A 59-year-old woman with a history of chronic alcohol abuse and no other past medical history presented with knee pain and shortness of breath. She reported that her symptoms had grown worse over the previous few days. She also mentioned having a dental infection for a few weeks.
Her oxygen saturation was 85% on room air, she was tachycardic to the 120s, and febrile to 38.2°C. She had diminished breath sounds in bilateral bases and a right knee that was warm with a moderate effusion but no erythema. The left side of her neck had focal swelling with fluctuance, but it was not appreciably tender or erythematous. She had normal range of motion of her neck and poor dentition but no tongue elevation. Her posterior oropharynx was normal.
What is on your differential given this constellation of symptoms and exam findings?
Find the diagnosis and case discussion on p. 27.
Diagnosis: Lemierre's Syndrome
Scientists first described Lemierre's syndrome in the literature in 1900. It was named after André Lemierre, who published a 20-patient case series patients in 1936 with what was then termed postanginal sepsis. Lemierre described the disease as a history of oropharyngeal infection followed by anaerobic sepsis (specifically with Fusobacterium necrophorum) and thrombus of the internal jugular vein.
The constellation of symptoms and findings Lemierre described remain core to the definition of the diagnosis. (Lancet Infect Dis 2012;12:808.) Most commonly, physicians will detect it in patients with recent tonsillitis, though it can also be associated with dental infections and other odontogenic or pharyngeal infections. The bacteria are thought to spread to the parapharyngeal space and the carotid sheath. The exact mechanism for this is unclear, but the result is thrombophlebitis of the internal jugular vein. The infected thrombus is then the source for bacteremia, septic emboli, and sepsis. F. necrophorum is the infectious pathogen in about 80 percent of Lemierre's cases. Other pathogens include F. nucleatum, Bacteroides species, and Streptococcus species.
Lemierre's occurs in 0.6 to 3.2 patients per million, but it is as high as 14.4 per million in the 15-24 age range, according to one systematic review that found roughly 50 percent of cases of Lemierre's syndrome occur in that age group. (Laryngoscope 2009;119:1552.) Still, Lemierre's is a rare disease, and researchers have reported some variability in the data and epidemiology. Some studies report a preponderance of cases in men over women (as high as 2:1), and some report an increasing incidence of the disease over the past 20 years, which they hypothesize this is the result of the decreasing use of antibiotics for pharyngitis. (CMAJ 2015;187:1229.) The increasing incidence and the gender differences do not seem to be supported by all studies and case reviews. (LancetInfect Dis 2012;12:808.)
Besides being rare, Lemierre's syndrome has a number of features that make the diagnosis difficult. Its course is initially indolent, with typically one to three weeks from time of onset of initial symptoms (sore throat, dental infection etc.) to time of presentation. Frequently, the initial site of infection is no longer symptomatic.
Common local findings on exam include tenderness along the neck over the internal jugular, fluctuance, or mass. These can frequently be confused with lymphadenopathy. Only about 47 percent of patients in one case series of 109 patients had neck symptoms on presentation. The presenting chief complaint is more commonly related to disseminated disease. It is not uncommon for a patient to have a Fusobacterium, which then prompts the search for the thrombophlebitis. Pulmonary involvement is very common, and 92 percent of patients had septic pulmonary emboli in one study.
The second most common site for metastatic disease is large joints. Anywhere between 16 and 26 percent of patients have sterile effusions or suppurative arthritis on testing. Less common are hepatic abscess, central nervous system infection, osteomyelitis, and endocarditis. (Clin Microbiol Rev 2007;20:695.) Our patient's chest x-ray showed bilateral pleural effusions without obvious infiltrate. She went on to have both drained with fluid studies consistent with empyema. She also had an arthrocentesis of her right knee that was consistent with infection. She went to the OR for a washout but never had any bacteria grow from the culture.
A CT scan is the diagnostic modality of choice for Lemierre's evaluation. Some cases have been diagnosed by ultrasound, but experts agree that a CT scan is the definitive study if the ultrasound is negative and there is concern for thrombus. Of note, we only discovered her neck symptoms on review of systems and physical exam. They were not her presenting complaint.
Treatment for Lemierre's syndrome is typically a multispecialty endeavor. Antibiotics are the mainstay of treatment, and should be initiated in the emergency department. It is important to cover broadly for oral flora and to include Fusobacteriumnecrophorum because it is the most common pathogen. The combination of ceftriaxone and metronidazole will cover both streptococcal infections as well as Fusobacterium. Both have reasonable CNS penetration. Ampicillin/sulbactam, clindamycin, or some carbapenems could also be considered for monotherapy. Penicillins alone should be avoided because of the high prevalence of beta-lactamase-producing bacteria. (LancetInfect Dis 2012;12:808.) No definitive studies currently recommend for or against anticoagulation for these patients. (Am J Emerg Med 2015;33:1319.)
Surgical management of these patients is determined by the extent of their embolic and metastatic disease. Frequently otolaryngology will be involved for local abscess management. General or thoracic surgery is also typically involved because of the very high incidence of empyemas and lung abscesses secondary to septic emboli. Further specialists can be involved as indicated by exam findings and imaging studies.
Most patients have a prolonged hospital course (case series range from 14 days to six weeks), but generally have a good outcome. Prior to antibiotics, this was a fatal disease with death occurring one to two weeks after the onset of symptoms. (Clin Microbiol Rev 2007;20:695.)
We started our patient on vancomycin and cefepime in the emergency department before other providers put her on ampicillin-sulbactam when her blood cultures grew group A Streptococcus. Otolaryngology performed an incision and drainage of her left neck abscess, she went to the OR with orthopedics for a washout of her right knee, and she had bilateral chest tubes placed for empyemas. Ultimately, she left the hospital with ampicillin/sulbactam via a PICC line to complete a four-week course from the time of her last positive blood cultures, per infectious disease recommendations.
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