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Lemierre syndrome: a complication of acute pharyngitis
International Journal of Pediatric Otorhinolaryngology 45 (1998) 51 – 57
Lemierre syndrome: a complication of acute pharyngitis Andrea Williams a, Mark Nagy a,b,*, Jennifer Wingate a, Luna Bailey c, Mark Wax a,d a
Department of Otolaryngology at the State Uni6ersity of New York, Buffalo, NY, USA b Childrens Hospital of Buffalo, Buffalo, NY, USA c School of Medicine and Biomedical Sciences, the Children’s Hospital of Buffalo, Buffalo, NY, USA d Buffalo General Hospital, Buffalo, NY, USA Received 18 April 1998; received in revised form 16 June 1998; accepted 20 June 1998
Abstract Lemierre syndrome, otherwise known as postanginal sepsis or necrobacillosis, is an illness that originates as an acute pharyngitis or tonsillitis which progresses to sepsis, usually fusobacterial, due to suppurative thrombophlebitis of the internal jugular vein. Septic thromboemboli then seed various organs, resulting in multiple organ system pathology, most commonly affecting pulmonary and hepatic systems and joints. Although rare in the age of antibiotics, this disease typically affects previously healthy adolescents with varied clinical manifestations depending upon organ system involvement (A. Lemierre, Lancet March (1936) 701 – 703; J. Barker, H.T. Winer-Muram, S. Grey, Southern Med. J. 89 (1996) 1021–1023). Prompt diagnosis based on clinical presentation, radiologic findings, particularly CT scanning with contrast and a high index of suspicion, is necessary in order to institute often life saving therapy (J. Barker, H.T. Winer-Muram, S. Grey, Southern Med. J. 89 (1996) 1021 – 1023). We will present two cases of Lemierre syndrome, review it’s clinical presentation, anatomic considerations, particularly it’s relationship to the parapharyngeal space, radiographic findings, potential life threatening complications and finally, a unique approach to therapy. © 1998 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Lemierre syndrome; Acute pharyngitis; Multiple organ system pathology
1. Introduction
* Corresponding author: Present address: Department of Pediatric Otolaryngology, Children’s Hospital of Buffalo, 219 Bryant Street, Buffalo, NY 14222 200; USA. Tel.: + 1 716 8787852; fax: + 1 716 8787585.
Lemierre syndrome, previously known as ‘postanginal septicemia’, was first described in 1936 [1]. Classically it consists of thrombophlebitis of the internal jugular vein following an episode of acute pharyngitis or tonsillitis [3]. Patients present with persistent pyrexia, rigor, lateral neck pain and
0165-5876/98/$ - see front matter © 1998 Elsevier Science Ireland Ltd. All rights reserved. PII S0165-5876(98)00092-5
52
A. Williams et al. / Int. J. Pediatr. Otorhinolaryngol. 45 (1998) 51–57
swelling. If untreated, it progressed by way of septic thromboemboli to pulmonary complications, renal impairment, hepatitis, suppurative peritonitis and joint involvement. Thyroiditis and mastoiditis have also been reported [3,4]. Lemierre syndrome is caused by Fusobacterium necrophorum, an anaerobic bacteria that can be isolated on blood culture. Other anaerobes that have been less commonly isolated include, Fusobacterium nucleatum, Fusobacterium gonidiaformans and anaerobic streptococci. The incidence of Lemierre syndrome has significantly decreased and outcomes improved with the wide spread use of antibiotics [5]. In Lemierre’s original study [1], 18 of 20 patients died from complications of their illness. In the Sinave et al., study, from 1974 to 1989, only two of 23 patients died [4]. Today this disease occurs sporadically. It is important, however, to maintain a high index of suspicion since otolaryngologists are usually involved in the management of the patient with Lemierre syndrome. From an anatomical point of view, the pathogenesis of Lemierre syndrome can be explained by the intimate association of the internal jugular vein to the parapharyngeal space. The internal jugular vein and surrounding carotid sheath are a part of the post-styloid compartment of the parapharyngeal space [4]. Although all three layers of the deep fascia make up the carotid sheath, pharyngeal infections such as tonsillitis or peritonsillar abscesses can transgress these fascial planes and subsequently infect the wall of the internal jugular vein, leading to partial or complete thrombosis. By definition then, Lemierre syndrome is actually an infection that has progressed from it’s pharyngeal origins to involve the parapharyngeal space.
