Infectious or Allergic Chronic Laryngitis

Chronic laryngitis refers to an inflammatory process that determines irreversible alterations of the laryngeal mucosa. Reactive and reparative processes of the larynx represent the main pathogenetic factor, which can persist even when the causative stimulus ends. Depending on the causes, the pattern of changes can be very different. Inflammation, edema, hyperemia, and infiltration and proliferation of the mucosa can represent different levels of response to insults.

The inflammatory process damages the ciliated epithelium of the larynx, particularly in the posterior wall. This impairs the important function of moving the mucous flow out of the tracheobronchial tree. When the ciliary beating motion of the epithelium is impaired, the resultant mucus stasis on the posterior wall of the larynx and around the vocal cords provokes a reactive cough. Mucus across the vocal cords may manifest with laryngospasm. Significant changes may arise in the vocal cord epithelium in the form of hyperkeratosis, dyskeratosis, parakeratosis, acanthosis, and cellular atypia.

Frequency

United States

The authors found no data regarding precise frequency. Because chronic laryngitis is usually part of a more complex disease, it is probably underreported.

Mortality/Morbidity

Chronic laryngitis presents a frustrating treatment problem. Voice loss, chronic cough, and airway obstruction, respectively, are the most likely complications. An association with cancer of the larynx is unclear. Mortality is obviously related to the main disease with which chronic laryngitis is associated.

Race

The condition apparently affects all races equally.

Sex

Traditionally, men have been mostly affected. In recent reports, a 2:1 male predominance still exists; however, the trend is changing, probably because of more women smoking cigarettes and their increasing involvement in work activities in toxic environments.

Age

Adults in the sixth decade of life are mainly affected. Neonates and infants share similar risk factors with adults for developing chronic laryngitis. Additionally, various congenital lesions of the larynx may present with voice changes.

Signs and symptoms derive from anatomic functional alterations of the larynx and from involvement of contiguous structures. When chronic laryngitis is a manifestation of a systemic disease, then the stigmata of the main pathologic process predominate.

• Hoarse voice and dysphonia are frequently described. Voice quality and quantity may fluctuate, although complete recovery never occurs.

• Chronic cough is reportedly most marked at night. If gastroesophageal reflux disease (GERD) is the causative factor, the cough can be described as either dry or productive of small amounts of mucus, depending on the degree of involvement of the posterior wall of the larynx. Belching can occur.

• Stridor due to laryngospasm may occur if mucus strands cross the vocal cords.

• Dysphagia and otalgia are identified when the pharynx is involved because of the shared innervation between the throat and the pharynx.

• Personal history

  • Time of symptom onset and symptom quality and variation, along with precipitating or relieving factors

  • General state of health, symptoms and signs of thyroid disease or lung cancer, and any medical conditions that could elicit or mimic chronic laryngitis

  • Occupational history, including contact with toxic substances, fumes, dusts, and/or rapid temperature changes

  • Vocal abuse, professionally related or otherwise

  • Heartburn, regurgitation, dysphagia, cough, wheezing, hoarseness, chest pain, or otalgia, which raise suspicion for GERD. According to a recently published survey, ENT physicians who diagnosed GERD-related laryngitis often relied on the presence of globus and throat clearing.[1]

  • Presence of asthma, which should alert physicians to the possibility of vocal cord dysfunction (ie, history of throat but not chest tightness, difficult phonation, laryngeal stridor and wheezing that is worse on inspiration), allergies, GERD, or processes involving the tracheobronchial tree

  • Prescriptions or over-the-counter medications (eg, diuretics, antihypertensives, psychotropic drugs, antihistamines, decongestants) that may cause predisposition to or determine the onset of chronic laryngitis

    • These agents may cause local drying, mucosal injury, or both.

    • If a patient provides a history of immunosuppressant or inhaled steroid use, then candidal laryngitis must be suspected.

