Lemierre's syndrome: Acute oropharyngeal infection leading to septic thrombophlebitis of the internal jugular vein with pulmonary septic emboli

Interdisciplinary Neurosurgery 19 (2020) 100573

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Case Reports & Case Series

Lemierre's syndrome: Acute oropharyngeal infection leading to septic thrombophlebitis of the internal jugular vein with pulmonary septic emboli

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David R. Hansberry (M.D., Ph.D)a,b, , Michael D'Angelo (B.S.)c, Arpan V. Prabhu (M.D.)d, Michael D. White (B.S.)c, Shiv Tilwa (M.D.)a,b, Zhengteng Li (M.D.)a,b, Mougnyan Cox (M.D.)a,b, Nitin Agarwal (M.D.)c, Vinay Kandula (M.D.)b a

Department of Radiology, Thomas Jefferson University Hospital, Philadelphia, PA, United States of America Department of Radiology, Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, United States of America c Department of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, United States of America d Department of Radiation Oncology, UPMC Hillman Cancer Institute, Pittsburgh, PA, United States of America b

A R T I C LE I N FO

A B S T R A C T

Keywords: Lemierre's syndrome Abscess Venous thrombosis Pulmonary septic emboli

Case presentation: A 12-year-old boy with no significant past medical imaging presented to the emergency department with 1 week of fever, sore throat, and left neck swelling. The patient was febrile with a leukocytosis and subsequently underwent contrast-enhanced computed tomography (CT) for further evaluation. Imaging findings: Contrast-enhanced CT demonstrated a hypodense lesion with peripheral rim enhancement in the left tonsil, consistent with an abscess. There was extensive surrounding inflammation and surrounding edema. Additionally, there were central filling defects in the left internal and external jugular veins consistent with thrombosis. The apex of the lungs found bilateral peripherally based lung nodules that represented septic emboli. This was confirmed with subsequent dedicated CT chest. Discussion: The constellation of peritonsillar abscess with associated thrombophlebitis of the jugular veins and pulmonary septic emboli is Lemierre's Syndrome. This is an uncommon and important diagnosis as it is lifethreatening even with aggressive treatment (8% mortality) and the radiologist can often be the first to suggest the diagnosis. Classically the offending agent is the anaerobic gram-negative rod, Fusobacterium necophorum, although polymicrobial bacteremia is seen in up to a third of the cases. Cultures in the current case grew Streptococcus constellatus, a rare cause of Lemierre's Syndrome. Lemierre's Syndrome was first described in 1936 and is less commonly seen with the advent of antibiotics and thus also referred to as the ‘Forgotten Disease’, although there has been a reemergence more recently likely due to antibiotic resistance. It is most commonly seen in immunocompetent teenagers and young adults, more typically in males. Treatment includes antibiotics plus or minus abscess drainage and/or anticoagulation. Conclusions: Lemierre's Syndrome has the classic imaging triad of ipsilateral pharyngeal fullness and neck vein thrombosis with pulmonary septic emboli. Our patient underwent a prolonged course of intravenous antibiotics with resolution of infection.

1. Introduction Lemierre's syndrome (LS), otherwise known as suppurative thrombophlebitis, is a disease characterized by oropharynx infection that leads to septic thrombophlebitis of the jugular vein with distant metastatic infection. A jugular vein thrombus is likely to embolize to the pulmonary circulation, forming a pulmonary septic embolus, a characteristic finding of LS on chest computed tomography (CT) [10]. The infection generally begins as an oropharyngeal bacterial infection

leading to pharyngitis, which spreads via direct or venolymphatic route to the parapharyngeal and carotid spaces leading to venous thrombosis of the internal jugular vein [7,12,13]. Untreated thrombophlebitis can lead to sepsis, which ultimately results in multisystemic organ damage and death if left untreated [22]. Collectively, pharyngitis, jugular vein thrombosis, and septic pulmonary emboli make the classic triad for the diagnosis of LS [9]. With the advent of antibiotics, Lemierre's syndrome has become an extremely rare disease (0.8 persons per million per year) [29]. LS is

⁎ Corresponding author at: Department of Radiology, Thomas Jefferson University Hospitals, 132 South 10th Street, Philadelphia, PA 19107, United States of America. E-mail address: david.hansberry@jefferson.edu (D.R. Hansberry).

https://doi.org/10.1016/j.inat.2019.100573 Received 9 May 2019; Received in revised form 21 August 2019; Accepted 25 August 2019 2214-7519/ © 2019 Published by Elsevier B.V.

