INTERNATIONAL JOURNAL OF CLINICAL AND MEDICAL CASES (ISSN:2517-7346)

Lemierre’s syndrome (LS) is a rare, potentially fatal syndrome characterized by sore throat complicated with septic thrombosis of the internal jugular vein and distal organ septic emboli Fusobacterium Necrophorum is the most common causative bacterium Previous viral infection is a possible predisposing factor

Case presentation
A healthy 27-year-old male, five weeks after recovering from a mild COVID-19 infection, presented with a 5-day fever (40 °C) with rigors, vomiting and sore throat Physical and laboratory examinations have shown acute renal failure and signs of sepsis Blood cultures isolated Fusobacterium Necrophorum and a computer tomography scan showed thrombophlebitis of the right internal jugular vein, parapharyngeal abscess, pulmonary emboli and pleural effusion The patient was empirically treated with broad spectrum antibiotics; the abscess and pleural infusion were drained The patient was treated with broad spectrum antibiotics and anticoagulant therapy for 6 weeks At follow-up at 6 weeks the patient was asymptomatic

Conclusion
We present a case of LS after a COVID-19 infection in a healthy young male, where high clinical suspicion and multidisciplinary collaboration led to a timely diagnosis and treatment Clinical awareness of the disease should be encouraged as COVID-19 pandemic could lead to increased incidence of LS

 Lemierre´s syndrome; Fusobacterium; Septic thrombophlebitis; COVID-19 infection

Lemierre’s syndrome (LS) was reported for the first time by Courmont and Cade in 1900, but the syndrome was clearly described by Lemierre in 1936 after reviewing 20 cases [1, 2] It is a severe illness, which could be fatal with mortality rate ranging from 5%to 25% [3, 4] and is characterized by tonsillopharyngitis followed by the septic thrombophlebitis of the tonsillar vein and internal jugular vein It could be complicated by septic emboli to the lung, liver, spleen, joints, and bones It is commonly caused by the anaerobic gram negative bacterium, Fusobacterium Necrophorum, and it typically occurs in healthy teenagers and young adults [3] 

A healthy 27-year-old male patient, active smoker, five weeks after recovering from a mild COVID-19 infection, was admitted to a tertiary hospital due to a 5-day fever (40 °C), rigors, vomiting and sore throat Upon admission to our clinic, the patient was oriented, hemodynamically stable with blood pressure 118/86mmHg, tachycardia (heart rate 130bpm), and febrile (38 7 °C) The physical examination was unremarkable except for right tonsillar white exudate and tenderness of the anterior and posterior right cervical chain lymph nodes

Laboratory examination showed normal white blood cell count and high C-reactive protein [40mg/dL, laboratory normal limit <0 5mg/dL] and high procalcitonin [36 29ng/mL (upper laboratory limit <0 09ng/mL)], normal erythrocyte sedimentation rate (24mm/ hr), acute renal failure (Urea 84mg/dL, Creatinine 2 9mg/dL), high conjugated hyperbilirubinemia (total bilirubin 3 18mg/dL), thrombocytopenia (platelet count 57, 900/μL), slightly increased international normalized ratio(1 4), high levels of D-dimers (5, 045ng/ mL) A PCR RNA test forSARS-COV2 was negative

No pulmonary infiltrations were found on lung x-ray Contrastenhanced computer tomography showed thrombophlebitis of the right jugular vein (Figure 1), a parapharyngeal abscess on the right, at the same height as the thrombosis, infiltrations in the lower lobes bilaterally and in the posterior upper right lobe Lemierre´s syndrome was diagnosed

Esophageal echocardiogram excluded the diagnosis of endocarditis but small pericardial collection was observed and a pleural effusion of the left lung Diagnostic drainage of the pleural effusion showed empyema

Upon admission, empirical antibiotic therapy was administered with broad-spectrum antibiotics intravenously (piperacillin/ tazobactam) and metronidazole was added based to the positive blood culture for Fusobacterium Necrophorum Therapeutic dose of low-molecular weight heparin (tinzaparin) was added due to the jugular thrombophlebitis Drainage of the parapharyngeal abscess was performed, however the culture of the aspirated material was negative On day 15, antibiotic treatment was modified to clindamycin, ampicillin/sulbactam plus metronidazole due to the septic emboli of the lungs found on the follow-up chest CT scan

On ultrasound and radiographic re-examination of the lungs, the pleural effusion had completely receded on day 18 The patient was discharged after 3 weeks of hospitalization and was prescribed amoxicillin/clavulanate, clindamycin per os and therapeutic dose of tinzaparin for 3 additional weeks At the 6-week follow-up, the patient was asymptomatic and has resumed normal activities 

We present a case of LS in a healthy young adult male following a mild COVID-19 respiratory infection, showcasing that early detection and therapy can lead to favourable outcomes The key finding leading to prompt diagnosis was the positive blood culture for Fusobacterium Necrophorum, showing the importance of the laboratory contribution and the high clinical suspicion

Lemierre’s syndrome typically occurs in teenagers and young adults [3] just as in the present case The patient was young and healthy Several predisposing factors have been described, such as smoking Smoking has been associated with aggressive oropharyngeal infection by anaerobes [5]

