Croup

Etiology

Croup is most commonly caused by viral infections, though bacterial cases can occur. The typical incubation period ranges from 2 to 6 days.

Viral Etiology

Parainfluenza virus, primarily types 1 and 2, is the most common cause of croup. Sporadic cases of croup caused by parainfluenza type 3 are less common but more severe than those caused by types 1 and 2.[CDC. Clinical Overview of Human Parainfluenza Viruses (HPIVs) June 5, 2024].

In a study evaluating the etiological agent causing croup in 144 children who presented to the emergency department with stridor and hoarseness, 80% of patients with croup and 71% of controls tested positive for a viral infection. Children with croup symptoms had more positive results for PIV 1 and 2 and fewer positive results for respiratory syncytial virus. Positive tests for influenza A, rhinoviruses, and enteroviruses were present equally in croup and control patients. The study concluded that PIV1 and PIV2 were the most common etiological agents associated with croup.[2]

Other viral causes include influenza A and B, adenovirus, rhinovirus, SARS-CoV-2, respiratory syncytial virus, and measles. Less frequently, enteroviruses such as coxsackie, echovirus, and herpes simplex can cause sporadic cases of mild croup. SARS-CoV-2 has become a common cause of croup, especially the Omicron variant. Croup caused by SARS-CoV-2 may present with severe symptoms requiring intense treatment and hospitalization compared to croup caused by other viral etiologies.[3]

 Bacterial Etiology

Bacterial croup can lead to several conditions, including bacterial tracheitis, laryngotracheobronchitis, laryngotracheobronchopneumonitis, and diphtheria, which is caused by Corynebacterium diphtheria. Secondary bacterial infections, particularly bacterial tracheitis, can occur due to Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. Mycoplasma pneumoniae can also cause a mild croup-like illness.[4]

Epidemiology

The majority of patients with croup, more than 85%, exhibit mild symptoms, and severe croup is rare, fewer than 1%. In the United States, croup accounts annually for approximately 7% of pediatric hospitalizations, with fewer than 3% of admitted cases requiring intubation, and contributes to up to 15% of emergency department visits among children younger than 5.[5]

Croup typically affects children between the ages of 6 months and 3 years, but can occur as early as 3 months and up to 15 years. The annual incidence is approximately 532 cases per 100,000 individuals, affecting 3% of children younger than 5 globally. Croup rarely occurs in adults. PIV is responsible for more than two-thirds of croup infections. Croup is more common in boys than in girls, with a 1.5:1 ratio, and shows no preference for any race. Croup is more prevalent in resource-limited countries, likely due to a higher proportion of children younger than 6 and suboptimal nutritional status.[6][7]

Pathophysiology

The pathophysiology underlying airway inflammation is responsible for the symptoms of croup. Clinically, croup is classified into viral, spasmodic, and recurrent atypical forms. Viral or classic croup is typically a self-limited illness and resolves within 3 days.[6]

Spasmodic croup mostly occurs at night, with an abrupt onset and a short duration. Episodes may recur within the same night and persist for the next 2 to 3 nights. Spasmodic croup is sometimes called allergic croup, as it may be associated with a positive family history of allergies and atopy. The episodic symptoms of spasmodic croup in an otherwise healthy child differentiate it from viral croup. Symptoms are continuous, not intermittent, in viral croup. The typically benign yet dramatic presentation of spasmodic croup typically resolves with supportive care, including comfort measures and humidified air.[7]

Recurrent or atypical croup is characterized by frequent episodes of croup-like symptoms, occurring more than twice per year, with severe or prolonged symptoms that may occur outside the typical age range.[8] This pattern raises the suspicion of another underlying condition, such as congenital airway abnormalities, gastroesophageal reflux, eosinophilic esophagitis, and atopy, and requires further evaluation by an otolaryngologist.[9][10]

Stridor due to laryngeal obstruction or compression, most commonly caused by epiglottitis, can be misdiagnosed as croup. In a published case, clinicians incorrectly attributed stridor to croup in a 9-month-old infant with a laryngeal mass caused by disseminated Coccidioidomycosis.[11]

Croup infection starts a cascade of pathophysiological reactions, including the infiltration of white blood cells, edema of the upper airway, partial airway obstruction, increased work of breathing, and turbulent, noisy airflow known as stridor (see Image. Croup: Narrowing of the Upper Airway).

