The Efficacy And Safety Of Botulinum Toxin Type A For Treating Benign Parotid Gland Hypertrophy

Background and ObjectiveBenign parotid hypertrophy is a non-neoplastic;non-inflammatory,chronic and painless benign enlargement of the salivary gland.It is characterized by bilateral enlargement of the parotid gland,without salivary secretion disorder,and is generally characterized by hypertrophy of acinar cells,accompanied by enlargement or atrophy of ductal cells.The pathogenesis of benign parotid hypertrophy is still unclear,and it may be associated with autonomic neuropathy.Some studies have suggested that it is caused by hyperfunction of aquaporin 5(AQP5)in acinus cells of parotid gland.In terms of etiology,current studies suggest the following reasons:(ⅰ)age(the parotid gland volume increases with age);(ⅱ)alcohol abuse;(ⅲ)overweight;(ⅳ)endocrine.disorder,anorexia nervosa or disorder of autonomic nerves.The anatomic position of the parotid glands is relatively shallow.Parotid gland hypertrophy affects the lower facial appearance by making it appear swollen,and can affect the psychological health of patients.Efficacious treatment for benign parotid hypertrophy is lacking.In general,it is not treated because of the absence of clinical symptoms.For patients with an obvious desire for treatment,partial parotidectomy may be adopted.However,the surgical trauma is considerable,complications(parotid fistulae,injury to the parotid duct,nerves,or blood vessel)are common,and scars remain after surgery.In recent years,several studies have demonstrated that injection of botulinum to xin is efficacious for the treatment of hypersalivation due to diseases such as acquired immune deficiency syndrome or Parkinson’s disease.Studies have found that botulinum toxin can reduce saliva secretion bur also reduce the volume of hypertrophic parotid gland,but the underlying mechanism is not clear.Woffles et al.reported that injection of botulinum toxin type A into the parotid glands of a patient with parotid hypertrophy improved his facial contour.Case reports also stated that injection of botulinum toxin type A used to treat patients with salivary glands hypertrophy achieved good results.Botulinum toxin injection is undoubtedly a better option than surgical removal of part of the parotid gland tissue.However,due to the few cases in clinical practice,its clinical efficacy and safety have not been widely verified,which limits its clinical application.Based on those research results as well as anatomic and medical imaging supporting,we designed a prospective study to assess the efficacy and safety of botulinum toxin type A injection on the treatment of benign parotid hypertrophy.MethodsThis clinical trial was registered in The Chinese Clinical Trial Registry(ChiCTR2000037934)after the ethical review of study protocol.Patients with benign parotid hypertrophy were enrolled according to inclusion and exclusion criteria.The patients’ medical history was recorded,and digital facial photos were retained,facial parameters were measured,and parotid gland ultrasounds were performed.Thirty-six patients were enrolled and signed informed consent Different doses of Botulinum toxin Type A(BTX-A,100U,Lanzhou,China)were injected into the parotid glands according to age,gender,degree of hypertrophy(the degrees of parotid gland hypertrophy were classified as "mild"(11-15 mm),"moderate"(16-20 mm),and"severe"(>20 mm).)and other parameters.Each side of parotid gland was injected with three points,of which,the injection dose was 10U/point for mild hypertrophy,12U/point for moderate hypertrophy and 15U/point for severe hypertrophy.The patients were observed for 30 minutes after injection.After follow-up,complications or discomforts were recorded.At 3 and 6 months after injection,parotid gland ultrasound was performed in the hospital,and digital facial photos were taken again at the 6 months after injection.After data collated,the thickness and longitudinal diameter of parotid gland were statistically analyzed,followed by image analysis and subgroup analysis so that to clarify the effectiveness and safety of botulinum toxin type A in the treatment of benign parotid hypertrophy.ResultsThirty-three patients received the treatment and completed the follow-up.The mean total parotid thickness of 33 patients(66 parotid glands)was 28(3.75)mm.According to the grading standard for benign parotid hypertrophy in this study,14 patients were included with mild parotid hypertrophy,15 with moderate parotid hypertrophy,and 4 with severe parotid hypertrophy.The mean dose of botulinum toxin that patients have received was 69U(range 60U-90U);Among them,14 patients with mild parotid hypertrophy were given 30U/side injection,15 patients with moderate hypertrophy were given 36U/side,and severe hypertrophy was given 45U/side.1.In 33 patients(66 parotid glands),the thickness(in mm)of the superficial lobe of parotid gland before treatment was 16(4),was 14(2)at 3-month follow-up,and 13(2)at 6-month follow-up.The superficial lobe of parotid gland thickness at 3 months and 6 months after treatment was significantly lower than that before treatment(p<0.001 and p<0.001,respectively).There was a significant reduction in superficial lobe of parotid gland thickness at 6 months compared with that at 3 months after treatment(p<0.001).2.The long diameter of the parotid gland(in mm)before treatment was 55(5.75),was 54(5.75)at 3-month follow-up,and 54(5)at 6-month follow-up.The long diameter of the parotid gland at 3 months and 6 months after treatment was not significantly different from that before treatment(p=0.338 and p=0.146,respectively).There was no significant difference in the long diameter of the parotid gland at 6 months compared with that at 3 months after treatment(p=0.634).3.Image analyses showed improvement in the facial contour(p<0.05).4.Subgroup analyses showed that the degree of parotid gland hypertrophy affected treatment efficacy and degree of improvement,but age and sex did not(p<0.001,p=0.137,and p=0.138,respectively).5.Serious adverse reactions or complications were not observed.ConclusionsBotulinum toxin type A can be used to treat benign parotid hypertrophy,reduce parotid gland volume,and improve the facial contour.