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 - 23/09/17
Doi : 10.1016/j.jpeds.2017.06.005
Francesca Minoia, MD 1, * 
, Francesca Bovis, PhD 2, Sergio Davì, MD 1, Antonella Insalaco, MD 3, Kai Lehmberg, MD 4, Susan Shenoi, MD 5, Sheila Weitzman, MD 6, Graciela Espada, MD 7, Yi-Jin Gao, MD 8, Jordi Anton, MD 9, Toshiyuki Kitoh, MD 10, Ozgur Kasapcopur, MD 11, Helga Sanner, MD 12, Rosa Merino, MD 13, Itziar Astigarraga, MD 14, Maria Alessio, MD 15, Michael Jeng, MD 16, Vyacheslav Chasnyk, MD 17, Kim E. Nichols, MD 18, Zeng Huasong, MD 19, Caifeng Li, MD 20, Concetta Micalizzi, MD 1, Nicolino Ruperto, MD, MPH 1, Alberto Martini, MD 1, Randy Q. Cron, MD 21, Angelo Ravelli, MD 1, 2, *, AnnaCarin Horne, MD 22, *
on behalf of the
, Francesca Bovis, PhD 2, Sergio Davì, MD 1, Antonella Insalaco, MD 3, Kai Lehmberg, MD 4, Susan Shenoi, MD 5, Sheila Weitzman, MD 6, Graciela Espada, MD 7, Yi-Jin Gao, MD 8, Jordi Anton, MD 9, Toshiyuki Kitoh, MD 10, Ozgur Kasapcopur, MD 11, Helga Sanner, MD 12, Rosa Merino, MD 13, Itziar Astigarraga, MD 14, Maria Alessio, MD 15, Michael Jeng, MD 16, Vyacheslav Chasnyk, MD 17, Kim E. Nichols, MD 18, Zeng Huasong, MD 19, Caifeng Li, MD 20, Concetta Micalizzi, MD 1, Nicolino Ruperto, MD, MPH 1, Alberto Martini, MD 1, Randy Q. Cron, MD 21, Angelo Ravelli, MD 1, 2, *, AnnaCarin Horne, MD 22, *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†
Mario Abinun, MD 1, Amita Aggarwal, MD 2, Jonathan Akikusa, MD 3, Sulaiman Al-Mayouf, MD 4, Maria Alessio, MD 5, Jordi Anton, MD 6, Maria Teresa Apaz, MD 7, Itziar Astigarraga, MD 8, Tadej Avcin, MD 9, Nuray Aktay Ayaz, MD 10, Patrizia Barone, MD 11, Bianca Bica, MD 12, Isabel Bolt, MD 13, Francesca Bovis, PhD 14, Luciana Breda, MD 15, Vyacheslav Chasnyk, MD 16, Rolando Cimaz, MD 17, Fabrizia Corona, MD 18, Randy Q. Cron, MD 19, Ruben Cuttica, MD 20, Sergio Davì, MD 21, Zane Davidsone, MD 22, Carmen De Cunto, MD 23, Jaime De Inocencio, MD 24, Erkan Demirkaya, MD 25, Eli M. Eisenstein, MD 26, Sandra Enciso, MD 27, Graciela Espada, MD 28, Michel Fischbach, MD 29, Michael Frosch, MD 30, Romina Gallizzi, MD 31, Maria Luz Gamir, MD 32, Yi-Jin Gao, MD 33, Thomas Griffin, MD 34, Alexei Grom, MD 35, Soad Hashad, MD 36, Teresa Hennon, MD 37, Jan-Inge Henter, MD, PhD 38, AnnaCarin Horne, MD, PhD 39, Gerd Horneff, MD 40, Zeng Huasong, MD 41, Adam Huber, MD 42, Norman Ilowite, MD 43, Antonella Insalaco, MD 44, Maka Ioseliani, MD 45, Michael Jeng, MD 46, Agneza Marija Kapović, MD 47, Ozgur Kasapcopur, MD 48, Raju Khubchandani, MD 49, Toshiyuki Kitoh, MD 50, Isabelle Koné-Paut, MD, PhD 51, Sheila Knupp Feitosa de Oliveira, MD 52, Bianca Lattanzi, MD 53, Kai Lehmberg, MD 54, Loredana Lepore, MD 55, Caifeng Li, MD 56, Jeffrey M. Lipton, MD 57, Silvia Magni-Manzoni, MD 58, Despoina Maritsi 59, Alberto Martini, MD 60, Deborah McCurdy, MD 61, Rosa Merino, MD 62, Concetta Micalizzi, MD 63, Paivi Miettunen, MD 64, Francesca Minoia, MD 65, Velma Mulaosmanovic, MD 66, Kim E. Nichols, MD 67, Susan Nielsen, MD 68, Seza Ozen 69, Priyankar Pal 70, Sampath Prahalad, MD 71, Angelo Ravelli, MD 72, Donato Rigante, MD 73, Ingrida Rumba-Rozenfelde, MD, PhD 74, Nicolino Ruperto, MD 75, Ricardo