Successful Tocilizumab Therapy for Macrophage Activation Syndrome Associated with Adult-Onset Still's Disease: A Case-Based Review.

Eri Watanabe,Takeshi Yamashita,Hitoshi Sugawara,Akira Ishii,Chihiro Terai,Aya Oda

doi:10.1155/2016/5656320

Abstract

We report the case of a 71-year-old Japanese woman with adult-onset Still's disease (AOSD) in whom macrophage activation syndrome (MAS) developed despite therapy with oral high-dose prednisolone and intravenous methylprednisolone pulse therapy twice. She was successfully treated with tocilizumab (TCZ). Soon afterward, her fever ceased and high levels of both ferritin and C-reactive protein levels decreased. Her course was complicated by disseminated intravascular coagulation, cytomegalovirus infection, and Pneumocystis jirovecii pneumonia. After these were resolved, AOSD-associated MAS was well controlled. She was discharged on hospital day 87. Although biologics such as TCZ are becoming established for the treatment of AOSD, there is no recommended therapy for AOSD-associated MAS. Several biologics have been tried for this complication, but their efficacy and safety remain controversial. We reviewed reported cases of AOSD-associated MAS successfully treated with various biologics. TCZ initiation after adequate nonselective immunosuppressive therapy, such as methylprednisolone pulse therapy or a prednisolone-based combination of immunosuppressants, can be an effective treatment for AOSD-associated MAS. On the other hand, biologics given after insufficient immunosuppressive therapy may cause MAS. A strategy combining adequate immunosuppression and a biologic could be safe if special attention is given to adverse events such as opportunistic infections or biologic-associated MAS.

Highlights

Adult-onset Still’s disease (AOSD) is a rare systemic febrile inflammatory disorder of unknown etiology, with an estimated prevalence of 0.16 cases per 100,000 in western France [1], 0.4 cases per 100,000 in northern Norway [2], and 3.7 cases per 100,000 in Japan [3]
AOSD can cause macrophage activation syndrome (MAS) [3], which is an acute systemic inflammatory syndrome characterized by cytopenia, organ dysfunction, and coagulopathy associated with an excessive activation of macrophages, but there are no classification criteria of AOSD-associated MAS
We report the case of a patient with AOSD-associated MAS who had undergone nonselective immunosuppressive therapy with high-dose oral prednisolone (PSL) and intravenous methylprednisolone pulse therapy twice but who only improved after TCZ was administered

Summary

Introduction

Adult-onset Still’s disease (AOSD) is a rare systemic febrile inflammatory disorder of unknown etiology, with an estimated prevalence of 0.16 cases per 100,000 in western France [1], 0.4 cases per 100,000 in northern Norway [2], and 3.7 cases per 100,000 in Japan [3]. AOSD is characterized by four major symptoms: high spiking fever, arthralgia or arthritis, evanescent salmon-pink maculopapular rash, and hyperleukocytosis [4]. It is essentially diagnosed by exclusion of a wide range of disorders, including infection, malignancy, and autoimmune conditions [5]. We report the case of a patient with AOSD-associated MAS who had undergone nonselective immunosuppressive therapy with high-dose oral prednisolone (PSL) and intravenous methylprednisolone (mPSL) pulse therapy twice but who only improved after TCZ was administered. For improving clinical outcomes by prompt management, we review previously reported cases of AOSD-associated MAS in which the pathological evidence of hemophagocytosis was documented and treatment with a biologic succeeded

Case Report

Discussion

Our patient

Findings

Conclusions