Oesophageal cancer presenting as Lemierre’s syndrome caused by Streptococcus anginosus

Abstract

A 59-year-old man presented to the emergency department with complaints of dysphagia, right-sided neck swelling, fever and chills. Physical examination was remarkable for fever and tender swelling over the right side of the neck. Laboratory investigations revealed leucocytosis with neutrophilia. CT of the neck showed right internal jugular vein thrombosis with an overlying abscess and a nodular opacity in the right lung apex with air locules. He underwent surgical drainage of the neck abscess. Aerobic cultures from the drainage and blood cultures grew Streptococcus anginosus. Given his initial complaint of dysphagia, upper endoscopy was performed which showed a mass in the upper oesophagus. Histopathology confirmed squamous cell carcinoma. The patient received 6 weeks of antibiotics therapy.

Background

Lemierre’s syndrome (LS) (postanginal sepsis) is a septic thrombophlebitis of the internal jugular vein secondary to upper respiratory tract infection with Fusobacterium necrophorum as the identified pathogen.¹

Streptococcus anginosus belongs to a group carrying the same name which contains two other streptococci, S. constellatus and S. intermedius. To our knowledge, three cases of LS secondary to S. constellatus and three cases secondary to S. intermedius have been described in the literature.^2–7

The associations between S. anginosus and its carcinogenic role in the pathogenesis of oesophageal cancer has been postulated in different studies.^8–10

To our knowledge, our case will be the first to report of LS secondary to S. anginosus as an initial presentation of squamous cell carcinoma of the oesophagus.

Case presentation

A 59-year-old man with no medical history presented to the emergency department with complaints of swelling of the right side of the neck, fever, chills and difficulty swallowing. Two months before his presentation, the patient noted pain on swallowing that ultimately progressed to difficulty swallowing solids and then to liquids. Ten days before admission, the patient noticed a painful right-sided neck swelling. He reported 25 pounds weight loss over the preceding months. The patient was a chronic alcoholic with an 80 pack-year smoking history.

Physical examination revealed a temperature of 38.2°C, erythema, diffuse swelling and tenderness over the right side of the neck. There were coarse crackles over the right upper lung zone. Mouth examination revealed only three remaining teeth with no signs of infection.

Investigations

Haematological and biochemical laboratory parameters were notable for leucocytosis with neutrophilia and left shift.

CT angiography (CTA) of the neck revealed thrombosis of the right internal jugular vein (figure 1). CT of the neck shows air-containing soft tissue swelling in the right supraclavicular region (figure 2). Nodular opacity in the right lung apex with air locules suspicious for an abscess was detected on CT of the neck (figure 3).

Figure 1.

Axial section of CT angiography of the neck showing absence of contrast in the right internal jugular vein (arrow) indicating thrombosis of the right internal jugular vein.

Figure 2.

Coronal section of the CT neck with contrast showing air in the soft tissue with swelling in the right supraclavicular region.

Figure 3.

Coronal section of the CT neck showing air filled opacity in the upper lobe of the right lung (arrow).

Cultures of the blood and the abscess drainage were positive for S. anginosus. Upper gastrointestinal endoscopy revealed squamous cell carcinoma in the upper oesophagus.

Treatment

The patient was intubated due to impending respiratory failure secondary to upper airway obstruction. He was started empirically on vancomycin, cefepime and clindamycin. Based on culture and sensitivity results, antibiotics were changed to ceftriaxone and metronidazole. The patient received a 6-week course of antibiotics.

Outcome and follow-up

The hospital course was complicated by ventilator-associated pneumonia with highly resistant Pseudomonas aeruginosa that was treated with piperacillin-tazobactam. The patient required tracheostomy due to persistent upper airway obstruction. The patient improved clinically and repeat blood cultures were negative. On discharge, the patient was tracheostomy dependent.

