Lemierre´s Syndrome

What is Lemierre´s Syndrome?

Lemierre´s disease or syndrome, also known as the Forgotten disease or postanginal septicemia is a severe case of sore throat caused by Fusobacterium necrophorum and it is potentially lethal. It usually affects healthy young adults after a recent oropharyngeal infection ^[1]. This disease causes thrombophlebitis of internal jugular vein and further dissemination of the bacteria to various locations in the body.

Pathophysiology

Fusobacterium necrophorum is a bacterium that occurs normally in the upper respiratory and gastrointestinal tract. Lemierre´s syndrome starts out as an infection in the head and neck region, in most cases- pharyngitis ^[2]. It can also be caused by otitis, parotitis, mastoiditis or sinusitis.

The bacterium colonizes the affected site and spreads further to the parapharyngeal space. The area is intensively supplied with blood. The bacterium spreads from this anatomical location to internal jugular vein. From there, the bacterium forms a thrombus and can be disseminated throughout the body.

The internal jugular vein itself also becomes inflamed. The septic micro-emboli can cause abscesses and infarctions in different parts of the body. The bacteria produce toxins and the body produces cytokines to fight these toxins. That leads to symptoms of sepsis. Fusobacterium necrophorum also produces hemagglutinin- a substance that causes clumping of red blood cells and can lead to disseminated intravascular coagulation syndrome. It can also cause thrombocytopenia ^[3]

Symptoms

There are generalized and localized symptoms of Lemierre´s syndrome. They vary for each patient, depending on the location the infection has spread to.

Symptoms associated with severe sore throat:

• High fever
• Tenderness and pain when palpating the neck
• Fatigue

When the disease progresses, there is a spike of high fever, lymph nodes in the neck area become more swollen, general condition worsens. Other symptoms depend on the distribution of bacteria:

• Lung related symptoms- chest pain, cough, crepitation sound over lungs
• Gastrointestinal symptoms- nausea, vomiting, abdominal pain, jaundice
• Joint pain ^[2]

Infection

The most common site where the infection spreads is lungs. Pulmonary infiltrates on both sides, empyema, pulmonary effusion, and abscess might be present. In severe cases cavitating lung lesions can occur. The infection can spread to skeletal and joint system, causing septic arthritis or osteomyelitis.

If the infection spreads to brain tissue it can cause septic meningitis. In abdomen, the bacteria can affect spleen, kidneys and liver. In this case splenomegaly, hepatomegaly and jaundice can be present ^[4]. This occurs due to rapid hemolysis, similar to Myelodysplastic syndrome.

Complications

There are various complications of this disease. If caught early, this disease can be treated. Still it can cause very severe complications. Pulmonary infection can cause complications like pneumatocele (a cavity in the lungs filled with air), pneumothorax (collapsing of the lung) and respiratory distress syndrome.

In rare cases pneumonia can cause hemolytic-uremic syndrome. Infection can cause lung, brain and kidney abscess. If this disease is not treated, the infection can lead to septic shock and death ^[5].

Diagnosis

The diagnosis of this disease depends on the symptoms patient is presenting. The diagnosis of Lemierre´s syndrome can be made only after microbiological detection of Fusobacterium necrophorum in the acquired specimen. Bacterial cultures can be taken from blood, aspirates from joints and abscesses.

Since the microbiology results can take time, the doctor has to be very suspicious and start treatment based on the observed clinical manifestations ^[4]. After doing physical examination, the doctor can detect possible sites of infection and order further investigations.

In laboratory studies, elevated inflammation markers can be seen: increased CPR, erythrocyte sedimentation rate and white blood cells are usually present. In case liver or/and kidneys are involved, there can be increase of liver enzymes and kidney function tests.

Radiology

In case Lemierre´s syndrome is suspected, a variety of radiological imaging studies can be done:

• CT with contrast dye is one of the best ways to diagnose this syndrome. The dye will enhance the infected vein walls, defects of soft tissues and abscesses.
• X-ray and CT of the chest can reveal pulmonary involvement
• For suspected abdominal involvement, ultrasound is used
• If surgical ligation of internal jugular vein is considered, retrograde venography can be used.

Treatment

Once Lemierre´s syndrome has been suspected, antibiotic treatment has to be started immediately. Fusobacterium necrophorum is usually sensitive to penicillin, metronidazole and clindamycin. The patients are usually hospitalized and antibiotics are given intravenously.

Antibiotic treatment has to be continued for at least 2 weeks or even longer, because of the endovascular involvement. The hospital stay and further procedures depend on the severity of the condition.

• If there is continuation of septic emboli and severe lung involvement, the extraction or ligation of internal jugular vein can be required.
• Anticoagulation therapy- heparin can be given to faster dissolve clots. It can also be helpful in treating thrombophlebitis. Usual course of action is giving intravenous heparin for a week, followed by month course of oral warfarin ^[4]
• Hyperbaric oxygenation nowadays is rarely used, but it is suggested to benefit the improvement of the patient. It is also used to treat toxic shock syndrome^[6]
• Drainage of large abscess can be helpful in improving patients condition
• If complications like liver damage or kidney failure have occurred, transplantation can be required. Some patients might need long term dialysis.

Prognosis

If the treatment is started with appropriate antibiotics, the outcome is usually positive and patient can fully recover. Delayed treatment is associated with poor outcome. Mortality rate from this syndrome varies around 2-5%. Lately it has been suggested, that Lemierre´s syndrome is not as rare as it is thought to be.

The increase of antibiotic resistance can be a cause for increased incidence of this syndrome ^[7]. The prognosis depends on the involvement of organ systems. Severe lung involvement and meningitis is associated with poor prognosis.

Septic manifestations can also cause various other diseases, for example, meningitis is a possible cause for Brown Sequard syndrome. The patient might have a permanent disability and require long term treatment ^[4].

References

1. http://www.lemierresyndrome.com/enrollment.html
2. http://journals.lww.com/md-journal/pages/articleviewer.aspx?year=2002&issue=11000&article=00006&type=abstract
3. http://www.medscape.com/viewarticle/410830_3
4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2813609/
5. http://www.rightdiagnosis.com/l/lemierres_syndrome/intro.htm
6. https://www.ncbi.nlm.nih.gov/pubmed/12964852/
7. https://www.ncbi.nlm.nih.gov/pubmed/19554637