Background Macrophage activation syndrome (MAS) is a potentially fatal and hard to manage complication of rheumatic diseases (RD). MAS early diagnosis is a real challenge, whiles timely and adequate therapy has the paramount importance for reduction of associated mortality.
Objectives To analyze clinical and laboratory parameters, therapeutic regimens and MAS outcomes in pediatric patients with RD.
Methods Retrospective analysis of 35 RD and MAS patients in the last 5 years.
Results MAS was diagnosed in 35 pediatric RD pts (17girls/18boys) during the period of 2010-2014y: in 25 with sJIA, 5 - SLE, 2 - JDM, 1 overlap-syndrome, 2 Kawasaki disease. Mean age at MAS diagnosis was 7.9±4.6y, average disease duration 3,8 (1,0; 6,5) y, in 57,2% pts MAS manifestation accompanied the disease onset. Max. interval between the onset of the disease and MAS development was 12 years. Subclinical MAS was diagnosed in 32% sJIA pts; fulminant course, requiring intensive care in 31%. Most common MAS clinical manifestations were: febrile fever 100%, hepatomegaly 88%, splenomegaly 75%, CNS lesion 51%, coagulopathy 40%, lymphadenopathy 37%, respiratory distress syndrome 37%, carditis 28%, hemorrhagic rash 26%, urticaria 20%. In 3 pts MAS manifested with hepatitis complicated by acute liver failure. Among common MAS laboratory markers the following should be mentioned: hyperferritinemia 82% (<1000μkg/l – 31%, 1000-10.000μkg/l – 18%, >10.000μkg/l – 27%), ← transaminases LDH 82%, hypertriglyceridemia 68%, thrombocytopenia 63%, cytopenia 40%, DIC – syndrome (hypofibrinogenemia, ←D-dimers) – 37%, bone marrow haemophagocytosis was confirmed in 22/35 pts 63%. Most severe MAS course was documented in pts with ferritine levels >10000μkg/l. Low NK-cell count was diagnosed in 36% cases. MAS therapy included: GCs in 100% of pts (methylprednisolone pulse-therapy 74%, dexamethasone 37%), IVIGs 86%, cyclosporine A (CsA) 31%, etoposide 2,8%. In 6 sJIA pts with GCs, IVIG, and CsA failure tocilizumab (Tcz) 10-12 mg/kg once in 14 days was initiated at Week 4, with subsequent MAS resolution documented at Weeks 2-4 after initiation of therapy. In 4 sJIA pts developing MAS at different time points in the course of the disease (from 1 to 5 years) Tcz was administered following the outbreak of sJIA flare; kanakinumab was administered in 1 patient, rituximab – in 4 SLE pts. There were 5 deaths registered (3 sJIA, 2 SLE) on days 1 through 257 from MAS onset.
Conclusions RD – associated MAS is most common in sJIA patients (71%), with subclinical course in 1/3 of all cases. Our data indicates that CNS involvement is the most common MAS sign. Fulminant MAS is associated with liver failure and respiratory distress-syndrome. We've accumulated positive experience with successful use of biological agents in patients with secondary MAS (Tcz, rituximab, kanakinumab).
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Miettunen PM, Narendran A, et al. Successful treatment of severe paediatric rheumatic disease-associated macrophage activation syndrome with interleukin-1 inhibition following conventional immunosuppressive therapy: case series with 12 patients. Rheumatology 2011;50:417–9
Disclosure of Interest None declared