Lemierre syndrome making an encore in the post-antibiotic era: A case report

ABSTRACT

Lemierre syndrome is a rare complication of an acute oropharyngeal infection. The disease is characterized by antecedent protracted pharyngitis, septic thrombophlebitis of the internal jugular vein, and secondary septic embolization to distant sites. We present a case of a previously healthy 17-year-old female with a sore throat and unilateral neck pain of 3-day duration. She tested positive for cytomegalovirus, Epstein-Barr virus, and Mycoplasma pneumoniae. Lemierre syndrome was diagnosed by contrast-enhanced computed tomography (CT) of the neck and chest. She experienced full recovery after four weeks of combined beta-lactam antibiotic and metronidazole and no anticoagulant therapy. Lemierre syndrome remains a diagnostic challenge due to its rarity. In the post-antibiotic era, atypical causative pathogens are commonly seen. Contrast-enhanced CT of the neck serves as the gold standard for the diagnosis of Lemierre syndrome. This case highlights the importance of having a high index of suspicion for an early accurate diagnosis, appropriate treatment, and optimal outcome.

Introduction

Lemierre syndrome is characterized by an antecedent oropharyngeal infection, septic thrombophlebitis of the internal jugular vein, and secondary septic embolization to distant sites.[1] The incidence and associated high mortality rate of Lemierre syndrome declined dramatically during the antibiotic era, to be followed by a rise in incidence in the post-antibiotic era.[2] Clinicians should suspect Lemierre syndrome in a previously healthy young adult with prolonged pharyngitis associated with unilateral neck pain.[3] The availability of contrast-enhanced computed tomography (CT) is crucial in identifying thrombophlebitis of the internal jugular vein and septic emboli for a prompt diagnosis and appropriate treatment. We report this case to underscore the merits of early diagnosis of a rare condition, aggressive antibiotic therapy, and a multidisciplinary approach to achieve a favorable outcome.

Case Presentation

A previously healthy 17-year-old female presented to the emergency department with symptoms of sore throat, left ear pain, and a fever of 3-day duration. She was evaluated at an urgent care walk-in clinic 2 days prior, where she was prescribed azithromycin and acetaminophen. On examination, her weight was 45.4 kg, height 158 cm, blood pressure 118/72 mmHg, heart rate 130 beats/min, respiratory rate 28 breaths/min, temperature 39.1°C, and peripheral oxygen saturation in room air 99%. She was ill appearing, drooling saliva, and spoke with a muffled voice. The palatine tonsils were asymmetrical, erythematous, and swollen with exudate. Uvular deviation was not appreciated. The left ear canal and tympanic membrane were not erythematous and without otorrhea. Left anterior cervical lymph nodes were tender to palpation and soft in consistency. Full range of motion of the neck was observed. Cardiorespiratory examination was normal. There was no skin rash, and she was neurologically intact.

Laboratory test results are shown in Table 1. Plain radiographs of the neck excluded peritonsillar abscess, retropharyngeal abscess, and epiglottitis. Contrast-enhanced CTs of the neck and chest were diagnostic, see Figures 1a, b, and 2. The patient received intravenous ceftriaxone 1 g every 12 h (75 mg/kg/day divided twice a day) and metronidazole 500 mg every 8 h for 2 weeks. An additional two weeks of oral cefdinir 300 mg every 12 h (7.0 mg/kg/dose every 12 h) and metronidazole 500 mg every 8 h (7.5 mg/kg/dose every 8 h) were recommended at hospital discharge.

Table 1.

Laboratory investigations

Test (SI units)	Result	Reference range
Complete blood count
Hemoglobin (g/L)	123.00	120.00–160.00
Hematocrit (%)	37.0	37.0–47.0
Platelets (109/L)	450.00	130.00–400.00
White blood cells (109/L)	14.3	4.8–10.8
Neutrophils (109/L)	11.9	2.1–8.6
Lymphocytes (109/L)	1.1	0.6–4.6
Monocytes (109/L)	1.3	0.1–1.6
Eosinophils (109/L)	0.0	0.0–0.9
C-reactive protein (mg/L)	35.00	7.00–10.00
Erythrocyte sedimentation rate (mm/h)	59	0–20
Microbiology
Blood	No growth	No growth
Throat (group A beta hemolytic streptococcus)	No growth	No growth
Partial thromboplastin time (seconds)	39.10	27.60–37.50
Prothrombin time (seconds)	11.80	10.80–12.90
Respiratory viruses (nasopharyngeal swab) PCR
Influenza A	Negative	Negative
Influenza B	Negative	Negative
Respiratory syncytial virus	Negative	Negative
Severe acute respiratory syndrome coronavirus 2	Negative	Negative
Serology
Cytomegalovirus IgG (U/mL)	0.60	<0.60
Cytomegalovirus IgM (U/mL)	>240.00	<30.00
Epstein-Barr virus
Nuclear antigen antibody IgG (U/mL)	<18.00	<18.00
Viral capsid antigen antibody IgG (U/mL)	21.70	<18.00
Viral capsid antigen antibody IgM (U/mL)	>160.00	<36.00
Mycoplasma pneumoniae IgG (U/mL)	181	<100
Mycoplasma pneumoniae IgM (U/mL)	5,602	<770

IgG: immunoglobulin G, IgM: immunoglobulin M, PCR: polymerase chain reaction

Figure 1.

