Keywords Lemierre syndrome - external jugular vein - pharyngitis - thrombosis
Introduction
A common complaint in the pediatric population is a “sore throat.” Physicians should be aware that, in rare cases, this common symptom may develop into a potentially life-threatening disease called Lemierre syndrome (LS). Lemierre syndrome is a disease characterized with the evolution of septic thrombophlebitis of the internal jugular vein (IJV) secondary to local spread of infection, usually originating in the oropharyngeal cavity. It may be complicated by disseminated infections with more distal emboli, most frequently to the lungs. Presenting symptoms include pharyngotonsillitis or peritonsillar abscess, followed by ipsilateral painful swelling of the neck, fever, odynophagia, dysphagia, trismus, and other systemic symptoms. Lemierre syndrome typically involves the IJV, but the involvement of the external jugular vein (EJV) has rarely been reported.
We present a unique case of LS involving the EJV following an episode of tonsillitis and review the literature regarding LS involving the EJV.
Case Report
The ethics committee of our institution waived the need for ethics approval and the need to obtain consent for this report. We present a unique case of LS involving the EJV followed by a literature review ([Table 1 ]).
Table 1
Characteristics of the literature review
Title
Year
Age (years)
Sex
Side
Presentation
Pathogen
Thrombosis
Treatment
Outcome
Lemierre's syndrome: Acute oropharyngeal infection leading to septic thrombophlebitis of the internal jugular vein with pulmonary septic emboli
2019
12
Male
Left
Fever, sore throat, and neck swelling
Streptococcus constellatus
Ext jugular
+ Int jugular
Antibiotics
Completely recovered
Fissuration of vertebral artery mycotic aneurysm due to Lemierre syndrome
2018
26
Female
Left
Shortness of breath, weakness, hypokinesis on the right arm
N/A
Ext jugular
Right vertebral artery septic false aneurysm
Antibiotics
Surgery
Embolization
N/A
Lemierre Syndrome: A Retrospective Study of the Role of Anticoagulation and Thrombosis Outcomes
2017
16
18
32
42
Female
Male
Male
Male
Right
Left
Left
Left
N/A
N/A
N/A
N/A
N/A
N/A
N/A
N/A
Ext jugular
+ Int jugular
Ext jugular
Ext jugular
Ext jugular
Antibiotics
Antibiotics Anticoagulation
Antibiotics
Antibiotics Anticoagulation
Partial response
complete response
Complete response
Complete response
Lemierre's Syndrome Variant with External Jugular Vein Thrombosis
2017
51
Female
Left
Fever
Sore throat
Jaw pain
Group C streptococcus
Ext jugular
Antibiotics
Completely recovered
To anticoagulate? Controversy in the management of thrombotic complications of head & neck infections
2016
17
Male
N/A
Peritonsillar
abscess
Unknown
Ext jugular
+Int jugular
Antibiotics Anticoagulation
Residual VII palsy
17
Male
N/A
Odontogenic
Fusobacterium necrophorum
Ext jugular
+Int jugular
Antibiotics Anticoagulation
Completely recovered
MRSA-Associated Lemierre's Syndrome in an Intravenous Drug User
2015
24
Female
Right
Fever, neck pain Odynophagia
Methicillin-resistant Staphylococcus aureus (MRSA)
Ext jugular
+Int jugular
Antibiotics
Abscess drainage
Completely recovered
Lemierre syndrome involving external jugular vein
2014
74
Female
Left
Pharyngeal pain
Cold symptoms
Fusobacterium nucleatum
Ext jugular
Antibiotics Anticoagulation
Completely recovered
Lemierre's syndrome secondary to community-acquired methicillin-resistant Staphylococcus aureus infection presenting with cardiac tamponade, a rare disease with a life-threatening presentation: a case report
2014
45
Female
Left
Sore throat and mild fever
Methicillin-resistant Staphylococcus aureus (MRSA)
Ext jugular
+Int jugular Subclavian and axillary veins
Antibiotics Anticoagulation
Completely recovered
Lemierre syndrome: a pediatric case series and review of literature
2010
16
Male
Right
Fever, sore throat, right neck pain, right facial swelling, and right eye
Fusobacterium necrophorum
Ext jugular
+Int jugular
Antibiotics Anticoagulation
Completely recovered
An unusual case of Lemierre's syndrome due to methicillin-resistant Staphylococcus aureus
2010
33
Female
Bilateral
Face and neck swelling Dyspnea Hoarseness
Methicillin-resistant Staphylococcus aureus (MRSA)
Ex jugular
+Int jugular
Antibiotics
Completely recovered
A teenager with sore throat and neck pain
2010
15
Female
Right
Fever, joint pain, shortness of breath