2. Case presentations
2.1. Case no. 1 A 15-year-old male presented to the emergency room 1 week prior to admission with a history of sore throat and fever. He left prior to being
assessed. During the next week, the patient was started on penicillin by his mother, but as his condition deteriorated, he returned to the emergency room. There he complained of right upper quadrant pain, shaking chills, nausea, diarrhea, vomiting and malaise. On review of systems he reported tea colored urine and severe neck pain. On examination, he appeared very ill. His temperature was 39.9°C with a blood pressure of 78/44 mmHg and a pulse rate of 130 beats per min. He was not in respiratory distress. Head and neck exam revealed trismus, a bulging erythematous soft palate with fluctuance and tonsils that were mildly hypertrophied. These findings were consistent with a peritonsillar abscess so 2 ml of pus was aspirated with a large bore needle. There was full range of cervical motion, however, the right side of the neck was exquisitely tender with lymphadenopathy present. The chest was clear to auscultation, abdominal examination revealed tenderness and guarding in the right upper quadrant with hepatosplenomegaly. The rest of the physical exam was unremarkable. Laboratory work up included: white blood count 8.7× 10/I (89% neutrophils, 0% bands, 10% lymphocytes and 1% monocyte); hemoglobin 15.7 g/dl; platelet count 56 × 10/I. Liver function tests: alanine transaminase 2355 i.u./I; aspartate transaminase 242 i.u./I; alkaline phosphotase 143 i.u./I; lactate dehydrogenase 12900 i.u./I which were all elevated. Electrolytes were within normal limits except for slightly elevated glucose levels. Urine was amber with 2 + protein, large amounts of blood, moderate red blood cells, small amounts of urobilogen and bacteria and 0–2 white blood cells. A chest X-ray revealed patchy areas of opacification in the right upper lung field and bilateral lower lung fields. Hepatomegaly was confirmed on abdominal ultrasound, but the rest of the abdomen was within normal limits. The patient was fluid resuscitated with 2.5 l of dextrose with lactated ringers and started on emperic antibiotic therapy (cefotaxime, vancomycin, clindamycin and diflucan). Shortly after admission to the floor, the patient became hypotensive and desaturated, requiring transfer to the intensive care unit. The next day, he remained febrile
A. Williams et al. / Int. J. Pediatr. Otorhinolaryngol. 45 (1998) 51–57
53
with exquisite neck tenderness and dysphagia so a CT scan of the neck was obtained. The CT scan revealed an area of decreased attenuation and ring enhancing in the right peritonsillar and parapharyngeal spaces (Fig. 1), as well as thrombosis of the right internal jugular vein (Fig. 2). As a result of the above findings, a Quincy tonsillectomy and intraoral drainage of the parapharyngeal space abscess was performed. Streptococcus 6iridians was isolated from intra-operative cultures. Over the next week, the patient became hematologically stable and vasopressors were weaned. Despite resolution of pharyngeal symptoms, he remained febrile and complained of pleuritic chest pain and intermittent extremity weakness. A CT scan of the chest revealed multiple cavitary lesions and bronchiectasis in bilateral lung fields (Fig. 3).
Fig. 2. Contrast enhanced CT of the neck at the level of hyoid demonstrating right internal jugular vein thrombosis.
Fig. 1. Case no. 1: Contrast enhanced CT scan of the neck demonstrating decreased attenuation and ring enhancement in the right peritonsillar and parapharyngeal spaces.
There was no definite pleural effusion. An echocardiogram was obtained and there was no evidence of endocarditis. Muscle biopsy was unremarkable. On the eighth day of hospitalization, antibiotics were discontinued except for clindamycin when blood cultures identified F. necrophorum as the pathogen. Antibiotic therapy was recommended for 3 weeks. No anticoagulation was administered for the internal jugular thrombosis during hospitalization. The patient’s condition improved slowly and he was discharged home after 19 days of hospitalization. On follow up visit, the patient was slowly returning to baseline. He continued to take intravenous clindamycin via long term intravenous catheter. Liver function tests and a complete blood count revealed total resolution of liver im-
54
A. Williams et al. / Int. J. Pediatr. Otorhinolaryngol. 45 (1998) 51–57
Fig. 3. Case no. 1: Contrast enhanced CT scan of the thorax showing multiple cavitary lesions and bronchiectasis in bilateral lung fields.
pairment and thrombocytopenia. Repeat CT scan demonstrated near total resolution of previous bronchiectasis and cavitary lesions of the lung. There continued to be scattered areas of opacification and some scarring.
