Botulinum neurotoxin treatment of salivary gland disorders

last modified on: Thu, 02/15/2018 - 13:40

Botulinum neurotoxin treatment of salivary gland disorders

 

return to: Botulinum Toxin Protocols

see also:Sialendoscopy Course LSU New Orleans Lectures (Hoffman) Feb 1-2, 2014

  Hypersalivation Ptyalism Sialorrhea

Botox injection to salivary glands for hypersalivation

Botulinum Toxin (Btx) use in salivary disorders

Selected articles from pubmed search 2009 – 2013 “Botulinum toxin and salivary gland”

Abnormality Treated

Study

Study Characteristics

Conclusion

Disfiguring salivary gland enlargement

 

 

*note controversial conclusions are statements marked by * and with bold italics.

Induce atrophy of prominent salivary glands

Bae et al 2013 [i]

Report of two cases  - (4 U/0.1mL)

first case: 30 U (BtxA)  into 6 sites of left parotid after right parotidectomy

second case: 38 U (BtxA) to each parotid

     20 U (BtxA) to each smg

(repeated two subsequent injections at two month intervals used same 20 units to each SMG with slightly lower dose to parotids - 32 U to each parotid (2nd time) and 28 U to each parotid (3rd time)

*Btx may be used as a new treatment for lower face contouring.

Adjunctive parotid instillation of Botox to supplement more standard masseter injection for ‘facial slimming”

 

 

 

password protected:

Case Presentation Use of Botulinum Toxin Following Partial Submandibular Gland Resection

Wu (2009)[ii]

Historical description of authors use beginning in 1998 to treat over 600 patients with wide ‘boxy’ face or ‘square jaws”. Repeat injections until no palpable masseter muscle activity and ramus of mandible felt. (average initial does to masseter is 40 units Btx-A repeated twice at one month intervals.)   Parotid injections done to address ‘bull necked’ look with 40 units of Botox injected into the parotid gland monthly until the swelling becomes less obvious (usually 3-4 sessions “no complaints of dryness of mouth or decrease in saliva production”

*“Botulinum toxin-A is a

highly efficacious and cost effective, nonsurgical option for reducing the width and shape of the lower face and jawline.”

 

*“Botulinum toxin-A can also be effectively used to reduce the bulk of an enlarged parotid gland without affecting saliva production.”

Persistent Sialocoele / Salivary Fistula

 

 

 

After SMG resection for stone with residual gland left behind

Capaccio et al  2007[iii]

Case report – aspirate fluid – U/S guided 3 separate injections (total 30 U BtxA)

‘First case of Iatrogenic postop smg sialocoele and first use of Btx for that purpose’ (successful)

After unsuccessful surgery to remove stone in distal 1/3 of Stensen’s duct with success ultimately with lithotripsy

Capaccio et al 2004[iv]

Case report – aspirate fluid – U/S guided injection 50 U Btx A; subsequent series of two sialendoscopies

Promising use of Botox, ultrasound and sialendoscopy to replace traditional invasive tx of sialocoeles

Salivary fistula after transparotid approach to parapharyngeal tumor

 

go to: Complication from open (transfacial) approach to parotid stone removal

Lim and Choi 2008[v]

Case report – two injections totaling 10 U BtxA on POD #1 after parotidectomy; ‘disappearance of salivary fistula one day after injection”

highly effective and relatively safe primary method, for the treatment of an acute

postparotidectomy salivary fistula,

 

Salivary sialocele after parotidectomy rx with aspiration and BtxB

Pantel et al [vi]

Case report – sialocele after parotidectomy with 2500 mouse units of botulinum toxin type B in residual parotid gland tissue with repeated aspirations before and after BtxB injection

“Botulinum toxin type B is effective in the management of postoperative sialocele after parotid gland surgery”

Sialorrhea

(note separate excellent

review article by Lakraj et al (2013))

 

 

 

   Vashishta R et  al (2013)  Meta-analysis  of 8 studies showed botulinum toxin to significantly decrease the severity of drooling in patients with sialorrhea. Conversion factor to equivalent units of botulinum toxin A (Botox) was 2.5:1 for Dysport and 50:1 for Myobloc of Neurobloc (botulinum toxin B).  "...botulinum toxin A has a longer duration of action and fewer systemic autonomic adverse effects, which suggests that it may be preferred for the management of sialorrhea."
Ultrasound-guided versus 'blind' intraparotid injections Dogu et al (2004)

