Infection Is the Major Trigger of Adult Hemophagocytic Syndrome, an Orphan Systemic Hyperinflammatory, Life-Threatening Disease: Analysis in 147 Patients (GEAS-SEMI Registry)

Pilar Brito-Zerón¹, Alejandra Flores-Chavez^2,3,4, Pedro Moral Moral⁵, A. Martínez-Zapico⁶, Pilar Hernández-Jimenez⁷, Guadalupe Fraile Rodriguez⁸, Patricia Perez Guerrero⁹, Eva Fonseca¹⁰, Angel Robles¹¹, María Vaquero Herrero¹², Angela Ruiz de Temiño de la Peña¹³, Maria José Forner¹⁴, José Ramón Larrañaga¹⁵, Mónica Rodriguez Carballeira¹⁶, Luis Fernando Viejo Llorente¹⁷, Manuel Ruiz Muñoz¹⁸, Roberto Hurtado¹⁹, César Morcillo²⁰, Soledad Retamozo²¹ and Manuel Ramos-Casals^22,23, ¹Laboratory of Systemic Autoimmune Diseases “Josep Font”, CELLEX, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Department of Systemic Autoimmune Diseases, ICMID, Hospital Clinic, Barcelona, Barcelona, Spain, ²Department of Autoimmune Diseases, ICMiD, Hospital Clínic Barcelona, Spain., Barcelona, Spain, ³Programa de Doctorado en Ciencias Médicas, Centro Universitario de Investigaciones Biomédicas (CUIB), Universidad de Colima, Colima, Mexico, Mexico, Mexico, ⁴Unidad de Investigación Biomédica 02 (Unidad de Investigación en Epidemiología Clínica), UMAE, Hospital de Especialidades, Centro Médico Nacional de Occidente, Instituto Mexicano del Seguro Social, Jalisco, Mexico, ⁵Hospital La Fé Valencia, Valencia, Spain, ⁶Hospital Universitario de Asturias, Oviedo, Oviedo, Spain, ⁷Internal Medicine, Hospital 12 de Octubre, Madrid, Spain, ⁸Internal Medicine, Hospital Ramón y Cajal, Madrid, Madrid, Spain, ⁹Department of Internal Medicine, Hospital Universitario Puerta del Mar, Cádiz, Cadiz, Spain, ¹⁰Internal Medicine, Hospital de Cabueñes, Gijón, Gijón, Spain, ¹¹Internal Medicine, Hospital La Paz, Madrid, Madrid, Spain, ¹²Complejo Asistencial Universitario de Salamanca, Salamanca, Spain, ¹³Hospital Rio Hortega Valladolid, Valladolid, Spain, ¹⁴Department of Internal Medicine, Hospital Clínico de Valencia, Valencia, Spain, ¹⁵Department of Internal Medicine, Hospital Xeral, Vigo, Vigo, Spain, ¹⁶Hospital Mutua de Terrasa, Terrasa, Spain, ¹⁷Hospital Virgen de la Salud Toledo, Toledo, Spain, ¹⁸Department of Internal Medicine, Hospital Universitario Fundacion Alcorcón, Madrid, Spain, ¹⁹Hospital Vega Baja de Orihuela, Alicante, Spain, ²⁰Department of Medicine, Hospital CIMA-Sanitas, Barcelona, Barcelona, Spain, ²¹Rheumatology Unit, Hospital Privado Universitario de Córdoba, Institute University of Biomedical Sciences University of Córdoba (IUCBC), Cordoba, Argentina, ²²Laboratory of Systemic Autoimmune Diseases “Josep Font”, CELLEX, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Department of Systemic Autoimmune Diseases, ICMID, Hospital Clinic, Barcelona, Spain, Barcelona, Spain, ²³Department of Medicine, University of Barcelona, Barcelona, Spain., Barcelona, Spain

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: Infection, inflammation and registry

Session Information

Date: Tuesday, November 7, 2017

Title: Infection-related Rheumatic Disease

Session Type: ACR Concurrent Abstract Session

Session Time: 4:30PM-6:00PM

Background/Purpose: Hemophagocytic syndrome or hemophagocytic lymphohistiocytosis (HLH) is an increasingly-recognized condition in adults, characterized by a wide range of etiologies, symptoms and outcomes, but with a common etiopathogenic pathway leading to organ damage: an excessive hyperinflammatory response. We analyzed the role of infections as triggers of adult hemophagocytic syndrome in a National Cohort Registry.

