Infectious and Inflammatory Diseases of the Larynx

The majority of patients with disorders of the larynx and voice suffer from infectious and noninfectious inflammatory conditions. It is important to remember that the term inflammation implies a local response to tissue injury, characterized by capillary dilation and leukocyte infiltration. The typical signs and symptoms of inflammation are swelling, redness, and, sometimes, discomfort or pain. The term laryngitisis synonymous with laryngeal inflammation, although not with hoarseness. 

Laryngitis (laryngeal inflammation) may result from infection by an invading microorganism or from irritative, traumatic, metabolic, allergic, autoimmune, or idiopathic causes. 

Acute and chronic laryngitis are very common in oto-laryngologic practice, and the causes (differential diagnoses) in pediatric and in adult patients are different. In infants and children, for example, the most common cause of laryngitis is acute infection, whereas, in adults, laryngitis generally tends to have a chronic, noninfectious cause. 

Within the last 20 years, laryngopharyngeal (gastroesophageal) reflux has been discovered to be a far more important cause of laryngeal inflammation than was previously recognized. In addition, primarily because of acquired immune deficiency syndrome (AIDS), infecting microorganisms that were rarely encountered in the practice of oto-laryngology just a few years ago are re-emerging. Thus, the otolaryngologist today must again become familiar with the clinical manifestations of infection by a wide spectrum of microorganisms. 

Laryngeal inflammatory disorders are unusual in that often more than one causative factor or condition can be identified. For example, patients with Reinke’s edema are frequently smokers who also misuse their voices and have reflux. Such patients may also develop laryngeal carcinoma. Each of the underlying causes must be identified and corrected if treatment is to be successful. As more has been learned about the larynx, environmental influences, and the effects of systemic disorders on the larynx, imprecise diagnostic terms, such as “nonspecific laryngitis,”have appropriately begun to disappear from the otolaryngologic literature. 

Laryngopharyngeal (gastroesophageal) reflux disease 

It has been estimated that 10% of Americans have heartburn on a daily basis and an additional 30 to 50% have it less frequently. Of all of the causes of laryngeal inflammation, gastroesophageal reflux disease (GER, GERD) is the most common cause, and as many as 10 to 50% of patients with laryngeal complaints have a GER-related underlying cause. The term reflux literally means “back flow.”Reflux of stomach contents into the esophagus is common, and many patients with GERD have symptoms such as heartburn and regurgitation related to inflammation of the esophagus by acid and digestive enzymes. When refluxed material escapes the esophagus and enters the laryngopharynx above, the event is termed laryngopharyngeal reflux(LPR). 

Although the terms gastroesophageal reflux and laryngopharyngeal reflux are often used interchangeably, the latter is more specific. Laryngopharyngeal reflux is the preferred term for use in oto-laryngology because the patterns, mechanisms, and manifestations of LPR differ from classic GERD. Laryngopharyngeal reflux affects both children and adults and may be associated with an acute, chronic, or intermittent pattern of laryngitis, with or without granuloma formation. Indeed, LPR has also been implicated in the development of laryngeal carcinoma and stenosis, recurrent laryngospasm, and cricoarytenoid joint fixation, as well as with many other otolaryngology-related conditions, including globus pharyngeus, cervical dysphagia, and subglottic stenosis.

The symptoms of LPR are quite different from those of classic GERD, as seen in the gastroenterology patient, who characteristically has heartburn, regurgitation, and esophagitis. Patients with “reflux laryngitis” (LPR) present with hoarseness, but almost two-thirds deny ever having heartburn. Other throat symptoms, such as globus pharyngeus (a sensation of a lump in the throat), dysphagia, chronic throat clearing, and cough, are often associated with LPR. The pattern of reflux is predominantly during the day in the upright position in LPR, whereas it is more likely nocturnal in the supine position with GERD. 