Fusobacterium necrophorum
Ex jugular
Antibiotics Anticoagulation
Completely recovered
Lemierre Syndrome Following Oropharyngeal Infection: A Case Series
2009
19
Female
Right
Sore throat, low-grade fever, and malaise
Fusobacterium necrophorum
Ex jugular
Antibiotics
Completely recovered
Lemierre's syndrome with fourth nerve palsy
2009
3
Male
Left
Fever, sore throat, and intermittent headache
Streptococcus viridians, Streptococcus salivarius
Ex jugular
+Int jugular
Antibiotics Anticoagulation
IV nerve palsy
A Lemierre syndrome variant caused by Staphylococcus aureus
2008
22
Female
Right
Oropharyngeal infection
Facial cellulitis
Staphylococcus aureus
Ext jugular
+Int jugular
Antibiotics Anticoagulation
Surgery
Completely recovered
Case 2: An unusual presentation of an unusual condition (Case Presentation)
2008
14
Female
Left
Sore throat
Unknown
Ex jugular
Antibiotics Anticoagulation
Surgery
Completely recovered
Lemierre's syndrome: three cases and a review
2005
28
Female
Right
Sore throat Fever
Fusobacterium necrophorum
Ext jugular
+Int jugular
Antibiotics
Completely recovered
Cerebral infarctions and brain abscess due to Lemierre syndrome
2005
59
Male
Left
Temporal pain
Dentoalveolitis Right maxillary abscess
Unknown
Ext jugular
Antibiotics Anticoagulation
Improved
Unusual presentation of Lemierre's syndrome due to Fusobacterium nucleatum
2003
19
Male
Right
Fever, rigors, sore throat, pleuritic chest pain, and productive cough with blood-tinged sputum
Fusobacterium nucleatum
Ext jugular
Antibiotics Anticoagulation
Completely recovered
Postanginal septicaemia with external jugular venous thrombosis: case report
1999
49
Male
Right
Anterior gingiva trauma
Klebsiella pneumoniae
Ext jugular
Antibiotics Anticoagulation
Completely recovered
Lemierre syndrome: forgotten but not extinct—report of four cases
1999
22
Male
Right
Fever, cough, mild sore throat, weight loss
Enterococcus species
Ext jugular
+Int jugular
Antibiotics
Completely recovered
A case of Lemierre syndrome
1998
30
Male
Left
Cold symptoms
Lockjaw, facial pain
Unknown
Ext jugular
Antibiotics Anticoagulation
Completely recovered
Present study
2019
17
Female
Left
Sore throat
Fever
Unknown
Ext jugular
Antibiotics Anticoagulation
Completely recovered
We present the case of an otherwise healthy 17-year-old girl who arrived at the pediatric emergency department (PED) presenting with lymphadenitis, pleuritic chest pain, and fever. She was diagnosed with tonsillitis a week prior to admission and was started on oral antibiotics. Due to a negative throat culture, she received only 3 doses of oral antibiotics that were discontinued. Three days prior to her arrival, she began suffering from left submandibular lymphadenitis, tenderness, and trismus. On the morning of her arrival she complained of chest pain and dyspnea.
On arrival, she was alert and oriented and had a temperature of 38.3 Celsius, tachycardia of 116 beats/min, and a normal blood pressure. On physical examination, there was swelling with extreme tenderness on palpation over the left cheek and neck ([Fig. 1 ]). Throat examination revealed a swollen left tonsil covered with exudates, and multiple left lymphadenopathies of the Jugulodigastric region were palpated. Laboratory analysis revealed an elevated white blood count of 14.2 × 106 cells/L (norm 4.0–11.0), elevated C-reactive protein of 57 mg/L (norm ≤ 5), and all other laboratory examinations were unremarkable. Blood cultures were negative.
Fig. 1 (A ) Hyperemia and edema of the left neck along the sternocleidomastoid muscle (arrow) (B ) Hyperemia and edema of the left cheek and mandibular region (arrow).
A Doppler ultrasound study was performed revealing enlarged cervical lymph nodes with small areas of necrosis and thrombosis of the left EJV. Due to this finding, the patient was referred for a neck contrast-enhanced computed tomography (CT) scan that demonstrated signs of extensive deep neck infection with lymphadenopathy and EJV and facial vein thrombosis ([Fig. 2A ]&[B ]). An anatomical variant was noted, with anomalous facial vein drainage into the EJV ([Fig. 3 ]). The lung apices demonstrated 2 small nodular ground glass opacities that, in the context of the EJV infective thrombophlebitis, may be suggestive of a metastatic infection. The patient's respiratory symptoms improved, and her chest X-ray was normal, so we decided not to perform a lung CT scan.
