Lemierre's syndrome

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Lemierre's syndrome
Classification and external resources
DiseasesDB 31108

Lemierre's syndrome (or Lemierre's disease, also known as postanginal shock including sepsis and human necrobacillosis) refers to thrombophlebitis of the internal jugular vein.[1] It most often develops as a complication of a bacterial sore throat infection in young, otherwise healthy adults. The thrombophlebitis is a serious condition and may lead to further systemic complications such as bacteria in the blood or septic emboli.

Lemierre's syndrome occurs most often when a bacterial (e.g. Fusobacterium necrophorum) throat infection progresses to the formation of a peritonsillar abscess. Deep in the abscess, anaerobic bacteria can flourish and eventually may penetrate the abscess to infect nearby structures. Spread of infection to the nearby jugular vein may lead to clot formation or spread of bacteria through the bloodstream. Pieces of the infected clot break off and travel to the lungs as emboli blocking branches of the pulmonary artery bringing deoxygenated blood from the heart to the lungs.

Sepsis following from a throat infection was described by Scottmuller in 1918.[2] However it was André Lemierre, in 1936, who published a series of 20 cases where throat infections were followed by identified anaerobic septicemia, of whom 18 patients died.[3]

Signs and symptoms[edit]

The symptoms vary, but usually start with a sore throat, fever, and general body weakness. These are followed by extreme lethargy, spiked fevers, rigors, swollen cervical lymph nodes, and a swollen, tender or painful neck. Often there is abdominal pain, diarrhea, nausea and vomiting during this phase. These signs and symptoms usually occur several days to 2 weeks after the initial symptoms.

Symptoms of pulmonary involvement can be shortness of breath, cough and painful breathing (pleuritic chest pain). Rarely, blood is coughed up. Painful or inflamed joints can occur when the joints are involved.

Septic shock can also arise. This presents with low blood pressure, increase heart rate, decreased urine output and an increased rate of breathing. Some cases will also present with meningitis, which will typically manifest as neck stiffness, headache and sensitivity of the eyes to light.

Liver enlargement and spleen enlargement can be found, but are not always associated with hepatic or splenic abscesses.[4][5]

Other signs and symptoms that may occur:

Cause[edit]

The bacteria causing the thrombophlebitis are anaerobic bacteria that are typically normal components of oropharyngeal flora. Species of Fusobacterium, specifically Fusobacterium necrophorum, are most commonly the causative bacteria, but various bacteria have been implicated. One 1989 study found that 81% of Lemierres's syndrome had been infected with Fusobacterium necrophorum, while 11% were caused by other Fusobacterium species.[6] MRSA might also be an issue in Lemierre infections.[7] Rarely Lemierre's syndrome is caused by other (usually Gram-negative) bacteria, which include Bacteroides fragilis and Bacteroides melaninogenicus, Peptostreptococcus spp., Streptococcus microaerophile, Staphylococcus aureus, and Eikenella corrodens.[6][8]

Pathophysiology[edit]

Lemierre's syndrome is initiated by an infection of the head and neck region. Usually this infection is a pharyngitis (which occurred in 87.1% of patients as reported by a literature review[5]), but it can also be initiated by an otitis, a mastoiditis, a sinusitis or a parotitis.

During the primary infection, F. necrophorum colonizes the infection site and the infection spreads to the parapharyngeal space. The bacteria then invade the peritonsillar blood vessels where they can spread to the internal jugular vein.[4] In this vein, the bacteria cause the formation of a thrombus containing these bacteria. Furthermore, the internal jugular vein becomes inflamed. This septic thrombophlebitis can give rise to septic microemboli[9] that disseminate to other parts of the body where they can form abscesses and septic infarctions. The first capillaries that the emboli encounter where they can nestle themselves are the pulmonary capillaries. As a consequence, the most frequently involved site of septic metastases are the lungs, followed by the joints (knee, hip, sternoclavicular joint, shoulder and elbow[10]). In the lungs, the bacteria cause abscesses, nodulary and cavitary lesions. Pleural effusion is often present.[5] Other sites involved in septic metastasis and abscess formation are the muscles and soft tissues, liver, spleen, kidneys and nervous system (intracranial abscesses, meningitis).[4]

Production of bacterial toxins such as lipopolysaccharide leads to secretion of cytokines by white blood cells which then both lead to symptoms of sepsis. F. necrophorum produces hemagglutinin which causes platelet aggregation that can lead to diffuse intravascular coagulation and thrombocytopenia.[11][12]

Diagnosis[edit]

Diagnosis and the imaging (and laboratory) studies to be ordered largely depend on the patient history, signs and symptoms. If a persistent sore throat, with the symptoms are found, physicians are cautioned to screen for Lemierre's syndrome.