Methods: In June 2013, the Study Group on Autoimmune Diseases (GEAS) of the Spanish Society of Internal Medicine created the national registry of patients with HLH. Patients fulfilled the diagnostic guidelines for HLH proposed by the Histiocyte Society in 1991 and updated in 2004. We investigated infections (viruses, bacteria, parasites and fungi) as causative external factors potentially involved in initiate the disease.

Results: On June 15, 2017, a total of 147 patients with HLH were included in the GEAS-SEMI Registry, 87 (59%) men and 60 (41%) women, with a mean age at diagnosis of HLH of 44; 18% were not born in Spain. The main signs and symptoms at presentation consisted of fever in 132 (90%) patients, splenomegaly in 80 (54%), polyadenopathies in 71 (48%) and hepatomegaly in 22 (15%) patients. The main internal organ involvements included pulmonary in 49 (33%) patients, renal in 46 (31%), gastrointestinal in 41 (28%) and CNS in 32 (22%) patients. The main analytical markers consisted of ferritin > 500 ng/mL in 143 (97%, mean 15498 ng/mL), thrombocytopenia <100,000/mm3 in 123 (84%), anemia < 9 g/dL in 106 (72%), and neutropenia <1000/mm3 in 65 (44%). Tissular hemophagocytosis was confirmed in 133/143 (93%) patients. Death occurred in 79 (54%) patients; a higher mortality rate was found in patients with an underlying neoplasia (33% vs 16% in survivals, p=0,023) and in those with severe anemia (85% vs 60%, p=0.001) and thrombocytopenia (95% vs 72%, p<0.001). Mean age at diagnosis was higher in patients who died in comparison with survivors (56.8 vs 42.1 yrs, p<0.001). An infectious trigger was detected in 88 (60%) of patients, mainly viruses in 37 (25%, Epstein-Barr virus infection in 16 cases), bacteria in 23 (16%, mycobacterium infection in 9 cases), fungi in 14 (10%, candida in 5 cases) and parasites in 9 (6%, leishmaniasis in 8 cases).

Conclusion:

The rate of mortality of adult patients diagnosed with hemophagocytic syndrome exceeds 50% of cases, especially in patients with underlying hematological diseases and in those with advanced age. An infection as trigger of the hyperinflammatory response was demonstrated in 60% of cases, with EBV, mycobacterium and leishmanial being the microorganisms more frequently isolated. Active infections in a patient with suspected HLH should always be treated appropriately.

Disclosure: P. Brito-Zerón, None; A. Flores-Chavez, None; P. Moral Moral, None; A. Martínez-Zapico, None; P. Hernández-Jimenez, None; G. Fraile Rodriguez, None; P. Perez Guerrero, None; E. Fonseca, None; A. Robles, None; M. Vaquero Herrero, None; A. Ruiz de Temiño de la Peña, None; M. J. Forner, None; J. R. Larrañaga, None; M. Rodriguez Carballeira, None; L. Fernando Viejo Llorente, None; M. Ruiz Muñoz, None; R. Hurtado, None; C. Morcillo, None; S. Retamozo, None; M. Ramos-Casals, None.

To cite this abstract in AMA style:

Brito-Zerón P, Flores-Chavez A, Moral Moral P, Martínez-Zapico A, Hernández-Jimenez P, Fraile Rodriguez G, Perez Guerrero P, Fonseca E, Robles A, Vaquero Herrero M, Ruiz de Temiño de la Peña A, Forner MJ, Larrañaga JR, Rodriguez Carballeira M, Fernando Viejo Llorente L, Ruiz Muñoz M, Hurtado R, Morcillo C, Retamozo S, Ramos-Casals M. Infection Is the Major Trigger of Adult Hemophagocytic Syndrome, an Orphan Systemic Hyperinflammatory, Life-Threatening Disease: Analysis in 147 Patients (GEAS-SEMI Registry) [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/infection-is-the-major-trigger-of-adult-hemophagocytic-syndrome-an-orphan-systemic-hyperinflammatory-life-threatening-disease-analysis-in-147-patients-geas-semi-registry/. Accessed .

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