2.2. Case no. 2 A previously health 23-year-old male presented to the emergency room with a 5 day history of sore throat and low grade fever. Three days prior to admission he was seen as an out-patient and thought to have a viral infection. At that time he was hydrated and discharged home. He subsequently developed high fevers to 40.5°C accompanied by chills, cough, neck pain, myalgias and nausea and vomiting. On follow-up visit, the patients symptoms and pharyngitis had improved but he continued to have pyrexia and neck pain with new complaints of dysuria and pleuritic chest pain with a productive cough. Physical exam revealed scleral icterus and the patient was referred directly to the emergency room. On admission, the patient appeared toxic with a temperature of 39.7°C, a pulse rate of 138 beats
per min and a blood pressure of 108/54 mmHg. There was no evidence of respiratory distress. Head and neck exam was remarkable for icteric sclerae and injected conjunctiva. The patient had trismus with enlarged exudative tonsils. There was no uvula deviation. There was left cervical lymphadenopathy with decreased range of cervical motion secondary to pain. Hepatomegaly and abdominal tenderness were present. The rest of the physical exam was normal. Laboratory work-up included: white blood count 10.2× 10/I (53% neutrophils, 34% bands, 9% monocytes and 4% lymphocytes); platelet count 85 × 10/I. Liver function tests: alanine transaminase 45 i.u./I; aspartate transaminase 36 i.u./I; alkaline phosphatase 371 i.u./I. Electrolytes were within normal limits, except for a decreased potassium level. Serum titers were negative for Q fever, toxoplasmosis, CMV and Legionella. Hepatitis profile was normal. Blood cultures were negative, however, anaerobic cultures were not obtained. A chest X-ray revealed a right lower lobe infiltrate with right upper lobe nodular densities. CT scan of the neck showed left internal jugular
A. Williams et al. / Int. J. Pediatr. Otorhinolaryngol. 45 (1998) 51–57
Fig. 4. Case no. 2: Contrast enhanced CT scan of the neck demonstrating thrombosis of the left internal jugular vein.
vein thrombosis from the level of the innominate vein to the skull base along with thrombosis of the palatine and lingual veins (Fig. 4). There were inflammatory changes within the carotid space
55
that resulted in anteromedial displacement of the parapharyngeal space. There was no evidence of an abscess. CT scan of the chest revealed bilateral septic emboli and pleural effusions (Fig. 5). Abdominal ultrasound confirmed hepatosplenomegaly. The patient was admitted and started on intravenous antibiotics (ampicillin–sulbactam, doxycycline) and heparin. On the fifth hospital day, the left peritonsillar space was aspirated because the patient continued to have trismus and palatal swelling. There was no pus on aspiration. Over the next few days, oropharyngeal swelling gradually decreased and cervical motion slowly improved. With continued conservative management, the patient defervesed and was discharged home on hospital day seven with oral antibiotics (amoxicillin–clavulanate) and coumadin. Prior to discharge, a repeat CT scan of the neck was obtained and showed a decrease in parapharyngeal edema and inflammation with no abscess present. On follow-up visit 1 week later, the patient had markedly improved except for moderate persistence of the left-sided oropharyngeal edema.
Fig. 5. Case no. 2: Contrast enhanced CT scan of the thorax showing bilateral septic emboli.
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A. Williams et al. / Int. J. Pediatr. Otorhinolaryngol. 45 (1998) 51–57
3. Discussion Prior to the advent of antibiotics, Lemierre syndrome was commonly seen in Europe and the US. Today, it only occurs sporadically, usually in previously healthy young adults and adolescents with a recent history of oropharyngitis or tonsillitis that was partially treated with antibiotics [2,3]. The pathogenesis of Lemierre syndrome is progressive dissemination of septic emboli from the tonsillar and peritonsillar veins to the internal jugular vein, resulting in bacteremia [3]. The particular organism primarily responsible for Lemierre syndrome is the gram-negative obligate anaerobe, F. Necrophorum. Other names for this organism include; Bacillus funduloformis, Bacillus necrophorus and Bacteroides funduliformis [2,5]. As the pharyngitis symptoms subside, patients with Lemierre syndrome develop localized swelling and tenderness of the neck. Depending on the degree of inflammation there may be a marked decrease in range of motion of the neck, because of the infectious involvement of the parapharyngeal space. These individuals will present with a septic picture including pyrexia, tachycardia and hypotension. By history, there will be an antecedent interval of dysphagia or odynophagia which has worsened, often despite medical therapy. Pulmonary septic emboli manifested as pleuritic chest pain, dyspnea or respiratory distress are seen in 95% of cases reported [2 – 5]. Other pulmonary sequelae such as hemoptysis, pleural effusion and empyema also frequently occur. Respiratory distress from the multiple pulmonary septic emboli can be severe enough to necessitate intensive care observation and ventilatory support. Another frequent complication of Lemierre syndrome is metastatic septic joint effusion and arthralgia, as seen in our patients. This infective arthritis can be easily confused with polymyositis or other neuromuscular diseases resulting in an unnecessary extensive work-up. In one of our cases, a muscle biopsy was recommended by Rheumatology and the administration of high dose steroids was entertained which could have worsened the clinical course. Renal involvement is not uncommon and this clinical entity must be
