From the Journals

Macrophage activation syndrome’s impact in childhood SLE felt mostly early

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Is it lupus or lupus complicated by macrophage activation syndrome?

As we learn more about the role of macrophage activation syndrome (MAS), a secondary form of hemophagocytic lymphohistiocytosis in rheumatic diseases, it has become clear that patients may develop this syndrome in a variety of settings. The most common presentation of MAS is in association with systemic onset juvenile idiopathic arthritis, but is has been described in other forms of childhood rheumatic diseases, including other types of juvenile idiopathic arthritis, lupus, mixed connective tissue disease, Kawasaki disease, and sarcoidosis. Study of secondary MAS has led to suggested diagnostic criteria; however, those criteria are very similar to the presentation of adult and childhood systemic lupus with cytopenias, hepatitis, and coagulopathy.

Dr. Marisa S. Klein-Gitelman is a professor of pediatrics at Northwestern University, Chicago

Dr. Marisa S. Klein-Gitelman

The paper by Borgia, et al. describes a 10% rate of MAS in childhood lupus with two-thirds of patients having both diagnoses at presentation. They also noted a higher mortality than previous studies but found MAS recurrences to be rare. Given that adolescent lupus patients present to pediatric and adult providers, this information is highly relevant to the rheumatologists and intensivists who care for these patients. Elevation of lactate dehydrogenase out of proportion to other liver function tests, ferritin, and prolonged d-dimer are helpful immediate syndrome markers. Finding out soluble interleukin-2 receptor level can be helpful but requires more time to acquire the results. Severe MAS was seen in several patients, requiring escalation of therapy. It is notable that many of the identified MAS patients responded to corticosteroids. Thus, if the physician had not recognized MAS criteria, the diagnosis may not have been realized.

The work by Borgia et al. encourages us to look for evidence of MAS in our lupus patients as it allows us to identify patients at risk for poor outcomes and to provide interventions to reduce those risks.

Marisa S. Klein-Gitelman, MD , is a professor of pediatrics at Northwestern University, Chicago, and is a pediatric rheumatologist at the Ann & Robert H. Lurie Children’s Hospital of Chicago. She has no relevant disclosures.



Nearly 10% of children with systemic lupus erythematosus (SLE) developed macrophage activation syndrome (MAS) at some point during a mean follow-up time of more than 3 years at one center, and most were concomitantly diagnosed with the syndrome.

Although the investigators from the University of Toronto reported significantly higher mortality among patients with MAS, most cases were successfully treated with corticosteroids, and no relapses were observed during follow-up.

MAS was first identified in patients with juvenile idiopathic arthritis and is most well known as a complication of that broadly named disease, but data on outcomes and disease course in SLE patients are limited, first author Roberto Ezequiel Borgia, MD, and his colleagues wrote in their report in Arthritis & Rheumatology.

The researchers identified 403 children with SLE seen at the Hospital for Sick Children in Toronto during 2002-2012. Overall, 38 patients (9%) had MAS; of those patients, 68% received a MAS diagnosis within 7 days of the SLE diagnosis – termed “concomitant” diagnosis – while another 29% received a MAS diagnosis within 180 days of their SLE diagnosis.

The researchers explained that “since there are no validated nor universally accepted diagnostic criteria for MAS in SLE, the definition of MAS was based on the treating pediatric rheumatologist’s expert opinion at the time of the initial presentation.” The most common presenting feature of MAS was fever (100%), followed by generalized lymphadenopathy (24%), hepatomegaly (18%), CNS dysfunction secondary to MAS (18%), hemorrhage (13%), and splenomegaly (10%).

The average age of the children at diagnosis was nearly 14 years, and 79% were female. The average follow-up was 3.5 years. There were no significant differences in the demographic features of children with and without MAS nor were there any in variables used to assess lupus outcomes, which included immunosuppressive drug use, average daily corticosteroid dose (18.3 mg/day with MAS vs. 18.6 mg/day without MAS), and the number of pediatric ICU visits (incidence rate ratio for MAS vs. non-MAS, 1.60 [95% CI, 0.74-3.18]).

Mortality was significantly higher in children with MAS, compared with those without MAS (5.3% vs. 0.3%; P = .02), although the overall number of deaths in the cohort was small (n = 3). Apart from the “acute illness which was associated with 2 deaths secondary to MAS,” the investigators said that they “did not find any significant differences in the number of deaths or damage accrual between the cohorts, including overall SLICC [Systemic Lupus International Collaborating Clinics] damage score or any specific damage feature within the score.”

The study findings were limited by several factors including the lack of validated MAS criteria for children with SLE and a lack of follow-up data on the patients beyond 18 years of age, the researchers said.

The results suggest that MAS remains a life-threatening complication in children with SLE and should be considered an important cause of mortality for them, but “if the initial presentation does not result in death, the long-term outcome seem[s] to be comparable to those without MAS,” the investigators wrote.

The researchers had no financial conflicts to disclose.

SOURCE: Borgia R et al. Arthritis Rheumatol. 2018 Jan 17. doi: 10.1002/art.40417

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