Author: Ian Bodford, MD (EM Resident Physician, UTSW/Parkland) // Edited by: Alex Koyfman, MD (@EMHighAK), Brit Long, MD (@long_brit, EM Resident Physician at SAUSHEC, USAF)

It’s a busy night shift in your emergency department. You are seeing several sick patients, and EMS brings in a patient that tops them all. He presents as a 27 year-old previously healthy male who appears slightly obtunded and tachypneic. EMS reports that the patient is tachycardic with hypotension. They have established IV access and have given the patient a liter of saline without much change in his vital signs. In your ED, the nurses report similar findings on their assessment of his vitals, but they also report a temperature of 39.1 °C. Speaking with the patient’s family, you establish that the patient’s only complaint over the past several days has been a sore throat. You then mutter under your breath “Yeah right, septic shock from a sore throat.” On physical exam, you look in the back of the patient’s throat, and sure enough, he has erythema, likely pharyngitis. You also palpate the patient’s neck and feel several enlarged lymph nodes, and the patient arouses to the painful palpation of his neck. Otherwise, the physical exam is benign and does not point to any other infectious symptoms. Seriously? Septic shock from a sore throat? It happens and is due in part to Lemierre’s syndrome.

Classification : Lemierre’s syndrome is suppurative thrombophlebitis of the jugular vein. It also is called postanginal sepsis, as well as necrobacillosis. First described by Coumont and Cade in 1900, it is named for a French physician named Andre Lemierre after he described 20 cases in 1936.

Epidemiology : Although extremely rare now, Lemierre’s syndrome was common prior to the age of penicillins. Currently it is thought that the prevalence of the syndrome is on the rise due to the practice of decreasing prescriptions for pharyngitis-like symptoms, as well as increasing bacterial resistance. Rates as low as 0.8 per million people in the general population have been reported. This has led to the syndrome being known as a “forgotten disease” when coming up with a differential diagnosis for patients. Prior to antibiotics, mortality rates exceeded 90%; however, now rates are less than 15% if diagnosed in a reasonable amount of time.

Risk Factors : Lemierre’s syndrome occurs most often in young, previously healthy males. It is most frequently preceded by pharyngitis; however, all infections involving the oropharynx have been implicated, including peritonsillar abscesses and dental infections.

Features : The cause of the infection is almost always a member of the Fusobacterium species, most commonly Fusobacterium necrophorum. This bacteria is a normal component of the flora of the oropharynx. Other causative bacteria are anaerobes making up the normal flora of the mouth, including Eikenella corrodens and Bacteroides. A topic of debate is whether the anaerobic bacteria is the cause of the initial infection of the oropharynx or if it is a bystander that invades the mucosa after an infection has been caused by a more typical pathogen like Streptococcus or Epstein-Barr virus. Either way, the anaerobes then spread to the parapharyngeal space and then further spread into the sheath of peritonsillar vasculature, which includes the internal jugular vein. The bacterial invasion causes a thrombus to form in the internal jugular vein that contains the invading pathogen. This thrombus can then lead to the septic embolization of end organs, most commonly the lung (up to 97% or patients) with the second most common being joint involvement. The bacteria also produces hemagglutinin, not only leading to platelet aggregation and clot formation, but potentially causing the deadly condition of DIC. Rarely, central line insertion into the internal jugular vein can also lead to Lemierre’s syndrome.

This syndrome should always be considered in a patient with preceding pharyngitis who appears more ill than what would be thought. If the patient has septic emboli in their lungs or is not improving despite antimicrobial therapy, it should also be considered. Most patients present with fever and rigors with respiratory distress, and most will have some type of neck or throat pain with enlarged lymph nodes. Abdominal pain with nausea, vomiting, and diarrhea can be seen. End-organ damage can also be detected, including decreased urine output, as well as spleen and liver enlargement. Occasionally, meningitis will also occur. Patients can also complain of generalized malaise with muscle aches.

Differential Diagnosis : Initially, Lemierre’s syndrome appears as all other causes of septic shock, so the differential is wide; however, with further information from the patient’s history and physical exam, it begins to narrow. If the lungs are involved with other symptoms including fever, malaise, and mental status change, it is important to consider other diagnoses, including Q fever, tuberculosis, and pneumonia.

