title: Incidence, associated factors and clinical impact of severe infections in a large, multicentric cohort of patients with systemic lupus erythematosus.
abstract: To estimate the incidence of severe infection and investigate the associated factors and clinical impact in a large systemic lupus erythematosus (SLE) retrospective cohort.
  
  
  
  All patients in the Spanish Rheumatology Society Lupus Registry (RELESSER) who meet ≥4 ACR-97 SLE criteria were retrospectively investigated for severe infections. Patients with and without infections were compared in terms of SLE severity, damage, comorbidities, and demographic characteristics. A multivariable Cox regression model was built to calculate hazard ratios (HRs) for the first infection.
  
  
  
  A total of 3658 SLE patients were included: 90% female, median age 32.9 years (DQ 9.7), and mean follow-up (months) 120.2 (±87.6). A total of 705 (19.3%) patients suffered ≥1 severe infection. Total severe infections recorded in these patients numbered 1227. The incidence rate was 29.2 (95% CI: 27.6-30.9) infections per 1000 patient years. Time from first infection to second infection was significantly shorter than time from diagnosis to first infection (p < 0.000). Although respiratory infections were the most common (35.5%), bloodstream infections were the most frequent cause of mortality by infection (42.0%). In the Cox regression analysis, the following were all associated with infection: age at diagnosis (HR = 1.016, 95% CI: 1.009-1.023), Latin-American (Amerindian-Mestizo) ethnicity (HR = 2.151, 95% CI: 1.539-3.005), corticosteroids (≥10mg/day) (HR = 1.271, 95% CI: 1.034-1.561), immunosuppressors (HR = 1.348, 95% CI: 1.079-1.684), hospitalization by SLE (HR = 2.567, 95% CI: 1.905-3.459), Katz severity index (HR = 1.160, 95% CI: 1.105-1.217), SLICC/ACR damage index (HR = 1.069, 95% CI: 1.031-1.108), and smoking (HR = 1.332, 95% CI: 1.121-1.583). Duration of antimalarial use (months) proved protective (HR = 0.998, 95% CI: 0.997-0.999).
  
  
  