Russo, MD 76, Claudia Saad Magalhães, MD 77, Helga Sanner, MD 78, Wafaa Mohamed Saad Sewairi, MD 79, Susan Shenoi, MD 80, Clovis Artur Silva, MD 81, Valda Stanevicha, MD 82, Gary Sterba, MD 83, Kimo C. Stine, MD 84, Gordana Susic, MD 85, Flavio Sztajnbok, MD 86, Syuji Takei, MD 87, Ralf Trauzeddel, MD 88, Elena Tsitsami, MD 89, Erbil Unsal, MD 90, Yosef Uziel, MD 91, Olga Vougiouka, MD 92, Carol A. Wallace, MD 93, Lehn Weaver, MD 94, Jennifer E. Weiss, MD 95, Sheila Weitzman, MD 96, Carine Wouters, MD 97, Nico Wulffraat, MD 98, Mabruka Zletni, MD 99, Maurizio Arico, MD 100, R. Maarten Egeler, MD 101, Alexandra H. Filipovich, MD 102, Helmut Gadner, MD 103, Shinsaku Imashuku, MD 104, Gritta Janka, MD, PhD 105, Stephan Ladisch, MD 106, Ken L. McClain, MD, PhD 107, David Webb, MD 108
1 Great North Children's Hospital, Newcastle, UK
2 Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
3 Royal Children's Hospital, Melbourne, Australia
4 King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
5 University of Napoli Federico II, Naples, Italy
6 Hospital Sant Joan de Déu, Barcelona, Spain
7 Catholic University of Cordoba, Cordoba, Argentina
8 BioCruces Health Reasearch Institute, Hospital at the University of Cruces, University of the Basque Country, Barakaldo, Bizkaia, Spain
9 University Children's Hospital, Ljubljana, Slovenia
10 Bakırkoy Maternity and Children Education and Research Hospital, Istanbul, Turkey
11 Policlinic of the University of Catania, Catania, Italy
12 Clementino Fraga Filho University Hospital, Rio de Janeiro, Brazil
13 University Hospital Pediatrics Clinic, Berne University Hospital, Berne, Switzerland
14 University of Genova, Genoa, Italy
15 Hospital Clinic, Chieti, Italy
16 Saint Petersburg State Pediatric Medical University, Saint Petersburg, Russian Federation
17 Pediatrico A. Meyer Hospital, Florence, Italy
18 Ca' Granda Italian Research Hospital Foundation, Maggiore Hospital, Milan, Italy
19 University of Alabama, Birmingham, AL, USA
20 Pedro de Elizalde Children's' Hospital, Buenos Aires, Argentina Gianfranco D'Angelo, MD, G. Salesi Children's Hospital, Ancona, Italy
21 G. Gaslini Institute, Genoa, Italy
22 Children's University Hospital, Riga, Latvia
23 Italian Hospital in Buenos Aires, Buenos Aires, Argentina
24 12 de Octubre University Hospital, Madrid, Spain
25 Gulhane Military Medical Faculty, Ankara, Turkey
26 Hadassah–Hebrew University Medical Center, Jerusalem, Israel
27 Federico Gomez Children's Hospital of Mexico, Mexico City, Mexico
28 Ricardo Gutierrez Children's Hospital, Buenos Aires, Argentina
29 Hautepierre University Hospital, Strasbourg, France
30 University Children's Hospital, Munster, Germany
31 University of Messina, Messina, Italy
32 Hospital Ramon and Cajal, Madrid, Spain
33 Children's Hospital of Fudan University, Shanghai, China
34 Carolinas HealthCare System, Charlotte, NC, USA
35 Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
36 Tripoli Children's Hospital, Tripoli, Libya
37 Women and Children's Hospital, Buffalo, NY, USA
38 Karolinska Instiututet, Stockholm, Sweden
39 Karolinska Instiututet, Stockholm, Sweden
40 Center for General Pediatrics and Neonatology, St. Agustin, Germany
