How is macrophage activation syndrome (MAS) complicating systemic juvenile idiopathic arthritis (SJIA) diagnosed?

Updated: Nov 21, 2018
  • Author: Angelo Ravelli, MD; Chief Editor: Lawrence K Jung, MD  more...
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To identify criteria for macrophage activation syndrome complicating systemic juvenile idiopathic arthritis (SJIA), the diagnostic sensitivity and specificity of the clinical and laboratory features of the syndrome were recently scrutinized. [18, 35, 36] Based on these results, preliminary diagnostic guidelines for macrophage activation syndrome complicating SJIA were established.

The diagnosis of macrophage activation syndrome requires the presence of any 2 or more the following laboratory criteria or 2 or more of the following clinical criteria:

  • Laboratory criteria

    • Decreased platelet count (< 262 x 109/L)

    • Elevated aspartate aminotransferase levels (>59 U/L)

    • Decreased WBC count (< 4 x 109/L)

    • Hypofibrinogenemia (≤2.5 g/L)

  • Clinical criteria

    • CNS dysfunction (eg, irritability, disorientation, lethargy, headache, seizures, coma)

    • Hemorrhages (eg, purpura, easy bruising, mucosal bleeding)

    • Hepatomegaly (≥3 cm below the costal margin)

  • Histopathologic criterion: Evidence of macrophage hemophagocytosis is found in the bone marrow aspirate sample. The demonstration of hemophagocytosis in bone marrow samples may be required in doubtful cases.

The above criteria are of value only in patients with active SJIA. The thresholds of laboratory criteria are provided only as an example. The clinical criteria are probably more useful as classification criteria rather than as diagnostic criteria because they often occur late in the course of macrophage activation syndrome and, therefore, may be of limited value in the early diagnosis of the syndrome.

Other abnormal clinical features in macrophage activation syndrome associated with SJIA not listed above include nonremitting high fever, splenomegaly, generalized lymphadenopathy, and paradoxical improvement of signs and symptoms of arthritis.

Other abnormal laboratory findings in macrophage activation syndrome associated with SJIA not listed above include anemia, a lowered erythrocyte sedimentation rate, elevated alanine aminotransferase levels, increased bilirubin levels, presence of fibrin degradation products, elevated lactate dehydrogenase levels, hypertriglyceridemia, low sodium levels, decreased albumin, and hyperferritinemia.

Because universally agreed on diagnostic criteria for macrophage activation syndrome complicating SJIA are not available, a multinational collaborative effort aimed to generate new criteria for diagnosing macrophage activation syndrome as a complication of SJIA is currently underway. The first step of the project has led to the identification of, by means of a Delphi survey, the clinical, laboratory and histopathologic features of macrophage activation syndrome that were felt to be most important by a large sample of international pediatric rheumatologists with experience with macrophage activation syndrome in children with SJIA. [37]

The diagnostic performance of potential criteria will be scrutinized further in the second phase of the study, through the analysis (ongoing) of real patient data. The final set of criteria is meant to be established in a consensus conference of experts using a combination of statistical and consensus formation techniques. The ultimate goal of the project is to develop a core set of criteria that is both highly sensitive and specific. These criteria will assist physicians in macrophage activation syndrome diagnosis in children with SJIA and enable quick institution of appropriate therapy.

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