The Changing Face of an Old Disease: Case Report of Nonclassical Lemierre's Syndrome Caused by a Panton-Valentine Leucocidin-Positive Methicillin-Susceptible Staphylococcus aureus Isolate

LETTER

Chanin et al. published a review of methicillin-resistant Staphylococcus aureus (MRSA) causing Lemierre's syndrome (4). We present another case of Lemierre's syndrome caused by Panton-Valentine leucocidin (PVL)-positive methicillin-susceptible Staphylococcus aureus (MSSA) in a healthy 18-year-old Indian student. He had been a resident in the United Kingdom for a year. He presented with 3 days of right-sided facial swelling and fevers and a history of a sore throat in the 2 weeks prior to admission. Examination revealed a temperature of 38.9°C, a pulse of 135 beats per minute, blood pressure of 113/66 mmHg, and marked right facial and neck swelling with tenderness and induration of the right external jugular vein and pustules on his right cheek and lip. Examination of the oropharynx was unremarkable.

Investigations revealed negative HIV serology, a C-reactive protein level of 226 mg/liter (normal value, <5 mg/liter), and a white cell count of 17.1 × 10⁹/liter (normal value, 4 × 10⁹ to 11 × 10⁹/liter), and a chest X ray showed airspace infiltrates and a cavitating lesion. Blood cultures taken on admission grew MSSA. Computerized tomography (CT) of the head and neck showed gross tissue edema in the face and neck and suggested a clot in the right jugular venous system. A Doppler ultrasound of his neck showed a free-floating nonocclusive thrombus extending from the right external jugular vein into the common jugular vein. A transthoracic echocardiogram revealed no cardiac vegetations.

A diagnosis of Lemierre's syndrome caused by MSSA was made, and he was treated with 2 g of intravenous (IV) floxacillin four times a day (QD) for 14 days, followed by oral floxacillin for a further 2 weeks and warfarin therapy for 6 months. Toxin gene profiling of the initial blood culture isolate of MSSA by the reference laboratory confirmed that it was PVL positive.

The patient had a good response to treatment and made a full recovery.

As in most cases presented by Chanin et al., our case consisted of unilateral jugular vein thrombosis with metastases to the lungs and was caused by community-acquired S. aureus in an immunocompetent host.

We would like to reiterate the importance of early recognition of Lemierre's disease, as emphasized by Chanin et al., to achieve earlier diagnosis and prevent complications. Despite the decline in cases of Lemierre's syndrome in the later half of the 20th century (12), increasing prevalence of antibiotic-resistant pathogens, increasing virulence of organisms, and perhaps judicious use of antibiotics to curb the development of resistance mean that Lemierre's syndrome is reported more frequently and less typically (2, 3, 7, 8). Lemierre's syndrome is often described as a condition of the preantibiotic era; we suggest that Lemierre's syndrome now belongs to the modern era of increasingly virulent and antibiotic-resistant organisms.

As noted by Chanin et al., S. aureus has been reported as a notable cause of Lemierre's syndrome since 2002. Most isolates in the review were either PVL producers or MRSA, well recognized as significant pathogens. MSSA is emerging as a cause of Lemierre's syndrome (Table 1), and pathogenic strains of MSSA are increasingly PVL producers (9, 14). PVL appears to have pathogenic synergism with alpha-hemolysin, which is almost ubiquitously expressed by staphylococci (5). The ability to lyse leukocytes and erythrocytes to assist immune evasion and bacterial replication seems to be a shared feature of PVL-producing S. aureus and Fusobacterium necrophorum, the pathogen classically associated with Lemierre's syndrome (11), and may explain why both organisms appear to be capable of causing the constellation of clinical features described by Lemierre.

Table 1.

Yr	Case (reference)	Patient age (yr)	Bacterium	PVL	Internal jugular vein affected	Complications	Interventions other than antibioticsa	Outcome
2008	Puymirat et al. (10)	22	MSSA	Not reported	Right	Multiple pulmonary nodules; cavitation; cavernous sinus thrombosis	SC heparin, excision of internal and external jugular	Recovered
2008	Shivashankar et al. (13)	32	MSSA	+	Left	Bilateral pulmonary nodules; pulmonary abscesses; cavernous sinus thrombosis; bilateral cerebellar, left frontal, and brain stem infarcts	IV heparin, activated protein C, warfarin	Recovered
2009	Gokce Ceylan et al. (6)	80	MSSA	Not reported	Right	Bilateral pulmonary nodular infiltrates; bibasal pleural effusions	None	Died
2010	Aouad, Melkane, and Rassi (1)	4	MSSA	Not reported	Right	Extension of thrombophlebitis to cavernous sinus; multivisceral emboli to the brain, orbits, lungs, and heart valves	Anticoagulation therapy, abscess drainage	Died
2012	Our case	18	MSSA	+	Right	Pulmonary infiltrates; cavitation	SC heparin, warfarin	Recovered

^aSC, subcutaneous.

Our case reemphasizes the emergence of nonclassical Lemierre's syndrome and raises awareness of S. aureus as a significant cause. We also postulate that alpha-hemolysin plays a role in the pathogenesis of this aggressive condition.