Lemierre's syndrome

# Overview
Lemierre's syndrome (or Lemierre's disease) is a disease usually caused by the  bacterium Fusobacterium necrophorum, and occasionally by other members of the genus Fusobacterium (F. nucleatum, F. mortiferum and F. varium etc.) and usually affects young, healthy adults.  Fusobacteria are normal inhabitants of the oropharyngeal flora. The infection leads to inflammation of and formation of a thrombus (blood clot) in the internal jugular vein.  Many of the resulting symptoms are due to the septic emboli that break off from this initial area and travel through the blood to other areas of the body.  Symptoms of Lemierre's syndrome include sore throat, extreme lethargy, fever, generalized body weakness, rigors, and swollen cervical lymph nodes. The mainstay of therapy for Lemierre's syndrome is antimicrobial therapy. Lemierre's disease is a very rare disease with only approximately 160 cases in the last 40 years.

# Historial Perspective
Sepsis following from a throat infection was described by Scottmuller in 1918. 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.

# Pathophysiology

## Microscopic Pathology
Fusobacterium necrophorum
- It is a nonmotile, filamentous, nonfusiform pleomorphic non-spore-forming obligate anaerobic gram negative rod.
- Normal microbiota of the oropharynx, GI tract, and genitourinary tract.
- It is not known why F. necrophorum penetrates mucosa in some patients.
- Reduced host defense (EBV); synergistic, pathogenic complex with other bacteria.

# Differentiating Lemierre's Syndrome from Other Diseases
Lemierre's disease needs to be differentiated from the following diseases:
- Descending necrotizing mediastinitis
- Meningitis (mostly in children with otitis media)
- Beware false positive chlamydia PCR

# Epidemiology and Demographics

## Age
- Children: otitis media
- Young Adults: tonsillitis or peritonsillar abscess
- Adults: tooth infections
- All ages: mastoiditis, sinusitis

# Diagnosis

## Symptoms
The first symptoms are a sore throat, extreme lethargy, fever, and general body weakness, but after a week or two these symptoms are followed by a spiked fever, rigors, swollen cervical lymph nodes and septicemia (infection of the blood) which can cause complications in other parts of the body including abscesses of lung, brain, and other organs, kidney failure and also effects on liver and joints if untreated.

## Physical Examination

### Throat
Ipsilateral neck tenderness parallel with sternocleidomastoid muscle

### Lungs
Metastatic abscesses mainly to lungs (85%), but also joints (26%)

### Abdomen
Abdominal pain  2nd to microabscesses vs. thrombophlebitis of abdomino- pelvic veins

# Medical Therapy
Lemierre's syndrome is easily treated with antibiotics, but because sore throats are most commonly caused by viruses, for which antibiotic treatment is unnecessary, such treatment is not usual in the first phase of the disease.  Lemierre's disease proves that, rarely, antibiotics are sometimes needed for 'sore throats'. If a persistent sore throat, with the symptoms are found, physicians are cautioned to screen for Lemierre's syndrome. 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.

## Antimicrobial Regimen
- Septic jugular thrombophlebitis (Lemierre's syndrome)
- 1. Causative pathogens
- Fusobacterium
- Viridans and other streptococci
- Staphylococcus
- Peptostreptococcus
- Bacteroides
- Other oral anaerobes
- 2. Empiric antimicrobial therapy
- 2.1 Immunocompetent host
- Preferred regimen (1): Penicillin G 24 MU IV q46h
- Preferred regimen (2): Metronidazole 0.5 g IV q6h
- Preferred regimen (3): Ampicillin-Sulbactam 2 g IV q4h
- Preferred regimen (4): Clindamycin 600 mg IV q6h
- 2.2 Immunocompromised host
- Preferred regimen (1): Cefotaxime 2 g IV q6h
- Preferred regimen (2): Ceftizoxime 4 g IV q8h
- Preferred regimen (3): Piperacillin 3 g IV q4h
- Preferred regimen (4): Imipenem 500 mg IV q6h
- Preferred regimen (5): Imipenem 500 mg IV q6h
- Preferred regimen (6): Gatifloxacin 400 mg IV q24h

# Incidence
Lemierre's syndrome is currently a very rare disease, but was quite common in the early 20th century before the discovery of penicillin.  The reduced use of routine antibiotics for sore throats by doctors may have increased the risk of this disease, with 19 cases in 1997 and 34 cases in 1999 reported in the UK..  The incidence rate is currently 0.8 cases per million in the general population, leading it to be termed the "forgotten disease". The mortality rate was 90% prior to antibiotic therapy, but is now generally quoted as 15% with proper medical treatment, although one series of cases reported mortality as low as 6.4%.