Croup (laryngotracheal bronchitis)

Croup is a respiratory disease that generally affects infants and young children, typically aged between 3 months and 3 years. The most prominent symptoms of croup, barking cough and stridor, are the result of a narrowed airway due to the inflammation of the larynx and upper airway. These symptoms are usually accompanied by fever. Parainfluenza viruses type 1 and 2 and influenza A are the most common pathogens, but croup can also be caused by respiratory syncytial virus, adenovirus, and even enterovirus . Although rare, some children may have more than one attack a year, defined as recurrent croup, which has a more rapid onset, and a lack of fever. When a child with recurrent croup is seen, other accompanying disease such as gastroesophageal reflux, recurrent laryngeal papillomatosis, laryngotracheal stenosis, and congenital abnormalities should be considered . In croup, there is circumferential mucosal inflammation in the subglottic larynx and trachea, which easily compromises the airway, as the subglottis is the narrowest point of the airway and the only part that has a complete tracheal ring. The main differential diagnosis includes epiglottitis. While croup generally has a 12- to 72-hour prodrome, epiglottitis exhibits a rapid onset with high fever, muffled voice, and dysphagia. Also, croup is more often seen at a younger age. The two conditions can be distinguished by a lateral neck radiograph, which reveals an enlarged epiglottis or the so-called “thumb sign” in acute epiglottitis, versus a tapered narrowing of the subglottis, or the “steeple sign” in croup. A foreign body may cause cough and stridor, but there is no viral prodrome. Subglottic hemangioma, vocal fold palsy, and subglottic stenosis can all result in stridor.

Children with croup have been treated with humidified air, with the presumed effect being reducing the subglottic inflammation and thinning the secretions allowing better expectoration. Two studies looking at the efficacy of humidified air have not shown any statistically significant difference between treatment and nontreatment groups; however, the true difference may have been missed because of the small number of patients in both studies . Determining the degree of airway obstruction is the most important consideration when evaluating children with croup. As airway obstruction can worsen rapidly, repeated, careful clinical assessment is essential . Mild obstruction can be assumed when the child appears happy and takes interest in the surroundings. The child may have mild chest wall retractions and tachycardia, but no stridor at rest. A patient with moderate obstruction shows persistent stridor at rest, chest wall retractions, use of accessory respiratory muscles, and tachycardia, while still being interested in the surroundings. As airway obstruction increases, the child appears increasingly worried and exhausted. Tachycardia persists, accompanied by agitation, decreased level of consciousness, cyanosis, and marked pallor .

Major changes in croup management over the past 25 years include the introduction of nebulized epinephrine, and the more generous use of systemic and nebulized corticosteroids . Humidification and oxygen supplementation are started when the patient arrives in the emergency room. Nebulized racemic epinephrine can be administered, which is believed to result in the vasoconstriction of the airway mucosa and subsequent decrease in edema . It is now recommended that children with mild to moderate croup who require nebulized epinephrine be monitored in the emergency department for 3 hours; if they are stable at that time, it is probably safe to discharge them . Two meta-analyses including 24 trials have shown a clinically significant benefit of systemic corticosteroids; therefore, corticosteroid use in the treatment of croup is no longer controversial . On the other hand, its mechanism of action remains unclear. While anti-inflammatory effects probably play a significant role, the rapid onset of action also suggests a possible role for vasoconstriction and reduced vascular permeability . Oral and nebulized dexamethasone, nebulized budenoside, and oral prednisolone can all be used. Management of severe croup requires hospitalization, and may require intubation.

