Abstract
BackgroundSecondary hemophagocytic lymphohistiocytosis (sHLH) is a rare but fatal complication in idiopathic inflammatory myopathy (IIM) patients. The clinical value of radiological manifestations and serum cytokines remain unknown in this systemic crisis. This study aims to investigate the clinical value of PET/CT scan and cytokine profiles in predicting and understanding sHLH in IIM patients.MethodsAdult IIM patients who were admitted to the four divisions of the First Affiliated Hospital, Zhejiang University School of Medicine (FAHZJU) from January 1, 2017 to December 31, 2020 were reviewed. PET/CT scan, cytokine profiles, and other factors of patients who met the inclusion and exclusion criteria were collected and analyzed.ResultsSixty-nine out of 352 IIM patients were finally enrolled into the study. Ten patients developed sHLH and 70.0% of them died within 6 months. After false discovery rate (FDR) correction and multivariate logistic regression analysis, increased serum interferon (IFN)-γ level (p = 0.017), higher spleen mean standard uptake value (SUVmean, p = 0.035), and positivity of anti-MDA5 antibody (p = 0.049) were found to be significantly correlated with development of sHLH in IIM patients. The combination of serum IFN-γ, spleen SUVmean, and anti-MDA5 antibody found a balanced and satisfying predictor with a cutoff value of 0.047 and AUC of 0.946. A moderate correlation was identified between ferritin and spleen SUVmean (p = 0.001, r = 0.380) as well as serum IFN-γ(p = 0.001, r = 0.398). Before FDR correction, higher bilateral lung SUVmean (p = 0.034) and higher colon/rectum SUVmean (p = 0.013) were also observed in IIM patients who developed sHLH. By narrowing down to IIM patients with sHLH, anti-MDA5-antibody-positive DM patients tended to suffer from unfavorable outcome (p = 0.004) in Kaplan–Meier survival analysis.ConclusionIncreased serum level of IFN-γ, elevated splenic FDG uptake, and positivity of anti-MDA5 antibody were significantly correlated with development of sHLH in IIM patients. Lung and lower digestive tract might also be affected due to systemic immune activation in IIM patients with sHLH. In addition, splenic FDG uptake, in combination with serum IFN-γand anti-MDA5 antibody, was found valuable in predicting development of sHLH in IIM patients. Among IIM patients with sHLH, anti-MDA5-antibody-positive DM patients showed higher tendency for unfavorable outcome.
Highlights
Hemophagocytic lymphohistiocytosis (HLH) is a rare but lifethreatening disorder featuring multiple clinical manifestations including continuous fever, cytopenia, excessive cytokine production, splenomegaly, hyperferritinemia, coagulopathy, and multiorgan failure [1, 2], with an estimated annual incidence of 1 per 800,000 adults and 1 to 10 per 1 million children in western Europe and the USA [2]
With much remains unknown in these patients, it is necessary to continuously dig into the rare but fatal complication to figure out biomarkers and tools for early identification as well as impairment beyond bone marrow since Idiopathic inflammatory myopathy (IIM) and secondary HLH (sHLH) were both systemic crises
Based on data from four centers, the incidence of sHLH was 3.1% in adult IIM patients, which was similar to the preceding finding (4.2%) but much lower compared with those in adult-onset Still’s disease (AOSD) and systemic juvenile idiopathic arthritis (sJIA) (10.0%–30.0%) [7, 13]
Summary
Hemophagocytic lymphohistiocytosis (HLH) is a rare but lifethreatening disorder featuring multiple clinical manifestations including continuous fever, cytopenia, excessive cytokine production, splenomegaly, hyperferritinemia, coagulopathy, and multiorgan failure [1, 2], with an estimated annual incidence of 1 per 800,000 adults and 1 to 10 per 1 million children in western Europe and the USA [2]. With much remains unknown in these patients, it is necessary to continuously dig into the rare but fatal complication to figure out biomarkers and tools for early identification as well as impairment beyond bone marrow since IIM and sHLH were both systemic crises. Secondary hemophagocytic lymphohistiocytosis (sHLH) is a rare but fatal complication in idiopathic inflammatory myopathy (IIM) patients. This study aims to investigate the clinical value of PET/CT scan and cytokine profiles in predicting and understanding sHLH in IIM patients
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
