Lemierre's syndrome: what is it, symptoms, treatment, prognosis

What is Lemierre Syndrome?

Lemierre syndrome (SL) is named after the French physician André Lemierre, who in 1936 reported 20 cases of anaerobic sepsiscaused by infections of the oropharynx. This is a rare complication of bacterial pharyngitis/ tonsillitis and includes the spread of infection to the lateral pharyngeal spaces of the neck, followed by septic thrombophlebitis of the internal jugular vein (s). It is associated with anaerobic septicemia and death in young healthy patients. Due to the high incidence of benign oropharyngeal infections in this population, the diagnosis of Lemierre syndrome is often elusive at the initial presentation, which can lead to delayed treatment.

Causes and risk factors

Lemierre syndrome occurs as a complication of bacterial throat infections. The most common responsible bacteria are Fusobacterium necrophorum, obligate anaerobic, gram-negative bacilli and 

Fusobacterium nucleatum. These bacteria can cause invasive diseases secondary to several virulence factors, including endotoxins and exotoxins. Other organisms such as species Streptococcus, Bacteroides, Staphylococcus aureus, Klebsiella pneumoniae and others have also been reported in other case studies.

F. necrophorum is part of the normal bacterial flora of the pharynx, gastrointestinal tract and female reproductive tract. In addition to primary infection, it has been postulated that infections of the oropharynx of other etiology may lead to conditions conducive to the growth of fusobacteria. These can be viral infections, such as acute infections. Epstein-Barr virus, or bacterial infections such as streptococcal. Conditions conducive to anaerobic growth, such as peritonsillar abscess, allow for growth and penetration F. necrophorum into the surrounding tissue. The spread of infection from the oropharynx into the lateral pharyngeal space leads to the culture of the internal jugular veins, septic thrombophlebitis and subsequent access to the venous system, which leads to sepsis and septic emboli.

Epidemiology

The highest incidence of Lemierre syndrome was before the antibiotic era. With the widespread use of penicillin in the 1960s and 1970s, the incidence of SL dropped dramatically. There has been a steady increase in the number of reported cases since the late 1970s, which may be due to a decrease in the use of empiric antibiotics for oropharyngeal infections. It is still a rare syndrome with an estimated worldwide incidence of 1 / 1,000,000. Lemierre's syndrome usually affects young, previously healthy, adolescents and young adults. The average age of patients with SL is 19 to 22 years, depending on the study, with a male to female ratio of 2: 1. Approximately 90% of patients who develop SL are between the ages of 10 and 35 years.

Pathophysiology

Lemierre syndrome begins as a localized oropharyngeal infection. It is not known exactly whether F. necrophorum predominantly as a primary or secondary pathogen in the early stages of SL. In addition to direct infection, it has been postulated that damage to the pharyngeal mucosa caused by other bacterial or viral infections, leading to conditions conducive to fusobacterial superinfection. The infection then spreads to the lateral space of the pharynx and the soft tissues of the neck. Venous thrombosis occurs locally in the peritonsillar veins and then spreads to the internal jugular veins. F. necrophorumhas been shown to aggregate human platelets in vitro, subsequently provoking intravascular coagulation. In combination with venous congestion due to external compression and internal occlusion of the vessel, secondary to in relation to inflammation and edema, this leads to the development of septic thrombosis of the internal jugular veins. Release of septic emboli into the systemic circulation leads to widespread F. necrophorum to the lungs, pleura, joints, bones, muscles, spleen, liver, kidneys and other endpoints of blood circulation. Direct expansion or spread of a blood clot can lead to the formation of an abscess of the central nervous system, as well as thrombosis of the cavernous sinus.

Signs and symptoms

The manifestation and clinical progression of Lemierre's disease can usually be divided into 3 main phases. These phases can also serve to diagnose the syndrome.

