Lemierre Syndrome: A Meta-analysis

THIEME Systematic Review Lemierre Syndrome: A Meta-analysis Mitchell R. Gore1 1 Department of Otolaryngology, State University of New York Upstate Medical University, Syracuse, New York, United States Int Arch Otorhinolaryngol 2020;24 (3) :379–385. Abstract Keywords ► sepsis ► thrombosis ► fusobacterium Introduction Lemierre syndrome, or postpharyngitis anaerobic sepsis, is an infrequent but life-threatening infection that often involves thrombosis of the internal jugular vein. The role of anticoagulation in addition to antibiotics and surgical treatment remains uncertain. Objectives 1) To perform a meta-analysis on outcomes and treatment of Lemierre syndrome; and 2) to evaluate the effect of anticoagulation in Lemierre syndrome on vessel recanalization and on mortality. Data Synthesis A Pubmed database search was conducted using the keywords Lemierre syndrome. A total of 427 studies were identified and reviewed. Data were extracted on patient demographics, treatment type including use and type of anticoagulation, type of antibiotics, presence and location of vessel thrombosis, presence of cranial neuropathies, recanalization of thrombosed vessels on follow-up imaging, organisms isolated on wound or blood cultures, and mortality. The primary outcome variables examined were the effect of anticoagulation on vessel recanalization and mortality. After the review, 359 studies totaling 394 patients between 1990 and 2017 had partial or complete data that could be analyzed. In total, 50 patients had sufficient data on the effect of anticoagulation on vessel recanalization, and 194 had sufficient data on the effect of anticoagulation on mortality. The odds ratio for anticoagulation and vessel recanalization was 1.6 (95% confidence interval ¼ 0.3 to 9.4; p ¼ 0.6). The odds ratio for anticoagulation and death was 0.6 (95% confidence interval ¼ 0.1 to 2.9; p ¼ 0.5). Conclusion The present meta-analysis did not demonstrate a statistically significant effect on vessel recanalization or mortality for patients treated with anticoagulation versus patients not anticoagulated in the Lemierre syndrome literature. Introduction Pharyngitis leading to sepsis was reported by Schottmuller1 in 1918, and in 1936 Andre Lemierre reported on a series of 20 similar cases of postpharyngitis anaerobic sepsis.2 Only two of the 20 patients survived, and the syndrome, classically comprised of pharyngeal infection, metastatic septic emboli, internal jugular vein thrombosis, and the presence of the anaerobic bacterium Fusobacterium necrophorum, was eventually named after Lemierre. Lemierre syndrome is an uncommon disease in received August 23, 2017 accepted October 20, 2019 published online April 24, 2020 Address for correspondence Mitchell R. Gore, MD, PhD, Department of Otolaryngology, State University of New York Upstate Medical University, Physicians Office Building North, Suite 4P, 4900 Borad Road, Syracuse, NY 13215, United States (e-mail: ). DOI https://doi.org/ 10.1055/s-0039-3402433. ISSN 1809-9777. the postantibiotic era, but can carry a high mortality rate if not recognized and treated aggressively.3 The most commonly associated organism, F. necrophorum, is a gram-negative, anaerobic rod-shaped bacterium that is part of the normal oral flora, but multiple other bacteria have been implicated in Lemierre syndrome, such as streptococcal species, Eikenella corrodens, and Staphylococcus aureus.4 The venous thrombosis seen in Lemierre syndrome is likely the result of endothelial dysfunction caused by inflammatory factors from the local infection. ►Fig. 1 shows axial magnetic resonance imaging Copyright © 2020 by Thieme Revinter Publicações Ltda, Rio de Janeiro, Brazil 379 380 Lemierre Syndrome Gore Fig. 1 Axial MRI image showing left jugular vein thrombosis in a patient with Lemierre syndrome. (MRI) demonstrating left internal jugular vein thrombosis resulting from streptococcal Lemierre syndrome in a young female patient. Recent studies have examined the role of anticoagulation in the treatment of Lemierre syndrome,5,6 but there is no current consensus on the role of anticoagulation and its effect on vessel recanalization in this syndrome. Recent studies have shown equivocal results, with 1 recent retrospective study showing that all patients had improvement in their thrombi by 3 months, with no evident effect on thrombosis outcomes regardless of anticoagulation,5 and another showing  91% thrombosis improvement and a low complication rate, but with no non-anticoagulated group for comparison.6 To our knowledge, there is no meta-analysis available examining the effect of anticoagulation in Lemierre syndrome on vessel recanalization/thrombus resolution, or on mortality. In the present meta-analysis, the aim was to evaluate the effect of anticoagulation on vessel recanalization in patients with Lemierre syndrome with documented follow-up imaging, to examine the effect of anticoagulation on mortality, and to collect data regarding location of thrombosed vessels, antimicrobial treatment type, causative microorganisms isolated on culture, and frequency of associated complications such as cranial nerve palsies. Review of the Literature A thorough literature search of published studies was performed in the Pubmed database using the keywords Lemierre syndrome. Studies not published in English were translated using Google translate (Google/Alphabet, Inc., Mountain View, California, US). Each study was reviewed for relevance and availability of individual patient data. The present study was exempt from Institutional Review Board evaluation, given the International Archives of Otorhinolaryngology Vol. 24 No. 3/2020 use of de-identified retrospective patient data, non-involvement of human subjects, and published literature. The present study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines statement.7 ►Fig. 2 shows the flow diagram of the study selection. Patients were included in the meta-analysis if they had evidence of a head-and-neck infection such as pharyngitis/tonsillitis or mastoiditis with at least one other aspect of Lemierre syndrome: metastatic septic emboli or thrombosis of the internal jugular vein, or other documented venous or arterial septic thrombus. Patients with a purely orthopedic or abdominal variant of Lemierre syndrome (extremity infection with thrombosis only of an extremity vessel such as the iliac vein, for example) were excluded, but patients with an abdominal, spinal, or orthopedic thrombosis in conjunction with a head-and-neck infectious source or thrombosed head-and-neck vessel were included. Patients in whom anticoagulation was stopped prior to the attainment of therapeutic levels due to thrombocytopenia or allergic reaction were considered not anticoagulated. Statistical analyses were performed using the Prism (Graphpad Software, San Diego, California, US) software for the Fisher, chi-squared (...truncated)