Epiglottitis

Epiglottitis is an acute, life-threatening inflammation of the epiglottis and surrounding supraglottic structures that can rapidly progress to complete airway obstruction. Historically a disease of young children (peak incidence 2–7 years), the epidemiology has dramatically shifted in developed countries with routine Haemophilus influenzae type b (Hib) vaccination, now occurring predominantly in unvaccinated or incompletely vaccinated children and occasionally in adults. The condition represents a medical emergency requiring immediate recognition and intervention, as airway compromise can develop within hours. Despite its relative rarity in vaccinated populations, epiglottitis remains clinically significant because mortality approaches 5–15% if airway management is delayed, and misdiagnosis as other causes of acute upper airway obstruction (croup, foreign body aspiration) can be fatal. Clinically astute providers must maintain a high index of suspicion, particularly in unimmunized populations or atypical presentations.

Epiglottitis results from bacterial invasion and acute inflammation of the epiglottis and aryepiglottic folds, leading to rapid tissue edema, swelling, and progressive airway compromise through several interconnected mechanisms:

Haemophilus influenzae type b and other encapsulated bacteria (notably Streptococcus pneumoniae) are naturally tropistic for the respiratory mucosa. These organisms possess lipopolysaccharide (LPS) endotoxins in their outer membranes that directly activate pattern recognition receptors (TLRs, particularly TLR-4) on resident epithelial cells and infiltrating immune cells. The bacterial capsule of Hib, composed of polyribose phosphate, confers antigenicity and resistance to opsonophagocytosis in unvaccinated or partially vaccinated individuals. Once bacterial adherence occurs via pili and adhesins to epithelial receptors, local mucosal invasion and breach proceed with release of bacterial toxins and superantigens.

Tissue invasion triggers massive upregulation of pro-inflammatory cytokines (IL-1, IL-6, TNF-α, IL-8) and chemokines (CXCL8, MCP-1) from epithelial cells, macrophages, and mast cells. These mediators recruit neutrophils, eosinophils, and lymphocytes to the supraglottic region. Simultaneously, bradykinin and complement cascade activation (particularly C3a and C5a) increase local vascular permeability through endothelial cell retraction and tight junction disruption. The epiglottis and surrounding structures, being composed of loosely organized lymphoid tissue with abundant mucous glands and highly compliant mucosa, are particularly prone to rapid, non-pitting edema. Histologically, affected tissue shows neutrophilic infiltration, interstitial and submucosal edema, and microabscess formation. This edema is not localized—it extends rapidly into the false vocal cords and aryepiglottic folds, which themselves become cherry-red and swollen.

The epiglottis normally hangs freely in the supraglottic space, protecting the true vocal cords during swallowing. Edema causes the epiglottis to swell and assume a "thumb-like" appearance, progressively occluding the laryngeal inlet from above. As swelling advances, the aryepiglottic folds (which normally form a narrow anterior-posterior channel) bulge medially into the laryngeal lumen. The geometric anatomy of the pediatric larynx (naturally narrower and more funnel-shaped than adults) means that even modest epiglottic swelling causes disproportionate obstruction. The combination of reduced airway diameter and increased turbulence (per the Hagen-Poiseuille relationship, resistance ∝ 1/radius⁴) results in dramatically increased work of breathing and potential for sudden, complete obstruction. Progressive hypoxia, hypercapnia, and respiratory acidosis ensue if airway intervention is delayed.

Severe infections may progress to sepsis with bacterial translocation, SIRS (systemic inflammatory response syndrome), and eventual septic shock. Endotoxin-mediated activation of tissue factor and the extrinsic coagulation cascade can lead to consumptive coagulopathy and disseminated intravascular coagulation (DIC), particularly in severe Hib disease. Adrenal insufficiency from sepsis-induced adrenal dysfunction (relative or absolute) may contribute to cardiovascular collapse.

H. influenzae type b remains the predominant etiologic agent in unvaccinated or incompletely vaccinated populations, responsible for approximately 80–90% of cases historically and currently in low-income regions without universal Hib immunization. The pathogenicity of Hib is conferred by its polyribose phosphate (PRP) capsule, which mimics polyribose phosphate found in mammalian cell membranes and thus evades immune recognition in unvaccinated hosts. Effective vaccination with Hib conjugate vaccines (PRP-T, PRP-OMP, HbOC) has reduced incidence in developed countries by >95% but pockets of unimmunized or under-immunized children remain (religious exemptions, late-arriving immigrants, healthcare access disparities). Hib strains are typically beta-lactamase producers, necessitating third-generation cephalosporins or fluoroquinolones rather than older agents.

