An international consensus survey of diagnostic criteria for macrophage activation syndrome in systemic juvenile idiopathic arthritis.

Istituto di Ricovero e Cura a Carattere Scientifico G. Gaslini, Genova, Italy.
The Journal of Rheumatology (Impact Factor: 3.17). 02/2011; 38(4):764-8. DOI: 10.3899/jrheum.100996
Source: PubMed

ABSTRACT To identify candidate diagnostic criteria for macrophage activation syndrome (MAS) complicating systemic juvenile idiopathic arthritis (sJIA) using international consensus formation through a Delphi questionnaire survey.
A questionnaire listing 28 clinical, laboratory, and histopathologic features of MAS elicited by literature review was sent to 505 pediatric rheumatologists worldwide. Respondents were asked to select the 10 features that they felt were most important and useful in the diagnosis of MAS, and to order the 10 selected features by assigning the number 10 to the most important, and ending with 1 as the least important.
The response rate was 46% (232 physicians from 47 countries). The items selected by more than 50% of respondents were, in order of frequency, falling platelet count, hyperferritinemia, evidence of macrophage hemophagocytosis in the bone marrow, increased liver enzymes, falling leukocyte count, persistent continuous fever ≥ 38°C, falling erythrocyte sedimentation rate, hypofibrinogenemia, and hypertriglyceridemia.
Our process led to identification of features that were felt to be most important as candidate diagnostic criteria for MAS by a large sample of international pediatric rheumatologists.

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    ABSTRACT: Objective. To compare the capacity of hemophagocytic lymphohistiocytosis (HLH)-2004 diagnostic guidelines and preliminary diagnostic guidelines for systemic juvenile idiopathic arthritis (sJIA)-associated macrophage activation syndrome (MAS) to discriminate MAS complicating sJIA from two potentially confusable conditions, represented by active sJIA without MAS and systemic infection. Methods. International pediatric rheumatologists and hemato-oncologists were asked to collect retrospectively the clinical information of patients with sJIA-associated MAS and confusable conditions. The ability of guidelines to differentiate MAS from control diseases was evaluated by calculating sensitivity and specificity and with kappa statistics. Owing to unavailability of assessment of bone marrow hemophagocytosis, NK cell activity and soluble CD25 levels, HLH-2004 guidelines were adapted to enable the diagnosis of MAS when 3/5 or 4/5 of the remaining items were present. Results. The study sample included 362 patients with sJIA and MAS, 404 patients with active sJIA without MAS, and 345 patients with systemic infection. The best capacity to differentiate MAS from sJIA without MAS was shown by the preliminary MAS guidelines. The adapted 3/5 HLH-2004 guidelines performed better than the adapted 4/5 guidelines in distinguishing MAS from active sJIA without MAS. The adapted 3/5 HLH-2004 guidelines and preliminary MAS guidelines with the addition of ferritin ≥ 500 ng/mL discriminated best between MAS and systemic infections. Conclusion. Preliminary MAS guidelines showed the strongest ability to identify MAS in sJIA. The addition of hyperferritinemia enhanced their capacity to differentiate MAS from systemic infections. HLH-2004 guidelines are likely not appropriate for identification of MAS in children with sJIA. © 2014 American College of Rheumatology.
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    ABSTRACT: Objectives The purpose of our study was to detect early clinical and laboratory signs able 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 cut-off 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: oligoarthicular disease course (OR=5.6), splenomegaly (OR=67.6), hemorrages (OR=33.0), respiratory failure (OR=11.3). The involvement of wrist (OR=0.2), MCP (OR=0.1) and PIP joints (OR=0.1) were protective against MAS development. The best cut-offs for laboratory parameters were PLT≤211109/l, WBC≤9.9109/l, AST>59.7 U/l, LDH>882 U/l, albumin≤2.9 g/dl, ferritin>400 μg/l, fibrinogen≤1.8 g/l, 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.
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