  • Medications (eg, calcium channel blockers, nitrates, beta-blockers, progesterone) that may cause predisposition to GERD by decreasing the tone of the lower esophageal sphincter (LES) (Fuchs and Bucheler described a case of chronic hyperplastic laryngitis following the prolonged use of Cibacen 10, an angiotensin converting enzyme inhibitor.[2] )

  • Inhalation treatments, such as those in thermal baths

  • Surgical history, especially if intubation occurred

    • Thoracic and abdominal surgery point to the possibility of iatrogenic damage to the recurrent laryngeal nerve and resultant dysphonia.

    • These surgeries may cause consequent anatomic alterations that may predispose patients to GERD.

  • History of neck trauma

  • Ingestion of caustic substances

  • Travel history (for the possibility of parasitic infections)

• Family history

  • Family history is important when autoimmune diseases (eg, amyloidosis, systemic lupus erythematosus, Wegener granulomatosis, rheumatoid arthritis) are suspected.

  • Similar symptoms in other family members could help identify possible environmental pollutants responsible for chronic laryngitis.

  • Family members should be checked for infectious diseases with a propensity to spread (eg, tuberculosis).

• Social history

  • Cigarette smoking, recreational drugs, and alcohol abuse

  • Any practices that may pose a risk for infectious diseases (eg, promiscuity, risk factors for HIV/AIDS, syphilis)

  • Eating habits, with special attention to the consumption of chocolate and caffeine that may determine relaxation of the LES and eventually cause irritative laryngitis and GERD

General appearance and vital signs may provide useful clues.

• Accessory muscle use during respiration must be detected, if present. Auscultation of the airways and pulse oximetry measurement can be performed, if indicated.

• In case of infection, fever or parameters indicating toxicity may be present. Findings that point to a systemic condition as the etiologic factor can be detected.

• A thorough head and neck examination is a fundamental initial tool. Special attention to masses and lymphadenopathies may help localize malignancies.

• The thyroid gland and the laryngeal and tracheal cartilages must be evaluated.

• Indirect laryngoscopy can be performed during a routine physical examination. Direct techniques allow a more thorough examination of the larynx, using a flexible endoscope in patients who are awake or a rigid laryngoscope in patients under general anesthesia.

• Rarely, the inflammatory process is localized to the larynx. The surrounding structures may be involved. According to recent literature, some ENT physicians most often relied on the nonspecific findings of laryngeal erythema and edema to diagnose and treat GERD-related laryngitis.[1]

  • Particular attention must be paid to the base of the tongue, tonsil, nasopharynx, and sinuses to find an eventual primary source of infection.

  • The tracheobronchial tree and lungs must be considered as potential sources of infection.

  • Mucus (especially in the posterior wall of the larynx), erythema, and swelling are the most common findings in the nonspecific form of laryngitis. Pus may be present in cases of bacterial infection.

• Many conditions may look similar, such as histoplasmosis and blastomycosis, which are 2 fungal infections that may mimic tuberculosis or squamous cell cancer of the larynx.

• The epiglottis and vocal cords must be examined. The latter must be assessed during phonation.

• Stroboscopic examination helps determine if the mucosal stiffness is secondary to epithelial hyperplasia or chronic inflammation.

Cigarette smoke is chronically irritating to the laryngeal mucosa. At the extreme, it can provoke cancer.

Ethanol contains many impurities, such as mycotoxins, tannins, aldehydes, and pesticides, which may cause cancer, either by direct contact with the mucosa or through a systemic effect, or may act as an irritant.

Gastroesophageal reflux disease

Chronic laryngitis associated with GERD is particularly important. The irritant is the gastric content, and the most significant part of the injury occurs at night when patients lie down.

The posterior wall of the larynx is mainly involved in the common and mild forms of GERD, although the process can involve any part of the upper respiratory tract epithelium. Diagnosis can be made after excluding other causes and after confirming the condition with appropriate pH studies. Reflux from any cause can elicit chronic laryngitis.

Infections

The bacterium most commonly isolated in chronic infectious laryngitis is Staphylococcus aureus. Haemophilus influenzae and pneumococcal species may complicate the course of viral laryngitis.

