Prognostic Factors of Death in 151 Adults With Hemophagocytic Syndrome: Etiopathogenically Driven Analysis

Pilar Brito-Zerón, MD, PhD; Belchin Kostov, PhD; Pedro Moral-Moral, MD; Aleida Martínez-Zapico, MD; Carmen Díaz-Pedroche, MD, PhD; Guadalupe Fraile, MD; Patricia Pérez-Guerrero, MD; Eva Fonseca, MD; Angel Robles, MD; María P. Vaquero-Herrero, MD; María Andrés Calvo, MD; María José Forner, MD; Cesar Morcillo, MD; José Larrañaga, MD; Monica Rodriguez-Carballeira, MD; Manuel Ruiz-Muñoz, MD; Robert Hurtado-García, MD; Sergio Prieto-González, MD, PhD; Asun Aljibe Aguilar, MD; Luis Caminal-Montero, MD; Pilar Hernández-Jiménez, MD; Cristina Rodríguez Fernández-Viagas, MD; Pedro Castro, MD, PhD; Victoria Morell Massó, MD; Alejandra Flores-Chavez, MD; Manuel Ramos-Casals, MD, PhD

Mayo Clinic Proceedings: Innovations, Quality & Outcomes (Sep 2018)

Prognostic Factors of Death in 151 Adults With Hemophagocytic Syndrome: Etiopathogenically Driven Analysis

Pilar Brito-Zerón, MD, PhD,
Belchin Kostov, PhD,
Pedro Moral-Moral, MD,
Aleida Martínez-Zapico, MD,
Carmen Díaz-Pedroche, MD, PhD,
Guadalupe Fraile, MD,
Patricia Pérez-Guerrero, MD,
Eva Fonseca, MD,
Angel Robles, MD,
María P. Vaquero-Herrero, MD,
María Andrés Calvo, MD,
María José Forner, MD,
Cesar Morcillo, MD,
José Larrañaga, MD,
Monica Rodriguez-Carballeira, MD,
Manuel Ruiz-Muñoz, MD,
Robert Hurtado-García, MD,
Sergio Prieto-González, MD, PhD,
Asun Aljibe Aguilar, MD,
Luis Caminal-Montero, MD,
Pilar Hernández-Jiménez, MD,
Cristina Rodríguez Fernández-Viagas, MD,
Pedro Castro, MD, PhD,
Victoria Morell Massó, MD,
Alejandra Flores-Chavez, MD,
Manuel Ramos-Casals, MD, PhD

