Article, Infectious Diseases

Lemierre syndrome associated with group A streptococcal infection

Case Report

Lemierre syndrome associated with group A streptococcal infection


Lemierre syndrome is a Rare condition, characterized by an acute oropharyngeal infection with secondary internal jugular vein thrombosis, and subsequent metastatic infec- tion. Lemierre syndrome is usually caused by Fusobacte- rium necrophorum. We report a case of Lemierre syndrome caused by group A Streptococcus (GAS) in a 4-year-old girl. She was initially diagnosed with GAS pharyngitis but failed treatment with azithromycin and subsequently deve- loped right-sided neck swelling concerning for a deep neck abscess. A neck computed tomography scan revealed Right internal jugular vein thrombosis but no abscess. Blood culture grew GAS, sensitive to penicillin and ceftriaxone but resistant to clindamycin and azithromycin. The patient was treated with ceftriaxone and anticoagulation resulting in Complete recovery. Although very unusual, physicians must be aware that GAS can cause Lemierre syndrome. Penicillin should remain the drug of choice for GAS pharyngitis. early diagnosis and treatment of Lemierre syndrome is crucial to decrease morbidity and mortality.

A 4-year-old previously healthy white female patient presented to our emergency department with a 5-day history of fever. The patient had been in good health until

5 days earlier, when she began to have sore throat and fever. She was diagnosed with group A Streptococcus (GAS) pharyngitis by her pediatrician based on a positive rapid GAS antigen assay and prescribed a 5-day course of azithromycin. There was no clinical improvement, and over the following 4 days, the patient continued to have high spiking fevers up to 105?F, neck pain, vomiting, and decreased urine output. She denied any sick contacts, exposure to ticks, or recent travel.

On physical examination, the patient appeared ill with a temperature of 40.6?C (105.1?F) rectally, heart rate of 170 beats per minute, respiratory rate of 32 breaths per minute, and an oxygen saturation of 98% on room air. Both tympanic membranes were erythematous and her mucous membranes were dry. Her oropharynx was erythematous but no exudates

were noted. Her neck was supple but tender to palpation. The rest of her physical examination was within normal limits.

Laboratory studies showed a white cell count of 17.6 x 103/uL with 73% segmented neutrophils, 18% bands, and 8% lymphocytes; hemoglobin was 11.3g/dL and platelets were 389 x 103/uL. erythrocyte sedimentation rate was 70 mm/h. A comprehensive metabolic panel and urinalysis were normal. Cerebrospinal fluid analysis was normal and no organisms were seen on Gram stain. A chest radiograph was normal. A blood culture on admission was positive for GAS. Cerebrospinal fluid and urine cultures were sterile.

The patient was admitted and treated initially with intravenous ampicillin. The following morning, she also developed right neck swelling that was not erythematous but tender to palpation. At this point, a deep neck abscess was suspected and antibacterials were changed to vancomycin and clindamycin. A computed tomography (CT) scan of the neck with contrast showed a right internal jugular vein thrombosis extending from the right sigmoid sinus to the Hyoid bone with reactive lymphadenopathy (Fig. 1). A magnetic resonance Imaging study of the neck also showed the right internal jugular vein thrombosis (Fig. 2). The diagnosis of Lemierre syndrome (LS) was made. A CT scan of the chest, abdomen, and pelvis was normal. Thrombo- philia workup including antiphospholipid antibodies, factor

V Leiden, and prothrombin G20210A mutation were negative.

The GAS isolate from our patient was sensitive to penicillin, cefotaxime, and ceftriaxone but resistant to erythromycin, clindamycin, and azithromycin and her antibiotic regimen was changed to intravenous ceftriaxone. She was also started on anticoagulation therapy. Subsequent blood cultures remained negative and the patient clinically improved with resolution of fever and Neck tenderness and swelling. Also, her thrombophilia workup was negative. She was discharged home on the 10th day of hospitalization to complete a total of 3-week course of intravenous ceftriaxone followed by a 1-week course of oral amoxicillin. Antic- oagulation therapy was discontinued after 2 months when complete resolution of the thrombus was noted on ultrasound. The patient remained well on follow-up visits.

Although LS is often referred to as the “forgotten disease” due to its rarity [1-3], recent reports have suggested that its

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incidence is increasing over the past 10 years, especially in the pediatric population [4,5]. This increase in the incidence of LS has been attributed to the increasingly judicious use of antibiotics for pharyngitis in recent years [5]. Regardless of the reason for the rise in the incidence of LS, it is important for physicians to be aware of the disease and its clinical picture so that early intervention may be started to decrease fatal outcomes.

Most cases of LS occur in adolescents and young adults after primary infection in the oropharynx, although other sites have been reported including Otitis media, mastoiditis, and sinusitis [2,6,11]. The most common mechanism in the pathogenesis of LS include primary infection in the peritonsillar tissue followed by lateral pharyngeal space tissue invasion, resulting in internal jugular vein thrombo- phlebitis and severe sepsis with metastatic spread of bacteria/ septic emboli [2].

Although, LS has classically been associated with Fuso- bacterium necrophorum (82%), Polymicrobial infection can occur (10%); other organisms such as Fusobacterium nucleatum, Bacteroides spp, Peptostreptococcus spp, Staphylococcus aureus including community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA), viridans Streptococci spp, Eikenella corrodens, and Entero- coccus spp are relatively less common [2,6,7].

Lemierre syndrome caused by GAS as a sole pathogen is very rare. Table 1 shows the clinical details of 4 previously

Fig. 2 Post-gadolinium contrast gradient magnetic resonance image demonstrates right Internal jugular vein thrombosis. Note contrast within normal internal Carotid arteries (ICA) and left internal jugular (IJ) vein.