Prospective study of 15 patients with Parkinson's disease - 8 treated with BTX-A with U/S guidance, 7 treated without ultrasound guidance

Dry dental rolls placed intraorally were weighed after being retained for 5 minutes; subjective assessment scale (VAS = visual analog scale) daily assessment for 7 days after treatment; U/S machine used 12 mHz linear transducer with 15 units BTX-A into two separate sites (upper and lower poles of parotid with 30 gauge needle ('total 30 U of BTX-A" identified as 15 units to each parotid gland). Improvement in both groups seen, but statistically greater with U/S guidance.

"Use of ultrasound guidance during the injection procedure seems to improve efficacy and safety"

Drooling associated with neurodevelopmental problems in children

 

 

 

 

Chan et al (2013) [vii]

 

 

Retrospective study of 69 pts average age 9.9 ys all with neurodegenerative disease; 81% with pre-existing swallowing abn  

U/S guided 4 gland injection – initial 30 U Btx A to each smg and 20 U to each parotid – evolved to total dose of 12 U/kg of BTxA with 60% (30% per gland) to smg; 40% (20% per gland) to parotids; IV sedation with monitoring in radiology suite

 telephone f/u (51% response to call)

45% required supplemental treatment;

16% cpx rate

Satisfaction scale: 44% were either satisfied or very satisfied;

BtxA for sialorrhea in children is a useful tool but has safety and efficacy limitations

Drooling in patient with cerebral palsy complicated by sialadenitis with sialolithiasis

Yuan and Shelton (2011)[viii]

Case report of obstructing submandibular calculi developed on the 30th day after BoNT injection, “likely because of the reduced salivary flow rate.” BtxA 20 units to each smg gland and 30 units to each parotid (100 U) as well 50 units to each masseter for bruxism. They relate “There is no absolute evidence to prove that the calculus of the submandibular duct was originally formed after BoNT injection.”

*”Sialolithiasis and subsequent sialadenitis may be potential complications of intraglandular BoNT

injection for sialorrhea”.

 

Prophylaxis prior to surgery

 

 

 

Before oral cavity resection to saliva-related complications

Corradino et al (2012)[ix]

Prospective evaluation of 43 patients injected 4 days preop with 30-40 U BtxA bilaterally to parotids and 10 U to smg (not ipsilateral – to be removed) – total dose 80-100 U. Quantitative measurement: 50% reduction of section on third day after injection; 70% reduction after 8th day. Sialoscintigraphy – 90% reduction of function 15th day after injection. 45th day after injection return to normal salivation.

Careful assessment of gland function showed diminished salivary that ‘could enable a reduction in saliva-related local complications’ (no statistical significance seen)

Frey’s syndrome

 

 

 

Interfere with gustatory sweating after parotidectomy with intradermal Btx A (Dysport) injection

see: Botox Injection for Freys Syndrome

Steffen et al (2012)[x]

Retrospective review of 8 patients treated with botulinum toxin type A (Dysport 500 unit vial diluted in 2.5 ml saline) 10 units intradermally per cm2 skin (no starch iodine test); their literature review = 25 more cases – 6-18 month response

Responses are unpredictable

Prevent acetyl choline release across neuro-effector junction of aberrant parasympathetic reinnervation to sweat glands and blood vessels after parotidectomy. Btx –B is more effective in reducing sympathetic function than Btx-A

Cantarella et al (2010)[xi]

Retrospective review of 7 patients treated with 80 U of Btx type B per cm2 (mean total dose of 2,354 U) intradermal in region mapped by Minor test. Complete resolution of symptoms in 6 of 7 patients. At 12 months post tx all 7 reported some improvement persisting.

