Some thoughts on Lemierre’s syndrome

10

Category : Medical Rants

Readers know that I periodically write about Lemierre’s syndrome. I have given a number of talks on adolescent and adult pharyngitis recently – focusing on the importance of Lemierre’s syndrome.

As I have prepared for these talks, and some papers that I am writing, these thoughts have crystallized:

  • Lemierre’s, while an orphan disease, occurs frequently enough that at each talk several physicians come to discuss specific patients
  • Most Lemierre’s patients have significant delays in diagnosis and missed opportunities for admission
  • Adolescents and young adults are still dying or having significant morbidity
  • Even patients who do well usually have complex prolonged hospitalizations
  • The human suffering that these disease creates is beyond imagination
  • No one physician sees enough of this orphan disease to really understand it or champion this disease

Thus, I am struck with a growing realization that we have a disease that deserves CDC attention.  We have a disease that strikes otherwise health patients, predominantly between the ages 15-30, with a life threatening complex infection.  We have a disease that responds very well to early antibiotics.  We just need to attract more attention to either prevention or very early diagnosis.

Lemierre’s references

3

Category : Medical Rants

The Justin Rodgers Foundation (named after a teenager who died from Lemierre’s syndrome) has created a web site that will hopefully help patients and physicians.  I have decided to go through my references and suggest this list as an important reading list for physicians wanting to learn more about Lemierre’s.

References

1. Lemierre A. On Certain Septicemias due to anaerobic organisms. The Lancet. 1936;1:701-703.
2. Eykyn SJ. Necrobacillosis. Scandinavian journal of infectious diseases Supplementum. 1989;62:41-46.
3. Golledge CL, Beaman MH, Weeramanthri T, Riley TV. Necrobacillosis–primary anaerobic septicaemia due to Fusobacterium necrophorum. Australian and New Zealand journal of medicine. 1990;20:702-704.
4. Harar RP, MacDonald A, Pullen D, Ganesan S, Prior AJ. Lemierre’s syndrome: are we underdiagnosing this life-threatening infection? ORL J Otorhinolaryngol Relat Spec. 1996;58:178-181.
5. Hagelskjaer LH, Prag J, Malczynski J, Kristensen JH. Incidence and clinical epidemiology of necrobacillosis, including Lemierre’s syndrome, in Denmark 1990-1995. Eur J Clin Microbiol Infect Dis. 1998;17:561-565.
6. Brazier JS, Hall V, Yusuf E, Duerden BI. Fusobacterium necrophorum infections in England and Wales 1990-2000. Journal of Medical Microbiology. 2002;51:269-272.
7. Chirinos JA, Lichtstein DM, Garcia J, Tamariz LJ. The evolution of Lemierre syndrome: report of 2 cases and review of the literature. Medicine (Baltimore). 2002;81:458-465.
8. Ramirez S, Hild T, Rudolph C et al. Increased Diagnosis of Lemierre Syndrome and Other Fusobacterium necrophorum Infections at a Children’s Hospital. PEDIATRICS. 2003;112:e380-e380.
9. Bliss SJ, Flanders SA, Saint S. Clinical problem-solving. A pain in the neck. N Engl J Med. 2004;350:1037-1042.
10. Brazier J. Human infections with Fusobacterium necrophorum. Anaerobe. 2006;12:165-172.
11. Jensen A, Hagelskjaer Kristensen L, Prag J. Detection of Fusobacterium necrophorum subsp. funduliforme in tonsillitis in young adults by real-time PCR. Clin Microbiol Infect. 2007;13:695-701.
12. Riordan T. Human Infection with Fusobacterium necrophorum (Necrobacillosis), with a Focus on Lemierre’s Syndrome. Clinical Microbiology Reviews. 2007;20:622-659.
13. Hagelskjær Kristensen L, Prag J. Localised Fusobacterium necrophorum infections: a prospective laboratory-based Danish study. Eur J Clin Microbiol Infect Dis. 2008;27:733-739.
14. Hagelskjær Kristensen L, Prag J. Lemierre’s syndrome and other disseminated Fusobacterium necrophorum infections in Denmark: a prospective epidemiological and clinical survey. Eur J Clin Microbiol Infect Dis. 2008;27:779-789.
15. Lu MD, Vasavada Z, Tanner C. Lemierre syndrome following oropharyngeal infection: a case series. Journal of the American Board of Family Medicine : JABFM. 2009;22:79-83.

