Etiology and Epidemiology

With the exceptions of diphtheria, bacterial tracheitis, and epiglottitis, most acute infections of the upper airway are caused by viruses. The parainfluenza viruses (types 1, 2, and 3; Chapter 251) account for ∼75% of cases; other viruses associated with croup include influenza A and B, adenovirus, respiratory syncytial virus (RSV), and measles. Influenza A has been associated with severe laryngotracheobronchitis. Mycoplasma pneumoniae has rarely been isolated from children with croup and causes mild disease (Chapter 215). Most patients with croup are between the ages of 3 mo and 5 yr, with the peak in the 2nd yr of life. The incidence of croup is higher in boys; it occurs most commonly in the late fall and winter but can occur throughout the year. Recurrences are frequent from 3-6 yr of age and decrease with growth of the airway. Approximately 15% of patients have a strong family history of croup.

In the past, Haemophilus influenzae type b was the most commonly identified etiology of acute epiglottitis. Since the widespread use of the HiB vaccine, invasive disease due to H. influenzae type b in pediatric patients has been reduced by 80-90% (Chapter 186). Therefore, other agents, such as Streptococcus pyogenes, Streptococcus pneumoniae, and Staphylococcus aureus, now represent a larger portion of pediatric cases of epiglottitis in vaccinated children. In the prevaccine era, the typical patient with epiglottitis due to H. influenza type b was 2-4 yr of age, although cases were seen in the 1st year of life and in patients as old as 7 yr of age. The typical patient with epiglottitis is an adult with a sore throat, although cases still do occur in underimmunized children; vaccine failures have been reported.

Clinical Manifestations

Croup (Laryngotracheobronchitis)

Viruses most commonly cause croup, the most common form of acute upper respiratory obstruction. The term laryngotracheobronchitis refers to viral infection of the glottic and subglottic regions. Some clinicians use the term laryngotracheitis for the most common and most typical form of croup and reserve the term laryngotracheobronchitis for the more severe form that is considered an extension of laryngotracheitis associated with bacterial superinfection that occurs 5-7 days into the clinical course.

Most patients have an upper respiratory tract infection with some combination of rhinorrhea, pharyngitis, mild cough, and low-grade fever for 1-3 days before the signs and symptoms of upper airway obstruction become apparent. The child then develops the characteristic “barking” cough, hoarseness, and inspiratory stridor. The low-grade fever can persist, although temperatures can reach 39-40°C (102.2-104°F); some children are afebrile. Symptoms are characteristically worse at night and often recur with decreasing intensity for several days and resolve completely within a week. Agitation and crying greatly aggravate the symptoms and signs. The child may prefer to sit up in bed or be held upright. Older children usually are not seriously ill. Other family members might have mild respiratory illnesses with laryngitis. Most young patients with croup progress only as far as stridor and slight dyspnea before they start to recover.

Physical examination can reveal a hoarse voice, coryza, normal to moderately inflamed pharynx, and a slightly increased respiratory rate. Patients vary substantially in their degrees of respiratory distress. Rarely, the upper airway obstruction progresses and is accompanied by an increasing respiratory rate; nasal flaring; suprasternal, infrasternal, and intercostal retractions; and continuous stridor. Croup is a disease of the upper airway, and alveolar gas exchange is usually normal. Hypoxia and low oxygen saturation are seen only when complete airway obstruction is imminent. The child who is hypoxic, cyanotic, pale, or obtunded needs immediate airway management. Occasionally, the pattern of severe laryngotracheobronchitis is difficult to differentiate from epiglottitis, despite the usually more acute onset and rapid course of the latter.

Croup is a clinical diagnosis and does not require a radiograph of the neck. Radiographs of the neck can show the typical subglottic narrowing, or steeple sign, of croup on the posteroanterior view (Fig. 377-1). However, the steeple sign may be absent in patients with croup, may be present in patients without croup as a normal variant, and may rarely be present in patients with epiglottitis. The radiographs do not correlate well with disease severity. Radiographs should be considered only after airway stabilization in children who have an atypical presentation or clinical course. Radiographs may be helpful in distinguishing between severe laryngotracheobronchitis and epiglottitis, but airway management should always take priority.

