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 Table of Contents  
REVIEW ARTICLE
Year : 2020  |  Volume : 33  |  Issue : 2  |  Page : 333-338

Role of steroids injection in treatment of minimal associated pathological lesions


1 Department of Otorhinolaryngology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
2 Department of Otorhinolaryngology, Faculty of Medicine, Cairo University, Cairo, Egypt
3 Department of Otorhinolaryngology, Faculty of Medicine, Menoufia University, Menoufia, Egypt
4 Department of Otorhinolaryngology, Menoufia University, Menoufia, Egypt
5 Department, of Otorhinolaryngology, Elmenshawy General Hospital, Tanta, Egypt

Date of Submission07-May-2018
Date of Decision13-Jun-2018
Date of Acceptance24-Jun-2018
Date of Web Publication27-Jun-2020

Correspondence Address:
Reham M El-Ashry
Tanta, El-Gharbia
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_167_18

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  Abstract 

Objectives
This review aims to determine the effectiveness of glucocorticoids local intralesional injection in the treatment of minimal associated pathological lesions and counter its adverse effects and possible complications
Data sources
Medline databases (PubMed, laryngoscope, Arch Otoloaryngol Head Neck Surg, Journal of Voice) using the terms 'Steroid' or 'Dexamethasone' with the word 'Vocal fold' as a search criteria. Resulting materials are available in the internet from 1983 to 2017.
Study selection
This search presented 40 articles. The researches that met the inclusion criteria were six articles. The articles studied the Steroids Injection in Treatment of Vocal Folds Lesions.
Data extraction
If the studies did not fulfill the inclusion criteria, they were excluded. Study quality assessment included whether ethical approval was gained, eligibility criteria specified, appropriate controls used, adequate information collected, and assessment measures defined.
Data synthesis
Significant data were collected. It was heterogeneous. Thus, a structured review was performed with the results tabulated.
Conclusion
Treatment for minimal associated pathological lesions generally initiates with the behavioral modification of phonation habits. When conservative managements fail, laryngeal microsurgery might represent the only available treatment option. However, potential adverse effects following the laryngeal suspension include injury to the teeth or cervical spine or tongue paresthesia. Besides, violation of the layered structure of the vocal fold during surgery can also result in fibrosis of the lamina propria. Vocal fold steroid injection might provide an alternative treatment option for benign lesions of the vocal folds.

Keywords: dexamethasone, laryngoscope, steroid, vocal cyst, vocal fold, vocal nodule, vocal polyp


How to cite this article:
Baraka M, El-Dessouky H, Behiry EA, Ezzat E, El-Ashry RM. Role of steroids injection in treatment of minimal associated pathological lesions. Menoufia Med J 2020;33:333-8

How to cite this URL:
Baraka M, El-Dessouky H, Behiry EA, Ezzat E, El-Ashry RM. Role of steroids injection in treatment of minimal associated pathological lesions. Menoufia Med J [serial online] 2020 [cited 2020 Sep 20];33:333-8. Available from: http://www.mmj.eg.net/text.asp?2020/33/2/333/287751




  Introduction Top


Minimal associated pathological lesions (MAPLs), such as vocal fold nodules, polyp, cyst, and Reinke's edema refer to unilateral or bilateral lesions of the midmembranous portion of the vocal fold that lie within the superficial lamina propria (i.e. the Reinke's space)[1].

Common clinical presentations of these lesions include dysphonia, voice fatigue, dryness, or tightness of voice, narrowed vocal range, and deteriorated voice quality (husky or breathy character)[1].

Behavioral modification remains the first-line management, followed by laryngeal microsurgery (LMS). However, when compliance with conservative management is poor; when the risk from general anesthesia is high; when the patient is unwilling to have an operation; or in case of recurrence after surgery, very few options remain for patients[2].

First applied vocal fold steroid injection (VFSI) in the treatment of benign vocal fold disorders was in 1964, although the initial technique was inaccurate, with the advancement of modern endoscopy, recent studies have proposed that VFSI might provide an alternative treatment option for benign lesions of the vocal folds[3].


