Atypical involvement of the thyro-linguo-facial vein in Lemierre syndrome

Abstract

Fusobacterium necrophorum is a Gram-negative anaerobic bacterium that can lead to severe infection in young patients even without immunodeficiency. Due to the length of time for isolation and speciation of this Gram-negative bacillus (typically 5–8 days), and its potential mortality, broad-spectrum antibiotic therapy should be started without delay. With a cervical thrombosis, even on an unusual site and with a standard condition such as tonsillitis, Lemierre syndrome should be considered. We report a case of Lemierre syndrome in a previously healthy young woman.

Background

Lemierre syndrome (LS) is named after the French physician Andre Lemierre who in 1936 first described a group of patients with potentially lethal postanginal septicaemia defined by septic thrombophlebitis, usually of the internal jugular vein, followed by septic emboli.¹ The infection affected mostly young, healthy adults and adolescents. No difference between sexes was observed.

In the antibiotic era, incidence declined dramatically to be as low as between 0.6 and 2.3 per million in 2007.² Consequently, LS became the ‘Forgotten Disease’. Nowadays, it remains a disease of severe morbidity if left untreated or in case of delayed diagnosis.

Typical LS is caused by Fusobacterium necrophorum (FN), a commensal non-sporulating anaerobic Gram-negative bacillus.³ Atypical LS can be caused by other agents such as streptococci, staphylococci and Klebsiella pneumoniae^{4 5} and can be combined with FN or Fusobacterium nucleatum. Such combinations are presented in a recent case report involving a much older patient.⁶

The septic thrombophlebitis site usually involves the internal jugular vein from lateral extension of the bacterial pharyngitis/tonsillitis. This is followed by peripheral septic embolisation, very often to the lungs (up to 85.9%⁴ in typical LS) but is also possible in other sites such as the brain, liver, kidneys, peritoneum or joints.^{7 8}

We report here an unusual vein involvement adjacent to the infection site, with an exclusive thyro-linguo-facial venous thrombophlebitis.

Case presentation

In early March, a young woman in her mid-20s came to the emergency department with a 3-day history of sore throat, fever, chills and coughing that had substantially worsened during the 3 days.

Her background history revealed that, 3 months prior to the beginning of symptoms, she had travelled around South Africa for 4 months, without taking malaria prophylaxis. She did not have any known health problems. At admission, she was febrile (39.4°C), tachycardic at 118 beats/min and with a blood pressure of 94/68. Physical examination revealed enlarged erythematous tonsils without exudates, left-sided neck lymph node tenderness and neck stiffness without focal neurological signs.

The blood tests found a marked inflammatory response with a high C reactive protein (180 mg/L) and procalcitonin (>100 µg/L), the leucocyte count was 12.7 x10⁹ /L with 72.5% neutrophils. Liver tests demonstrated slightly unusual results namely alanine aminotransferase 64 IU/L, aspartate aminotransferase 56 IU/L, bilirubin 7.2 µmol/L, alkaline phosphatase 64 IU/L and gamma-glutamyl transferase 129 IU/L. Peripheral blood smear demonstrated severe thrombopaenia (34 g/L) without dysmorphia and acute normocytic anaemia (109 g/L) without schistocytes.

Because meningitis had initially been suspected due to neck stiffness and fever, intravenous ceftriaxone (2 g) was administered with 10 mg of dexamethasone and 600 mg of acyclovir. A lumbar puncture was performed revealing a clear cerebrospinal fluid, with 0.000001 x10¹²/L erythrocytes/µL and 2 leucocytes/µL, thus ruling out the potential meningitis diagnosis.

The rapid diagnosis test and microscopic examination for malaria and dengue fever were found negative, and a chest radiography was also performed which found no abnormalities. The patient was showing signs of distress and no clear diagnosis had been established. This, in conjunction with the abnormal laboratory tests, meant she was admitted to the Internal Medicine Department for further tests and for intravenous antibiotherapy to be continued.

On post admission day 2, the patient was still febrile, with cough and several episodes of loose stools.

Investigations

Serologies for HIV 1 and 2, cytomegalovirus and brucellosis were found to be negative, whereas Epstein-Barr virus serology demonstrated a past infection (Viral capsid antigen IgG and Epsterin-Barr nuclear antibodies IgG positive). Cultures were negative as was the cerebrospinal fluid PCR for varicella-zoster virus, Listeria monocytogenes, Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae B, enterovirus, herpes simplex I and II. PCR stool testing for norovirus 1 and 2 also produced negative results.