Gastroenterologists call reflux patients who deny gastrointestinal symptoms “atypical refluxers,”but these patients are quite typical of those encountered in otolaryngologic practice. The physical findings of LPR can range from mild, isolated erythema of the area of the arytenoid cartilages to diffuse laryngeal edema and hyperemia with granuloma formation and airway obstruction.

The particular laryngeal findings include pseudosulcus vocalis (subglottic edema that extends from the anterior commissure to the posterior part of the larynx; it appears like a groove or sulcus). It can easily be differentiated from a true sulcus (sulcus vergeture) that is the adherence of the vocal fold epithelium to the vocal ligament secondary to the absence of the superficial layer of lamina propria. It is scarring in the phonatory striking zone.

Although the particular laryngeal findings are highly suggestive of LPR, ambulatory 24-hour double-probe (simultaneous esophageal and pharyngeal) pH monitoring (pH-metry) is the current gold standard for the diagnosis of reflux in otolaryngology patients. The distal probe is placed 5 cm above the lower esophageal sphincter, and the proximal probe is placed in the hypopharynx 1 cm above the upper esophageal sphincter, just behind the laryngeal inlet.

There are three levels of antireflux treatment:

level I, dietary and lifestyle modification plus antacids;

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level II, level I plus use of a histamine H2-receptor antagonist (such as cimetidine, ranitidine, or famotidine); and

level III, antireflux surgery (eg, fundoplication) or proton pump inhibitor (PPI) therapy (eg, omeprazole, esomeprazole, lansoprazole, pantoprazole, or rabeprazole).

In contrast to GERD, which often responds to level I or II therapy, high-dose, prolonged treatment with PPIs is often required to reverse the tissue injury in patients with LPR.

Potentially life-threatening manifestations of LPR include paroxysmal laryngospasm, laryngeal stenosis, and laryngeal carcinoma. Laryngospasm is an uncommon complaint, but patients who experience this frightening symptom usually are able to describe the event in vivid detail. Laryngospasm is often paroxysmal and usually occurs without warning. The attacks may have a predictable pattern (eg, occurring post-cibal or during exercise), and some patients are aware of a relationship between reflux and the attacks (others are not).

Loughlin and Koufman studied 12 patients with recurrent paroxysmal laryngospasm, 11 of whom had documented LPR by pH-metry, and all of whom responded to treatment with PPIs by a cessation of laryngospastic episodes.

Excluding trauma, LPR is the primary cause of laryngeal stenosis, including subglottic stenosis and posterior laryngeal stenosis; pH-metry-documented LPR has been found in 92% of patients.

Treatment with PPIs or fundoplication will result in subsequent decannulation of the vast majority of patients with such stenosis, in some cases without surgery. The risk factors for the development of laryngeal carcinoma include LPR. Koufman reported a series of 31 consecutive patients with laryngeal carcinoma in whom abnormal reflux was documented in 84%, but only 58% were active smokers. The relationship between LPR and malignant degeneration remains unproven, but the available pH-metry data suggest that most patients who develop laryngeal malignancy both smoke and have LPR. In addition, apparently premalignant lesions may resolve with appropriate antireflux therapy.

Paediatric laryngitis 

Pediatric patients with laryngeal inflammation and edema present with one or more of the following symptoms: dysphonia, odynophonia, cough, dysphagia, odynophagia, stridor, and dyspnea.

Airway obstruction from inflammatory laryngeal edema is more common in children than in adults owing to the small size of the pediatric larynx. Equivalent amounts of mucosal swelling may result in critical narrowing and obstruction in a child, while causing only minimal symptoms in an adult.

Viral laryngotracheitis is the most common laryngeal inflammatory disorder of childhood. It is responsible for 15% of respiratory disease seen in pediatric practice. Usually, this condition is self-limiting, occurs in children under the age of 3 years, and has a seasonal peak, with most cases occurring during the winter.

The need for inpatient hospitalization depends on the degree of airway obstruction.

