recurrent contact granulomaexperience with excision and botulinum toxin injectionrecurrent contact...

ORIGINAL ARTICLE

Recurrent Contact Granuloma

Experience With Excision and Botulinum Toxin Injection

Taner Yılmaz, MD; Nilda Suslu, MD; Gamze Atay, MD; Serdar Ozer, MD;Rıza Onder Gunaydın, MD; Munir Demir Bajin, MD

Importance: Contact granuloma is a difficult-to-treatlaryngeal disorder associated with vocal abuse, habitualthroat clearing, and laryngopharyngeal reflux. It has a highpropensity for persistence and recurrence despite manytreatment alternatives.

Objective: To present our experience with recurrent con-tact granuloma treated with microlaryngoscopic exci-sion and botulinum toxin injection.

Design: Case series. The follow-up period had a mean(range) of 41 (11-88) months.

Setting: Tertiary referral university clinic.

Participants: Twenty patients with recurrent, grade 3and grade 4 contact granuloma whose lesion was excisedat least once after failure of conservative treatments.

Interventions: Microlaryngoscopic excision and-botulinum toxin type A injection into the region of

the bilateral thyroarytenoid and lateral cricoarytenoidmuscles.

Main Outcomes and Measures: Disappearance of con-tact granuloma.

Results: Seventeen patients were cured of their contactgranuloma. Three patients experienced recurrences: 2 re-ceived botulinum toxin injection only as outpatients andrecovered. The other patient required reexcision and re-injection under general anesthesia. These 3 patients werefree of granuloma at their last follow-up.

Conclusions and Relevance: After failed conserva-tive treatment, microlaryngoscopic excision and botuli-num toxin type A injection is successful in the treat-ment of recurrent contact granuloma. Removing recurrentgranulomas can result in a low recurrence rate if botu-linum toxin type A is added at the time of removal.

JAMA Otolaryngol Head Neck Surg. 2013;139(6):579-583

C ONTACT GRANULOMA IS A

relatively uncommon, dif-ficult-to-treat laryngealdisorder with multifacto-rial causes. It arises from

the vocal process of the arytenoid carti-lage, and less commonly from the body ofthe arytenoid cartilage. This is why it is alsocalled arytenoid granuloma. It is most com-monly associated with vocal abuse, ha-bitual throat clearing, and laryngopharyn-geal reflux. It has a high propensity forpersistence and recurrence despite manytreatment alternatives.1,2

Intubation trauma associated withgranuloma was once thought an impor-tant etiological factor; however, this le-sion is called intubation granuloma and isa different disease entity from contactgranuloma. Intubation granuloma is ob-served equally or more commonly in fe-male patients than in male patients. It hasa high rate of spontaneous resolution. If

it does not resolve spontaneously, its sur-gical excision yields a low recurrence rate,in contrast to contact granuloma.1,2

Perichondritis of the arytenoid carti-lage, infection, allergy, and psychoso-matic disorders are suspected to be in-volved in the etiology of contact granuloma.Individual susceptibility is also men-tioned as a possible etiological factor.1

In this article, we present our experi-ence with patients with recurrent contactgranuloma who received several differ-ent types of conservative treatments andunderwent surgical excision elsewhere be-fore being treated in our department.

METHODS

Participants consisted of 20 patients with re-current contact granuloma whose contactgranuloma was excised at least once after fail-ure of conservative treatments. Eighteen pa-tients were male and 2 were female, yielding a

Author AffDepartmenOtolaryngoSurgery, HaFaculty of MTurkey.

Author Affiliations:Department ofOtolaryngology–Head & NeckSurgery, Hacettepe UniversityFaculty of Medicine, Ankara,Turkey.

JAMA OTOLARYNGOL HEAD NECK SURG/ VOL 139 (NO. 6), JUNE 2013 WWW.JAMAOTO.COM579

©2013 American Medical Association. All rights reserved.

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male to female ratio of 9:1. Their mean (range) age was 47 (35-69) years. On first examination, 13 cases were graded as grade3 and 7 cases as grade 4. All patients had experienced at least1 surgical excision and recurrence: 11 underwent 1 excision,4 underwent 2 excisions, 2 had 3 excisions, and 3 had 4 exci-sions before visiting our department.

