Signs and Symptoms

Children may present with airway obstructive symptoms, particularly if they are presenting very young. Children may also have a husky cry or dysphonia. Secondary to the rare nature of the disease and the pediatrician′s inability to visualize the larynx, children are frequently misdiagnosed as having other airway problems such as asthma, bronchitis, or croup. Symptoms are present on average 1 year before diagnosis. In some cases, children will present with emergent airway obstruction. Adults typically present with dysphonia, rarely with acute airway compromise. Symptoms are present on average for 6 months before diagnosis.

Differential Diagnosis

Hoarseness in children may be caused by vocal nodules, reflux disease, vocal fold immobility, laryngotracheobronchitis, laryngeal cysts, congenital laryngeal abnormality, or neurologic conditions. Upper airway compromise causes may include congenital laryngeal lesions, laryngeal cysts, vocal fold immobility, subglottic stenosis, a foreign body, and infectious processes, such as epiglottitis or laryngotracheobronchitis.

Hoarseness in adults may be caused by vocal fold nodules, reflux laryngitis, vocal fold cysts or polyps, leukoplakia, vocal fold neoplasms, sulcus vocalis, inflammatory laryngitis (e.g., tobacco abuse, steroid inhalers), vocal fold immobility, hypothyroidism, and systemic illnesses such as sarcoidosis or amyloidosis.

Physical Exam

The physical exam should include a full head and neck examination. Attention should be made to the respiratory status of the patient, to assess whether acute interventions will be necessary to preserve the airway. Vocal quality should be noted. Indirect laryngoscopy can be done on adult patients. Flexible laryngoscopy may be done in adults and nondistressed children to assess location, extent, and functional limitations of the papilloma disease. Videostroboscopy can be useful, when available, to assess the impact of the papilloma on mucosal wave dynamics.

Imaging

Imaging has limited use, except in assessing for other issues causing airway compromise in children or assessing distal pulmonary papillomatosis. Highkilovoltage plain films or airway fluoroscopy may be helpful in this regard but do not specifically assist in the diagnosis of RRP.

Labs

No specific labs are helpful in RRP. Some otolaryngologists recommend HPV typing at the time of resection. This does not alter treatment but can offer some prognostic information, as HPV-11 patients tend to have more aggressive disease, more recurrences, more surgical procedures, and more use of adjuvant therapies.

Pathology

Papillomas contain a pedunculated, vascular, fibrous core with overlying nonkeratinized squamous epithelium. Multiple projections emanate off the central core, giving a frond- or wart-like configuration. Cellular atypia may occur in the epithelium and can be concerning for premalignant changes.

Medical

Although there are no primary medical therapies for RRP, adjuvant therapy to surgical resections may be necessary. Criteria for adjuvant methods include more than four procedures per year, rapid recurrence with airway compromise, and distant spread of disease. Approximately 10% of juvenile RRP patients require adjuvants.

The most commonly used therapy is recombinant α-interferon. This protein complex is a host defense to viral infection and immunomodulates the host into an antiviral condition. This has been shown to reduce the frequency of operative interventions. It is administered daily for 1 month, then tapered to three times weekly for at least 6 months. Side effects include flu-like symptoms, alopecia, leukopenia, coagulopathy, and neurologic side effects.

Indole-3-carbinol is an herbal supplement derived from cruciferous vegetables. The mechanism is unclear but is believed to be related to alterations in estrogen metabolism. Studies show a majority of patients receive partial to complete response. Dosages for children less than 25 kg are 100 to 200 mg daily and for adults 200 mg twice daily. Side effects include headache and dizziness.

Cidofovir is a cytosine nucleotide analog antiviral agent, designed for herpetic viruses and cytomegalovirus. Intralesional injections have shown good response in some patients. Concern for promoting progression to squamous cell carcinoma has been raised, but such progression is not proven.

Acyclovir has been used systemically, but the benefits are not well defined.

Photodynamic therapy utilizes the uptake of hematoporphyrins by papilloma to sensitize the tissue to red laser light. Disease progression is improved, but remission is not achieved.

Quadrivalent HPV vaccines have recently been released for HPV subtypes 6, 11, 16, and 18, with the indication for treating young girls before sexual activity to reduce the rate of cervical cancers. The hope exists that this use will influence the rate of laryngeal papilloma in future generations, and it may even be applied to males in the future.

Surgical

Surgical resection via microlaryngoscopy remains the mainstay of therapy. Recurrences are typical and multiple procedures are the norm. Juvenile RRP tends to be more aggressive and require more surgeries, likely related to increased growth rate of the RRP and the smaller dimensions of the juvenile larynx prompting earlier intervention for recurrence. Techniques for removal include several modalities and are influenced heavily by surgeon preference. Cold steel dissection of the papilloma may be useful for small isolated lesions, but not diffuse lesions. The CO₂ laser has been the workhorse of RRP for many years. Vaporization of the lesions is a viable treatment option. The laryngeal microdébrider can also be used; it is favored by some surgeons over laser, as it may have less “peripheral damage” given its lack of thermal injury and does not require special intraoperative laser precautions. Several new lasers have been utilized in RRP, even in the office setting via flexible scopes. These include flexible CO₂ and pulsed dye lasers.

Signs and Symptoms

Patients with various nonneoplastic vocal fold disorders generally complain of hoarseness of variable duration. A history of voice abuse or violent coughing is common. Vocal nodules are almost always seen in young women or young children with a history of voice abuse. Vocal fold polyps are more frequent in men. Stridor is occasionally associated with large vocal polyps. Vocal fold cysts present also with substantial voice changes and usually affect adults. Cysts are thought to be congenital or acquired and seem to arise in the setting of chronic irritation and inflammation after hemorrhage. Reinke′s edema, or polypoid chorditis, is a distinct entity from vocal polyps or nodules and usually presents with a pitch disturbance (e.g., females being mistaken for males on the telephone). It is caused by tobacco abuse.