NOTE: The case for this month was donated by Michael
Cater, MD, and although the patient is slightly out of the pediatric age range,
it is a case worth reviewing.
A 21-year-old female presented to the ED with a 2-day
history of worsening shortness of breath and chest pain. The history of her
illness began 2 weeks earlier with fever, sore throat and symptoms consistent
with an upper respiratory tract infection.
James H. Brien
She was initially diagnosed clinically with
streptococcal tonsillitis and treated with azithromycin (Zithromax, Pfizer).
However, her throat culture was subsequently negative for Streptococcus
pyogenes (group A strep). As her symptoms persisted, she began feeling weak
and fatigued; she was then diagnosed with mononucleosis 5 days later, which was
serologically confirmed with a strongly positive Epstein-Barr virus (EBV) IgM
antibody level and a weakly positive IgG antibody, which is supportive of a
current infection. She was then treated with a short “burst” of oral
prednisone for the tonsillar pain and hypertrophy. After an initial period of
slight improvement, she was again febrile with worsening throat pain, leading
up to the symptoms that brought her into the ED.
Her medical history was that of a normal female
adolescent and young adult. Her immunizations were documented to be up-to-date.
She has had no significant infectious disease problems in the past.
Examination on admission to the ICU revealed fever of 103·F with respiratory distress. Her throat appeared to have erythematous, swollen tonsils, greater on the left with left-sided cervical lymphadenopathy and diffuse, painful swelling. Her breath sounds were positive for scattered wheezing with rales on the left. The rest of her exam was unremarkable.
Figure 1. Her admitting chest radiograph.
Source: Cater M
Figure 2. Her chest CT scan.
Her lab tests revealed a WBC count of 10,100 cells/mcL
and a platelet count of 33,000 cells/mcL with anemia. Her admitting chest
radiograph is shown in Figure 1, followed by a chest CT scan in Figure 2.
Empiric, broad-spectrum antimicrobial therapy was begun, and because of rapid
deterioration in her respiratory status, she was intubated and had chest tubes
inserted the next day (Figure 3) revealing exudative fluid. Cultures of the
pleural fluid were negative, but a blood culture performed on admission became
positive for an anaerobic, pleomorphic, gram-negative bacillus.
Figure 3. She was intubated and had chest tubes inserted the next day revealing exudative fluid.
What’s Your Diagnosis?
A.Haemophilus influenzae b sepsis with pneumonia
B.Streptococcus pyogenes sepsis with pneumonia
D.Epstein-Barr virus pneumonia
This is a case of (C) Lemierre syndrome (LS).
André Lemierre first described this condition in Paris in 1936, which is
classically caused by Fusobacterium necrophorum; a gram-negative,
pleomorphic anaerobic bacillus with a propensity to invade through damaged
mucous membranes and vascular structures of the tonsil and posterior pharynx,
resulting in septic thrombophlebitis of the great vessels of the neck,
resulting in septic emboli, some of which can be seen as nodules on the chest
CT scan (Figure 4) 1 week after admission.
Figure 4. Some can be seen as nodules on the chest CT scan in Figure 4, 1 week after admission.
Many papers have been written on this condition in a
variety of journals in the past 10 years because of a resurgence after a long
absence of mainstream medical attention, probably because of the frequent use
of antimicrobials for sore throats since the early 1940s. The reason(s) for
this recent increase in the incidence of LS remain largely speculative, but a
couple of theories have been proposed: 1) decreased use of antimicrobials, in
general, as a part of antimicrobial stewardship; and 2) increased use of
antimicrobials that may have less activity against F. necrophorum, such
as broad-spectrum cephalosporins and long-acting macrolides, such as
azithromycin for the treatment of streptococcal tonsillopharyngitis.
One thing appears to be clear: Coinfection with other
agents, particularly EBV (Figure 5, an adolescent with infectious
mononucleosis, courtesy of Andy Margileth, MD), plays a role in the
pathogenesis by damaging the mucous membrane.
Figure 5. An adolescent with infectious mononucleosis, courtesy of Dr. Andy Margileth.
In the case of EBV, temporary impairment of the immune
response may also play an important role. The case presented was recognized
early by confirmation of the thrombophlebitis of the internal jugular vein by
ultrasound and treated by aggressive antimicrobial therapy and surgical
drainage. Additionally, the patient had thrombocytopenia that is often seen
with this condition. The patient went on to full recovery, but not before
developing seizures as a result of three brain abscesses, one of which is shown
in Figure 6. A good choice for empiric antimicrobial treatment would be
meropenem (Merrem, AstraZeneca) or a combination of ceftriaxone plus
metronidazole, especially if there is CNS involvement. If there are brain
abscesses, the duration of therapy could be 4 to 6 weeks or longer.
Figure 6. The patient developed seizures as a result of three brain abscesses, one of which is shown.
S. pyogenes can certainly cause severe disease,
from peritonsillar abscesses (Figure 7) to toxic shock. However, the blood
culture was inconsistent with that organism. The same can be said about
Haemophilus influenzae type b. Although Hib is typically described as a
gram-negative, pleomorphic bacillus, it is not anaerobic; plus, it would be
very rare to see an immunized adult have an infection with this organism.
Figure 7. S. pyogenes can certainly cause severe disease, from peritonsillar abscesses to toxic shock.
EBV can involve virtually all systems, including the
lungs, but it is not going to result in pneumonia with an empyema and septic
The presentation of this patient is fairly typical and
can serve as an example of when to become concerned in a patient with
mononucleosis and or a “strep” infection that suddenly gets worse.
I want to thank Dr. Cater, a frequent contributor to
this column, for once again bringing to our attention an important medical
issue through one of his recent cases. Dr. Cater practices general pediatrics
in Tustin, Calif., and the Children’s Hospital of Orange County in
The treatment recommendations above were taken from the
2012-2013 Nelson’s Pediatric Antimicrobial Therapy, 19th edition,
pocketbook. I have possessed every issue (usually multiple copies of each) of
this handy reference since it was first published more than 30 years ago. The
editor in chief is now John S. Bradley, MD, and its founder, John D.
Nelson, MD, is emeritus editor. There’s also now an all-star cast of
six other contributing editors, making this clearly a must for anyone taking
care of children who may have an infectious disease. At about $30 per copy,
it’s the best deal in pediatric publications, when one considers how often
the book is used — in my case, several times a day. It can be ordered
through the AAP Bookstore.
Lastly, if you can figure out what drug is represented
by the molecular structure on the cover of the book, I will mention your name
among other talented chemists in next month’s column. Just let me know at
firstname.lastname@example.org. Remember, no cheating: You can’t call the publisher.
- James H. Brien, DO, is a member of the Infectious Diseases in Children Editorial Board, as well as Vice Chair for Education at The Children’s Hospital at Scott and White, and is the Associate Professor of Pediatrics at Texas A&M University, College of Medicine, Temple, Texas. email: email@example.com. Disclosure: Drs. Brien report no relevant financial disclosures.