In a retrospective study of 15 patients with infectious laryngitis, by Thomas et al, cultures revealed the presence of methicillin-sensitive Staphylococcus aureus, methicillin-resistant S aureus, Pseudomonas aeruginosa, and Serratia marcescens, along with normal respiratory flora.[3]  A study by Carpenter and Kendall reported that of 23 patients with chronic bacterial laryngitis, seven (30.4%) were found to be infected with methicillin-resistant Staphylococcus aureus.[4]

Tuberculosis, caused by infection with the tubercle bacillus Mycobacterium tuberculosis hominis, was a common disease of the larynx. Overall incidence has declined. The hematogenous route and the infected sputum from pulmonary tuberculosis are the most likely sources of infection.

Leprosy, caused by infection with Mycobacterium leprae (also known as Hansen bacillus): This acid-fast bacilli has a propensity to invade nerves and to affect the larynx, primarily the epiglottis. The portal of entry is thought to be the nasal mucosa; hence, nasal perforation is common. The larynx is the second most commonly affected part.

Syphilis, caused by the spiral bacterium Treponema pallidum: Syphilis has 3 stages of disease, as follows: primary, in which the chancre is the main clinical finding; secondary, in which systemic and cutaneous involvement predominate; and tertiary, in which destructive noninfectious processes are prevalent. The larynx is involved in the secondary and tertiary stages. Laryngeal involvement in congenital syphilis is similar to that seen in secondary syphilis.

Rhinoscleroma is caused by the gram-negative rod Klebsiella rhinoscleromatis.

Actinomycosis, a granulomatous disease caused by the anaerobic gram-positive bacteria Actinomyces israelii, is part of the normal oropharyngeal flora and may manifest as an abscess.

Viruses, although most important in determining viral laryngitis, play a minor role in the etiology of chronic laryngitis.

Fungal infections are very common. Patients who are immunocompromised, either naturally or as a consequence of a pharmacologic treatment, are mainly affected. Fungi can be found on the mucosal surface of the larynx, or they can invade it. Immunosuppression can be congenital or acquired and can be derived from AIDS. Immunosuppression can be drug induced (eg, antibiotics, steroids, chemotherapeutic agents) or secondary to radiation therapy.

A case study and literature review by Worrall et al found that out of 29 cases of laryngeal cryptococcosis, each of which involved persistent or progressive hoarseness, 28% of patients were immunocompromised, while, prior to infection, 67% of the immunocompetent patients had used nebulized or inhaled corticosteroids.[5]

Candidal laryngitis almost invariably manifests with pharyngitis due to superficial colonization of the mucosa; the oral cavity is often involved. When a patient takes inhaled steroids, the larynx can be the only site involved.

Invasive infections can occur as with blastomycosis and histoplasmosis, which are endemic conditions in certain areas of the world. In the United States, Histoplasma capsulatum and Blastomyces dermatitis are prevalent in the Ohio River area (histoplasmosis) and in the southwestern United States (blastomycosis).

Paracoccidioidomycosis, coccidiosis, aspergillosis, and rhinosporidiosis represent other fungal organisms that are less frequently involved in the development of chronic fungal laryngitis.

Although no endemic laryngeal parasitic infections exist in the United States, sporadic cases may affect foreign travelers with local organisms and with leishmaniasis and sporotrichosis.

Kania et al reported of a primary MALT lymphoma of the larynx associated with extraesophageal reflux, chronic laryngitis, and gastric Helicobacter pylori infection.[6]

Other

Voice abuse can be pertinent to professional singers and to occasional shouters. Lesions can range from simple edema, in the occasional abuser, to hyperplastic reactions if the stimuli persist over time.

Allergic responses of immediate or delayed hypersensitivity types can cause chronic laryngitis.[7] Although the authors found no data quantifying the exact number of people affected, current thought seems to indicate an increasing prevalence.

Environmental factors, such as dust, fumes, chemicals, and toxins, can cause this condition.

Chronic laryngitis has been diagnosed in many people who 20 years earlier inhaled sulfur mustard, an alkylating warfare agent used in the Iran-Iraq war (1983-88).[8]

Systemic diseases

Systemic diseases, mostly autoimmune, may cause chronic laryngitis. They include the following:

• Wegener granulomatosis: Inflammation and granulomas may affect the larynx. It can be localized, involving only the upper airways. Clinically, patients may present with hemoptysis and stridor and upper airway stenosis of unexplained etiology, depending on the degree of involvement. Biopsy is not always diagnostic.

