This is a 2-1/2 year old male who presents to an 
acute care clinic with a chief complaint of coughing and 
fever.  He began coughing three days ago.  His cough 
is now sounding worse.  It sounds harsh and on further 
inquiry, it sounds like a barking seal.  He was noted to 
be warm yesterday, but his temperature was not 
measured.
     His past history is largely negative, but his 
immunization status is incomplete.  He immigrated from 
Asia two weeks ago.  He is known to have been 
immunized, at least partially, against typhoid and polio.  
He had a negative TB skin test at 12 months of age.  
He probably has not received any MMR or DPT 
immunizations.
     Exam:  T38.3 (rectal), P100, R24, BP 109/73, 
oxygen saturation 95% to 99% in room air.  He is alert, 
but is noted to be drooling.  He has stridor at rest with 
mild retractions.  An occasional croupy cough is noted.  
He does not appear to be toxic.  Head normocephalic.  
Eyes clear and moist.  No pallor.  Nose clear mucus.  
Oral mucosa pink and moist.  Thick yellow and white 
exudates are noted on the tonsils, the uvula, and the 
posterior pharynx.  The epiglottis is not visualized.  
Neck supple, with several 1 cm nodes.  Heart regular, 
no murmurs or gallops.  Lungs with inspiratory stridor at 
rest.  Aeration is good.  No wheezes or rales.  
Abdomen negative.  Normal genitalia.  Color, perfusion, 
pulses and turgor are good.  Strength and movement 
good.  Sensation intact.  He is able to ambulate.
      A lateral neck and chest radiographs are obtained.

View lateral neck radiograph.



View chest radiograph.

     This lateral neck radiograph shows a normal 
epiglottis and no pre-vertebral soft tissue widening.  
There is significant subglottic narrowing.  While this is 
radiographically consistent with croup, this patient 
clinically may have more than just croup.  The oral 
exam in croup is most often normal.  The epiglottis can 
often be visualized if the patient is cooperative and can 
open widely enough.  In other instances, the epiglottis 
can be visualized by depressing the tongue with a 
tongue blade.  In this patient's case, his exam reveals 
extensive exudates over his tonsils.  Additionally, 
exudates are noted on the posterior pharynx and uvula.
     Because of his lack of DPT immunization, diphtheria 
is suspected.  He is hospitalized in an intensive care 
unit.  He is treated with IV penicillin and diphtheria 
anti-toxin.  A cardiac work-up is negative.  During 
hospitalization, his stridor worsens and he requires 
intubation.  During intubation, his larynx and epiglottis 
are noted to be edematous.  Following intubation, his 
condition improves.  He is eventually extubated and is 
subsequently discharged in good condition.  Throat 
cultures for diphtheria are positive.  Nasopharyngeal 
cultures for diphtheria are negative.  Group A 
streptococcal cultures are negative. 

Discussion
     Corynebacterium diphtheriae are gram positive 
pleomorphic rods.  However, they stain irregularly and 
their morphology depends on the media that they are 
grown on.
     C. diphtheriae causes clinical disease by infection of 
tissues and/or through the elaboration of toxin.  The 
clinical signs and symptoms of diphtheria depend on 
the site of infection, the immunization status of the 
patient, and whether or not toxin is being produced by 
C. diphtheriae.
     C. diphtheriae generally infects mucosal surfaces.  
While the eyes and genital mucosal surfaces are 
occasionally involved, C. diphtheriae, most often infects 
nasal, tonsillar, pharyngeal, laryngeal, and tracheal 
mucosal surfaces.
     Nasal diphtheria presents as a mild upper 
respiratory infection progressing to serosanguinous and 
mucopurulent nasal discharge with nasal excoriation.  A 
white membrane may be visible on the nasal septum 
and a foul odor may be present.
     Tonsillar and pharyngeal diphtheria have symptoms 
similar to a severe tonsillitis.  A white membrane is 
visible covering the tissues including the uvula, palate, 
tonsils, and pharynx.  The membrane may extend down 
into the larynx and trachea (visible on laryngoscopy 
and/or bronchoscopy).  Attempts to remove this 
membrane, result in bleeding.  Lymphadenopathy 
and/or generalized edema of the neck may be evident.  
Partially immunized patients may have incomplete 
presentations such that the white membrane does not 
form.
     Laryngeal diphtheria results from downward 
extension of pharyngeal diphtheria.  Laryngeal 
involvement is characterized by croup-like symptoms 
such as stridor, drooling, hoarseness and a barking 
cough.  Airway obstruction is more likely to progress to 
a severe degree.  The trachea and bronchi may also be 
involved.  Radiologic features of laryngeal diphtheria 
may be identical to viral croup (i.e., mild to moderate 
subglottic edema).  However, the clinical features, 
especially the appearance of the pharynx is usually 
different.  In severe cases of laryngeal diphtheria, a 
membrane may be visible on the lateral neck 
radiograph and the degree of subglottic edema seen 
radiographically is more severe.  This radiographic 
appearance is termed, "membranous croup".

