Pulmonary embolism and internal jugular vein thrombosis as evocative clues of Lemierre's syndrome: A case report and review of the literature.

Lemierre's syndrome (LS) is an uncommon condition with oropharyngeal infections, internal jugular vein thrombosis, and systemic metastatic septic embolization as the main features. Fusobacterium species, a group of strictly anaerobic Gram negative rod shaped bacteria, are advocated to be the main pathogen involved. We report a case of LS complicated by pulmonary embolism and pulmonary septic emboli that mimicked a neoplastic lung condition. A Medline search revealed 173 case reports of LS associated with internal jugular vein thrombosis that documented the type of microorganism. Data confirmed high prevalence in young males with Gram negative infections (83.2%). Pulmonary embolism was reported in 8.7% of cases mainly described in subjects with Gram positive infections (OR = 9.786; 95%CI: 2.577-37.168, P = 0.001), independently of age and gender. Only four fatal cases were reported. LS is an uncommon condition that could be complicated by pulmonary embolism, especially in subjects with Gram positive infections.

Core tip: We report a case of Lemierre’s syndrome (LS) complicated by pulmonary embolism (PE) that mimicked a neoplastic lung condition. The case was related to previously reported cases in Medline that documented the type of microorganism. We associated PE with LS due to Gram positive infections.

INTRODUCTION

Lemierre’s syndrome (LS) is an uncommon condition characterized mainly by oropharyngeal infections complicated with internal jugular vein (IJV) thrombosis and subsequently metastatic infections secondary to septic emboli. This syndrome was first reported by Andrè Lemierre in 1936 in a personal experience describing 20 patients[1].

Primary sites of infection in these patients are the tonsils (palatine tonsils or peritonsillar tissue), pharynx and lower respiratory tract[2]. Fusobacterium represents the most common micro-organism related to this syndrome (about 90% of cases). Fusobacterium spp. are strictly anaerobic Gram-negative rod shaped bacteria, mainly isolated from the oral cavity[3]. The mechanisms underlying virulent clinical conditions are not known, and Fusobacterium is considered a rare cause of head and neck infections[4].

After local proliferation, neck infection is associated with IJV thrombosis and then hematogenous spread to other peripheral organs could happen such as the lung, joints, soft tissue, abdominal parenchyma, and central nervous system[5].

We report a case of LS complicated by pulmonary embolism and pulmonary septic emboli after IJV thrombosis.

CASE REPORT

A 53-year-old man presented to emergency department because of a history of occipital headache, malaise, hacking cough, chest pain exacerbated by inspiration, and fever for one month. He had a history of smoking, hypertension, hyperuricemia, and gastro-esophageal reflux. His general practitioner treated him unsuccessfully with clarithromycin and ceftriaxone. Blood chemistry panel showed increasing inflammatory indexes, such as white blood cells (WBC) 16.560/mm3, C-reactive protein (CRP) 13.60 mg/dL, and erythrocyte sedimentation rate (ESR) 70 mm. Chest X-ray did not show parenchymal lesions, and either spinal column X-ray or encephalic nuclear magnetic resonance (NMR) was unremarkable.

On admission, the physical examination was unremarkable except that pharyngeal and tonsil hyperemia was detected. He was diagnosed with chronic tonsillitis by an otorhinolaryngologist. Pharyngeal packing with cultural exam identified saprophytic flora. Levofloxacin and nebulizer therapies were prescribed.

Further laboratory tests showed WBC = 11.070/mm3, CRP = 3.70 mg/dL, ESR = 53 mm, fibrinogen = 706 mg/dL, and D-dimer = 773 ng/mL. Immunoglobulin-A was 559 mg/dL. Chest X-ray showed parenchymal and pulmonary consolidation associated with pleural effusion. Bronchoscopy with broncho-alveolar lavage (BAL) including microbiology and cytology was negative.