Fig. 1 Computed tomography scan of the neck with contrast demonstrating an occluded right internal jugular (IJ) vein (note absence of contrast within the vessel compared with normal left IJ vein). Note contrast within normal internal carotid arteries (ICA) and left IJ vein.

reported cases of LS (including present report) caused solely by GAS. Two cases occurred in adults and one was reported in a 13-year-old boy [8-10]. All patients presented initially with pharyngitis and subsequently developed sepsis. GAS was isolated from blood culture in all cases. In all cases, evidence of internal jugular vein thrombosis was found by ultrasound or CT scan of the neck. All cases were treated with prolonged Intravenous antibiotics and 3 also received anticoagulation therapy. One adult patient had a fatal outcome, whereas the other case developed metastatic infection but survived with residual proximal weakness. Both Pediatric cases (including our case) survived.

Our patient presented had 2 of the 3 criteria used to diagnose LS including internal jugular vein thrombosis secondary to an oropharyngeal infection and bacteremia due to GAS but did not develop cavitating pneumonia or any other metastatic foci of infection. This may be explained by the initiation of antibiotics early in the course of the illness. Recent reports indicate that metastatic infections such as cavitating pneumonia and Septic arthritis are less common in LS due to early antibiotic therapy for pharyngitis [2,12].

Our report illustrate that the differential diagnosis of any ill-appearing patient with a clinical picture of sepsis and deep neck infection should include LS. However, other causes of internal jugular vein thrombosis such as having a central venous catheter, history of intravenous drug use, and thrombophilia must be excluded. Our patient did not have

No./author Age/ Year Presentation Complications Blood Imaging study Management Outcome sex culture showing IJV


1/Wilson [9] 50/F 1995 Pharyngitis, Acute renal GAS Neck CT, Antibiotics alone Alive odynophagia, sepsis failure pneumonia, Doppler U/S

pleural effusion

2/ Anton [10] 80/M 2007 Pharyngitis, Shock GAS Neck CT Antibiotics and Died odynophagia, sepsis anticoagulation

3/ Blumberg [11] 13/M 2007 Pharyngitis, sepsis Thrombocytopenia GAS Doppler U/S Antibiotics and Alive

Acute renal failure anticoagulation

4/Present report 4/F 2009 Pharyngitis, sepsis None GAS Neck CT Antibiotics and Alive


IJV indicates internal jugular vein thrombosis; U/S, ultrasound.

any evidence of thrombophilia and did not have an indwelling central venous catheter in the neck.

Table 1 Reported cases of Lemierre syndrome caused by group A Streptococcus

Optimal treatment of LS includes high-dose intravenous antibiotics directed at the most common pathogens (especially anaerobes such as Fusobacterium necrophorum and Gram-positive and Gram-negative aerobes) associated with this disease [2,4]. Antibiotic choices must include anti- anaerobic agents such as clindamycin, penicillin plus ?-lactamase inhibitor (eg, piperacillin-tazobactam, ticarcil- lin-clavulanate), or meropenem [2,4]. It is important to note that Fusobacterium spp can be resistant to penicillin, primarily through production of ?-lactamase and some strains may be resistant to clindamycin [13]. Given the recent increase in the incidence of invasive infection associated with community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) including a recent report implicating CA-MRSA in LS [7], it is prudent to use vancomycin in combination with anti-anaerobic agents in suspected cases of LS.

In addition to appropriate antibiotic therapy, prompt drainage of the primary sites of infection (eg, neck abscess, mastoiditis, dental abscess, septic arthritis, empyema) is recommended in most circumstances [2]. During therapy, close observation for signs of continued sepsis, extension of septic thrombus, or metastatic infection is warranted. Treatment with prolonged courses (typically 4-6 weeks) of Intravenous antibiotic therapy is recommended [2,4].

In the present case, our patient initially received azithromycin for GAS pharyngitis. The GAS isolate was resistant to azithromycin resulting in treatment failure and development of LS. In the past decade, there have been reports of increased resistance of GAS to macrolide antibiotics globally resulting in treatment failures [14]. In most areas of the United States, approximately 5% to 8% of GAS strains are resistant to macrolides [15]. Because of the documented resistance of GAS to macrolides, penicillin should continue to be used as a first-line agent for GAS pharyngitis [15]. Not only does this case demonstrate the benefits of starting antibiotics early, it also illustrates the

importance of not prescribing macrolides as first-line therapy for GAS pharyngitis.

The role of anticoagulation therapy in the management of LS is controversial [2]. Some experts consider anticoagula- tion for cases of retrograde propagation of thrombosis (eg, cavernous sinus thrombosis) [6,7]. Surgical ligation or excision of the internal jugular vein may be indicated in severe sepsis and ongoing evidence of septic emboli [2].

Physicians must also be aware that LS can occur as a complication of GAS pharyngitis. Early recognition and appropriate antibiotic treatment are critical to reduce morbidity and mortality associated with this life-threaten- ing infection.

Rina K. Shah MD Marcia M. Wofford MD Department of Pediatrics

Wake Forest University Health Sciences and

Brenner Children’s Hospital

Winston Salem NC 27157, USA

Thomas G. West MD

Department of Neuroradiology Wake Forest University Health Sciences and

Brenner Children’s Hospital

Winston Salem NC 27157, USA

Avinash K. Shetty MD

Department of Pediatrics Wake Forest University Health Sciences and

Brenner Children’s Hospital

Winston Salem NC 27157, USA

E-mail address: [email protected] doi:10.1016/j.ajem.2009.09.011


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