Exploring Macrophage Activation Syndrome Secondary to Systemic Lupus Erythematosus in Adults: A Systematic Review of the Literature

Abstract

Among the autoimmune (AI) diseases, systemic lupus erythematosus (SLE) is known to mimic various disease processes and this can lead to under-diagnosis of macrophage activation syndrome (a dire complication). We aimed at performing a systematic review to identify trigger factors that could lead to the development of macrophage activation syndrome (MAS) in patients with SLE as well as identify factors that can affect mortality. We searched the following databases to extract relevant articles: PubMed, ScienceDirect, Cochrane library, Pro-Quest, and Google Scholar. We used search terms including but not limited to hemophagocytic syndromes OR hemophagocytic lymphohistiocytosis OR macrophage activation syndrome OR HLH OR secondary hemophagocytic lymphohistiocytosis AND systemic lupus erythematosus OR SLE. We screened the articles first by titles and abstracts and later by full text. After the application of our eligibility criteria, we identified eight studies to include in our final synthesis. The studies showed that lupus flare itself, as well as, time to onset and high systemic lupus erythematosus disease activity index (SLEDAI) scores, were major risk factors that led to the development of MAS. In addition, infections followed by drugs, underlying malignancy, and pregnancy were other potential trigger factors identified. Studies also detected that MAS development led to high intensive care unit (ICU) admissions and in-hospital mortalities with C-reactive protein (CRP) levels, age, presence of infection, leukopenia, thrombocytopenia, MAS throughout the hospital stay, and high liver function tests (LFTs) as signs of poor prognosis. Additionally, ferritin levels, LFTs, and triglyceride levels formed an important part of diagnostic criteria. However, our review was limited due to the absence of prospective studies and heterogeneity in the studies seen. More studies need to be done to identify various factors leading to hemophagocytic lymphohistiocytosis (HLH) in autoimmune diseases with validated criteria for MAS secondary to autoimmune diseases.

A Case of Macrophage Activation Syndrome Manifesting as the Initial Presentation of Systemic Lupus Erythematosus

“…Diagnosis of MAS is based on HLH-2004 clinical criteria, which require at least the presence of molecular diagnosis consistent with HLH or five out of eight findings that include fever >38.5 °C, splenomegaly, peripheral blood cytopenias (at least any two), hypertriglyceridemia, hemophagocytosis in either bone marrow, lymph node, spleen or liver biopsy, low or absent natural killer (NK) cell activity, hyperferritinemia, and elevated soluble interleukin-2 receptor alpha chain (CD25) or elevated chemokine (C-X-C motif) ligand 9 (CXCL9) [ 1 ]. Additional common findings include transaminitis, coagulopathy, hyponatremia, hypoalbuminemia, elevated lactate dehydrogenase (LDH), C-reactive protein, and D-dimer [ 12 - 13 ].…”

“…Macrophage activation syndrome (MAS) is a life-threatening complication of an autoimmune rheumatologic disease that falls in the spectrum of dysregulated immune disorders called hemophagocytic lymphohistiocytosis (HLH ) [1]. MAS/HLH is characterized by overwhelming inflammation and cytokine storm resulting from unchecked activation/proliferation of macrophages and T lymphocytes, ultimately resulting in multiorgan failure if untreated [1][2][3]. While MAS has been reported in almost any rheumatologic condition, the reported incidence of MAS in SLE is about 0.9% to 4.6% [4], with mortality reaching up to 35% [5][6][7].…”

“…While MAS has been reported in almost any rheumatologic condition, the reported incidence of MAS in SLE is about 0.9% to 4.6% [ 4 ], with mortality reaching up to 35% [ 5 - 7 ]. However, this incidence of MAS in SLE could be underestimated due to being misdiagnosed as a flare-up or complication of SLE [ 1 ]. We report a case of MAS presenting as an initial manifestation of a newly diagnosed SLE…”

Case report and literature review: Hemophagocytic lymphohistiocytosis in a pregnant woman with systemic lupus erythematosus with Syntaxin 11 gene defect

“…In Cohen et al.’s ( 30 ) study, increasing SLEDAI scores were found to be a risk factor for MAS development in SLE patients. Other studies showed that lupus flare itself, as well as time to onset and high SLEDAI scores, were crucial risk factors that led to the development of MAS ( 31 ).…”

“…Other studies showed that lupus flare itself, as well as time to onset and high SLEDAI scores, were crucial risk factors that led to the development of MAS (31).…”