Atypical presentation of Lemierre syndrome: role of imaging

Abstract

A 51-year-old male patient presented with breathlessness for 10 days. Chest radiograph revealed bilateral moderate pleural effusion. Ultrasound-guided diagnostic pleural aspirate revealed sterile transudative fluid. CT thorax revealed bilateral moderate pleural effusion with partial collapse of both lower lobes and thrombus in right brachiocephalic vein. Two-dimensional-echo revealed circumferential pericardial effusion with mild pericardial thickening and moderate tricuspid regurgitation. Cardiolipin antibodies were within normal limits. d-Dimer assay and C reactive protein were markedly raised. During the period of investigations, the patient had developed mild swelling and pain in right upper limb for which colour Doppler ultrasonography of his right upper limb and neck regions were done. Thrombi in right internal jugular, subclavian and brachiocephalic veins were noted. CT angiography, CT abdomen and chest confirmed the above findings. However, extent of the thrombus and lung lesions was better delineated by CT angiography. We have highlighted the pathognomonic imaging findings of Lemierre syndrome.

Background

Lemierre syndrome is a rare clinical entity, less than 160 cases are reported till date. After extensive search and review of literatures, we have concluded that unusual clinical presentation and asymptomatic ipsilateral maxillary sinusitis with contiguous thrombi in ipsilateral jugular vein, subclavian vein and brachiocephalic veins without septic embolic abscesses/nodule in both lungs and throat infection made this case as a first case, reported till date to the best of our knowledge.

Case presentation

A 51-year-old male patient presented in OPD of Pulmonary Medicine for breathlessness for 10 days. General physical examination revealed opaque right cornea with underlying cataract since childhood. Stony dullness on percussion and absence of breath sound in both lower lung fields was observed. Shifting dullness was present on abdominal percussion. Rest of the general physical examination was unremarkable including ear, nose and throat and the central nervous system.

Investigations

Laboratory tests of the patient including complete blood analysis, blood sugar, renal function test, liver function test, rheumatoid factor, uric acid, antiphospholipid antibody, plasma fibrinogen, antinuclear antibody/factor levels were within normal limits. HIV and HBsAG were non-reactive. Mantoux skin test was reported 4 mm after 48 h. Ultrasound-guided diagnostic pleural aspirate revealed sterile transudative fluid. Value of ADA in pleural fluid was 20 U/l. PCR from pleural fluid was negative for Mycobacterium tuberculosis and fluid was also negative for malignant cells. d-Dimer Assay and C reactive protein levels were markedly raised 7125 ng/ml (normal: 57–495.5 ng/ml) and 82.3 mg/ml (normal: <5 mg/l), respectively. ECG findings were within normal limit. Posteroanterior view of chest radiograph of patient revealed bilateral moderate pleural effusion without obvious lung parenchymal abnormality. Ultrasonography of abdomen and chest revealed mild ascitis and bilateral pleural effusion with partial collapse of both lower lobes. Two-dimensional echocardiography of heart revealed circumferential moderate pericardial effusion with mild pericardial thickening and moderate tricuspid regurgitation. CT of thorax revealed pericardial effusion, bilateral moderate pleural effusion with collapsed right lower lobe and subsegmental atelectasis of the left lower lobe (figure 1A). Concentric thrombus was seen in brachiocephalic vein (figure 1B). Diagnosis could not be made at this point of time, despite of all above positive findings. The patient was complaining of pain and swelling in the right upper limb during the period of investigations for which colour Doppler ultrasonography of his right upper limb and neck was performed which revealed thrombi in right internal jugular, subclavian and brachiocephalic veins (figures 2A and 3A). Right-sided cervical lymphadenopathy was seen adjacent to thrombosed internal jugular vein. Left jugular vein was over-distended (figure 3B). Thrombus was noted in right subclavian vein; however, left subclavian vein was normal in course and calibre (figure 4B). Multidetector CT angiography of right upper limb and neck regions was done on the same day which revealed contiguous thrombi in right internal jugular, subclavian and brachiocephalic veins (figure 2A). No septic pulmonary embolic nodule/abscess could be seen. His left jugular vein was over-distended (figure 6A,B). Incidentally, collection was noticed in right maxillary antrum suggesting maxillary sinusitis on axial CT scan (figure 5). No arterial abnormality was detected. Anteroposterior and oblique views of volume rendered topographic images revealed non-visualised right jugular, subclavian and brachiocephalic veins suggestive of thrombosis (figures 6A,B). All the above characteristic imaging findings were consistent with Lemierre syndrome.

