When contemplating the potential complications of a sore throat, it’s time to consider more than the usual suspects. Lemierrie’s syndrome might not be the zebra you thought it was.
The classic teaching, “When you hear hoof beats, think horses, not zebras,” holds true for many diseases. Not so for Lemierre’s, however. A zebra? Perhaps. However, it may be mislabeled due to a lack of awareness more so than a lack of occurrence. Although there have only been 160 cases reported in the past 100 years (American Journal of Roentgenology 187 (3): W324.), a resurgence of the disease has been reported (Postgrad Med J 2004;80:328–334). To avoid misdiagnosis, it’s wise to familiarize yourself with its characteristics.
Most of us were trained to be wary of the risks of undiagnosed and untreated group A Strep. But seriously, how many cases have any of us seen, particularly in contemporary times, of post-streptococcal glomerulonephritis or rheumatic fever, especially in the context of missed Strep pharyngitis presenting to the emergency department? It’s time to turn our attention to a more worthy pathogen, one that is much more likely to result in serious complications when missed. That etiologic agent is Fusobacterium necrophorum, an anaerobic, Gram-negative rod, which is the most common cause of Lemierre’s syndrome. Robert Centor, who developed the Centor criteria for Strep pharyngitis, reported in 2009, that 10% of pharyngitis cases in adolescents are caused by F. necrophorum. Thus, in 1 million cases of pharyngitis, 100,000 will be due to F. necrophorum, producing 250 cases of Lemierre’s, with 20 experiencing long-term complications and an additional 11 resulting in death. In an interesting comparison, Centor reported that with 100,000 cases of throat infection due to group A Streptococcus, 50 will develop rheumatic fever, 5 developing long-term complications and 1 death (Ann Intern Med 151(11):812, December 1, 2009).
Lemierre’s is defined as thrombophlebitis of the internal jugular and tonsilar veins. The infection originates in the pharynx and results in systemic, septic emboli seeding the central nervous system (i.e. cavernous sinus thrombosis and abscesses), lung, joints and even bones. The syndrome impacts previously healthy adolescents and young adults. Necrobacillosis is a term often used to describe infections from this etiologic agent due to its association with necrotic abscesses. The first case report of human infection was in 1900 by Courmont and Cade (Postgrad Med J 2004;80:328–334). However, Andre Lemierre defined this syndrome, his namesake, in 1936 publishing a case series of 20 patients, 18 of whom died. Based on his quote, once familiar with this syndrome, the diagnosis is easy to make. Unfortunately, just like sepsis, the diagnosis becomes more obvious as the severity of illness progresses. Also like sepsis, it is nearly impossible to predict which of those who appear less ill will actually develop more severe disease.
‘‘To anyone instructed as to the nature of these septicaemias it becomes relatively easy to make a diagnosis on the simple clinical findings, the appearance and repetition several days after the onset of a sore throat, of severe pyrexial attacks with an initial rigor and still more certainly the occurrence of pulmonary infarcts and arthritic manifestations make a syndrome that is so characteristic that mistake is almost impossible.”
(Lemierre A. Septicaemias and anaerobic organisms. Lancet 1936;i:701–3.)
The typical presentation is substantial increase in fever (39-41 oC), often associated with rigors, usually around 5 days after the onset of sore throat. By the time the diagnosis should be suspected, most will look pretty sick. Lemierre’s is only initially suspected in 15% of cases. However, one striking distinction may help the astute EP detect an early case. Although only seen in 26%-45% of cases, a hallmark finding of this disease is tenderness and swelling to the sternocleidomastoid (SCM) region of the neck. (Postgrad Med J 2004;80:328–334.) It’s time to change the way we examine patients and document those encounters. In cases of sore throat, particularly in adolescents and young adults, the presence or absence of SCM tenderness should be documented. The eye does not see what the mind does not know. Thus, if the patient presents with Lemierre’s, the focus of septic emboli may draw undue attention to that organ system and away from making the diagnosis. For instance, if the patient has a multiple pulmonary lesions, in an infectious context, Lemierre’s should move up the list, as pulmonary involvement is the most common seen in 80% of cases. (Journal of Medical Case Reports 2008, 2:374.) So, with multiple pulmonary lesions, the history and physical examination should include assessment for SCM tenderness and the presence or absence of recent sore throat with a more recent spike in fever.
In addition to pulmonary manifestations (i.e. pulmonary lesions, effusions and empyema), septic arthritis is reported in 13%-27% of cases, osteomyelitis may occur, cutaneous abscesses occur in up to 16%, splenic and/or hepatic abscesses have been reported (49% will have elevated liver function tests), cerebral abscesses and cavernous sinus thrombosis are possible, pericarditis and endocarditis are possible and DIC may be seen in up to 9%. (Postgrad Med J 2004;80:328–334.)
Diagnosis is challenging. Certainly, a negative rapid strep or culture for strep will not exclude this diagnosis or the presence of F. necrophorum. It is not easily detected. Thus, the gold standard is blood culture positive for the organism. Where does this leave us? We should have a high index of suspicion in adolescents and young adults and pursue the diagnosis when symptoms would suggest the possible development of Lemierre’s. Attempting to routinely screen for this organism would be pointless. Regarding internal jugular thrombosis, ultrasound, contrasted CT and MRI have all been utilized. The limitation to ultrasound is the anatomical obstructions created by the clavicles and the mandible. MRI probably has a slight advantage over CT. However, CT may be very useful in further defining the etiology of lung lesions detected on plain chest radiography. Regardless what imaging study is preferred, imaging should be performed when Lemierre’s is suspected and must be ruled out. This is not an outpatient diagnosis.
Management is largely supportive and includes hospitalization in all suspected cases. Systemic anticoagulation has been used in some cases. However, there is no clear consensus. Yet, if septic emboli seed to the cavernous sinus, anticoagulation is recommended. (Postgrad Med J 2004;80:328–334.) Broad-spectrum antimicrobials are essential. Interestingly, F. necrophorum has some unique characteristics. It is resistant to both gentamicin and fluoroquinolones. The organism is sensitive to clindamycin and metronidazole, with metronidazole prompting a more rapid treatment response. Although penicillin is not very effective against this organism, the addition of penicillin is recommended for the treatment of a possible polymicrobial infection. In case this disease wasn’t bad enough, cases of MRSA associated Lemierre’s have recently been reported in the literature. If MRSA is isolated, antimicrobial regimens should be adjusted accordingly.
Lemierre’s is a bad, bad disease. However, awareness goes a long way to making this diagnosis. Your suspicions should be high in previously healthy adolescent or young, adult patients with a recent history of sore throat and a new spike in temperature. Add tenderness to the SCM and throw in some pulmonary symptoms and this becomes a clinical diagnosis that can be easily made.
Lemierre’s: Horse or Zebra?
When you hear hoof beats, think horses, not zebras. However, the stealthiest diseases are the ones that seem to transform over time. For decades, our attention has been on group A Strep and it’s complications (i.e. rheumatic fever and glomerulonephritis). Perhaps, when concerns were much greater in the 1940s and 1950s, Strep was a pathogen to be concerned about. However, knowing that the incidence of rheumatic fever is less than 1 per million in the general populous, your worries should be over. Furthermore, as Dr. David Newman reported in EP Monthly in May, 2009, the incidence of post-streptococcal glomerulonephritis is so low that it would take treatment of more than 5,000 cases of Strep to prevent one case of glomerulonephritis. In the background of the Strep controversy has been the resurgence of Lemierre’s. Although considered by most to be an interesting cocktail party fascinoma, it has re-established itself as a diagnosis worthy of real consideration. This zebra is beginning to lose its stripes.