Figure 377-1 Radiograph of an airway of a patient with croup, showing typical subglottic narrowing (steeple sign).

Acute Epiglottitis (Supraglottitis)

This dramatic, potentially lethal condition is characterized by an acute rapidly progressive and potentially fulminating course of high fever, sore throat, dyspnea, and rapidly progressing respiratory obstruction. The degree of respiratory distress at presentation is variable. The initial lack of respiratory distress can deceive the unwary clinician; respiratory distress can also be the 1st manifestation. Often, the otherwise healthy child suddenly develops a sore throat and fever. Within a matter of hours, the patient appears toxic, swallowing is difficult, and breathing is labored. Drooling is usually present and the neck is hyperextended in an attempt to maintain the airway. The child may assume the tripod position, sitting upright and leaning forward with the chin up and mouth open while bracing on the arms. A brief period of air hunger with restlessness may be followed by rapidly increasing cyanosis and coma. Stridor is a late finding and suggests near-complete airway obstruction. Complete obstruction of the airway and death can ensue unless adequate treatment is provided. The barking cough typical of croup is rare. Usually, no other family members are ill with acute respiratory symptoms.

The diagnosis requires visualization of a large, cherry red, swollen epiglottis by laryngoscopy. Occasionally, the other supraglottic structures, especially the aryepiglottic folds, are more involved than the epiglottis itself. In a patient in whom the diagnosis is certain or probable based on clinical grounds, laryngoscopy should be performed expeditiously in a controlled environment such as an operating room or intensive care unit. Anxiety-provoking interventions such as phlebotomy, intravenous line placement, placing the child supine, or direct inspection of the oral cavity should be avoided until the airway is secure. If epiglottitis is thought to be possible but not certain in a patient with acute upper airway obstruction, the patient can undergo lateral radiographs of the upper airway first. Classic radiographs of a child who has epiglottitis show the thumb sign (Fig. 377-2). Proper positioning of the patient for the lateral neck radiograph is crucial in order to avoid some of the pitfalls associated with interpretation of the film. Adequate hyperextension of the head and neck is necessary. In addition, the epiglottis can appear to be round if the lateral neck is taken at an oblique angle. If the concern for epiglottitis still exists after the radiographs, direct visualization should be performed. A physician skilled in airway management and use of intubation equipment should accompany patients with suspected epiglottitis at all times. An older cooperative child might voluntarily open the mouth wide enough for a direct view of the inflamed epiglottis.

Figure 377-2 Lateral roentgenogram of the upper airway reveals the swollen epiglottis (thumb sign).

Establishing an airway by nasotracheal intubation or, less often, by tracheostomy is indicated in patients with epiglottitis, regardless of the degree of apparent respiratory distress, because as many as 6% of children with epiglottitis without an artificial airway die, compared with <1% of those with an artificial airway. No clinical features have been recognized that predict mortality. Pulmonary edema can be associated with acute airway obstruction. The duration of intubation depends on the clinical course of the patient and the duration of epiglottic swelling, as determined by frequent examination using direct laryngoscopy or flexible fiberoptic laryngoscopy. In general, children with acute epiglottitis are intubated for 2-3 days, because the response to antibiotics is usually rapid (see later). Most patients have concomitant bacteremia; occasionally, other infections are present, such as pneumonia, cervical adenopathy, or otitis media. Meningitis, arthritis, and other invasive infections with H. influenzae type b are rarely found in conjunction with epiglottitis.

Differential Diagnosis

These 4 syndromes must be differentiated from one another and from a variety of other entities that can present as upper airway obstruction. Bacterial tracheitis is the most important differential diagnostic consideration and has a high risk of airway obstruction. Diphtheritic croup is extremely rare in North America, although a major epidemic of diphtheria occurred in countries of the former Soviet Union beginning in 1990 from the lack of routine immunization. Early symptoms of diphtheria include malaise, sore throat, anorexia, and low-grade fever. Within 2-3 days, pharyngeal examination reveals the typical gray-white membrane, which can vary in size from covering a small patch on the tonsils to covering most of the soft palate. The membrane is adherent to the tissue, and forcible attempts to remove it cause bleeding. The course is usually insidious, but respiratory obstruction can occur suddenly. Measles croup almost always coincides with the full manifestations of systemic disease and the course may be fulminant (Chapter 238).