Figure 1.

A 51-year-old male patient with Lemierre syndrome. Contrast-enhanced axial CT (Philips MDCT Brilliance 64;120 kv, 300 ma, 3 mm thickness, 0.663 pitch, 100 ml non-ionic iodinated contrast media, arterial phase) panels (A and B) of chest revealed pericardial effusion, bilateral moderate pleural effusion (star) with collapsed right lower lobe (straight arrow) and subsegmental atelectasis of left lower lobe (curved arrow). Thrombus in brachiocephalic vein (labelled).

Figure 2.

A 51-year-old male patient with Lemierre syndrome. Contrast-enhanced reformatted coronal CT (Philips MDCT Brilliance 64;120 kv, 300 ma, 3 mm thickness, 0.663 pitch, 100 ml non-ionic iodinated contrast media, arterial phase) panels (A and B) of chest revealed thrombus in right jugular, subclavian and brachiocephalic veins (labelled). Pericardial effusion, bilateral moderate pleural effusion with collapsed right lower lobe, subsegmental atelectasis of left lower lobe and well-aerated bilateral upper lobes (star).

Figure 3.

A 51-year-old male patient with Lemierre syndrome. Colour Doppler ultrasonographic (GE Logiq P5) panels (A and B) of neck revealed thrombosis of right internal jugular vein and adjacent cervical lymphadenopathy (labelled as LN). Over distended left jugular vein (labelled as dilated JV).

Figure 4.

A 51-year-old male patient with Lemierre syndrome. Colour Doppler ultrasonographic (GE Logiq P5) panels (A and B) of both upper limbs revealed thrombosis of right subclavian vein (perpendicular arrows) and normal left subclavian vein (curved arrow).

Figure 6.

A 51-year-old male patient with Lemierre syndrome. Volume rendered multidetector CT (MDCT) angiographic (Philips MDCT Brilliance 64;120 kv, 300 ma, 3 mm thickness, 0.663 pitch, 100 ml non-ionic iodinated contrast media, arterial phase) panels (A and B) revealed non-visualised right jugular, subclavian and brachiocephalic veins with over distended left jugular vein (labelled).

Figure 5.

A 51-year-old male patient with Lemierre syndrome. Non-contrast axial CT (GE CT/e; 120 kv, 100 ma, 3 mm thickness) revealed collection in right maxillary antrum (arrow).

Differential diagnosis

• Pneumonia

• Disseminated Intravascular Coagulation

Treatment

Patient was put on Intravenous Piperacillin-Tazobactum and Metronidazole for 10 days. Subcutaneous Low-molecular-weight heparin (enoxaparin) was also given.

Outcome and follow-up

Bilateral pleural effusion, ascitis, dyspnoea and right upper limb pain were disappeared.