A chest computed tomography (CT) scan showed left pleural effusion, contralateral sub-pleural fibrosis and, above all, an important ovular lesion at the level of medial right lobe measuring 25.7 mm with central cavitation. Further three lesions of 5-6 mm at the superior right lobe, and enlargement of pulmonary hilar lymph nodes were evident (the largest was 13.4 mm). Since these images were suggestive of pulmonary neoplastic lesions (Figure 1A), a brain CT scan was planned. The latter detected a deficit of right sigmoid sinus and bulb of jugular vein filling, which were suggestive of thrombosis of the right jugular vein (Figure 2A). Doppler ultrasonography of upper and lower limbs and echocardiography were negative. A further careful re-evaluation of chest CT supported the hypothesis of septic pulmonary outbreaks, and filling defect in the upper and middle branches of the right pulmonary artery suggested pulmonary embolism (Figure 1B). A diagnosis of LS associated with IJV thrombosis secondary to tonsillitis and pulmonary emboli was made, and low molecular weight heparin (LMWH) was added to levofloxacin. Eleven days later, the patient was discharged in good general conditions. One month after discharge, a cerebral magnetic resonance angiogram (MRA) showed the complete re-canalization of the IJV (Figure 2B).

Figure 1

Chest computed tomography showing pulmonary lesions in the posterior region of the right lung (A) associated with left pulmonary embolism (B).

Figure 2

Internal jugular vein thrombosis (arrow) showed by brain TC (A), and further complete re-canalization demonstrated by cerebral magnetic resonance angiogram after antibiotic and anticoagulant therapy (B).

DISCUSSION

LS is an oropharyngeal infection complicated with IJV thrombosis and subsequently metastatic infections due to septic emboli[1]. LS represent an uncommon condition, and its prevalence is 0.6-2.3 cases per million population. Mortality rate is 4%-18%[6]. LS incidence is higher in people aged 14-24, and its annual rate is 14.4 cases per million people per year. Mean age of patients is reported to be 18-20 years[6,7]. Male patients seen to be at higher risk, especially in autumn and winter[5].

The most common etiology of LS is infection due to Fusobacterium necrophorum, an anaerobic, non-motile, filamentous and non-spore forming Gram negative rod, which is described in 80% of cases. Several other organisms have been reported, isolated as single pathogen (5% of cases) or in association with Fusobacterium necrophorum (10.1%), such as many bacteria of Bacteroides family, Group B and C Streptococcus, Streptococcus oralis, Staphylococcus epidermidis, Klebsiella pneumoniae, Enterococcus sp., Proteus mirabilis, Eubacterium sp., Eikenella corrodens, lactobacilli and Candida sp. On the other hand, culture results are negative in 12% of cases[7].

The main site of infection is palatine tonsils (87.1% of cases) and it could lead to exudative tonsillitis and peritonsillar tissue ulcer. However, it has been reported that only hyperemia or grey pseudo-membrane could be detected. Moreover, odontogenic infections, mastoiditis, parotitis, sinusitis, otitis, and skin or subcutaneous tissue infection of the head or neck may represent the primary infection site. Finally, the disease could happen even if the appearance of the pharynx was not remarkable[5-7].

Pulmonary embolism is not frequently described in LS. Lesions of the lungs are due to haematogenous spread of bacteria from the IJV, and necrotic cavitary lesions, infiltrates, pleural effusions or empyema, abscesses, pneumo-thoraces, or necrotising mediastinitis have been reported[5].

We performed a Medline literature search to identify papers reporting cases with LS associated with IJV thrombosis. The following search terms were used: “Lemierre syndrome” in combination with “internal jugular vein thrombosis” and “vein thrombosis”. We found that isolation of microorganism was available in 173 cases (Table 1). LS was described more frequently in males (61.3%), aged 25.5 ± 14 years. Gram negative bacteria (84.3%), particularly Fusobacterium spp (76.3%), were related to it. Multiple microorganisms were reported in 8.7% of cases. Complications such as IJV thrombosis, arterial thrombosis, and pulmonary embolism were reported in 71.7%, 2.9% and 8.7% of cases, respectively. Only four fatal cases (2.3%) were described. Univariate analysis (Table 2) showed that pulmonary embolism was more frequent in patients with Gram positive bacteria. This finding was further confirmed by multivariate analysis and we calculated an odd ratio of 9.786 (95%CI: 2.577-37.168, P = 0.001). The relationship was independent from age, gender, and site of thrombosis.