With Hib decline, penicillin-resistant and **cephalosporin-resistant *S. pneumoniae*** have emerged as the second most common cause of epiglottitis in some developed countries. Pneumococcal epiglottitis occurs across all age groups and should be suspected in vaccinated children or adults presenting with acute epiglottitis. The prevalence has increased parallel to the introduction of pneumococcal conjugate vaccines (PCV7, now PCV13), possibly due to serotype replacement.

Group A Streptococcus (S. pyogenes) occasionally causes epiglottitis, particularly in post-streptococcal pharyngitis scenarios. Staphylococcus aureus, including **methicillin-resistant S. aureus (MRSA), has been reported in post-intubation cases and immunocompromised hosts. Group B Streptococcus** (S. agalactiae) is rare but documented in neonates. Moraxella catarrhalis, Klebsiella pneumoniae, and gram-negative anaerobes are uncommon but may occur in patients with underlying immunosuppression, aspiration risk, or healthcare-associated exposure.

Incomplete Hib vaccination series (fewer than 3 primary doses), delay in booster vaccination, or religious/philosophical vaccine exemptions constitute the single largest modifiable risk factor. In the United States, pockets of under-immunized populations (Amish communities, some urban areas with low vaccination rates) experience periodic outbreaks.

Peak incidence: 2–7 years in unvaccinated populations; now increasingly seen in unvaccinated adults, adolescents, and immunocompromised individuals. Incidence in vaccinated children is <1 per 100,000 per year.

HIV/AIDS (CD4 <200 cells/μL), chemotherapy, organ transplantation, and asplenia increase risk for fulminant epiglottitis and atypical pathogens. These patients may present with less fever and more insidious onset.

Iatrogenic airway trauma increases risk of secondary bacterial invasion and post-extubation epiglottitis.

Inhalation of hot substances or caustic agents (ingestion of lye, caustic fumes) can cause supraglottic edema mimicking infectious epiglottitis, though true bacterial infection may supervene.

Patients typically present with an abrupt onset (hours to 1–2 days) of severe pharyngeal pain, often described as the most painful sore throat the patient has experienced. Dysphagia (difficulty swallowing) is prominent and often accompanied by refusal to swallow saliva; patients characteristically drool because swallowing is so painful. In children, this rapid onset distinguishes epiglottitis from the more gradual presentation of bacterial pharyngitis or strep throat. The pain is typically localized to the throat rather than lateralized to one tonsil, reflecting the midline epiglottic involvement.

Progressive inspiratory stridor develops as epiglottic edema worsens, reflecting turbulent airflow through the narrowed supraglottic inlet. Retractions (intercostal, subcostal, suprasternal) indicate increased work of breathing and impending decompensation. Patients may assume the tripod position (sitting upright, leaning forward, chin extended) to optimize airway diameter and leverage respiratory muscles. In advanced cases, biphasic stridor (both inspiratory and expiratory components) signals severe obstruction. Paradoxically, some patients with impending complete airway obstruction may have a paradoxically "quiet" appearance, as they can no longer generate sufficient airflow to produce stridor—this is an ominous sign requiring emergent intervention.

High fever (often >39°C) accompanied by malaise, tachycardia (out of proportion to fever), and tachypnea reflect systemic inflammation and bacteremia. Some patients rapidly progress to signs of sepsis and shock (hypotension, altered mental status, cool extremities) within 24 hours.

Severe throat pain makes swallowing dangerous; patients cannot safely swallow saliva and accumulate secretions in the oropharynx, increasing aspiration risk. Some patients develop a muffled voice ("hot potato voice," though more muffled than in croup) from supraglottic swelling limiting vocal cord movement. Drooling is prominent.

Throat examination: Direct visualization of the epiglottis is contraindicated in the acute setting unless immediate airway intervention (intubation or tracheostomy) can be performed, as instrumentation may precipitate complete airway obstruction or aspiration. However, if examination is performed (in a controlled setting like the operating room with airway equipment present), the epiglottis appears bright red, swollen, and edematous ("cherry-red appearance"). The aryepiglottic folds are also severely swollen. Cervical lymphadenopathy is typically absent or mild (distinguishing epiglottitis from viral croup or bacterial pharyngitis, both of which commonly have prominent lymphadenopathy).