Acute epiglottitis

In children, acute inflammation of the supraglottic larynx resulting in airway obstruction is usually accompanied by high fever and drooling, as well as stridor, and is generally caused by Haemophilus influenzae type B (Hib). Before the initiation of childhood vaccination programs with Hib-conjugated vaccines in 1998, epiglottitis was second only to meningitis as the most common presentation of Hib disease . Since then, a remarkable decline in the number of cases has been noted . The prodrome is generally very short with a potentially rapid progression that can be life threatening. The child usually appears toxic and “hot potato voice” is typical. The classic “tripod position” exhibited by the child, allows maximal air entry as they preferentially lean forward by using their arms to support and extend their neck . A cherry-red epiglottis is characteristic with edema and erythema of the surrounding pharyngeal mucosa, and possible involvement of the false vocal folds and aryepiglottic folds. The examination should be performed with caution, as sudden respiratory arrest can be caused by mucus plugs, plugging of the swollen epiglottis and aryepiglottic folds during inspiratory efforts, or laryngospasm. Therefore, interventions that can agitate the child should be avoided. The best environment to perform direct visualization of the larynx, needed for definitive diagnosis, would be a setting such as an operating room, where collaboration with an anesthesiologist is possible to secure the airway. Once a secure airway has been established, further diagnostic and therapeutic interventions can be initiated including a complete blood count, blood cultures, and soft tissue lateral neck radiographs . The child is usually observed in the intensive care unit (ICU) for 24 to 48 hours before extubation is attempted. Differential diagnosis consists of croup, foreign body aspiration, anaphylaxis, and retropharyngeal infections. The course of epiglottitis is generally shorter compared with croup with marked odynophagia in the former. Medical management should be started as soon as the airway is secured, with a broad-spectrum antibiotic against β-lactamase-positive H influenzae , such as a second- or third-generation cephalosporin or sulbactam-ampicillin. Systemic corticosteroids are widely used despite the absence of scientific evidence supporting their use .

In adults, supraglottitis has a more benign course with fewer patients showing airway compromise. Patients present with dysphagia, odynophagia, and fever, but rarely appear toxic. They may be stridorous and drooling. Organisms other than H influenzae , such as β- hemolytic streptococcus may be causative. In contrast to the child, indirect laryngoscopy can be performed in an adult to confirm the diagnosis. Admission to the ICU for observation and intravenous antibiotic treatment is indicated for all adult patients, although emergent intubations are rarely required. The antibiotic choice is similar to that of the pediatric population.

Diphtheria

Despite being encountered infrequently, Corynebacterium diphtheria can still infect children and adults who are immune-compromised or have not been vaccinated. It has a prodrome of several days with hoarseness progressing to airway compromise. Diagnosis is made by visualization of membranous exudates in the larynx by indirect laryngoscopy or in the oropharynx and with confirmatory cultures. The airway must be secured and medical management with parenteral antibiotics and antitoxin should be started. The antibiotic of choice is penicillin. Meanwhile, palatal and pharyngeal paralysis may necessitate nasogastric tube feeding .

Pertussis

Whooping cough is being seen more commonly in the United States, despite a clear explanation for its increased incidence. It is commonly seen in infants younger than 6 months and adolescents and adults . The causative agent is Bordetella pertussis . While adults generally present with a severe and protracted cough, children display fever and paroxysmal whooping cough. In conjunction with supportive management such as suctioning of secretions in children, antibiotic treatment with erythromycin is administered. Even though antibiotic treatment does not change the course of the disease, patients become noninfective earlier . Erythromycin can also be used for prophylaxis.

Laryngeal tuberculosis

Laryngeal tuberculosis has historically been a sequela of pulmonary tuberculosis. In recent decades, however, the pattern of involvement has been changing, with most patients showing no symptoms of pulmonary tuberculosis . While hematogenous or lymphatic spread of Mycobacterium tuberculosis is thought to cause most laryngeal infections , atypical forms of the acid-fast bacilli also play a role, especially in immune-compromised patients. Patients usually present with hoarseness that can be accompanied by dysphagia, odynophagia, weight loss, and cough. Twenty to forty percent of patients with laryngeal involvement do not show pulmonary involvement , whereas a laryngeal examination is recommended in all patients with pulmonary tuberculosis. In suspected cases of tuberculosis, the work-up should include placement of a purified protein derivative (PPD) skin test, chest radiographs, and sputum examination for cultures and the detection of acid-fast bacilli. The diagnosis of laryngeal tuberculosis is established by histopathology. Indirect laryngoscopy in the office is followed by a direct laryngoscopy with biopsies to show the typical caseous necrosis and acid-fast bacilli. Although the posterior glottis is a common site for infection, any part of the larynx can be involved, presenting as nodular or exophytic lesions or mucosal ulcerations . Differential diagnosis includes squamous cell carcinoma of the larynx. Results of culture and sensitivity testing are important, as multiple-drug–resistant mycobacteria are becoming prevalent.

