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Bilateral Lemierre's syndrome: a case report and literature review. (Original Article).


Abstract

Lemierre's syndrome is characterized by thrombosis of the internal jugular vein internal jugular vein
n.
A vein that is a continuation of the sigmoid sinus of the dura mater and unites behind the cartilage of the first rib with the subclavian vein to form the brachiocephalic vein.
 that develops following an oropharyngeal oropharyngeal /oro·pha·ryn·ge·al/ (-fah-rin´je-al)
1. pertaining to the mouth and pharynx.

2. pertaining to the oropharynx.
 infection. Sepsis and septic metastases frequently ensue and affect the lungs, the musculoskeletal system, and occasionally the liver. Most cases are caused by infection with Fusobacterium necrophorum. This infection responds to antibiotic therapy with beta-lactamaseresistant compounds that exert good anaerobic anaerobic /an·aer·o·bic/ (an?ah-ro´bik)
1. lacking molecular oxygen.

2. growing, living, or occurring in the absence of molecular oxygen; pertaining to an anaerobe.
 coverage. Anticoagulation and surgical intervention can be helpful in advanced cases. Fewer than 160 cases of classic Lemierre's syndrome have been described; approximately one-third of these reported cases have occurred since 1988. We describe a new case of Lemierre's syndrome that occurred in an otherwise healthy 27-year-old man. Thrombosis of both internal jugular veins extended through the subclavian subclavian /sub·cla·vi·an/ (sub-kla´ve-an) below the clavicle.
Subclavian
Located beneath the collarbone (clavicle).
 system and into both upper extremities. The patient was treated with intravenous antibiotics and heparin during 14 days of hospitalization. He was discharged on oral clindamycin and warfarin sodium, and after 6 months he was able to return to full activity. To our knowledge, this is the first reported case of Lemierre's syndrome in which internal jugular vein thrombosis occurred bilaterally. By reporting this previously undescribed manifestation of Lemierre's syndrome, we hope to increase practitioner awareness of this disease entity.

Introduction

Internal jugular vein thrombosis is an uncommon disease that has been associated with central intravenous catheterization catheterization

Threading of a flexible tube (catheter) through a channel in the body to inject drugs or a contrast medium, measure and record flow and pressures, inspect structures, take samples, diagnose disorders, or clear blockages.
, IV drug abuse, hypereoagulability, infection, and atherosclerosis. (1) Virchow's triad (stasis, endothelial injury, and hypercoagulability) promotes clot development and propagation in the internal jugular vein (as it does in any other vascular bed), but fewer than 5% of deep venous thromboses occur in the head and neck. (2) Trauma from indwelling indwelling /in·dwell·ing/ (in´dwel-ing) pertaining to a catheter or other tube left within an organ or body passage for drainage, to maintain patency, or for the administration of drugs or nutrients.  central venous catheterization or from the repeated use of the internal jugular vein by IV drug abusers is the most common cause of internal jugular vein thrombosis. (3) This has not always been the case; during the pre-antibiotic era, internal jugular vein thrombosis was a common sequela sequela /se·que·la/ (se-kwel´ah) pl. seque´lae   [L.] a morbid condition following or occurring as a consequence of another condition or event.

se·quel·a
n. pl.
 to oropharyngeal infection.

In 1936, Lemierre described a syndrome that was characterized by anaerobic septicemia septicemia (sĕptĭsē`mēə), invasion of the bloodstream by virulent bacteria that multiply and discharge their toxic products. The disorder, which is serious and sometimes fatal, is commonly known as blood poisoning. , internal jugular vein thrombosis, and septic emboli emboli /em·bo·li/ (em´bo-li) plural of embolus.
Emboli
Plural of embolus. An embolus is something that blocks the blood flow in a blood vessel.
 that arose secondary to infections of the head and neck, particularly in the oropharynx oropharynx /oro·phar·ynx/ (-far´inks) the part of the pharynx between the soft palate and the upper edge of the epiglottis.

o·ro·phar·ynx
n.
. (4) (Lemierre was not the first to describe the syndrome that bears his name, but he is accorded the eponymous honor nonetheless.) Lemierre found that approximately 90% of patients with this illness had died within several weeks of its onset. Subsequent reports of this syndrome-which is also known as postanginal septicemia and a form of necrobacillosis-appeared intermittently in the literature until the 1950s. Most notably, Alston described 21 cases of classic Lemierre's syndrome in his review of 280 cases of necrobacillosis that had been published in the world literature between 1933 and 1955. (5)

Following the introduction of antibiotics, only a small number of cases was reported during the next 30 years. In 1989, Sinave et al published a thorough analysis of 38 cases that had occurred between 1974 and 1988. (6) In the same year, Eykyn commented on 45 cases of necrobacillosis in England and Wales England and Wales are both constituent countries of the United Kingdom, that together share a single legal system: English law. Legislatively, England and Wales are treated as a single unit (see State (law)) for the conflict of laws. , 29 of which exhibited the clinical characteristics of Lemierre's syndrome. (7) Since then, only sporadic case reports of Lemierre's syndrome have appeared in the English-language literature, and it came to be characterized as a "forgotten" disease. (8,9)

In order to raise awareness of this entity, we describe a new case of Lemierre's syndrome that featured a previously undocumented manifestation, and we provide an overview of those cases that have been reported since 1988.

Case report

A 27-year-old man (a soldier on active duty) was transferred to our institution for evaluation of bilateral internal jugular vein thrombosis, fever, and pharyngitis pharyngitis

Inflammation and infection (usually bacterial or viral) of the pharynx. Symptoms include pain (sore throat, worse on swallowing), redness, swollen lymph nodes, and fever.
 from a suspected occult malignancy. The patient had no significant medical history and denied IV drug abuse. He had been in his usual state of health until approximately 4 weeks prior to transfer, when he began experiencing fever and sore throat. He had received several courses of antibiotics--including erythromycin erythromycin (ĭrĭth'rōmī`sĭn), any of several related antibiotic drugs produced by bacteria of the genus Streptomyces (see antibiotic).  and ceftriaxone--and a tapered steroid regimen for culture-proven group A beta-hemolytic streptococcal pharyngitis, but he had failed to improve. The results of monospot tests were repeatedly negative. With the onset of anterior neck pain and tenderness, coupled with the persistence of his odynophagia, the patient had been admitted to an outside facility 5 days prior to transfer.

