Efficacy of Long-term Interferon-alpha Therapy in Adult Patients with Recurrent Respiratory Papillomatosis

성인의 재발성 호흡기계 유두종증 환자에서 장기간 인터페론 치료의 유효성

  • Nam, Hae-Seong (Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Koh, Won-Jung (Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Suh, Gee Young (Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Chung, Man Pyo (Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Kwon, O Jung (Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Kim, Hojoong (Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine)
  • 남해성 (성균관대학교 의과대학 내과학교실 삼성서울병원 호흡기내과) ;
  • 고원중 (성균관대학교 의과대학 내과학교실 삼성서울병원 호흡기내과) ;
  • 서지영 (성균관대학교 의과대학 내과학교실 삼성서울병원 호흡기내과) ;
  • 정만표 (성균관대학교 의과대학 내과학교실 삼성서울병원 호흡기내과) ;
  • 권오정 (성균관대학교 의과대학 내과학교실 삼성서울병원 호흡기내과) ;
  • 김호중 (성균관대학교 의과대학 내과학교실 삼성서울병원 호흡기내과)
  • Received : 2008.09.05
  • Accepted : 2008.10.14
  • Published : 2008.11.30

Abstract

Background: Since the early 1980s, interferon-alpha ($IFN-{\alpha}$) has been used as adjuvant therapy in pediatric patients with recurrent respiratory papillomatosis (RRP). However, its efficacy in adults needs to be validated. Since 2002, Samsung Medical Center's guidelines have mandated regular injection of $IFN-{\alpha}$ in patients with RRP to prevent recurrence. To evaluate these guidelines, patient data were investigated. Methods: Five patients diagnosed as having RRP by bronchoscopy and histopathology were included. After initial bronchoscopic intervention, including laser cauterization, all patients received subcutaneous injection of 6 million units of $IFN-{\alpha}$ every 2 months. Further bronchoscopic intervention was carried out as needed. Patients were regularly evaluated using bronchoscopy or computed tomography. Results: The median age of the patients was 44 years (range 13~68), and the median duration of papillomatosis was 31 years (range 1~45). Three and two patients had juvenile-onset and adult-onset disease, respectively. Two patients had a history of tracheostomy at the time of diagnosis. The median duration of $IFN-{\alpha}$ therapy was 56 months (range 12~66). Two patients showed complete remission at 12 and 36 months after $IFN-{\alpha}$ injection, respectively. The other three patients showed partial remission, and the number of laser therapy sessions was significantly reduced.Conclusion: Intermittent $IFN-{\alpha}$ injection is effective in patients with long-standing RRP and can reduce the number of laser therapy sessions required in their treatment.

연구배경: 재발성 호흡기계 유두종증은 기관을 따라 다발성 유두종이 반복적으로 재발하는 매우 드문 질환이다. 1980년대 이후, 소아의 재발성 유두종증에 보조적 치료로 인터페론이 사용되어 왔다. 그러나, 성인 환자에서의 유효성 등에 대하여는 많은 연구 등이 필요하다. 2002년 이후, 삼성서울병원에서는 성인의 재발성 호흡기계 유두종증 환자들에서 재발을 예방하기 위해, 인터페론을 사용하여 왔다. 이에 본 저자들은 재발성 호흡기계 유두종증 성인 환자에서 인터페론의 장기간 사용 효과를 알아보고자 하였다. 방 법: 기관지내시경과 조직학적으로 확인된 5명의 재발성 호흡기계 유두종증 환자에서 타 병원에서 치료한 기록 등을 포함한 의무기록 등을 조사하였다. 레이저 소작술을 포함한 치료적 기관지내시경 시술 후, 모든 환자는 2개월 간격으로 인터페론-알파 600만 단위를 피하주사 하였다. 추가적인 치료적 기관지내시경 시술은 추적 검사 중 환자의 증상 등을 확인하여 필요 시 시행하였으며, 기관지 내시경 또는 켬퓨터 단층 촬영 등을 추적 조사하였다. 결 과: 모든 환자들의 연령의 중앙값은 44세(범위 13~68세), 남녀비는 3 : 2, 유두종증 기간의 중앙값은 31년(범위 1~45년)이었다. 소아형과 성인형 유두종증은 각각 3명과 2명이었으며, 2명의 환자는 진단 당시 기관절개술을 시행 받았던 과거력이 있었다. 인터페론 치료기간의 중앙값은 56개월(범위 12~66개월)이었다. 인터페론 치료 후 2명의 환자는 12개월과 36개월에 각각 완전완화를 보였으며, 나머지 3명의 환자는 부분완화를 보여 레이저 치료의 횟수가 중요하게 감소하였다. 결 론: 재발성 호흡기계 유두종증 환자에서 인터페론의 보조적 치료의 적정 용량과 기간 등은 향후 더 많은 연구 등을 필요로 하며, 오랜 기간 지속된 성인의 재발성 호흡기계 유두종증 환자에서 2개월 간격의 인터페론의 치료는 안정적이며 효과적이다.

