INFECTION OF THE LARYNX

Viral Laryngitis

• The most common viral pathogens in the upper respiratory tract include rhinovirus, influenza A. B, C, and parainfluenza viruses.

• normal duration of 5 to 7 days • usually dysphonic• Odynophagia• laryngeal phonotory trauma (phonation and

coughing, pollutants)

• Patients with substantive vocal fold edema from viral laryngitis are at increased risk of repetitive phone trauma leading to more significant vocal fold injury.

• Such as midmembranous vocal fold lesions, epithelial and subepithelial trauma ulceration, and scar

• Hydration • Systemic corticosteroids• Antibiotics are not indicated in patients

presenting with symptoms typical of viral laryngitis

• Acute dysphonia lasting longer than 2 weeks is unlikely to result from viral laryngitis, and other etiologies should be investigated, including a detailed laryngoscop~

Bacterial Laryngitis

• Clinical presentation may be similar to that of viral laryngitis, but supraglottitis and epiglottitis may result.

• As with the pediatric population, given the potential for airway demise.

• Haemophilus injluenz.ae, Streptococcus species, and Staphylococcus species.

• Haemophilus species remain the most common but methicillin-resistant

Diagnosis relies on endoscopic examination

Radiologic imaging

• Classic "thumb-print" sign of supraglottic inflammation.

Treatment• Medical treatment is targeted to the pathogen identified

by culture. • Additional supportive measures such as hydration and

steroids are indicated (9). • Though not common in the United States, rhinoscleroma

can also affect the larynx. Caused by Klebsiella rhinoscleromatis, patients tend to have laryngeal involvement (13/22 patients) and may need emergent tracheotomy to maintain airway patency (3/13 with laryngeal involvement)

• Pathologic examination demonstrates the gram-negative coccobaccillus of Klebsiella on culture, as well as Mikulicz cells on mucosal biopsy.

Fungal Infection

• Fungal laryngitis often occurs in immunocompromised patients, such as patients with systemic causes far immunsuppression (HIV, chemotherapy, diabetes, etc.)

• and individuals who are locally imm.unocompromised because of steroid inhaler use.

• Patients will present with laryngopharyngeal symptoms, such as dysphagia and dysphonia.

• Physical examination demonstrates white plaque-like epithelial lesions of the mucosa surfaces, which may be focal or diffuse

• Though the majority of fungal infections are Candida other fungal organisms, such as blastomycosis, cocdioidomycosis, and histoplasmosis

• These infections target immunocompromised patients as seen with Candida sp. infections but tend to occur in endemic geographic regions.

• Blastomycosis and stoplasmosis are prevalent in the Mississippi and Ohio river valleys, and coccidioidomycosis is endemic in the outhwestern United States and Central America.

• Theatment involves long-term systemic antifungal therapy with agents such as amphotericin or triazole.

• topical antifungal

Mycobacterial Infection

• Laryngeal tubercular infection from Mycobacterium tuberculosis is classically associated with active pulmonary disease but can present as isolated laryngitis

• Laryngeal M. tuberculosis infections follow similar natural history to pulmonary tuberculosis and most commonly present as lesions in the posterior glottis.

• Patient factors include increased prevalence in underdeveloped countries, areas of over-crowding and communal living, and immunocompromised populations.

• While laryngeal infections present with similar symptoms as pulmonary infections (cough, hemoptysis, unintentional weight loss, fever, night sweats

• Patients may also present with laryngopharyngeal symp-toms such as dysphonia, dysphagia, and odynophagia.

• Physical examination can demonstrate exophytic masses that mimic malignancy

• Pathologic examination demonstrates caseating granulomas that are pathognomonic to M. tuberculos1s infection.

• Treatment is targeted with multidrug regimens with culture guidance,.

• as multidrug resistant M. tuberculosis strains are on the rise.

Other Infections

• Less common infections of the larynx include leprosy and syphilis. Mycobacterial leprae and Mycobacterium lepromatosis, the causative infectious agents of leprosy, cause dramatic systemic and laryngeal epithelial changes.

• As with the other laryngeal infections, patients can present with variable severity in symptoms, with the most severe being occult aspiration or complete upper airway obstruction requiring tracheotomy

• The World Health Organization recommends multidrug treatment with combinations of dapsone and rifampin with possible adjunctive clofazimine.

Syphilis• Caused by 'Iteporl£ma pallidum infection and

generally presents in stages. The primary stage generally presents to the otolaryngologist as a painless oropharyngeal change.

• During the secondary stage, patients can present with laryngeal manifestations, including leukoplakia, exophytic mass( es ), and very rarely, decreased vocal fold mobility .

• Diagnosis involves serologic studies (venereal disease research laboratory or rapid .