  Materials and Methods Top


Search strategy

We reviewed papers on the steroids injection in treatment of MAPLs Medline databases (PubMed, laryngoscope, Arch Otoloaryngol Head Neck Surg, Journal of Voice) and also materials available in the internet from 1983 to 2017. We used steroids injection as a main term of search plus one of these items: Dexamethasone/laryngoscope/Steroid/Vocal cyst/Vocal fold/Vocal nodule/Vocal polyp.

Study selection

All the studies were independently assessed for inclusion. They were included if they fulfilled the following criteria:

  1. Original work study
  2. Well designed with clear selection criteria and clear results
  3. Published in English language
  4. Published in peer-reviewed journals
  5. Focused on steroid injection and MAPLs
  6. If a study had several publications on certain aspects we used the latest publication giving the most relevant data.


Data extraction

If the studies did not fulfill the above criteria, they were excluded. The analyzed publications were evaluated according to evidence-based medicine criteria using the classification of the U.S. Preventive Services Task Force.

U.S. Preventive Services Task Force:

Level I: evidence obtained from at least one properly designed randomized controlled trial

Level II-1: evidence obtained from well-designed controlled trials without randomization

Level II-2: evidence obtained from well-designed cohort or case–control analytic studies, preferably from more than one center or research group

Level II-3: evidence obtained from multiple times series with or without the intervention. Dramatic results in uncontrolled trials might also be regarded as this type of evidence

Level III: opinions of respected authorities, based on clinical experience, descriptive studies, or reports of expert committees.

Quality assessment

The quality of all the studies was assessed. Important factors included study design, attainment of ethical approval, evidence of a power calculation, specified eligibility criteria, appropriate controls, adequate information, and specified assessment measures. It was expected that confounding factors would be reported and controlled for and an appropriate data analysis, which was made in addition to an explanation of missing data.

Data synthesis

A structured systematic review was performed with the results tabulated.


  Results Top


On the basis of our selection criteria, 40 well-designed studies were included. Studies which were not original or poorly designed were excluded from our review. Recent articles have proposed that VFSI might provide an alternative treatment option for benign lesions of the vocal folds.

About six studies that applied VFSI as the primary management of benign vocal fold lesion was taken in to consideration. This studyreported disease entities suitable for VFSI, which included Reinke's edema, vocal nodules, polyp/cyst, granuloma, and vocal scar. Except for one study using methylprednisolone for VFSI, all the other studies injected triamcinolone acetonide into the vocal folds, possibly due to its depot nature and long-standing effects. The summary of these studies and the treatment outcomes were measured between 3 weeks to 1 month, following VFSI, as shown in [Table 1].
Table 1: Summary of the recruited studies and reported treatment outcomes measured between 3 weeks to 1 month following the vocal fold steroid injection

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There was one study that applied steroid injection transnasal via the operating channel of a flexible endoscope. Results of this study is shown in [Table 2].
Table 2: Results of video laryngostroboscopy at 1 and 3 months following transnasal endoscopic steroid injection in 30 patients with vocal polyps and nodules

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Also one study supports the performance of steroid injection percutaneously under local anesthesia by a single surgeon under transnasal flexible fiberscopic monitoring treatment response rate as shown in [Table 3].
Table 3: Treatment response rate after percutaneous steroid injection for each benign laryngeal lesion

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  Discussion Top


Benign vocal fold lesions, such as vocal nodules, polyp, cyst, and Reinke's edema usually result from chronic overuse and abuse of the voice. Although pathological examination reveals subtle differences between these lesions, mostly present as phonotrauma, chronic inflammation, and subsequent remodeling of the Reinke's space[12].