Another possible predisposing factor for the development of LS could be a recent viral infection which could impair the immune system In the present case the patient had a recent COVID-19 respiratory infection a few weeks prior to the presentation As the virus of SARS-CoV2 has been associated with long-lasting postCOVID health effects, the existence of a causative relationship could not be excluded Many cases have previously been published showing that several viral infections such as influenza A and Epstein-Barr virus (EBV) infection preceded LS [3, 6, 7] To our knowledge, this is the first case of LS following a COVID-19 infection

The incidence of Lemierre’s syndrome has declined since the introduction of antibiotics [3, 8, 9] However, a resurgence has been documented in recent years [3] and could be attributed to antibioticprescribing restrictions in some countries, a fall in the rate of tonsillectomy and the widespread use of macrolides for sore throat, which has weak activity against Fusobacterium [6] Some studies have linked the use of non-steroidal anti-inflammatory drugs (NSAIDs) and steroids, both commonly prescribed to treat pharyngitis, with the enhanced bacterial virulence and spread observed in LS [10, 11] The recent pandemic of COVID-19 and the subsequent increased use of steroids and antibiotics (macrolides) could lead to increased incidence of LS It should raise clinical awareness of the syndrome especially in all involved medical specialties

The clinicians should be trained to search for clinical signs of septicemia In the present case, the signs of septicemia triggered the immediate collection of blood culture and empirical treatment with broad spectrum antibiotics [12]

Many cases of LS present with severe thrombocytopenia (<50 000/ μL) [13-15] Possible causes include the Fusobacterium Necrophorum haemagglutinin activity which can trigger platelet activation and aggregation [6, 8], use of NSAIDs, sepsis, disseminated intravascular coagulation andsecondary immune thrombocytopenic purpura [13] In the present case, the patient had used NSAIDs and suffered from sepsis

Cervical lymphadenopathy, either unilateral or bilateral, may be present often in the anterior triangle Lymphadenopathy should not be confused with the tender, unilateral swelling at the angle of the jaw or anterior to, and parallel with, the sternomastoid muscle, due to the internal jugular venous thrombophlebitis [3, 4, 6, 7, 11, 14, 16] In accordance, the presented patient exhibited the tender swelling of the neck which prompted the contrast-enhanced CT scan examination

Contrast-enhanced CT scan of the neck is the appropriate method to diagnose vascular thrombosis of the internal jugular vein [11] Furthermore, it can easily diagnose parapharyngeal and paratracheal abscesses which are often present [17]

Common complication of LSare the metastatic septic emboli of various organs The lungs are commonly affected in up to 85% of cases Lung lesions usuallyappear as necrotic cavitary lesions but can also present as infiltrates, pleural effusions, empyema, lung abscesses, and necrotizing mediastinitis Patients with pulmonary involvement might present with pneumonia or empyema and can develop acute respiratory distress syndrome which has increased mortality risk [16-18] Less common presentations of metastatic septic emboli include soft tissue abscesses, pyomyositis, splenic and liver abscesses, osteomyelitis, endocarditis, pericarditis, renal abscess, and brain abscess [4, 15]

The management of LS warrants an integrated approach from different specialties [15] Quite often pharyngitis besides otolaryngologists [Ear, Nose, throat and Neck (ENT)], who have high clinical suspicion for LS, is treated by internists and family doctors who are not familiar with this syndrome Furthermore, radiologists and microbiologists play a significant role in reaching the correct diagnosis Therapy is also delivered by many specialties such as ENT physicians who would perform the surgical incision of a neck abscess, pulmonologists for treating lung diseases and even intensive care unit physicians in case of mechanical ventilation Indeed, in our case several specialties were involved in the management of the patient

Fusobacterium Necrophorum is intrinsically resistant to macrolides, fluoroquinolones, tetracyclines, and aminoglycosides [9, 19] Treatment of LSshould include a prolonged course of intravenous beta-lactam antibiotic plus metronidazole [9, 20] Furthermore, a β-lactamase inhibitor should also be included, because β-lactamase-producing strains of F Necrophorum have been reported Furthermore, co-infecting pathogens might also produce β-lactamases In accordance, metronidazole is the most commonly prescribed antibiotic [5, 16] Six weeks of antibiotic treatment should be completed in most patients in order to achieve an appropriate penetration into fibrin clots [6]

There are no randomized clinical trials concerning the need for anticoagulation and the optimal anticoagulant therapy for patients with LS Anticoagulation should be considered in some cases [9] An association between the use of anticoagulants and faster dissolution of thrombus and shortened course of LS has been reported [14] On the other hand, a meta-analysis of the effect of anticoagulation on vessel recanalization and mortality failed to show a significant benefit for either outcome [21] In the present case, anticoagulation therapy was added for 6 weeks without any adverse effect

We present a case of LS after a COVID-19 infection in a healthy young male, where high clinical suspicion and the use of appropriate examinations such as blood culture and contrast-enhanced CT scan led to a timely diagnosis of the LS Multidisciplinary collaboration led to prompt treatment of the disease and its complications Clinical awareness of the disease should be encouraged as COVID-19 pandemic could lead to increased incidence of LS 

No acknowledgments need to be included

Ethical Approval
Ethics approval was not required for this study

Consent to participate
Written informed consent to participate was obtained from the patient 

The patient has consented to the submission of the case report to the journal

No potential conflict of interest was reported by the authors

Kyriazidou Anastasia and Sarigianni Maria wrote the main manuscript text and prepared figures All authors reviewed the manuscript

No funding received

The data that support the findings of this study are available from the corresponding author upon reasonable request All the material is owned by the authors and no permissions are required

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