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Fig. 1. Axial computed tomographic image of left tonsillar abscess (yellow arrow) and internal and external jugular vein thrombosis (red arrows). (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 2. Computed tomographic image with coronal view of internal and external jugular vein thrombosis (red arrows). (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

pharyngeal mucosa. The close proximity of the jugular veins to the mucosa explains the thrombophlebitis in the internal jugular vein and less commonly in the external jugular vein [5,10]. Untreated LS results in a 90% mortality rate. Antibiotic resistance, a decrease in tonsillectomies, and the hesitation for many physicians to prescribe antibiotics to younger patients has led to an increasing number of LS cases [5,9,11]. Here, we present a case of LS with a patient who presents to a pediatric emergency department with clinical course and review of LS.

generally found in younger immunocompetent patients between the ages of 16 and 30 years-old who present with a persistent sore throat, neck pain, and fever [13]. LS is rarely seen in patients over 40 years of age. The oropharyngeal infection is most often attributed to the anaerobic, gram-negative bacterium Fusobacterium necrophorum [2,4]. The bacteria spreads locally through direct invasion or venolymphatic route, causing infection of the internal jugular vein, leading to the classical presentation of thrombophlebitis. Although the exact pathogenesis of LS is not fully understood, the bacteria must penetrate the 2

Interdisciplinary Neurosurgery 19 (2020) 100573

D.R. Hansberry, et al.

Fig. 3. Computed tomographic chest image of bilateral septic emboli (red arrows). (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

2. Case report

ampicillin and gentamicin, resulting in resolution of symptoms. Surgical drainage of the abscess was not performed given the small size of the abscess and its location.

A 12-year-old boy with no significant past medical imaging presented to the pediatric emergency department with 1 week of fever, sore throat, and now new left neck swelling that prompted the emergency room visit. The patient was febrile with a leukocytosis and subsequently underwent a contrast-enhanced CT of the soft tissues of the neck for further evaluation. Imaging with contrast-enhanced CT demonstrated a hypodense lesion with peripheral rim enhancement in the left tonsil with extensive surrounding fat infiltration and inflammation, consistent with an abscess (Fig. 1). Additionally, there were central filling defects in the left internal and external jugular veins consistent with thrombosis (Fig. 2). The apex of the lungs revealed bilateral peripherally based lung nodules that represented septic emboli. This was confirmed with subsequent dedicated CT chest for complete evaluation (Fig. 3). Blood cultures grew Streptococcus constellatus, and the patient was admitted and underwent a three-week course of intravenous antibiotics consisting of

3. Discussion Due to the rarity of LS, a diagnosis can be difficult to make and thus, clinicians must maintain a high degree of suspicion. Sore throat with pleuritic chest pain in a febrile patient, symptoms of LS, can help focus a clinical diagnosis towards LS [3]. The differential diagnosis for a patient with LS includes mononucleosis, Group A streptococcal pharyngitis, peritonsillar abscess, jugular vein thrombosis, and pulmonary metastasis [3]. Patients may report recent history of an upper respiratory infection including pharyngitis or otitis media that resolved, but now report neck tenderness/pain and fever, myalgias, dyspnea, and/or sore throat. Patients with LS do not usually have tonsillar exudates, which may help in differentiating it from other diseases presenting with peritonsillar abscesses [3]. Bacteremia with Fusobacterium 3