differentiated from possible post-streptococcal glomerulonephritis which may have similar findings on urinalysis. Varying degrees of liver involvement may also be seen with symptoms ranging from mild hepatomegaly and tenderness over the liver, to frank jaundice and liver abscesses. Elevated liver enzymes commonly occur and these findings must be distinguished from that of infectious mononucleosis. Other abdominal complications such as purulent peritonitis have been reported. Less frequent complications of Lemierre syndrome include, meningitis and a few reports of mastoiditis, thyroiditis and endocarditis [3]. The diagnosis of Lemierre syndrome is based on clinical presentation, supported by bacteriological and radiological findings [3]. Blood cultures should confirm an anaerobic septicemia caused by Fusobacterium, but may be negative because of the use of antibiotics prior to hospitalization. Ultrasonography or contrast-enhanced CT of the neck will reveal thrombosis of the internal jugular vein and may or may not show a peritonsillar or parapharyngeal space abscess. A CT scan is usually more beneficial in the presence of an abscess, because the extent of the abscess is better delineated, the location of the great vessels identified and internal jugular vein involvement revealed. This will prove to be very helpful if surgical drainage is necessary. Chest X-ray or CT scan of the chest, frequently demonstrates multiple cavitary lesions, nodular shadowing and pleural effusion. One may also see several areas of bronchiectasis in the lungs. A CT scan of the abdomen may show hepatomegaly, hepatic microabscesses or splenomegaly. Abnormal laboratory findings such as an elevated white count, elevated liver enzymes, proteinuria and hematuria are not specific but support a diagnosis of Lemierre syndrome and can be used to follow it’s course. F. necrophorum is a common saprophyte of the oral cavity but when it results in septicemia, a fulminant infection occurs, necessitating early and prolonged intravenous antibiotic therapy. It is usually sensitive to benzylpenicillin, clindamycin, metronidazole, or chloramphenicol. Some cases report a better response with metronidazole be-
A. Williams et al. / Int. J. Pediatr. Otorhinolaryngol. 45 (1998) 51–57
cause of good tissue penetration [2]. Others support the use of clindamycin because of the rising rate of resistance of Fusobacterium to penicillin. Once a culture sensitive antibiotic is chosen for treatment, several weeks of antibiotics are required to completely eradicate the multiple organ system thromboemboli [2 – 4]. If a parapharyngeal or peritonsillar abscess is present, surgical drainage is necessary. Until recently, the only recommended surgical management of deep neck infections consisted of an external approach to the parapharyngeal space. In Case 1, the peritonsillar and parapharyngeal space abscesses were drained by a Quincy tonsillectomy and subsequent transoral drainage of the parapharyngeal space. CT scanning with contrast can clearly outline the limits of an abscess, which consists of a homogenous hypodense area with surrounding ring enhancement, the location of the great vessels and the presence of internal jugular vein thrombosis. At present, ligation and resection of the internal jugular vein are no longer advocated and anticoagulation therapy is controversial [2]. Because of the severity of this illness, supportive care in the intensive care unit may be necessary. Even with the appropriate management of this disease, it is not uncommon for the patient to have prolonged elevation of temperature and a slow recovery.
.
57
4. Conclusion Lemierre syndrome is a rare sporadic illness characterized by Fusobacterial septicemia and thrombosis of the internal jugular vein. It is a disease that requires a high index of suspicion for diagnosis. Prompt intervention with intravenous antibiotic therapy and drainage of a deep neck abscess, if present on CT scanning with contrast, is essential to prevent the metastatic dissemination of septic emboli and to decrease the morbidity and mortality of this disease. Though rare, Lemierre syndrome still exists and remains potentially life threatening.
References [1] A. Lemierre, On certain septicaemias due to anaerobic organisms, Lancet 1936 March: 701 – 703. [2] J. Barker, H.T. Winer-Muram, S. Grey, Lemierre syndrome, Southern Med. J. 89 (1996) 1021 – 1023. [3] C.B. Koay, T. Heyworth, P. Burden, Lemierre syndrome — a forgotten complication of acute tonsillitis, J. Laryngol. Otol. 109 (1995) 657 – 661. [4] C.P. Sinave, G.J. Hardy, P.W. Fardy, The lemierre syndrome: supportive thrombophlebitisof the internal jugular vein secondary to oropharyngeal infection, Medicine 68 (1989) 85 – 94. [5] S. DeSena, D.L. Rosenfeld, S. Santos, I. Keller, Jugular thrombophlebitis complicating bacterial pharyngitis (Lemierre’s syndrome), Pediatr. Radiol. 26 (1996) 141 – 144.