Fig. 2 Contrast-enhanced computed tomography (A ) Axial view demonstrating extensive soft tissue swelling in the upper neck with necrotic lymph nodes in both levels 1 and 2 (arrowheads) and thrombosis of the external jugular vein with vessel wall enhancement (arrow) (B ) 3D reconstruction showing no filling of contrast material in the middle third of the external jugular vein (between arrows).
Fig. 3 (A ) Normal vascular anatomy of the neck (B ) Contrast enhanced computed tomography (curved multiplanar reformation reconstruction) displaying the thrombus of the external jugular and facial veins.
The patient was hospitalized in the pediatric intensive care unit (PICU) and treated with broad spectrum intravenous antibiotics (amoxicillin-clavulanic acid), which was switched to ceftriaxone and metronidazole as well as anticoagulation therapy (enoxaparin) following the diagnosis of LS. Her hospitalization and follow-up were uneventful.
Review of the Literature
Methods
We identified studies published in English language by searching electronic databases. The search was performed on multiple databases, which included: PubMed, Embase, Scopus, and Web of Science. Our search for the following medical subject headings (MESH) terms: suppurative thrombophlebitis OR septic thrombophlebitis OR Lemierre syndrome AND external jugular revealed 21 relevant articles.
Inclusion and Exclusion Criteria
Inclusion Criteria
Studies detailing the findings of patients with LS and EJV thrombosis were included. We also included retrospective studies and case reports. Only studies in English language were included. Letters, commentaries, and abstracts were eligible for evaluation.
Exclusion Criteria
Studies not specifying external jugular thrombosis in the patients. Papers without radiological evidence of thrombophlebitis were also excluded.
Data Extraction
The extracted data included anatomical considerations, age and incidence, sex, pathogens, presenting symptoms, imaging, management, and outcomes.
Discussion
The classical description of LS was published in 1936 as thrombophlebitis of the tonsillar or peritonsillar veins that can spread to the internal jugular vein (IJV).[1 ] The variant of LS involving the EJV is rare. In the patient discussed in the present article, LS involved the EJV and not the IJV.
Anatomical Considerations
The anatomy of tonsillar venous drainage is via the peritonsillar plexus, which drains into the lingual and pharyngeal veins, which, in turn, drain into the IJV. The EJV is formed by the connection of the posterior division of the retromandibular vein with the posterior auricular vein ([Fig. 3A ]). To explain the formation of a thrombus in the EJV, an anatomical variant should be considered. The facial vein, which is part of the tonsillar drainage, may have a variant. In our case, the facial vein drained directly into the EJV and not into the IJV ([Fig. 3B ]). This anatomical variant is not rare and is found in 9% of the population.[2 ] In 12 patients described in our review of the literature, the thrombosis involved the EJV and IJV. This could be explained by the inflammation ascending in a retrograde manner into the EJV or by the anatomical variation of the cervical venous drainage.[2 ] Another explanation for the involvement of the IJV is by septic emboli of this infection through the mucosa. This is followed by local invasion of the lateral pharyngeal space and IJV septic thrombophlebitis. A primary infection, such as Epstein-Barr virus (EBV), may facilitate the penetration of the mucosa.[3 ] This local involvement may eventually progress to involve the EJV.
Age and Incidence
Lemierre syndrome occurs mostly in the 2nd and 3rd decades of life. In our review, there were 16 patients (61%) in their 2nd and 3rd decades of life.[4 ]
[5 ]
[6 ]
[7 ]
[8 ]
[9 ]
[10 ]
[11 ]
[12 ]
[13 ]
[14 ]
[15 ] A review by Karkos et al. revealed 51% incidence rate in the 2nd decade.[16 ] Although this is mainly a young age group disease, in our review, LS was also found to be present in the 5th to 8th decades of life.[6 ]
[17 ]
[18 ]
[19 ]
[20 ]
[21 ] Males are more commonly affected,[4 ] although for EJV thrombosis, there is an equal gender distribution.
The annual incidence of LS is reported to be 3.6 per million persons/year. In the young age group (14 − 24 years of age), in which LS has been found to occur more frequently, the annual incidence is 14.4 cases/million.[22 ] Due to the paucity of reports regarding LS involving the EJV, we estimate that the incidence is even lower.