An outside otolaryngology service aspirated purulent pu·ru·lent
adj.
Containing, discharging, or causing the production of pus.


Purulent
Consisting of or containing pus

Mentioned in: Lacrimal Duct Obstruction


purulent

containing or forming pus.
 matter from the anterior neck, diagnosed an infected thyroglossal duct cyst, and eventually incised incised /in·cised/ (in-sizd´) cut; made by cutting.  the area and drained a large collection of fluid. However, despite IV antibiotic therapy with alternating clindamycin and ceftriaxone ceftriaxone /cef·tri·ax·one/ (cef?tri-ak´son) a semisynthetic, ß–resistant, third-generation cephalosporin effective against a wide range of gram-positive and gram-negative bacteria, used as the sodium salt.  for 3 days, the patient's condition worsened and he began to evince e·vince  
tr.v. e·vinced, e·vinc·ing, e·vinc·es
To show or demonstrate clearly; manifest: evince distaste by grimacing.
 right-sided facial and supraclavicular swelling in addition to left upper extremity swelling. Venous duplex ultrasonography ultrasonography /ul·tra·so·nog·ra·phy/ (-so-nog´rah-fe) the imaging of deep structures of the body by recording the echoes of pulses of ultrasonic waves directed into the tissues and reflected by tissue planes where there is a change in  documented the presence of bilateral internal jugular and subclavian venous thrombosis that extended to the axillary vein on the right and the basilic vein on the left (figure 1). Based on this finding, the patient was transferred to our facility.

Our otolaryngology--head and neck surgery service was consulted shortly after the patient's arrival. On initial evaluation, the patient had a temperature of 99.1[degree]F and appeared to be toxic. Examination of the oropharynx revealed an asymmetric tonsillar tonsillar /ton·sil·lar/ (ton´si-lar) of or pertaining to a tonsil.

ton·sil·lar or ton·sil·lar·y
adj.
Of or relating to a tonsil, especially the palatine tonsil.
 enlargement without erythema erythema (ĕr'əthē`mə), more or less diffuse redness of the skin due to concentration of an abnormally large amount of blood within the small vessels of the skin (hyperemia), as in burns. , exudates, or lesions. The patient's neck was marked by diffuse swelling and exquisite tenderness to palpation palpation /pal·pa·tion/ (pal-pa´shun) the act of feeling with the hand; the application of the fingers with light pressure to the surface of the body for the purpose of determining the condition of the parts beneath in physical diagnosis. , and there was a distinct nodularity along the anterior aspect of both sternocleidomastoid muscles. A 1-cm transverse midline incision was noted at the level of the thyroid cartilage. The incision had been packed with NuGauze and the surrounding area was marked by edema edema (ĭdē`mə), abnormal accumulation of fluid in the body tissues or in the body cavities causing swelling or distention of the affected parts.  and erythema; minimal mucopurulent mucopurulent /mu·co·pu·ru·lent/ (-pur´ah-lint) containing both mucus and pus.

mu·co·pu·ru·lent
adj.
Containing mucus and pus.
 drainage was noted. A palpable cord was noted in the right supraclavicular fossa, and there was obvious swelling of the left antecubital fossa fossa /fos·sa/ (fos´ah) pl. fos´sae   [L.] a trench or channel; in anatomy, a hollow or depressed area.

acetabular fossa  a nonarticular area in the floor of the acetabulum.
 and the medial aspect of the arm. No edema, asymmetry, erythema, or lesion was evident on flexible fiberoptic nasopharyngoscopy. On auscultation auscultation

Procedure for detecting certain defects or conditions by listening for normal and abnormal heart, breath, bowel, fetal, and other sounds in the body. The invention of the stethoscope in 1819 improved and expanded this practice, still very useful despite the
, the lungs were clear, but a I I/VI systolic Systolic
The phase of blood circulation in which the heart's pumping chambers (ventricles) are actively pumping blood. The ventricles are squeezing (contracting) forcefully, and the pressure against the walls of the arteries is at its highest.
 ejection murmur was noted. The patient also had hepatosplenomegaly.

Results of initial laboratory evaluations were obtained (table 1). Among the significant findings were a normal leukocyte count, hypoalbuminemia, normal clotting, and elevated liver enzyme levels. Contrast-enhanced computed tomography (CT) of the neck (figure 2) and chest (figure 3) detected thrombosis of the right jugular, distal right subclavian, right brachiocephalic brachiocephalic /bra·chio·ce·phal·ic/ (bra?ke-o-se-fal´ik) pertaining to the arm and head.

bra·chi·o·ce·phal·ic
adj.
Relating to the arm and the head.
, and left jugular veins. The right jugular vein clot extended from the skull base to just above the aortic arch. The left internal jugular vein thrombus thrombus /throm·bus/ (throm´bus) pl. throm´bi   a stationary blood clot along the wall of a blood vessel, frequently causing vascular obstruction.  was only partially occlusive occlusive /oc·clu·sive/ (o-kloo´siv) pertaining to or causing occlusion.

oc·clu·sive
adj.
1. Occluding or tending to occlude.

2.
 and limited to the area of the thyroid gland. A collection of fluid and surrounding inflammation occupied the anterior midline of the neck superior to the thyroid gland. Multiple pulmonary nodules Nodules
A small mass of tissue in the form of a protuberance or a knot that is solid and can be detected by touch.

