Alejandra Flores-Chávez1, Belchin Kostov2, Roser Solans3, Guadalupe Fraile4, Brenda Maure5, Carlos Feijoo-Massó6, Francisco-Javier Rascón7, Roberto Pérez-Alvarez8, Mónica Zamora-Pasadas9, Alicia García-Pérez10, Miguel Lopez-Dupla11, Miguel-Ángel Duarte-Millán12, Mar Ripoll13, Eva Fonseca-Aizpuru14, Pablo Guisado-Vasco15, Blanca Pinilla16, Gloria de-la-Red17, Antonio-J Chamorro18, César Morcillo19, Patricia Fanlo20, Mª José Soto-Cárdenas21, Soledad Retamozo22, Manuel Ramos-Casals23, Pilar Brito-Zerón24. 1. Lab. Autoimmune Dis. Josep Font, IDIBAPS, ICMiD, Hosp. Clínic, Barcelona; Biomedical Res. Unit 02, Clin.Epidemiol.Res. Unit, UMAE, Specialties Hosp., Western Med. Center, Mexican Inst.for Social Security, Guadalajara; & Univ. of Colima, Mexico. 2. Primary Care Research Group, IDIBAPS, Centre d'Assistència Primària ABS Les Corts, GESCLINIC, Barcelona, Spain. 3. Systemic Autoimmune Diseases Unit, Hospital Vall d'Hebron, Barcelona, Spain. 4. Systemic Autoimmune Diseases Unit, Hospital Ramón y Cajal, Madrid, Spain. 5. Systemic Autoimmune Diseases Unit, Complejo Hospitalario Universitario, Vigo, Spain. 6. Systemic Autoimmune Diseases Unit, Hospital Parc Taulí, Sabadell , Spain. 7. Systemic Autoimmune Diseases Unit, Hospital Son Espases, Palma de Mallorca, Spain. 8. Department of Internal Medicine, Hospital do Meixoeiro, Vigo, Spain. 9. Systemic Autoimmune Diseases Unit, Hospital Virgen de las Nieves, Granada, Spain. 10. Systemic Autoimmune Diseases Unit, Hospital Universitario Central de Asturias, Oviedo, Spain. 11. Systemic Autoimmune Diseases Unit, Hospital Joan XXIII, Tarragona, Spain. 12. Systemic Autoimmune Diseases Unit, Hospital de Fuenlabrada, Madrid, Spain. 13. Systemic Autoimmune Diseases Unit, Hospital Infanta Sofía, Madrid, Spain. 14. Systemic Autoimmune Diseases Unit, Hospital de Cabueñes, Gijón, Spain. 15. Department of Internal Medicine, Complejo Hospitalario Ruber Juan Bravo, Madrid, Spain. 16. Systemic Autoimmune Diseases Unit Medicine, Hospital Gregorio Marañón, Madrid, Spain. 17. Systemic Autoimmune Diseases Unit, Hospital Esperit Sant, Santa Coloma de Gramenet, Spain. 18. Systemic Autoimmune Diseases Unit, Hospital Universitario de Salamanca, Spain. 19. Systemic Autoimmune Diseases Unit, Hospital CIMA-Sanitas, Barcelona, Spain. 20. Systemic Autoimmune Diseases Unit, Hospital Virgen del Camino, Pamplona, Spain. 21. Department of Medicine, University of Cadiz, Spain. 22. Laboratory of Autoimmune Diseases Josep Font, IDIBAPS, ICMiD, Hospital Clínic, Barcelona, Spain; Hospital Privado Universitario de Córdoba, Institute University of Biomedical Sciences University of Córdoba (IUCBC), Cordoba, Argentina. 23. Laboratory of Autoimmune Diseases Josep Font, IDIBAPS, ICMiD, Hospital Clínic, Barcelona; Department of Autoimmune Diseases, ICMiD, Hospital Clinic, Barcelona, Spain. 24. Laboratory of Autoimmune Diseases Josep Font, IDIBAPS, ICMiD, Hospital Clínic, Barcelona; Systemic Autoimmune Diseases Unit, Hospital CIMA-Sanitas, Barcelona, Spain.