• Amyloidosis: Amyloid deposition can involve the larynx and the upper aerodigestive tract. Patients may present with symptoms of upper airway obstruction, dyspnea, and hoarseness. The amyloid can cause vascular fragility and consequent bleeding.

• Relapsing polychondritis: Adults in the fifth decade are mostly affected. They may present with hoarseness, airway obstruction, and pain. Clinically, the larynx can be tender. Symptoms and signs are secondary to inflammation and swelling of the glottic and subglottic areas. Repeated inflammation may result in tracheomalacia.

Cutaneous diseases

The larynx and the skin share similar microcharacteristics and macrocharacteristics. Pemphigus, Stevens-Johnson syndrome, systemic lupus erythematous, and epidermolysis bullosa are among the most important conditions.

Systemic lupus erythematous may manifest with laryngeal ulceration, erythema, and edema. Rheumatoid type nodules and necrotizing vasculitis can be seen.

With rheumatoid arthritis, the joints and the mucosa of the larynx can be affected to the same extent that other parts of the body are affected.

Neurologic causes

Neurologic causes may contribute to chronic laryngitis. Two branches of the vagus nerve supply the larynx, the superior laryngeal nerve and the recurrent laryngeal nerve (RLN). Alterations of the nerve supply and the larynx muscles determine abnormal motility of the various components of the larynx with resultant irritation.

Possible outcomes include the following:

• Unilateral paralysis of the vagus nerve or the RLN

• Bilateral abductor paralysis, in almost all cases caused by extensive thyroid surgery, with injury to the RLN

• Superior laryngeal nerve paralysis, most often secondary to thyroidectomy or supraglottic laryngectomy

Additional causes

Spastic dysphonia is a discrete vocal disorder characterized by strained, choked vocal attacks (laryngeal stuttering). The onset usually follows a stressful period in middle life. This condition is probably a vocal expression of psychoneurotic behavior or a CNS and/or proprioceptive disorder of the larynx.

Vocal folds atrophy and lose tension with age, causing changes in phonation. Loss of thyroarytenoid ligament elasticity results in breathiness and loss of breath support because of bowed vocal folds.

Muscular disorders may contribute to chronic laryngitis. Weakness of the larynx and the pharynx is present in one third of patients with myasthenia gravis.

Laryngitis can be secondary to pellagra.[9]

See the list below:

• Complete blood cell count with differential if an infection is suspected

• Sputum cultures and sensitivities for bacteria, fungi, and viruses

• Swab of the laryngeal mucosa, culture and sensitivities for bacteria, fungi, and viruses

• Serologic markers for autoimmune disorders

• Studies for tuberculosis and syphilis when such conditions are being considered

See the list below:

• A lateral plain neck radiograph can help visualization of supraglottic and retropharyngeal swelling and soft tissue density in the subglottic airway. It is especially helpful in the emergency department.

• Chest radiograph

• CT scanning and MRI better define soft tissue alterations and provide the best information regarding the structure of the larynx.

• Barium swallow study, double-contrast upper GI series, and manometry are often used to evaluate otolaryngologic manifestations of GERD.

• A videostrobe is probably the single most important study after excluding a tumor. It provides significant information regarding vocal fold vibration, which can be recorded on a monitor.

See the list below:

• Skin tests if allergies are suspected

• Twenty-four–hour pH monitoring if GERD is in the differential diagnosis

The larynx can be directly examined with a flexible fiberoptic nasopharyngolaryngoscope. Direct laryngoscopy with a rigid laryngoscope (under general anesthesia) may be required for a detailed laryngeal inspection and may help obtain tissue for biopsy, cultures, and smears to identify the presence of organisms. Undertake this examination when noninvasive studies fail.

Accomplish a thorough evaluation of the aerodigestive tract, including bronchoscopy and esophagoscopy, when indicated. Stroboscopic examination may help to differentiate mucosal stiffness secondary to epithelial hyperplasia that may be caused by chronic inflammation. Endoscopic removal of polyps and lysis of adhesions can be surgically accomplished.

