A three-year-old girl is put to bed by her parents with a low grade fever. She awakes in the middle of the night, and her parents discover that her fever is higher and her voice does not sound normal. The girl is irritable and has difficulty swallowing when given some water to drink. She is also starting to experience considerable difficulty in breathing, so her parents become alarmed and call their pediatrician. They are told to take the girl to the emergency room of the local hospital immediately, which they do. On physical examination at the ER, the physicians note that the girl tends to sit leaning forward, with her mouth open and chin extended, in what appears to be an effort to breathe more easily. She is also drooling. Her voice sounds muffled, as if she is talking with a hot potato in her mouth (a condition known as "hot potato voice"). The child is transported sitting up to the operating room, where her airway is secured by insertion of an endotracheal tube. After the airway is secured, examination with a fiberoptic laryngoscope shows that her epiglottis is cherry red and swollen.

Question 2.1: What is your diagnosis?

The symptoms are consistent with a diagnosis of acute epiglottitis (also known as supraglottitis), a rapidly progressing, life threatening cellulitis of the epiglottis that can cause obstruction of the airway and subsequent asphyxiation. (The differential includes croup, angioedema, peritonsilar abscess, retropharyngeal abscess, diphtheria, foreign body aspiration, and lingual tonsillitis.)

Question 2.2: Why was the airway secured before the throat was examined?

Epiglottitis constitutes a medical emergency because occlusion of the airway can occur suddenly. Immediate treatment is essential. Direct viewing of the pharynx by use of a tongue blade should not be attempted when epiglottitis is suspected, because this can lead to reflex laryngospasm and immediate airway obstruction. When diagnosing a child, the examination must be done expediently, but with careful attention so as not to increase the child's anxiety. Increased anxiety from even minor annoyances (e.g., placement of ECG leads) might also result in reflex laryngospasm, acute airway obstruction and respiratory arrest. The child should remain with a trusted caretaker at all times, preferably in their arms. Lateral neck x-rays that indicate an enlarged epiglottis (the "thumb sign") are useful if they are positive but may be falsely negative. The value of obtaining such films has also been questioned because doing so might cause a critical delay in securing the airway. The epiglottis may be visualized with a fiberoptic laryngoscope, but this should be done only in an operating room or similar environment in which all preparations for immediate airway control are in place.

Most hospitals have a predetermined protocol for management of patients with epiglottitis, and it is the physician's responsibility to be aware of this protocol and to institute it promptly. The necessary personnel include an anesthesiologist skilled at performing pediatric intubation, an endoscopist in the event of difficult intubation and the need for direct visualization of the airway, and an intensivist to manage the patient postoperatively.

Question 2.3: What is the most likely causative agent?

Nearly all cases of epiglottitis in children are caused by Haemophilus influenzae type b, which is a Gram-negative, rod shaped (sometimes pleomorphic) bacterium. Type b H. influenzae can be isolated from the bloodstream of nearly 100% of affected children. In adults, blood cultures are positive in about 25% of cases, all of which are caused by H. influenzae. Other bacteria isolated from the pharynx of adults with epiglottitis include Streptococcus pneumoniae, group B streptococci, Haemophilus parainfluenzae, and (rarely) Staphylococcus aureus. It is not clear whether these organisms are the actual causative agents of epiglottitis, as opposed to being coincidentally present in the throat area.

Question 2.4: How does this agent cause epiglottitis?

Haemophilus influenzae is an obligate parasite. Type b strains are uncommon in the upper respiratory tract or are present in only very low numbers, but they have been a very frequent cause of disease in children. Pili and other adhesins mediate the colonization of this bacterium in the oropharynx, and components of the cell wall (e.g., LPS) impair ciliary function, resulting in damage to the respiratory epithelium. The bacteria may then be translocated across the epithelial and endothelial membranes and can enter the bloodstream. Epiglottitis usually begins as a cellulitis between the base of the tongue and epiglottis that pushes the epiglottis posteriorly. The epiglottis itself then becomes swollen, threatening to block the airway.

Question 2.5: How should this case be treated?

All patients should be closely monitored in an intensive care unit and should be given antibiotics that are active against H. influenzae. Recommended routines include ceftriaxone (80-100 mg/kg per day, in two divided doses), cefotaxime (50-180 mg/kg per day, in four divided doses), or ampicillin (200 mg/kg per day, in four divided doses) with chloramphenicol (75-100 mg/kg per day, in four divided doses). The drugs are given intravenously, usually for at least 7 days. Blood and epiglottis cultures are routinely ordered during the initial examination and securing of the airway, and the antibiotic regimen may be altered on the basis of the culture results if needed (e.g., in the case of a resistant strain or unexpected causative agent). The lab should be asked to look specifically for Haemophilus influenzae because specialized media are required to culture it. The most common choice is "chocolate" (heated-blood) agar, which contains the X factor (hematin) and V factor (nicotinaminde adenine dinucleotide) that are required by most H. influenzae strains.

Question 2.6: How is this disease prevented?

A vaccine against H. influenzae type b is now available and has greatly reduced the incidence of childhood diseases caused by this organism. The vaccine stimulates the production of antibodies against the polysaccharide capsule of the bacterium, which contains polyribitol phosphate (PRP) and inhibits phagocytosis. The antibodies attach to the surface of the capsule, thus rendering the bacterium more susceptible to phagocytosis and subsequent digestion. If a patient with H. influenzae epiglottitis has had household contact that includes an unvaccinated child less than 4 years old, all members of the household should receive prophylactic rifampin to eradicate the possible carriage of H. influenzae.