Treatment is aimed at decreasing laryngeal edema and preventing stasis and crusting of secretions within the airway. Therapy usually includes hydration, humidification of inspired air, and treatments with nebulized racemic epinephrine. Antipyretics, decongestants, and parenteral corticosteroids are often administered.

Artificial airway support (eg, intubation) is necessary in only a small proportion of patients.

Acute supraglottitis (epiglottitis)

This is a life-threatening infection of the supraglottic larynx traditionally caused by Haemophilus influenzae type B.

Since childhood immunization against type B H. influenzae has become commonplace, however, the disease is significantly less prevalent, and epidemiologic data suggest that non–type B H. influenzae is more frequent among those vaccinated children who are affected.

The illness begins rapidly over 2 to 6 hours with the onset of fever, sore throat, and inspiratory stridor. The voice tends to be muffled, and there is no “barky”cough, as in croup. As the supraglottic structures become more edematous, airway obstruction develops. The child is generally ill-appearing, stridulous, sitting upright, and drooling because swallowing is painful.

The diagnosis is usually based purely on the history and clinical findings.

Examination of the epiglottis (in the emergency room) may precipitate airway obstruction and thus is not recommended.

Lateral soft tissue radiographs may reveal the classic “thumb” sign of the edematous epiglottis with a dilated hypopharynx.

In severe cases, treatment should not be delayed to obtain radiographs. If radiographs are deemed necessary, the study should be carried out in the presence of personnel capable of immediately intubating the patient should airway obstruction occur.

The child with suspected epiglottitis should be taken to the operating room immediately to establish the diagnosis and secure an airway. Treatment is directed at airway maintenance and then toward providing appropriate antimicrobial and supportive care.

Diphtheria, spasmodic croup, and vocal misuse and abuse are other less frequent causes of pediatric laryngitis.

Laryngeal diphtheria is caused by Corynebacterium diphtheriae and generally affects children over the age of 5 years. A febrile illness of slow onset associated with sore throat and hoarseness is then followed by progressive airway obstruction. 

Treatment consists of establishing a safe airway via a tracheostomy (intubation is contraindicated because it may dislodge a portion of the plaque and cause airway obstruction) and administering diphtheria antitoxin and penicillin or erythromycin to eradicate the microorganisms.

Spasmodic croup, or “false croup,”is a noninfectious form of laryngeal inflammation, associated with a mild, chronic-intermittent, croup-like pattern. Although the aetiology of spasmodic croup remains uncertain, recent evidence suggests that extra-esophageal reflux may frequently be the cause.

When spasmodic croup is suspected, 24-hour pH monitoring may be diagnostic. If, after a positive pH study, the patient’s condition is alleviated by antireflux therapy, it may be concluded appropriately that reflux was the cause.

Traumatic laryngitis is most commonly caused by vocal abuse, such as excessive shouting or yelling, but it also can result from persistent coughing, inhalation of toxic fumes, or direct endolaryngeal injury. Such patients present with varying degrees of hoarseness and odynophonia.

The mucosa of the true vocal folds is hyperemic from dilated vessels present on the superior and free surfaces. Oedema within Reinke’s space develops, and submucosal hemorrhage may occur. This form of laryngitis is self-limiting and subsides within a few days when treated with voice conservation and humidification.

Vocal nodules may become chronic in children who continually abuse their voices. Surgical treatment is only rarely indicated. 

Acute laryngeal infections of adults 

Acute viral laryngitis in adults is common, and it is generally less serious than in children because of the larger adult airway, which is able to accommodate more swelling without compromise of the airway. The typical type of acute laryngitis seen in adults is almost always viral.

Influenza and parainfluenza viruses, rhinoviruses, and adenoviruses are the most common causative agents, although many other viruses have been implicated. The disease is self-limiting and is best treated symptomatically with humidification, voice rest, hydration, cough suppressants, and expectorants.