• The mainstay of treatment is penicillin.

Idiopathic Ulcerative Laryngitis

• Idiopathic ulcerative laryngitis (IUL) was first described in 2000 and a large clinical series was presented in 2011

• This condition involves dysphonia and severe cough following an upper respiratory tract infection and ulceration of the midmembranous vocal fold.

• IUL appears to occur more in females than males • An etiologic agent has not been identified and medical

therapy with antibiotics, antifungal, and proton pump inhibitors are typically used but without an obvious positive response.

INFILTRATION OF THE LARYNX

Wegener Granulomatosis

• Wegener granulomatosis is associated with necrotizing granulomatous inflammation and vasculitis of small blood vessels.

• The disease tends to affect the upper airway, the lungs, and the kidneys

• nonhealing ulcers in the nasal cavity or, • more rarely, subglottic airway stenosis. • nasal and laryngeal endoscopy, and testing for

classical antineutrophil cytoplasm antibody (c-ANCA).

• Medical management with systemic corticosteroids and/or cyclophosphamide is used to obtain remission, and medications such as methotrexate, trimethoprim methoxazole, or azathioprine are used for maintenance therapy .

• Surgical treatments include subglottic expansion (subglottic releasing incisions with balloon or rigid dilation)

• Subglottic stenting is generally avoided in favor of tracheotomy for recalcitrant presentations

• intralesional injection of corticosteroids .

Rheumatoid Arthritis

• Rheumatoid arthritis affects millions of people worldwide with a predilection for females.

• It affects the larynx in just over one-fourth of cases • Active rheumatoid arthritis tends to present with a

substantial laryngitis with erythematous arytenoid mucosa

• Chronic rheumatoid arthritis also selectivdy targets the arytenoid cartilages, but more specifically seems to affect the cricoarytenoid joint causing ankylosis and possible joint fixation

• Patients may also present with rheumatoid nodules, also known as bamboo nodes, which are focal subepithelial lesions, typically on the superior surface of the membranous vocal fold.

• Theatment of rheumatoid arthritia relies upon medical management with immnomodular and anti-inflammatoty treatments.

• Surgical management may be indicated to manage airway symptoms or to judiciously remove rheumatoid nodules to improve phonation

• vocal fold steroid injections

Relapsing Polychondritis • Relapsing polychondritis is characterized by intermittent

recurrent episodes and inflammation of cartilaginous structures.

• While the ears and nose are most commonly affected, the lacynx can also become involved.

• (MRI) and computed tomography can identify cartilaginous changes.

• Patients with ear, nasal, and/or airway complaints such as exertional dyspnea or stridor.

• Medical management is low dose corticosteroids and/or methotrexate.

• Dapsone has also shown to be beneficial .• Surgical intervention may be indicated to secure the airway with

tracheotomy.

Pemphigus and Pemphigoid

• Pemphigus and pemphigoid are related autoimmWle conditions differentiated by the target of their autoantibodies.

• While both conditions lead to a robust/хүчтэй/ infflammatory reaction that can possibly lead to epithelial injury, pemphigus autoantibodies are directed against intraepithelial targets while pemphigoid autoantibodies target subepithelial antigens.

• ImmWlofiuorescence of tissue biopsy is used to identify the characteristic autoantibodies for definitive diagnosis.

• Patients may present with signs of disease within the nasal cavity or the larynx. The prevalence of laxyngeal involvement seems to differ between the diseases for unknown reasons.

• One study demonstrated that 21 of 53 ( 40%) patients with head and neck manifestations pemphigus had laryngeal involvement { 45).

• However a separate study of pemphigoid patients demonstrated that 10 of 38 (26%) patients with head and neck symptoms had laryngeal involvement

• Other studies have demonstrated relatively similar prevalence in pemphigus

• Both pemphigus and pemphigoid appear to have a predilection for supraglottic mucosa (Fig. 67 .S).

• High-dose corticosteroids are utilized to control active disease and are decreased for maintenance therapy.

• Other immunomodulators, such as azathioprine. cyclophosphamide, and cyclosporine, have also been utilized for medical management.

• Surgical intervention is limited to diagnostic biopsy and for ait:way intervention, such as tracheotomy or less invasive airway surgery: (dilation) to provide a stable airway.

External Beam Radiation

• As the role of external beam radiation has increased for the treatment of head and neck malignancies, many of these patients later present with laryngopharyngeal complaints, such as dysphonia, dysphagia. and globus sensation post treatment.

• Electron beam radiation induces gradual, dose dependent fibrotic changes to include muscle atrophy and fibrosis in the larynx as well as desiccation of mucosa

• Fibrosis within the lamina propria can be appreciated as decreased mucosal pliability on stroboscopy.

