High risk and low prevalence diseases: Lemierre's syndrome

Abstract

Introduction

Lemierre's syndrome is a serious condition that carries with it a high rate of morbidity and even mortality.

Objective

This review highlights the pearls and pitfalls of Lemierre's syndrome, including presentation, diagnosis, and management in the emergency department (ED) based on current evidence.

Discussion

Lemierre's syndrome is a condition marked by septic thrombophlebitis of the internal jugular vein (IJV), with the classic triad of pharyngotonsillitis, IJV thrombosis, and septic emboli resulting in metastatic abscess. It typically begins as pharyngitis, often caused by Fusobacterium necrophorum. Patients most commonly present with fever, recently diagnosed pharyngitis, and neck pain or swelling. Septic emboli may affect multiple organ systems, most commonly the pulmonary system. The disease should be considered in patients with prolonged symptoms of pharyngitis, pharyngitis that improves but then worsens, critically ill patients with pharyngitis, patients with pharyngitis and infection at a secondary site, and neck signs/symptoms. Diagnosis includes throat and blood cultures, as well as imaging to include computed tomography of the neck and chest with intravenous contrast. Additional imaging of other areas should be performed as clinically indicated. Initial management includes hemodynamic stabilization with intravenous fluids and vasopressors as needed, as well as broad-spectrum antibiotics. Anticoagulation for the primary thrombus and possible septic emboli is controversial and should be considered in a multidisciplinary approach with admission.

Conclusions

An understanding of Lemierre's syndrome can assist emergency clinicians in diagnosing and managing this potentially deadly disease.

Introduction

This article series addresses high risk and low prevalence diseases that are encountered in the emergency department (ED). Much of the primary literature evaluating these conditions is not emergency medicine focused. By their very nature, many of these disease states and clinical presentations have little useful evidence available to guide the emergency physician in diagnosis and management. The format of each article defines the disease or clinical presentation to be reviewed, provides an overview of the extent of what we currently understand, and finally discusses pearls and pitfalls using a question and answer format. This article will discuss Lemierre's syndrome, a constellation of findings centered around post-pharyngitis septic thrombophlebitis. This condition's low prevalence but high morbidity, as well as its variable atypical patient presentations and challenging diagnosis, makes it a high risk and low prevalence disease. The aim of this paper is to provide emergency clinicians with clinical knowledge concerning this rare but potentially lethal condition so that they can diagnose this condition expeditiously and provide acute stabilization and management.

Lemierre's syndrome most commonly refers to septic thrombophlebitis of the internal jugular vein (IJV), with the classic triad of pharyngotonsillitis, IJV thrombosis, and septic emboli resulting in metastatic abscess [1]. However, there is no standardized definition for the syndrome with variable criteria utilized throughout the literature [[2], [3], [4]]. The condition most commonly begins with an oropharyngeal infection, but other infections have been associated with the disease [1,[5], [6], [7]].

Andre Lemierre published a case series in 1936 of 20 patients (of which 18 died) with post-pharyngitis anaerobic sepsis and IJV thrombosis, although similar presentations were reported as early as 1898 [[8], [9], [10]]. Fusobacterium necrophorum, an obligate anaerobic gram negative rod often found as part of the normal oral flora, is the most common cause of Lemierre's syndrome, isolated in 48–82% of cases, as well as the most common cause of anaerobic septicemia originating from the oropharynx [2,4,5,8,[11], [12], [13]]. Fusobacterium necrophorum has several factors that increase its virulence including adhesins, endotoxins, leukotoxins, and hemolysins, which increase its ability to cause a necrotic abscess [[2], [3], [4], [5],10,13]. This microbe can also produce beta-lactamase [[2], [3], [4], [5],10,13]. Polymicrobial cases demonstrate that Fusobacterium necrophorum-produced leukotoxin can facilitate the growth of aerobic Streptococci and other microbes [3,10,14]. Other bacterial causes include streptococci, Eikenella corrodens, Klebsiella pneumonia, Bacteroides species, and Staphylococcus aureus [[14], [15], [16]]. Several reports propose that preceding localized infections, to include infectious mononucleosis caused by Epstein-Barr virus (EBV), weaken oropharyngeal tissue integrity and the local immune response, allowing for direct penetration and extension of the bacterial infection [8,10,11,13,15,[17], [18], [19], [20], [21]].

The causative microbe enters through the oropharyngeal mucosa via inflammation, trauma, or tissue destruction. The organism then spreads through deep connective cervical tissues into the local hematogenous and/or lymphatic supply, extending to the veins of the head and neck, most commonly the IJV [[5], [6], [7]]. The bacteria cause inflammation of the blood vessel wall and activate platelets and the coagulation cascade, leading to thrombus formation. This initial thrombus may result in septic emboli that affect other organs, most commonly the pulmonary system [13,22].

Large septic thrombus in the IJV and the propensity for metastatic septic emboli in Lemierre's syndrome create significant concerns for morbidity and mortality. The initially reported mortality of 90% dropped in the modern era largely due to early antibiotic use, but the current mortality rate remains significant, ranging from 2 to 18% [2,8,9,14,21,23,24]. Approximately 52% of patients require a prolonged hospital or intensive care unit (ICU) length of stay (median 25 days) [23]. Literatures suggests diffuse spread of septic emboli, most notably involving the lungs (37–100%), joints (11–27%), and brain (3%) [4,5,8,9,13,15,25,26]. There are no reported cases of a hemodynamically significant pulmonary embolism (PE) [4]. Limited data demonstrate up to 12% of patients experience a recurrence or clinical sequelae after hospital discharge, including cranial nerve palsies, paralysis, paresis, limb amputation, or blindness, and case reports describe airway compromise due to Lemierre's syndrome [2,4,27].

Overall, Lemierre's syndrome is rare, with an incidence of 0.8–3.6 cases per 1,000,000 per year [25,[28], [29], [30]]. However, rates are disproportionately concentrated in adolescent populations, with 14.4–16 cases per 1,000,000 per year in persons aged 16–24 years-old compared to 1.4 million cases per 1,000,000 per year in persons over 40 years-old [15,23,25,28,30]. Some studies limit Lemierre's syndrome diagnosis only to those who reported a preceding oropharyngeal infection, which likely underestimates the rate of diagnosis [2,29]. While some note there is an increasing rate of occurrence, particularly amongst younger populations, overall there are no consistent frequency trends [2,18,25,28,30,31]. Nevertheless, the incidence of Lemierre's syndrome may be increasing due to several factors, primarily the increasingly conservative use of antibiotics and decreased rates of tonsillectomies [2,13,18,29].