Antibiotic treatment is not usually necessary.

In the professional vocalist, corticosteroids are sometimes used to reduce the vocal fold oedema, particularly during the recovery phase.

Bacterial laryngitis may develop secondary to purulent rhinosinusitis or tracheobronchitis and generally is less commonly diagnosed in adults than in children.

Supraglottic involvement (epiglottitis), as in pediatric patients, is the most common form of bacterial laryngitis. Supraglottitis in adults has a slightly different clinical picture. In adults, the infectious agent is less likely Haemophilus and more likely group A streptococcus. The clinical course appears less severe, with less seasonal variation and airway compromise. Although one must never be complacent with management of the airway, conservative airway management in an intensive care setting is often successful, and tracheostomy is rarely required.

In adults, two useful clinical predictors of the need for endotracheal intubation are presentation to the emergency department less than 8 hours after the onset of a sore throat and drooling (in preference to swallowing because of severe odynophagia) at presentation.

Conservative measures include oxygenation, humidification, hydration, corticosteroids, and intravenous antibiotics. A high index of suspicion should be maintained for progression to laryngeal/epiglottic abscess that is more common in adults. 

Chronic infections (granulomatous diseases)

Granulomatous infections (eg, tuberculosis and syphilis) were recognized long ago and continued to be common afflictions throughout the world in the preantibiotic era. During the twentieth century, these conditions appeared to be on the decline, and some of them had all but disappeared, until relatively recently.

With the advent of effective anticancer chemotherapy, organ transplantation, and human immunodeficiency virus (HIV) infection, it was discovered that the microorganisms causing many of the granulomatous diseases thrive in the immunocompromised host.

Granulomas are nodular histopathologic lesions, characterized by a central mass of epithelioid and giant cells surrounded by lymphocytes and other inflammatory cells. Central necrosis (caseation) is seen in many granulomatous conditions and is conspicuously absent in others. Unlike children, adults have many chronic forms of granulomatous laryngitis, and these may go unrecognized for many years.

Chronic granulomatous conditions involving the larynx may be attributable to numerous different types of microorganisms (bacteria, fungi, viruses), to an autoimmune process, or to an idiopathic cause. Some parasitic infections may also cause laryngeal granulomas.

Granulomatous lesions of the larynx may appear as smooth, diffuse swellings of the affected tissues; diffuse cobblestone mucosa; well-defined, discrete nodules; or an ulcerated inflammatory mass.

Sometimes granulomatous diseases mimic laryngeal carcinoma. The necessity for biopsy cannot be understated.

Granulomatous diseases caused by bacteria include tuberculosis, leprosy, syphilis, and scleroma, among others. In the past, tuberculous laryngitis usually was accompanied by advanced pulmonary tuberculosis. More recently, slightly more than one-third of patients with tuberculous laryngitis have active cavitary lung disease.

Tuberculous laryngitis remains one of the most common granulomatous diseases of the larynx. Approximately one-quarter of the patients present with airway obstruction. In the past, tuberculosis tended to involve the posterior part of the larynx, but, more recently, the true vocal folds appear to be the most commonly involved site.

Mycotic granulomatous diseases of the larynx include candidiasis, blastomycosis, and histoplasmosis.

A relatively benign but common isolated form of laryngeal candidiasis (without the involvement of other contiguous anatomic structures) occurs in some patients who use corticosteroid inhalers for asthma. Treatment is targeted at the specific aetiologic agent. Idiopathic granulomatous diseases include sarcoidosis and Wegener’s granulomatosis.

Recommended treatment includes corticosteroids and possibly other immunosuppressive agents.

Allergic, immune and idiopathic disorders 

Anaphylaxis, an acute and profoundly life-threatening immune-mediated allergic response, is made up of a triad of clinical manifestations:

  1. flushing, pruritus, and/or urticaria;
  2. airway obstruction (angioedema, laryngospasm, and/ or bronchospasm); and
  3. circulatory collapse (shock).