Pathogen
The pathogen most commonly isolated in LS is Fusobacterium necrophurium , which is an anaerobic, gram negative bacteria. In our case, the culture was negative, similar to 4 of the reviewed cases.[5 ]
[10 ]
[20 ]
[23 ] In 10 to 15% of the cases, no organism was identified.[24 ] Other bacteria that might cause LS include group C streptococcus, Klebsiella pneumoniae and Enterococcus species. An interesting finding is that methicillin-resistant Staphylococcus aureus (MRSA) was found in 3 cases,[13 ]
[21 ]
[25 ] and polymicrobial infections were found in 10 to 30% of cases.[3 ]
Presenting Symptoms
Our patient was diagnosed with tonsillitis, which then progressed to left submandibular lymphadenitis, cheek and neck tenderness upon palpation, trismus, and dyspnea. It is notable that LS is diagnosed clinically, and should be taken into consideration, when respiratory symptoms or neck swelling occur a week following a throat infection. Righini et al. described LS as developing in 2 clinical phases; the primary phase, which corresponds to an oropharyngeal infection of the mucosa, with or without signs of peritonsillar abscess, fever, and cervical lymphadenopathy and the secondary phase, with the spreading of infection to the parapharyngeal space with thrombophlebitis of the IJV and sepsis. During the 2nd stage, clinical examination reveals painful skin induration and inflammation anterior to the sternocleidomastoid muscle ipsilateral to oropharyngeal infection.[26 ] In our case, as well as in the reviewed literature cases involving the EJV, the presenting symptoms were sore throat and fever.[3 ]
[4 ]
[7 ]
[8 ]
[12 ]
[14 ]
[18 ]
[21 ]
[27 ] These symptoms, usually indicate involvement of the peri(tonsillar) area. As for the side involving thrombophlebitis of the EJV, the left side was more often involved.
Imaging
In our case, the diagnosis of LS was made by ultrasonography (US). This was followed by a contrast-enhanced CT scan to enable better assessment of the blood vessels, to evaluate the extent of the inflammatory process and to rule out potential complications.
There are 3 imaging modalities that can yield the diagnosis of LS. Doppler US is an available tool that can detect JV thrombosis; however, it is operator-dependent and may be less sensitive in the area deep to clavicle or below the mandible.
Magnetic resonance imaging (MRI) is an excellent modality to assess anatomic structures and to demonstrate venous thrombosis; however, it is expensive, not readily available, and requires either sedation or general anesthesia in younger patients.
Computed tomography with contrast material has been shown to be the modality of choice for the diagnosis of LS.[28 ]
[29 ] It is cheaper and is available in most hospital settings, though it involves radiation exposure. It can accurately demonstrate signs of infection and detect thrombosis of cervical veins. Furthermore, CT is the modality of choice for the diagnosis of regional or distant complications, such as abscesses, metastatic pulmonary or systemic infection.
Treatment
There is no consensus regarding the treatment of LS. The treatment requires antibiotics, occasionally anticoagulation, and, infrequently, surgery. In our case, we decided to treat conservatively with antibiotics and anticoagulation. In a review performed by Rebelo et al. regarding pediatric patients with LS, 11 patients were started on anticoagulation with low molecular weight heparin (LMWH) within a median of 2 days from diagnosis. Ten patients (90.9%) had thrombus improvement or resolution within a median of 3.4 months. There were no adverse effects from anticoagulation therapy. The review of the literature revealed the use of anticoagulation in 63.7% of pediatric LS cases.[5 ] Even though we have seen a high rate of anticoagulation therapy among LS patients, in our review the routine use of anticoagulation in LS cases cannot be recommended because of limited data. Furthermore, the use of anticoagulation may not affect thrombus resolution.[6 ] Other authors recommend using anticoagulation therapy in specific cases such as the potential for retrograde progression to the cavernous sinus or extensive thrombosis.[28 ] In our review, when there was EJV involvement, there was no consensus regarding the need for treatment with anticoagulation therapy.
Ligation or resection of the IJV was proposed in uncontrolled sepsis or ongoing emboli.[28 ] Although accessibility to the EJV is easier than the IJV, ligation or resection are rarely recommended today.
Outcome
Following discharge, the patient's follow-up was uneventful. In the review of the literature performed, all 26 patients with involvement of the EJV had a favorable outcome, except for 3 subjects. The 1st patient was a 17-year-old with a peritonsillar abscess, which deteriorated into LS with a residual VII nerve palsy.[5 ] The authors state that the patient was non-compliant with anticoagulation therapy.[5 ] The 2nd patient, with partial response, which was defined as an improvement of the thrombi with a decrease in size or partial recanalization, was not given anticoagulation treatment.[6 ] The 3rd patient developed trochlear nerve palsy and was treated with antibiotics and anticoagulation.[27 ]
Final Comments
Lemierre syndrome is a life-threatening complication of a common clinical condition seen by the general physician. Lemierre syndrome involving the EJV is extremely rare, which may be attributed to an anatomical variant in our patient. Diagnosing LS still requires thorough history taking and clinical examination as well as awareness of the connection between current acute medical illness and a recent pharyngeal infection. This case has a significant educational value, which teaches us not to underestimate even a “simple” tonsillitis.