Diagnosis : The organism can usually be obtained from both blood cultures and the expression of purulent fluid from a nidus in the oropharynx (if present). The causative bacteria can take up to one week to grow in the laboratory. The most effective tool that can be used in the ED is high-resolution CT with contrast of the soft tissue of the neck. Ultrasound has been shown to be capable of seeing a thrombus in the jugular vein and can usually detect the extent of the thrombus, but keep in mind that it cannot detect a thrombus deep to the mandible or clavicle. Blood work can also be obtained, including ESR, CRP, and WBCs. LFTs and renal function tests may also be elevated if these end organs are damaged. If the lung is involved, a CXR or CT chest can show septic emboli. Also, aspirates of infected joints will demonstrate an infectious picture with cell count and culture.

Management : As with all patients, the airway, breathing, and circulation should be assessed first. A Lemierre’s syndrome patient could very well have a peritonsillar abscess obstructing their airway and require intubation. They can also be septic, causing hypotension. Fluid resuscitation is appropriate. IV antibiotics should be administered immediately. Fusobacterium necrophorum is a beta-lactamase producer, so this should be kept in mind when selecting an antibiotic regimen. Some acceptable regimens include ampicillin-sulbactam (3 g q6h), ticarcillin-clavulanic acid (3.1 g q6h), Zosyn (4.5 g q6h), or single therapy with a carbapenem; however, metronidazole is the most commonly used antibiotic as it has activity against all species of Fusobacterium and has good tissue penetration. If the infection is caused by skin flora from a central venous catheter, vancomycin is used. Duration of antibiotic therapy can be guided by resolution of septic emboli, but is usually no less than 4 weeks. The nidus of infection should also be removed i.e. CVC, PTA, infected tooth, etc. Surgery is typically withheld unless a patient has ongoing sepsis unresponsive to antibiotic therapy. Occasionally, the whole jugular vein must be excised. Anticoagulation is very controversial and clinical trials have yet to be conducted.

Major Points :

Lemierre’s syndrome is a suppurative thrombophlebitis of the internal jugular vein, usually caused by direct invasion of oropharynx anaerobes , specifically Fusobacterium necrophorum.

, specifically Fusobacterium necrophorum. Although once rare, Lemierre’s syndrome is becoming more and more common. This is likely due to enhanced forms of diagnosis, bacterial antibiotic resistance, and providers not prescribing antibiotics for oropharyngeal infections .

. Known as a “forgotten disease,” it is important for physicians to have a basic knowledge of Lemierre’s syndrome as it has a high mortality if missed. Any young, previously healthy patient with fever, neck pain, and respiratory involvement should have Lemierre’s syndrome in their differential diagnosis .

. Diagnosis is made through labwork (CRP, ESR, WBCs), blood/aspirate cultures, and CT soft tissue neck with contrast /US of the jugular vein.

/US of the jugular vein. Management includes airway protection and fluid resuscitation if needed, followed by IV antibiotic infusion. If patients remain in septic shock despite fluids and IV antibiotics, surgery might be needed for thrombectomy. Anticoagulation remains controversial and needs further study.

References / Further Reading

– Coultas, et. al. “Lemierre’s Syndrome: Recognising a Typical Presentation of a Rare Condition.” Case Reports in Infectious Diseases. Volume 2015. Article ID 797415. 5 pages. 14 Nov 2014.

– Crowley, et. al. “Sore throat… don’t forget Lemierre’s syndrome.” BMJ Case Reports. 9 Jan 2015. <http://casereports.bmj.com/content/2015/bcr-2014-208225.long>

– Frederick and Urwiler. “Lemierre’s syndrome.” Journal of Neuroscience Nursing. Volume 47. Issue 1. Pg. 55. Feb 2015.

– Spelman, Denis. “Suppurative (septic) thrombophlebitis.” UpToDate. 14 Aug 2013. www.uptodate.com

– http://www.ncbi.nlm.nih.gov/pubmed/22809766

– http://www.ncbi.nlm.nih.gov/pubmed/23216731

– http://www.ncbi.nlm.nih.gov/pubmed/22033390

– http://www.ncbi.nlm.nih.gov/pubmed/21035986

– http://www.ncbi.nlm.nih.gov/pubmed/19327936

– http://www.ncbi.nlm.nih.gov/pubmed/18799283