Pediatric Patient with Lemierre Syndrome of the External Jugular Vein: Case Report and Literature Review

Abstract

Introduction  Lemierre syndrome (LS) involving the external jugular vein (EJV) is rare, and only a few cases have been reported in the literature.

Objectives  To report a case of LS involving the external jugular vein as well as to make a review of the literature regarding both diagnosis and management strategies.

Data Synthesis  We describe a case of LS involving the EJV and review the literature of previously published articles to search for additional cases. A PubMed, Embase, Scopus, and Web of science-based search was performed to determine the scope of coverage in well-reported articles in English. Twenty-one papers were retrieved and documented for age, incidence, pathogen, presenting symptoms, imaging, treatment, and outcome, which were noted for each of these cases. In our literature review of 21 papers, there were 16 patients (61%) in their 2nd and 3rd decades of life. Lemierre syndrome was shown to affect females and males equally. The presenting symptoms were a sore throat and fever. Treatment requires intravenous antibiotics, and there is no consensus regarding treatment with anticoagulation.

Conclusions  The present case report and review of the literature emphasize the importance of history taking as well as physical examination in what seems to be a case of simple tonsillitis.

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 × 10 ⁶ 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 2 ^nd and 3 ^rd decades of life. In our review, there were 16 patients (61%) in their 2 ^nd and 3 ^rd 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 2 ^nd decade. ¹⁶ Although this is mainly a young age group disease, in our review, LS was also found to be present in the 5 ^th to 8 ^th 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 2 ^nd 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 1 ^st 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 2 ^nd 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 3 ^rd 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.