View source for Lemierre's syndrome

{{Infobox medical condition (new)
| name            = Lemierre's syndrome
| synonyms        = Septic phlebitis of the internal jugular vein, postanginal sepsis secondary to oropharyngeal infection, postanginal shock including sepsis, Lemierre's disease, human necrobacillosis
| image           = Fusobacterium novum 01.jpg
| caption         = ''Fusobacterium necrophorum'', the most common cause of Lemierre's syndrome
| pronounce       =
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| symptoms        = Early:[[Fever]], [[sore throat]], [[fatigue]]
                    Later:Variable, [[Sepsis]], [[vomiting]], [[muscle pain]], [[meningitis]], [[hepatosplenomegaly]]
| complications   = [[Septic shock]], [[kidney failure]], [[liver failure]], [[cerebral edema]], [[organ failure]], [[death]]<ref>{{Cite web | vauthors = Mueller DK, Dacey MJ | date = 2 February 2024 | veditors = Rowe VO | work = Medscape |url=https://emedicine.medscape.com/article/461577-clinical#b4 |title= Internal Jugular Vein Thrombosis Clinical Presentation: History and Physical Examination, Complications }}</ref>
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}}
'''Lemierre's syndrome''' is infectious [[thrombophlebitis]] of the [[internal jugular vein]].<ref>{{DorlandsDict|nine/100019144|Lemierre syndrome}}</ref> It most often develops as a complication of a bacterial [[pharyngitis|sore throat infection]] in young, otherwise healthy adults.  The thrombophlebitis is a serious condition and may lead to further systemic complications such as [[bacteremia|bacteria in the blood]] or [[Septic embolism|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. When the abscess wall ruptures internally, the drainage carrying bacteria seeps through the soft tissue and infects the nearby structures. Spread of infection to the nearby internal jugular vein provides a gateway for the spread of bacteria through the bloodstream. The inflammation surrounding the vein and compression of the vein may lead to [[thrombosis|blood clot formation]]. Pieces of the potentially infected clot can break off and travel through the right heart into the lungs as emboli, blocking branches of the [[pulmonary artery]] that carry deoxygenated blood from the right side of the heart to the lungs.{{citation needed|date=June 2022}}

<!-- History -->
[[Sepsis]] following a throat infection was first described by Hugo Schottmüller in 1918.<ref name="Schottmuller H 1918 1440">{{Cite journal|author=Schottmuller H |title=Ueber die Pathogenität anaërober Bazillen |language=de |journal=Dtsch Med Wochenschr |year=1918 |volume=44 |pages=1440}}</ref> In 1936, [[André Lemierre]] published a series of 20 cases where throat infections were followed by identified anaerobic sepsis, of whom 18 died.<ref name="Lemierre">{{Cite journal|author=Lemierre A |title=On certain septicemias due to anaerobic organisms |journal=Lancet |year=1936 |volume=1 |issue= 5874|pages=701–3 |doi=10.1016/S0140-6736(00)57035-4}}</ref>

==Signs and symptoms==
The signs and symptoms of Lemierre's syndrome 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 node]]s, 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 two weeks after the initial symptoms.
Symptoms of pulmonary involvement can be shortness of breath, cough and painful breathing ([[pleurisy|pleuritic chest pain]]). Rarely, [[hemoptysis|blood is coughed up]]. [[Arthralgia|Painful]] or [[septic arthritis|inflamed joints]] can occur when the joints are involved.{{citation needed|date=July 2020}}

[[Septic shock]] can also arise. This presents with [[hypotension|low blood pressure]], [[tachycardia|increased heart rate]], [[oliguria|decreased urine output]] and an [[tachypnea|increased rate of breathing]]. Some cases will also present with [[meningitis]], which will typically manifest as [[meningism|neck stiffness]], headache and [[photophobia|sensitivity of the eyes to light]].{{citation needed|date=July 2020}} [[Hepatomegaly|Liver enlargement]] and [[splenomegaly|spleen enlargement]] can be found, but are not always associated with liver or spleen abscesses.<ref name="Syed"/><ref name="Chirinos"/> Other signs and symptoms that may occur:{{citation needed|date=May 2021}}
* Headache (unrelated to meningitis)
* Memory loss
* Muscle pain
* [[Jaundice]]
* [[Trismus|Decreased ability to open the jaw]]
* [[Rales|Crepitations]] are sometimes heard over the lungs
* [[Pericardial friction rub]]s as a sign of [[pericarditis]] (rare)
* [[Cranial nerve]] [[paralysis]] and [[Horner's syndrome]] (both rare)