Our treatment protocol for any contact granuloma startedwith a 3-month regimen of 8 to 12 sessions of voice therapy,double-dose proton pump inhibitors, and lifestyle changes de-signed to prevent reflux. For patients with grade 1 or 2 lesionsthat did not respond to the aforementioned regimen, we ad-vised botulinum toxin type A (BTA) injection (2�1.25 U to2�5 U) into the region of the bilateral thyroarytenoid musclesas an office procedure through thyrohyoid injection; for the non-responding grade 3 and 4 lesions, we applied microlaryngo-scopic excision and BTA injection (2�1.25 U to 2�5 U) intothe region of the bilateral thyroarytenoid and lateral cricoary-tenoid muscles. The operation was performed using general an-esthesia with endotracheal intubation or jet ventilation. An ap-propriately sized surgical laryngoscope was inserted into thelarynx to expose the contact granuloma and suspended fromthe anterior chest wall. The granuloma was grasped with for-ceps close to its neck and drawn to the opposite side. This ma-neuver makes its base more visible. With the aid of microscis-sors, the granuloma was cut at its base superficial to theperichondrium of the arytenoid cartilage and totally removed.Preserving the perichondrium is crucial because it will reepi-thelialize easily in a short time; however, if the perichondriumis removed, bare cartilage is difficult to epithelialize and maybecome infected and undergo necrosis as a result of a decreasein the blood supply that was provided by the perichondrium.Under these circumstances, inflammatory granulation tissue willtry to cover the bare cartilage; hence, granuloma will recur. Af-ter the granuloma was removed, BTA injections were per-formed. No corticosteroids were administered, neither oral, norinhaled, nor injected around the base of the lesion.

The BTA injection sites are shown in Figure 1. For the thy-roarytenoid route, the injection needle is aimed lateral to thevocal ligament of the midmembranous vocal fold at the floorof the laryngeal ventricle. For the lateral cricoarytenoid route,

the lateral cricoid lamina is palpated laterally and deep into thevocal process of the arytenoid. After palpation of the cricoid,the BTA is injected just lateral to the cricoid lamina. For theinterarytenoid muscle, the injection is performed deep into themucosa right between both arytenoids. For the aryepiglotticmuscle, the injection is performed deep into the mucosa in themiddle of the aryepiglottic fold.

RESULTS

The follow-up period had a mean (range) of 41 (11-88)months. Treatment of contact granuloma was success-ful for 17 patients. However, 3 patients experienced re-currences; 2 received another BTA injection as an out-patient procedure and recovered. The other patientrequired reexcision and reinjection under general anes-thesia. These 3 patients were free of granuloma at theirlast follow-up appointment. Detailed information on pa-tients is given in the Table.

Patient 4 had a right-sided grade 4 lesion (Figure2A).He has been free of granuloma for more than 7 years(Figure 2B).

Patient 14’s lesion did not respond to office BTA in-jection, so she underwent reoperation; because her le-sion was located superiorly on the body of the aryte-noid, we injected 2 � 5 U BTA into the region of thebilateral aryepiglottic muscle and interarytenoid muscleto relax the supraglottic sphincter.

DISCUSSION

Contact granuloma results from continued hammering of1 vocal process against the other during phonation, re-ferred to as “hammer and anvil.” This is especially truefor loud phonations and hard glottal attacks. Treatmentstrategy should be aimed at decreasing this hammering ac-tion by teaching the patient to speak with softer phona-tion and without hard glottal attack. This is the aim of thevoice therapy. However, voice therapy is not always suc-cessful in alleviating granuloma because some patients can-not follow the recommendations of a voice therapist andare unable to diminish hard glottal attacks.

Contact granuloma has been observed 10 to 20 timesmore commonly in men than in women. In our series, itis 9 times more common in men than in women. Thequestion of how women are protected against contactgranuloma is answered by noting the presence of a pos-terior chink at their vocal process during phonation.