Laboratory investigations reveal signs of a bacterial infection with elevated C-reactive protein, erythrocyte sedimentation rate and white blood cells (notably neutrophils). Platelet count can be low or high. Liver function tests and renal function tests are often abnormal.

Thrombosis of the internal jugular vein can be displayed with sonography. Thrombi that have developed recently have low echogenicity or echogenicity similar to the flowing blood, and in such cases pressure with the ultrasound probe show a non-compressible jugular vein - a sure sign of thrombosis. Also colour or power Doppler ultrasound identify a low echogenicity thrombus. A CT scan or an MRI scan is more sensitive in displaying the thrombus of the intra-thoracic retrosternal veins, but are rarely needed.

Chest X-ray and chest CT may show pleural effusion, nodules, infiltrates, abscesses and cavitations.

Bacterial cultures taken from the blood, joint aspirates or other sites can identify the causative agent of the disease.

Other illnesses that can be included in the differential diagnosis are:

Treatment[edit]

Lemierre's syndrome is primarily treated with antibiotics given intravenously. Fusobacterium necrophorum is generally highly susceptible to beta-lactam antibiotics, metronidazole, clindamycin and third generation cephalosporins while the other fusobacteria have varying degrees of resistance to beta-lactams and clindamycin.[12] Additionally, there may exist a co-infection by another bacterium. For these reasons is often advised not to use monotherapy in treating Lemierre's syndrome. Penicillin and penicillin-derived antibiotics can thus be combined with a beta-lactamase inhibitor such as clavulanic acid or with metronidazole.[4][8] Clindamycin can be given as monotherapy.

If antibiotic therapy does not improve the clinical picture, it may prove useful to drain any abscesses and/or perform ligation of the internal jugular vein where the antibiotic can not penetrate.[5][8][13]

There is no evidence to opt for or against the use of anticoagulation therapy. The low incidence of Lemierre's syndrome has not made it possible to set up clinical trials to study the disease.[8]

The disease can often be un-treatable, especially if other negative factors occur, i.e. various diseases occurring at the same time, such as meningitis, pneumonia.

Prognosis[edit]

When properly diagnosed, the mortality of Lemierre's syndrome is about 4.6%.[14] Since this disease is not well known and often remains undiagnosed, mortality might be much higher.

Epidemiology[edit]

Lemierre's syndrome is currently rare, but was more common in the early 20th century before the discovery of penicillin. The reduced use of antibiotics for sore throats may have increased the risk of this disease, with 19 cases in 1997 and 34 cases in 1999 reported in the UK.[15] The incidence rate is currently 0.8 cases per million in the general population,[16] leading it to be termed the "forgotten disease".[17] The disease is known to affect healthy young adults. The disease is becoming less rare with many cases being reported, however it is still known as "the forgotten disease" as many doctors are unaware of its existence, therefore often not even diagnosed which might considerably change the above-mentioned statistics. The mortality rate was 90% prior to antibiotic therapy,[3] but is now generally quoted as 15% once this illness is correctly diagnosed and cured with proper medical treatment, although one series of cases reported mortality as low as 6.4%.[5]

History[edit]

Sepsis following from a throat infection was described by Scottmuller in 1918.[2] However it was Andre Lemierre, in 1936, who published a series of 20 cases where throat infections were followed by identified anaerobic septicemia, of whom 18 patients died.[3]

References[edit]

