ObjectiveTo compare the capacity of the 2004 diagnostic guidelines for
hemophagocytic lymphohistiocytosis (HLH-2004) with the capacity of the
preliminary diagnostic guidelines for systemic juvenile idiopathic
arthritis (JIA)-associated macrophage activation syndrome (MAS) to
discriminate MAS complicating systemic JIA from 2 potentially confusable
conditions, represented by active systemic JIA without MAS and systemic
infection.
MethodsInternational pediatric rheumatologists and hemato-oncologists
were asked to retrospectively collect clinical information from patients
with systemic JIA-associated MAS and confusable conditions. The ability
of the guidelines to differentiate MAS from the control diseases was
evaluated by calculating the sensitivity and specificity of each set of
guidelines and the kappa statistics for concordance with the physician’s
diagnosis. Owing to the fact that not all patients were assessed for
hemophagocytosis on bone marrow aspirates and given the lack of data on
natural killer cell activity and soluble CD25 levels, the HLH-2004
guidelines were adapted to enable the diagnosis of MAS when 3 of 5 of
the remaining items (3/5-adapted) or 4 of 5 of the remaining items
(4/5-adapted) were present.
ResultsThe study sample included 362 patients with systemic JIA and MAS,
404 patients with active systemic JIA without MAS, and 345 patients with
systemic infection. The best capacity to differentiate MAS from systemic
JIA without MAS was found when the preliminary MAS guidelines were
applied. The 3/5-adapted HLH-2004 guidelines performed better than the
4/5-adapted guidelines in distinguishing MAS from active systemic JIA
without MAS. The 3/5-adapted HLH-2004 guidelines and the preliminary MAS
guidelines with the addition of ferritin levels 500 ng/ml discriminated
best between MAS and systemic infections.
ConclusionThe preliminary MAS guidelines showed the strongest ability to
identify MAS in systemic JIA. The addition of hyperferritinemia enhanced
their capacity to differentiate MAS from systemic infections. The
HLH-2004 guidelines are likely not appropriate for identification of MAS
in children with systemic JIA