Identification of the best cutoff points and clinical signs specific for early recognition of macrophage activation syndrome in active systemic juvenile idiopathic arthritis

Semin Arthritis Rheum. 2015 Feb;44(4):417-22. doi: 10.1016/j.semarthrit.2014.09.004. Epub 2014 Sep 11.


Objectives: The purpose of our study was to detect early clinical and laboratory signs that help to discriminate macrophage activation syndrome (MAS) from active systemic juvenile idiopathic arthritis (SJIA) without MAS.

Methods: Our retrospective study was based on reviewing the medical charts of the children admitted to the rheumatology department with active SJIA and definite MAS (n = 18) and without MAS (n = 40). We evaluated the data related to SJIA and MAS at the moment of the patient׳s admission. If the patient had signs of MAS since admission or developed definite MAS later during this flare, he was referred to the main group. The children who did not have MAS during the flare episode and did not have MAS in the past medical history were in the control group. We calculated the cutoff points for MAS parameters, performed the analysis of sensitivity and specificity, identified the predictors, and provided the preliminary diagnostic rule through "the-number-of-criteria-present" approach.

Results: The clinical signs were relevant to MAS in SJIA: oligoarticular disease course (OR = 5.6), splenomegaly (OR = 67.6), hemorrhages (OR = 33.0), and respiratory failure (OR = 11.3). The involvement of wrist (OR = 0.2), MCP (OR = 0.1), and PIP joints (OR = 0.1) was protective against MAS development. The best cutoffs for laboratory parameters were PLT ≤ 211 × 10(9)/l, WBC ≤ 9.9 × 10(9)/l, AST > 59.7U/l, LDH > 882U/l, albumin ≤ 2.9g/dl, ferritin > 400μg/l, fibrinogen ≤ 1.8g/l, and proteinuria. The laboratory variables were more precise in the discrimination of early MAS than clinical: any 3 or more laboratory criteria provided the highest specificity (1.0) and sensitivity (1.0) and OR = 2997.

Conclusions: We detected clinical and laboratory markers and created preliminary diagnostic (laboratory) guidelines for early discrimination of MAS in active SJIA.

Keywords: Macrophage activation syndrome (MAS); Systemic juvenile idiopathic arthritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arthritis, Juvenile / blood
  • Arthritis, Juvenile / complications*
  • Arthritis, Juvenile / diagnosis*
  • Arthritis, Juvenile / etiology
  • Biomarkers / blood
  • Child
  • Child, Preschool
  • Diagnosis, Differential
  • Early Diagnosis*
  • Female
  • Ferritins / blood
  • Fibrinogen / metabolism
  • Hemorrhage / diagnosis
  • Hemorrhage / etiology
  • Humans
  • Infant
  • L-Lactate Dehydrogenase / blood*
  • Leukocyte Count
  • Macrophage Activation Syndrome / blood
  • Macrophage Activation Syndrome / diagnosis*
  • Macrophage Activation Syndrome / epidemiology*
  • Male
  • Respiratory Insufficiency / diagnosis
  • Respiratory Insufficiency / etiology
  • Retrospective Studies
  • Risk Factors
  • Splenomegaly / diagnosis
  • Splenomegaly / etiology


  • Biomarkers
  • Fibrinogen
  • Ferritins
  • L-Lactate Dehydrogenase