  1. ^ "Lemierre syndrome" at Dorland's Medical Dictionary
  2. ^ a b Schottmuller H (1918). "Ueber die Pathogenität anaërober Bazillen". Dtsch Med Wochenschr (in German) 44: 1440. 
  3. ^ a b c Lemierre A (1936). "On certain septicemias due to anaerobic organisms". Lancet 1 (5874): 701–3. doi:10.1016/S0140-6736(00)57035-4. 
  4. ^ a b c d Syed MI, Baring D, Addidle M, Murray C, Adams C (September 2007). "Lemierre syndrome: two cases and a review". The Laryngoscope (The American Laryngological, Rhinological & Otological Society; Lippincott Williams & Wilkins) 117 (9): 1605–1610. doi:10.1097/MLG.0b013e318093ee0e. PMID 17762792. 
  5. ^ a b c d e Chirinos JA, Lichtstein DM, Garcia J, Tamariz LJ (November 2002). "The evolution of Lemierre syndrome: report of 2 cases and review of the literature". Medicine (Baltimore) (Lippincott Williams & Wilkins) 81 (6): 458–465. doi:10.1097/00005792-200211000-00006. PMID 12441902. 
  6. ^ a b Sinave CP, Hardy GJ, Fardy PW (March 1989). "The Lemierre's syndrome: suppurative thrombophlebitis of the internal jugular vein secondary to oropharyngeal infection". Medicine (Baltimore) (Williams & Wilkins) 68 (2): 85–94. doi:10.1097/00005792-198903000-00002. PMID 2646510. 
  7. ^ NCBI PubMed, Bentley TP, Brennan DF (August 2009). "Lemierre's syndrome: methicillin-resistant Staphylococcus aureus (MRSA) finds a new home.". Medicine (Orlando) (Bentley & Brennan) 37 (2): 131–4. doi:10.1016/j.jemermed.2007.07.066. PMID 18280087. 
  8. ^ a b c d Puymirat E, Biais M, Camou F, Lefèvre J, Guisset O, Gabinski C (March 2008). "A Lemierre's syndrome variant caused by Staphylococcus aureus". American journal of emergency medicine test (Elsevier) 26 (3): 380–387. doi:10.1016/j.ajem.2007.05.020. PMID 18358967. 
  9. ^ Screaton NJ, Ravenel JG, Lehner PJ, Heitzman ER, Flower CD (November 1999). "Lemierre Syndrome: Forgotten but Not Extinct-Report of Four Cases". Radiology (Radiological Society of North America) 213 (2): 369–374. doi:10.1148/radiology.213.2.r99nv09369. PMID 10551214. The absence of proximal thrombus at CT pulmonary angiography suggests that microemboli, rather than the macroembolic clot burden more typical of acute pulmonary embolism, are responsible for the pulmonary findings in Lemierre syndrome 
  10. ^ Beldman TF, Teunisse HA, Schouten TJ (November 1997). "Septic arthritis of the hip by Fusobacterium necrophorum after tonsillectomy: a form of Lemierre syndrome?". European journal of pediatrics (Springer-Verlag) 156 (11): 856–857. doi:10.1007/s004310050730. PMID 9392400. 
  11. ^ Kanoe M, Yamanaka M, Inoue M (1989). "Effects of Fusobacterium necrophorum on the mesenteric microcirculation of guinea pigs". Medical Microbiology and Immunology (Springer Berlin / Heidelberg) 178 (2): 99–104. doi:10.1007/bf00203305. PMID 2659950. 
  12. ^ a b Hagelskjaer Kristensen L, Prag J (Aug 2000). "Human necrobacillosis, with emphasis on Lemierre's syndrome". Clinical Infectious Diseases 31 (2): 524–532. doi:10.1086/313970. PMID 10987717. 
  13. ^ Aspesberro F, Siebler T, Van Nieuwenhuyse JP, Panosetti E, Berthet F (September 2008). "Lemierre syndrome in a 5-month-old male infant: Case report and review of the pediatric literature". Pediatric Critical Care Medicine (The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies) 9 (5): e35-37. doi:10.1097/PCC.0b013e31817319fa. PMID 18779698. 
  14. ^ "Sign In — Ann Intern Med". 
  15. ^ UK Chief Medical Officer Update 29 February 2001 (CMO Update29 Feb 2001)
  16. ^ Sibai K, Sarasin F (2004). "[Lemierre syndrome: a diagnosis to keep in mind]". Revue médicale de la Suisse romande (in French) 124 (11): 693–5. PMID 15631168. 
  17. ^ Weesner CL, Cisek JE (1993). "Lemierre syndrome: the forgotten disease". Annals of Emergency Medicine 22 (2): 256–8. doi:10.1016/S0196-0644(05)80216-1. PMID 8427443.