Mentioned in: Leprosy
 (including a cavitary nodule nodule: see concretion.
nodule

In geology, a rounded mineral concretion that is distinct from, and may be separated from, the formation in which it occurs.
 in the anterior basal segment of the right lower lobe), bilateral lower lobe infiltrates, and bilateral pleural effusions were also evident.

A diagnosis of Lemierre's syndrome was made, and the patient was started on IV clindamycin (900 mg q8h) and IV ceftriaxone (2 g ql2h). Following an initial deterioration in his respiratory status (decreased oxygen saturations and pleuritic pleu·rit·ic
adj.
Of or relating to pleurisy.



pleuritic

pertaining to or emanating from pleurisy. See also pleural.


pleuritic ridge
 chest pain that did not require mechanical ventilation), the patient improved and began to experience less pain, swelling, and shortness of breath Shortness of Breath Definition

Shortness of breath, or dyspnea, is a feeling of difficult or labored breathing that is out of proportion to the patient's level of physical activity.
. However, a chest radiograph radiograph /ra·dio·graph/ (-graf?) the film produced by radiography.

ra·di·o·graph
n.
 showed that his pulmonary disease was persistent (figure 4). After consultations with both the infectious disease and hematology services, the patient was started on IV heparin therapy. He required twice-daily dressing changes of the midline neck wound and received 14 days of IV antibiotics. After discharge, he continued on oral clindamycin for 4 weeks and warfarin sodium for 6 months. Venous duplex ultrasonography documented a gradual reduction in the size of the extensive bilateral thrombi thrombi /throm·bi/ (throm´bi) plural of thrombus.  (figure 5). At his last evaluation, the patient's warfarin warfarin (wôr`fərĭn), anticoagulant used to treat blood clots. In large doses it causes bleeding. Warfarin, mixed with bait, is used in rodent control.
warfarin

Anticoagulant drug, marketed as Coumadin.
 was stopped, and he was able to return to active duty.

Review of the literature

Our examination of the English-language medical literature published since 1988 revealed that 54 patients were reported to have had clinical evidence of Lemierre's syndrome. However, in keeping with the criteria espoused by Sinave et al, (6) not all of these cases are included in this review. Classic Lemierre's syndrome is characterized by (1) primary infection in the oropharynx, (2) septicemia documented by at least one positive blood culture, (3) clinical or radiographic radiographic (rā´dēōgraf´ik),
adj relating to the process of radiography, the finished product, or its use.
 evidence of internal jugular vein thrombosis, and (4) at least one metastatic focus. (6) We determined that 40 of the 54 cases that were described by others since the publication of the report by Sinave et al were documented to have met all four criteria, and these are the cases that we discuss in this article, in addition to our own case (table 2). Although the clinical criteria for Lemierre's syndrome might have been met in the other 14 cases, (9-22) we did not include them in this review because there was either an absence of documented metastatic foci, absent or negative blood cultures, undocumented internal jugular vein thrombosis, or a primary infection that arose either outside the oropharynx or as a sequela to trauma. Moreover, another 29 patients were described in two series that examined necrobacillosis and septic internal jugular vein thrombosis, but insufficient data preclude these patients from consideration in this study. (23,24)

As was the case in the review by Sinave et al, (6) all 41 patients in our study were presumed to have had internal jugular vein thrombosis if they exhibited pleuropulmonary involvement. The 27 males (65.9%) and 14 females ranged in age from 8 to 49 years (mean: 20.6). Thirty-nine patients (95.1%) had developed Lemierre's syndrome following an episode of pharyngitis; the other two patients had evidence of gingivitis gingivitis (jĭn'jəvī`tĭs), inflammation of the gums. It may be acute, subacute, chronic, or recurrent. The gums usually become red, swollen, and spongy, and bleed easily. . Pleuropulmonary involvement--including infiltrates, nodular nodular

marked with, or resembling, nodules.


nodular dermatofibrosis
see dermatofibrosis.

nodular episcleritis
see nodular fasciitis (below).

nodular fasciitis
a firm painless nodular swelling, 0.
 densities, pleural effusions, empyema empyema (ĕmpē-ē`mə), persistent purulent discharge into a cavity such as the pleural space or the gallbladder. Empyema results as a complication of bacterial infections such as pneumonia and lung abscess. , and adult respiratory distress syndrome--occurred in 38 patients (92.7%). (8-10,14,18,25-45)

Other sites of septic emboli or direct extension of thrombosis included the liver, (9,14,41) long bone and extremity joints, (25,32,34,36) the gluteal gluteal /glu·te·al/ (gloo´te-al) pertaining to the buttocks.

glu·te·al
adj.
Of or relating to the buttocks.



gluteal

pertaining to the buttocks.
 region, (9,46,47) the sternum sternum: see rib. , (32) and the cranial vault, (48) Patients also experienced systemic manifestations of illness, such as derangements of liver function with elevations of intracellular enzymes and bilirubin Bilirubin

The predominant orange pigment of bile. It is the major metabolic breakdown product of heme, the prosthetic group of hemoglobin in red blood cells, and other chromoproteins such as myoglobin, cytochrome, and catalase.
, (9,14,41) cytopenias, (32,43) and disseminated intravascular coagulation disseminated intravascular coagulation
n.
Abbr. DIC A hemorrhagic disorder that occurs following the uncontrolled activation of clotting factors and fibrinolytic enzymes throughout small blood vessels, resulting in tissue necrosis and
.37 Four patients manifested significant thrombosis beyond the internaijugular vein, including the external jugular vein external jugular vein
n.
A vein that is formed by the junction of the posterior auricular and the retromandibular veins, passes down the side of the neck superficial to the sternocleidomastoid muscle, and empties into the subclavian vein.
, sigmoid sinus, and superior vena cava superior vena cava
n. Abbr. SVC
A large vein formed by the union of the two brachiocephalic veins and the azygos vein that receives blood from the head, neck, upper limbs, and chest, and empties into the right atrium of the heart.
. (27,33,44,48)