Contact granuloma is usually seen in people older than30 years. The patients characteristically abuse their voiceandhabituallyclear their throat.The lesionsaremostlyuni-lateral; however, bilateral cases are also seen. Seventy-fivepercentofcontactgranulomasare locatedat themedial faceof the vocal process of the arytenoid, and the other 25% areseen posterosuperiorly on the body of the arytenoid.

The voice characteristics of patients with contact granu-loma include intensity above 80 dB and low pitch. Theyfrequently perform hard glottal attacks during phona-tion. Their mean flow rate is low and range is narrow.Their voice is usually strained, pressed, and loud. Theydemonstrate excess vocal fry.1

A

BD

C

Figure 1. Botulinum toxin A injection sites within the larynx. A,Thyroarytenoid muscle; B, lateral cricoarytenoid muscle; C, interarytenoidmuscle; D, aryepiglottic muscle.




Diagnosis of contact granuloma is simple to performby means of clinical examination alone, because of its char-acteristic location and peculiar appearance. No other testsare necessary. Biopsy is performed rarely—only if ma-lignancy is suspected.

Despite its name, contact granuloma is not a granu-loma in the pathological sense. On a specimen of con-tact granuloma, under light microscopy we may ob-serve focal ulceration, epithelial hyperplasia, necrotictissue with desquamating epithelium, acute and/or chronicinflammation, capillary proliferation, fibrosis, and par-tially necrotic arytenoid cartilage.2

Farwell et al3 have proposed a grading system for con-tact granuloma based on its endoscopic appearance. Agrade 1 lesion is limited to the vocal process, there is noulceration, and the lesion is sessile. A grade 2 lesion islimited to the vocal process and is ulcerated or pedun-

culated. A grade 3 lesion extends beyond the vocal pro-cess but does not cross the midline of the fully abductedvocal fold. A grade 4 lesion extends beyond the vocal pro-cess and crosses over the midline of the fully abductedvocal fold. Unilateral cases are designated as “A” and bi-lateral ones as “B.”

There are many treatment options available for con-tact granuloma. Such a high number of alternatives in-dicates lack of satisfaction from a single therapy modal-ity. Furthermore, physicians are in search of better options.Wang et al4 claim that observation alone yields an 81%remission rate within a mean of 30.6 weeks (approxi-mately 7 months). According to our experience, a highspontaneous remission rate is a characteristic of intuba-tion granuloma, whereas contact granulomas rarely dis-appear without treatment. Contact granuloma is a be-nign lesion and does not have to removed. However, all

Table. Characteristics of Patients With Recurrent Contact Granuloma

PatientNo.

PEs,No.

LesionGrade

VTSs,No.

PreopSymptoms

Recurrences,No.

Additional Treatment, No. PostopSymptoms

Follow-up,moBTA Surgery

1 4 4 8 Dysphonia,dyspnea,throat irritation

0 0 0 Throat irritation 36

2 2 3 9 Dysphonia 0 0 0 None 113 1 3 8 Dysphonia,

throat irritation0 0 0 None 18

4 3 4 10 Dysphonia,dyspnea,lump in throat

1 1 0 None 88


throat irritation0 0 0 Throat irritation 48


0 0 0 None 56


0 0 0 None 52

9 2 3 9 Dysphonia,throat irritation

0 0 0 None 40

10 4 3 12 Dysphonia,lump in throat

2 2 0 None 16


0 0 0 None 60


throat irritation0 0 0 Throat irritation 32

14 1 4 10 Lump in throat 1 2 1 None 1115 1 3 12 Dysphonia 0 0 0 None 4416 1 3 11 Dysphonia,

throat irritation0 0 0 None 54

17 2 4 12 Dysphonia,dyspnea,lump in throat,throat irritation


18 1 3 10 Dysphonia,lump in throat,throat irritation

0 0 0 None 32


lump in throat,throat irritation


Abbreviations: BTA, botulinum toxin A; PE, previous excision; postop, postoperative; preop, preoperative; VTS, voice therapy session.




of our patients complained of a change in their voice andfeeling a lump in their throat. Patients with grade 4 le-sions also reported dyspnea on exertion. Throat irrita-tion, which is more commonly observed in patients withchronic pharyngitis, may persist after the granuloma hasdisappeared. These symptoms are given in the Table. Fur-thermore, once our patients see the mass on a video moni-tor, no matter what we say they want get rid of it oneway or another. Although the prior pathology report in-dicates that it is benign, they still ask, “Why doesn’t itdisappear?” or “Why does it come back again and again?”This attitude may be peculiar to our patients. Many yearsago when endoscopic camera facilities were unavailableor underdeveloped, patients were unable to see their le-sion and more readily followed their physician’s adviceto treat it more conservatively. Today, however, havingseen it with their own eyes, they are afraid of the massand want it to go away, especially if it is a grade 3 or 4granuloma. They seem to suspect cancer despite beinginformed of the benign results of pathologic analysis.