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Funding statement

necrophorum may aid in confirmation of a physician's clinical suspicion of LS, although other bacteria can be seen [13]. The current case had positive blood cultures growing Streptococcus constellatus, a rare cause of LS. Cases involving S. constellatus are often more severe than those with the classic F. necrophorum, with a tendency to be more invasive and frequently result in abscess formation [23]. Due to the rarity of LS, a standard of care regarding antibiotic therapy has not been established. The most common cases involving fusobacteria infection are often treated with metronidazole as the antibiotic of choice; however, due to the polymicrobial nature of LS, it is generally combined with β-lactam/β-lactamase inhibitor, carbapenem, or moxifloxacin [1]. Clindamycin, tazocilline, and carbapenem have all been prescribed as monotherapies with clinical success due to their effectiveness in treating Fusobacterium necrophorum infections [13,21]. Cases of LS secondary to Streptococcus constellatus infection often require a combination of antibiotic drugs. β-lactam antibiotics are used in combination with aminoglycosides, tetracyclines, or macrolides. In the current case, a three-week course of penicillin and gentamicin resulted in resolution of symptoms. In all cases, antibiotic therapy is recommended for three to six weeks to allow for complete penetration of the fibrin clot and necrotic abscesses [26]. Anticoagulation combined with antimicrobial therapy is the most frequently employed approach to treatment despite the controversy concerning anticoagulation therapy and its impact on thrombosis outcomes [18,19]. In some cases, antibiotics by themselves are sufficient to treat LS and the associated thrombus [8,16,20,28]. More recent evidence states that thrombosis outcomes are independent of the use of anticoagulation therapy [6]. With excessive bleeding being a primary concern regarding anticoagulants, utilization of such treatment must be carefully considered in the management of LS patients. Surgical drainage is also commonly performed if there are accessible abscesses [14]. Within the oropharynx, the palatine tonsils and peritonsillar tissue are the most commonly infected structures [27]. Although Fusobacterium necrophorum is the most frequently reported bacterium (81%), Fusobacterium nucleatum, unspecified fusobacteria, and Streptococcus constellatus are also possible microbiological causes, though more unusual [13,15,24]. Other than pharyngitis, additional causes of LS includes mastoiditis, otitis media, dental infections, and parapharyngeal abscesses [28]. Fever, tachycardia, and leukocytosis are commonly seen in LS following resolution of oropharyngeal infection [25,28]. It is most common for patients to experience fever and chills roughly one week after pharyngitis [28]. Additionally, thrombophlebitis is only seen 1–3 weeks after the initial oropharyngeal infection [25]. Pain and swelling along the sternocleidomastoid muscle are common symptoms of thrombophlebitis, and are only experienced by roughly 50% of LS patients, making this a sometimes difficult diagnosis [25]. For this reason, a correct diagnosis may only be made with a high degree of clinical suspicion. Should LS be suspected, it is important to initiate a proper course of treatment as early as possible to lower morbidity and prevent mortality [11,17].