==Cause==
The bacteria causing the thrombophlebitis are anaerobic bacteria that are typically normal components of the microorganisms that inhabit the mouth and throat. 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.<ref name="Sinave">{{cite journal | vauthors = Sinave CP, Hardy GJ, Fardy PW | title = The Lemierre syndrome: suppurative thrombophlebitis of the internal jugular vein secondary to oropharyngeal infection | journal = Medicine | volume = 68 | issue = 2 | pages = 85–94 | date = March 1989 | pmid = 2646510 | doi = 10.1097/00005792-198903000-00002 | s2cid = 36002793 | doi-access = free }}</ref> [[Methicillin-resistant Staphylococcus aureus|MRSA]] might also be an issue in Lemierre infections.<ref name="NCBI">{{cite journal | vauthors = Bentley TP, Brennan DF | title = Lemierre's syndrome: methicillin-resistant Staphylococcus aureus (MRSA) finds a new home | journal = The Journal of Emergency Medicine | volume = 37 | issue = 2 | pages = 131–134 | date = August 2009 | pmid = 18280087 | doi = 10.1016/j.jemermed.2007.07.066 }}</ref> Rarely Lemierre's syndrome is caused by other (usually [[Gram staining|Gram-negative]]) bacteria, which include ''[[Bacteroides fragilis]]'' and ''[[Bacteroides melaninogenicus]]'', ''[[Peptostreptococcus]] spp.'', ''[[Streptococcus microaerophile]]'', ''[[Staphylococcus aureus]]'', ''[[Streptococcus pyogenes]]'', and ''[[Eikenella corrodens]]''.<ref name="Sinave"/><ref name="Puymirat">{{cite journal | vauthors = Puymirat E, Biais M, Camou F, Lefèvre J, Guisset O, Gabinski C | title = A Lemierre syndrome variant caused by Staphylococcus aureus | journal = The American Journal of Emergency Medicine | volume = 26 | issue = 3 | pages = 380.e5–380.e7 | date = March 2008 | pmid = 18358967 | doi = 10.1016/j.ajem.2007.05.020 }}</ref>

==Pathophysiology==
Lemierre's syndrome begins with an infection of the head and neck region, with most primary sources of infection in the palatine tonsils and peritonsillar tissue.<ref name=":0">{{cite journal | vauthors = Eilbert W, Singla N | title = Lemierre's syndrome | journal = International Journal of Emergency Medicine | volume = 6 | issue = 1 | pages = 40 | date = October 2013 | pmid = 24152679 | pmc = 4015694 | doi = 10.1186/1865-1380-6-40 | doi-access = free }}</ref> Usually this infection is a pharyngitis (which occurred in 87.1% of patients as reported by a literature review<ref name="Chirinos">{{cite journal | vauthors = Chirinos JA, Lichtstein DM, Garcia J, Tamariz LJ | title = The evolution of Lemierre syndrome: report of 2 cases and review of the literature | journal = Medicine | volume = 81 | issue = 6 | pages = 458–465 | date = November 2002 | pmid = 12441902 | doi = 10.1097/00005792-200211000-00006 | s2cid = 28941739 | doi-access = free }}</ref>), and can be preceded by infectious mononucleosis as reported in several cases.<ref name=":0" /> It can also be initiated by infections of the [[otitis|ear]], [[mastoiditis|mastoid bone]], [[sinusitis|sinuses]], or [[parotitis|saliva glands]].{{citation needed|date=May 2021}}