Fusobacterium necrophorum was isolated from the blood of 36 patients (87.8%), including two who had polymicrobial infections. Fusobacterium nucleatum (37) and Streptococcus san guis (18) appeared in one patient each, and both Peptostreptococcus and group C Streptococcus spp. were isolated from a single patient. (10) Kiebsiella pneumoniae was isolated from both the sputum and blood of one patient who developed Lemierre's syndrome following a periodontal infection. (44)

All patients received intravenous antibiotics. The most common were metronidazole metronidazole /met·ro·ni·da·zole/ (-ni´dah-zol) an antiprotozoal and antibacterial effective against obligate anaerobes; used as the base or the hydrochloride salt. It is also used as a topical treatment for rosacea. , penicillin, gentamicin gentamicin /gen·ta·mi·cin/ (jen?tah-mi´sin) an aminoglycoside antibiotic complex isolated from bacteria of the genus Micromonospora, , clindamycin, and various second- and third-generation cephalosporins Cephalosporins Definition

Cephalosporins are medicines that kill bacteria or prevent their growth.
Purpose

Cephalosporins are used to treat infections in different parts of the body—the ears, nose, throat, lungs, sinuses, and
. More than one antibiotic was administered to 35 patients; specific data on antibiotic selection and regimen are unavailable for two of these patients. (31, 46) Eleven patients (26.8%) required anticoagulation over a period of 1 week to 6 months. Thirty-nine of the 41 patients (95.1%) survived; of the two who did not, one died from fulminant ful·mi·nant
adj.
Occurring suddenly, rapidly, and with great severity or intensity, usually of pain.



ful
 pneumonia and the other from severe sepsis. (28, 46)

Our analysis revealed that there are striking similarities between our 41 cases and the cases of Lemierre's syndrome that were reported from 1974 through 1988 by Sinave et al with respect to patient demographics, sites of metastatic involvement, types of pathogen, treatment modalities, and outcomes. (6)

Discussion

We report the first case of bilateral internal jugular vein thrombosis in a patient with Lemierre's syndrome. When Lemierre first described the syndrome of postanginal sepsis, he noted that most cases developed in the setting of oropharyngeal infection. (4) Furthermore, he acknowledged that internal jugular vein thrombophlebitis thrombophlebitis: see phlebitis.  could exhibit manifestations in the ear, mastoid mastoid /mas·toid/ (mas´toid)
1. breast-shaped.

2. mastoid process.

3. pertaining to the mastoid process.


mas·toid
n.
The mastoid process.
, and sinuses, as well. (4)

Clinical features. Lemierre's syndrome is characterized by thrombosis of the internal jugular vein that develops following oropharyngeal infection. Sepsis and septic metastases frequently ensue, and they can affect the lungs, the musculoskeletal system, and on occasion the liver. Pharyngitis, tonsillitis tonsillitis

Inflammatory infection of the tonsils, usually with hemolytic streptococci (see streptococcus) or viruses. The symptoms are sore throat, trouble in swallowing, fever, and enlarged lymph nodes on the neck.
, or gingivitis accounts for the initial infection and fever, which are typically followed in 1 to 3 weeks by the development of neck pain and swelling, respiratory decompensation decompensation /de·com·pen·sa·tion/ (de?kom-pen-sa´shun)
1. inability of the heart to maintain adequate circulation, marked by dyspnea, venous engorgement, and edema.

2.
, or myalgias and arthralgias. This pattern of events is fairly pathognomonic pathognomonic /pa·thog·no·mon·ic/ (path?ug-no-mon´ik) specifically distinctive or characteristic of a disease or pathologic condition; denoting a sign or symptom on which a diagnosis can be made. ; in fact, Lemierre noted that this syndrome is so characteristic that "mistake is almost impossible." (4) Even so, delays in diagnosis are common.

The incidence of Lemierre's syndrome and associated mortality have decreased substantially since the dawn of the antibiotic age. (6) In fact, only two deaths have been documented since 1990. (28,46) Nevertheless, prolonged morbidity (and its attendant financial and social costs) can persist, as it did in our patient.

Although Streptococcus, Bacteroides, and Lactobacillus lactobacillus

Any of the rod-shaped, gram-positive (see gram stain) bacteria that make up the genus Lactobacillus. They are widely distributed in animal feeds, manure, and milk and milk products.
 spp. as well as other Fusobacterium spp. have been implicated in the pathogenesis of Lemierre' s syndrome, F necrophorum is the most common pathogen isolated from blood cultures in these patients. The Fusobacterium organism is a normal component of the flora of the oral cavity, and it exists in large numbers in the gingival crevice and the subgingival plaque of adults. This genus also resides in the large bowel and in the female genital tract. An anaerobic, gram-negative bacillus, F necrophorum can be filamentous or fusiform fusiform /fu·si·form/ (-form) shaped like a spindle; tapered at each end.

fu·si·form
adj.
Tapering at each end; spindle-shaped.



fusiform

spindle-shaped.
 in appearance. (49) In addition to oropharyngeal infections, Fusobacterium spp. have been implicated in the development of endocarditis endocarditis (ĕn'dōkärdī`tĭs), bacterial or fungal infection of the endocardium (inner lining of the heart) that can be either acute or subacute. , soft-tissue infections, and brain, hepatic, and intra-abdominal abscesses. Fusobacterium spp. have been associated with as many as 46% of all head and neck infections, frequently in conjunction with other organisms. (50)

A disruption of normal host mucosal defenses through trauma or hypoxia hypoxia

Condition in which tissues are starved of oxygen. The extreme is anoxia (absence of oxygen). There are four types: hypoxemic, from low blood oxygen content (e.g., in altitude sickness); anemic, from low blood oxygen-carrying capacity (e.g.
 can provide a supportive environment for the proliferation of these bacteria. (50) Bacterial production of proteolytic enzymes, lipopolysaccharide lipopolysaccharide /lipo·poly·sac·cha·ride/ (-pol?e-sak´ah-rid)
1. a molecule in which lipids and polysaccharides are linked.