• Patients will exhibit atrophy that is disproportionate to their expected age-related vocal fold volume loss.

• Vocal fold hypervascularity is a common finding due to prior vasculitis incurred during radiation therapy.

• Improvement in voice is commonly reported following laryngeal radiation for early lacyngeal cancar but voice outcomes associated with late radiation :fibrosis of the vocal folds uncertain (50,51). A prior report of postradiation vocal

• quality suggests that vocal fold stripping or exdsional

• biopsy rather than limited biopsy for initial diagnosis and

• continued tobacco smoking after treatment are significantly associated with an increased risk of perceived worse voice quality after treatment

• As radiation oncologists develop more sophisticated techniques to avoid collateral damage to uninvolved structures, the extent of radiation changes may decrease.

BENIGN NEOPLASIA OF THE LARYNX

Hamartoma

• Hamartomas are rare, benign lesions that can present as congenital malformations or lesions later in life.

• They are generally loosely oiganized neoplasms with multiple types of tissue, all of which are native to the affected subsite of the larynx.

• Hamartomas can be incidentally identified or cause significant airway symptoms, especially in a young child.

• Presentation and symptomatology are related to the location of the neoplasm, and hamartomas have been mostly commonly identified in the supraglottis and subglottis

• Exisional biopsy is both diagnostic and curative if resection is complete

Chondroma• Chondromas are benign tumors consisting of cartilaginous cells.• They are slow-growing lesions that do not metasta-size, and they

generally present as a smooth, submucosal lesion. Laryngeal chondromas may be difficult to differentiate from low-grade chondrosarcomas and clinically follow a similar courSe.

• While the bulk of these tumors present within the posterior cricoid cartilage, lesions have been found within other subsites of the larynx as well as the hyoid bone .

• Patients may be relatively asymptomatic. but lesions can cause airway obstruction or external neck masses .

• cr is generally the preferred imaging modality to define the crtent of the lesion .

• Surgical excision is the treatment of choice for chondromas.

• Surgical excision is the treatment of choice for chondromas.

• Surgery has been traditionally performed via open procedures involving laryngofissure, but, more recently, endoscopic ablation techniques have been shown to be successful

• Comparative efficacy between open and endoscopic surgical excision is unknown.

Respiratory Papillomatosis • Though primarily seen in the pediatric population, adult-

onset recurrent respiratory papillomatosis (RRP) is not an uncommon presentation.

• For further information regarding juvenile onset RRP, please refer to Chapter 94.

• Caused by human papillomavirus (HPV) subtypes 6 and 11, RRP occurs most commonly at the level of the vocal folds.

• The virus can be transmitted vertically or by sexual transmission. RRP can present anywhere within the upper aerodigestive tract from the nasal vestibule to the bronchioles with a predilection for areas of transition from pseudostratified columnar to stratified squamous epithelium.

• Lesions can be relatively small, noticeable only because of resultant dysphonia from decreased vocal fold mucosal wave propagation, dysphonia related to mass-effect that impairs glottal closure, or variable degrees of airway obstruction

• Though benign, they do have significant morbidity and have the potential for malignant transformation

• A recent study including 54 adults demonstrated that dysplasia was identified in 50% of patients, and dysplasia was diagnosed on biopsy specimens at an average of 16.2 months from initial diagnosis.

• Of the initial 54 patients, 3 progressed to carcinoma in situ while 1 patient progressed to squamous cell carcinoma

• Use of inhaled corticosteroids, increasing number of procedures, distal spread of disease, and previous exposure to cidofovir have been implicated as risk factors for dysplastic reaction .

• In addition, history of radiation therapy, cigarette smoking, and systemic immunosuppression have been implicated in malignant transformation.

• lhe verrucous papillomatous growth of the lesions are pathognomonic. • lhough. multiple treatment modalities are available. conservative removal of

disease is the firstline treatment.• If cold instrumentation is to be utilized, careful attention must be dedicated

to only removing the • papilloma and leaving the superficial lamina propria undisturbed. Ablation

with CO2 or potassium titanyl phosphate (KI'P) Jasen has also been shown to be a successful treatment modality for both initial and subsequent treatments

• A great benefit of fiber-based laser treatment is that it can be performed in an awake patient using a channeled endoscope through which the fiber am be advanced. Awake procedures decrease use of operative resources and eliminate the need and dangers of general anesthetic.

• Regardless of the surgical technique utilized, the physician must avoid deepithelialized surfaces in juxtaposition to avoid anterior glottic webbing and/or posterior glottic stenosis.

• While swgical removal of lesions remains the first-line teatment for RRP, other adjuvant therapies have been developed.

• Cidofovir is an antiviral shown to deaease disease burden in both intralesional injection and inhaled forms .