Lemierre syndrome: a complication of acute pharyngitis Andrea Williams a, Mark Nagy a,b,*, Jennifer Wingate a, Luna Bailey c, Mark Wax a,d a
Department of Otolaryngology at the State Uni6ersity of New York, Buffalo, NY, USA b Childrens Hospital of Buffalo, Buffalo, NY, USA c School of Medicine and Biomedical Sciences, the Children’s Hospital of Buffalo, Buffalo, NY, USA d Buffalo General Hospital, Buffalo, NY, USA Received 18 April 1998; received in revised form 16 June 1998; accepted 20 June 1998
Abstract Lemierre syndrome, otherwise known as postanginal sepsis or necrobacillosis, is an illness that originates as an acute pharyngitis or tonsillitis which progresses to sepsis, usually fusobacterial, due to suppurative thrombophlebitis of the internal jugular vein. Septic thromboemboli then seed various organs, resulting in multiple organ system pathology, most commonly affecting pulmonary and hepatic systems and joints. Although rare in the age of antibiotics, this disease typically affects previously healthy adolescents with varied clinical manifestations depending upon organ system involvement (A. Lemierre, Lancet March (1936) 701 – 703; J. Barker, H.T. Winer-Muram, S. Grey, Southern Med. J. 89 (1996) 1021–1023). Prompt diagnosis based on clinical presentation, radiologic findings, particularly CT scanning with contrast and a high index of suspicion, is necessary in order to institute often life saving therapy (J. Barker, H.T. Winer-Muram, S. Grey, Southern Med. J. 89 (1996) 1021 – 1023). We will present two cases of Lemierre syndrome, review it’s clinical presentation, anatomic considerations, particularly it’s relationship to the parapharyngeal space, radiographic findings, potential life threatening complications and finally, a unique approach to therapy. © 1998 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Lemierre syndrome; Acute pharyngitis; Multiple organ system pathology
1. Introduction
* Corresponding author: Present address: Department of Pediatric Otolaryngology, Children’s Hospital of Buffalo, 219 Bryant Street, Buffalo, NY 14222 200; USA. Tel.: + 1 716 8787852; fax: + 1 716 8787585.
Lemierre syndrome, previously known as ‘postanginal septicemia’, was first described in 1936 [1]. Classically it consists of thrombophlebitis of the internal jugular vein following an episode of acute pharyngitis or tonsillitis [3]. Patients present with persistent pyrexia, rigor, lateral neck pain and
0165-5876/98/$ - see front matter © 1998 Elsevier Science Ireland Ltd. All rights reserved. PII S0165-5876(98)00092-5
52
A. Williams et al. / Int. J. Pediatr. Otorhinolaryngol. 45 (1998) 51–57
swelling. If untreated, it progressed by way of septic thromboemboli to pulmonary complications, renal impairment, hepatitis, suppurative peritonitis and joint involvement. Thyroiditis and mastoiditis have also been reported [3,4]. Lemierre syndrome is caused by Fusobacterium necrophorum, an anaerobic bacteria that can be isolated on blood culture. Other anaerobes that have been less commonly isolated include, Fusobacterium nucleatum, Fusobacterium gonidiaformans and anaerobic streptococci. The incidence of Lemierre syndrome has significantly decreased and outcomes improved with the wide spread use of antibiotics [5]. In Lemierre’s original study [1], 18 of 20 patients died from complications of their illness. In the Sinave et al., study, from 1974 to 1989, only two of 23 patients died [4]. Today this disease occurs sporadically. It is important, however, to maintain a high index of suspicion since otolaryngologists are usually involved in the management of the patient with Lemierre syndrome. From an anatomical point of view, the pathogenesis of Lemierre syndrome can be explained by the intimate association of the internal jugular vein to the parapharyngeal space. The internal jugular vein and surrounding carotid sheath are a part of the post-styloid compartment of the parapharyngeal space [4]. Although all three layers of the deep fascia make up the carotid sheath, pharyngeal infections such as tonsillitis or peritonsillar abscesses can transgress these fascial planes and subsequently infect the wall of the internal jugular vein, leading to partial or complete thrombosis. By definition then, Lemierre syndrome is actually an infection that has progressed from it’s pharyngeal origins to involve the parapharyngeal space.