41 Guangzhou Children's Hospital, Guangzhou, China
42 IWK Health Center, Halifax, Canada
43 Albert Einstein College of Medicine and Children's Hospital at Montefiore, New York, NY, USA
44 Pediatric Hospital of the Baby Jesus, Rome, Italy
45 M. Iashvili Children's Central Clinic, Tbilisi, Georgia
46 Stanford School of Medicine, Palo Alto, CA, USA
47 Department for Immunology and Rheumatology, Children's Hospital of Zagreb, Zagreb, Croatia
48 Istanbul University, Cerrahpasa Medical School, Istanbul, Turkey
49 Jaslok Hospital and Research Center, Mumbai, India
50 Aichi Medical University, Nagakute, Japan
51 University Hospital Center at Le Kremlin Bicêtre, Le Kremlin Bicêtre, France
52 Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
53 Consolidated University Hospitals, Ancona, Italy
54 University Medical Center, Hamburg, Germany
55 Burlo Garofolo Maternal and Infant Italian Research Hospital Foundation, Trieste, Italy
56 Beijing Children's Hospital, Beijing, China
57 Steven and Alexandra Cohen Children's Hospital of New York, New York, NY, USA
58 Pediatric Hospital of the Baby Jesus, Rome, Italy
59 Athens Medical School, Athens, Greece
60 G. Gaslini Institute, Genoa, Italy
61 University of California, Los Angeles and Mattel Children's Health Center UCLA, Orange, Los Angeles, CA, USA
62 University Hospital La Paz, Madrid, Spain
63 G. Gaslini Institute, Genoa, Italy
64 University of Calgary, Calgary, Canada
65 G. Gaslini Institute, Genoa
66 Children's Hospital University Clinical Center Sarajevo, Sarajevo, Bosnia and Herzegovina
67 St. Jude Children's Research Hospital, Memphis, TN, USA
68 Juliane Marie Center and Rigshospitalet, Copenhagen, Denmark
69 Hacettepe University, Ankara, Turkey
70 Institute of Child Health, Kolkata, India
71 Emory University and Children's Healthcare of Atlanta, Atlanta, GA, USA
72 G. Gaslini Institute and University of Genova, Genoa, Italy
73 Sacred Heart Catholic University, Rome, Italy
74 University of Latvia, Riga, Latvia
75 G. Gaslini Institute, Genoa, Italy
76 Juan P. Garrahan Pediatric Hospital, Buenos Aires, Argentina
77 Clinical Hospital, Botucatu, Brazil
78 Oslo University Hospital, Rikshospitalet, Oslo, Norway
79 King Fahad National Guard Hospital, Riyadh, Saudi Arabia
80 Seattle Children's Hospital and University of Washington, Seattle, WA, USA
81 Sao Paulo University, Sao Paulo, Brazil
82 Riga Stradins University, Riga, Latvia
83 Mount Sinai Medical Center, Miami Beach, Miami, FL, USA
84 Arkansas Children's Hospital, Little Rock, AK, USA
85 Institute of Rheumatology, Belgrade, Serbia
86 Pedro Ernesto University Hospital, Rio de Janeiro, Brazil
87 Kagoshima University Hospital, Kagoshima City, Japan
88 Helios Clinic, Berlin, Germany
89 Athens Medical School and Children's Hospital Aghia Sofia, Athens, Greece
90 Dokuz Eylül University Medical School, Izmir, Turkey
91 Meir Medical Center, Kfar Saba, Israel
92 Kyriakou Children's Hospital of Athens, Athens, Greece
93 Seattle Children's Hospital, Seattle, WA, USA
94 The Children's Hospital of Philadelphia, Philadelphia, PA, USA
95 New Jersey Medical School and Hackensack University Medical Center, Hackensack, NJ, USA
