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Journal Article
Research Support, Non-U.S. Gov't
Infection is the major trigger of hemophagocytic syndrome in adult patients treated with biological therapies.
Seminars in Arthritis and Rheumatism 2016 Februrary
INTRODUCTION: Hemophagocytic syndromes (hemophagocytic lymphohistiocytosis, HLH) are characterized by a wide range of etiologies, symptoms, and outcomes, but have a common etiopathogenic pathway leading to organ damage: an excessive inflammatory response. Biological therapies have been proposed as a therapeutic option for refractory HLH, but have also been related to the development of HLH in severe immunosuppressed patients.
OBJECTIVES AND METHODS: The purpose of this study was to analyze the clinical characteristics and outcomes of adult patients who developed HLH after receiving biological therapies.
RESULTS: We identified 30 patients (29 from the PubMed search and one unpublished case), including 19 women and 11 men, with a mean age of 46.5 years. Underlying diseases consisted of rheumatologic/autoimmune diseases in 24 patients and hematological neoplasia in the remaining 6. Biological agents received before the development of HLH were mainly anti-TNF agents (n = 19). Search for microorganisms confirmed systemic infection in 20 (67%) patients, including Mycobacterium tuberculosis (n = 5), cytomegalovirus (CMV) (n = 4), Epstein-Barr virus (EBV) (n = 3), Histoplasma capsulatum (n = 3), Escherichia coli (n = 2), Staphylococcus aureus, Leishmania amastigotes and Brucella melitensis (n = 1, respectively); viral infections were mainly reported in inflammatory bowel disease (IBD) patients. Patients with infections had more frequently received previous immunosuppressive therapies (p = 0.036) and had lower leukocyte counts (p = 0.020) in comparison with patients without associated infections. The outcome was described in 29 patients. After a mean follow-up of 6.3 months, 8 patients died (28%) and 6 had received anti-TNF agents. There was a high mortality rate in patients aged >65 years and those with tuberculosis (62% and 60%, respectively).
CONCLUSIONS: In patients receiving biological therapies who develop HLH, searching for a concomitant infectious process is mandatory, and specific surveillance for EBV/CMV infections (in patients with IBD) and for bacteria, including mycobacteria (in elderly patients receiving anti-TNF therapy), is recommended.
OBJECTIVES AND METHODS: The purpose of this study was to analyze the clinical characteristics and outcomes of adult patients who developed HLH after receiving biological therapies.
RESULTS: We identified 30 patients (29 from the PubMed search and one unpublished case), including 19 women and 11 men, with a mean age of 46.5 years. Underlying diseases consisted of rheumatologic/autoimmune diseases in 24 patients and hematological neoplasia in the remaining 6. Biological agents received before the development of HLH were mainly anti-TNF agents (n = 19). Search for microorganisms confirmed systemic infection in 20 (67%) patients, including Mycobacterium tuberculosis (n = 5), cytomegalovirus (CMV) (n = 4), Epstein-Barr virus (EBV) (n = 3), Histoplasma capsulatum (n = 3), Escherichia coli (n = 2), Staphylococcus aureus, Leishmania amastigotes and Brucella melitensis (n = 1, respectively); viral infections were mainly reported in inflammatory bowel disease (IBD) patients. Patients with infections had more frequently received previous immunosuppressive therapies (p = 0.036) and had lower leukocyte counts (p = 0.020) in comparison with patients without associated infections. The outcome was described in 29 patients. After a mean follow-up of 6.3 months, 8 patients died (28%) and 6 had received anti-TNF agents. There was a high mortality rate in patients aged >65 years and those with tuberculosis (62% and 60%, respectively).
CONCLUSIONS: In patients receiving biological therapies who develop HLH, searching for a concomitant infectious process is mandatory, and specific surveillance for EBV/CMV infections (in patients with IBD) and for bacteria, including mycobacteria (in elderly patients receiving anti-TNF therapy), is recommended.
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