Tocilizumab modifies clinical and laboratory features of macrophage activation syndrome complicating systemic juvenile idiopathic arthritis

Masaki Shimizu,Mariko Mohri,Hiroaki Umebayashi,Noriko Kinjo,Yuka Okura,Junko Yasumura,Kenichi Nishimura,Naomi Iwata,Mao Mizuta,Nami Okamoto,Hiroyuki Wakiguchi,Masato Yashiro,Takahiro Yasumi,Masaaki Mori,Tomohiro Kubota,Yasuo Nakagishi

doi:10.1186/s12969-020-0399-1

Abstract

BackgroundThis study aimed to determine the influence of tocilizumab (TCZ) in modifying the clinical and laboratory features of macrophage activation syndrome (MAS) complicating systemic juvenile idiopathic arthritis (s-JIA). Furthermore, we assessed the performance of the 2016 MAS classification criteria for patients with s-JIA-associated MAS while treated with TCZ.MethodsA panel of 15 pediatric rheumatologists conducted a combination of expert consensus and analysis of real patient data. Clinical and laboratory features of s-JIA-associated MAS in 12 TCZ-treated patients and 18 untreated patients were evaluated. Possible MAS was defined as having characteristic laboratory features but lack of clinical features of MAS, or atypical MAS, or early treatment that prevented full-blown MAS.ResultsClinically, the TCZ-treated patients with s-JIA-associated MAS were less likely febrile and had significantly lower ferritin, triglyceride, and CRP levels than the untreated patients with s-JIA-associated MAS. Other laboratory features of MAS including lower platelet counts and lower fibrinogen were more pronounced in TCZ-treated patients. The TCZ-treated patients with s-JIA-associated MAS were less likely to be classified as MAS based on the MAS classification criteria (25% vs 83.3%, p < 0.01). This is ascribed to the absence of fever or insufficient ferritin elevation, compared with the untreated patients.ConclusionTCZ could modify the clinical and laboratory features of s-JIA-associated MAS. When evaluating the s-JIA patients while treated with TCZ, it is not applicable to use MAS classification criteria. Care must be taken to not underdiagnose MAS based on the MAS classification criteria.

Highlights

This study aimed to determine the influence of tocilizumab (TCZ) in modifying the clinical and laboratory features of macrophage activation syndrome (MAS) complicating systemic juvenile idiopathic arthritis (s-JIA)
The pathophysiology of s-JIA remains obscure, it has been suggested that s-JIA is an auto-inflammatory condition driven by continuous activation of innate immune pathways, leading to aberrant induction of proinflammatory cytokines, such as interleukin (IL)-6, IL-1β, and IL-18 [1]
No significant differences were noted in other clinical features including hepatosplenomegaly and lymphadenopathy

Summary

Introduction

This study aimed to determine the influence of tocilizumab (TCZ) in modifying the clinical and laboratory features of macrophage activation syndrome (MAS) complicating systemic juvenile idiopathic arthritis (s-JIA). Macrophage activation syndrome (MAS) is a severe, potentially life-threatening complication of rheumatic diseases, which is clinically characterized by fever, hepatosplenomegaly, lymphadenopathy, profound depression of all three blood cell lines, deranged liver function, intravascular coagulation, and central nervous system dysfunction. The hallmark of MAS is an uncontrolled and dysfunctional immune response with s-JIA is a severe systemic inflammatory disorder of unknown etiology characterized by arthritis and systemic features such as spiking fever, skin rash, generalized (2020) 18:2 lymphadenopathy, hepatosplenomegaly, and serositis. TCZ has been reported to modify and mask the clinical symptoms and laboratory findings of MAS in patients with s-JIA [3, 4]

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