Vocal overuse (excessive quantity of voice use), abuse (yelling), and misuse (vocal hyperfunction with excessive muscular tension) presumably leads to excessive mechanical stress and trauma in the midmembranous vocal fold, resulting in wound formation. Wound healing leads to remodeling of the superficial layer of the lamina propria. It is this tissue remodeling that results in the formation of vocal fold nodules, polyps, and cysts. Several studies have demonstrated that the pathologic changes in vocal fold polyps, nodules, and cysts occur within the superficial layer of the lamina propria[13].

Vocal fold nodules are bilateral with a classic location at the junction of anterior and middle third of the vocal fold. Nodule are most often observed in women age 20–50 years, but they are also found commonly in children (more frequently in boys than in girls) who are prone to excessive shouting or screaming[14].

Vocal fold polyps are generally unilateral, as they involve the free edge of the vocal fold mucosa. Polyps have a broad spectrum of appearances. They occur more often in males, after intense intermittent voice abuse, history of aspirin, anticoagulant use, or other vocal trauma, such as endotracheal intubation[15].

Two types of cysts are found within Reinke's space. Mucus retention cyst are often translucent and are lined with cuboidal or columnar epithelium. Mucus retention cyst may occur spontaneously or may be associated with poor vocal hygiene or secondary to ductal obstruction. Epidermoid cyst contains epithelium or accumulated keratin. Epidermoid cyst may occur secondary to vocal abuse and overuse, or may be secondary to a remnant of epithelium trapped within the lamina propria. The term intrafoldal refers to the allocation just below the cover of the vocal fold within Reinke's space and outside of the vocalis muscle[14].

Reinke's edema is one of the common benign lesions causing dysphonia of voice. The accumulation of fluid under the epithelium of the true vocal folds is generally known as Reinke's edema. The Reinke's space is superficial to the vocal ligament, bound anteriorly by Broyles' ligament and limited posteriorly by the arytenoid. It contains loose areolar tissue. The attachment of the vocal ligament along the medial edge and underneath the vocal cord by the lamellar fibers extending to the conus elasticus restricts the edema to the superior surface of the vocal folds[16].

Treatment for benign vocal fold disorders generally initiates with behavioral modification of phonation habits. Vocal nodules usually reduce in size following voice therapy; however, voice therapy alone might not be effective in the management of other lesions with significant anatomic variations, such as polyp, Reinke's edema, or scar[2].

When conservative managements fail, LMS might be the only available treatment option. However, potential adverse effects following laryngeal suspension include injury to the teeth or cervical spine or tongue paresthesia. Besides, violation of the layered structure of the vocal fold during surgery can also result in fibrosis of the lamina propria[17].

In recent decades, various studies have demonstrated the role of intralesional steroid injection as an alternative treatment for benign vocal fold lesions. Besides, a recent systematic review and meta-analysis had showed significant subjective and objective improvements following intralesional steroid injection for vocal nodules, polyp, cyst, and Reinke's edema[10].

Intralesional steroid injection has been advocated in the management of inflammatory laryngeal diseases, such as sarcoidosis, systemic lupus erythematosus, and Wegener's granulomatosis[18].

Six articles, mentioned earlier, applied VFSI as the primary management of benign vocal fold lesion. These articlesreported disease entities suitable for VFSI, which included Reinke's edema, vocal nodules, polyp/cyst, granuloma, and vocal scar. Except for one study using methylprednisolone for VFSI, all the other studies injected triamcinolone acetonide into the vocal folds, possibly due to its depot nature and long-standing effects. Suggested voice rest after the VFSI ranged from 1 to 7 days[19].

VFSI performed on 42 patients of Reinke's edema, demonstrated improvements in 27 patients, disappeared in 14 patients, and no change in one patient[4].

VFSI performed on 28 patients of nodules, demonstrated improvements in 10 patients, disappeared in 17 patients, and no change in one patient[5].

VFSI performed on 34 patients of nodules, polyp, and cyst, demonstrated improvements of edge, amplitude, wave, and vibration[6].

VFSI performed on 22 patients of polyp, demonstrated improvements in 15 patients, disappeared in five patients, and no change in two patients[7].

