Abstract
Juvenile respiratory laryngeal papillomatosis is a subset of a larger clinical entity of recurrent respiratory papillomatosis. It is characterised by the development of recurrent papillomata in the vocal folds. Human papillomavirus types 6 and 11 has been implicated to be the most common strain of virus associated with the formation of laryngeal papilloma. Clinical diagnosis is based on typical appearance of warty lesion on endoscopy. Surgery is the primary line of management along with adjuvant therapy like antiviral drugs and immunomodulators. Thuja occidentalis is a tree native to North America whose leaves and leaf oil have antiviral, antibacterial and antifungal properties. It has been widely used for the treatment of condylomatous skin lesions and warts. Here we discuss the outcome of thuja as an adjuvant therapy in the treatment of laryngeal papillomatosis in an 8-year-old child.
Keywords: ear, nose and throat, human papilloma virus
Background
Laryngeal papillomatosis is a benign, papillary, squamous cell tumour caused by human papillomavirus (HPV) types 6 and 11.1 It is the most common benign lesion of the paediatric larynx. It predominantly presents as multiple laryngeal papillomas and may also involve the entire respiratory tract and upper gastrointestinal tract.2 Children who present with hoarseness of voice, stridor and chronic cough are often misdiagnosed as asthma, laryngitis or bronchitis owing to delay in diagnosis of laryngeal papillomatosis.
Surgical excision of the lesion remains the mainstay of treatment but recurrence is a common problem. Use of interferon alpha, bevacizumab and cidofovir with successful outcome has been described in few case reports.3 Thuja occidentalis commonly known as arborvitae is widely used in homeopathy for its immunopharmacological and antiviral potential.4 This case report demonstrates the use of thuja in the management of laryngeal papillomatosis which is a unique and newer adjuvant treatment.
Case presentation
An 8-year-old man presented to our outpatient department with complaints of change in voice for 3 years and difficulty in breathing on exertion for 1 year along with history of snoring and mouth breathing. Child was a term baby delivered by vaginal delivery. No history of past medical or surgical treatment. No relevant family history. On examination, child was in stridor and showed signs of respiratory distress on exertion. Examinaton of the nose, oral cavity, oropharynx and neck revealed no abnormality.
Investigations
Video laryngoscopy showed multiple, warty, papillomatous growth involving both vocal cords. (figure 1) (video 1) Routine investigations were done and a diagnosis of laryngeal papillomatosis was made. Owing to the airway compromise, child was planned for tracheostomy followed by microlaryngeal surgery.
Figure 1.
Pedunculated, papillomatous growth involving both the vocal cords.
Video 1.
Treatment
Under intravenous sedation, elective tracheostomy was done and airway secured using 6 mm cuffed portex tracheostomy tube. Under general anaesthesia, multiple papillomatous growth arising from subglottis, ventricles and vocal cords were excised using cold knife microlaryngeal instrument and sent for histopathological examination. In the same sitting, local Kenacort injection was given and acyclovir ointment was applied over the surgical site. Postoperatively, child showed no signs of respiratory distress.
After a trial of spigotting, patient was decannulated on the 7th day. Histopathology showed features suggestive of a recurrent respiratory papillomatosis. Child was started on oral acyclovir (800 mg/day) and interferon alpha intramuscular injection (3 MU/m2) three times a week for 3 months. A monthly follow-up routine was established to monitor recurrence of lesion.
Outcome and follow-up
At 8 months postoperative a papillomatous lesion arising from the left arytenoids was noted. (figure 2) (video 2) Revision surgeries were performed twice to achieve clearance of the disease. Later, the child was started on thuja medication 1M (1000 potency) monthly dose for 3 months followed by 10M (10 000 potency) monthly dose for 3 months. Video laryngoscopy done post completion of thuja showed no evidence of recurrence. (figure 3) (video 3) The patient was on regular follow-up and there has been no evidence of recurrence until now (7 years from last surgery). No complications related to the use of drug was noted during this period of time.
Figure 2.
Papillomatous lesion arising from left arytenoids.
Video 2.
Figure 3.
No evidence of papillomatous lesions.
Video 3.
Discussion
Papillomas are the most common respiratory tract neoplasms in children.5 Lindeberg and Elbrond reported an annual incidence of 4 per 100 000 children. Dekay and Darrow reported an incidence of 1. 7 to 4. 3 per 100 000 children in the USA.1 Recurrent respiratory papillomatosis (RRP) is potentially a life-threatening disease involving papillomatous growth anywhere in the respiratory tract from the nasal vestibules to the terminal bronchi. Predominant sites are where there is a transition of epithelium. There is a bimodal distribution at 3 to 4 years and 20 to 30 years of age.2 Juvenile respiratory papillomatosis was first described by Morrell Mackenzie in 1880 and its infective aetiology was first demonstrated by Ullmann in 1923. Sixty-seven per cent of RRP are born to mothers who had condylomas (HPV types 6 and 11) during pregnancy or parturition.5 The mode of transmission of HPV is unclear. Though RRP is associated with vaginal codylomata, only 1 in 231 to 400 vaginal births acquire the disease.
