Detection and Prediction of Macrophage Activation Syndrome in Still’s Disease

Abstract

Distinguishing between macrophage activation syndrome (MAS) and a simple flare of Still’s disease (SD) may be challenging. We sought to clarify the clinical features and outcome of MAS in SD and to explore predictive factors of MAS development. Demographic and clinical data, treatments, and outcomes were recorded in a cohort of 206 SD patients. SD patients with and without MAS were compared. To explore predictive factors for the development of MAS, patients were compared at the time of SD diagnosis. Twenty (9.7%) patients experienced MAS, which was inaugural in 12 cases. Patients with MAS were more likely to have hepatomegaly (OR, 3.71; 95% CI, 1.14–11.2; p = 0.03) and neurological symptoms (OR, 4.43; 95% CI, 1.08–15.3; p = 0.04) than patients without MAS. Cytopenias, abnormal liver tests, and coagulation disorders were significantly more frequent in patients with MAS; lactate dehydrogenase and serum ferritin levels were significantly higher. An optimized threshold of 3500 μg/L for serum ferritin yielded a sensitivity (Se) of 85% and a negative predictive value (NPV) of 97% for identifying patients with/without MAS. Survival analysis showed that a high ferritin level at the time of SD diagnosis was predictive of MAS development (p < 0.001). Specific factors, including neurological symptoms, cytopenias, elevated LDH, and coagulopathy, may contribute to the early detection of MAS. Extreme hyperferritinemia at the onset of SD is a prognostic factor for the development of MAS.

Evaluation of Glycosylated Ferritin in Adult-Onset Still’s Disease and Differential Diagnoses

“…Yet, considering our findings, the best recommendation is probably to alert the clinician who has to manage a patient with overlapping symptoms that the main (and almost only) differential diagnosis of AOSD flare is a hematological malignancy complicated by HLH. Javaux et al have published different parameters that are useful for distinguishing HLH and AOSD flare, including lower fibrinogen, leukocyte and platelet counts, but no difference in GF fraction [ 7 ]. Another study showed that interleukin (IL)-18 levels have high accuracy for the differential diagnosis of AOSD and HLH but IL-18 is rarely available routinely [ 19 ].…”

“…Importantly, GF reduction has been observed in other conditions, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or hemophagocytic lympho-histiocytosis (HLH) [ 4 , 5 , 6 ]. It is noteworthy that Still’s disease and HLH are closely related, as 5–19.5% of patients have overt HLH [ 7 , 8 , 9 , 10 , 11 ], and 16.7–53% have bone marrow features of hemo-phagocytosis [ 12 , 13 , 14 ]. Some authors have even raised the question of a unique continuum between the two diseases.…”

Adult-Onset Still’s Disease—A Complex Disease, a Challenging Treatment

“…Although they are primarily designed for research, most physicians use the Yamaguchi [ 9 ] and Fautrel [ 9 , 14 ] classification criteria for AOSD in practice. These two are the most sensitive and specific diagnostic criteria [ 15 ].…”

“…Odynophagia and occasionally pharyngitis are symptoms that accompany fever [ 7 ]. Additionally, increased liver enzymes, lymphadenopathy, hepatosplenomegaly, hyperferritinemia, and white-blood-cell count (WBC) of 10,000/mm 3 , primarily neutrophilic polymorphonuclear (PMNs) cells, are frequently detected and supportive of the diagnosis [ 8 , 9 ]. Myalgia is common, although myositis and polymyositis are rare [ 1 ].…”

Biomarkers in Systemic Juvenile Idiopathic Arthritis, Macrophage Activation Syndrome and Their Importance in COVID Era

“…The dramatic decrease in the number of figurative elements of the blood, coagulation abnormalities, significant liver cytolysis, and the increase in LDH as well as serum ferritin are important laboratory data for the identification of patients with sJIA-MAS. A concentration above 3500 μg/L has 85% sensitivity and 97% predictability for sJIA-MAS, and extreme hyperferritinemia detected at the time of sJIA diagnosis may be a biomarker to foreshadow sJIA-MAS [ 227 ].…”