No study yet determine ideal dose for Btx-B (estimate 50 units of  Btx-B has about same efficacy as 1 unit of Btx-A

 

Laccourreye et al (1999)

 

 

Recurrent parotitis (Sjogrens)

 

 

 

Recurrent cystic parotid swelling in child with after and persistent unilateral fistula tract

Daniel and Diamond (2011)[xii]

Case report of 8 yo with serology and lip bx supporting Sjogrens syndrome as cause of recurrent parotid swelling – persistent fistula developed from needle bx tract responded to 20 U of BtxA bilaterally to each parotid with disappearance of parotid cysts (one year f/u) with no concomitant therapy

2 potential mechanisms postulated

1. decrease in saliva production in cysts alleviated compression on ducts

2. high prevalence of anti-muscarinic-3 acetylcholine receptor autoantibodies in children with Sjogrens – possibly protecting gland from autoantibodies by inhibiting acetyl choline release

“botulinum toxin injection into the parotid glands appears as a safe,effective, and novel treatment option for patients suffering from recurrent cystic parotitis related to Sjogren syndrome

Adjunct to Sialendoscopy

 

 

 

Selective use to provide temporary relief of obstructive symptoms in stenoses that could not be addressed endoscopically

Gillespie et al (2011)

100 U of BtxA mixed with 2 cc of sterile saline injected with ultrasound guidance into 3 locations (33 units per injection) Five patients (23%)

with proximal, intraglandular strictures within the second or third order ducts that could not be fully dilated or stented underwent ultrasound-guided Botox injection at the time of the procedure to transiently control obstructive symptoms

Outcome from Btx injection not reported.

Our series

found no support for routine screening for Sjogrens syndrome in patients without a history of xerostomia, periglandular lymphadenopathy, or a

rheumatologic disorder.

Chronic Parotitis associated with duct stricture

 

 

 

Ultrasound guided parotid injections to address painful gustatory swelling refractory to other tx

Kruegel et al (2010)[xiii]

Case report of recurrent painful parotid swelling occurring with meals with previous h/o radioiodine tx -  structures seen on sialogram with unsuccessful efforts at duct dilation and treatment with “percutaneous radiotherapy with 7.5 Gy”. Initial tx Btx-A 7.5 U in three injections (22.5U), then three subsequent injections with 30 Units (3 sites 10 units each)

After initial injection 2 weeks passed before full effect (relief of symptoms) that recurred after 6 weeks; second and third injections provided relief for 4 months each.

First Bite Syndrome

 

 

 

Address denervation supersensitivity of the sympathetic receptors controlling the myoepithelial cells after parapharyngeal space surgery by inducing a Btx-A parasympathetic nerve paralysis of the parotid

Lee et al (2009)[xiv]

Retrospective review of 5 cases of first bite syndrome treated with 3 intra-parotid injections of 11 U of Btx-A (total 33 units).  Hypothesized that Btx interferes with parasympathetic neurotransmitters released with oral intake that cross-stimulate the hypersensitive sympathetic receptors.

BTA injection into affected

parotid gland produces a decrease in the severity

of first bite syndrome and improves the

patient’s quality of life.

 

Further studies are needed on effective

and safe doses of BTA injections to management

the first bite syndrome.

Obstructive Parotitis Due to Acute Masseteric Bend      
   Reddy et al (2012) xv Three cases of obstructive parotitis diagnosed with sialendoscopy and imaging were treated successfully by relieving the acute bend around the masseter in two cases of masseter muscle hypertrophy by inducing atrophy of the masseter and in one case by resection of fibrous dysplasia affecting the masseter muscle and mandible. In addition to use of bite blocks to treat bruxism, success with use of botox in one adult followed 25 U of Btx-A to the masseter and 75 U (three separate sites) to the parotid - requiring one re-treatment after 3-4 months.   Kinking of parotid duct around the masseter can be addressed by botox injection to masseter to induce atrophy
 

Smg = submandibular gland

Btx = botulinum toxin

Btx-A= botulinum toxin A

Btx-B= botulinum toxin B

U = units

 

[i] Bae GY, Yune YM, Seo K, and Hwang SI: Botulinum Toxin Injection for Savliary Gland enlargement Evaluted Using Compted Tomogrphic Volumetry   Dermatologic Surgery volum 39, Issue 9 pp 1404-1407, Sept 2013

[ii] Wu WT.Botox facial slimming/facial sculpting: the role of botulinum toxin-A in the treatment of hypertrophic masseteric muscle and parotid enlargement to narrow the lower facial width. Facial Plast Surg Clin North Am. 2010 Feb;18(1):133-40. doi: 10.1016/j.fsc.2009.11.014.

[iii] Capaccio P, Cuccarini V, Benicchio V, Minorati D, Spadari F, Ottaviani F: Treatment of iatrogenic submandibular sialocele with botulinum toxin. Case report. Br J Oral Maxillofac Surg. 2007 Jul;45(5):415-7. Epub 2006 Apr 11.