  Severe infection constitutes a predictor of poor prognosis in SLE patients, is more common in Latin-Americans and is associated with age, previous infection, and smoking. Antimalarials exerted a protective effect.
authors.affiliation: Rheumatology Department, Doctor Negrín University Hospital Las Palmas de Gran Canaria, Bco. de la Ballena s/n, 35020 Las Palmas, Spain. Electronic address: iruafer@gobiernodecanarias.org.
authors.forename: Íñigo
authors.initials: Í
authors.lastname: Rúa-Figueroa
authors.affiliation: Rheumatology Department, Gregorio Marañón University Hospital, Madrid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: López-Longo
authors.affiliation: Rheumatology Department, Doce de Octubre University Hospital, Madrid, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Galindo-Izquierdo
authors.affiliation: Rheumatology Department, Sierrallana Hospital, Torrelavega, Spain.
authors.forename: Jaime
authors.initials: J
authors.lastname: Calvo-Alén
authors.affiliation: Preventive Medicine Service, Biomedical Research Institute of Vigo (IBIV), University Hospital Complex of Vigo, Vigo, Spain.
authors.forename: Víctor
authors.initials: V
authors.lastname: Del Campo
authors.affiliation: Rheumatology Department, German Trials i Pujol Hospital, Badalona, Spain.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Olivé-Marqués
authors.affiliation: Statistical Department, Research Unit, Spanish Society of Rheumatology (SER), Madrid, Spain.
authors.forename: Sabina
authors.initials: S
authors.lastname: Pérez-Vicente
authors.affiliation: Rheumatology Department, Carlos Haya University Hospital, Málaga, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Fernández-Nebro
authors.affiliation: Rheumatology Department, Hospital of Alicante, Alicante, Spain.
authors.forename: Mariano
authors.initials: M
authors.lastname: Andrés
authors.affiliation: Rheumatology Department, Doctor Negrín University Hospital Las Palmas de Gran Canaria, Bco. de la Ballena s/n, 35020 Las Palmas, Spain.
authors.forename: Celia
authors.initials: C
authors.lastname: Erausquin
authors.affiliation: Rheumatology Department, La Princesa University Hospital, Madrid, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Tomero
authors.affiliation: Rheumatology Department, Hospital of Navarra, Pamplona, Spain.
authors.forename: Loreto
authors.initials: L
authors.lastname: Horcada
authors.affiliation: Rheumatology Department, Donostia Hospital, Donostia, Guipuzcoa, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Uriarte
authors.affiliation: Rheumatology Department, University Hospital Complex of A Coruña, A Coruña, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Freire
authors.affiliation: Rheumatology Department, Salamanca University Hospital, Salamanca, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Montilla
authors.affiliation: System Diseases and Oncology Service, Príncipe de Asturias University Hospital Alcalá de Henares, Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Sánchez-Atrio
authors.affiliation: Rheumatology Department, Marina Baixa Hospital, Alicante, Spain.
authors.forename: Gregorio
authors.initials: G
authors.lastname: Santos
authors.affiliation: Rheumatology Department, Ramon y Cajal University Hospital, Madrid, Spain.
authors.forename: Alina
authors.initials: A
authors.lastname: Boteanu
authors.affiliation: Rheumatology Department, Hospital of León, León, Spain.
authors.forename: Elvira
authors.initials: E
authors.lastname: Díez-Álvarez
authors.affiliation: Rheumatology Department, Bellvitge Hospital, Barcelona, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Narváez
authors.affiliation: Rheumatology Department, Marqués de Valdecilla University Hospital, Santander, Spain.
authors.forename: Víctor
authors.initials: V
authors.lastname: Martínez-Taboada
authors.affiliation: Rheumatology Department, University Hospital Complex of Ferrol, Ferrol, Spain.
authors.forename: Lucía
authors.initials: L
authors.lastname: Silva-Fernández
authors.affiliation: Rheumatology Department, Basurto Hospital, Bilbao, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Ruiz-Lucea
authors.affiliation: Rheumatology Department, Puerta de Hierro-Majadahonda Hospital, Madrid, Spain.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Andreu
authors.affiliation: Rheumatology Department, Hospital Insular of Gran Canaria, Las Palmas de Gran Canaria, Spain.
authors.forename: José Ángel
authors.initials: JÁ
authors.lastname: Hernández-Beriain
authors.affiliation: Rheumatology Department, University Hospital of Canarias, Tenerife, Spain.
authors.forename: Marian
authors.initials: M
authors.lastname: Gantes
authors.affiliation: Rheumatology Department, Virgen Macarena Hospital, Sevilla, Spain.
authors.forename: Blanca
authors.initials: B
authors.lastname: Hernández-Cruz
authors.affiliation: Rheumatology Department, Jerez de la Frontera University Hospital, Cádiz, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Pérez-Venegas
authors.affiliation: Rheumatology Department, Miguel Servet University Hospital, Zaragoza, Spain.
authors.forename: Ángela
authors.initials: Á
authors.lastname: Pecondón-Español
authors.affiliation: Rheumatology Department, Virgen de la Arrixaca University Hospital, Murcia, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Marras
authors.affiliation: Rheumatology Department, Son Llatzer Hospital, Mallorca, Spain.
authors.forename: Mónica
authors.initials: M
authors.lastname: Ibáñez-Barceló
authors.affiliation: Rheumatology Department, La Paz University Hospital, Madrid, Spain.
authors.forename: Gema
authors.initials: G
authors.lastname: Bonilla
authors.affiliation: Rheumatology Department, Hospital of Hospitalet-Moisés Broggi CSI, Barcelona, Spain.
authors.forename: Vicente
authors.initials: V
authors.lastname: Torrente
authors.affiliation: Rheumatology Unit, Santa Creu i Sant Pau Hospital, Barcelona, Spain.
authors.forename: Iván
authors.initials: I
authors.lastname: Castellví
authors.affiliation: Rheumatology Department, Dr. Peset Hospital, Valencia, Spain.
authors.forename: Juan José
authors.initials: JJ
authors.lastname: Alegre
authors.affiliation: Rheumatology Department, Parc Taulí Hospital, Barcelona, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Calvet
authors.affiliation: Rheumatology Department, Virgen de Valme University Hospital, Sevilla, Spain.
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Marenco
authors.affiliation: Rheumatology Department, San Cecilio Hospital, Granada, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: Raya
authors.affiliation: Rheumatology Department, Lucus Augusti Hospital, Lugo, Spain.
authors.forename: Tomás
authors.initials: T
authors.lastname: Vázquez
authors.affiliation: Rheumatology Unit, Monforte Hospital, Lugo, Spain.
authors.forename: Victor
authors.initials: V
authors.lastname: Quevedo
authors.affiliation: Rheumatology Department, Infanta Sofía University Hospital, Madrid, Spain.
authors.forename: Santiago
authors.initials: S
authors.lastname: Muñoz-Fernández
authors.affiliation: Rheumatology Department, Hospital Complex of Ourense, Orense, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Rodríguez-Gómez
authors.affiliation: Rheumatology Unit, POVISA Medical Center, Vigo, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Ibáñez
authors.affiliation: Rheumatology Department, Biomedical Research Institute of Vigo (IBIV), University Hospital Complex of Vigo, Vigo, Spain.
authors.forename: José M
authors.initials: JM
authors.lastname: Pego-Reigosa
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D000328:Adult; D000962:Antimalarials / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D015994:Incidence; D007239:Infections / Q000453:epidemiology*; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy / Q000453:epidemiology*; D008297:Male; D009173:Mycophenolic Acid; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index
chemical_list: D000305:Adrenal Cortex Hormones; D000962:Antimalarials; D018501:Antirheumatic Agents; D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid
keywords: Antimalarials; Infection; Systemic lupus erythematosus