since completing his last treatment at 4 years and 4 months of age. As of the writing of this case report, our patient has required minimal debulking treatments every four months, compared to every four weeks prior to current treatment. His debridement at 5 years and 1 month old( Figure 2, 3) revealed further improvements. His bilateral true vocal fold fixation had previously progressed to near-total fixation requiring laryngoplasty. It was approximately 40 % at this debridement, again requiring laryngoplasty. Grade II subglottic stenosis was appreciated as well.
DISCUSSION
RRP is due to human papillomavirus( HPV), and it is generally benign, but it can be life-threatening when it progresses to cause airway obstruction. Treatment includes surgical excision or ablative procedures for debulking while preserving normal structures. In recent times, for patients who require surgical intervention greater than four times per year, adjuvant therapy is suggested.
Systemic and intralesional bevacizumab has been used in RRP with promising results. 1 It is a vascular endothelial growth factor( VEGF) inhibitor. VEGF inhibitor slows down angiogenesis and, thus, the growth of papillomas. There are several reports of using intralesional cidofovir in the treatment of RRP. 2, 3, 4, 5, 6, 7 In 2000, the first known case involving the systemic use of cidofovir to treat RRP was published. 1 Systemic cidofovir is usually avoided due to the risk of nephrotoxicity. Since that time, three other reported cases of systemic cidofovir have been used for treating RRP with varying degrees of success. 1, 5, 8, 9
Cidofovir is a cytosine nucleotide analog that blocks the replication of DNA viruses by inhibiting DNA polymerase. The Food and Drug Administration currently approves cidofovir for treating cytomegalovirus retinitis in patients with acquired immunodeficiency syndrome. Both systemic and intralesional treatment for RRP are prescribed. 5, 9 The exact mechanism of action of cidofovir on HPV is unknown. It is thought that it may down-regulate the expression of oncoproteins in HPV-infected cells. 1 According to a 2013 RRP task force survey, 74 otolaryngologists previously used cidofovir for RRP. 3 Intralesional cidofovir should be considered an adjunctive agent when patients require frequent debridement procedures. 3 Adjuvant cidofovir was indicated in patients who underwent six or more debridement procedures per year, had an increased frequency of surgery, or if extra laryngeal spread was noted in pediatric patients. 7 A study of 16 patients with juvenile-onset RRP treated with intralesional cidofovir reported a 75 % remission rate and stable disease( mean of 33.6 months). 1 According to a study evaluating systemic cidofovir in the treatment of RRP, few side effects were reported and without reported cases of nephrotoxicity. 5 The concurrent use of oral probenecid and intravenous hydration remains essential to mitigate side effects.
CONCLUSION
RRP is a condition that, while benign, presents significant challenges in the medical field due to its propensity for severe disease progression and extensive spread to distal airways. This complexity is further compounded by the lack of a standardized therapy for such advanced stages of the disease. Our case report, however, adds to the promising outlook on this issue already present in the medical literature. We found the usage of antiviral therapy with cidofovir in managing extensive RRP to be efficacious. This therapeutic approach could significantly improve disease progression, providing a much-needed solution for affected patients. Furthermore, our case indicates that the side effects associated with cidofovir are tolerable. The manageable side effects of cidofovir, coupled with its potential to significantly halt or even reverse disease progression, make it a compelling option for the treatment of severe RRP. Further research is warranted to validate our findings and potentially establish cidofovir as a standard treatment for severe RRP.
REFERENCES
1. Valckenborgh I, Wellens W, Boek K, et al. Systemic cidofovir in papillomatosis. Clin Infect Dis. 2001; 32( 3): e62-e64. doi: 10.1086 / 3184971.
2. Shehab N, Sweet BV, Hogikyan ND. Cidofovir for the treatment of recurrent respiratory papillomatosis: A review of the literature. Pharmacotherapy. 2005; 25( 7): 977-989. doi: 10.1592 / phco. 2005.25.7.977.
3. Ivancic R, Iqbal H, deSilva B, et al. Current and future management of recurrent respiratory papillomatosis. Laryngoscope Investig Otolaryngol. 2018; 3( 1): 22-34. doi: 10.1002 / lio2.132.
4. Fortes HR, von Ranke FM, Escuissato DL, et al. Recurrent respiratory papillomatosis: A state-of-the-art review. Respir Med. 2017; 126:116-121. doi: 10.1016 / j. rmed. 2017.03.030.
5. Broekema FI, Dikkers FG. Side-effects of cidofovir in the treatment of recurrent respiratory papillomatosis. Eur Arch Otorhinolaryngol. 2008; 265( 8): 871-879. doi: 10.1007 / s00405-008-0658-0.
6. Hoesli RC, Thatcher AL, Hogikyan ND, et al. Evaluation of safety of intralesional cidofovir for adjuvant treatment of recurrent respiratory papillomatosis. JAMA Otolaryngol Head Neck Surg. 2020; 146( 3): 231-236. doi: 10.1001 / jamaoto. 2019.4029.
7. Derkay CS, Volsky PG, Rosen CA, et al. Current use of intralesional cidofovir for recurrent respiratory papillomatosis. Laryngo. 2013; 123( 3): 705-712. doi: 10
8. Dancey DR, Chamberlain DW, Krajden M, et al. Successful treatment of juvenile laryngeal papillomatosisrelated multicystic lung disease with cidofovir: case report and review of the literature. Chest. 2000; 118( 4): 1210-1214. doi: 10.1378 / chest. 118.4.1210.
9. Armbruster C, Kreuzer A, Vorbach H, et al. Successful treatment of severe respiratory papillomatosis with intravenous cidofovir and interferon alpha-2b. Eur Respir J. 2001; 17( 4): 830- 831. doi: 10.1183 / 09031936.01.17408300.
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