Abstract
OBJECTIVES: To analyse the clinical features and outcomes of patients presenting with life-threatening systemic disease in a large cohort of Spanish patients with primary Sjögren's syndrome (SS). METHODS: The GEAS-SS multicentre registry was formed in 2005 with the aim of collecting a large series of Spanish patients with primary SS, and included more than 20 Spanish reference centres with substantial experience in the management of SS patients. By January 2018, the database included 1580 consecutive patients fulfilling the 2002 classification criteria for primary SS. Severe, life-threatening systemic disease was defined as an activity level scored as "high" in at least one ESSDAI domain. RESULTS: Among 1580 patients, 208 (13%) were classified as presenting a severe, potentially life-threatening systemic disease: 193 presented one ESSDAI domain classified as high, 14 presented two high scored domains and only one presented three high activity domains. The ESSDAI domains involved consisted of lymphadenopathy in 78 (37%) cases, CNS in 28 (13%), PNS in 25 (12%), pulmonary in 25 (12%), renal in 21 (10%), cutaneous in 19 (9%), articular in 18 (9%), haematological in 7 (3%) and muscular in 4 (2%). Patients with severe systemic disease were more frequently men (p=0.001) and had a higher frequency of anaemia (p<0.001), lymphopenia (p<0.001), rheumatoid factor (p=0.021), low C3 levels (p=0.015), low C4 levels (p<0.001) and cryoglobulins (p<0.001). From a therapeutic point of view, systemic patients received more frequently glucocorticoids (p<0.001), immunosuppressants (p<0.001), intravenous immunoglobulins (p=0.008) and rituximab (p<0.001). We found an overall mortality rate of 20% in severe systemic patients, a rate that reached to 33% in patients presenting two or more high systemic involvements; these patients had a higher frequency of low C4 levels (p=0.012) and cryoglobulins (p=0.001) in comparison with those with a single severe organ involved. CONCLUSIONS: 13% of patients with primary SS develop a potentially life-threatening systemic disease (mainly lymphoma, but also severe internal organ involvements including nervous system, the lungs and the kidneys). This subset of patients requires intensive therapeutic management with a mortality rate of nearly 20% of cases.
OBJECTIVES: To analyse the clinical features and outcomes of patients presenting with life-threatening systemic disease in a large cohort of Spanish patients with primary Sjögren's syndrome (SS). METHODS: The GEAS-SS multicentre registry was formed in 2005 with the aim of collecting a large series of Spanish patients with primary SS, and included more than 20 Spanish reference centres with substantial experience in the management of SS patients. By January 2018, the database included 1580 consecutive patients fulfilling the 2002 classification criteria for primary SS. Severe, life-threatening systemic disease was defined as an activity level scored as "high" in at least one ESSDAI domain. RESULTS: Among 1580 patients, 208 (13%) were classified as presenting a severe, potentially life-threatening systemic disease: 193 presented one ESSDAI domain classified as high, 14 presented two high scored domains and only one presented three high activity domains. The ESSDAI domains involved consisted of lymphadenopathy in 78 (37%) cases, CNS in 28 (13%), PNS in 25 (12%), pulmonary in 25 (12%), renal in 21 (10%), cutaneous in 19 (9%), articular in 18 (9%), haematological in 7 (3%) and muscular in 4 (2%). Patients with severe systemic disease were more frequently men (p=0.001) and had a higher frequency of anaemia (p<0.001), lymphopenia (p<0.001), rheumatoid factor (p=0.021), low C3 levels (p=0.015), low C4 levels (p<0.001) and cryoglobulins (p<0.001). From a therapeutic point of view, systemic patients received more frequently glucocorticoids (p<0.001), immunosuppressants (p<0.001), intravenous immunoglobulins (p=0.008) and rituximab (p<0.001). We found an overall mortality rate of 20% in severe systemic patients, a rate that reached to 33% in patients presenting two or more high systemic involvements; these patients had a higher frequency of low C4 levels (p=0.012) and cryoglobulins (p=0.001) in comparison with those with a single severe organ involved. CONCLUSIONS: 13% of patients with primary SS develop a potentially life-threatening systemic disease (mainly lymphoma, but also severe internal organ involvements including nervous system, the lungs and the kidneys). This subset of patients requires intensive therapeutic management with a mortality rate of nearly 20% of cases.