Lemierre's Syndrome
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Lemierre's syndrome is infectious
thrombophlebitis Thrombophlebitis is a phlebitis (inflammation of a vein) related to a thrombus (blood clot). When it occurs repeatedly in different locations, it is known as thrombophlebitis migrans (migratory thrombophlebitis). Signs and symptoms The following ...
of the
internal jugular vein The internal jugular vein is a paired jugular vein that collects blood from the brain and the superficial parts of the face and neck. This vein runs in the carotid sheath with the common carotid artery and vagus nerve. It begins in the posteri ...
. 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. 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 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 A pulmonary artery is an artery in the pulmonary circulation that carries deoxygenated blood from the right side of the heart to the lungs. The largest pulmonary artery is the ''main pulmonary artery'' or ''pulmonary trunk'' from the heart, and ...
that carry deoxygenated blood from the right side of the heart to the lungs.
Sepsis Sepsis is a potentially life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage of sepsis is followed by suppression of the immune system. Common signs and s ...
following a throat infection was first described by Hugo Schottmüller in 1918. In 1936, André Lemierre published a series of 20 cases where throat infections were followed by identified anaerobic sepsis, of whom 18 died.


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 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 two 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, increased heart rate, decreased urine output and an increased rate of breathing. Some cases will also present with
meningitis Meningitis is acute or chronic inflammation of the protective membranes covering the brain and spinal cord, collectively called the meninges. The most common symptoms are fever, intense headache, vomiting and neck stiffness and occasion ...
, 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 liver or spleen abscesses. Other signs and symptoms that may occur: * Headache (unrelated to meningitis) * Memory loss * Muscle pain *
Jaundice Jaundice, also known as icterus, is a yellowish or, less frequently, greenish pigmentation of the skin and sclera due to high bilirubin levels. Jaundice in adults is typically a sign indicating the presence of underlying diseases involving ...
* Decreased ability to open the jaw * Crepitations are sometimes heard over the lungs * Pericardial friction rubs as a sign of
pericarditis Pericarditis () is inflammation of the pericardium, the fibrous sac surrounding the heart. Symptoms typically include sudden onset of sharp chest pain, which may also be felt in the shoulders, neck, or back. The pain is typically less severe whe ...
(rare) *
Cranial nerve Cranial nerves are the nerves that emerge directly from the brain (including the brainstem), of which there are conventionally considered twelve pairs. Cranial nerves relay information between the brain and parts of the body, primarily to and f ...
paralysis Paralysis (: paralyses; also known as plegia) is a loss of Motor skill, motor function in one or more Skeletal muscle, muscles. Paralysis can also be accompanied by a loss of feeling (sensory loss) in the affected area if there is sensory d ...
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 ''Fusobacterium'' is a genus of obligate anaerobic, Gram-negative, non-sporeforming bacteria belonging to Gracilicutes. Individual cells are slender, rod-shaped bacilli with pointed ends. ''Fusobacterium'' was discovered in 1900 by Courmont an ...
'', 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.
MRSA Methicillin-resistant ''Staphylococcus aureus'' (MRSA) is a group of gram-positive bacteria that are genetically distinct from other strains of ''Staphylococcus aureus''. MRSA is responsible for several difficult-to-treat infections in humans. ...
might also be an issue in Lemierre infections. Rarely Lemierre's syndrome is caused by other (usually
Gram-negative Gram-negative bacteria are bacteria that, unlike gram-positive bacteria, do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. Their defining characteristic is that their cell envelope consists ...
) bacteria, which include '' Bacteroides fragilis'' and '' Bacteroides melaninogenicus'', '' Peptostreptococcus spp.'', '' Streptococcus microaerophile'', ''
Staphylococcus aureus ''Staphylococcus aureus'' is a Gram-positive spherically shaped bacterium, a member of the Bacillota, and is a usual member of the microbiota of the body, frequently found in the upper respiratory tract and on the skin. It is often posi ...
'', ''
Streptococcus pyogenes ''Streptococcus pyogenes'' is a species of Gram-positive, aerotolerant bacteria in the genus '' Streptococcus''. These bacteria are extracellular, and made up of non-motile and non-sporing cocci (round cells) that tend to link in chains. They ...
'', and '' Eikenella corrodens''.