Affiliations

Pilar Brito-Zerón, MD, PhD: Autoimmune Diseases Unit, Department of Medicine, Hospital CIMA-Sanitas, Barcelona, Spain
Belchin Kostov, PhD: Laboratory of Autoimmune Diseases Josep Font, CELLEX-IDIBAPS, Department of Autoimmune Diseases, ICMiD, Hospital Clínic, Barcelona, Spain; Primary Healthcare Transversal Research Group, IDIBAPS, Barcelona, Spain
Pedro Moral-Moral, MD: Immunopathology Section, Department of Internal Medicine, Hospital Universitari i Politècnic La Fe, Departament de Salut Valencia La Fe, Valencia, Spain
Aleida Martínez-Zapico, MD: Autoimmune Diseases Unit, UGC Internal Medicine, Hospital Universitario Central de Asturias, Oviedo, Spain
Carmen Díaz-Pedroche, MD, PhD: Department of Internal Medicine, Hospital Universitario 12 de Octubre, Madrid, Spain
Guadalupe Fraile, MD: Department of Internal Medicine, Hospital Ramón y Cajal, Madrid, Spain
Patricia Pérez-Guerrero, MD: UGC Internal Medicine Hospital Puerta del Mar de Cádiz, Cádiz, Spain
Eva Fonseca, MD: Department of Internal Medicine, Hospital de Cabueñes, Gijón, Spain
Angel Robles, MD: Department of Internal Medicine, Hospital La Paz, Madrid, Spain
María P. Vaquero-Herrero, MD: Department of Internal Medicine, Complejo Asistencial Universitario de Salamanca, Salamanca, Spain
María Andrés Calvo, MD: Department of Internal Medicine, Hospital Rio Hortega Valladolid, Valladolid, Spain
María José Forner, MD: Department of Internal Medicine, Hospital Clínico de Valencia, Valencia, Spain
Cesar Morcillo, MD: Autoimmune Diseases Unit, Department of Medicine, Hospital CIMA-Sanitas, Barcelona, Spain
José Larrañaga, MD: Department of Internal Medicine, Hospital Xeral, Vigo, Spain
Monica Rodriguez-Carballeira, MD: Department of Internal Medicine, Hospital Mutua de Terrasa, Terrassa, Spain
Manuel Ruiz-Muñoz, MD: Department of Internal Medicine, Hospital Universitario Fundacion Alcorcón, Alcorcón, Spain
Robert Hurtado-García, MD: Department of Internal Medicine, Hospital Vega Baja, Orihuela, Spain
Sergio Prieto-González, MD, PhD: Department of Autoimmune Diseases, ICMiD, Hospital Clínic, Barcelona, Spain
Asun Aljibe Aguilar, MD: Immunopathology Section, Department of Internal Medicine, Hospital Universitari i Politècnic La Fe, Departament de Salut Valencia La Fe, Valencia, Spain
Luis Caminal-Montero, MD: Autoimmune Diseases Unit, UGC Internal Medicine, Hospital Universitario Central de Asturias, Oviedo, Spain
Pilar Hernández-Jiménez, MD: Department of Internal Medicine, Hospital Universitario 12 de Octubre, Madrid, Spain
Cristina Rodríguez Fernández-Viagas, MD: UGC Internal Medicine Hospital Puerta del Mar de Cádiz, Cádiz, Spain
Pedro Castro, MD, PhD: Medical Intensive Care Unit, Department of Medicine, ICMiD, Hospital Clínic, Barcelona, Spain
Victoria Morell Massó, MD: Immunopathology Section, Department of Internal Medicine, Hospital Universitari i Politècnic La Fe, Departament de Salut Valencia La Fe, Valencia, Spain
Alejandra Flores-Chavez, MD: Laboratory of Autoimmune Diseases Josep Font, CELLEX-IDIBAPS, Department of Autoimmune Diseases, ICMiD, Hospital Clínic, Barcelona, Spain; Biomedical Research Unit 02, Clinical Epidemiology Research Unit, UMAE, Specialties Hospital, Western Medical Center, Mexican Institute for Social Security (IMSS), Guadalajara, Mexico; Postgraduate Program of Medical Science, University Center for Biomedical Research (CUIB), University of Colima, Colima, Mexico
Manuel Ramos-Casals, MD, PhD: Laboratory of Autoimmune Diseases Josep Font, CELLEX-IDIBAPS, Department of Autoimmune Diseases, ICMiD, Hospital Clínic, Barcelona, Spain; Department of Autoimmune Diseases, ICMiD, Hospital Clínic, Barcelona, Spain; Department of Medicine, University of Barcelona, Barcelona, Spain; Correspondence: Address to Manuel Ramos-Casals, MD, PhD, Servei de Malalties Autoimmunes, Hospital Clínic, C/Villarroel, 170, 08036 Barcelona, Spain.

Journal volume & issue: Vol. 2, no. 3
pp. 267 – 276

Abstract

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Objective: To characterize the etiologies and clinical features at diagnosis of patients with hemophagocytic lymphohistiocytosis (HLH) and correlate these baseline features with survival using an etiopathogenically guided multivariable model. Patients and Methods: The Spanish Group of Autoimmune Diseases HLH Study Group, formed in 2013, is aimed at collecting adult patients with HLH diagnosed in internal medicine departments between January 3, 2013, and October 28, 2017. Results: The cohort consisted of 151 patients (91 men; mean age, 51.4 years). After a mean follow-up of 17 months (range, 1-142 months), 80 patients died. Time-to-event analyses for death identified a worse survival curve for patients with neoplasia (P<.001), mixed microbiological infections (P=.02), and more than 1 infection (P=.01) and glucocorticoid monotherapy (P=.02). According to univariate analyses, platelets of less than 100,000/mm3 (hazard ratio [HR], 3.39; 95% CI, 1.37-8.40), leukopenia (HR, 1.81; 95% CI, 1.01-3.23), severe hyponatremia (HR, 1.61; 95% CI, 1.02-2.54), disseminated intravascular coagulation (HR, 1.87; 95% CI, 1.05-3.34), bacterial infection (HR, 1.99; 95% CI, 1.09-3.63), mixed microbiological infections (HR, 3.42; 95% CI, 1.38-8.46), and 2 or more infectious triggers (HR, 2.95; 95% CI, 1.43-6.08) were significantly associated with death. In contrast, peripheral adenopathies (HR, 0.63; 95% CI, 0.40-0.98) and the immunosuppressive drug/intravenous immunoglobulin/biological therapies (HR, 0.44; 95% CI, 0.20-0.96) were protective against all-cause mortality. Multivariable Cox proportional hazards regression analysis identified 2 or more infectious triggers (HR, 3.14; 95% CI, 1.28-7.68) as the only variable independently associated with death. Conclusion: The mortality rate of adult patients diagnosed with HLH exceeds 50%. Infection with more than 1 microbiological agent was the only independent variable associated with mortality irrespective of the underlying disease, epidemiological profile, clinical presentation, and therapeutic management.

Published in Mayo Clinic Proceedings: Innovations, Quality & Outcomes

ISSN: 2542-4548 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Medicine (General)
Website: https://www.journals.elsevier.com/mayo-clinic-proceedings-innovations-quality-and-outcomes/

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