Clinical features and correct diagnosis of macrophage activation syndrome

Abstract

Macrophage activation syndrome (MAS) is increasingly recognized among febrile hospitalized patients. Clinically, MAS resembles multiorgan dysfunction and shock. Laboratory features include hepatobiliary dysfunction, coagulopathy, pancytopenia, hyperferritinemia and markers of immune activation. Pathologically, hemophagocytosis is commonly seen but is only present in 60% of MAS patients. MAS, or secondary hemophagocytic lymphohistiocytosis (HLH), is triggered by infectious (e.g., herpes family viruses), rheumatologic (e.g., systemic lupus erythematosus [SLE]) and oncologic (e.g., T-cell leukemia) conditions. Formal HLH criteria, while specific, are frequently insensitive for MAS diagnosis. Thus, disease-specific (e.g., SLE) and generic MAS criteria have been published. Recently, novel criteria for MAS in children with systemic juvenile idiopathic arthritis (sJIA) were developed and are a key focus of this review.

A Heterozygous RAB27A Mutation Associated with Delayed Cytolytic Granule Polarization and Hemophagocytic Lymphohistiocytosis

“…An extensive infectious work-up was unrevealing with notably negative or normal evaluations for hepatitis A/B/C, HIV-1, EBV, CMV, Ehrlichia chaffeensis , and enterovirus. Her ANA test was negative, but her serum complement levels were low [C3 - 20 mg/dL (51–95), C4 - 3 mg/dL (8–44)], a feature of MAS (35). The bone marrow biopsy specimen was essentially normal except that CD163 staining revealed increased numbers of activated macrophages.…”

“…fHLH criteria are often too restrictive for a timely diagnosis of sHLH or MAS. Attempts to develop disease-specific sHLH/MAS criteria have been proposed but these are limited to a few diseases (8). Most recently, propensity scores for all forms of sHLH and MAS have been proposed which are not disease-specific, but have yet to be validated (9).…”

Recurrent macrophage activation syndrome since toddler age in an adolescent boy with HLA B27 positive juvenile ankylosing spondylitis

“…MAS is used to describe secondary hemophagocytic lymphohistiocytosis (HLH) associated with autoimmune disease. Primary HLH developed in genetic disorder, but secondary HLH is triggered by various etiologies including infection, medication, malignancies, and autoimmune diseases123).…”

Síndrome de ativação macrofágica: diferenças clínicas e laboratoriais entre pacientes com lúpus eritematoso sistêmico juvenil versus adulto

“…Esta é uma complicação hematológica rara e grave que pode estar presente em pacientes com infecções e doenças reumáticas ativas 28 . A SAM ocorre frente a um estado de hiperinflamação crônica e aumento da produção de citocinas inflamatórias, desencadeando então um processo que determina liberação de interferon gama e ativação do macrófago 29,30 .…”

“…Hemofagocitose é somente vista em até 60% dos casos no momento do diagnóstico de SAM, e pode ser completamente ausente em alguns pacientes, bem como em modelos animais com SAM 28,32 . Além disso, hemofagocitose pode não aparecer nos estágios iniciais da doença, como relatado para a artrite idiopática juvenil de início sistêmico 30,32 .…”