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]].<ref name="Syed">{{cite journal | vauthors = Syed MI, Baring D, Addidle M, Murray C, Adams C | title = Lemierre syndrome: two cases and a review | journal = The Laryngoscope | volume = 117 | issue = 9 | pages = 1605–1610 | date = September 2007 | pmid = 17762792 | doi = 10.1097/MLG.0b013e318093ee0e | s2cid = 12675030 }}</ref> 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 [[Septic embolism|microemboli]]<ref>{{cite journal | vauthors = Screaton NJ, Ravenel JG, Lehner PJ, Heitzman ER, Flower CD | title = Lemierre syndrome: forgotten but not extinct--report of four cases | journal = Radiology | volume = 213 | issue = 2 | pages = 369–374 | date = November 1999 | pmid = 10551214 | doi = 10.1148/radiology.213.2.r99nv09369 | quote = 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 }}</ref> that disseminate to other parts of the body where they can form abscesses and septic infarctions. The first [[capillary|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 articulation|sternoclavicular joint]], shoulder and elbow<ref>{{cite journal | vauthors = Beldman TF, Teunisse HA, Schouten TJ | title = Septic arthritis of the hip by Fusobacterium necrophorum after tonsillectomy: a form of Lemierre syndrome? | journal = European Journal of Pediatrics | volume = 156 | issue = 11 | pages = 856–857 | date = November 1997 | pmid = 9392400 | doi = 10.1007/s004310050730 | s2cid = 30745447 }}</ref>). In the lungs, the bacteria cause abscesses, nodulary and cavitary lesions. Pleural effusion is often present.<ref name="Chirinos"/> Other sites involved in septic metastasis and abscess formation are the muscles and soft tissues, liver, spleen, kidneys and nervous system (intracranial abscesses, meningitis).<ref name="Syed"/>

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]].<ref name="Kanoe">{{cite journal | vauthors = Kanoe M, Yamanaka M, Inoue M | title = Effects of Fusobacterium necrophorum on the mesenteric microcirculation of guinea pigs | journal = Medical Microbiology and Immunology | volume = 178 | issue = 2 | pages = 99–104 | year = 1989 | pmid = 2659950 | doi = 10.1007/bf00203305 | s2cid = 35453227 }}</ref><ref name="Hagelskjaer">{{cite journal | vauthors = Hagelskjaer Kristensen L, Prag J | title = Human necrobacillosis, with emphasis on Lemierre's syndrome | journal = Clinical Infectious Diseases | volume = 31 | issue = 2 | pages = 524–532 | date = August 2000 | pmid = 10987717 | doi = 10.1086/313970 | doi-access = free }}</ref>

==Diagnosis==
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 signs of sepsis are found, physicians are cautioned to screen for Lemierre's syndrome.<ref>{{cite journal | vauthors = Eilbert W, Singla N | title = Lemierre's syndrome | journal = International Journal of Emergency Medicine | volume = 6 | issue = 1 | pages = 40 | date = October 2013 | pmid = 24152679 | pmc = 4015694 | doi = 10.1186/1865-1380-6-40 | doi-access = free }}</ref>

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 and kidney function tests are often abnormal.{{citation needed|date=November 2020}}

Thrombosis of the internal jugular vein can be displayed with [[Medical ultrasonography|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 color or power Doppler ultrasound identify a low echogenicity blood clot. A CT scan or an MRI scan is more sensitive in displaying the thrombus of the intra-thoracic retrosternal veins, but are rarely needed.{{citation needed|date=November 2020}}

[[Chest X-ray]] and chest CT may show pleural effusion, nodules, infiltrates, abscesses and cavitations.{{citation needed|date=November 2020}}

[[Microbiological culture|Bacterial cultures]] taken from the blood, [[Arthrocentesis|joint aspirates]] or other sites can identify the causative agent of the disease.{{citation needed|date=June 2022}}

Other illnesses that can be included in the [[differential diagnosis]] are:{{citation needed|date=November 2020}}
* [[Q fever]]
* [[Tuberculosis]]
* [[Pneumonia]]

==Treatment==
Lemierre's syndrome is primarily treated with [[antibiotics]] given intravenously. ''Fusobacterium necrophorum'' is generally highly susceptible to [[beta-lactam antibiotic]]s, [[metronidazole]], [[clindamycin]] and third generation [[cephalosporins]] while the other fusobacteria have varying degrees of resistance to beta-lactams and clindamycin.<ref name="Hagelskjaer"/> 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.<ref name="Syed"/><ref name="Puymirat"/> Clindamycin can be given as monotherapy.{{citation needed|date=October 2022}}

