Resolution of vocal fold leukoplakia with proton-pump inhibitor therapy.

Laryngopharyngeal reflux (LPR) has been linked to a variety of inflammatory conditions in the laryngopharynx, including vocal process granuloma, subglottic stenosis, polypoid corditis, and laryngeal carcinoma. (1,2) Aggressive antireflux treatment has been shown to diminish laryngeal signs of inflammation (e.g., erythema and edema), (3) and it is considered to be the primary treatment for LPR; digital laryngovideostroboscopy has demonstrated that a 6-week course of twice-daily proton-pump inhibitor (PPI) therapy lessens the effects of LPR. (4) In addition, a limited amount of data has shown that antireflux treatment can also lead to a reversal or resolution of vocal fold epithelial changes such as dysplasia and hyperkeratosis (Jamie A. Koufman, MD; personal communication, 2002). In fact, our experience includes a case of biopsy-proved vocal fold epithelial dysplasia and hyperkeratosis that resolved over a 2-year course of PPI therapy.

Our patient was a 71-year-old man who had been referred to our clinic for evaluation of a 2-year history of persistent vocal fold leukoplakia. The lesion, which had been initially biopsied at another facility, was made up of hyperplastic and reactive squamous epithelium with mild dysplasia. It had recurred within 4 weeks of the previous biopsy. Upon presentation to our clinic, the patient complained of worsening dysphonia, a strained voice, excessive throat mucus, and throat clearing. Of note, he had a 45- to 60-pack/year smoking history, but he had quit smoking 1 month earlier.

The initial videolaryngostroboscopy showed that the leukoplakia was confined to the anterior half of the left vocal fold (figure). The mucosal wave was absent in the area of the lesion, and the amplitude was severely diminished. Posterior laryngitis and pseudosulcus were present, suggesting the presence of LPR.

The patient was started on a twice-daily proton-pump inhibitor and was followed every month stroboscopically. As treatment continued, he experienced a gradual improvement in his voice and in the appearance of the leukoplakia (figure). At 2 years, the dysplastic lesion had disappeared (figure). In addition, his vibratory function and mucosal pliability were restored, and the mucosal wave had fully returned. At 2V2 years, the patient showed no sign of recurrence of the leukoplakia.

LPR may be a cofactor in the development of dysplastic and premalignant changes in the laryngeal epithelium. When it is, PPI treatment can lead to a reversal of vocal fold leukoplakia and/or epithelial dysplasia in carefully selected patients--that is, in those with coexisting pseudosulcus or interarytenoid erythema or edema. (5) Malignancy should be excluded prior to medically treating a suspected dysplastic vocal fold lesion. (1)

References

(1.) Koufman JA. The otolaryngologic manifestations of gastroesophageal reflux disease (GERD): A clinical investigation of 225 patients using ambulatory 24-hour pH monitoring and an experimental investigation of the role of acid and pepsin in the development of laryngeal injury. Laryngoscope 1991; 101 (4 pt 2 suppl 53): 1-78.

(2.) Zeitels SM, Hillman RE, Bunting GW, Vaughn T. Reinke's edema: Phonatory mechanism and management strategies. Ann Otol Rhinol Laryngol 1997; 106:533-43.

(3.) Belafsky PC, Postma GN, Koufman JA. Laryngopharyngeal reflux symptoms improve before changes in physical findings. Laryngoscope 2001; 111:979-81.

(4.) Beaver ME, Stasney CR, Weitzel E, et al. Diagnosis of laryngopharyngeal reflux disease with digital imaging. Otolaryngol Head Neck Surg 2003; 128:103-8.

(5.) Zeitels SM. Premalignant epithelium and microinvasive cancer of the vocal fold: The evolution of phonomicrosurgical management. Laryngoscope 1995; 105:1-51.

C. Blake Simpson, MD; Alfredo S. Archilla, MD; Ruben A. Velazquez, MD, PhD; H. Stan McGuff, DDS

From the Department of Otolaryngology-Head and Neck Surgery (Dr. Simpson and Dr. Velazquez) and the Department of Pathology (Dr. McGuff), University of Texas Health Science Center at San Antonio, and the Department of Otolaryngology (Dr. Archilla), University of Rochester Medical Center, Rochester, N.Y.