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. Usually this infection is a pharyngitis (which occurred in 87.1% of patients as reported by a literature review), and can be preceded by infectious mononucleosis as reported in several cases. It can also be initiated by infections of the ear, mastoid bone, sinuses, or saliva glands. 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 The internal jugular vein is a paired jugular vein that collects blood from the brain and the superficial parts of the face and neck. This vein runs in the carotid sheath with the common carotid artery and vagus nerve. It begins in the posteri ...
. In this vein, the bacteria cause the formation of a
thrombus A thrombus ( thrombi) is a solid or semisolid aggregate from constituents of the blood (platelets, fibrin, red blood cells, white blood cells) within the circulatory system during life. A blood clot is the final product of the blood coagulatio ...
containing these bacteria. Furthermore, the
internal jugular vein The internal jugular vein is a paired jugular vein that collects blood from the brain and the superficial parts of the face and neck. This vein runs in the carotid sheath with the common carotid artery and vagus nerve. It begins in the posteri ...
becomes inflamed. This septic
thrombophlebitis Thrombophlebitis is a phlebitis (inflammation of a vein) related to a thrombus (blood clot). When it occurs repeatedly in different locations, it is known as thrombophlebitis migrans (migratory thrombophlebitis). Signs and symptoms The following ...
can give rise to septic microemboli that disseminate to other parts of the body where they can form abscesses and septic infarctions. The first
capillaries A capillary is a small blood vessel, from 5 to 10 micrometres in diameter, and is part of the microcirculation system. Capillaries are microvessels and the smallest blood vessels in the body. They are composed of only the tunica intima (the in ...
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 The sternoclavicular joint or sternoclavicular articulation is a Synovial joint, synovial Saddle joint, saddle joint between the sternum#Manubrium, manubrium of the sternum, and the clavicle bone, clavicle, and the first costal cartilage. The joi ...
, shoulder and elbow). In the lungs, the bacteria cause abscesses, nodulary and cavitary lesions. Pleural effusion is often present. Other sites involved in septic metastasis and abscess formation are the muscles and soft tissues, liver, spleen, kidneys and nervous system (intracranial abscesses, meningitis). Production of bacterial toxins such as lipopolysaccharide leads to secretion of
cytokines Cytokines () are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are produced by a broad range of cells, including immune cells like macrophages, B cell, B lymphocytes, T cell, T lymphocytes ...
by white blood cells which then both lead to symptoms of
sepsis Sepsis is a potentially life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage of sepsis is followed by suppression of the immune system. Common signs and s ...
. ''F. necrophorum'' produces hemagglutinin which causes platelet aggregation that can lead to diffuse intravascular coagulation and
thrombocytopenia In hematology, thrombocytopenia is a condition characterized by abnormally low levels of platelets (also known as thrombocytes) in the blood. Low levels of platelets in turn may lead to prolonged or excessive bleeding. It is the most common coag ...
.


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. 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. Thrombosis of the internal jugular vein can be displayed with
sonography Medical ultrasound includes diagnostic techniques (mainly imaging) using ultrasound, as well as therapeutic applications of ultrasound. In diagnosis, it is used to create an image of internal body structures such as tendons, muscles, joints ...
. 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.
Chest X-ray A chest radiograph, chest X-ray (CXR), or chest film is a Projectional radiography, projection radiograph of the chest used to diagnose conditions affecting the chest, its contents, and nearby structures. Chest radiographs are the most common fi ...
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 In healthcare, a differential diagnosis (DDx) is a method of analysis that distinguishes a particular disease or condition from others that present with similar clinical features. Differential diagnostic procedures are used by clinicians to di ...
are: * Q fever *
Tuberculosis Tuberculosis (TB), also known colloquially as the "white death", or historically as consumption, is a contagious disease usually caused by ''Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can al ...
*
Pneumonia Pneumonia is an Inflammation, inflammatory condition of the lung primarily affecting the small air sacs known as Pulmonary alveolus, alveoli. Symptoms typically include some combination of Cough#Classification, productive or dry cough, ches ...


Treatment

Lemierre's syndrome is primarily treated with
antibiotics An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy ...
given intravenously. ''Fusobacterium necrophorum'' is generally highly susceptible to beta-lactam antibiotics,
metronidazole Metronidazole, sold under the brand name Flagyl and Metrogyl among others, is an antibiotic and antiprotozoal medication. It is used either alone or with other antibiotics to treat pelvic inflammatory disease, endocarditis, and bacterial vagino ...
, clindamycin and third generation
cephalosporins The cephalosporins (sg. ) are a class of β-lactam antibiotics originally derived from the fungus ''Acremonium'', which was previously known as ''Cephalosporium''. Together with cephamycins, they constitute a subgroup of β-lactam antibiotic ...
while the other fusobacteria have varying degrees of resistance to beta-lactams and clindamycin. 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. Clindamycin can be given as monotherapy. If antibiotic therapy is unsuccessful, additional treatments include draining of any abscesses and ligation of the internal jugular vein where the antibiotic cannot penetrate. 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.


Prognosis

The mortality rate was 90% prior to antibiotic therapy. In the contemporary era, a mortality of 4% has been estimated. 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.


Epidemiology

Lemierre's syndrome is currently rare, but was more common in the early 20th century before the discovery of
penicillin Penicillins (P, PCN or PEN) are a group of beta-lactam antibiotic, β-lactam antibiotics originally obtained from ''Penicillium'' Mold (fungus), moulds, principally ''Penicillium chrysogenum, P. chrysogenum'' and ''Penicillium rubens, P. ru ...
. 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. 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.


History

Sepsis Sepsis is a potentially life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage of sepsis is followed by suppression of the immune system. Common signs and s ...
following from a throat infection was described by Hugo Schottmüller in 1918. In 1936, André Lemierre published a series of 20 cases where throat infections were followed by identified anaerobic sepsis, of whom 18 patients died.


References

{{DEFAULTSORT:Lemierre's Syndrome Bacterial diseases Syndromes caused by microbes Rare infectious diseases