Voice therapy comprises the first step in treating a pa-tient with contact granuloma because the lesion devel-ops as a result of hard glottal attack and voice misuse.5

Because laryngopharyngeal reflux is thought to be a fac-tor in causing contact granuloma, it is also treated withantireflux medication and lifestyle modifications, such

as changing the diet, avoiding reflux-provoking foods andbeverages, eating small volume meals, avoiding recum-bency after meals, and elevating the head of the bed dur-ing sleep. Antireflux medications include single-dose ordouble-dose proton pump inhibitors with or without H2

receptor blockers administered before bedtime, alginicacid, and prokinetics. However, the rarity of contact granu-loma and frequency of laryngopharyngeal reflux makesus think that such an association, if it ever exists, is vague.

Botulinum toxin was suggested for the first time as aform of treatment for patients with contact granulomaby Nasri et al6 in 1995. Damrose and Damrose7 claimedthat percutaneous injection of BTA is a safe and effec-tive therapy in resolving vocal process granulomas in pa-tients whose disease was refractory to traditional therapy.It is used in total doses ranging from 2.5 to 30 U. It isinjected into the region of the thyroarytenoid and lat-eral cricoarytenoid muscles to relax their adducting ac-tion on the arytenoid vocal process to decrease traumaof 1 vocal process to the other one. This injection re-laxes the glottic sphincter. It can be used as a sole treat-ment or combined with microlaryngoscopic excision. In-jections of BTA can be performed as an office procedurevia the oral cavity, via the thyrohyoid membrane, via thethyroid cartilage, via the cricothyroid membrane, or usinggeneral anesthesia. The resultant temporary paresis ofthe vocal folds allows for a window of time during whichthe vocal process can heal and the granulomas can re-solve without being exposed to ongoing intermittent con-tact and friction with the opposing arytenoid.8 Our pa-tients with recurrent contact granuloma responded wellto our treatment protocol. Three of 20 patients had con-tinued recurrence; however, their recurring lesions werealso successfully managed with the same protocol. In acase resistant to regular BTA injection, injection into theregion of the aryepiglottic muscle and interarytenoidmuscle to relax the supraglottic sphincter may be an al-ternative method. This was successfully used for 1 of ourpatients.

The use of antibiotics against chondritis of the aryte-noid and Helicobacter pylori–induced reflux may be ben-eficial in some patients with contact granuloma. Corti-costeroids have been administered as topical spray,intralesional injection, and systemically to prevent in-flammation in contact granuloma. However, inflamma-tion is secondary to mucosal trauma and ulceration onthe vocal process, and without acting on the primarycause, that is, mucosal trauma, corticosteroids are notlikely to cure contact granuloma. Hillel et al9 treated 54patients with granuloma with proton pump inhibitors andinhaled triamcinolone acetonide; 20 of their patients(37%) had intubation granuloma. They found a 69% com-plete response rate with a mean (range) follow-up of 21(5.9-84.6) weeks. The main drawback of their study isthe inclusion of patients with intubation granuloma inthe study sample.