2.
 endotoxin Endotoxin

A biologically active substance produced by bacteria and consisting of lipopolysaccharide, a complex macromolecule containing a polysaccharide covalently linked to a unique lipid structure, termed lipid A.
, leukocidin, and hemagglutinin hemagglutinin /he·mag·glu·ti·nin/ (-gloo´ti-nin) an antibody that causes agglutination of erythrocytes.

cold hemagglutinin  one which acts only at temperatures near 4° C.
 accounts for the pathogenicity of F necrophorum, which then invade the regional veins. (36) The hemagglutinin moiety moiety: see clan.  has been shown to aggregate bovine platelets, which might account for the internal jugular vein thrombosis of Lemierre's syndrome. (49)

The nomenclature of this class of bacteria has undergone significant evolution over the past 50 years. The current classification is based on selective culturing techniques and analysis of fatty-acid end products. Although other anaerobic bacilli such as Bacteroides spp. can be involved in oropharyngeal infections, Fusobacterium spp. can be differentiated by their production of n-butyric acid alone. (50)

The oropharynx--particularly the palatine tonsils--provides the source of infection in most cases of Lemierre's syndrome. The anatomy of the lateral pharyngeal pharyngeal /pha·ryn·ge·al/ (fah-rin´je-al) pertaining to the pharynx.

pha·ryn·geal or pha·ryn·gal
adj.
Of, relating to, located in, or coming from the pharynx.
 space promotes invasion of the internal jugular vein in the retrostyloid compartment. An inverted cone extending from the skull base to the hyoid hyoid /hy·oid/ (hi´oid) shaped like Greek letter upsilon (?); pertaining to the hyoid bone.

hy·oid
adj.
1. Shaped like the letter U.

2. Of or relating to the hyoid bone.
, the lateral pharyngeal space is bounded medially by the superior pharyngeal constrictor and laterally by the medial pterygoid. The styloid styloid /sty·loid/ (sti´loid) resembling a pillar; long and pointed; relating to the styloid process.

sty·loid
n.
 process divides this anatomic space into anterior and posterior compartments; the contents of the carotid sheath and cranial nerves IX through XII reside in the posterior compartment. Tonsillar infection can involve the jugular vein by direct extension through this fascial space or by hematogenous hematogenous /he·ma·tog·e·nous/ (he?mah-toj´e-nus)
1. produced by or derived from the blood.

2. disseminated through the blood stream.


he·ma·tog·e·nous
adj.
1.
 or lymphatic spread from peritonsillar vessels. (32)

After the development of internal jugular vein thrombosis, septic emboli can emerge and affect distant sites. Numerous reports of pulmonary involvement--ranging from discrete nodularity to empyema thoracis and adult respiratory distress syndrome--have been published. (8-10,14,18,25-45) Patients can experience decreased oxygen saturation, pleuritic chest pain, or hemoptysis Hemoptysis Definition

Hemoptysis is the coughing up of blood or bloody sputum from the lungs or airway. It may be either self-limiting or recurrent. Massive hemoptysis is defined as 200-600 mL of blood coughed up within a period of 24 hours or less.
. Liver abscesses can occur, but elevations in both intra- and extra-cellular liver enzyme levels appear to be more common, (9,10) as was evident in our patient. The long bones can be affected by osteomyelitis osteomyelitis (ŏs'tēōmī'əlī`tĭs), infection of the bone and bone marrow. Direct infection of bone usually occurs through open fractures, penetrating wounds, or surgical operations. , and joints such as the elbow, knee, and ankle can also be affected. (25,32,34,36) Soft-tissue abscesses have also been described, and they often required drainage before systemic improvement was noted. (9,34,46,47) Multiple hematologic hematological, hematologic

pertaining to or emanating from blood cells.


hematological tests
total and differential white cell counts, hematocrit estimation, erythrocyte count.
 abnormalities have been reported, including thrombocytopenia Thrombocytopenia Definition

Thrombocytopenia is an abnormal drop in the number of blood cells involved in forming blood clots. These cells are called platelets.
 and disseminated intravascular coagulation. (9,10,21) Neurologic and intracranial intracranial /in·tra·cra·ni·al/ (-kra´ne-al) within the cranium.

in·tra·cra·ni·al
adj.
Within the cranium.
 complications such as meningitis and cranial nerve palsies can even occur. (48)

The myriad manifestations of Lemierre's syndrome often complicate its diagnosis and cause a delay in appropriate therapy. Evaluation of the patient with suspected Lemierre's syndrome should begin with a thorough history and physical examination, because abnormalities can be present in more than one organ system.

Chest radiography is indicated when pulmonary symptoms are present, and appropriate laboratory studies--including measurements of the complete blood count and electrolyte and liver enzyme levels--can provide insight into the extent of disease. Blood culture results, both aerobic and anaerobic, should be obtained prior to initiating antibiotic therapy.

Imaging studies. Radiographic evaluation of the neck and internal jugular veins can be accomplished in several ways: via venous duplex ultrasonography, CT with IV contrast (in patients with adequate renal function), magnetic resonance imaging magnetic resonance imaging (MRI), noninvasive diagnostic technique that uses nuclear magnetic resonance to produce cross-sectional images of organs and other internal body structures.  (MRI 1. (application) MRI - Magnetic Resonance Imaging.
2. MRI - Measurement Requirements and Interface.
), magnetic resonance venography Venography Definition

Venography is an x-ray test that provides an image of the leg veins after a contrast dye is injected into a vein in the patient's foot.
, nuclear scintigraphy scintigraphy /scin·tig·ra·phy/ (sin-tig´rah-fe) the production of two-dimensional images of the distribution of radioactivity in tissues after the internal administration of a radiopharmaceutical imaging agent, the images being obtained , and gallium-67 scanning.