This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors. Declaration of competing interest The authors have no personal or institutional interest with regards to the authorship and/or publication of this manuscript. References [1] M. Agrafiotis, E. Moulara, D. Chloros, V. Tsara, Lemierre syndrome and the role of modern antibiotics and therapeutic anticoagulation in its treatment, Am. J. Emerg. Med. 33 (2015) 733 e733–734. [2] M. Alfreijat, A case of Lemierre's syndrome with a brief literature review, J. Infect. Public Health 9 (2016) 681–683. [3] J. Asnani, S. Jones, Case review. Lemierre's syndrome, J. Fam. Pract. 63 (2014) 193–196. [4] I. Brook, Fusobacterial infections in children, Curr. Infect. Dis. Rep. 15 (2013) 288–294. [5] J.A. Coultas, N. Bodasing, P. Horrocks, A. Cadwgan, Lemierre's syndrome: recognising a typical presentation of a rare condition, Case Rep. Infect. Dis. 2015 (2015) 797415. [6] M.C. Cupit-Link, A. Nageswara Rao, D.M. Warad, V. Rodriguez, Lemierre syndrome: a retrospective study of the role of anticoagulation and thrombosis outcomes, Acta Haematol. 137 (2016) 59–65. [7] S. Dholakia, Y. Hashimi, Doctor, I have a sore throat, BMJ Case Rep. 2013 (2013). [8] C. Edibam, R. Gharbi, J.W. Weekes, Septic jugular thrombophlebitis and pulmonary embolism: a case report, Crit. Care Resusc. 2 (2000) 38–41. [9] D. Frederick, L. Urwiler, Lemierre's syndrome, J. Neurosci. Nurs. 47 (2015) 55–57. [10] A.V. Hadjinicolaou, Y. Philippou, Lemierre's syndrome: a neglected disease with classical features, Case Rep. Med. 2015 (2015) 846715. [11] D. Hawes, M.J. Linney, R. Wilkinson, S.P. Paul, Lemierre's syndrome: the importance of early detection, Br. J. Nurs. 22 (2013) 1075–1078. [12] K. Johannesen, U. Bodtger, O. Heltberg, Lemierre's syndrome: the forgotten disease, J. Thromb. Thrombolysis 37 (2014) 246–248. [13] K.M. Johannesen, U. Bodtger, Lemierre's syndrome: current perspectives on diagnosis and management, Infect. Drug Resist. 9 (2016) 221–227. [14] P.D. Karkos, C.D. Karkos, S.C. Leong, N. Sivaji, D. Papadopoulos, A.D. Assimakopoulos, Lemierre syndrome: no delays in management, Am. J. Emerg. Med. 28 (2010) 844 e841–842. [15] M. Kumar, R. Singh, K.K. Sawlani, S. Kumar, Atypical presentation of Lemierre syndrome: role of imaging, BMJ Case Rep. 2013 (2013). [16] M.D. Lu, Z. Vasavada, C. Tanner, Lemierre syndrome following oropharyngeal infection: a case series, J. Am. Board Fam. Med. 22 (2009) 79–83. [17] V. Marulasiddappa, C.A. Tejesh, Lemierre's syndrome presenting with septic shock, Indian J. Crit. Care Med. 17 (2013) 382–384. [18] D. McGouran, A. Keene, R. Walklin, J. Carter, A complex case of bilateral Lemierre syndrome with suggestions on anticoagulation management, Intern. Med. J. 43 (2013) 728–730. [19] C.K. Phua, V.M. Chadachan, R. Acharya, Lemierre syndrome-should we anticoagulate? A case report and review of the literature, Int. J. Angiol. 22 (2013) 137–142. [20] J.M. Ridgway, D.A. Parikh, R. Wright, P. Holden, W. Armstrong, F. Camilon, et al., Lemierre syndrome: a pediatric case series and review of literature, Am. J. Otolaryngol. 31 (2010) 38–45. [21] C.A. Righini, A. Karkas, R. Tourniaire, J.M. N'Gouan, S. Schmerber, E. Reyt, et al., Lemierre syndrome: study of 11 cases and literature review, Head Neck 36 (2014) 1044–1051. [22] T. Riordan, Human infection with fusobacterium necrophorum (Necrobacillosis), with a focus on Lemierre's syndrome, Clin. Microbiol. Rev. 20 (2007) 622–659. [23] M. Shimada, Y. Morinaga, T. Kitazaki, M. Fukuda, K. Hashiguchi, K. Yanagihara, et al., A severe case of Lemierre syndrome with streptococcus constellatus infection, Jpn. J. Infect. Dis. 67 (2014) 488–489. [24] C.P. Sinave, G.J. Hardy, P.W. Fardy, The Lemierre syndrome: suppurative thrombophlebitis of the internal jugular vein secondary to oropharyngeal infection, Medicine (Baltimore) 68 (1989) 85–94. [25] N. Srivali, P. Ungprasert, W. Kittanamongkolchai, N. Ammannagari, Lemierre's syndrome: an often missed life-threatening infection, Indian J. Crit. Care Med. 18 (2014) 170–172. [26] C. Tromop-van Dalen, A.M. Mekhail, Lemierre syndrome: early recognition and management, CMAJ 187 (2015) 1229–1231. [27] S. Turedi, S. Turkmen, M. Yadigaroglu, An unusual cause of sore throat and neck swelling, Emerg. Med. J. 625 (32) (2015) 646. [28] S. Udassi, S.Y. Tuli, B.P. Giordano, J. Udassi, Adolescent with fever, hypotension, and respiratory distress, J. Pediatr. Health Care 29 (2015) 289–293. [29] P. Wani, N. Antony, M. Wardi, C.E. Rodriguez-Castro, M. Teleb, The forgotten one: Lemierre's syndrome due to Gram-Negative rods prevotella bacteremia, Am. J. Case Rep. 17 (2016) 18–22.

4. Conclusion Lemierre's syndrome is characterized by an oropharyngeal infection frequently attributed to Fusobacterium necrophorum, although it can also be secondary to Streptococcus constellatus resulting in a more invasive and severe disease course. Penetration of the pharyngeal mucosa leads to thrombophlebitis of the internal jugular vein and less commonly the external jugular vein. One of the major concerns of LS is the formation of septic pulmonary embolisms, which can progress to sepsis if left untreated. Given the almost certain mortality without appropriate treatment and not insignificant mortality with treatment, it is important for the clinician to have a high degree of suspicion when evaluating the patient and equally important for the radiologist to be aware of the constellation of findings. 4