Aug 11, 2017 - Concetta Micalizzi, MD1, Nicolino Ruperto, MD, MPH1, Alberto Martini, MD1, ...... Sheila Knupp Feitosa de Oliveira, MD, Federal University.
ARTICLE IN PRESS THE JOURNAL OF PEDIATRICS • www.jpeds.com
ORIGINAL ARTICLES
Development and Initial Validation of the Macrophage Activation Syndrome/Primary Hemophagocytic Lymphohistiocytosis Score, a Diagnostic Tool that Differentiates Primary Hemophagocytic Lymphohistiocytosis from Macrophage Activation Syndrome Francesca Minoia, MD1, Francesca Bovis, PhD2, Sergio Davì, MD1, Antonella Insalaco, MD3, Kai Lehmberg, MD4, Susan Shenoi, MD5, Sheila Weitzman, MD6, Graciela Espada, MD7, Yi-Jin Gao, MD8, Jordi Anton, MD9, Toshiyuki Kitoh, MD10, Ozgur Kasapcopur, MD11, Helga Sanner, MD12, Rosa Merino, MD13, Itziar Astigarraga, MD14, Maria Alessio, MD15, Michael Jeng, MD16, Vyacheslav Chasnyk, MD17, Kim E. Nichols, MD18, Zeng Huasong, MD19, Caifeng Li, MD20, Concetta Micalizzi, MD1, Nicolino Ruperto, MD, MPH1, Alberto Martini, MD1, Randy Q. Cron, MD21, Angelo Ravelli, MD1,2,*, and AnnaCarin Horne, MD22,*, on behalf of the Pediatric Rheumatology International Trials Organization, the Childhood Arthritis and Rheumatology Research Alliance, the Pediatric Rheumatology Collaborative Study Group, and the Histiocyte Society† Objective To develop and validate a diagnostic score that assists in discriminating primary hemophagocytic lymphohistiocytosis (pHLH) from macrophage activation syndrome (MAS) related to systemic juvenile idiopathic arthritis. Study design The clinical, laboratory, and histopathologic features of 362 patients with MAS and 258 patients with pHLH were collected in a multinational collaborative study. Eighty percent of the population was assessed to develop the score and the remaining 20% constituted the validation sample. Variables that entered the best fitted model of logistic regression were assigned a score, based on their statistical weight. The MAS/HLH (MH) score was made up with the individual scores of selected variables. The cutoff in the MH score that discriminated pHLH from MAS best was calculated by means of receiver operating characteristic curve analysis. Score performance was examined in both developmental and validation samples. Results Six variables composed the MH score: age at onset, neutrophil count, fibrinogen, splenomegaly, platelet count, and hemoglobin. The MH score ranged from 0 to 123, and its median value was 97 (1st-3rd quartile 75123) and 12 (1st-3rd quartile 11-34) in pHLH and MAS, respectively. The probability of a diagnosis of pHLH ranged from 5 and a P < .05) were scrutinized further on multivariable logistic regression procedures to evaluate their independent contribution to the outcome (ie, the diagnosis of pHLH). The characteristics of patients with missing variables were compared with those of
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Minoia et al FLA 5.4.0 DTD ■ YMPD9259_proof ■ August 11, 2017
■■ 2017
ORIGINAL ARTICLES
Table I. Comparison of demographic, clinical, laboratory, and histopathologic features at disease onset between patients with MAS and pHLH n Demographic characteristics Median (1st-3rd quartile) age, y Female Clinical manifestations Fever Hepatomegaly Splenomegaly Generalized lymphadenopathy CNS involvement Jaundice Median (1st-3rd quartile) values of laboratory tests Hemoglobin, g/dL Neutrophil count, × 109/L Platelet count, × 109/L Aspartate aminotransferase, U/L Lactate dehydrogenase, U/L Triglycerides, mg/dL Albumin, g/dL Bilirubin, mg/dL Fibrinogen, mg/dL Ferritin, ng/mL Histopathologic features Bone marrow aspiration and/or other biopsy Hemophagocytosis
Patients with MAS (n = 362)
n
Patients with pHLH (n = 258)
P value
362 362
8.1 (4.0-13.0) 208 (57.5)
258 258
0.3 (0.2-1.2) 128 (49.6)
