Reinke's edema

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Reinke's edema
Other namesReinke's oedema, [1] polypoid degeneration, polypoid corditis, edematous hyptertrophy
Reinke-Oedem.jpg
Reinke's edema
Specialty Otorhinolaryngology   OOjs UI icon edit-ltr-progressive.svg

Reinke's edema is the swelling of the vocal cords due to fluid (edema) collected within the Reinke's space. [2] First identified by the German anatomist Friedrich B. Reinke in 1895, the Reinke's space is a gelatinous layer of the vocal cord located underneath the outer cells of the vocal cord. [3] [4] When a person speaks, the Reinke's space vibrates to allow for sound to be produced (phonation). The Reinke's space is sometimes referred to as the superficial lamina propria. [5]

Contents

Reinke's edema is characterized by the "sac-like" appearance of the fluid-filled vocal cords. [6] The swelling of the vocal folds causes the voice to become deep and hoarse. Therefore, the major symptom of Reinke's edema is a hoarseness similar to laryngitis. The major cause associated with Reinke's edema is smoking. In fact, 97% of patients diagnosed with Reinke's edema are habitual smokers. Other identified risk factors include overuse of the vocal cords, gastroesophageal reflux, and hypothyroidism. [7] The disease is more often cited in women than in men, because lower voice changes are more noticeable in women. [2] [4] [7]

The first cases of Reinke's edema were recorded in 1891 by M. Hajek, [8] followed by F. Reinke in 1895. In his investigations, Reinke injected a stained glue into the superficial lamina propria (Reinke's space) to mimic edema. [9] Reinke's edema is considered to be a benign (non-cancercous) polyp (protrusion) that represents 10% of all benign laryngeal pathologies. [4] Treatment of Reinke's edema starts with the elimination of associated risk factors, such as smoking, gastric reflux, and hypothyroidism. Advanced cases may undergo phonosurgery to remove the fluid from the vocal cords. [7]

Signs and symptoms

List of common symptoms:

Reinke's edema is characterized by a "sac-like" appearance of the vocal folds. [6] The edema is a white translucent fluid that causes a bulging (distension) of the vocal cord. [2] [12] The most common clinical symptom associated with Reinke's edema is an abnormally low pitched voice with hoarseness. The low pitch voice is a direct result of increased fluid in the Reinke's space, which vibrates at a lower frequency than normal (females <130 Hz; males <110 Hz). [10] Hoarseness is a common problem of many laryngeal diseases, such as laryngitis. It is described as a harsh and breathy tone of voice. Hoarseness is often seen alongside dysphonia, a condition in which the individual has difficulty speaking. [7]

The swelling of the vocal cords and the lowering of the voice are warning signs that an individual has Reinke's edema. At the microscopic level, an examination of the vocal cords in patients with Reinke's edema will show lowered levels of collagen, elastin, and extracellular matrix proteins. [4] These characteristics can be used to diagnose Reinke's edema. Reinke's edema is considered a benign polyp that may become precancerous if smoking is involved. [12] An indicator of cancer is the development of leukoplakia, which manifests as white patches on the vocal folds. [7]

Smoking, gastric reflux, and hypothyroidism are all risk factors for Reinke's edema. The symptoms of Reinke's edema are considered to be chronic symptoms because they develop gradually over time and depend on how long the individual is exposed to the risk factor. In the case of smoking, as long as the individual continues the habit of smoking, the Reinke's edema will continue to progress. This is true for other risk factors as well, such as untreated gastric reflux and overuse of the voice, which is common to professions such as singers and radio announcers. [2] [4] [7]

Causes

Smoking is the number one cause of Reinke's edema. Other factors include gastroesophageal reflux, hypothyroidism and chronic overuse of the voice. Smoking and reflux are the only risk factors that may lead to cancer. [7] Additionally, the combination of several risk factors increase the likelihood of an individual developing Reinke's edema. For example, an individual who smokes and also has gastric reflux would have an increased susceptibility for developing Reinke's edema over time. [4]