Due to the clinical severity with tonsil pain and cervical stiffness, a contrast-enhanced spiral cerebral and neck CT was performed. It showed an isolated thyro-linguo-facial venous thrombosis (figure 1) and infiltration of the fat of parapharyngeal deep spaces with oedema of the mucous membranes of the oropharynx. As she had pulmonary symptoms, a chest CT was also performed and showed two emboli, one of 15 mm in the right lower lobe and another of 2 mm in the left lower lobe (figure 2).

Figure 1.

Neck CT showing thyro-linguo-facial venous thrombosis.

Figure 2.

Chest CT showing septic pulmonary emboli.

The throat smear culture found commensal flora, but on day 3 anaerobic blood cultures became positive with FN and stayed positive for 3 days after the start of the course of antibiotics confirming a case of LS.

Treatment

She was treated with intravenous amoxicillin–clavulanic acid at 2.2 g four times per day and on the sixth day, after clinical improvement, was switched to ertapenem for 3 weeks to allow home intravenous therapy. Ertapenem was used, rather than ceftriaxone, as the patient had developed a light transient rash after the dose of ceftriaxone but had tolerated amoxicillin–clavulanic acid well.

After the 3-week course of the intravenous antibiotic at home, she was reassessed at the Infectious Diseases Outpatient Consultation where it was decided to continue treatment with 500 mg metronidazole three times daily for an additional 2 weeks. In all, antibiotics were employed for a total of 6 weeks during the course of therapy.

The left thyro-linguo-facial venous thrombosis was initially anticoagulated with low-molecular-weight heparin at day 3 (thrombocytopaenia had already partially resolved), then by 15 mg rivaroxaban two times per day for 3 weeks followed by 20 mg per day for 3 months.

Outcome and follow-up

The thrombocytopaenia resolved completely after 4 days of antibiotic treatment.

A duplex cervical ultrasound 3 months later excluded any residual thrombosis.

The patient is now well and not suffering from any residual disability.

Discussion

The major clinical point of interest in this case is the fact that the venous thrombosis was not localised in the typical site of the internal jugular vein, but rather in the unusual thyro-linguo-facial vein⁹ which in itself has many anatomical variations.

Initial treatment by broad-spectrum antibiotics was adapted after reception of the results of blood cultures to the antibiogram of FN. Following clinical improvement, the most convenient at-home therapy was chosen. Thus, ertapenem was selected as the intravenous antibiotic as it required only one treatment per day.

With FN being intrinsically resistant to macrolides, fluoroquinolones, tetracyclines and aminoglycosides, antibiotics associated with the most favourable outcomes (alone or combined) are metronidazole (the most used), clindamycin, penicillin (which is associated with clavulanate or sulbactam), cephalosporins and carbapenems.⁹

Total duration of antibiotic treatment is an ongoing subject of debate with an average course lasting 3–6 weeks¹⁰ depending on the extent of the infection and clinical response to initial treatment.

FN has been found to aggregate human platelets in vitro without associated lysis. This could lead to an anaerobic atmosphere and then to the creation of septic thrombophlebitis.¹¹ Interestingly it appears that there is no significant effect on mortality rates for patients treated with anticoagulation therapy versus patients not anticoagulated. It is proposed, however, for patients who do not respond to initial antibiotic treatment (as was the case in our patient) or for patients with underlying thrombophilia.¹¹ Nonetheless, the use of anticoagulation remains unclear due to the lack of randomised controlled studies.⁵

In our case, after initiating anticoagulation there was no evidence of further embolisation or seeding of infection. The thrombocytopaenia had already partially resolved at introduction; no complication was noted under anticoagulation. Thrombocytopaenia is often found in cases of LS¹² probably caused by haemagglutination; disseminated intravascular coagulation is less common.^{2 13} Some cases of thrombocytopaenic purpura have been observed.¹⁴ Surgery is rare but can be performed in some cases of non-response to medical therapy with a subsequent worsening of the patient’s condition⁸ and when collection(s) can be easily drained. This was not the case with our patient.

Learning points.

• Fusobaterium necrophorum is an anaerobic oropharyngeal commensal bacteria that can lead to severe infection in young patients even without immunodefıciency.

• Lemierre syndrome should be considered as a potential diagnosis in young patients with febrile neck stiffness, and broad-spectrum antibiotics should be started without delay.

• Diagnosis of thrombus is best made by contrast-enhanced CT of the neck and should be extended to the chest because of very frequent spread of embolic sepsis to the lungs even when the patient does not exhibit respiratory symptoms.

• Thrombocytopaenia is common and often self-limiting and is resolved with antibiotic treatment.

• Anticoagulation is to be considered depending on thrombosis site and any extensions.

Ethics statements

Patient consent for publication

Obtained.