Sudden onset of respiratory obstruction can be caused by aspiration of a foreign body (Chapter 379). The child is usually 6 mo-3 yr of age. Choking and coughing occur suddenly, usually without prodromal signs of infection, although children with a viral infection can also aspirate a foreign body. A retropharyngeal or peritonsillar abscess can mimic respiratory obstruction (Chapter 374). CT scans of the upper airway are helpful in evaluating the possibility of a retropharyngeal abscess. A peritonsillar abscess is often a clinical diagnosis. Other possible causes of upper airway obstruction include extrinsic compression of the airway (laryngeal web, vascular ring) and intraluminal obstruction from masses (laryngeal papilloma, subglottic hemangioma); these tend to have chronic or recurrent symptoms.

Upper airway obstruction is occasionally associated with angioedema of the subglottic areas as part of anaphylaxis and generalized allergic reactions, edema after endotracheal intubation for general anesthesia or respiratory failure, hypocalcemic tetany, infectious mononucleosis, trauma, and tumors or malformations of the larynx. A croupy cough may be an early sign of asthma. Vocal cord dysfunction can also occur. Epiglottitis, with the characteristic manifestations of drooling or dysphagia and stridor, can also result from the accidental ingestion of very hot liquid.

Complications

Complications occur in ∼15% of patients with viral croup. The most common is extension of the infectious process to involve other regions of the respiratory tract, such as the middle ear, the terminal bronchioles, or the pulmonary parenchyma. Bacterial tracheitis may be a complication of viral croup rather than a distinct disease. If associated with S. aureus, toxic shock syndrome can develop. Bacterial tracheitis can produce a two-phased illness, with the second phase associated with high fever, toxicity, and airway obstruction. Alternatively, the onset of tracheitis occurs without a second phase and appears as continued but higher fever and worsening respiratory distress rather than the usual recovery after 2-3 days of viral croup. Pneumonia, cervical lymphadenitis, otitis media, or, rarely, meningitis or septic arthritis can occur in the course of epiglottitis. Mediastinal emphysema and pneumothorax are the most common complications of tracheotomy.

Treatment

The mainstay of treatment for children with croup is airway management and treatment of hypoxia. Treatment of the respiratory distress should take priority over any testing. Most children with either acute spasmodic croup or infectious croup can be managed safely at home. Despite the observation that cold night air is beneficial, a Cochrane review has found no evidence supporting the use of cool mist in the emergency department for the treatment of croup. Children with both wheezing and croup can experience worsening of their bronchospasm with cool mist.

Nebulized racemic epinephrine is an accepted treatment for moderate or severe croup. The mechanism of action is believed to be constriction of the precapillary arterioles through the β-adrenergic receptors, causing fluid resorption from the interstitial space and a decrease in the laryngeal mucosal edema. Traditionally, racemic epinephrine, a 1:1 mixture of the D– and L-isomers of epinephrine, has been administered. A dose of 0.25-0.5 mL of 2.25% racemic epinephrine in 3 mL of normal saline can be used as often as every 20 min. Racemic epinephrine was initially chosen over the more active and more readily available L-epinephrine to minimize anticipated cardiovascular side effects such as tachycardia and hypertension. There is evidence that L-epinephrine (5 mL of 1:1,000 solution) is equally effective as racemic epinephrine and does not carry the risk of additional adverse effects. This information is both practical and important, because racemic epinephrine is not available outside the USA.