Contrast-enhanced CT of the neck soft tissue demonstrating a filling defect of the left retro-mandibular and facial veins extending into the internal jugular vein on (a) coronal view and (b) sagittal view (arrows) is consistent with septic thrombophlebitis. Internal jugular vein thrombosis is the gold standard for the diagnosis of Lemierre syndrome (Lavalle et al. 2024)[15]

Figure 2.

Contrast-enhanced CT of the chest detected numerous ground-glass nodules bilaterally, and one such nodule without cavitation is seen on this axial view (arrow). The lung is the most frequently affected site by septic emboli

At 2 weeks, both C-reactive protein (<0.50 mg/L) and erythrocyte sedimentation rate (13 mm/h) normalized, repeat CT of the neck was unchanged, and CT of the chest showed fewer and smaller pulmonary nodules. She underwent tonsillectomy and adenoidectomy 6 months later and remained asymptomatic one year after the procedure.

Discussion

Lemierre syndrome, also known as necrobacillosis and postanginal sepsis, is a rare infectious disease associated with a high mortality rate when left untreated or when treatment is delayed.[4] The clinical triad of the disease includes antecedent protracted pharyngitis, septic thrombophlebitis of the internal jugular vein, and secondary septic embolization to distant sites.[5] Although Fusobacterium necrophorum remains the primary causative pathogen in the majority of cases of Lemierre syndrome, its isolation is not a requirement for the diagnosis.[6] Other bacteria, including streptococci and staphylococci, and viruses have been implicated in recent case reports.[7] The incidence of this infectious disease declined significantly during the antibiotic era due to the regular use of penicillin.[8] In the post-antibiotic era, case reporting proliferated suggesting its re-emergence that may be due to better awareness, antibiotic stewardship, antibiotic-resistant bacteria, improved anaerobic culturing techniques, and restrictive guidelines for tonsillectomy.[9] The initial site of infection may be age dependent; the oropharynx in young adults and other than the head and neck regions in older adults.[10] The lung, joints, and brain are the most common metastatic site of septic emboli.[11] In addition to the classic cases, atypical cases of Lemierre syndrome, including novel antecedent infections, uncommon causative pathogen, unusual affected veins and metastatic sites, are appearing increasingly in the literature.[12]

Contrast-enhanced CT of the neck and chest is the imaging study of choice to confirm the diagnosis.[13] Other modalities such as ultrasound and positron emission tomography scan can be useful.[14] Standardized guidelines on appropriate antibiotics, duration of antimicrobial treatment, and use of anticoagulant therapy have not been established. The administration of a beta-lactam antibiotic combined with metronidazole for three to six weeks is commonly recommended, while the use of an anticoagulant remains controversial.[15]

In our patient, the neutrophilia and elevated acute phase reactants indicate the presence of an infection. The negative cultures were attributed to being partially treated prior to the patient’s presentation to the emergency department. The common causes of asymmetrical palatine tonsils and muffled voice were excluded on plain radiograph. Of the common bacterial and viral causes, our patient tested positive for cytomegalovirus (CMV), Epstein-Barr virus (EBV), and Mycoplasma pneumoniae. Although the possibility of having both EBV and CMV simultaneously or sequentially or even a reactivation of a past infection of either is plausible, it is more likely that the CMV immunoglobulin M is a false positive result due to antigenic cross-reactivity.[16] In a systematic review by Delcò et al.,[17] a quarter of the patients with Lemierre syndrome were serology positive for EBV, suggesting a strong link. Besides direct invasion and hematogenous spread, transient immunosuppression, lymphatic obstruction, and impaired migration of peripheral leukocytes are possible proposed mechanisms involved in the development of Lemierre syndrome after EBV infection.[18] The association of M. pneumoniae and Lemierre syndrome has also been described as a co-infection or as a preceding infection in the literature.[19] There were no culture or serology tests in the recent past or at time of discharge for comparison. Similarly, Frehner et al.[20] observed a high prevalence of negative cultures and a high incidence of atypical causative pathogens in their sample of patients diagnosed with Lemierre syndrome in the early 2000s. We linked EBV and M. pneumoniae as the pathogens damaging the mucosal surface of the pharynx, and septic thrombophlebitis and emboli on CT to the diagnosis of Lemierre syndrome. Our patient was treated with prolonged combined beta-lactam antibiotic and metronidazole, and no anticoagulant therapy.

The limitations of this descriptive study include being a retrospective chart review and having a single case. The strengths of this report include providing knowledge on the diagnosis and treatment when standardized guidelines are not in place, and adding evidence to the changing epidemiology of this syndrome.

In conclusion, we present this case of Lemierre syndrome to familiarize clinicians with this rare condition. In the post-antibiotic era, both bacterial and viral etiologic agents can contribute to this complication of pharyngitis. Contrast-enhanced CT of the neck is essential to confirm the diagnosis of Lemierre syndrome. Clinicians should be aware of the heterogeneous presentations in Lemierre syndrome for early accurate diagnosis and optimal outcomes.

Declaration of patient consent

Written informed consent was obtained from the patient for publication of this case and accompanying images.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.