Table 1

Reported cases of Lemierre’s syndrome with internal jugular vein documenting microbiology

Ref.	Pathogen
Vogel et al, Am J Dis Child 1980	FN
	FN
Sinave et al, Medicine (Baltimore) 1989	FN
	FN, Staphy. epidermidis
Jones et al, Postgrad Med J 1990	FN
Blok et al, Ned Tijdschr Geneeskd 1993	FN
	FN
	FN
Ahkee et al, Ann Otol Rhinol Laryngol 1994	FN
Bader-Meuiner et al, Eur J Pediatr 1994	FN
Dykhuizen et al, Eur Respir J 1994	FN and Bacteroides fragilis
Hughes et al, Clin Infect Dis 1994	Multiple microrganisms
Kubota et al, Nihon Kyobu Shikkan Gakkai Zasshi 1994	FN
Alvarez et al, Pediatrics 1995	FN
Gupta et al, Clin Pediatr (Phila) 1995	FN and Staphy. epidermidis
Karanas et al, Ann Plast Surg 1995	FN
Bhagat et al, Infect Dis Clin Pract (Baltim Md) 1996	Klebsiella pneumoniae
De Sena et al, Pediatr Radiol 1996	FN
	FN
Harar et al, ORL J Otorhinolaryngol Relat Spec 1996	FN
Lee et al, South Med J 1997	Strepto. viridans
Bouton et al, Rev Med Brux 1998	FN
Dhawan et al, Indian J Pediatr 1998	Peptostrepto. anaerobius, Bacteroides fragilis, Eikenella corrodens
Williams et al, Int J Pediatr Otorhinolaryngol 1998	Strepto. viridians
	Strepto. viridians
Gong et al, Eur Radiol 1999	FN
Stokroos et al, Arch Otolaryngol Head Neck Surg 1999	FN
Agarwal et al, J Laryngol Otol 2000	FN
Alifano et al, Ann Thorac Surg 2000	FS and Propionibacterium
Chemlal et al, Presse Med 2000	Strepto. intermedius
Edibam et al, Crit Care Resusc 2000	FN
Gowan et al, Can Respir J 2000	FN
Ockrim et al, J R Soc Med 2000	FN
Shaham et al, Clin Imaging 2000	FS
Abele-Horn et al, Eur J Clin Microbiol Infect Dis 2001	FN
De Vos et al, Neth J Med 2001	FN
Singhal et al, South Med J 2001	FN
Turay et al, Respirology 2001	FN
Chirinos et al, Medicine (Baltimore) 2002	FN
	FN
Hoehn et al, Crit Care Med 2002	FN
Hope et al, J Laryngol Otol 2002	FN
Nguyen-Dinh et al, J Neuroradiol 2002	Strepto. species
Boo et al, Ir Med J 2003	FN
Dalamaga et al, Anaerobe 2003	FN
de Lima et al, Pediatr Radiol 2003	FN
Figueras et al, Acta Paediatr 2003	FN
Hodgson et al, Undersea Hyperb Med 2003	FN
Jarmeko et al, CMAJ 2003	FN
Velez et al, J Oral Maxillofac Surg 2003	FN
Williams et al, J Clin Microbiol 2003	FN
Ramirez et al, Pediatrics 2003	FN
	FN
	FN
	FN
	FN
Ahad et al, Eye (Lond) 2004	FN
Bentham et al, Pediatr Neurol 2004	FN
Giridharan et al, J Laryngol Otol 2004	FN
	FN
	FN
Lai et al, N Engl J Med 2004	FN
Litterio et al, Anaerobe 2004	FN
Ritter et al, Ultraschall Med 2004	FN
Aliyu et al, Eur J Clin Microbiol Infect Dis 2005	FN
Charles et al, J Vasc Surg 2005	FN
Dool et al, Eur Arch Otorhinolaryngol 2005	FN
	FN
	FN
Kuduvalli et al, Acta Anaesthesiol Scand 2005	FN
Libeer et al, Acta Clin Belg 2005	FN
	FN and Bacteroides spp
Masterson et al, Int J Pediatr Otorhinolaryngol 2005	FN
Min et al, Angiology 2005	Staphy. haemolyticus and himinis
Morizono et al, Intern Med 2005	Porphyromonas asaccharolytica
Nadkarni et al, J Emerg Med 2005	FN
Nakamura et al, Angiology 2000	FN
Ochoa et al, Acad Emerg Med 2005	FN
Peng et al, J Formos Med Assoc 2005	FN
Rivero Marcotegui et al, An Med Interna 2005	Mycoplasma pneumoniae
Schmid et al, Pediatrics 2005	FN
Shah et al, J Ayub Med Coll Abbottabad 2005	FN
	FN
Touitou et al, Eur J Neurol 2006	FN
Venkateswaran et al, Ann Acad Med Singapore 2005	FS and Bacteroides fragilis
Varkey Maramattom et al, Cerebrovasc Dis 2005	FN
Hochmair et al, Wien Klin Wochenschr 2006	FN
Fleskens et al, Ned Tijdschr Geneeskd 2006	FN
	FN
Constantin et al, BMC Infect Dis 2006	FN
Ravn et al, Scand J Infect Dis 2006	FN