The indications for the administration of nebulized epinephrine include moderate to severe stridor at rest, the possible need for intubation, respiratory distress, and hypoxia. The duration of activity of racemic epinephrine is <2 hr. Therefore, observation is mandated. The symptoms of croup might reappear, but racemic epinephrine does not cause rebound worsening of the obstruction. Patients can be safely discharged home after a 2-3 hr period of observation provided they have no stridor at rest; have normal air entry, normal pulse oximetry, and normal level of consciousness; and have received steroids (see later). Nebulized epinephrine should still be used cautiously in patients with tachycardia, heart conditions such as tetralogy of Fallot, or ventricular outlet obstruction because of possible side effects.

The effectiveness of oral corticosteroids in viral croup is well established. Corticosteroids decrease the edema in the laryngeal mucosa through their anti-inflammatory action. Oral steroids are beneficial, even in mild croup, as measured by reduced hospitalization, shorter duration of hospitalization, and reduced need for subsequent interventions such as epinephrine administration. Most studies that demonstrated the efficacy of oral dexamethasone used a single dose of 0.6 mg/kg; a dose as low as 0.15 mg/kg may be just as effective. Intramuscular dexamethasone and nebulized budesonide have an equivalent clinical effect; oral dosing of dexamethasone is as effective as intramuscular administration. A single dose of oral prednisolone is less effective. There are no controlled studies examining the effectiveness of multiple doses of corticosteroids. The only adverse effect in the treatment of croup with corticosteroids is the development of Candida albicans laryngotracheitis in a patient who received dexamethasone, 1 mg/kg/24 hr, for 8 days. Corticosteroids should not be administered to children with varicella or tuberculosis (unless the patient is receiving appropriate antituberculosis therapy) because they worsen the clinical course.

Antibiotics are not indicated in croup. Over-the-counter cough and cold medications should not be used in children <4 yr of age. A helium-oxygen mixture (Heliox) may be effective in children with severe croup for whom intubation is being considered. Children with croup should be hospitalized for any of the following: progressive stridor, severe stridor at rest, respiratory distress, hypoxia, cyanosis, depressed mental status, poor oral intake, or the need for reliable observation.

Epiglottitis is a medical emergency and warrants immediate treatment with an artificial airway placed under controlled conditions, either in an operating room or intensive care unit. All patients should receive oxygen en route unless the mask causes excessive agitation. Racemic epinephrine and corticosteroids are ineffective. Cultures of blood, epiglottic surface, and, in selected cases, cerebrospinal fluid should be collected after the airway is stabilized. Ceftriaxone, cefotaxime, or meropenum should be given parenterally, pending culture and susceptibility reports, because 10-40% of H. influenzae type b cases are resistant to ampicillin. After insertion of the artificial airway, the patient should improve immediately, and respiratory distress and cyanosis should disappear. Epiglottitis resolves after a few days of antibiotics, and the patient may be extubated; antibiotics should be continued for 7-10 days. Chemoprophylaxis is not routinely recommended for household, child-care, or nursery contacts of patients with invasive H. influenzae type b infections, but careful observation is mandatory, with prompt medical evaluation when exposed children develop a febrile illness. Indications for rifampin prophylaxis (20 mg/kg orally once a day for 4 days; maximum dose, 600 mg) for all household members are any contact <48 mo of age who is incompletely immunized, any contact <12 mo who has not received the primary vaccination series, or an immunocompromised child in the household.

Acute laryngeal swelling on an allergic basis responds to epinephrine (1:1,000 dilution in dosage of 0.01 mL/kg to a maximum of 0.5 mL/dose) administered intramuscularly or racemic epinephrine (dose of 0.5 mL of 2.25% racemic epinephrine in 3 mL of normal saline) (Chapter 143). Corticosteroids are often required (2-4 mg/kg/24 hr of prednisone). After recovery, the patient and parents should be discharged with a preloaded syringe of epinephrine to be used in emergencies. Reactive mucosal swelling, severe stridor, and respiratory distress unresponsive to mist therapy may follow endotracheal intubation for general anesthesia in children. Racemic epinephrine and corticosteroids are helpful.