Although contrast venography is the gold standard, the attendant radiation exposure, invasiveness, and risk of perforation or embolic events might outweigh its utility. Venous duplex ultrasonography is accurate and provides reproducible detection of intraluminal thrombosis or abscess, but its application can be limited by the anatomic location of the clavicle clavicle /clav·i·cle/ (klav´i-k'l) collar bone; a bone, curved like the letter f, that articulates with the sternum and scapula, forming the anterior portion of the shoulder girdle on either side.  and mandible, as well as variability in the skill level of the technician. Although acute thrombus can be missed because of its low degree of echogenicity, thrombosed thrombosed /throm·bosed/ (throm´bozd) affected with thrombosis.

throm·bosed
adj.
1. Clotted.

2. Of, being, or characterizing a blood vessel that is the seat of thrombosis.
 veins are typically dilated and incompressible in·com·press·i·ble  
adj.
Impossible to compress; resisting compression: mounds of incompressible garbage.



in
, and they feature either a lack of venous pulsations or a flow that does not vary during sniffing or Valsalva's maneuver. (51) Venous duplex ultrasonography is an inexpensive method of documenting improvement or resolution of thrombosis (figure 5).

The most common modality employed to diagnose internal jugular vein thrombosis is CT with IV contrast. (16) Radiographically, the internal jugular vein will be dilated and there will be a low-attenuation intraluminal content and enhancement of the vessel wall and surrounding tissue. The wall enhancement has been attributed to the uptake of the contrast material by the vasa vasorum.

Although CT does involve radiation exposure and the administration of intravenous contrast, it is rapid and reliable. (51)

MRI provides an excellent delineation of soft tissues without radiation exposure and with the benefit of multiplanar viewing. Some authors attest that magnetic resonance venography is the most accurate and reliable method of detecting the presence and extension venous thrombosis, and its correlation to contrast venography has been reported to be as high as 97%. (12) Neither nuclear scintigraphy nor gallium-67 scanning approaches the reliability and ease of CT, MRI, or magnetic resonance venography. (22, 51)

Treatment. Antibiotic therapy--particularly with a beta-lactamase-resistant compound that provides excellent anaerobic coverage--is the mainstay of treatment. Metronidazole, penicillin, and clindamycin are the most frequently used drug therapies. However, the emergence of beta-lactamase-producing strains can minimize the efficacy of penicillin. Therefore, beta-lactamase-resistant antibiotics are becoming more popular because they typically overcome this type of bacterial resistance. (52) Depending on the severity of the infection, antibiotics should be administered intravenously for 7 to 14 days, followed by an additional 2 to 4 weeks of oral antibiotics. (10)

The use of additional measures--such as surgical drainage of abscesses, ligation ligation /li·ga·tion/ (li-ga´shun) the application of a ligature.

tubal ligation  sterilization of the female by constricting, severing, or crushing the uterine tubes.
 of thrombosed vessels, and administration of an anticoagulant--depends on both the severity of the illness and its response to antibiotic treatment. Surgical intervention is indicated if there is a lack of improvement after 48 to 72 hours of intravenous antibiotic therapy, a worsening of systemic illness, or the development of sepsis. Our patient likely benefited from the incision and drainage Incision and drainage is a minor surgical procedure to release pus or pressure built up under the skin, such as from an abscess or boil. It is performed by treating the area with an antiseptic, such as iodine based solution, and then making a small incision to puncture the skin  of his midline neck mass, which was initially presumed to be a thyroglossal duct cyst. Other authors have documented improvement following surgical intervention. (10, 44)

The fact that 11 of the 41 patients (26.8%) in this review improved following the addition of anticoagulation therapy supports its use in cases of extensive thrombosis. (8, 12, 25, 32, 33, 44, 48)

In conclusion, Lemierre's syndrome is less common now than it was during the pre-antibiotic era, but it remains a serious entity. It carries significant morbidity and a low but consistent risk of mortality. Despite intermittent reports of this illness, delays in diagnosis continue to occur. It is our hope that this article will increase awareness of this rare clinical entity and minimize diagnostic and therapeutic delay.
Table 1

Admission laboratory values for the patient in this case report

Test                            Value             Normal range

Leukocyte count                 9.3 [10.sup.9]/L  4.0 to 11.0
% Polymorphonuclear             77.9%             42 to 77
 leukocytes
% Lymphocytes                   14.9%             25 to 40
Hemoglobin                      9.2 g/dl          14.0 to 18.0
Packed cell volume              27%               42 to 50
Prothrombin time                13.7 sec          13.0 to 15.0
International normalized ratio  1.0               N/A
Partial thromboplastin time     33.7 sec          34.0 to 60.0
Fibrinogen                      441 mg/dl         185 to 400
Sodium                          136 mEq/L         135 to 145
Potassium                       4.4 mEq/L         3.5 to 5.0
Chloride                        101 mEq/L         95 to 105
Carbon dioxide                  29 mEq/L          23 to 30
Blood urea nitrogen (BUN)       9 mg/dl           5 to 25
Creatinine                      0.9 mg/dl         0.7 to 1.5
Glucose                         112 mg/dl         70 to 110
Albumin                         1.9 g/dl          3.5 to 5.0
Total bilirubin                 0.8 mg/dl         0.2 to 1.2
Alkaline phosphatase            169 U/L           40 to 110
Serum glutamic oxaloacetic      69 U/L            4 to 40
 transaminase (SGOT)
Serum glutamate pyruvate        73 U/L            4 to 40
 transaminase (SGPT)
Table 2.