Morris et al, Ir Med J 2006	FN
Olson et al, Br J Ophthalmol 2006	FN
Park et al, J Bone Joint Surg Br 2006	FN
Perović et al, Acta Med Croatica 2006	FN
Singaporewalla et al, Singapore Med J 2006	Klebsiella pneumoniae
Boga et al, J Thromb Thrombolysis 2007	Staphy. aureus
Brown et al, J Laryngol Otol 2007	FN
Chiu et al, Australas Radiol 2007	FN
Cholette et al, Pediatr Pulmonol 2007	FN
	FN
Juárez Escalona et al, Med Oral Patol Oral Cir Bucal 2007	Strepto. intermedius and Bacteroides fragilis
Thompson et al, Infect Dis Obstet Gynecol 2007	Peptostrepto. anaerobius, Bacteroides fragilis, and Eikenella corrodens
Wang et al, Anaesth Intensive Care 2007	FN
Westhout et al, J Neurosurg 2007	FN
Garimorth et al, Wien Klin Wochenschr 2008	FN
Georgopoulos et al, J Laryngol Otol 2008	FN
Kadhiravan et al, J Med Case Rep 2008	Staphy. aureus
Bentley et al, J Emerg Med 2009	Staphy. aureus
Goyal et al, Neurol Sci 2009	FN
Lee et al, J AAPOS 2009	Strepto. viridans and salivarius
Lu et al, J Am Board Fam Med 2009	FN
	FS
	FS
Takazono et al, Jpn J Infect Dis 2009	FN
van Wissen et al, Blood Coagul Fibrinolysis 2009	FN
	FN
Castro-Marín et al, J Emerg Med 2010	FN
Chacko et al, J Laryngol Otol 2010	FN
Herek et al, J Emerg Med 2010	Staphy. aureus
Courtin et al, Ann Fr Anesth Reanim 2010	FN
Bonhoeffer et al, Klin Padiatr 2010	FN
Lim et al, Auris Nasus Larynx 2010	Staphy. aureus
Nakayama et al, Auris Nasus Larynx 2010	FN
Ridgway et al, Am J Otolaryngol 2010	FN
Vargiami et al, Eur J Pediatr 2010	Abiotrophia defective
Vincent et al, J Pediatr 2010	FN
Gülmez et al, Mikrobiyol Bul 2011	FN
Huynh-Moynot et al, Ann Biol Clin (Paris) 2011	FN
Maalikjy Akkawi et al, Neurol Sci 2001	Klebsiella pneumoniae
Naito et al, Nihon Kokyuki Gakkai Zasshi 2011	FN
O'Dwyer et al, Ir J Med Sci 2011	FN
Yamamoto et al, Nihon Rinsho Meneki Gakkai Kaishi 2011	FN
Garbati et al, J Med Case Rep 2012	Klebsiella pneumoniae
Hile et al, J Emerg Med 2012	Peptococcus anaerobius
Kuppalli et al, Lancet Infect Dis 2012	FN
Lee et al, J Microbiol Immunol Infect 2012	Klebsiella pneumoniae
Lim et al, Med J Malaysia 2012	Klebsiella pneumoniae
Teai et al, J Formos Med Assoc 2012	Klebsiella pneumoniae
Teng et al, J Emerg Med 2012	FN
Tsai et al, J Formos Med Assoc 2012	Klebsiella pneumoniae
Abhishek et al, Braz J Infect Dis 2013	Staphy. aureus
Blessing et al, Int J Pediatr Otorhinolaryngol 2013	FN
Khan et al, Indian J Pediatr 2013	FN
Klein et al, Heart Lung 2013	Mycoplasma pneumoniae
Marulasiddappa et al, Indian J Crit Care Med 2013	Staphylococcus aureus
Nguyen et al, Malays J Med Sci 2013	Klebsiella pneumoniae
Phua et al, Int J Angiol 2013	Klebsiella pneumoniae
Righini et al, Head Neck 2014	FN
	FN
	FN
	Strepto. costellatus
	Enterococcus faecalis
	Strepto. anginosus
	Neisseria species
	FN
	FN
Gunatilake et al, Int J Emerg Med 2014	Staphy. aureus
Asnani et al, J Fam Pract 2014	FN
Galyfos et al, Scand J Infect Dis 2014	FN
Aslanidis et al, Pan Afr Med J 2014	Candida albicans, Staphy. epidermidis, and Klebsiella pneumonia
Karnov et al, Open Forum Infect Dis 2014	FN
Choi et al, Tuberc Respir Dis (Seoul) 2015	Staphy. epidermidis
Chuncharunee et al, Hawaii J Med Public Health 2015	Klebsiella pneumoniae
Croft et al, Respir Med Case Rep 2015	FN
Fischer et al, Infect Dis Rep 2015	FN
He et al, BMJ Case Rep 2015	FN
Kempen et al, Eur Spine J 2015	Strepto. milleri and FS
Prakashchandra et al, J Clin Diagn Res 2015	FN
Oya et al, Intern Med 2015	FS
Takano et al, BMC Res Notes 2015	FN
Wong et al, J Am Board Fam Med 2015	FN
Habert et al, Rev Mal Respir 2016	FN