2. Case presentations
2.1. Case no. 1 A 15-year-old male presented to the emergency room 1 week prior to admission with a history of sore throat and fever. He left prior to being
assessed. During the next week, the patient was started on penicillin by his mother, but as his condition deteriorated, he returned to the emergency room. There he complained of right upper quadrant pain, shaking chills, nausea, diarrhea, vomiting and malaise. On review of systems he reported tea colored urine and severe neck pain. On examination, he appeared very ill. His temperature was 39.9°C with a blood pressure of 78/44 mmHg and a pulse rate of 130 beats per min. He was not in respiratory distress. Head and neck exam revealed trismus, a bulging erythematous soft palate with fluctuance and tonsils that were mildly hypertrophied. These findings were consistent with a peritonsillar abscess so 2 ml of pus was aspirated with a large bore needle. There was full range of cervical motion, however, the right side of the neck was exquisitely tender with lymphadenopathy present. The chest was clear to auscultation, abdominal examination revealed tenderness and guarding in the right upper quadrant with hepatosplenomegaly. The rest of the physical exam was unremarkable. Laboratory work up included: white blood count 8.7× 10/I (89% neutrophils, 0% bands, 10% lymphocytes and 1% monocyte); hemoglobin 15.7 g/dl; platelet count 56 × 10/I. Liver function tests: alanine transaminase 2355 i.u./I; aspartate transaminase 242 i.u./I; alkaline phosphotase 143 i.u./I; lactate dehydrogenase 12900 i.u./I which were all elevated. Electrolytes were within normal limits except for slightly elevated glucose levels. Urine was amber with 2 + protein, large amounts of blood, moderate red blood cells, small amounts of urobilogen and bacteria and 0–2 white blood cells. A chest X-ray revealed patchy areas of opacification in the right upper lung field and bilateral lower lung fields. Hepatomegaly was confirmed on abdominal ultrasound, but the rest of the abdomen was within normal limits. The patient was fluid resuscitated with 2.5 l of dextrose with lactated ringers and started on emperic antibiotic therapy (cefotaxime, vancomycin, clindamycin and diflucan). Shortly after admission to the floor, the patient became hypotensive and desaturated, requiring transfer to the intensive care unit. The next day, he remained febrile
A. Williams et al. / Int. J. Pediatr. Otorhinolaryngol. 45 (1998) 51–57
53
with exquisite neck tenderness and dysphagia so a CT scan of the neck was obtained. The CT scan revealed an area of decreased attenuation and ring enhancing in the right peritonsillar and parapharyngeal spaces (Fig. 1), as well as thrombosis of the right internal jugular vein (Fig. 2). As a result of the above findings, a Quincy tonsillectomy and intraoral drainage of the parapharyngeal space abscess was performed. Streptococcus 6iridians was isolated from intra-operative cultures. Over the next week, the patient became hematologically stable and vasopressors were weaned. Despite resolution of pharyngeal symptoms, he remained febrile and complained of pleuritic chest pain and intermittent extremity weakness. A CT scan of the chest revealed multiple cavitary lesions and bronchiectasis in bilateral lung fields (Fig. 3).
Fig. 2. Contrast enhanced CT of the neck at the level of hyoid demonstrating right internal jugular vein thrombosis.
Fig. 1. Case no. 1: Contrast enhanced CT scan of the neck demonstrating decreased attenuation and ring enhancement in the right peritonsillar and parapharyngeal spaces.
There was no definite pleural effusion. An echocardiogram was obtained and there was no evidence of endocarditis. Muscle biopsy was unremarkable. On the eighth day of hospitalization, antibiotics were discontinued except for clindamycin when blood cultures identified F. necrophorum as the pathogen. Antibiotic therapy was recommended for 3 weeks. No anticoagulation was administered for the internal jugular thrombosis during hospitalization. The patient’s condition improved slowly and he was discharged home after 19 days of hospitalization. On follow up visit, the patient was slowly returning to baseline. He continued to take intravenous clindamycin via long term intravenous catheter. Liver function tests and a complete blood count revealed total resolution of liver im-
54
A. Williams et al. / Int. J. Pediatr. Otorhinolaryngol. 45 (1998) 51–57
Fig. 3. Case no. 1: Contrast enhanced CT scan of the thorax showing multiple cavitary lesions and bronchiectasis in bilateral lung fields.
pairment and thrombocytopenia. Repeat CT scan demonstrated near total resolution of previous bronchiectasis and cavitary lesions of the lung. There continued to be scattered areas of opacification and some scarring.