Characteristics of 41 cases of Lemierre's syndrome reported since 1988

                           Age/    Primary         Area of
Author                    sex (*)  symptom         extension

Goldhagen et al,           11/M    Gingivitis      Lungs,
 1988 (25)                                         elbow

                           15/F    Pharyngitis     Lungs


                           16/F    Pharyngitis     Lungs

Shapiro et al,             31/F    Pharyngitis     Lungs
 1989 (18)
                           23/F    Pharyngitis     Lungs
Moreno et al,              18/M    Pharyngitis     Lungs
 1989 (26)
Shadowen and               15/M    Pharyngitis     Lungs
 Trevor, 1989 (27)                 (hearing loss)  (hearing loss)
Golledge et al,            20/M    Pharyngitis     Lungs
 1990 (28)
                           17/M    Pharyngitis     Lungs

Chippindale et al,         17/M    Pharyngitis     Lungs
 1990 (29)

Chalstrey et al,           19/M    Pharyngitis     Lungs
 1992 (30)
Weesner and                21/M    Pharyngitis     Lungs
 Cisek, 1993 (8)
Cosgrove et al,            19/M    Pharyngitis     Lungs
 1993 (31)
Carlson et al,             16/M    Pharyngitis     Lungs
 1994 (32)
                           16/M    Pharyngitis     Lungs,
                                                   sternum,
                                                   joints

Ahkee et al,               14/M    Pharyngitis     Lungs
 1994 (33)
Koay et al, 1995 (9)       17/F    Pharyngitis     Lungs, liver


                           23/F    Pharyngitis     Lungs,
                                                   hip (abscess)
Lustig et al, 1995 (10)    27/M    Pharyngitis     Lungs


Karanas et al,             22/M    Pharyngitis     Lungs,
 1995 (34)                                         thigh

Goyal et al, 1995 (48)      8/M    Pharyngitis     Hip (abscess)
Barker et al, 1996 (35)    16/M    Pharyngitis     Lungs

Stahlman et al,            13/M    Pharyngitis     Lungs, joints
 1996 (38)
De Sena et al,             14/F    Pharyngitis     Lungs
 1996 (37)

                           15/F    Pharyngitis     Lungs, blood
                                                   (disseminated
                                                   intravascular
                                                   coagulation)
Moller and Dreijer,        43/M    Pharyngitis     Lungs
 1997 (38)
                           25/M    Pharyngitis     Lungs





                           15/M    Pharyngitis     Lungs

                           33/F    Pharyngitis     Lungs
                                                   (respiratory
                                                   distress
                                                   syndrome)
Gudinchet et al,           15/F    Pharyngitis     Lungs
 1997 (39)

                           17/F    Pharyngitis     Lungs


Venkataraman               20/M    Pharyngitis     Lungs
 and Policar, 1997 (40)

Stallworth and             17/F    Pharyngitis     Lungs, liver
 Carroll, 1997 (41)

Lee et al, 1997  (47)      22/M    Pharyngitis     Gluteal area
                                                   (abscesses)



Williams et al,            15/M    Pharyngitis     Lungs, liver
 1998 (14)

Vandenberg and             17/M    Pharyngitis     Lungs
 Hartig, 1998 (42)

Ellis et al, 1998 (43)     19/M    Pharyngitis     Lungs


Schwartz and               49/M    Gingivitis      Lungs
 Nguyen, 1999 (44)





Alifano at al, 2000 (45)   31/F    Pharyngitis     Lungs


Agarwal et al,             37/F    Pharyngitis     Cranial
 2000 (48)                                         nerves,
                                                   intracranial
                                                   vault

Moore et al, 2OO2 (+)      27/M    Pharyngitis     Lungs



                          Isolated
Author                    pathogen            Treatment

Goldhagen et al,          Fusobacterium       Nafcillin, chloram-
 1988 (25)                necrophorum         phenicol, penicillin;
                                              anticoagulation
                          F necrophorum       Cefoxitin,
                                              gentamicin,
                                              clindamycin
                          F necrophorum       Clindamycin, penicillin;
                                              anticoagulation
Shapiro et al,            Streptococcus       Clindamycin,
 1989 (18)                sanguis             vancomycin, gentamicin
                          F necrophorum       Clindamycin, penicillin
Moreno et al,             F necrophorum       Chloramphenicol,
 1989 (26)                                    cefoxitin; thoracotomy
Shadowen and              F necrophorum       Metronidazole
 Trevor, 1989 (27)
Golledge et al,           F necrophorum       Metronidazole,
 1990 (28)                                    cloxacillin, gentamicin
                          F necrophorum       lmipenem/cilastatin,
                                              tobramycin
Chippindale et al,        F necrophorum       Erythromycin,
 1990 (29)                                    metronidazole;
                                              decortication
Chalstrey et al,          F necrophorum       Penicillin,
 1992 (30)                                    metronidazole
Weesner and               F necrophorum       Penicillin; warfarin
 Cisek, 1993 (8)
Cosgrove et al,           F necrophorum       Antibiotics
 1993 (31)
Carlson et al,            F necrophorum       Cefoxitin, clindamycin
 1994 (32)
                          F necrophorum       Clindamycin,
                                              ceftizoxime, penicillin,
                                              metronidazole;
                                              anticoagulation x 6 mo
Ahkee et al,              F necrophorum       Ticarcillin/clavulanate;
 1994 (33)                                    heparin
Koay et al, 1995 (9)      F necrophorum       Metronidazole,
                                              cefuroxime,
                                              gentamicin
                          F necrophorum       Cefuroxime,
                                              metronidazole
Lustig et al, 1995 (10)   Peptostreptococcus  Vancomycin,
                          spp., group C       ciprofloxacin,
                          Streptococcus spp.  metronidazole
Karanas et al,            F necrophorum       Gentamicin,
 1995 (34)                                    vancomycin,
                                              metronidazole
Goyal et al, 1995 (48)    F necrophorum       Antibiotics
Barker et al, 1996 (35)   F necrophorum       Ampicillin/sulbactam,
                                              gentamicin
Stahlman et al,           F necrophorum       Penicillin; incision
 1996 (38)                                    and drainage
De Sena et al,            Fusobacterium       Ticarcillin/clavulanate,
 1996 (37)                nucleatum           vancomycin;
                                              anticoagulation x 3 mo
                          F necrophorum       Ceftazidime,
                                              ticarcillin/clavulanate,
                                              metronidazole;
                                              anticoagulation x 3 mo
Moller and Dreijer,       Hemolytic Strepto-  Penicillin, gentamicin,
 1997 (38)                coccus spp.         metronidazole
                          F necrophorum,      Cefuroxime,
                          microaerophilic     netilmicin,
                          Streptococcus,      metronidazole
                          Lactobacillus, and
                          Peptostreptococcus
                          spp.
                          F necrophorum       Penicillin, gentamicin,
                                              metronidazole
                          F necrophorum,      Penicillin,
                          Streptococcus,      metronidazole,
                          Bacteroides, and    ciprofloxacin,
                          Candida spp.        fluconazole
Gudinchet et al,          F necrophorum       Ceftriaxone,
 1997 (39)                                    amoxicillin/clavulanate