Discussion

Schotmuller in 1918 first described the sepsis following throat infection. In preantibiotic era it was Andre Lemierre, in 1936 who published a series of 20 cases of anaerobic throat infections causing septicaemia, of which 18 patients died. Lemierre syndrome is also known as ‘Post anginal sepsis’, ‘Forgotten disease’ or ‘Human necrobacillosis’. It is an uncommon but potentially life-threatening complication of sino-oro-nasopharyngeal anaerobic infection.^{1 2} It can also be initiated by an otitis, mastoiditis, sinusitis or parotiditis. Sinave and colleagues recently reviewed that Fusobacterim necrophorum accounts for 81% of cases, 11% by other Fusobacterium species, which include Fusobacterium nucleatum, Fusobacterium mortiferum and Fusobacterium varium, etc and 8% by other gram negative bacteria, which include Bacteroides fragilis, Bacteroides melaninogenicus, Peptostreptococcus spp, Streptococcus microaerophile, Staphylococcus aureus and Eikenella corrodens.³ However, it is commonly caused by virulent anaerobic bacteria, mainly F necrophorum which is a part of the normal oro-pharyngeal flora and it has the unique ability to invade as primary pathogen without underlying disease which may result in subsequent septicaemia and septic embolisation resulting in metastatic abscesses.¹ Production of bacterial toxins such as lipopolysaccharide causes secretion of cytokines by white blood cells, both of which lead to symptoms of sepsis producing haemagglutinin which causes platelet aggregation that leads to diffuse intravascular coagulation and thrombocytopenia.⁴ In a recent literature review, 97% of 38 patients had pleuro-pulmonary septic emboli, 15% had septic arthritis, hepatic abscesses, splenic abscesses, osteomyelitis, meningitis and intracranial abscesses.^{5 6} Lower cranial nerve involvement and diffuse encephalopathy are also described in association with Lemierre syndrome. Patients with Lemierre syndrome typically present with pharyngitis, malaise, cervical lymphadenopathy, swollen or painful tender neck before onset of septicaemia. Abdominal pain, diarrhoea, nausea and vomiting commonly occur during early phase. Breathlessness, cough and pleuritic chest pain occur in pulmonary involvement. Hypotension, tachycardia, oliguria and tachypnoea occur in situation of septic shock. Nuchal rigidity, headache and photophobia occur if there is meningitis. Other signs and symptoms that may occur are muscle pain, trismus, pericardial friction rub, jaundice, cranial nerve palsy and Horner's syndrome. However, many patients may present with non-specific signs and symptoms, like in this case. Hall et al⁷ has emphasised that “Be not deceived by a comparatively innocent appearing pharynx, as the veins of the pharynx may be carrying the death sentence for your patient.”. F necrophorum is susceptible to β-lactam antibiotics, metronidazole, clindamycin and third generation cephalosporins while the other Fusobacteria have varying degrees of resistance to β-lactams and clindamycin.⁶ Coinfection may exist by another bacterium. For these reasons monotherapy is not advisable in treating Lemierre syndrome. If antibiotic therapy does not cause improvement, drainage of abscesses or ligation of the internal jugular vein is necessary.⁷ Low incidence of Lemierre syndrome has not made it possible to set up clinical trials of anticoagulant therapy to opt or refute its use. The disease can often be untreatable and fatal if multiorgan involvement occurs. Mortality of Lemierre syndrome is 4.6%.⁸ Role of imaging is the most important aspect of Lemierre syndrome because imaging findings usually precede clinical symptoms and blood culture results. Chest radiograph may show pleural effusion, pulmonary nodules and infiltrates. Colour Doppler ultrasonography is also very helpful and is a crucial imaging tool due to its easy availability, non-ionising property and cost effectiveness in imaging and follow-up of Lemierre syndrome. It depicts the thrombus in internal jugular vein, pleural effusion, underlying collapsed lung, ascitis and hepato-splenomegaly. Contrast-enhanced CT (CECT) is the modality of choice in a suspected case of Lemierre syndrome which objectively demonstrates internal jugular venous distension, thrombus, its extent, thickened, enhancing venous wall and surrounding soft tissue oedema. CECT is 67% sensitive in detection of pulmonary embolism and septic nodule by better depiction of feeding vessel sign and central cavitating nodules. MRI has a limited role because of its cost and availability.⁹ We would like to concise the Lemierre syndrome by making a triad of anaerobic bacterial infection of sino-oro-nasopharyngeal regions, thrombus in internal jugular vein and metastatic thrombi/abscesses.

Learning points.

• Lemierre syndrome is a triad of sino-oro-nasopharyngeal infection, thrombus in internal jugular vein and metatstatic thrombi/abscesses.

• Contrast-enhanced CT and colour Doppler imaging are modalities of choice in diagnosis and follow-up of Lemierre syndrome.

• β-Lactam antibiotics, Metronidazole, Clindamycin and third generation Cephalosporins are main drugs for treatment of Lemierre syndrome.