Syphilis

Syphilis, which can be acquired or congenital, is caused by the spirochete Treponema pallidum . Acquired syphilis, which is contracted through sexual contact, can present in primary, secondary, or tertiary forms. The spirochete initiates an inflammatory response at the site of inoculation and is disseminated during the primary infection. As with other organisms that cause chronic disease, T pallidum has evolved mechanisms for evading immune responses . The primary chancre is a painless ulcer that appears at the point of entrance of the spirochete, usually the genital, oral, or anal mucosa. These ulcers start as papular lesions, have a clean base and raised edges, and heal in 3 to 6 weeks. Following this, in secondary syphilis, fever, headaches, and bone and joint pain are accompanied by skin rashes. Elevated flat-topped lesions covered by hyperkeratotic membranes are observed on mucosal surfaces, such as in the oral cavity. The latency stage where the patient is asymptomatic lasts for years and precedes the tertiary stage. In the tertiary stage, granulomatous nodules consisting of giant cells, lymphocytes, and necrotic centers referred to as gummas can be seen in any organ system of the body. Left untreated, they heal with fibrosis and can result in destruction of the cartilage and scarring, which may result in breathing difficulties if there is laryngeal involvement. While secondary syphilis may present as diffuse laryngeal hyperemia and a coalescing, maculopapular rash, tertiary syphilis usually exhibits a diffuse, nodular, gummatous infiltrate . The diagnosis needs to be confirmed by serology and pathological examination. Parenteral penicillin G is the drug of choice. The prognosis in early disease is quite good. In advanced cases, however, progressive perichondritis may lead to vocal fold immobility, and laryngeal stenosis requiring tracheotomy.

Leprosy

Leprosy, also known as Hansen disease is caused by Mycobacterium leprae . It is a rare disease in the United States, but is prevalent in tropical and warm temperate countries. Currently 83% of cases occur in only six countries, including India and Brazil, and because of the long incubation period , the disease can be seen among immigrants long after they have left their countries. This disease, which is highly contagious, is transmitted as aerosol droplets, usually entering via the nasal mucosa. Breaks in the epidermis can be another portal of entry. It is believed that 75% of people who are exposed to M leprae will clear the disease spontaneously, since despite widespread exposure in endemic areas, clinical leprosy is relatively infrequent . Almost all individuals affected by leprosy will develop cutaneous disease, with 30% to 55% of them showing laryngeal involvement . The epiglottic tip is the most commonly involved site by the disease followed by the vocal folds . Symptoms vary with the anatomical site affected. Large lesions of the supraglottis cause a muffled voice known as “leprous huskiness” . Glottic lesions can present with hoarseness, dyspnea, or cough, although patients are generally pain free. At the early stages of the disease, erythema and nodular edema are common, which can progress into ulcers that heal by fibrosis and scarring. This scarring can lead to laryngeal stenosis and airway compromise . Diagnosis is made by pathological evaluation of either nasal smears or laryngeal biopsies, which show chronic inflammation and infiltration of foamy cells containing the bacilli. M leprae can be demonstrated by acid-fast staining. Treatment is tailored according to the presentation of the disease, and dapsone or dapsone with rifampin are administered. Treatment is continued for 1 to 2 years until the organism has been eradicated from the specimens.

Actinomycosis

The anaerobic saprophyte Actinomyces may become pathogenic causing actinomycosis, with occasional laryngeal involvement. The patient presents with hoarseness, cough, and dysphagia. Direct laryngoscopy reveals swollen tissues with a light gray-red hue , and the diagnosis needs to be confirmed by histopathology, which will show the characteristic sulfur granules. Cultures are hard to grow, but should be sent. Management consists of a prolonged course of antimicrobial therapy for as long as 6 months with penicillin and debridement of the necrotic tissues.

Candidiasis

Candida albicans , part of the normal flora of the oral cavity and gastrointestinal tract, is a budding, yeastlike fungus that causes opportunistic infections. Hoarseness, pharyngeal discomfort, and dysphagia are common symptoms of laryngeal involvement, displaying white plaques scattered in the endolarynx and pharyngeal tissues during indirect laryngoscopy. Infections are more common in immune-suppressed patients, as well among immune-competent patients using inhaled steroids or prolonged courses of antibiotics. The incidence of oropharyngeal and laryngeal candidiasis varies from 0% to 77% in the literature . The diagnosis of laryngeal candidiasis may need to be confirmed by histopathology as the differential diagnosis includes other causes of leukoplakia . Pathological specimens are stained for fungus, which demonstrate the filaments, and treatment includes oral fluconazole. Use of the lowest effective inhaled corticosteroid dose possible, as well as rinsing the mouth, gargling, and washing the face after inhalation are recommended to decrease the incidence of laryngeal candidiasis due to inhaled steroid use in asthma patients .