2.2. Case no. 2 A previously health 23-year-old male presented to the emergency room with a 5 day history of sore throat and low grade fever. Three days prior to admission he was seen as an out-patient and thought to have a viral infection. At that time he was hydrated and discharged home. He subsequently developed high fevers to 40.5°C accompanied by chills, cough, neck pain, myalgias and nausea and vomiting. On follow-up visit, the patients symptoms and pharyngitis had improved but he continued to have pyrexia and neck pain with new complaints of dysuria and pleuritic chest pain with a productive cough. Physical exam revealed scleral icterus and the patient was referred directly to the emergency room. On admission, the patient appeared toxic with a temperature of 39.7°C, a pulse rate of 138 beats
per min and a blood pressure of 108/54 mmHg. There was no evidence of respiratory distress. Head and neck exam was remarkable for icteric sclerae and injected conjunctiva. The patient had trismus with enlarged exudative tonsils. There was no uvula deviation. There was left cervical lymphadenopathy with decreased range of cervical motion secondary to pain. Hepatomegaly and abdominal tenderness were present. The rest of the physical exam was normal. Laboratory work-up included: white blood count 10.2× 10/I (53% neutrophils, 34% bands, 9% monocytes and 4% lymphocytes); platelet count 85 × 10/I. Liver function tests: alanine transaminase 45 i.u./I; aspartate transaminase 36 i.u./I; alkaline phosphatase 371 i.u./I. Electrolytes were within normal limits, except for a decreased potassium level. Serum titers were negative for Q fever, toxoplasmosis, CMV and Legionella. Hepatitis profile was normal. Blood cultures were negative, however, anaerobic cultures were not obtained. A chest X-ray revealed a right lower lobe infiltrate with right upper lobe nodular densities. CT scan of the neck showed left internal jugular
A. Williams et al. / Int. J. Pediatr. Otorhinolaryngol. 45 (1998) 51–57
Fig. 4. Case no. 2: Contrast enhanced CT scan of the neck demonstrating thrombosis of the left internal jugular vein.
vein thrombosis from the level of the innominate vein to the skull base along with thrombosis of the palatine and lingual veins (Fig. 4). There were inflammatory changes within the carotid space
55
that resulted in anteromedial displacement of the parapharyngeal space. There was no evidence of an abscess. CT scan of the chest revealed bilateral septic emboli and pleural effusions (Fig. 5). Abdominal ultrasound confirmed hepatosplenomegaly. The patient was admitted and started on intravenous antibiotics (ampicillin–sulbactam, doxycycline) and heparin. On the fifth hospital day, the left peritonsillar space was aspirated because the patient continued to have trismus and palatal swelling. There was no pus on aspiration. Over the next few days, oropharyngeal swelling gradually decreased and cervical motion slowly improved. With continued conservative management, the patient defervesed and was discharged home on hospital day seven with oral antibiotics (amoxicillin–clavulanate) and coumadin. Prior to discharge, a repeat CT scan of the neck was obtained and showed a decrease in parapharyngeal edema and inflammation with no abscess present. On follow-up visit 1 week later, the patient had markedly improved except for moderate persistence of the left-sided oropharyngeal edema.
Fig. 5. Case no. 2: Contrast enhanced CT scan of the thorax showing bilateral septic emboli.
56
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3. Discussion Prior to the advent of antibiotics, Lemierre syndrome was commonly seen in Europe and the US. Today, it only occurs sporadically, usually in previously healthy young adults and adolescents with a recent history of oropharyngitis or tonsillitis that was partially treated with antibiotics [2,3]. The pathogenesis of Lemierre syndrome is progressive dissemination of septic emboli from the tonsillar and peritonsillar veins to the internal jugular vein, resulting in bacteremia [3]. The particular organism primarily responsible for Lemierre syndrome is the gram-negative obligate anaerobe, F. Necrophorum. Other names for this organism include; Bacillus funduloformis, Bacillus necrophorus and Bacteroides funduliformis [2,5]. As the pharyngitis symptoms subside, patients with Lemierre syndrome develop localized swelling and tenderness of the neck. Depending on the degree of inflammation there may be a marked decrease in range of motion of the neck, because of the infectious involvement of the parapharyngeal space. These individuals will present with a septic picture including pyrexia, tachycardia and hypotension. By history, there will be an antecedent interval of dysphagia or odynophagia which has worsened, often despite medical therapy. Pulmonary septic emboli manifested as pleuritic chest pain, dyspnea or respiratory distress are seen in 95% of cases reported [2 – 5]. Other pulmonary sequelae such as hemoptysis, pleural effusion and empyema also frequently occur. Respiratory distress from the multiple pulmonary septic emboli can be severe enough to necessitate intensive care observation and ventilatory support. Another frequent complication of Lemierre syndrome is metastatic septic joint effusion and arthralgia, as seen in our patients. This infective arthritis can be easily confused with polymyositis or other neuromuscular diseases resulting in an unnecessary extensive work-up. In one of our cases, a muscle biopsy was recommended by Rheumatology and the administration of high dose steroids was entertained which could have worsened the clinical course. Renal involvement is not uncommon and this clinical entity must be