 

Another Lemierre’s story

0

Category : Medical Rants

 

'It almost killed my daughter.' Tracking down a rare and lethal disease

 

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Questions on Lemierre’s

0

Category : Medical Rants

 

Woody writes:

1. Do not use macrolides (erythromycin or azithromycin) as empiric therapy for pharyngitis. Stick with penicillin or cephalosporins. Macrolides do not treat Fusobacterium necrophorum.

in the patient who has pencillin allergy (non-anaphylactic), and unwilling to accept the 10% chance of cross-reactivity with cephalosporins, are you then choosing clindamycin rather than a macrolide?

First, I always make certain that the patient really does have a penicillin allergy.  With a history of rash, I favor using a cephlosporin.  Clindamycin is probably a reasonable second choice.

2. Remember the natural history of pharyngitis. Most pharyngitis improves over 2-5 days. When pharyngitis is worsening, with or without treatment, physicians should re-evaluate the patient and consider suppurative complications – peritonsillar abscess and Lemierre’s

let’s say you have a negative rapid strep. you are presuming a viral etiology. patient gets symptomatically worse over the next few days, but no peritonsillar abscess/cellulitis, trismus, submandibular or anterior cervical swelling other than adenopathy, and they are swallowing saliva and fluids, but with some difficulty. are you treating these patients with penicillin despite the negative rapid strep or throat culture? going broader to get better anaerobic coverage, with say augmentin?

One final comment…i am starting to think that finding lemierre’s in it’s early stages is like trying to figure out who among the typical sore throats that i see is going to get a peritonsillar abscess. i have not figured out a way to do that. all i know to do is educate the patient to return promptly if their voice becomes muffled, problems opening mouth, neck swelling, or great difficulty in swallowing.

Negative rapid strep and worsening pharyngitis raises an interesting differential diagnosis.  Remember that the rapid strep test only has a sensitivity of 80-90%.  Sometimes we do not get an adequate throat swab.  Sometimes we have sampling error.  So a negative rapid test does not eliminate group A strep as a possibility. 

Next, consider the non-group A strep – groups C and G.  In adolescents they cause approximately 1/3 as many sore throats as group A strep (this is not true for pre-adolescents. 

Always consider infectious mononucleosis in adolescents with worsening pharyngitis.  Also remember that acute HIV infection can present as a sore throat.

Finally, we must consider peritonsillar abscess and Lemierre’s.  We should get clues from a careful physical examination.  We should examine the patient for neck swelling or asymmetric tonsillar swelling.

The key point is patient education.  We should tell patients that if they are worsening in 3-5 days that we should re-examine them, perhaps do further testing and generally view the patient as having a potentially serious infection.

 

I hope this discussion is worthwhile.

 

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Considering Lemierre’s and fusobacterium necrophorum

2

Category : Medical Rants

 

A reader writes:

I am curious about your current approach in screening for fusobacterium. As I understand it, you would need an anaerobic culture to isolate this organism. Under what circumstances are you ordering this test? Are you doing this if a patient returns to you within 72 hours with a worsening sore throat…or are you simply empirically treating with pencillin or metronidazole in the penicillin allergic patient without culture in that circumstance?

We do not have enough evidence to look for Fusobacterium necrophorum in routine pharyngitis.  I know of 2 cultures studies and 2 PCR studies which suggest an incidence of 10% in adolescent pharyngitis.  We need more studies on the clinical manifestations of Fusobacterium necrophorum  pharyngitis.  We do not know what the clincial presentation is.  Hopefully, we can develop a rapid test to screen for this infection.

In the meantime, I recommend two things:

  1. Do not use macrolides (erythromycin or azithromycin) as empiric therapy for pharyngitis.  Stick with penicillin or cephalosporins.  Macrolides do not treat Fusobacterium necrophorum. 
  2. Remember the natural history of pharyngitis.  Most pharyngitis improves over 2-5 days.  When pharyngitis is worsening, with or without treatment, physicians should re-evaluate the patient and consider suppurative complications – peritonsillar abscess and Lemierre’s.

 

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Lemierre’s – what we do not know and what we do know

2

Category : Medical Rants

 

  1. Not all cases of Lemierre’s occur secondary to Fusobacterium necrophorum – probably about 80%
  2. Standard culture techniques will not grow Fusobacterium necrophorum
  3. We do not know the clinical manifestations of Fusobacterium necrophorum pharyngitis – does this pharyngitis look like strep throat or is it less severe
  4. Would treatment of Fusobacterium necrophorum pharyngitis prevent Lemierre’s – one would think so – but we have no data

We are in the early stages of developing knowledge about Fusobacterium necrophorum pharyngitis.  We need much more knowledge about the infection and development of Lemierre’s.  We can make educated guesses, but they are only guesses.

