Background Macrophage activation syndrome (MAS) is a severe complication of systemic juvenile idiopathic arthritis (sJIA) often leading to multiple organ failure. Biological agents including tocilizumab are used extensively in the treatment of JIA, but can trigger MAS development in some patients and therefore MAS is often considered as a contraindication to tocilizumab. We have experience of successful use of tocilizumab in sJIA complicated by MAS.
Objectives Clinical narrative of MAS in two sJIA patients.
A 10 year old boy has suffered from sJIA for over 2 years, presents with fever, serositis, lymphadenopathy, hepatomegaly, polyarthritis, leukocytosis 22×109, CRP 120 g/L, ESR 64 mm/hr. Treatment with glucocorticoids (GCs), methotrexate, and cyclosporine A was inadequately effective. While on intravenous administration of methotrexate 30 mg the patient presented with persistent febrile hyperthermia, hepatosplenomegaly, nephritis, rapid decrease in ESR - 2 mm/hr, cytopenia (platelet count 116×1012, WBC 5.4×109, HB 90 g/L), ferritin – 905 µg/L, transaminase increases (LDH - 723 U/L, ALT), increase in triglycerides, and decrease in fibrinogen. The use of methylprednisolone 15 mg/kg for 3 days, GCs, cyclosporine and administration of tocilizumab 10 mg/kg every 12 weeks resulted in MAS resolution. Normalization of LDH and ferritin was observed after the second administration of tocilizumab.
A 3 year old girl with sJIA and primary hyperinsulinism has been ill for 1 year. Following 2-month therapy with IL-1 receptor antagonist anakinra 2-4 mg/kg she developed sJIA relapse (fever, rash, polyserositis, arthritis) with symptoms of MAS (uncontrolled fever, CNS lesion, nephritis, splenomegaly +10 cm, hepatomegaly, lymphadenopathy, ESR 10 mm/hr, thrombocytopenia 115×1012, anaemia - HB 89 g/l, ferritin >10000 µg/L, transaminase increases - LDH 1702 U/L, increase in triglycerides; coagulation disorders. Anakinra was discontinued, GCs were administered orally 1 mg/kg, following which the disease activity persisted but cytopenia resolved. After 2 weeks, tocilizumab 12 mg/kg iv once every 2 weeks was administered with favorable effect. Normalization of ferritin and LDH was achieved after the third administration of tocilizumab. No adverse events were observed.
The both patients continue to receive tocilizumab infusions every 2 weeks with good therapeutic response corresponding to ACR70-90%.
Conclusions Our experience with tocilizumab given in combination with GCs in patients with sJIA complicated by MAS showed its high efficacy and good tolerability superior to that of GCs alone.
Journal of Rheumatology.2011;38
Current Opinion inRheumatology. 2002;14
Disclosure of Interest None Declared