A study by Witt et al suggested that hue and texture analysis of laryngoscopic images can be used to diagnose laryngopharyngeal reflux (LPR) in patients with chronic laryngitis. The study, which included 20 patients with LPR and 42 controls, used hue calculation and two-dimensional Gabor filtering to evaluate color and texture features of the images, with 80.5% classification accuracy found when hue and texture were assessed together.[10]

Frequently, the histologic examination may not distinguish the different possibilities. For example, reflux laryngitis and pachydermia associated with long-term smoking provide a similar clinical picture. In both cases, acute and chronic inflammatory cellular infiltrates predominate, with or without epithelial hyperplasia. Different patterns of chronic tissue response can result from the following insults:

• Infiltrative disorders (eg, amyloidosis). Lipoid proteinosis of the larynx, represented by hyaline deposits, may mimic singer's nodules or chronic laryngitis.[11]

• Chronic granulomatous diseases (eg, sarcoidosis, tuberculosis, fungal laryngitis)

• Chronic nonspecific inflammation (eg, bacterial laryngitis, laryngitis sicca)

• Proliferative processes involving the epithelial layer, hyperkeratosis, dyskeratosis, parakeratosis, acanthosis, and cellular atypia can cause chronic tissue responses. The most extreme clinical picture is laryngeal ulceration and presence of granuloma.

Medication therapies directed mainly against the causative agents vary on a case-by-case basis. With GERD, H2-receptor antagonists, proton pump inhibitors, and prokinetics are the main classes of drugs used. A study failed to provide evidence to support treatment with esomeprazole 40 mg twice a day for 16 weeks compared with placebo for chronic posterior laryngitis (CPL).[12]

A study by Mirić et al suggested that in patients with GERD and chronic laryngitis, gas diffusion capacity should be controlled, even when lung function is normal. The study included 30 children with chronic or recurrent laryngitis who tested positive for GERD. Increases in reflux indexes correlated with decreases in values for single-breath diffusing capacity of the lung for carbon monoxide (DLCO); ie, the odds for a significant reduction in the DLCO increased by 3.9% and 5.5% for each unit change in the Johnson-DeMeester and Boix-Ochoa scores, respectively.[13]

Supportive measures include the following:

• Hydration with about 2 liters of fluid intake per day

• Steam inhalation or room humidifier

• Avoidance of pollutant or irritative/toxic substances

• Identification and avoidance of environmental and occupational sensitizers: Limitation of exposure or change in the work environment if noxious fumes and organic solvents are responsible; avoidance of cigarette smoking, even secondhand smoke

From a therapeutic standpoint, the following procedures may be indicated:

• Reduction of stenosis is indicated if infiltrative processes or conditions, such as amyloidosis, Wegener granulomatosis, rheumatoid arthritis, or systemic lupus erythematous, have significantly narrowed the lumen of the larynx. Aggressive surgical intervention may be required.

• Exophytic mass removal by surgical means

• Laser vaporization

• Laparoscopic antireflux surgery, using the Nissen fundoplication technique, has shown appreciable results in the treatment of GERD.

Consultations with the following specialists may be necessary:

• Allergists, particularly when chronic inflammation of the larynx is suspected to be secondary to allergens and/or pollutants (after excluding other potential causes)

• Gastroenterologists

• Pulmonologists, particularly because Wegener granulomatosis, systemic lupus erythematous, rheumatoid arthritis, and asthma affect not only the larynx but also the lungs

• Otolaryngologists

• Speech therapists, especially when assessing and/or rehabilitating voice and swallowing (eg, after laryngeal surgery)

If swallowing difficulties exist, then the patient must be fed according to recommendations of a speech pathologist after appropriate swallowing evaluation.

• With GERD, avoidance of fat, alcohol, and caffeine should be practiced.

• Foods thought to play a role in the allergic pathogenesis of the chronic laryngitis must be avoided.

