies aimed at reducing systemic inflammation is critical to the management of MAS.…”

“…Treatment initiation for MAS generally starts with high‐dose glucocorticoid monotherapy, with the subsequent use of additional immunosuppressive agents in refractory cases (6,13,14). In particularly resistant cases, the HLH‐2004 protocol may be followed (14).…”

“…Over the past few years, with the advent of biologics and immunotherapies, case reports have described other therapeutic options for MAS, including intravenous immunoglobulin (IVIG) and biologics targeting different phases of the cytokine cascade (6). Anakinra, a recombinant IL‐1 receptor antagonist, is currently US Food and Drug Administration (FDA) approved for the treatment of rheumatoid arthritis and neonatal‐onset multisystem inflammatory disease.…”

Hemophagocytic Lymphohistiocytosis and Inflammatory Bowel Disease: Case Report and Systematic Review

“…Examples of viral triggering factors are herpesvirus (Epstein-Barr virus [EBV], Cytomegalovirus [CMV], VHH8, HSV), HIV, HTLV, hepatitis virus (A, B and C), measles, mumps, rubella, adenovirus, dengue, hantavirus, parvovirus B19, enterovirus and influenza [3]. Macrophage activation syndrome is a form of secondary HLH that occurs in patients with autoimmune diseases [4]. The most frequent are systemic juvenile idiopathic arthritis, followed by systemic lupus erythematosus, Kawasaki disease and juvenile dermatomyositis [5].…”