Prognosis

In general, the length of hospitalization and the mortality rate for cases of acute infectious upper airway obstruction increase as the infection extends to involve a greater portion of the respiratory tract, except in epiglottitis, in which the localized infection itself can prove to be fatal. Most deaths from croup are caused by a laryngeal obstruction or by the complications of tracheotomy. Rarely, fatal out-of-hospital arrests due to viral laryngotracheobronchitis have been reported, particularly in infants and in patients whose course has been complicated by bacterial tracheitis. Untreated epiglottitis has a mortality rate of 6% in some series, but if the diagnosis is made and appropriate treatment is initiated before the patient is moribund, the prognosis is excellent. The outcome of acute laryngotracheobronchitis, laryngitis, and spasmodic croup is also excellent. As a group, children who need to be hospitalized for croup have somewhat increased bronchial reactivity compared with normal children when tested several yr later, but the significance is uncertain.

Clinical Manifestations

Typically, the child has a brassy cough, apparently as part of a viral laryngotracheobronchitis. High fever and “toxicity” with respiratory distress can occur immediately or after a few days of apparent improvement. The patient can lie flat, does not drool, and does not have the dysphagia associated with epiglottitis. The usual treatment for croup (racemic epinephrine) is ineffective. Intubation or tracheostomy may be necessary, but only 50-60% of patients require intubation for management; younger patients are more likely to need intubation. The major pathologic feature appears to be mucosal swelling at the level of the cricoid cartilage, complicated by copious, thick, purulent secretions, sometimes causing pseudomembranes. Suctioning these secretions, although occasionally affording temporary relief, usually does not sufficiently obviate the need for an artificial airway.

Diagnosis

The diagnosis is based on evidence of bacterial upper airway disease, which includes high fever, purulent airway secretions, and an absence of the classic findings of epiglottitis. X-rays are not needed but can show the classic findings (Fig. 377-3); purulent material is noted below the cords during endotracheal intubation (Fig. 377-4).

Figure 377-3 Lateral radiograph of the neck of a patient with bacterial tracheitis, showing pseudomembrane detachment in the trachea.

(From Stroud RH, Friedman NR: An update on inflammatory disorders of the pediatric airway: epiglottitis, croup, and tracheitis, Am J Otolaryngol 22:268–275, 2001. Photo courtesy of the Department of Radiology, University of Texas Medical Branch at Galveston.)

Figure 377-4 Thick tracheal membranes seen on rigid bronchoscopy. The supraglottis was normal. A, Thick adherent membranous secretions. B, The distal tracheobronchial tree is unremarkable. In contrast to croup, tenacious secretions are seen throughout the trachea, and in contrast to bronchitis, the bronchi are not affected.

(From Salamone FN, Bobbitt DB, Myer CM, et al: Bacterial tracheitis reexamined: is there a less severe manifestation? Otolaryngol Head Neck Surg 131:871–876, 2004.

Treatment

Appropriate antimicrobial therapy, which usually includes antistaphylococcal agents, should be instituted in any patient whose course suggests bacterial tracheitis. Current empiric therapy recommendations for life-threatening infections such as bacterial tracheitis include vancomycin and a β-lactamase–resistant β-lactam antimicrobial agent (e.g., naficillin or oxacillin). When bacterial tracheitis is diagnosed by direct laryngoscopy or is strongly suspected on clinical grounds, an artificial airway should be strongly considered. Supplemental oxygen is usually necessary.

Complications

Chest radiographs often show patchy infiltrates and can show focal densities. Subglottic narrowing and a rough and ragged tracheal air column can often be demonstrated radiographically. If airway management is not optimal, cardiorespiratory arrest can occur. Toxic shock syndrome has been associated with staphylococcal tracheitis (Chapter 174.2).

Prognosis

The prognosis for most patients is excellent. Patients usually become afebrile within 2-3 days of the institution of appropriate antimicrobial therapy, but prolonged hospitalization may be necessary. In recent years, there appears to be a trend toward a less-morbid condition. With a decrease in mucosal edema and purulent secretions, extubation can be accomplished safely, and the patient should be observed carefully while antibiotics and oxygen therapy are continued.