Lemierre's syndrome is frequently due to infection with a strictly anaerobic Gram negative bacillus, Fusobacterium necrophorum, a saprophyte of the oropharynx, digestive tract and genital pathways. Lemierre's syndrome, which mainly affects young patients without any previous medical history, consists of a combination of fever, shivering, deterioration of the general condition, and pain and/or cervical tumefaction along the sterno-cleido-mastoid muscle, resulting from a suppurative thrombophlebitis of the tonsillar and peri-tonsillar veins that can extend to the internal jugular vein. This rare syndrome usually occurs following a banal pharyngitis. The appearance of pulmonary symptomatology (cough, dyspnea, thoracic pain) and/or abdominal symptomatology (hepato and/or spleno-megaly, hepatalgia, cholestasis and/or biological cytolysis) suggesting septic metastases, points to Lemierre's syndrome and justifies the implementation of a suitable antibiotic regimen. Other septic phenomena, such as arthritis, mediastinitis, meningitis and/or endocarditis, are found more rarely.
The physiopathology of Lemierre's syndrome remains controversial.
Fusobacterium necrophorum [
3] is a commensal of the normal flora of the human oropharynx, digestive tract, genital and urinary pathways and normally does not invade those mucosae. It is not known why
Fusobacterium necrophorum becomes pathogenic in certain individuals, although a lowering of local pharyngeal defenses following a viral or bacterial infection may encourage this invasion by creating an anaerobic micro environment [
4]. Another explanation is based on the capacity of these bacteria to secrete hemolysins, hemagglutinins and leukocidins, resulting in the formation of micro-abscesses by fibrin and platelet aggregation.
The recent discovery of anti-infection defense mechanisms, in particular Toll like receptors, and the finding that these receptors have functional variations open up new avenues in the pathophysiology of the Lemierre's syndrome, as illustrated in this clinical case.
The innate immune response to
Fusobacterium necrophorum is complex and involves both tissue immunity (cathelicidins and defensins) and cellular immunity (TLR receptors). Although
Fusobacterium necrophorum is not a flagellate bacterium, it is capable of synthesizing Pilin [
5]. Pilin and type IV pili (monomer), may be one of the TLR5 triggers. The TLR5-F616L and TLR5-R392 mutations, which are associated with infections by flagellate bacteria, such as
Legionella pneumophila [
6], may also be associated with
Fusobacterium necrophorum infections. To date, there is no scientific proof with this assertion.
A second facet of the symptomatology of Lemierre's syndrome is the presence of hypercoagulability, resulting in thrombophilia. A procoagulating mutation of prothrombin was recently associated with this syndrome [
7]. Interestingly, we observed a combination of one prothrombogenic and one anti-fibrinolytic variations in our patient. The last one was the 4G-4G homozygous gentotype of the PAI-1 gene which encodes for a primary anti-fibrinolytic molecule. This gentotype is responsible for an increase in plasma concentrations of PAI-1. Moreover, this mutation alone [
8] or in combination with other prothrombotic genetic anomalies [
9,
10] is a risk factor for myocardial infarction and venous thrombo-embolic phenomena. The pathophysiology of sepsis is due to imbalances in the coagulation and fibrinolysis systems, and any factor that accentuates these imbalances can influence the host response. Patients suffering from meningococcemia and whose close relatives were carriers of the 4G-4G genotype were found to be 6 times more likely to develop septic shock rather than meningitis [
11]. Moreover, this genotype was also found to be associated for an increase in the mortality of patients suffering from multiple injuries [
12] and meningococcemia [
13]. This SNP can therefore partly explain the physiopathology of Lemierre's syndrome, as well as the severity of the clinical picture in our patient. Similarly, the variation in tissue factor promoter results in a spontaneous and induced overexpression of this trigger of coagulation during sepsis. Of course we have assayed a selection of previously reported SNPs, but many other potentially important reported candidate SNPs have not been examined.
1 Jean-Paul Mira,2 Renaud Guerin,1 Sophie Cayot-Constantin,1 Olivier Lesens,3 Florence Gourdon,3 Jean-Pierre Romaszko,4 Philippe Linval,5 Henri Laurichesse,3 and Jean-Etienne Bazin1
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