Information on the following diseases can be found in the Related Disorders section of this report:

• Tumors of the Larynx (General)
• Congenital Laryngeal Cysts
• Vocal Cord Polyps
• Vocal Cord Nodules

There are two types of Respiratory Papillomatosis, with similar symptoms but distinguished by the age of onset. Juvenile Recurrent Respiratory Papillomatosismay begin at birth or during childhood, usually before five years of age. Adult Onset Recurrent Respiratory Papillomatosisbegins after the age of 18.

The initial symptoms of both types of Recurrent Respiratory Papillomatosismay include hoarseness and/or a change in voice. Affected individuals may have the sensation of a foreign object in their throat, and/or have difficulty breathing (dyspnea) and/or swallowing (dysphagia). Upon medical examination (laryngoscopy) multiple stem-like growths (papillomas) can be seen in the respiratory tract, most often on the vocal cords. Papillomas may also develop in the nose, oral cavity, windpipe (trachea), air passages to the lungs (bronchi and/or bronchioles), and/or lungs.

Recurrence of papillomas is a characteristic feature of Respiratory Papillomatosis, and multiple surgical procedures may be required to keep the respiratory tract clear. Respiratory distress and/or other life-threatening situations may arise if the papillomas block the airway and/or interfere with lung function.

Rarely, the papillomas may become malignant (cancerous) and invade surrounding areas, causing tissue damage and/or leading to serious life-threatening complications. Affected individuals who have received previous radiation treatment may have an increased risk of malignant transformation.

Recurrent Respiratory Papillomatosisis caused by the human papillomavirus (HPV-6 or HPV-11). This virus is responsible for some types of warts or growths in the genital region (genital condyloma). Juvenile Recurrent Respiratory Papillomatosis may be transmitted to newborns during childbirth or before birth by a mother who is infected with the papillomavirus.

The mode of transmission of Adult Onset Recurrent Respiratory Papillomatosis has not been determined. It has been suggested by scientists that some affected adults may have been infected at birth, with the virus remaining inactive (latent) until adulthood. Slow viruses may stay dormant in humans for extended periods of time, then for reasons yet unknown may unexplainably become reactivated. The role of heredity which may make a person susceptible to slow viruses is not well understood. Other adults may acquire the virus when they come in contact with people infected with the human papillomavirus (i.e., oral contact with infected genitals).

In some cases of Respiratory Papillomatosis, the disease may spread due to the breaking off of tissue particles during surgical procedures. When the affected individual breathes in, these particles may be carried through the airway into other areas of the respiratory system and lead to the development of papillomas. One case reported in the medical literature was that of a physician who became infected when he inhaled airborne virus particles while performing laser surgery on an infected individual.

One study suggests that individuals with a certain enzyme deficiency (lysozyme) and a low intake of proteins and vitamin B complex may be more susceptible to the virus. More research is needed to determine whether this theory is valid.

Recurrent Respiratory Papillomatosisis a rare disorder that affects males and females in equal numbers, and is most frequently diagnosed in children under five years of age. About one-third of affected individuals are adults. Firstborn children, delivered vaginally, and/or who have teenage mothers, may be more frequently affected than other infants. One study suggests that Adult Onset Recurrent Respiratory Papillomatosis may occur more frequently in adults who have multiple lifetime sexual partners and/or have a higher frequency of oral sex.

Symptoms of the following disorders can be similar to those of Respiratory Papillomatosis. Comparisons may be useful for a differential diagnosis:

Tumors of the Larynx may be malignant (cancerous) or benign (non-cancerous). Malignant tumors are characterized by the rapid spread of disease to other areas (metastasis) of the body. Typically, benign tumors do not metastasize, but symptoms may develop due to the location of the tumor. The earliest symptom of laryngeal tumors is usually hoarseness, which may be followed later by breathing difficulties (dyspnea) if the airway becomes obstructed. Persistent hoarseness without apparent cause should be investigated by direct medical examination of the larynx (laryngoscopy). Early treatment with surgery or radiation therapy usually results in a high cure rate.

Congenital Laryngeal Cysts are rare, fluid-filled sacs located on the walls of or within the larynx. Symptoms typically begin in the first six months of life, with 40 percent of reported cases being discovered within the first few hours after birth. Major symptoms may include a harsh, high-pitched cry (stridor), difficulty breathing (dyspnea), a bluish discoloration to the skin and mucous membranes (cyanosis), and/or periods when breathing stops (apnea). Feeding problems may also occur. Direct medical examination of the larynx (laryngoscopy) establishes the diagnosis and allows for treatment by incision and drainage of the cyst.