We do know that early diagnosis leads to better outcomes.  We cannot blame physicians for their lack of knowledge, no pharyngitis guidelines even mention Lemierre’s. 

What philosophy should we take towards a rare disease?

I would always argue that we must know all about diseases that cause great morbidity and mortality, yet are treatable.  We cannot afford to miss these diagnoses.  We must develop new strategies for Lemierre’s.

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Lisa Sanders on Lemierre’s

5

Category : Medical Rants

 

Tomorrow’s NY Times Sunday Magazine features Justin’s story – The Strep Throat that wasn’t

As readers know, I write frequently about this orphan disease.  Let me quote from the newspaper interview that I recently gave:

Extrapolating data from the Denmark study, he figures there are between 500 and 1,000 cases of Lemierre’s annually in the United States, 10 percent of which are fatal. It strikes approximately one in 70,000 adolescents, he surmises.

But the thing about Lemierre’s, which Centor said many doctors know nothing about, is that it’s treatable if detected early.

Smith’s elixir, as his mother put it, was "good old-fashioned" penicillin.

Centor believes the disease can be controlled if patients can be diagnosed much earlier.

"It’s a rare disease that kills adolescents that shouldn’t kill adolescents," he said. "That’s what makes my blood boil."

I have nothing personal to gain here.  I have a major administrative position and already have national recognition.  But someone in medicine has to champion this disease.  Because of this blog, I have decided to be the temporary champion.

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Another Lemierre’s story

1

Category : Medical Rants

 

I am quoted extensively in this newspaper report – Fighting for his life

This reporter did a wonderful job of researching and summarizing what we know about Lemierre's syndrome.

Should Lemierre’s Syndrome re-emergence change pharyngitis guidelines?

1

Category : Medical Rants

That is the title of the article that I have worked on for the past 3 weeks.  The writing process involves thinking for a long time, writing a first draft, and then revise, revise, revise.

Clearly my recent Grand Rounds presentation was the impetus for writing and submitting this article (I do plan to submit it tomorrow).

This is not the first article that blogging has stimulated.  As I tell the story at Grand Rounds, my interest in Lemierre’s comes directly from a 2002 rant.  Each time that I would write about Lemierre’s I would learn more and thus realize that no one else in the US is currently writing about this syndrome.

I hope that I can get this published at my first choice journal, but if not, I will keep submitting until I find the proper journal.

In advance, I thank the readers who have kindled my interest.  I especially thank the families of Lemierre’s syndrome victims.  I think about them whenever I discuss this disease.

 

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Why championing Lemierre’s is worthwhile

3

Category : Medical Rants

 

A reader resorts to an ad hominem attack.

I don’t want to sound insulting, but you sound like an academic physician in an ivory tower with a moral mission looking for publications. This is very clearly a very rare disease, and although in a perfect world nobody would die from anything they don’t have to die from, your goals to totally prevent or consistently diagnose Lemierre’s is not only bound for failure, but misdirected energy. Doesn’t the fact that you’ve never personally seen a case of Lemierrre’s clue you in? If you look at the how Lemierre’s is described, most are rapidly progressive and may respond to IV antibiotics if at all, and with anticoagulation; the only clue is a prior dental procedure. Now, tell me how many patients with sore throat after a dental procedure you have, and how many of those you are going to send to the hospital for immediate antibiotics/anticoagulation and cause significant morbidity or mortality? Your goal just doesn’t make sense. Perhaps a much better goal is creating a clinical picture of how a Lemierre’s patient looks like, and making physicians aware. Before emotionally pledging yourself to a goal and getting caught in the drama of Lemierre’s, you should look at this from a medical scientist’s position.

Please go back and read me rant, because I do not believe that this commenter has read the literature or the rant carefully.  There are 2 key strategies which I am endorsing.  First, we need to understand Fusobacterium necrophorum pharyngitis.  Perhaps we can figure out which patients deserve empiric antibiotics.  Second, all pharyngitis patients should have a careful evaluation when they are not improving within 2-3 days, and especially if they are getting worse.  If we do not carefully reevaluate those patients we can miss either Lemierre’s or peritonsillar abscess (I have seen abscess several times.)  These are not radical nor pie in the sky solutions.

Lemierre’s rarely follows dental procedures.  Early diagnosis leads to much better outcomes than delayed diagnosis.  We can expect early diagnosis with a better approach to pharyngitis.

I am a practicing physician as well as an academician.  I am approaching this scientifically. 

Why do I care?  I have talked to the parents of two adolescents who died, probably both because of late diagnosis.  I care because I am a physician.  I care because this disease strikes innocent young people, and they deserve having someone care.

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