A series of pathophysiological events follows, culminating in the clinical presentation of croup (see Image. Pathophysiology of Croup and Its Role in Causing Signs and Symptoms in Children).[The Calgary Guide to Understanding Disease]

History and Physical

The typical presentation of croup is characterized by 1 to 2 days of runny nose, cold symptoms, and low-grade fever, which precede a barking cough, without drooling or dysphagia. The illness lasts typically 3 to 7 days, with the most severe symptoms occurring on days 3 or 4. Croup is characterized by a seal-like barking cough, stridor, hoarseness, and difficulty breathing, which typically worsens at night. Agitation increases the stridor, which can occur at rest. Fever may be absent. Patients may also present with tachypnea and tachycardia. Visual signs such as nasal flaring, retractions, and, in rare cases, cyanosis, increase the suspicion of severe croup. Croup, an upper respiratory condition with stridor, must be differentiated from wheezing associated with lower respiratory conditions such as asthma, pneumonia, or bronchiolitis, rather than croup. Differentiating between stridor and wheezing is crucial, as it directly influences the treatment plan.[12]

Evaluation

The Westley score is the most commonly used system for classifying the severity of croup, ranging from 0 to 17 points, based on 5 factors. The score assesses the severity of croup (see Table. Westley Score for the Classification of Croup).[13]

Table 1. Westley Score for the Classification of Croup

Table 2. Westley Score Defining the Severity of Croup

A study involving 192 children with croup was conducted to identify factors that influence the Westley score and its impact on outcomes in the pediatric emergency department. Based on the study results, cyanosis and altered consciousness were not clinically significant, even in patients with severe croup, whereas retraction and air entry were the significant factors predicting clinical outcomes. Patients with an initial Westley score of 1 to 2 were safely discharged home, whereas those with a Westley score greater than 5 required hospitalization for further treatment.[13]

Although croup is primarily a clinical diagnosis, laboratory studies and imaging can guide management in selected cases. Nasopharyngeal swabs for influenza, respiratory syncytial virus, and parainfluenza serologies may confirm alternative diagnoses and change management. Clinicians must differentiate other obstructive conditions, such as epiglottitis, bacterial tracheitis, inhaled foreign bodies, subglottic stenosis, retropharyngeal abscess, and angioedema. A frontal x-ray of the neck is not routinely performed, but it may demonstrate a steeple sign characteristic of croup due to narrowing of the trachea, which resembles a church steeple. Blood tests and viral cultures are not routinely recommended, as they may cause increased agitation, potentially leading to further airway edema and obstruction. Viral cultures, obtained through nasopharyngeal aspiration, can confirm the etiology but are typically limited to research settings. Bacterial infection is considered a primary or secondary factor if the patient does not respond to standard treatments.[Clarke M, Allaire J. An evidence-based approach to the evaluation and treatment of croup in children. Pediatr Emerg Med Pract 2012; 9:1] Patients with recurrent croup need evaluation by a multidisciplinary team, including an otolaryngologist. A study by Quraishi et al in 2022 recommended some key points for evaluating recurrent croup. They concluded that children younger than 1 or 3 with a history of intubation presenting with recurrent croup should undergo triple endoscopy to identify structural airway abnormalities. If no airway abnormalities exist, patients should be screened for asthma and gastroesophageal reflux disease and treated empirically. The study concluded that the treatment of gastroesophageal reflux disease and asthma improves the symptoms of recurrent croup.[8]

Treatment / Management

Based on the Westley croup score, treatment depends on the severity of signs and symptoms. Children with mild croup receive a single dose of dexamethasone, symptomatic treatment, and supportive care. Children with moderate-to-severe croup are given nebulized epinephrine and dexamethasone.[14](A1)

All patients with diminished oxygen saturation should receive supplemental oxygen. Moderate-to-severe cases require observation and admission if the symptoms do not improve.[15]

