Fusobacteria are nonmotile, sporulating, obligate anaerobic Gram-negative rods that are normal flora in the human upper respiratory tract, gastrointestinal tract, and female genital tract. Fusobacterium
exhibit classic tapered ends and filamentous forms, with or without swollen areas and large round bodies. Various toxins have been identified that are produced by Fusobacteria that may play a role in the pathogenicity. Unlike other anaerobic bacteria, Fusobacteria produce a lipopolysaccharide endotoxin with strong biologic activity, as well as a leukocidin and hemolysin, assisting in destruction of white and red blood cells[1
]. Hemagglutinin production augments the fulminant nature of the disease, causing platelet aggregation and septic thrombus formation [2
]. Fusobacterium necrophorum and F nucleatum
are the species most often the causative agents of Lemierre's syndrome, but other Fusobacterium
species can occasionally be found.
The exact mechanism of invasion and penetration of the pharyngeal mucosa has not been determined. Current hypothesis include the help of an underlying synergistic infectious process (bacterial or viral), with a concomitant decline in host resistance [3
]. When pharyngitis due to Fusobacterium
species occurs, the physical proximity of the vessels in the lateral pharyngeal space permits extension from the peritonsillar space to the internal jugular vein. This usually occurs in less than a week from the development of pharyngitis. Once invasion of the internal jugular vein is achieved, the resultant bacteremia triggers platelet aggregation and thrombus formation [4
]. Thrombus formation and rapid bacterial growth result in a nidus for metastatic septic embolization.
The major clinical features of Lemierre's syndrome include primary infection of the oropharynx, bacteremia, radiographic or clinical evidence of internal jugular vein thrombosis, and septic metastatic foci. Accurate history and physical examination are needed for diagnosis. The syndrome should be suspected in young, otherwise healthy patients who have an underlying oropharyngeal infection and follow a worsening clinical course, requiring hospitalization for sepsis and worsening pulmonary symptoms in the setting of a recent pharyngeal infection. The patient's lateral neck swelling and tenderness (representing thrombophlebitis of the internal jugular or surrounding veins) is often mistaken for cervical lymphadenopathy. Patients can also demonstrate the "cord sign", an induration of the internal jugular vein beneath the anterior border of the sternocleidomastoid muscle [5
]. Emboli from these veins metastasize to the pulmonary vasculature in up to 85% of patients, resulting in complicated pleural effusions, pulmonary abscesses, and Empyema [6
]. The chest radiograph typically shows multiple nodular infiltrates scattered throughout both lung fields [7
]. Adult respiratory distress syndrome (ARDS) occurs in a relatively small proportion of cases and fewer than 10% of cases reported in cited literature since 1990 have required mechanical ventilation. Other manifestations can include localized arthralgias and diffuse abdominal pain, which may represent septic embolic seeding of joints and abdominal microabscesses [8
]. The hip is the most commonly infected joint in published series, but osteomyelitis in Lemierre's syndrome is rare. Abnormal coagulation studies and liver function tests, in the situation of hepatic seeding and abscess formation, may also be seen [9
Imaging of the internal jugular vein and associated vasculature may be accomplished with ultrasound, computed tomography, magnetic resonance imaging to establish presence of thrombophlebitis [10
]. Contrast computed tomography of the neck provides the definitive diagnosis, showing distended veins with enhancing walls, intraluminal filling defects, and swelling of adjacent soft tissues [11
]. Ultrasonography can also confirm internal jugular vein thrombosis, showing localized echogenic regions within a dilated vessel [12
]. Confirmation of Lemierre's syndrome is provided by demonstration of Fusobacterium
species in anaerobic blood culture [13
The recommended treatment of Fusobacterium
species in Lemierre's syndrome is combination therapy with parenteral high dose penicillin and metronidazole. Intravenous clindamycin may be used in penicillin-allergic patients [14
]. Pulmonary abscess and empyema must be addresses with definitive surgical drainage and evacuation. The role of anticoagulant therapy is controversial and is not presently recommended as a standard of care [15
In conclusion, Lemierre's syndrome is a rare disorder caused by Fusobacterium species characterized by internal jugular vein thrombosis, oropharyngeal infection, septicemia, and presence of metastatic foci may be encountered today. The implications of this case are several and important. First, while many publications have discouraged the use of routine anaerobic blood cultures to guide antimicrobial therapy, this case illustrates the usefulness of having anaerobic bottles in blood culture sets. For a syndrome that is so characteristic, it is notable how often the diagnosis is missed until an anaerobic gram-negative rod is isolated from blood culture or other sterile site. There are several contributing factors for this. The variable manifestations of the septic emboli can distract clinicians from the initial oropharyngeal sepsis. In addition, the cases can present to a wide variety of specialties, including general medicine, otorhinolaryngology, pulmonology, orthopedics, and general surgery. The differential diagnosis of Lemierre's syndrome is vast and includes viral pharyngitis, infectious mononucleosis, acute retroviral syndrome, leptospirosis, acute bacterial pneumonia, atypical pneumonia, aspiration pneumonia, infective endocarditis, intra-abdominal sepsis.
Perhaps most importantly, most clinicians and even medical microbiologists have never seen a case. Although Lemierre's syndrome remains a rare disease, recent papers have suggested that the incidence of the condition is rising. More prudent and judicious antibiotic-prescribing habits in the setting of upper respiratory tract infections attributed to viral etiologies may lead to clinical reappearance of this often forgotten disease. Not only do antibiotics shorten the duration of symptoms related to bacterial pharyngitis, but can also prevent suppurative complications such as peritonsillar abscess. The typical clinical picture of Lemierre's syndrome is characteristic but many general practitioners are unaware of this condition and diagnosis is often delayed with potentially fatal complications. Physicians should be aware of this syndrome and should consider it in the differential diagnosis of a young patient suffering from a fulminant oropharyngeal infection with a deteriorating clinical course.