Vocal Cord Polyps are a common result of voice abuse, chronic laryngeal allergies, or irritation of the vocal cords by industrial fumes or cigarette smoke. Symptoms may include hoarseness and a breathy voice quality.

Vocal Cord Nodules (Singer's, Teacher's, or Screamer's Nodules) may be caused by chronic voice abuse and/or using an unnaturally low voice. The nodules are concentrations of connective tissue on the vocal cords that result in hoarseness and a breathy voice quality.
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Diagnosis
Diagnosis of Recurrent Respiratory Papillomatosisis is made when medical examination of the larynx (laryngoscopy) reveals typical stem-like growths (papillomas). The diagnosis is confirmed through laboratory examination of tissue samples, which shows the presence of human papillomavirus (HPV 6 and/or HPV 11).

Treatment
Surgical removal of papillomas may be easily accomplished. However, papillomas may recur requiring additional surgery. In severe cases multiple surgical procedures (i.e., every two weeks) may be necessary. Many individuals with both Juvenile and Adult Onset Recurrent Respiratory Papillomatosis may experience long periods without recurrence (regression) of the symptoms. In a significant number of individuals with Juvenile Laryngeal Papillomatosis there may be complete recovery. Some cases of Juvenile Laryngeal Papillomatosis may clear up without treatment (spontaneous remission).

The preferred treatment of Recurrent Respiratory Papillomatosis consists of surgical removal of the papillomas, combined with laser therapy. Destruction of the growths with a laser beam (laser ablation) or by freezing (cryotherapy) may be considered as alternative treatments. Care must be taken to avoid damage to the surrounding healthy tissue, as scarring can cause permanent changes in voice and respiratory function.

Earlier treatments for Recurrent Respiratory Papillomatosis included radiation therapy. This treatment has been discontinued because research suggests that radiation therapy may result in an increased risk of malignant (cancerous) transformation.
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Research into possible treatments for Recurrent Respiratory Papillomatosisis ongoing. Drugs that inhibit the development of abnormal growths (antineoplastic) are being tested in the treatment of recurrent Respiratory Papillomatosis, usually in combination with surgical therapy (excision or laser). These drugs include recombinant interferon alfa-2b and interferon alpha-n1, which have received orphan drug designations for the treatment of Laryngeal Papillomatosis, and interferon alfa-n3. Further research is necessary to determine the long-term safety and effectiveness of these medications in the treatment of Respiratory Papillomatosis. For further information on these drugs contact the manufacturers:

For information on Interferon Alfa-2b (Recombinant), contact:

Schering Corporation
2000 Galloping Hill Road
Kenilworth, NJ 07033

For information on Interferon Alfa-n1, contact:

Burroughs Wellcome Co.
3030 Cornwallis Road
Research Triangle Park, NC 27709

For information on Interferon Alda-n3, contact:

The Purdue Frederick Company
100 Connecticut Avenue
Norwalk, CT 06850-3590

Photodynamic laser therapy is being tested on some people with Respiratory Papillomatosis. Further research is necessary to determine the long-term safety and effectiveness of photodynamic therapy in the treatment of Respiratory Papillomatosis.

Drugs that are used to treat viral disorder (antiviral agents) are being studied as potential treatments for Recurrent Respiratory Papillomatosis. One specific antiviral agent is ribavirin, which is being tested in the treatment of children and adults with Recurrent Respiratory Papillomatosis. Further research is necessary to determine the long-term safety and effectiveness of antiviral agents such as ribavirin in the treatment of Recurrent Respiratory Papillomatosis.

The drug cidofovir, alone or in combination with interferon alpha-2b, has been used to treat children with severe respiratory papillomatosis. More research is necessary to determine the safety and effectiveness of cidofovir for the treatment of individuals with Recurrent Respiratory Papillomatosis.

Cimetidine has been used to treat individuals with Recurrent Respiratory Papillomatosis. More research is necessary to determine the long-term safety and effectiveness of this potential treatment for individuals with Recurrent Respiratory Papillomatosis.

Researchers are studying the use of a mechanical device known as a microdebrider as an alternative treatment to carbon dioxide laser for the treatment of individuals with Juvenile Recurrent Respiratory Papillomatosis. Initial results demonstrated that the microdebrider was less time-consuming than the carbon dioxide laser and that there were no soft tissues complications.
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TEXTBOOKS
Behrman RE, ed. Nelson Textbook of Pediatrics, 15th ed. Philadelphia, PA: W.B. Saunders Company; 1996:1209-10.

Gorbach SL, et al., eds. Infectious Diseases. Philadelphia, PA: W. B. Saunders Company; 1992:88.

Ballenger JJ, ed. Diseases of the Nose, Throat, Ear, Head & Neck, 14th ed. New York, NY: Lea & Febiger Co; 1991:576.