Steroids

• Dexamethasone, a glucocorticosteroid, helps accelerate recovery, lowers the need for additional medical care, and shortens the length of hospital stay.
• Dexamethasone is superior to budesonide for improving symptom scores, but does not appear to reduce readmission rates.
• Dexamethasone doses of 0.15, 0.3, or 0.6 mg/kg appear equally effective; 0.6 mg/kg is the most commonly used dose.[16]
• Oral dexamethasone is the preferred treatment for children with croup because it is effective, widely available, safe, and easily administered. A single dose is sufficient for most children. If symptoms persist for 3 to 4 days after the first dose of dexamethasone, a second dose can be administered.
• The oral route is less invasive than an injection, making it more comfortable for children already experiencing respiratory distress. However, in cases where the child is unable to swallow, is vomiting, or has severe respiratory distress, intramuscular or intravenous dexamethasone may be necessary. Oral medication is also less costly and may be prescribed for home use in cases of mild croup.
• If an intravenous line is already in place, the parenteral route is preferred over intramuscular injections because they cause additional discomfort and distress.[17]
(A1)

Epinephrine

• Nebulized racemic epinephrine has been shown to improve symptom scores within 30 minutes, but its effects may diminish after 2 hours in patients with moderate-to-severe croup, who, therefore, require a prolonged period of observation after receiving racemic epinephrine. If symptoms improve, they can be discharged home after 4 hours of observation, with instructions for close follow-up.
• Administering approximately 0.5 mL/kg of L-epinephrine 1:1000 using a nebulizer appears more effective than racemic epinephrine at 2 hours due to its longer duration of action.[18]
(A1)

Oxygen: Administration of medications using less invasive techniques is recommended in patients with croup, as any agitation can worsen the symptoms. Therefore, oxygen delivery by blow-by administration may be more effective than using a mask or nasal cannula.[15]

Intubation

• Approximately 0.2% of children require endotracheal intubation for respiratory support. Two retrospective studies found that fewer than 3% of children hospitalized for croup needed intubation.[15]
• Clinicians should use an endotracheal tube 0.5 size smaller than typical for the patient's age and size to account for airway narrowing due to swelling and inflammation.

Hot Steam: Studies have not shown significant improvement with the administration of inhaled hot steam or humidified air. Exposure to cold outdoor night air is more effective in lessening croup symptoms.[19](A1)

Cough Medicine: Guidelines discourage the use of cough medicines, which typically contain dextromethorphan or guaifenesin. These medications can cause drowsiness in a child, requiring increased effort to breathe, which may exacerbate the symptoms of croup.[U.S. Food and Drug Administration. Use Caution When Giving Cough and Cold Products to Kids]

Heliox: Heliox is a mixture of helium and oxygen; however, there is limited evidence to support its routine use. This mixture can decrease the increased work of breathing by reducing turbulent airflow in patients with severe croup. Heliox is an option if respiratory distress persists despite other therapies, and it can serve as a temporary measure to prevent intubation while waiting for steroids to take effect in reducing airway edema.[20](A1)

Antibiotics

• Croup is primarily a viral illness. Antibiotics are considered when a primary or secondary bacterial infection is suspected.
• Secondary bacterial infection should be treated based on the possible causative bacterial agent. Vancomycin and cefotaxime are preferred antibiotics.
• Severe symptoms of croup caused by influenza A or B may respond to antiviral neuraminidase inhibitors.[7]
(A1)

Approximately 5% of children treated for croup in the outpatient setting have repeat visits for recurrent symptoms within 7 days. Children with recurrent croup episodes should be referred to an otolaryngologist to evaluate for underlying airway abnormalities, such as laryngomalacia, subglottic stenosis, gastroesophageal reflux disease pathology, or hemangiomas. Airway abnormalities are identified in approximately 10% of children with recurrent croup referred to otolaryngologists and 45% of those who undergo airway endoscopy.[21][22][23](B2)

Differential Diagnosis

The differential diagnosis of croup includes other causes of stridor and respiratory distress, such as bacterial tracheitis, epiglottitis, foreign body aspiration, hemangioma, peritonsillar abscess, neoplasm, retropharyngeal abscess, and smoke inhalation. Rarely, neurological causes can cause stridor that mimics croup. In a report, 3 children presented with stridor and were treated for croup but were eventually found to have a neurological cause of stridor.[24]