Angioedema, which may occur with or without anaphylaxis, is an acute, allergic, histamine-mediated, inflammatory reaction characterized by acute vascular dilation and capillary permeability.

Angioedema can be precipitated by medications (eg, penicillin, aspirin, other nonsteroidal anti-inflammatory drugs, and angiotensin converting enzyme inhibitors), food additives and preservatives, blood transfusions, infections, or insect bites.

Hereditary angioedemais an autosomally dominant inherited deficiency of C1 esterase inhibitor that leads to recurrent attacks of mucocutaneous edema.

Treatment of both types of angioedema includes epinephrine (adrenaline), corticosteroids, antihistamines, and aminophylline.

Intubation or tracheostomy may be required.

“Pretreatment” of hereditary angioedema with danazol appears to elevate levels of functional C1 esterase inhibitor and to help prevent recurrent episodes.

Immunocompromised patients, whether immunocompromised from diabetes, long-term corticosteroid therapy, chemotherapy, or AIDS, are at risk of developing opportunistic infections of the aerodigestive tract. The most commonly reported opportunistic infections that affect the larynx are candidiasis, tuberculosis, and herpes infections.

Systemic autoimmune disorders that affect the larynx include rheumatoid arthritis, systemic lupus erythematosus, cicatricial pemphigoid, relapsing polychondritis, and Sjögren’s syndrome.

Presenting symptoms and findings include dysphonia, ulceration, granulation tissue, glottic and subglottic stenosis, and vocal fold immobility secondary to cricoarytenoid arthritis.

Treatment includes airway maintenance, systemic corticosteroids, and other immunosuppressive agents. 

Miscellaneous inflammatory conditions 

Parasitic infections that affect the larynx include trichinosis, leishmaniasis, schistosomiasis, and syngamosis.

Trichinosis is suspected from the history and eosinophilia, and the diagnosis is made with serologic testing and muscle biopsy. The diagnosis of leishmaniasis is based on demonstrating the parasite in a biopsy of the granuloma. Diagnosis of schistosomiasis may be suspected by the histologic examination. Confirmation of the diagnosis may be made by identification of parasitic ova in the urine or feces.

Treatment of schistosomiasis is with the appropriate antihelminthic medication (praziquantel or oxamniquine).

The size and anatomic configuration of the larynx (having the narrowest and most convoluted lumen of the upper airway) make it particularly susceptible to inhalation laryngitis.

Acute thermal and toxic injuries are often seen in patients with facial burns. In this regard, thermal injury usually plays a greater role than chemical injury in the larynx. Intense heat produces excessive vasodilation, capillary permeability, massive oedema, and thus airway obstruction. The oedema usually peaks at 8 to 24 hours following injury and resolves within 4 to 5 days.

The severity of permanent damage depends on the severity of the burn. Complete laryngeal stenosis can occur.

Treatment consists of providing humidified oxygen and maintaining the airway. In most cases, corticosteroids and antibiotics should be avoided. Weeks after the acute injury has resolved, laryngeal dilation and surgical procedures to re-establish the airway, if necessary, may be performed.

The common clinical manifestations of allergy to inhalants are well known to otolaryngologists: sneezing, watery rhinorrhea, nasal congestion, and obstruction. The most common offending allergens are dusts, pollens, molds, and chemicals. Allergic reactions of the larynx, similar to those seen in the nose, are uncommon but do occur.

The diagnosis is made by the history, clinical findings, and intradermal skin testing.

Treatment should be removal of the offending allergen(s), if possible, and desensitization. Corticosteroid inhalers are ineffective in laryngeal allergy and should be avoided.

Tobacco and several other carcinogens cause chronic inflammation of the larynx. These substances can cause mucosal thickening, submucosal edema, hyperkeratosis, dysplasia, and, eventually, carcinoma. In the larynx, leukoplakia, pachydermia, and Reinke’s edema (polypoid degeneration) should be viewed as precursors to the development of carcinoma.