VFSI performed on 80 patients of nodules, demonstrated improvements in 39 patients, disappeared in 35 patients, and no change in six patients[8].

VFSI performed on 115 patients with nodules, Reinke's edema, and polyp, demonstrated mucosal wave 1.86 → 2.23 and glottis closure 1.89 → 2.34[9].

Most of these studies focused on the advantageous features of intralesional steroid injection; that is, the maintenance of regional drug concentration while preventing systemic adverse effects[10].

Techniques of intralesional vocal fold steroid injection

Transoral injection

Corticosteroid can be injected into vocal folds as an office procedure through a transoral, transnasal, or percutaneous route. Transoral injection requires passing a long curved needle along the sensitive tongue base and pharyngeal mucosa. However, the gag reflex tends to be stronger using the transoral approach and a long and curved needle also makes this technique difficult to master[19].

Office-based application is frequently limited by the associated technical demands, especially regarding the need for adequate local anesthesia and precise placement of the needle into the Reinke's space. The completion rate of transoral steroid injection is around 85%. For patients who could not tolerate transoral injection, shift to other treatment modalities[5].

Transnasal endoscopic steroid injection

Local anesthesia of the nasal cavity was performed using a cotton pledget soaked with 1 : 1000 epinephrine and 2% lidocaine solution, followed by spraying 2% lidocaine solution over the pharynx, tonsils, and vallecula. An experienced resident doctor operated the transnasal flexible laryngoscope, which was connected to a high-definition video processor. The patient was instructed to phonate a sustained/i/sound when 5 ml of 2% lidocaine was dripped into the laryngeal introitus. A transnasal endoscopic steroid injection (TESI) was injected using a specially designed endoscopic injection apparatus, which includes a reusable metallic external sheath and a disposable flexible needle tract with a 27-G rigid tip. After the needle tract was filled with 0.3 ml of dexamethasone sodium phosphate, 0.1 ml of dexamethasone was injected into the Reinke's space just beneath the vocal lesions. Precise placement of needle tip can be assured by the formation of a subepithelial translucent bleb over the Reinke's space. In the meantime, injection into the vocal ligament or vocalis muscles was avoided. The duration of the procedure was ~15–20 min All patients were prescribed voice rest for 3 days following the procedure to prevent leakage of the injected material. In TESI, local anesthesia can be administered easily by dripping topical anesthetics into the laryngeal introitus via the operating channel of a flexible endoscope. Magnified endoscopic field and direct visualization of the needle tip also ensures that corticosteroids can be injected precisely into the Reinke's space. Furthermore, TESI does not require needle penetration through the mucosa of the upper aerodigestive tract; therefore, it prevents subsequent bleeding during the procedure[10].

Percutaneous steroid injection

Percutaneous steroid injection (PSI) procedures were performed percutaneously under local anesthesia by a single surgeon under transnasal flexible fiberscopic monitoring, and was injected into Reinke's space to avoid deeper injection into the vocalis muscle to prevent vocal fold atrophy[6].

With respect to the choice of approach of PSI, a surgeon chooses from the cricothyroid approach, transcartilaginous approach, and thyrohyoid approach depending on the vocal fold and neck conditions of the patients[20].

Steroid injection after microsurgical removal of minimal associated pathological lesions

VFSI has emerged as an alternative treatment option for MAPLs. However, difficulty in precise injection and the gag reflex resulting from a percutaneous approach and transoral approach under local anesthesia remain problematic. In addition, the recurrence rate after steroid injection is relatively high and repeated injection is needed[21].