If antibiotic therapy is unsuccessful, additional treatments include draining of any abscesses and ligation of the internal jugular vein where the antibiotic cannot penetrate.<ref name="Chirinos"/><ref name="Puymirat"/><ref name="Aspesberro">{{cite journal | vauthors = Aspesberro F, Siebler T, Van Nieuwenhuyse JP, Panosetti E, Berthet F | title = Lemierre syndrome in a 5-month-old male infant: Case report and review of the pediatric literature | journal = Pediatric Critical Care Medicine | volume = 9 | issue = 5 | pages = e35–e37 | date = September 2008 | pmid = 18779698 | doi = 10.1097/PCC.0b013e31817319fa | s2cid = 52858512 }}</ref>
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.<ref name="Puymirat"/>

==Prognosis==
The mortality rate was 90% prior to antibiotic therapy. In the contemporary era, a mortality of 4% has been estimated.<ref name="JIM">{{cite journal | vauthors = Valerio L, Zane F, Sacco C, Granziera S, Nicoletti T, Russo M, Corsi G, Holm K, Hotz MA, Righini C, Karkos PD, Mahmoudpour SH, Kucher N, Verhamme P, Di Nisio M, Centor RM, Konstantinides SV, Pecci A, Barco S | display-authors = 6 | title = Patients with Lemierre syndrome have a high risk of new thromboembolic complications, clinical sequelae and death: an analysis of 712 cases | journal = Journal of Internal Medicine | volume = 289 | issue = 3 | pages = 325–339 | date = March 2021 | pmid = 32445216 | doi = 10.1111/joim.13114 | doi-access = free }}</ref> Since this disease is not well known and often remains undiagnosed, mortality might be much higher. Approximately 10% of those with the condition experience clinical sequelae, including cranial nerve palsy and orthopaedic limitations.<ref name="JIM"/>

==Epidemiology==
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 [[United Kingdom|UK]].<ref name="cmo_update29">{{cite web | work = UK Chief Medical Officer Update 29 | publisher = Department of Health, UK | title = Lemierre's Disease | url = http://www.dh.gov.uk/PublicationsAndStatistics/LettersAndCirculars/CMOUpdate/CMOUpdateArticle/fs/en?CONTENT_ID=4003620&chk=8Ifdm1 | archive-url = https://web.archive.org/web/20070311031304/http://www.dh.gov.uk/PublicationsAndStatistics/LettersAndCirculars/CMOUpdate/CMOUpdateArticle/fs/en?CONTENT_ID=4003620&chk=8Ifdm1 | archive-date = 11 March 2007 | date = February 2001 }}</ref> The estimated incidence rate is 0.8 to 3.6 cases per million in the general population, but is higher in healthy young adults. The number of cases reported is increasing; however, because of its rarity, physicians may be unaware of its existence, possibly leading to underdiagnosis.<ref>{{cite journal | vauthors = Valerio L, Corsi G, Sebastian T, Barco S | title = Lemierre syndrome: Current evidence and rationale of the Bacteria-Associated Thrombosis, Thrombophlebitis and LEmierre syndrome (BATTLE) registry | journal = Thrombosis Research | volume = 196 | pages = 494–499 | date = December 2020 | pmid = 33091703 | doi = 10.1016/j.thromres.2020.10.002 | doi-access = free }}</ref>

==History==
[[Sepsis]] following from a throat infection was described by Hugo Schottmüller in 1918.<ref name="Schottmuller H 1918 1440"/> In 1936, [[André Lemierre]] published a series of 20 cases where throat infections were followed by identified anaerobic sepsis, of whom 18 patients died.<ref name="Lemierre"/>

== References ==
{{Reflist}}

{{Medical resources
|  DiseasesDB     = 31108
|  ICD10          = ICD-10: I80.8
|  ICD9           = <!-- {{ICD9|xxx}} -->
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|  MeshID         = D057831
|  Orphanet       = 137839
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{{Gram-negative non-proteobacterial bacterial diseases}}

{{DEFAULTSORT:Lemierre's Syndrome}}
[[Category:Bacterial diseases]]
[[Category:Syndromes caused by microbes]]
[[Category:Rare infectious diseases]]