Buyce ML, ed. Birth Defects Encyclopedia. Dover, MA: Blackwell Scientific Publications; For: The Center for Birth Defects Information Services Inc; 1990:1361-62.

Fields BN, et al. Fields Virology, 2nd ed. New York, NY: Raven Press; 1990:1666-67.

JOURNAL ARTICLES
El-Bitar MA, Zalzal GH. Powered instrumentation in the treatment of recurrent respiratory papillomatosis: an alternative to the carbon dioxide laser. Arch Otolaryngol Head Neck Surg. 2002;128:425-28.

Armbruster C, et al. Successful treatment of severe recurrent respiratory papillomatosis with intravenous cidofovir and interferon alpha-2b. Eur Respir J. 2001;17:830-31.

Batra PS, et al. Recurrent respiratory papillomatosis with esophageal involvement. Int J Pediatr Otorhinolaryngol. 2001;58:233-38.

Derkay CS. Recurrent respiratory papillomatosis. Laryngoscope. 2001;111:57-69.

Kimberlin DW, Malis DJ. Juvenile onset recurrent respiratory papillomatosis: possibilities for successful antiviral therapy. Antiviral Res. 2000;45:83-93.

Harcourt JP, et al. Cimetidine treatment for recurrent respiratory papillomatosis. Int J Pediatr Otorhinolaryngol. 1999;51:109-13.

Pransky SM. Intralesional cidofovir for recurrent respiratory papillomatosis in children. Arch Otolaryngol Head Neck Surg. 1999;125:1143-48.

Perkins JA, et al. Iatrogenic airway stenosis with recurrent respiratory papillomatosis. Arch Otolaryngol Head Neck Surg. 1998;124281-87.

Rady PL, et al. Malignant transformation of recurrent respiratory papillomatosis associated with integrated human papillomavirus type 11 DNA and mutation of p53. Laryngoscope. 1998;108:735-40.

Gabbott M, et al. Human papillomatosis and host variables as predictors of clinical course in patients with juvenile-onset recurrent respiratory papillomatosis. J Clin Microbiol. 1997;35:3098-103.

Erisen L, et al. Late recurrences of laryngeal papillomatosis. Arch Otolaryngol. 1996;122:942-44.

Elo J, et al. Papova viruses and recurrent laryngeal papillomatosis. Acta Otolaryngol. 1995;115:322-25.

Mahnke CG. Laser surgery for laryngeal papillomatosis. Adv Otorhinolaryngol. 1995;49:162-65.

Franzmann MB, et al. Tracheobronchial involvement of laryngeal papillomatosis at onset. J Laryngol Otol. 1994;108:164-65.

Toussaint B, et al. Malignant transformation of juvenile-type laryngeal papillomatosis. Ann Otolaryngol Chir Cervicofac. 1993;110:285-90.

Bujia J, et al. Photodynamic therapy with derivatives from hematoporphyrines for recurrent laryngeal papillomatosis of the children. Early results. An Otorrinolaringol Ibero Am. 1993;20:251-59.

Morrison GA, et al. Ribavirin treatment for juvenile respiratory papillomatosis. J Laryngol Otol. 1993;107:423-26.

Anderson KC. Juvenile laryngeal papillomatosis: a new complication. South Med J. 1993;86:447-49.

McGlennen RC. Pilot trial of ribavirin for the treatment of laryngeal papillomatosis. Head Neck. 1993;15:504-12.

Feyh J. Treatment of laryngeal papillomatosis with photodynamic laser therapy. Laryngorhinootologie. 1992;71:190-92.

Abramson AL, et al. Clinical effects of photodynamic therapy on recurrent laryngeal papillomas. Arch Otolaryngol Head Neck Surg. 1992;118:25-29.

Kashima HK, et al. A comparison of risk factors in juvenile-onset and adult-onset recurrent respiratory papillomatosis. Laryngoscope. 1992;102:9-13.

Smith EM, et al. Perinatal vertical transmission of human papillomavirus and subsequent development of respiratory tract papillomatosis. Ann Otol Rhinol Laryngol. 1991;100:479-83.

Perrick D, et al. Evaluation of immunocompetency in juvenile laryngeal papillomatosis. Ann Allergy. 1990;65:69-72.

Wright RG, et al. Comparative in situ hybridisation study of juvenile laryngeal papillomatosis in Papua New Guinea and Australia. J Clin Pathol. 1990;43:1023-25.

Altamar-Rios J. Lysozyme in the treatment of juvenile laryngeal papillomatosis. A new concept in its etiopathogenesis. An Otorrinolaringol Ibero Am. 1990;17:495-504.