Vitamin and mineral supplementation has been triedto treat patients with contact granuloma. Recently, Sunet al10 claimed that zinc sulfate (ZnSO4) supplementa-tion was successful in contact granuloma treatment, eitheras an initial or compensatory treatment. However, zincsupplementation can cure vocal process granuloma only

A

B

Figure 2. Images of patient 4. A, Right-sided grade 4 lesion; B, afterfollow-up of more than 7 years.




in the presence of a zinc deficiency. If the patients havenormal blood and tissue levels of zinc, zinc supplemen-tation, even in large doses (the authors gave 22 times thedaily requirement), is not expected to solve the prob-lem.11 Microlaryngoscopic excision with or without la-ser, cryotherapy, and electrocautery are other alterna-tives for contact granuloma treatment. Mucosal graft wasused to cover the mucosal defect after surgical excisionto prevent granuloma recurrence. Low-dose radio-therapy has been suggested for cases resistant to otherforms of treatment.12

Surgery alone should not be used as a first-line andsole treatment of contact granuloma because this leadsto a mean of 3 removals per patient. Surgery alone yieldeda 90% recurrence rate for contact granuloma.1 Some claimthat surgery has no role in the treatment of this condi-tion and should be used only for histologic diagnosis incase malignancy is suspected. However, Hirano et al13 pro-posed fiberoptic laryngeal surgery as an office proce-dure to facilitate repeated surgical removals.

If there is glottal insufficiency due to paresis and pa-ralysis, contact granuloma develops as a result of the com-pensatory stronger action of the healthy vocal process onthe paretic one. In such cases, vocal fold augmentationin the form of injection laryngoplasty may alleviate thegranuloma. Halum et al14 pointed out the association ofvocal process granulomas with unilateral superior laryn-geal nerve paresis, potentially related to altered contactpoints between the vocal processes of the arytenoids.

Removing a part of the arytenoid cartilage, usually thevocal process, to stop trauma to the other side has beensuggested; however, we believe that this is an unethicaland unacceptable form of treatment for a benign disor-der because it will lead to permanent dysphonia.

First-line therapy for contact granuloma is conserva-tive, taking the form of voice therapy together with an-tireflux therapy. The recommended duration of this treat-ment, 3, 6, 9, or 12 months or longer, has not yet beendetermined. We have used this conservative treatmentfor 3 months and, if unsuccessful, have switched to BTAinjection for grade 3 and 4 lesions. Thus far, we have beensuccessful with this treatment regimen for recurrent ornonresponsive contact granuloma. In a case resistant toregular BTA injection to the thyroarytenoid and lateralcricoarytenoid muscles, injection to the aryepiglotticmuscle and interarytenoid muscle to relax the supraglot-tic sphincter may be an alternative method.

In conclusion, removing recurrent granulomas canresult in a low recurrence rate if BTA is added at the timeof removal.

Submitted for Publication: January 7, 2013; final revi-sion received February 21, 2013; accepted March 17, 2013.Correspondence: Taner Yılmaz, MD, Department of Oto-laryngology,HacettepeUniversityFacultyofMedicine,06100Sıhhiye, Ankara, Turkey ([email protected]).Author Contributions: All authors had full access to allthe data in the study and take responsibility for the in-tegrity of the data and the accuracy of the data analysis.Study concept and design: Yılmaz. Acquisition of data: Allauthors. Analysis and interpretation of data: Yılmaz, Atay,Ozer, Gunaydın, and Bajin. Drafting of the manuscript: Allauthors. Critical revision of the manuscript for importantintellectual content: Yılmaz and Bajin. Administrative, tech-nical, and material support: All authors. Study supervi-sion: Yılmaz.Conflict of Interest Disclosures: None reported.Previous Presentation: This study was presented at theFall Voice Conference; October 5, 2012; New York, NewYork.Additional Contributions: We thank Ebru Oralli for cre-ating Figure 1 for us.

REFERENCES

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10. Sun GB, Sun N, Tang HH, Zhu QB, Wen W, Zheng HL. Zinc sulfate therapy ofvocal process granuloma. Eur Arch Otorhinolaryngol. 2012;269(9):2087-2090.

11. Yılmaz T. Zinc sulfate treatment of vocal process granuloma. Eur ArchOtorhinolaryngol. 2013;270(3):1175.

12. Song Y, Shi L, Zhao Y, Zhao D, Shi M, Deng Z. Surgical removal followed byradiotherapy for refractory vocal process granuloma. J Voice. 2012;26(5):e1-e5, e15.

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14. Halum SL, Miller P, Early K. Laryngeal granulomas associated with superior la-ryngeal nerve paresis. J Voice. 2010;24(4):490-493.




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