Radiation therapy for laryngeal carcinoma, as well as for tumors in other head and neck sites, may deliver significant radiation doses to normal laryngeal tissue. The initial effects produce an intense inflammatory response, characterized by increased capillary permeability, edema, neutrophilic infiltration, vascular thrombosis, and obliteration of lymphatic channels. 

Patients undergoing radiation treatment complain of a globus sensation, dysphagia, odynophagia, dysphonia, and odynophonia.

On laryngeal examination, the larynx appears red and swollen, and a fibrinous exudate may be present. The symptoms tend to worsen as the treatment progresses; they are worst at the completion of treatment and gradually abate thereafter. Late tissue sequelae consist of degenerative changes and fibrosis in adipose, connective, and glandular tissues and a pronounced obliterative endarteritis of small blood vessels. These changes may take place over a period of years, and the symptoms of many patients worsen with time.

Treatment is symptomatic, consisting of hydration, adminis-tration of expectorants, and environmental humidification.

Radionecrosis is a late complication of laryngeal irradiation, being the result of ischemia of the cartilaginous framework. When a patient presents after radiation therapy with increasing symptoms and laryngeal edema, the clinician must determine the cause or causes.

The differential diagnosis of laryngeal radionecrosis also includes tumor recurrence and reflux. Which of these, known as “the three r’s”(radionecro-sis, recurrence, reflux), has caused the patient’s increasing symptoms will determine the treatment. Each patient must be evaluated for each of the three possibilities.

Treatment for radionecrosis should be individualized. In some cases, necrotic cartilage and soft tissue can be removed through an endoscopic approach. Often, however, an open surgical procedure is needed.

Screaming and other forms of vocal abuse can lead to acute submucosal hemorrhage of the vocal folds. By history, such hemorrhage occurs abruptly and produces severe dysphonia. On examination, the appearance of hematoma is unmistakable.

Voice rest is the usual treatment, although some laryngologists recommend surgical drainage in selected cases.

Muscle tension dysphonia is a generic term for any “functional”voice disorder caused by chronic vocal abuse or misuse.

Patients with vocal nodules, contact ulcers, and granulomas or the Bogart-Bacall syndrome fit into this category, as do patients with psychogenic voice disorders.

Muscle tension dysphonia can be classified as primary or secondary. Primary muscle tension dysphonia is attributable to nonorganic vocal fold pathology. The behavior may be learned or entirely psychogenic. Secondary, or compensatory, muscle tension dysphonia is a result of an underlying glottal insufficiency. The glottal incompetence may be caused by presby-laryngis, vocal fold paralysis, or vocal fold paresis.

The findings are supraglottic hyperfunction that may be a physiologic attempt to compensate for underlying glottal closure problems. Muscle tension dysphonias are common in professional voice users and are frequently initiated or complicated by reflux laryngitis.

Treatment with voice therapy, surgery, and, when appropriate, antireflux therapy often successfully resolves the problem.

Anatomically, only a thin layer of mucosa and perichondrium overlies the cartilaginous vocal processes, so ulceration over a vocal process can occur from a variety of insults, including vocal abuse, coughing, viral infection, GER, and endotracheal intubation.

Granulomas over the vocal process are five times more common than ulcers.

Chronic ulcers over the vocal processes are uncommon because most either heal or go on to form granulomas.

Regardless of the inciting cause, patients with these lesions should initially be treated with “voice modification”(not voice rest) to reduce continual vocal process trauma and antireflux therapy (preferably with a PPI).

This regimen will result in healing in the majority of cases within 6 months.

Although surgical removal is seldom necessary, it should be considered

  1. when there is concern about the pos-sibility of carcinoma,
  2. when the lesion has matured and taken on the appearance of a fibroepithelial polyp, and
  3. when the airway is obstructed

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