[iv] Capaccio P, Paglia M, Minorati D, Manzo R, Ottaviani F.Diagnosis and therapeutic management of iatrogenic parotid sialocele. Ann Otol Rhinol Laryngol. 2004 Jul;113(7):562-4.

[v] Lim YC, Choi EC Treatment of an acute salivary fistula after parotid surgery: botulinum toxin type A injection as primary treatment. Eur Arch Otorhinolaryngol. 2008 Feb;265(2):243-5. Epub 2007 Aug 18

[vi] Pantel M, Volk GF, Guntinas-Lichius O, Wittekindt C.Botulinum toxin type b for the treatment of a sialocele after parotidectomy. Head Neck. 2013 Jan;35(1):E11-2. doi: 10.1002/hed.21778. Epub 2011 Jun 17

[vii] Chan KH, Liang C, Wilson P, Higgins D, Allen GC  Long-term safety and efficacy data on botulinum toxin type A: an injection for sialorrhea. JAMA Otolaryngol Head Neck Surg. 2013 Feb;139(2):134-8. doi: 10.1001/jamaoto.2013.1328.

[viii] Yuan M, Shelton J.Acute sialadenitis secondary to submandibular calculi after botulinum neurotoxin injection for sialorrhea in a child with cerebral palsy.Am J Phys Med Rehabil. 2011 Dec;90(12):1064-7. doi: 10.1097/PHM.0b013e31823285c7.

[ix] Corradino B, Di Lorenzo S, Moschella F  Botulinum toxin A for oral cavity cancer patients: in microsurgical patients BTX injections in major salivary glands temporarily reduce salivary production and the risk of local complications related to saliva stagnation. Toxins (Basel). 2012 Oct 24;4(11):956-61. doi: 10.3390/toxins4110956.

 

[x] Steffen A, Rotter N, König IR, Wollenberg B.Botulinum toxin for Frey's syndrome: a closer look at different treatment responses. J Laryngol Otol. 2012 Feb;126(2):185-9. doi: 10.1017/S0022215111002581. Epub 2011 Oct 3.

 

[xi] Cantarella G, Berlusconi A, Mele V, Cogiamanian F, Barbieri S.Treatment of Frey's syndrome with botulinum toxin type B.Otolaryngol Head Neck Surg. 2010 Aug;143(2):214-8. doi: 10.1016/j.otohns.2010.04.009.

 

[xii] Daniel SJ, Diamond M.Botulinum toxin injection: a novel treatment for recurrent cystic parotitis Sjögren syndrome. Otolaryngol Head Neck Surg. 2011 Jul;145(1):180-1. doi: 10.1177/0194599811398596

[xiii] Kruegel J, Winterhoff J, Koehler S, Matthes P, Laskawi R.Botulinum toxin: A noninvasive option for the symptomatic treatment of salivary gland stenosis - a case report. Head Neck. 2010 Jul;32(7):959-63. doi: 10.1002/hed.21150.

 

[xiv] Lee BJ, Lee JC, Lee YO, Wang SG, Kim HJ Novel treatment of first bite syndrome using botulinum toxin type A. Head Neck. 2009 Aug;31(8):989-93. doi: 10.1002/hed.21054

xv Reddy R, White Dr, and Gillespie MG: Obstructive parotitis secondary to an acute masseteric bend. ORL J Otorhinolaryngol Relat Spec. 2012;74(1);12-5

Lakraj AA, Moghimi N and Jabbari B: Sialorrhea: Anatomy, Pathophysiology and Treatment with Emphasis on the Role of Botulinum Toxins.  Toxins 2013,5,1010-1031

Vashishta R, Nguyen SA, White DR, and Gillespie MB: Botulinum Toxin for the Treatment of Sialorrhea: A Meta-analysis.Otolaryngology–Head and Neck Surgery 2013; 148(2) 191-196

Dogu O, Apaydin D, Sevim S, Talas DU, Aral. Ultrasound guided versus 'blind' intraparotid injections of botulinum toxin-A for the treatment of sialorrhoea in patients with Parkinson's disease. Colin Neurol Neurosurg. 2004; 106:93-6

Ondo WG, Hunter C, Moore W. A double-blind placebo-controlled trial of botulinum toxin B for sialorrhea in Parkinson's disease. Neurology. 2004; 62:37-40