Indirect signs of airway obstruction: Tachypnea, intercostal/subcostal/suprasternal retractions, nasal flaring, diminished air movement on auscultation, hypoxemia (SpO₂ <95%), and hypercapnia (rising CO₂) indicate worsening obstruction.

Signs of systemic infection: Fever, tachycardia, altered mental status (concerning for shock or hypoxia), hepatomegaly, and petechial rash (in severe Hib or pneumococcal sepsis) may be present.

Adult epiglottitis: Often more insidious, with sore throat and dysphagia as predominant features, less dramatic respiratory distress initially. May present with referred otalgia or complaint of "lump in throat." Progression can still be rapid.

Immunocompromised hosts: May have blunted fever response, more indolent course, atypical pathogens, and delayed diagnosis.

Partially treated or resolving epiglottitis: Patients who received some antibiotics (e.g., from an urgent care visit for "severe strep throat") may have partial clinical improvement while remaining at high risk for sudden decompensation.

Diagnosis begins with high clinical suspicion based on the triad of: (1) acute severe sore throat; (2) dysphagia with drooling; (3) respiratory distress/stridor in a febrile patient. Key historical elements include: unimmunized or incompletely vaccinated status (critical risk factor), rapid onset over hours, and severity out of proportion to typical pharyngitis. Contrast this with croup (which presents with barking, seal-like cough, more gradual onset over days, less severe dysphagia), retropharyngeal abscess (often unilateral neck pain, torticollis, often following strep pharyngitis), and peritonsillar abscess (unilateral, often post-strep, trismus). The acute, fulminant presentation with marked dysphagia and respiratory distress in an unimmunized child should immediately raise suspicion for epiglottitis.

Neck radiographs (posteroanterior and lateral views) were historically the primary diagnostic tool and remain useful when clinical diagnosis is uncertain and airway is relatively stable. The classic "thumbprint" sign on lateral neck X-ray shows a swollen, rounded epiglottis at the C3 vertebral level (normally thin and leaf-like), with loss of the normal hypopharyngeal air space. The "aryepiglottic fold sign" reveals swelling and obliteration of normal anatomy. Sensitivity is approximately 60–80% for true epiglottitis, with specificity >90%; false negatives occur when edema is mild or localized to aryepiglottic folds. Important caveat: Do not delay airway intervention or send an acutely ill child to radiology unmonitored if clinical suspicion is high—X-rays are adjunctive only and should not delay treatment.

CT of the neck with IV contrast provides superior visualization of the epiglottis, aryepiglottic folds, and surrounding spaces. Findings include marked epiglottic enlargement, decreased density of surrounding fat planes, and distortion of the hypopharyngeal airway. CT sensitivity exceeds 95% but should only be performed if the airway is stable and under continuous monitoring. CT is more commonly used for confirming diagnosis in less acute cases or in adults where the differential includes other causes of dysphagia.

Indirect laryngoscopy via flexible fiberoptic scope can directly visualize the epiglottis and aryepiglottic folds in controlled settings (operating room or ICU with full airway equipment and surgeon/anesthesiologist present). Findings include bright red, massively swollen epiglottis and aryepiglottic folds occluding the laryngeal inlet. This procedure is diagnostic but carries high risk of precipitating complete airway obstruction; it should be performed only when immediate intubation or surgical airway is available.

Blood cultures should be obtained before antibiotics are started; bacteremia is present in >90% of Hib epiglottitis and >50% of pneumococcal cases. Culture results guide antibiotic choice, particularly if beta-lactamase resistance or cephalosporin resistance is demonstrated. Throat culture is less reliable due to contamination with normal flora but may yield the pathogen. Culture of aspirated material (if drainage or needle aspiration is performed) is higher yield.

Typically shows leukocytosis (WBC 15,000–40,000 cells/μL) with left shift (increased immature neutrophils) reflecting acute bacterial infection. However, WBC may be low or normal in severe sepsis (poor prognostic sign).

Epiglottic antigen detection (latex aggl

Contraindicated: tongue-depressor or blind oropharyngeal examination outside a prepared airway setting, forcing the patient supine, sedating without airway control, and sending an unstable child to radiology.