Discussion

LS was first described by the French bacteriologist Andre-Alfred Lemierre in 1936 who labelled his observation as ‘anaerobic post anginal septicaemia’.¹ It was not until 1983 that the disease was labelled as ‘Lemierre's syndrome’ by Shannon et al in his description of a case of oropharyngeal septicaemia.¹¹ The syndrome is classically described in young patients with a mean age of 20 years.^{12 13} The incidence of this rare disease is increasing in the last 10 years possibly due to change in the pattern of antibiotic prescription or increase in bacterial resistance.¹² In a large prospective study in Denmark, the incidence of the disease was 14.4 cases per million per year in 15–24 years of age and it was rare in adults over 40 years of age, with an incidence of 1.4 cases per million per year.¹³

F. necrophorum is the classical culprit of LS, with reported incidence of 63%.¹³ Other organisms causing the syndrome have been described and include Staphylococcus, Streptococcus and Klebsiella.4 7 12 14 15

The syndrome presents initially as upper respiratory tract infection with sore throat being the most commonly observed complaint.^{12 16} Neck pain, which develops secondary to internal jugular vein thrombosis or neck abscess, is the second common presenting symptom.11 12 16–19 Atypical presentations include otalgia, otorrhoea, arthritis, dental pain, seizures and blindness in rare cases with extension to cranial venous sinuses.^{12 16 20}

The diagnosis of LS needs a high index of suspicion, and it is crucial for starting early therapy. The proposed criteria for the diagnosis are symptoms of upper respiratory tract infection, thrombosis of the internal jugular vein with subsequent septic emboli with bacteraemia and isolation of the causative bacteria in blood cultures.1 11 12 16–19 21–23

In our case, the causative organism was S. anginosus, a member of the anginosus group (previously was named as milleri group) of streptococci which also includes S. intermedius and S. constellatus. ²⁴ Virtually all strains (93%) of S. intermedius are non-haemolytic while 38% of S. constellatus and 12% of S. anginosus are β-haemolytic.^{25 26} S. anginosus group are normal flora of the oral cavity and genitourinary tract.²⁷ They are known for their association with purulent infection, which usually occurs after local disruption of the mucosal barrier that leads to ulceration, perforation, inflammation and surgery.^{27 28}

The DNA of S. anginosus has been linked to malignancy of the upper gastrointestinal tract.⁸ Moreover, the bacteria has been isolated in oesophageal dysplasia and cancer tissues and the bacterial DNA fragments are frequently found in samples from oesophageal and gastric cancers as well as oesophageal dysplasia suggesting S. anginosus infection or colonisation happen in the initial phases of the cancerous process, and it is related to carcinogenesis through induction of inflammation which promotes the cancerous process.^8–10

The infection in our case probably originated at the site of oesophageal cancer with subsequent invasion of the blood stream and involvement of the internal jugular vein leading to septic thrombophlebitis.

The cornerstone of therapy is prolonged course of antibiotics.¹² Although the final choice of antimicrobial therapy must be based on the result of culture and sensitivity, clinical judgement is crucial for the initial decision while awaiting the results of the culture.^{12 13} Suggested empiric antibiotic therapy includes clindamycin, ampicillin–sulbactam, piperacillin–tazobactam or a combination of penicillin G with metronidazole.12 13 18 19 22 29

There is no agreement on the use of anticoagulation, and no clear guidelines exists. An acceptable approach is to reserve the use of anticoagulation for patients with underlying thrombophilia, clot extension to cranial sinuses or poor clinical response to antibiotics.13 18 30 31 A recent systematic review found a rise in the rate of anticoagulation to 68% from 21% to 23% which was observed in previous systematic reviews.^{17 22}

In the presence of abscesses, surgical drainage is usually considered in the form of incision and drainage.^{18 19 29} An old surgical approach at the time of Lemierre was ligation of the internal jugular veins which is rarely used in the modern era unless there is persistent septic embolisation.^{18 32}

Learning points.

• Streptococcus anginosus should be considered as a causative organism for Lemierre’s syndrome.

• Oesophageal cancer can be associated with S. anginosus bacteraemia.

• Antibiotics and abscess drainage are the cornerstones of treatment for Lemierre’s syndrome; anticoagulation can be used in special situations.