1. Oropharyngeal infection: Clinical signs of Lemierre syndrome begin with an infection of the oropharynx followed by bouts of fever and chills 4 to 7 days after the initial illness. Early diagnosis can be challenging because symptoms are nonspecific and are usually associated with self-limiting pharyngeal infections. More than two thirds of patients report a pharyngeal infection at the onset of the disease, but rarely has the disease been described in context. mumps, otitis media, mastoiditis, sinusitis and dental infections. Patients with confirmed Epstein-Barr infection may also develop SL, and seropositive patients with mononucleosis delays in diagnosis may occur if SL is not considered as an alternative diagnosis. Persistence of fever and worsening clinical condition after 1 week may be an important clinical sign.
2. The spread of infection to the parapheral space of the neck with thrombophlebitis of the internal jugular vein: soreness and swelling of the neck may be early clinical signs that pharyngitis has spread beyond the oropharynx. Unilateral tenderness and swelling at the angle of the mandible, indicates internal thrombosis of the jugular vein, but is present only in 25–45% of cases. It is also necessary to conduct a targeted examination of the neck, including the suprasternal and supraclavicular regions, for signs of skin cellulitis, which may indicate the spread of infection to the cervical veins and structures mediastinum.
3. Septic emboli: once F. necrophorum penetrates into the cervical veins, there are septic emboli. The most commonly affected organ is the lungs (85%), but joints, liver, kidneys, brain, bones, heart and meninges can be affected. Bacteremia associated with fever, lethargy, or shockas well as damage to target organs. Septic shock occurs in about 7% of cases. Acute Respiratory Distress Syndromerequiring mechanical ventilation can affect up to 10% of patients.

Diagnostics

The diagnosis of Lemierre's syndrome is predominantly clinical, but additional testing may be helpful. Comprehensive laboratory assessment is indicated for patients with suspected sepsis or with criteria for systemic inflammatory response syndrome (SIRS). Some of the more common laboratory abnormalities include leukocytosis, mild to severe renal failureabnormal liver function tests, including elevated bilirubin, thrombocytopenia, as well as other signs of disseminated intravascular coagulation. Blood cultures should be collected, growth usually takes 2 to 7 days and in more than 70% of cases shows the species Fusobacterium. Blood cultures can be negative in Lemierre syndrome because of the difficulties that can be associated with the cultivation of anaerobic organisms.

The lungs are the most common site for metastatic infection, and imaging should include chest x-ray to evaluate septic embolism and other pulmonary complications, including effusion into the lungs, lung abscess and empyema. Additional sites of bacterial metastases can lead to septic arthritis, osteomyelitis, meningitis, pericarditis and liver abscess. Other imaging techniques used to evaluate septic internal jugular vein thrombosis may include ultrasound, contrast-enhanced CT of the neck, and magnetic resonance imaging (MRI). Magnetic resonance phlebography has the highest sensitivity (97%) for detecting internal thrombosis jugular vein, while CT is usually the most readily available and widely used in clinical conditions. Ultrasound can be useful given its relatively lower cost and no radiation risk.

Treatment

The mainstay of treatment for Lemierre's syndrome is antibiotic therapy. A beta-lactam antibiotic resistant to beta-lactamase is recommended as an empiric therapy due to reports of treatment failure with penicillin secondary to F. necrophorum, producing beta-lactamase. Antibiotics should be tailored to culture and susceptibility data, if available. Alternatives include clindamycin or metronidazole for patients with significant clinical beta-lactam allergy. In most patients, antibiotic therapy is continued for 6 weeks to achieve proper penetration of fibrin clots.

Surgical treatment may be required in cases of abscess formation, respiratory distress, caused by pulmonary thrombosis, metastases, as well as in patients with the spread of a thrombus into the mediastinum or brain. Surgical incision and drainage of the abscess in the affected area may be indicated to control the infection.

Anticoagulant therapy in Lemierre's syndrome is controversial. Uncomplicated SL without evidence of extensive clotting is resolved with appropriate antibiotic and supportive therapy and does not require anticoagulation. There are no controlled trials to confirm this practice, but anticoagulant therapy is usually recommended when a blood clot has spread to the sinuses of the head. brain, with a large or bilateral blood clot, or when the patient's condition does not improve within the first 72 hours with appropriate antibiotics and / or surgery therapy.

Forecast

Progressive Lemierre syndrome is a life-threatening condition. Even with appropriate antibiotics and therapy, mortality is reported to be between 5% and 18%. Hospitalization usually requires intensive care unit (ICU) status, and the average hospital stay is approximately 3 weeks. Septic embolism and target organ exposure can lead to long-term complications.