Clinical manifestations include hoarseness of voice, exertional dyspnoea and stridor. In addition children may present with recurrent respiratory infections or failure to thrive. It is often mistaken for asthma, laryngitis or bronchitis and hence diagnosed late. Video laryngoscopy or flexible endoscopy allows visualisation of the lesion. Microlaryngeal surgery enables tissue diagnosis following excision. Symptomatic treatment for dyphonia and airway compromise is prioritised as there is no curative treatment for laryngeal papillomatosis. Unpredictable course of the disease and recurrence is the reason for lack of definitive treatment. Surgical treatment is for removal of papilloma, restoration of airway with minimal damage to the mucosa and vocal cords. Various options include microdebrider, cold steel, laser, coblater and photodynamic therapy. CO2 (carbon dioxide) laser is the mainstay of treatment since it can be used with ease and has the ability to ablate the papilloma with minimal bleeding. Galletti et al have reported a case of recurrent respiratory papillomatosis treated primarily with surgery using cold instrumentation and CO2 laser. Intralesional cidofovir and oral indole-3-carbinol were given as adjuvant therapy. No signs of recurrence were reported over the 8-year follow-up period. They have emphasised the use of non-aggressive surgical techniques and role of adjuvant therapy in this study.6
Interferon alpha, bevacizumab, cidofovir, ribavirin, acyclovir, indole-3-carbinol and cimetidine are the drugs used as an adjuvant to prevent recurrence. No individual drug has an established role in the management of laryngeal papillomatosis.7 Gazia et al have reviewed the literature on use of intralesional cidofovir in the management of recurrent respiratory papillomatosis. Cidofovir is an antiviral agent which acts by decreasing the efficiency of DNA transcription following incorporation into the growing DNA chain. Average dose of 2.5 to 37.5 mg/mL given 3 times over three weekly intervals has a good adjuvant action and seems to be relatively safe.8
Thuja occidentalis is a white cedar, indigenous to eastern North America and is grown in Europe.9 It was first identified by native Indians in Canada in a 16th century expedition and was found to be useful for treating weakness caused by scurvy. The dried herbal substance contains essential oils like thujone, coumarins and flavonoids which give it a medicinal value. Various extraction procedures result in different concentrations of thujone.10 Hänsel et al have described the drug to contain 1.44% essential oil (critical factor as medicinal herb), 60% of which is thujone, which corresponds to 2.4% thujone in the whole drug.11 Antiviral and immunostimulant properties of thujone have been demonstrated in numerous in vitro and in vivo test models. Three good clinical practice compliant, double-blinded, placebo controlled clinical studies have verified the efficacy and safety of a herbal medicine containing thuja for treatment of common cold and as an adjuvant to standard antibiotic treatment for bacterial infections. It acts on skin, blood, gastrointestinal tract, kidneys and brain. Symptoms of intoxication from the fresh plant include vomiting, stomach ache, diarrhoea, headache, nervous agitation and chronic convulsions.12
Thuja has been widely used in the management of plantar warts caused by HPV.13 Laryngeal papilloma is also caused by HPV. Hence in our case oral thuja has been administered to the patient. In a study by Joseph et al a renal transplant recipient with cutaneous warts was treated with local thuja application and oral thuja. The warts withered off following days of therapy.14 In a study by Bodinet et al the presence of interleukin 1, interleukin 6 and tumour necrosis factor alpha with local activation of cytokine producing cells has been demonstrated following thuja administration.15 Antibody producing lymphocytes were found to be increased in the haemolytic plaque assay in vitro by Freudenstein et al.16 Gohla et al proved that thuja causes T cell induction specifically of cluster differentiation 4 (CD 4) positive T helper cells.17 Hence antihuman immunodeficiency virus 1 activity is a specific role of thuja. Gimeno established that thuja helped to eradicate the papillomatous lesions caused by HPV.18
This property of thuja has been applied in the management of laryngeal papillomatosis caused by HPV. In a study by Nanda et al a total of five patients with recurrent laryngeal papillomatosis were subjected to microlaryngeal scalping followed by thuja 1M monthly dose for 3 months and monthly dose of 10M for the next 3 months. These patients did not show any recurrence upto a period of 2 years follow-up and showed significant improvement in voice.19 Our patient was followed up for 7 years with no evidence of recurrence. Similar results have been documented in a study by Khangarot et al.20 In our case, oral thuja was administered for 6 months following surgery. Though thuja has been beneficial to this patient, a large scale multi-institutional study is recommended to further evaluate the role of this drug in the management of laryngeal papillomatosis.
Patient’s perspective.
I am the patient’s uncle and would like to thank the doctors for their effort to treat the child and I would like to state that he is active and healthy at present with no complications.
Learning points.
Laryngeal papillomatosis is a difficult disease to manage due to recurrence. Multimodal treatment is required for complete remission.
Though several adjuvant therapies have been used along with microlaryngeal scalping as a combined approach, none have been proven completely effective.
The disease has been successfully managed in our case by using thuja as an auxiliary treatment.
Hence thuja may be used as adjuvant therapy though further clinical research would be warranted to prove the efficacy of this drug.
Footnotes
Contributors: I, ND have written the case report. SM has contributed and helped with designing the case report. Professor PKS has dealt with the case.
Funding: The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests: None declared.
Patient consent for publication: Parental/guardian consent obtained.
Provenance and peer review: Not commissioned; externally peer reviewed.
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