Baseline clinical features predicting macrophage activation syndrome in patients with systemic adult-onset Still's disease receiving interleukin-6 inhibitor treatment.

AIM: Macrophage activation syndrome (MAS), a severe complication of systemic adult-onset Still's disease (AOSD), has been reported to occur during interleukin-6 (IL-6) inhibitor treatment. However, predictors for MAS development are unknown. Therefore, this study investigated predictive features for MAS development after starting IL-6 inhibitor treatment in systemic AOSD patients. METHOD: In a single-center retrospective study involving systemic AOSD patients who were refractory to high-dose glucocorticoids with immunosuppressants and started IL-6 inhibitor treatment between April 2008 and March 2020, we compared the baseline clinical features between patients who developed AOSD flare with MAS features (MAS group) and those who did not (non-MAS group) during IL-6 inhibitor treatment. RESULTS: Only tocilizumab was used as an IL-6 inhibitor. Six of 14 refractory systemic AOSD patients developed AOSD flares with MAS features during tocilizumab treatment, including 4 who developed them shortly after initiation. The MAS group had significantly lower neutrophil counts, fibrinogen, and higher IL-18/C-reactive protein (CRP) ratio at starting tocilizumab (baseline) than the non-MAS group. Before starting tocilizumab, neutrophil counts were trending downward and upward in the MAS and non-MAS groups, respectively, with significant differences in changes. Receiver operating characteristic analysis showed that baseline neutrophil counts and fibrinogen and their changes before tocilizumab treatment and baseline IL-18/CRP ratio had significant discriminatory abilities for subsequent MAS development. CONCLUSION: We identified baseline laboratory features associated with MAS development after initiating an IL-6 inhibitor in refractory systemic AOSD patients. These features may reflect the suppression of IL-6 signaling, and further suppression of IL-6 signaling might trigger early-onset MAS.

Macrophage activation syndrome in patients with adult-onset Still's disease under tocilizumab treatment: A single-center observational study.

OBJECTIVES: Macrophage activation syndrome (MAS) developed under tocilizumab treatment poses a diagnostic challenge. This study aims to demonstrate the frequency and the clinical features of MAS developed in patients with adult-onset Still's disease (AOSD) receiving tocilizumab. METHODS: The consecutive AOSD patients treated with tocilizumab in our institution from April 2008 to March 2020 were studied. The frequency of clinically diagnosed MAS during tocilizumab treatment, their conformity to the several criteria relevant for MAS, and laboratory characteristics compared to AOSD flare were investigated. RESULTS: Of the 20 AOSD patients treated with tocilizumab, six developed clinically diagnosed MAS, four immediately after starting tocilizumab and two after long-term treatment. Some of them had already met the MAS criteria before starting tocilizumab. At MAS diagnosis, although some did not meet the MAS criteria due to lack of fever and/or the lower ferritin levels, all consistently showed sharp increases in ferritin along with marked abnormal changes in two or more different markers of organ damage, unlike the AOSD flares. CONCLUSION: MAS is not a rare complication in AOSD patients receiving tocilizumab. The clinical similarities between systemic AOSD and MAS, and substantial alterations in MAS features by inhibition of interleukin-6 signaling may limit the utility of the existing diagnostic/classification criteria in diagnosing MAS under tocilizumab treatment. The emergence of abnormalities in MAS-related organ damage markers with a rapid elevation of ferritin should be considered as MAS development in AOSD patients receiving tocilizumab even if the patients are afebrile or have relatively low ferritin levels.

Reintroduction of tocilizumab elicited macrophage activation syndrome in a patient with adult-onset Still's disease with a previous successful tocilizumab treatment.

Macrophage activation syndrome (MAS) is a form of secondary hemophagocytic lymphohistiocytosis and is a rapidly progressive, life-threatening complication of adult-onset Still's disease (AOSD). An anti-IL-6 receptor monoclonal antibody, tocilizumab, has shown to be effective in the treatment of AOSD but may precipitate MAS in patients with AOSD. The precise mechanism of MAS developed during anti-cytokine biologic agents remains unknown, but selective inhibition of a subset of pathways could impact other immune signalling pathways and trigger MAS. We herein describe a case of AOSD with the opposite outcomes of tocilizumab therapy, remission and development of MAS, after tocilizumab treatment at the initial flare and the relapse. From the comparison of clinical characteristics and concomitant treatment around the time of starting tocilizumab in both flares, the type and intensity of concomitant immunosuppressive therapy might strongly affect MAS development during tocilizumab therapy.

[Influence of postoperative lens status on intraocular pressure and corneal endothelium following vitrectomy with silicone oil tamponade].

PURPOSE: To evaluate the influence of postoperative lens status on intraocular pressure elevation and corneal endothelial cell loss in patients who underwent pars plana vitrectomy with silicone oil injection for the management of complex retinal detachment. PATIENTS AND METHODS: The medical records of 80 eyes of 79 patients who underwent silicone oil removal were reviewed retrospectively. For analysis, eyes were divided by postoperative lens status into 2 groups: pseudophakic eyes (IOL group) and aphakic eyes(aphakic group). RESULTS: There was a significantly greater decrease in intraocular pressure after silicone oil removal in the aphakic group but not in the IOL group. As compared with the IOL group, the aphakic group showed a significant reduction in endothelial cell density at the time of silicone oil removal. CONCLUSION: Patients who underwent silicone oil injection with pseudophakic eyes may have a lower risk of intraocular pressure elevation and corneal endothelial cell loss than those with aphakic eyes.

Characteristics and surgical outcomes of pediatric rhegmatogenous retinal detachment.

PURPOSE: To describe the characteristics and surgical outcomes of pediatric rhegmatogenous retinal detachment. METHODS: A retrospective study of pediatric patients (15 years old or younger) who had undergone primary surgery for rhegmatogenous retinal detachment was conducted. Patients were divided into five groups according to the predisposing factors: trauma (group 1), myopia (group 2), atopic dermatitis (group 3), congenital or developmental anomalies (group 4), and others (group 5). RESULTS: A total of 48 eyes of 44 patients were included in this study. There were 18 eyes (37.5%) in group 1, twelve eyes (25.0%) in group 2, six eyes (12.5%) in group 3, five eyes (10.4%) in group 4, and seven eyes (14.6%) in group 5. The initial retinal reattachment rate was 89% in group 1, 100% in group 2, 83% in group 3, 20% in group 4, and 86% in group 5 (P = 0.002). The final retinal reattachment rate was 100% in group 1, 100% in group 2, 100% in group 3, 80% in group 4, and 86% in group 5 (P = 0.16). The frequency of visual acuity of 0.1 or better after surgery was 100% in group 1, 92% in group 2, 83% in group 3, 40% in group 4, and 71% in group 5 (P = 0.01). CONCLUSION: The overall surgical outcome was successful, but the patients in group 4 had the lowest initial reattachment rate and the worst visual prognosis.