Acute Epiglottitis

Acute epiglottitis is rare due to vaccination against Haemophilus influenzae type B. The patient does not have a barking cough but has anxiety out of proportion to the degree of respiratory distress. Symptom onset is generally rapid; the child appears febrile and ill-appearing. Affected children prefer to sit upright in a tripod position, and cough is rare. The thumb sign due to a swollen epiglottis may be noted on a radiograph. A cough is highly sensitive and specific for croup, whereas drooling may indicate bacterial epiglottitis. Other symptoms include acute onset of dysphagia, odynophagia, high fever, and a muffled voice.[12]

Distinguishing croup from epiglottitis is essential because patients with the latter may deteriorate rapidly. If acute epiglottitis is suspected, it is imperative to keep the child calm and avoid asking them to open their mouth wide, as this could precipitate fatal airway obstruction. An emergent ear, nose, and throat (ENT) consultation for airway evaluation in the operating room is essential for suspected epiglottitis. The Haemophilus influenzae vaccine, licensed in 1985, decreased cases of epiglottitis, but with the current rates of vaccine refusals, acute epiglottitis cases are likely to occur. All patients with epiglottitis should be admitted to the intensive care unit for close monitoring.[25]

Bacterial Tracheitis

Bacterial tracheitis is also called bacterial croup. An exudative bacterial infection invades tracheal soft tissue and occurs as a primary infection or secondary to viral croup. In secondary bacterial infection, mild viral croup symptoms worsen, and patients exhibit high fevers, a toxic appearance, and severe respiratory distress. Radiographs may show nonspecific edema and irregularities of the tracheal wall.[26]

Deep Neck Space Abscesses

Patients with peritonsillar, parapharyngeal, or retropharyngeal abscesses typically lack symptoms of croup, such as barking cough and stridor. Children may present with drooling, fever, difficulty swallowing, neck stiffness, enlargement of cervical lymph nodes, and a toxic appearance. With deep neck space abscesses, cellulitis of the cervical prevertebral tissues may occur. Children with a retropharyngeal abscess typically have fever, drooling, dysphagia, and odynophagia but also complain of neck pain with a bulging posterior pharyngeal wall on neck radiography. Children with a peritonsillar abscess often complain of a sore throat, fever, and a classic hot potato voice.[27]

Foreign Body

A previously healthy child presents with a sudden onset of choking and upper airway obstruction symptoms. A foreign body lodged in the larynx causes hoarseness and stridor. A large foreign body in the upper esophagus can pressurize the extra-thoracic trachea, resulting in a barking cough and inspiratory stridor. Late onset of stridor can occur due to the ingestion of a nonobstructive erosive foreign body, such as a button battery.[28]

Allergic Reaction or Acute Angioneurotic Edema

Patients present with a sudden onset of symptoms such as swollen lips and tongue without preceding respiratory symptoms or fever. The associated symptoms include urticarial rash, difficulty swallowing, and inspiratory stridor. Patients may have a history of allergies and a history of similar episodes in the past.[4]

Congenital and Acquired Anomalies

Congenital and acquired anomalies and upper airway injury can cause stridor. Anatomic abnormalities include laryngeal webs, papillomas, laryngomalacia, subglottic stenosis, hemangiomas, bronchogenic cysts, and vocal cord paralysis. Most patients present with stridor as a chronic symptom without other upper respiratory symptoms or fever.[Clarke M, Allaire J. An evidence-based approach to the evaluation and treatment of croup in children. Pediatr Emerg Med Pract 2012; 9:1]

Prognosis

Patients with mild croup have an excellent prognosis. Hospital admission and mortality rates are low and vary significantly between communities. Fewer than 0.5% of intubated children died in a 10-year study of hospitalized children with croup.[7]

Complications

Symptoms of mild croup subside in the majority of children within 2 days. However, a few patients have symptoms that persist for up to 1 week. Moderate-to-severe croup symptoms need treatment with epinephrine in addition to glucocorticoids. Complications such as pneumonia, pulmonary edema, and secondary bacterial infection may occur, leading to tracheitis, requiring antibiotics.[7]