FN: Fusobacterium necrophorum; FS: Fusobacterium species; Strepto: Streptococcus; Staphy: Staphylococcus.

Table 2

Univariate analysis comparing cases of Lemierre’s syndrome with and without pulmonary embolism

	No pulmonary embolism (n = 158)	Pulmonary embolism (n = 15)	P
Female, n (%)	61 (38.8)	6 (38.5)	NS
Male, n (%)	97 (61.2)	9 (61.5)
Age, (yr)	25.5 ± 14.1	26.2 ± 13.6	NS
Gram positive bacteria, n (%)	21 (13.3)	6 (40)	0.006
Gram negative bacteria, n (%)	137 (86.7)	9 (60)
Multiple microrganisms, n (%)	14 (8.9)	1 (6.7)	NS
Only jugular vein thrombosis, n (%)	113 (71.5)	11 (73.3)	NS
Arterial thrombosis, n (%)	5 (3.2)	0	NS
Fatal cases, n (%)	4 (2.5)	0	NS

NS: Not significant.

In conclusion, LS is a rare condition that can mimic a neoplastic disease. However, the careful evaluation of clinical evolution should suggest a correct diagnosis. Moreover, the presence of pulmonary embolism represents a serious complication, and should be suspected when infection is due to Gram positive bacteria.

ACKNOWLEDGMENTS

We are indebted to Mrs. Francesca Molinari and Mrs. Cristina Rinaldi, from the University of Ferrara Library Staff, and to Dr. Donato Bragatto, Dr. Claudia Righini, Mrs. Manuela Zappaterra, from the Health Science Library of the Azienda Ospedaliera-Universitaria of Ferrara, for their valuable and precious collaboration.

COMMENTS

Case characteristics

A 53-year-old man with a history of smoking, hypertension, hyperuricemia, and gastro-esophageal reflux presented with occipital headache, malaise, hacking cough, chest pain exacerbated by inspiration, and fever.

Clinical diagnosis

Physical examination showed only pharyngeal and tonsil hyperemia related to chronic tonsillitis in the patient with a history of gastro-esophageal reflux.

Differential diagnosis

Pulmonary infection with slow resolution, pulmonary abscess, and pulmonary neoplasia.

Laboratory diagnosis

Laboratory work-up showed increased white blood cells, C-reactive protein, and erythrocyte sedimentation rate.

Imaging diagnosis

Chest X-ray was negative for parenchymal lesions at first, but then it showed parenchymal and pulmonary consolidation associated with pleural effusion confirmed by a computed tomography scan. Moreover, filling defect in the upper and middle branches of the right pulmonary artery suggestive of pulmonary embolism was detected. A brain computed tomography scan excluded parenchymal lesions, but a deficit of the right sigmoid sinus and bulb of jugular vein filling suggestive of thrombosis of right jugular vein were shown.

Pathological diagnosis

Tonsillitis related to Fusobacterium infection complicated with internal jugular vein thrombosis and pulmonary embolism.

Treatment

The patient was treated with levofloxacin and low molecular weight heparin.

Related reports

Lemierre’s syndrome is a rare condition characterized by oropharyngeal infection complicated by internal jugular vein thrombosis and pulmonary embolism.

Experiences and lessons

Lemierre’s syndrome could mimic a neoplastic process. A careful follow-up of this condition is necessary.

Peer-review

The paper is well written.