If GERD is present, any habits or activities that cause acid reflux from the stomach to the esophagus (eg, lying down in bed after a rich meal, movements that may increase intra-abdominal pressure) must be avoided. Elevating the head of the bed is also beneficial. After treatable medical and surgical causes of chronic laryngitis have been resolved, voice rehabilitation under the guidance of a speech therapist is the major tool.

S aureus is a frequent causative organism in cases of chronic bacterial laryngitis. Antimicrobial therapy should cover gram-positive and gram-negative pathogens.

Class Summary

Initial empiric antimicrobial therapy must be comprehensive and should cover both aerobic and anaerobic gram-negative organisms.

Amoxicillin and clavulanate (Augmentin)

Provides broad coverage for gram-positive, gram-negative, and anaerobic bacteria. Peak serum levels are higher than those of ampicillin. Drug combination treats bacteria resistant to beta-lactam antibiotics. Children > 3 mo, dose based on amoxicillin content. Because of different amoxicillin/clavulanic acid ratios in 250-mg tab (250/125) vs 250-mg chewable tab (250/62.5), do not use 250-mg tab until child weighs >40 kg.

See the list below:

• Further outpatient care is indicated whenever adherence to therapy may not be optimal and verification is believed to be necessary.

• Further outpatient care is indicated when prophylactic and epidemiological recommendations must be reinforced (eg, abstinence from cigarette smoking, airborne isolation and medical treatments for household contacts of a patient with tuberculosis).

• Further outpatient care is indicated when the physician wants to ensure that the pathologic findings of the larynx are regressing according to treatment plan expectations.

See the list below:

• Hospital admission is necessary when signs and symptoms of toxemia exist and intravenous antibiotic therapy is needed (eg, severe bacterial or fungal infections).

• ICU monitoring may be required when stridor or any other symptom suggesting important involvement of the airways exists. This may occur in the late stages of diseases, such as Wegener granulomatosis, rheumatoid arthritis, relapsing polychondritis, or amyloidosis, or with conditions that severely compromise the structure and functions of the larynx. Airway monitoring becomes of paramount importance.

• When a risk of aspiration exists, alternative forms of feeding may be used until the risk subsides.

• When contagious diseases are suspected, the appropriate isolation procedures must be implemented before identification of the responsible organisms and initiation of the indicated medical treatment.

• Further inpatient care is required for all cases in which verification of the response to the therapy and its optimization prior to discharge are needed.

• If chronic laryngitis is part of a systemic disease, then the treatment plan must take into account the different necessities that vary from case to case.

Transfer may be problematic only when respiration is compromised and risk of acute insufficiency exists. In these circumstances, preventive measures must be undertaken, and appropriate surgical instrumentation to perform a tracheostomy should be available.

See the list below:

• The most difficult problems that occur in patients with chronic laryngitis are as follows:

  • Systemic spread or spread to the surrounding structures of the eventual infectious process

  • Laryngeal stenosis due to acute suprainfection of a chronic situation and consequent edema or stenosis secondary to a long-term process that has not been addressed

  • Vocal cords with excessive reactive growth and permanent damage to their structure and, consequently, to their function

  • Transformation into cancer

See the list below:

• Prognosis mainly relates to the causative process.

See the list below:

• Detailed information regarding occupational/environmental substances and/or habits that might have caused a patient's chronic laryngitis must be provided. Strategies to avoid the causative factors and their consequences must be taught.

• Avoidance of cigarette smoking and secondhand smoke are of paramount importance.

• A speech therapist must be consulted when voice rehabilitation is needed. Recommend appropriate use of the voice.

• Educate patients regarding appropriate handling of medications. Inhaled corticosteroids may cause chronic laryngitis, presumably because of the local immunosuppressive effect, thus causing oral candidiasis. Inhaled corticosteroids can cause dysphonia, probably secondary to a myopathic effect. These effects can be minimized through dose reduction, switching to twice-daily administration, mouth rinsing, and the use of a spacer device.

• Patients should be aware that obesity is a risk factor for the development of GERD, probably related to increased intra-abdominal pressure.

• For excellent patient education resources, visit eMedicineHealth's Ear, Nose, and Throat Center. Also, see eMedicineHealth's patient education article Laryngitis.