RRP, a disease of the respiratory mucosa characterized by benign nonkeratinizing squamous papillomata, is caused by the human papilloma virus (HPV). On the basis of shared genetic code homologies, HPV are grouped and numbered. Although there are approximately 100 different HPV types identified to date, with respect to RRP, two types stand out: HPV 6 and 11. They are not only the causative agents for RRP but are also responsible for 90% of genital warts (Condylomata acuminata). Recently, there has been evidence implicating infections with non-HPV agents in the pathogenesis of RRP.

HPV has been estimated to be present in the genital tract of as many as 25% of all women of childbearing age worldwide. Although RRP is the most common benign neoplasm of the larynx in children, its true incidence and prevalence are uncertain. It is estimated that each year, 1,500 to 2,500 new cases of childhood-onset RRP occur in the United States. Therefore, only a minority of children of virus-carrying mothers will become symptomatic, although the number of virus-carrying children may be much higher. Even in parturients with an active genital condyloma lesion, the neonate’s risk of contracting the disease when normal spontaneous vaginal delivery is chosen is only approximately 1 in 400.

The route of transmission (i.e., transplacental, perinatal, or postnatal) is not completely understood, and the preventive value of cesarean sections in parturients carrying the virus is unknown. Cesarean section with the sole intention of preventing the disease in the newborn is therefore not recommended. For reasons unknown, genital warts often increase in number and size during pregnancy and may make a vaginal delivery difficult leading to excessive maternal bleeding or pelvic outlet obstruction. In these cases, maternal considerations may make a cesarean delivery the delivery method of choice.

It is hoped that with the wider availability of vaccines effective against HPV 6 and 11 (GARDASIL, Merck & Co, Inc, Whitehouse Station, NJ), the incidence of RRP will decrease in the future.

Recurrence of voice changes despite repeated surgical interventions is unfortunately not that rare in patients with respiratory papillomatosis. Hoarseness, stridor, and—if severe enough—the development of respiratory distress from airway obstruction are the most consistent signs and symptoms of patients with RRP. Oral, tracheobronchial, and pulmonary involvements also are known to occur.

At present, there is no cure for RRP and no modality that would lead to eradication of the virus from the respiratory mucosa. Local recurrences are therefore to be expected.

As stated in the preceding text, there is no cure but only disease control for relentless and recurrent papillomatosis. The current standard of care is surgical therapy with the goal of complete removal of papillomata and preservation of normal structures as much as possible.

Because scarring from overaggressive laryngeal resections may lead to precisely the adverse clinical outcome that surgical therapy seeks to avoid or minimize (dysphonia, airway compromise), most experienced surgeons will accept incomplete papilloma resection, especially when near delicate structures such as the anterior laryngeal commissure. Even with the removal of all clinically evident papilloma, not all latent virus particles will have been eradicated.

With respect to surgical technique, the CO₂ laser had been the mainstay of therapy since the 1970s. According to a recent survey by the American Society of Pediatric Otolaryngology, this may be changing. Most members participating in this survey seem to rely on the use of the microdebrider as the preferred surgical therapy. The microdebrider is considered to be just as precise a surgical tool as the CO₂ laser; it may be easier to use and may limit the damage to underlying tissue, allowing for greater preservation of normal epithelium.

There continues to be an application for laser-based resections. Certain lesions, such as sessile ones, those with ventricular involvement, or those in the area of significant scarring, are still best dealt with by CO_2-, potassium titanyl phosphate (KTP), or pulsed-dye laser (PDL).

In addition, there seems to be an increasing role for adjuvant medical therapy: α-interferon and various antiviral agents, of which the most commonly used one is intralesional cidofovir.

Interferons (IFNs) are potent cytokines that possess antiviral, immunomodulating, and antiproliferative activities. Of the three known major classes of IFNs (α, β, and γ), only α-interferon is clinically used in RRP. A common therapeutic regimen entails daily subcutaneous applications for a month, followed by a 6-month period of injections three times a week, and then further slow weaning as tolerated. Known adverse effects associated with systemic application are an acute, relatively benign influenza-like syndrome, characterized by fever, chills, headache, myalgia, arthralgia, nausea, vomiting, and diarrhea, as well as more serious dose-limiting comorbidities, namely, myelosuppression and neurotoxicity. Neurotoxicity is characterized by somnolence, confusion, behavioral disturbance, and rarely,
seizures, debilitating neurasthenia, and depression. Alopecia and personality change are common in IFN-treated children. Cardiovascular toxicity (hypotension and tachycardia) and hepatotoxicity seem to be more rare.

Hoarseness always indicates some abnormality of laryngeal structure or function. Given the patient’s previous history, local papilloma recurrence and/or postoperative scarring of laryngeal structures seem likely causes in this patient. A broader differential diagnosis for hoarseness in children would be as follows:

First and foremost, it is important to quickly detect and address any serious respiratory compromise in this patient. In the absence of severe respiratory distress, a detailed history should be obtained. A review of previous anesthetic experiences with particular emphasis on problems pertaining to airway management would be a good starting point. Are there signs of obstruction? Does the patient snore at baseline? What position does the child sleep in? Sleep position can assist the team in maintaining airway patency particularly for masking. Weight, general health, associated comorbidities, recent respiratory infections, allergies, medications, and nothing-by-mouth status are all of obvious importance. A search for serious adverse effects from IFN therapy should be done.

With respect to the voice changes, a more in-depth investigation may offer some clues regarding the suspected location: A low-pitched, coarse, fluttering voice suggests a subglottic lesion, whereas a high-pitched, cracking voice, aphonia, or breathy voice suggests a glottic lesion. Associated high-pitched stridor also suggests a glottic or subglottic lesion. Because of the precision of laryngeal mechanics, hoarseness may result from a remarkably small lesion. On the other hand, if the origin of the lesion is remote from the vocal cords, hoarseness may result from a significantly larger lesion.

The concern here is to recognize a lesion that may potentially result in complete airway obstruction once anesthesia has been induced. A preoperative flexible nasopharyngoscopy examination is now routinely performed in most ear, nose, and throat (ENT) offices. If, however, it has not already been done before the patient’s arrival to the OR, an immediate preoperative flexible nasopharyngoscopic examination should be considered.

In recent years, the value of routine preoperative laboratory screening has been questioned. For a surgical procedure not associated with significant intraoperative blood loss in a child who is not at increased risk for severe and physiologic important anemia, no laboratory tests are required.

This patient may however no longer fall into this latter category. After all, α-interferon is associated with serious side effects, such as neurotoxicity and myelosuppression. Because the effects of myelosuppression may not be diagnosed easily by history and physical examination, a preoperative complete blood count may be beneficial in this particular patient.

Children with RRP are often quite anxious and apprehensive coming back to the OR for yet another reexcision. A reassuring preoperative visit by the anesthesiologist should help allay fears. Sedative premedication should be used very carefully, especially in the child with significant respiratory distress. It should not be administered without close monitoring and the immediate availability of oxygen, suction, and positive pressure ventilation. Dexmedetomidine, an α₂-agonist, given intranasally has no effect on respiration and has anxiolytic properties. Anticholinergic premedication may be used to dry up oral secretions.