Original Article
Preliminary diagnostic guidelines for macrophage activation syndrome complicating systemic juvenile idiopathic arthritis

https://doi.org/10.1016/j.jpeds.2004.12.016Get rights and content

Objective

To develop diagnostic guidelines for macrophage activation syndrome (MAS) complicating systemic juvenile idiopathic arthritis (S-JIA).

Study design

We followed the classification criteria approach that is based on the comparison of patients with the index disease with patients with a “confusable” disease. The former group included 74 patients with S-JIA-associated MAS reported in the literature or seen by the authors; the latter group included 37 patients with S-JIA who had 51 instances of “high disease activity” seen by the authors. The relative power of clinical, laboratory, and histopathologic variables in discriminating patients with MAS from patients with high disease activity was evaluated by calculating the sensitivity rate, specificity rate, area under the receiver operating characteristic curve, and diagnostic odds ratio (DOR). The combinations of variables that led to best separation between patients and control subjects were identified through “the number of criteria present” method.

Results

The strongest clinical discriminators were hemorrhages (DOR = 67) and central nervous system dysfunction (DOR = 63); the strongest laboratory discriminators were decreased platelet count (DOR = 1092), increased aspartate aminotransferase (DOR = 247), leukopenia (DOR = 70), and hypofibrinogenemia (DOR = 165). The best separation between patients and control subjects occurred when any 2 or more laboratory criteria (DOR = 1309) were simultaneously present; the second best performance was provided by the presence of any 2, 3, or more clinical and/or laboratory criteria (DOR = 765 and 743, respectively).

Conclusion

We identified preliminary diagnostic guidelines for MAS complicating S-JIA. These guidelines deserve prospective validation.

Section snippets

Study Design

To identify the features that were suitable candidates as diagnostic criteria for MAS, we followed the classification criteria approach.9, 10 The purpose of this approach is to separate patients with a disease from patients without the disease. Classification criteria, ideally, have a high sensitivity rate for the disease in question and a high specificity rate against other diseases (that is, a high proportion of cases of the disease are found to be positive and a high proportion of cases

Results

Table I shows the frequency of clinical, laboratory, and histopathological features in patients with S-JIA, and MAS who were reported in the literature and were seen at the authors' units and in patients with S-JIA who had active systemic disease. The frequency of features observed in our patients with MAS and in patients reported in the literature was comparable, with the exceptions of bilirubin increase and erythrocyte sedimentation rate decrease, which were more common in patients reported

Discussion

There are no formal and universally accepted criteria for the diagnosis of MAS in S-JIA. The recognition that this syndrome bears close resemblance to the clinical and laboratory picture of hemophagocytic lymphohistiocytosis (HLH) has led many clinicians to use in practice the diagnostic guidelines for this disease.35 There are, however, several problems with the use of HLH criteria in patients with MAS, the first of which is the need for tissue confirmation. As noted in patients with HLH36 and

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