96 The Hospital for Sick Children, Toronto, Ontario, Canada
97 University Hospital Gasthuisberg, Leuven, Belgium
98 Wilhelmina Children's Hospital and University Medical Center, Utrecht, The Netherlands
99 Tripoli Children's Hospital, Tripoli, Libya
100 Universitaria A. Meyer, Florence, Italy
101 Leiden University Medical Center, Leiden, The Netherlands
102 Children's Hospital Medical Center, Cincinnati, OH, USA
103 FRCP, St. Anna Children's Hospital, Vienna, Austria
104 Kyoto City Institute of Health and Environmental Sciences, Kyoto, Japan
105 Department of Hematology and Oncology, Children's University Hospital, Hamburg, Germany
106 Children's Research Institute, Washington, DC, USA
107 Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX, USA
108 Great Ormond Street Hospital, London, UK
1 G. Gaslini Institute, Genoa, Italy
2 University of Genova, Genoa, Italy
3 Pediatric Hospital of Bambino Gesù, Rome, Italy
4 University Medical Center, Hamburg, Germany
5 Seattle Children's Hospital and University of Washington, Seattle, WA
6 The Hospital for Sick Children, Toronto, Ontario, Canada
7 Ricardo Gutierrez Children's Hospital, Buenos Aires, Argentina
8 Children's Hospital of Fudan University, Shanghai, China
9 Hospital Saint Joan de Déu, Barcelona, Spain
10 Aichi Medical University, Nagakute, Japan
11 Istanbul University, Cerrahpasa Medical School, Istanbul, Turkey
12 Oslo University Hospital, Rikshospitalet, Oslo, Norway
13 La Paz University Hospital, Madrid, Spain
14 BioCruces Health Research Institute, Cruces University Hospital, University of the Basque Country, Barakaldo, Spain
15 University of Naples Federico II, Naples, Italy
16 Stanford School of Medicine, Palo Alto, CA
17 Saint Petersburg State Pediatric Medical University, Saint Petersburg, Russia
18 St. Jude Children's Research Hospital, Memphis, TN
19 Guangzhou Children's Hospital, Guangzhou, China
20 Beijing Children's Hospital, Beijing, China
21 University of Alabama, Birmingham, AL
22 Karolinska University Hospital, Stockholm, Sweden
*Reprint requests: Francesca Minoia, MD, Pediatria II-Reumatologia, Istituto G. Gaslini, via G. Gaslini 5, 16147 Genova, Italy.Pediatria II-ReumatologiaIstituto G. Gaslinivia G. Gaslini 5Genova16147Italy
Abstract |
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 75-123) and 12 (1st-3rd quartile 11-34) in pHLH and MAS, respectively. The probability of a diagnosis of pHLH ranged from <1% for a score of <11 to >99% for a score of ≥123. A cutoff value of ≥60 revealed the best performance in discriminating pHLH from MAS.
Conclusion |
The MH score is a powerful tool that may aid practitioners to identify patients who are more likely to have pHLH and, thus, could be prioritized for functional and genetic testing.
Le texte complet de cet article est disponible en PDF.Keywords : primary hemophagocytic lymphohistiocytosis, macrophage activation syndrome, hemophagocytic syndrome, diagnostic score
Abbreviations : HLH, MAS, pHLH, ROC, sJIA
Plan
| The authors declare no conflicts of interest. |
© 2017
Elsevier Inc. Tous droits réservés.
Vol 189
P. 72 - octobre 2017 Retour au numéro
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