Lemierre syndrome: early recognition and management

Diagnosis

Following the initial oropharyngeal infection, a parapharyngeal abscess forms and thrombophlebitis of the internal jugular vein occurs. The most common symptoms at the beginning are sore throat (33%), neck mass (23%) and neck pain (20%).5 Presentation with subsequent complications does not tend to occur until one to three weeks later.4^,6^,7

Riordan8 proposed a definition of the syndrome with three criteria: history of recent upper respiratory tract infection or compatible clinical findings; evidence of metastatic infectious lesions; and either evidence of internal jugular vein thrombophlebitis or isolations of F. necrophorum or Fusobacterium species from blood culture or a normally sterile site. Therefore, the diagnosis can be made based on clinical and radiologic findings in the absence of culture results.

The incidence is about 0.6–3.6 cases per million overall;6^,7 however, incidence rates appear to be increasing.2^,6 This may be a result of increased reporting or improved identification of cases with more advanced imaging techniques. It has also been hypothesized that the increasing incidence may be due to reduced antibiotic prescribing for sore throats in primary practice because of concerns about development of antibiotic resistance.2^,6

Incidence rates rise to 14.4 cases per million in those aged 15–24 years.3^,7 This rise is thought to be due to involution of tonsillar tissue, predisposing this age group to infections in tonsillar crypts.4

Complications of Lemierre syndrome are a result of septic emboli from the thrombus, systemic effects of sepsis and clot extension. Sites of metastatic infection, in order of frequency of involvement, are lung, joint, muscle, bone, liver, skin, spleen and endocardium.8 Pleuropulmonary involvement occurs in 97% of cases.6^,7

The most commonly implicated organism is F. necrophorum, a gram-negative anaerobic bacillus.2^,8 Unlike other anaerobic infections, which are frequently polymicrobial, it is often the sole isolate from blood cultures.2 It produces hemagglutinin, promoting platelet aggregation, which has been put forward as the explanation for thrombus formation.4^,5^,9 Detection of this organism should prompt clinicians to investigate for internal jugular vein thrombus; however, given the time required for anaerobic blood culture results, the diagnosis of Lemierre syndrome is first and foremost clinical.

Treatment

Fusobacterium necrophorum is usually susceptible to penicillin, clindamycin and metronidazole, whereas it tends to be resistant to macrolides.2 Antimicrobial combinations resistant to β-lactamase, such as piperacillin–tazobactam, are also recommended, because up to a quarter of F. necrophorum can be β-lactamase producing.2^,7^,8 Other bacteria that have been identified include Streptococcus and Staphylococcus species, and empiric therapy must also cover these organisms.6^,7 The mainstay of treatment for Lemierre syndrome is early administration of intravenous antibiotics and surgical drainage of collections. Prolonged therapy for three to six weeks is recommended to allow time for antibiotics to penetrate into the fibrin clot and necrotic abscesses.7

Owing to the rarity of the disease, the evidence for use of anticoagulation to break down the internal jugular vein thrombus is limited to anecdotal case observations.7 In our case, anticoagulation was started because of extension of the thrombus, soon after surgical drainage of the soft tissue collection on the dorsum of the hand. Because anticoagulation occurred within days of surgery, it is difficult to assess whether the addition of this treatment was a factor in clinical improvement.

Early detection

Fusobacterium necrophorum appears to be responsible for 10% of all throat infections,5 but early detection on clinical grounds is challenging because of the wide differential diagnosis for sore throat. The differential diagnosis includes viral pharyngitis, Epstein–Barr virus, streptococcal pharyngitis, peritonsillar abscess and retropharyngeal abscess. In unvaccinated patients, diphtheria and epiglottitis should also be considered. Infection with F. necrophorum is more likely in patients aged 15–24 years, those with recurrent sore throats and those with a raised C-reactive protein level.3^,5^,6 However, it is appreciated that these features are not unique to this bacteria.

In our patient’s case, a throat swab was taken during his first visit to the emergency department. The culture grew group G Streptococcus; this infection was not treated, because the hospital’s policy is to treat only group A Streptococcus infection, the primary culprit in rheumatic fever. Culturing Fusobacterium, however, requires a special medium, which our laboratory does not routinely use unless requested to do so. As a result, the throat culture in our patient would not have shown Fusobacterium.

This raises the question of the utility of testing for Fusobacterium in those with throat infections. The reasoning for testing for fusobacterial throat infections is similar to that of testing for group A streptococcal throat infections that can cause the rare, but severe, complication of rheumatic fever. Bank and colleagues3 conducted a detailed cost-effectiveness analysis of testing cases of pharyngitis in the high-risk age group (15–24 yr) with throat swabs to detect F. necrophorum and treatment of positive results with antibiotics. They found that, because of the high cost burden of Lemierre syndrome and peritonsillar abscess, it would take only a few cases to be prevented for testing for Fusobacterium to be cost-effective.3

Although it is plausible that giving treatment for throat cultures positive for F. necrophorum would lead to a reduction in incidence of Lemierre syndrome, this requires further investigation with a prospective study. If this were deemed to be an effective public health measure, throat swabs would need to be taken with the initial sore throat, because once thrombophlebitis has occurred, the infection is largely intravascular and there is rarely any pharyngeal exudate.7

• The classic presentation of Lemierre syndrome is that of a young (age 15–24 yr) patient with a recent oropharyngeal infection presenting with sepsis, unilateral neck pain from internal jugular thrombophlebitis, and clinical or radiologic evidence of septic emboli.

• Isolation of Fusobacterium species should prompt the clinician to consider a diagnosis of Lemierre syndrome.

• The mainstay of treatment for Lemierre syndrome is administration of intravenous antibiotics; empiric treatment should cover anaerobic organisms, Streptococcus and Staphylococcus species, and include a β-lactamase inhibitor, such as piperacillin–tazobactam.