Keywords

References

  1. Blackledge FA, Anand VK. Tracheobronchial extension of recurrent respiratory papillomatosis. Ann Otol Rhinol Laryngol 2000;109:812-8. https://doi.org/10.1177/000348940010900905
  2. Derkay CS. Task force on recurrent respiratory papillomas: a preliminary report. Arch Otolaryngol Head Neck Surg 1995;121:1386-91. https://doi.org/10.1001/archotol.1995.01890120044008
  3. Kramer SS, Wehunt WD, Stocker JT, Kashima H. Pulmonary manifestations of juvenile laryngotracheal papillomatosis. AJR Am J Roentgenol 1985;144:687-94. https://doi.org/10.2214/ajr.144.4.687
  4. Magid MS, Chen YT, Soslow RA, Boulad F, Kernan NA, Szabolcs P. Juvenile-onset recurrent respiratory papillomatosis involving the lung: a case report and review of the literature. Pediatr Dev Pathol 1998;1:157-63. https://doi.org/10.1007/s100249900021
  5. Byrne JC, Tsao MS, Fraser RS, Howley PM. Human papillomavirus-11 DNA in a patient with chronic laryngotracheobronchial papillomatosis and metastatic squamous-cell carcinoma of the lung. N Engl J Med 1987;317:873-8. https://doi.org/10.1056/NEJM198710013171406
  6. Lam CW, Talbot AR, Yeh KT, Lin SC, Hsieh CE, Fang HY. Human papillomavirus and squamous cell carcinoma in a solitary tracheal papilloma. Ann Thorac Surg 2004;77:2201-2. https://doi.org/10.1016/S0003-4975(03)01285-2
  7. Rady PL, Schnadig VJ, Weiss RL, Hughes TK, Tyring SK. Malignant transformation of recurrent respiratory papillomatosis associated with integrated human papillomavirus type 11 DNA and mutation of p53. Laryngoscope 1998;108:735-40. https://doi.org/10.1097/00005537-199805000-00021
  8. Armstrong LR, Derkay CS, Reeves WC. Initial results from the national registry for juvenile-onset recurrent respiratory papillomatosis. RRP Task Force. Arch Otolaryngol Head Neck Surg 1999;125:743-8. https://doi.org/10.1001/archotol.125.7.743
  9. Kashima H, Mounts P, Leventhal B, Hruban RH. Sites of predilection in recurrent respiratory papillomatosis. Ann Otol Rhinol Laryngol 1993;102:580-3. https://doi.org/10.1177/000348949310200802
  10. Avidano MA, Singleton GT. Adjuvant drug strategies in the treatment of recurrent respiratory papillomatosis. Otolaryngol Head Neck Surg 1995;112:197-202. https://doi.org/10.1016/S0194-5998(95)70236-9
  11. Chhetri DK, Shapiro NL. A scheduled protocol for the treatment of juvenile recurrent respiratory papillomatosis with intralesional cidofovir. Arch Otolaryngol Head Neck Surg 2003;129:1081-5. https://doi.org/10.1001/archotol.129.10.1081
  12. Gerein V, Rastorguev E, Gerein J, Jecker P, Pfister H. Use of interferon-alpha in recurrent respiratory papillomatosis: 20-year follow-up. Ann Otol Rhinol Laryngol 2005;114:463-71. https://doi.org/10.1177/000348940511400608
  13. Healy GB, Gelber RD, Trowbridge AL, Grundfast KM, Ruben RJ, Price KN. Treatment of recurrent respiratory papillomatosis with human leukocyte interferon. Results of a multicenter randomized clinical trial. N Engl J Med 1988;319:401-7. https://doi.org/10.1056/NEJM198808183190704
  14. Kimberlin DW. Pharmacotherapy of recurrent respiratory papillomatosis. Expert Opin Pharmacother 2002;3:1091-9. https://doi.org/10.1517/14656566.3.8.1091
  15. Leventhal BG, Kashima HK, Mounts P, Thurmond L, Chapman S, Buckley S, et al. Long-term response of recurrent respiratory papillomatosis to treatment with lymphoblastoid interferon alfa-N1. Papilloma Study Group. N Engl J Med 1991;325:613-7. https://doi.org/10.1056/NEJM199108293250904
  16. Mounts P, Shah KV. Respiratory papillomatosis: etiological relation to genital tract papillomaviruses. Prog Med Virol 1984;29:90-114.
  17. Mounts P, Shah KV, Kashima H. Viral etiology of juvenile- and adult-onset squamous papilloma of the larynx. Proc Natl Acad Sci U S A 1982;79:5425-9. https://doi.org/10.1073/pnas.79.17.5425
  18. McKaig RG, Baric RS, Olshan AF. Human papillomavirus and head and neck cancer: epidemiology and molecular biology. Head Neck 1998;20:250-65. https://doi.org/10.1002/(SICI)1097-0347(199805)20:3<250::AID-HED11>3.0.CO;2-O
  19. Summersgill KF, Smith EM, Levy BT, Allen JM, Haugen TH, Turek LP. Human papillomavirus in the oral cavities of children and adolescents. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2001;91:62-9. https://doi.org/10.1067/moe.2001.108797
  20. Silverberg MJ, Thorsen P, Lindeberg H, Grant LA, Shah KV. Condyloma in pregnancy is strongly predictive of juvenile-onset recurrent respiratory papillomatosis. Obstet Gynecol 2003;101:645-52. https://doi.org/10.1016/S0029-7844(02)03081-8
  21. Kashima HK, Shah F, Lyles A, Glackin R, Muhammad N, Turner L, et al. A comparison of risk factors in juvenile- onset and adult-onset recurrent respiratory papillomatosis. Laryngoscope 1992;102:9-13.
  22. Kashima H, Wu TC, Mounts P, Heffner D, Cachay A, Hyams V. Carcinoma ex-papilloma: histologic and virologic studies in whole-organ sections of the larynx. Laryngoscope 1988;98:619-24.
  23. Steinberg BM, Topp WC, Schneider PS, Abramson AL. Laryngeal papillomavirus infection during clinical remission. N Engl J Med 1983;308:1261-4. https://doi.org/10.1056/NEJM198305263082104
  24. Thurmond LM, Brand CM, Leventhal BG, Finter NB, Johnston JM. Antibodies in patients with recurrent respiratory papillomatosis treated with lymphoblastoid interferon. J Lab Clin Med 1991;118:232-40.