differentiated from possible post-streptococcal glomerulonephritis which may have similar findings on urinalysis. Varying degrees of liver involvement may also be seen with symptoms ranging from mild hepatomegaly and tenderness over the liver, to frank jaundice and liver abscesses. Elevated liver enzymes commonly occur and these findings must be distinguished from that of infectious mononucleosis. Other abdominal complications such as purulent peritonitis have been reported. Less frequent complications of Lemierre syndrome include, meningitis and a few reports of mastoiditis, thyroiditis and endocarditis [3]. The diagnosis of Lemierre syndrome is based on clinical presentation, supported by bacteriological and radiological findings [3]. Blood cultures should confirm an anaerobic septicemia caused by Fusobacterium, but may be negative because of the use of antibiotics prior to hospitalization. Ultrasonography or contrast-enhanced CT of the neck will reveal thrombosis of the internal jugular vein and may or may not show a peritonsillar or parapharyngeal space abscess. A CT scan is usually more beneficial in the presence of an abscess, because the extent of the abscess is better delineated, the location of the great vessels identified and internal jugular vein involvement revealed. This will prove to be very helpful if surgical drainage is necessary. Chest X-ray or CT scan of the chest, frequently demonstrates multiple cavitary lesions, nodular shadowing and pleural effusion. One may also see several areas of bronchiectasis in the lungs. A CT scan of the abdomen may show hepatomegaly, hepatic microabscesses or splenomegaly. Abnormal laboratory findings such as an elevated white count, elevated liver enzymes, proteinuria and hematuria are not specific but support a diagnosis of Lemierre syndrome and can be used to follow it’s course. F. necrophorum is a common saprophyte of the oral cavity but when it results in septicemia, a fulminant infection occurs, necessitating early and prolonged intravenous antibiotic therapy. It is usually sensitive to benzylpenicillin, clindamycin, metronidazole, or chloramphenicol. Some cases report a better response with metronidazole be-
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cause of good tissue penetration [2]. Others support the use of clindamycin because of the rising rate of resistance of Fusobacterium to penicillin. Once a culture sensitive antibiotic is chosen for treatment, several weeks of antibiotics are required to completely eradicate the multiple organ system thromboemboli [2 – 4]. If a parapharyngeal or peritonsillar abscess is present, surgical drainage is necessary. Until recently, the only recommended surgical management of deep neck infections consisted of an external approach to the parapharyngeal space. In Case 1, the peritonsillar and parapharyngeal space abscesses were drained by a Quincy tonsillectomy and subsequent transoral drainage of the parapharyngeal space. CT scanning with contrast can clearly outline the limits of an abscess, which consists of a homogenous hypodense area with surrounding ring enhancement, the location of the great vessels and the presence of internal jugular vein thrombosis. At present, ligation and resection of the internal jugular vein are no longer advocated and anticoagulation therapy is controversial [2]. Because of the severity of this illness, supportive care in the intensive care unit may be necessary. Even with the appropriate management of this disease, it is not uncommon for the patient to have prolonged elevation of temperature and a slow recovery.
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4. Conclusion Lemierre syndrome is a rare sporadic illness characterized by Fusobacterial septicemia and thrombosis of the internal jugular vein. It is a disease that requires a high index of suspicion for diagnosis. Prompt intervention with intravenous antibiotic therapy and drainage of a deep neck abscess, if present on CT scanning with contrast, is essential to prevent the metastatic dissemination of septic emboli and to decrease the morbidity and mortality of this disease. Though rare, Lemierre syndrome still exists and remains potentially life threatening.
References [1] A. Lemierre, On certain septicaemias due to anaerobic organisms, Lancet 1936 March: 701 – 703. [2] J. Barker, H.T. Winer-Muram, S. Grey, Lemierre syndrome, Southern Med. J. 89 (1996) 1021 – 1023. [3] C.B. Koay, T. Heyworth, P. Burden, Lemierre syndrome — a forgotten complication of acute tonsillitis, J. Laryngol. Otol. 109 (1995) 657 – 661. [4] C.P. Sinave, G.J. Hardy, P.W. Fardy, The lemierre syndrome: supportive thrombophlebitisof the internal jugular vein secondary to oropharyngeal infection, Medicine 68 (1989) 85 – 94. [5] S. DeSena, D.L. Rosenfeld, S. Santos, I. Keller, Jugular thrombophlebitis complicating bacterial pharyngitis (Lemierre’s syndrome), Pediatr. Radiol. 26 (1996) 141 – 144.