                          F necrophorum       Ceftriaxone,
                                              amoxicillin/clavulanate

Venkataraman              F necrophorum       Penicillin,
 and Policar, 1997 (40)                       metronidazole

Stallworth and            F necrophorum       Nafcillin, ceftriaxone,
 Carroll, 1997 (41)                           metronidazole

Lee et al, 1997  (47)     F necrophorum       Metronidazole,
                                              penicillin;
                                              heparin,
                                              warfarin x 6 mo

Williams et al,           F necrophorum       Clindamycin; quinsy
 1998 (14)                                    tonsillectomy

Vandenberg and            F necrophorum       Metronidazole
 Hartig, 1998 (42)

Ellis et al, 1998 (43)    F necrophorum       Penicillin, cefotaxime,
                                              metronidazole

Schwartz and              Klebsiella          Ampicillin,
 Nguyen, 1999 (44)        pneumoniae          ciprofloxacin,
                                              metronidazole;
                                              anticoagulation;
                                              external jugular vein
                                              excision

Alifano at al, 2000 (45)  F necrophorum       Penicillin,
                                              metronidazole

Agarwal et al,            F necrophorum       Penicillin,
 2000 (48)                                    metronidazole;
                                              anticoagulation


Moore et al, 2OO2 (+)     F necrophorum       Clindamycin,
                                              ceftriaxone;
                                              anticoagulation x 6 mo


Author                    Outcome

Goldhagen et al,           Cured
 1988 (25)

                           Cured


                           Cured

Shapiro et al,             Cured
 1989 (18)
                           Cured
Moreno et al,              Cured
 1989 (26)
Shadowen and               Cured
 Trevor, 1989 (27)
Golledge et al,            Cured
 1990 (28)
                           Died

Chippindale et al,         Cured
 1990 (29)

Chalstrey et al,           Cured
 1992 (30)
Weesner and                Cured
 Cisek, 1993 (8)
Cosgrove et al,            Cured
 1993 (31)
Carlson et al,             Cured
 1994 (32)
                           Cured



Ahkee et al,               Cured
 1994 (33)
Koay et al, 1995 (9)       Cured


                           Cured

Lustig et al, 1995 (10)    Cured


Karanas et al,             Cured
 1995 (34)

Goyal et al, 1995 (48)     Died
Barker et al, 1996 (35)    Cured

Stahlman et al,            Cured
 1996 (38)
De Sena et al,             Cured
 1996 (37)

                           Cured



Moller and Dreijer,        Cured
 1997 (38)
                           Cured





                           Cured

                           Cured



Gudinchet et al,           Cured
 1997 (39)

                           Cured


Venkataraman               Cured
 and Policar, 1997 (40)

Stallworth and             Cured
 Carroll, 1997 (41)

Lee et al, 1997  (47)      Cured




Williams et al,            Cured
 1998 (14)

Vandenberg and             Cured
 Hartig, 1998 (42)

Ellis et al, 1998 (43)     Cured


Schwartz and               Cured
 Nguyen, 1999 (44)





Alifano at al, 2000 (45)   Cured


Agarwal et al,             Cured
 2000 (48)



Moore et al, 2002 (+)      Cured



(*)Age in years.

(+)Present study.


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(51.) Duffey DC, Billings KR, Eichel BS, Sercarz JA. Internal jugular vein thrombosis. Ann Otol Rhinol Laryngol 1995;104:899-904.

(52.) Appelbaum PC, Spangler SK, Jacobs MR. Susceptibilities of 394 Bacteroides fragilis, non-B fragilis group Bacteroides species, and Fusobacterium species to newer antimicrobial agents. Antimicrob Agents Chemother 1991;35:1214-8.

From the Department of Otolaryngology-Head and Neck Surgery, the Vanderbilt Bill Wilkerson Center for Otolaryngology and Communication Sciences (Dr. Moore and Dr. Werkhaven), and the Department of Medicine (Dr. Dekle), Vanderbilt University Medical Center The Vanderbilt University Medical Center (VUMC) is a collection of several hospitals and clinics associated with Vanderbilt University in Nashville, Tennessee. It comprises the following units:[2]
  • Vanderbilt University Hospital
  • Monroe Carell, Jr.
, Nashville, Tenn.

Reprint requests: Brian A. Moore, MD, Department of Otolaryngology-Head and Neck Surgery, Suite 2900 TVC TVC Traditional Values Coalition
TVC Televisió de Catalunya (Catalan Public Broadcasting Company, Catalonia, Spain)
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, Vanderbilt University Medical Center, Nashville, TN 37232-5555. Phone: (615) 322-7267; fax: (615) 343-7604; e-mail: brian.moore@mcmail.vanderbilt.edu

Originally presented at the Southern Section meeting of the Triological Society; Marco Island, Fla.; Jan. 11-13, 2001.
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Comment:Bilateral Lemierre's syndrome: a case report and literature review. (Original Article).
Author:Werkhaven, Jay
Publication:Ear, Nose and Throat Journal
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Date:Apr 1, 2002
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