• Both treatment modalities have been shown safe. but hepatotoxicity has been identified with the injected form.

• Interferon-alpha and indole-3-carbinol an extract found in auciferous vegetables) have both been used to control disease propagation

• The United States Food and Drug Administration {FDA) approved Gardasil.. a vaccination against HPV subtypes 6, 11, 16, and 18, in June of 2006 as a means of potentially preventing cervical cancer.

• While cervical cancer is mainly caused by HPV subtypes 16 and 18, the vaccination against subtypes 6 and 11, could drastically affect the prevelence and presentation of RRP.

• Currently, there is no definitive association between vaccination and disease modulation, thus vaccination is not presently indicated in patients with prior exposure .

Hemangioma

Laryngeal hemangiomas are more prevalent in the pediatric population, and this is presented in Chapter 104. In contrast to pediatric hemangiomas, which usually present in the subglottis, adult laryngeal hemangiomas present in the supraglottis (Fig. 67.10) (72).

• Hemangiomas are usually asymptomatic but can cause airway obstructive symptoms

• As these are incredibly rare tumors, no standardized treatment exists.

• A conservative approach emphasizing medical management with either corticosteroids or radiation therapy was historically advocated.

• Though successful in the pediatric population, laser ablation was initially avoided in adults for concern that the vasculature would exceed C02 laser coagulation capacity.

• However, a repon of four laryngeal hemangiomas ablated without incident calls that initial theory into question

• Propanolol has also been successful in treating laryngeal hemangiomas in children, but there are no repons of its use in the adult population .

Fibroma

• Laryngeal fibromas are exceedingly rare with fewer than a dozen cases reported. Histologic examination demonstrates abundant extracellular matrix with interspersed paucicellular areas, and the extracellular matrix tends to be composed of •cytologically bland spindle cells.“

• The reported cases all appear to be isolated lesions that presented with dysphonia and cough (77).

• Radiographic imaging ( cr and MRI) can delineate the full extent of the lesion in planning for surgical resection.

• Excision with margins is advocated to minimize chance of recurrence

Schwannoma

• Schwannomas arise from ner:ve sheath fibers and account for less than 1% of all laryngeal tumon~.

• The endoscopic appearance may be mistaken for a laryngocele and commonly appear as smooth submucosal mass within the pyriform sinus or aryepiglottic space

• Patients may present with globus sensation, dysphagia. dysphonia. and if luge, airway obstruction (SO). Imaging with Cf and/or MRI help to plan surgical resection.

• Histopathologic examination demonstrates the classic Antoni A and Antoni B area seen with other schwannomas.

• The associated nerve was not identified in the available case reports.• Some patients have postoperative dysphonia and vocal fold paresis,

possibly implying recurrent laryngeal involvement {79).

LARYNGOCELES AND SACCULAR CYSTS

• While laryngoceles and saccular cysts are not neoplasms, they present as benign appearing masses in the larynx.

• The laryngealsacalle is a mucous gland containing appendage that lies between the false vocal fold and the thyroid cartilage.

• It is an out pouching of the normal laryngeal ventricle and atends as a blind-ended sac posterolateral to the edge of the laryngeal surface of the epiglottis.

• The function of the sacullar is unknown although it has been theorized that it may represent a vestigial air sac.

• Both laryngoceles and sacallar cysts involve expansion of the saccule to form a mass.

• LaJ:yngoceles by definition must have air contained within their lumen, while saccular cysts are strictly fluid filled masses.

• Laryngoceles contain air due to patent commWlication • with the laryngeal lumen. Further classification of laryn-• goceles depends on their location. They can be defined as

internal, externaL or combined. Internal laryngoceles are

• strictly confined within the Thyroid cartilage. extemallary:goceles lie exclusively outside the cartilaginous I~

• framework. and combined lar:yngoceles span bo1h the inside

• and outside of the thyroid cartilage (82,83) (Fig. 67.11).

To underline • Multiple infections, inflammatory, and benign processes can affect the

larynx. Each has its own unique presentation and treatment considerations.

• Infectious laryngitis is most commonly viral in etiology. and should be initially treated with voice rest and supportive measures in most cases. Bacterial, fungal, and mycobacterial infection is considerably more rare.

• Inflammatory and infiltrative processes of the larynx can occur from Wegener granulomatosis (typically subglottic involvement), sarcoidosis (typically supraglottic involvement), amyloidosis, and autoimmune processes (such as rheumatoid arthritis, SLE, and pemphigus/pemphigoid)

• The most common benign neoplasm of the larynx is laryngeal papillomatosis. Laryngeal chondromas, hamartomas, schwannomas, fibromas, pleomorphic adenomas, and granular cell tumors are far more rare.