Blastomycosis

Blastomyces dermatitidis is a dimorphic fungus that is endemic in the southeastern portion of the United States. It is a saprophyte found in the soil, and can be inhaled as spores. The portal of entry is the lungs, with other systems involved through hematogenous spread. The most commonly involved extrapulmonary site is the skin followed by the bones and the genitourinary tract. The disease, which is characterized by granulomatous and suppurative lesions, can frequently involve the larynx, resembling a carcinoma . There have been reports in the literature documenting patients who have undergone surgery or radiation therapy, with subsequent review of their histopathology reported to demonstrate blastomycosis . Laryngeal blastomycosis usually involves the vocal folds with frequent extension onto the false folds; therefore, the most common presenting symptom is hoarseness. Indirect laryngoscopy commonly reveals scattered granular, exophytic masses, and occasionally ulceration . Since the differential diagnosis includes malignancies, diagnosis is confirmed by histopathology, showing giant cells, granuloma formation, and pseudoepitheliomatous hyperplasia. Fungal stains are used to show the budding yeast. Intravenous amphotericin B, oral ketoconazole, or itroconazole have all been shown to be effective in the treatment of laryngeal blastomycosis.

Histoplasmosis

The dimorphic fungus, Histoplasma capsulatum , which is endemic in the Ohio and Mississippi valleys, is the causative organism in histoplasmosis. The organism exists in yeast form at normal body temperature, while its mycelia form is found in soil with high nitrogen content. The infection is contracted through inhalation of the spores. The disease, which may involve only the lungs or become disseminated, is generally self-limiting unless the patient is immune-compromised. The disseminated form presents itself in acute, subacute, or chronic form. Head and neck involvement has been reported in 66% of the chronic form, and 33% of the subacute form , most commonly manifesting itself as painful mucosal ulcers. As the acute form is rapidly fatal, very few patients are seen by the otolaryngologist. The differential diagnosis of laryngeal involvement includes malignancies and tuberculosis. Diagnosis is established by histopathology demonstrating chronic inflammation, granulomatous reaction, and occasionally pseudoepitheliomatous hyperplasia. Fungal stains are helpful, and the complement fixation test can be used to show positive titers . Treatment includes amphotericin B, ketoconazole, and itroconazole.

Coccidioidomycosis

Coccidioidomycosis is caused by the fungus Coccidioides immitis , which is endemic in the southwestern United States and northern Mexico, and is also known as valley fever. While inhabitants of these regions are generally affected, travelers may contract the disease and show symptoms on return. The infection spreads through spore inhalation, and approximately 40.0% of infected subjects will have pulmonary involvement, whereas 0.5% to 2.0% will have dissemination from the pulmonary foci. The larynx may be secondarily involved or may be the site of sputum inoculation . Boyle and colleagues report 12 cases of laryngeal coccidioidomycosis, showing predominance for male and African American patients. Interestingly, seven patients were children, and nine presented with airway compromise. Indirect laryngoscopy commonly shows granulation tissue or ulceration, and diagnosis is confirmed by histopathology revealing granuloma formation, chronic inflammatory cell infiltration, and the fungus on fungal stains. Serologic testing and complement fixation tests are helpful in the diagnosis . Treatment involves antifungals such as amphotericin B, ketoconazole, and itroconazole.

Cryptococcosis

Cryptococcosis is caused by the budding yeast Cryptococcus neoformans found in bird droppings and the surrounding soil worldwide. The spores are inhaled, generally resulting in a subacute pulmonary infection. On the other hand, especially in the immune-compromised host, this neurotropic organism can invade the central nervous system. Cryptococcosis is one of the most common life-threatening infections among patients with AIDS, affecting approximately 10% of advanced AIDS patients . Although laryngeal involvement occurs in similar patient populations, cases in immune-competent hosts have been reported . Commonly the vocal folds are affected resulting in hoarseness. Diagnosis is confirmed by histopathology showing pseudoepitheliomatous hyperplasia and the budding yeast on fungal stains . Amphotericin B and ketoconazole have been used in treatment.