Introduction
Laryngeal papillomatosis is a rare condition characterised by multiple benign papillomata affecting the upper respiratory passages; it is often localised to the larynx.Reference Snoeck, Wellens, Desloovere, Van Ranst, Naesens and De Clercq1 The causative agent is the human papilloma virus. Viral subtypes 6 and 11 are predominately associated with symptomatic disease.Reference Pudszuhn, Welzel, Bloching and Neumann2 Human papilloma virus can affect the respiratory tract and genital region and may also have cutaneous manifestations.
The incidence of laryngeal papillomatosis varies between adults and children, being 2 per 100 000 and 4.5 per 100 000, respectively. It presents in infancy or early childhood with stridor and a change in voice or crying pitch.
Patients often require multiple courses of treatment due to the recurrent nature of the disease, which is also referred to as recurrent respiratory papillomatosis. Tracheostomies are generally avoided but are occasionally required. Traditional surgical treatment modalities include ‘cold steel’, laser, microdebrider and photodynamic therapy. There are alternative or adjunctive treatments available, including antiviral therapy (e.g. interferon), chemotherapy, retinoids and vaccination.Reference Pawlita and Gissmann3
Intralesional cidofovir has been used over the last decade to treat recurrent respiratory papillomatosis, since the first report in 1998.Reference Snoeck, Wellens, Desloovere, Van Ranst, Naesens and De Clercq1 Cidofovir is a cytosine nucleoside analogue with antiviral activity.Reference Shehab, Sweet and Hogikyan4 Many publications have reported promising results for intralesional cidofovir.Reference Snoeck, Wellens, Desloovere, Van Ranst, Naesens and De Clercq1, Reference El-Hakim, Waddell and Crysdale5–Reference Bielecki, Mniszek and Cofała11 Side effects are rare, but include rash,Reference Snoeck, Wellens, Desloovere, Van Ranst, Naesens and De Clercq1 headache,Reference Snoeck, Wellens, Desloovere, Van Ranst, Naesens and De Clercq1 local inflammationReference Bielamowicz, Villagomez, Stager and Wilson8 and potential nephrotoxicity; in animal studies, concerns have been raised about carcinogenicity. A few authors have described dysplasia after use,Reference Snoeck, Wellens, Desloovere, Van Ranst, Naesens and De Clercq1, Reference Pudszuhn, Welzel, Bloching and Neumann2, Reference Dikkers10, Reference Wemer, Lee, Hoffman, Robinson and Smith12 and a 2–5 per cent rate of malignant change has been reported.Reference Snoeck, Wellens, Desloovere, Van Ranst, Naesens and De Clercq1, Reference Kimberlin13 Recent generalReference Broekema and Dikkers14 and histologicalReference Lindsay, Bloom, Pransky, Stabley and Shick15 reviews have suggested that the rate of malignant transformation with cidofovir is no higher than expected from the natural course of the disease; however, this remains contentious.
Surgical debridement with intralesional cidofovir is used for moderate to severe disease.Reference Tanna, Sidell, Joshi and Bielamowicz16 Currently, there is no literature on the method of administration of intralesional cidofovir. In the senior author's experience, and judging from reports from various centres, most clinicians appear to inject using a laryngeal needle after tumour debulking.
In this report, we share our experience of treating a particularly difficult, recalcitrant case of recurrent respiratory papillomatosis.
Case report
A 20-year-old woman had initially been diagnosed with laryngeal papillomatosis at the age of 18 months, due to stridor and a change in crying pitch. This condition had been very difficult to treat, and the patient had undergone a tracheostomy before the age of three years. Multiple attempts at surgical debulking with a laser had been attempted, without any significant improvement.
A second opinion had been sought at a specialist paediatric institute, and the patient had remained under their care for the next 13 years. Over this period, she had undergone over 250 surgical interventions (mainly involving KTP laser) plus adjuvant treatment with interferon. In the year prior to the current presentation, the patient had received systemic cidofovir to treat papillomas that had seeded further down her respiratory tree.
The patient's care had been transferred back to our centre when she reached the age of 16 years, with a tracheostomy still in situ. Initially, she had continued systemic cidofovir together with surgical management using a microdebrider.
At this stage, a literature review was performed, which brought to light reports of good results with intralesional cidofovir.Reference Snoeck, Wellens, Desloovere, Van Ranst, Naesens and De Clercq1, Reference El-Hakim, Waddell and Crysdale5–Reference Dikkers10 As a result, cidofovir was used intralesionally in an attempt to control the patient's recurrent, extensive papillomata in the larynx and upper trachea.
Administration technique
Intralesional cidofovir was delivered under general anaesthesia. A ventilating Storz paediatric bronchoscope was used. We used a Cook brand disposable variceal injector17 (Figure 1) (Cook, Medical Ltd, Cork, Ireland) to administer the cidofovir, using the side port of the Storz ventilating bronchoscope. The specific variceal injecting device used was a DVI-23 model, which is 200 cm in length and has a 5.0 Fr injector that requires a minimal channel size of 2.0 mm. This was used because the needle remained sheathed, thus decreasing the risk of iatrogenic injury or injection. When the needle tip was advanced, it had a range of 4 mm. Prior to use, the system was checked to ensure that the needle could be advanced; the system was then primed.
Variceal injector prepared for use with cidofovir.
Once appropriate views of the papillomata were obtained, the variceal injector was inserted down the side channel of the bronchoscope. The injector was advanced to lie upon a papilloma (Figure 2), an assistant advanced the tip into the lesion, and cidofovir was slowly injected (Figure 3). Once the lesion blanched (Figure 4), the injection was halted and the tip re-sheathed, and new papillomata were sought. This process was repeated as necessary until all relevant lesions had been treated.
Endoscopic view of variceal injector in trachea. The tip of the needle is visible.
Endoscopic view of variceal injector advanced into a lesion.
Endoscopic view showing successful injection of cidofovir, with blanching of the lesion.
Reported complications of such mucosal injections include ulceration, necrosis of injected tissue, venous thrombosis and stricture formation.
However, at the time of writing our patient had received 15 courses of treatment with no adverse consequences. Following the first few treatments, her papillomata decreased significantly in size, enabling decannulation after 14 years of tracheostomy dependence. Her frequency of treatment has decreased from monthly to three-monthly since commencement of intralesional cidofovir therapy.
Conclusion
In cases of recurrent respiratory papillomatosis, the use of a variceal injector to administer intralesional cidofovir is a cheap, safe and easily accessible method with no adverse effects in our experience. In our centre, we now use this method for all our patients requiring intralesional cidofovir to treat laryngotracheal papillomatosis.