Steroid injection might enhance the therapeutic effect of LMS for MAPLs. However, there have been only a few studies, which included small numbers of patients, on the effect of intralesional steroid administration during LMS. The rationale for steroid use in laryngology is likely related to the concept that many laryngeal diseases result from an abnormal inflammatory response. Local administration of steroid directly into the vocal fold has been widely reported mainly for MAPLs and other vocal fold diseases, such as vocal fold adhesions or scars. VFSI under local anesthesia is known to be an effective treatment for MAPLs. However, steroid injection alone is not a definite treatment for MAPLs. Campagnolo and colleagues demonstrated that steroid injection influences collagen deposition during acute wound healing and could ultimately prevent fibrosis. Therefore, we presumed that the steroid injection following immediate trauma, such as LMS, might lead to decreased fibrosis[6].

Patients over 50 years of age and with a long duration of dysphonia were at risk associated with the postoperative persistent dysphonia and should be considered for adjunctive steroid injection during LMS. Steroid injection combined with LMS could decrease the prevalence of persistent dysphonia. Mortensen and Woo reviewed the advantages of intralesional steroid injection, which include reduction of granulation tissue, promotion of primary healing, reduction of hypertrophic scar formation, and reduction of inflammation allowing surgery to be avoided. Adjunctive steroid injection can prevent formation of vocal fold granuloma. Presumed that two factors might contribute to this result. First, locally injected steroid works well to prevent excessive granulation tissue response. Second, vocal fold granuloma from repeated throat clearing and throat pain may be improved by local steroid injection, allowing the patient to break the vicious cycle of pain, throat clearing, and subsequent granuloma formation[22].

Adverse effects

No serious adverse events related to PSI were observed during the follow-up period, including airway obstruction or material migration. However, two patients exhibited minor vocal-fold hematoma that resolved spontaneously without any intervention[11].

Whitish deposition of the injected steroid (triamcinolone) after VFSI was reported in two studies, which mentioned that such whitish plaques had no effects on vocal fold vibration and that spontaneous resolution usually occurred after 1–2 months. Another common complication after VFSI is vocal fold hematoma, as mentioned in two studies[9].

Stroboscopy demonstrated decreased amplitude of the mucosal wave and vocal fold bowing. All the patients showed improvement after 2-month follow-up; thus, the condition might have been caused by atrophy of the mucosal glands, instead of the vocalis muscles[19].

Recurrence after VFSI was commonly reported in five studies and the overall recurrence rate was between 4 and 31%. Time taken for recurrence ranged from 4 weeks to 9 months after VFSI. The predominant reason for recurrence was persistent vocal abuse, which can be managed by administering repeated steroid injections with adjuvant voice therapy[19].


  Conclusion Top


Treatment for MAPLs generally initiates with behavioral modification of phonation habits. Vocal nodules usually reduce in size following voice therapy; however, voice therapy alone might not be effective in the management of other lesions with significant anatomic variations, such as polyp, Reinke's edema, or scar. When conservative managements fail, LMS might be the only available treatment option. However, potential adverse effects following laryngeal suspension include injury to the teeth or cervical spine or tongue paresthesia. Besides, violation of the layered structure of the vocal fold during surgery can also result in fibrosis of the lamina propria. Recent articles have proposed that VFSI might provide an alternative treatment option for the benign lesions of the vocal folds.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Wang CT, Lai MS, Hsiao TY. Comprehensive outcome researches of intralesional steroid injection on benign vocal fold lesions. J Voice 2015; 29 :578–587.  Back to cited text no. 1
    
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Tateya I, Omori K, Kojima H, Hirano S, Kaneko K, Ito J. Steroid injection for Reinke's edema using fiberoptic laryngeal surgery. Acta Otolaryngol 2003; 123 :417–420.  Back to cited text no. 4
    
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10.
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Cipriani NA, Martin DE, Corey JP, Portugal L, Caballero N, Lester R, et al. The clinicopathologic spectrum of benign mass lesions of the vocal fold due to vocal abuse. Int J Surg Pathol 2011; 19 :583–587.  Back to cited text no. 14
    
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Wang CT, Liao LJ, Cheng PW, Lo WC, Lai MS. Intralesional steroid injection for benign vocal fold disorders: a systematic review and metaanalysis. Laryngoscope 2013; 123 :197–203.  Back to cited text no. 19
    
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