View membranous croup radiograph.

     This radiograph shows subglottic narrowing.  The 
black arrow points to a distortion within the airway 
resembling a membrane.  To appreciate this, you must 
turn down the room lights and step back away from the 
monitor.  Hopefully, you can now appreciate some 
distortion in the airway.
     The differential of membranous croup is not limited 
to diphtheria.  It also includes bacterial tracheitis (also 
called bacterial croup or bacterial 
laryngotracheobronchitis) and anatomic laryngeal 
anomalies such as laryngeal/tracheal webs.  The 
presence of the membrane cannot be relied upon to 
make the diagnosis since it is only rarely visible.  The 
diagnosis of diphtheria, bacterial tracheitis, and 
laryngotracheal anomalies must often be made clinically 
and later confirmed by CT, fluoroscopy, laryngoscopy 
or bronchoscopy.  Patients with bacterial tracheitis will 
usually appear toxic.  They may have high fever and a 
leukocytosis.  Their airway symptoms are generally 
more severe and they may rapidly worsen.  
Laryngotracheal anomalies usually have a prolonged or 
recurrent course of airway difficulty.  

Systemic complications of Diphtheria
     Toxin elaborated by C. diphtheriae is cardiotoxic and 
neurotoxic.  Not all C. diphtheria infections result in 
toxin production since toxin production depends upon 
the strain of the bacteria and often whether a phage 
virus is present.  Early administration of antitoxin can 
prevent the toxin mediated complications.
     Myocarditis may develop during the second week of 
illness.  Signs and symptoms of myocarditis include 
congestive heart failure, tachycardia, muffled heart 
tones, murmurs, and dysrhythmia.  Myocardial 
complications are generally reversible following 
antibiotic treatment, anti-toxin administration, and 
eradication of the C. diphtheriae infection.
     Neurologic complications appear after varying latent 
intervals.  Examples include paralysis of the soft palate, 
oculomotor paresis, dysphagia, diaphragmatic 
weakness, peripheral neuropathy, etc.  Since these 
complications are largely motor and CSF protein is 
elevated, these findings are difficult to distinguish from 
Guillain-Barre syndrome.
     Rare complications include vascular instability, 
gastritis, hepatitis, nephritis and hemolytic uremic 
syndrome.
     The diagnosis of diphtheria should be made 
clinically.  Waiting for cultures to confirm the diagnosis 
may result in a delay in anti-toxin administration and 
toxin-mediated complications.  Material from beneath 
the white membrane or the membrane itself should be 
sent for gram stain and culture.  Fluorescent antibody 
and other rapid immunologic methods may be able to 
confirm the identification of the organism right away.  A 
"Schick" test may be used to determine diphtheria 
susceptibility, however, its interpretation is not simple 
and it cannot be read for 3 to 5 days (refer to other 
references for more discussion on the Schick test).

Diphtheria toxoid immunization and antitoxin
     Diphtheria vaccine is a toxoid which results in 
immunity against the C. diphtheriae toxin.  Note that 
while the vaccine is directed at the toxin and NOT at the 
bacteria, a well-immunized individual is protected from 
the toxin and the non-toxin mediated complications of 
diphtheria.  Diphtheria vaccine does not fully immunize 
against infection since carrier states and mild infections 
are still possible in immunized individuals.  However, 
vaccine does prevent severe infection.
     While most children in the U.S. are fully immunized 
against diphtheria, many adults are not routinely 
immunized.  While tetanus toxoid is commonly 
administered in emergency departments for tetanus 
wound prophylaxis, there is no routine for diphtheria 
vaccine.  For this reason, most emergency departments 
administer diphtheria-tetanus toxoid (combined dT) 
instead of plain tetanus toxoid when tetanus 
prophylaxis is indicated.  Pregnancy and known 
diphtheria toxoid hypersensitivity are indications for 
plain tetanus toxoid (without diphtheria toxoid) when 
tetanus prophylaxis is indicated.
     The patient in this case had probably not received 
any DPT vaccines.  Being susceptible, he developed a 
severe pharyngeal and laryngotracheal diphtheria 
infection.  Since antitoxin was administered early, he 
sustained no toxin mediated complications.
     Diphtheria anti-toxin is of horse serum origin, 
therefore horse serum hypersensitivity may occur.  
Antibiotics (penicillins and erythromycin) shorten the 
course of illness by limiting infection.  However, 
antibiotics may not be effective in preventing 
toxin-mediated complications.

References
     Feigin RD, Strechenberg BW, Strandgaard BH.  
Diphtheria.  In:  Feigin RD, Cherry JD (eds).  Textbook 
of Pediatric Infectious Diseases, third edition.  W.B. 
Saunders, Philadelphia, 1992, pp. 1110-1116.
     Fleisher GR.  Infectious Disease Emergencies.  In:  
Fleisher GR, Ludwig S (eds).  Textbook of Pediatric 
Emergencies, third edition.  Williams & Wilkins, 
Baltimore, 1993, p 621.