E55 Macrophagic activation syndrome in pediatric rheumatology: about 12 cases
Authors: Ryouni Karima , Sakhi Asmas , Ansari Ghita Benbrahim , Aboufaris Hanan , Bouayed Kenza 
Published: August 2023

Introduction

Macrophage activation syndrome (MAS) is a serious clinical condition due to inappropriate stimulation of macrophages. It can be primary or secondary to underlying neoplastic, infectious or autoimmune diseases. Some pediatric inflammatory diseases are highly complicated by MAS with a higher incidence in systemic juvenile idiopathic arthritis (SJIA) or systemic lupus erythematosus (SLE).

Objective

We aim to highlight the features of MAS occurring in the context of pediatric inflammatory diseases according to our epidemiology and local conditions.

Materials and methods

This is a retrospective, descriptive and analytical study seen over a period of 4 years (from January 2019 to December 2022).

The diagnosis of MAS was confirmed according to Ravelli criteria published in 2016 in the presence of mandatory persistent fever and at least four of the following abnormalities: hyperferritinemia&gt; 684 ng/ml, platelet count &lt; 181x103/mm3, liver cytolysis aspartate amino transferase (AST) &gt; 48UI/l, triglyceridemia &gt; 1.56 g/l, fibrinogenemia &lt; 3.6 g/l, after having ruling out infections. The presence of hemophagocytes in the bone marrow aspiration was considered sufficient for the diagnosis in presence of long lasting fever.

Results

Among 70 patients followed for inflammatory disease, 12 presented with MAS.

The age of the patients ranged from 8 months to 17 years during the MAS episode, with a mean age of 8 years 9 months and male: female ratio was 1.4 (7 boys/5 girls).

All patients had fever and altered general condition, two had associated hemorrhagic syndrome. On clinical examination, 3 patients had splenomegaly, 3 had hepatomegaly, 2 of which combined splenomegaly and hepatomegaly. Adenopathies were reported in 3 patients. No patient had jaundice or neurological signs.

Biological parameters revealed a platelet count&lt; 181 000/mm3 in 58.3% (7 cases), an AST level &gt; 48IU/l in 91,6% (11 cases), hypertriglyceridemia &gt; 156mg/l in 69.2% (9 cases), hypofibrinogenemia &lt; 360 mg/dl in 66.6% (8 cases), and hyperferritinemia &gt;684 ng/ml in 91,6% (11 cases). Eight had bone marrow aspiration, which was inflammatory in 37.5%, normal in 37.5% and hemophagocytosis in 25%.

In our series, MAS preceeded the diagnosis of paediatric inflammatory disease in 9 patients, and complicating the evolution of an inflammatory disease in 3 patients.

The main aetiology was SLE in 58.3% (7 cases). Other causes were reported such as SJIA in 1, NLRC 4 deficiency without genetic confirmation in 1, PIMS in 1, primary immune deficiency with hypogammaglobulinemia and sarcoidosis like picture in 1 and one case of primary MAS.

Recurrence was noted in 3 patients, including 1 SLE, 1 primary MAS and the NLRC 4 deficiency.

All patients received bolus intravenous corticosteroids, followed by oral corticosteroids which was weaned off over a period of four months if no disease progression. Ciclosporin A was added to corticosteroids in 4 (33,3%). Biotherapy was administered to 2 patients, the first with NLRC4 deficiency, who received Tocilizumab and infliximab before responding favorably to anakinra 10 mg/kg/d. The second for a PIMS complicated by severe MAS, who received Tocilizumab once without any improvement before switching to anakinra 2 mg/kg/day for 4 months with complete remission.

Conclusion and Discussion

MAS is a severe syndrome, characterized by non-specific clinical and biological signs, making the diagnosis very difficult. Recently, clinical and biological criteria have been proposed according to the disease, however, the most discriminating biological parameter is hyperferritinemia. This condition must be detected and treated without delay to avoid death.

Our series is characterized by the predominance of SLE as the major aetiology of MAS, by its inaugural presentation worsening the prognosis of the underlying inflammatory disease probably related to a delay in consultation, by the low percentage of hemophagocytes in bone marrow aspiration, which could be explained by a lack of knowledge on the part of our cytologists and by a low use of biotherapies.