Reinke's edema is commonly diagnosed in middle-aged females with a history of smoking (aged 50 years or older). Because males have lower pitched voices than females, males are less likely to observe a significant changes in the voice, and are therefore less likely to seek treatment. Females also report more physical discomfort due to Reinke's edema. The risk of Reinke's edema increases with age and also with prolonged exposure to smoking. Additionally, individuals in professions that require constant use of the voice, such as singers, teachers, and radio hosts, may be at an increased risk for developing the disease. [11]

Because the disease is heavily linked to smoking, there is no established way to screen for Reinke's edema. Similarly, the only way to prevent Reinke's edema is to avoid smoking. By adopting a non-smoking lifestyle after being diagnosed with Reinke's edema, it is possible to stop the disease's progression, although it is not possible to reverse it. Therefore, it is critical to maintain a non-smoking lifestyle even after surgery, because the fluid can re-emerge. In fact, in many cases surgeons will not perform surgery without the guarantee that the individual will stop smoking. [7]

Mechanism

The movement of the vocal folds during speech Vocal fold animated.gif
The movement of the vocal folds during speech

The vocal cords consist of five layers of cells:

In order for humans to produce sound for speech, the vocal folds must readily vibrate. The two layers of the vocal cords that vibrate are the Reinke's space and the overlying epithelium. In fact, these layers move freely over the more rigid intermediate and deep lamina proprias. [7] Accumulation of fluid within the Reinke's space alters the elasticity of the vocal cord, making it less stiff and more gelatinous. This slows the vocal cord vibration, which results in a deepened and hoarse voice. Because men normally have a lower voice than women, the change is more noticeable in women. [11]

Edema usually occurs on both vocal cords. This is known as bilateral Reinke's edema. [7] The pathophysiology or mechanism of Reinke's edema is not well known, however, chemicals contained within cigarette smoke are associated with an increased vascular permeability of blood vessels, which results in fluid leaking into the Reinke's space. Normally, the vocal cords are surrounded by neatly aligned blood vessels, however, these blood vessels can become disarranged and fragile in Reinke's edema. [13] In addition, cigarette smoke can create reactive oxygen species that alter the environment of the vocal cords. Tissue analysis of Reinke's edema shows decreased amounts of the proteins fibronectin, elastin, collagens I and III, and extracellular matrix proteins. This leads to an overall decreased stiffness of the tissue layer, which vibrates more slowly and produces a deeper sounding voice. [2] [4]

The progression of Reinke's edema is gradual and is directly related to the duration of exposure to risk factors, such as smoking and gastric reflux. [2] Disease progression is divided into two types: "pale" and "livid". The “pale” type of Reinke's edema is defined by a glazed appearance of the vocal cords with a clear (colorless) fluid underneath. This represents the early stage of the disease. The advanced “livid” type of Reinke's edema is identified by an increased amount of fluid, accompanied by a color change from colorless to yellow-grey. [2] The swelling of the vocal folds cause ballooned-like appearance, known as a polyp. The polyps of Reinke's edema are usually benign, however, there may be a risk of cancer if the patient is a smoker. Additionally, if the edema becomes too severe, patients may experience difficulty breathing due to blockage of the airway. [2] [10]

Diagnosis

Rigid laryngoscope instrument Laryngoscope (2).JPG
Rigid laryngoscope instrument

Reinke's edema is often diagnosed by an Ear, Nose & Throat (ENT) specialist or an Otolaryngologist by examination of the vocal cords. First, the doctor will review the patient's medical history and symptoms, such as hoarseness, dysphonia, and reduced vocal range. There is no familial or hereditary link to Reinke's edema. Because Reinke's edema is linked heavily to smoking, the doctor will need to know if the patient is a habitual smoker. Once the patient's history is reviewed, the vocal cords will be visualized using laryngoscopy, a technique in which a tube with a camera (endoscope) is passed through the nose and down the larynx. [10] [14] Laryngoscopes can be rigid or flexible. Flexible laryngoscopes, such as fiber laryngoscopes, allow the patient to produce sound as the tube is placed, and therefore allows the doctor to visualize movement of the vocal cord. [14] The use of rigid laryngoscopes generally requires general anaesthesia due to the discomfort involved in distracting the soft tissues of the mouth and pharynx.

Based on the results of the laryngoscopy, Reinke's edema can be classified using a standardized system set in place by Yonekawa. This system characterizes the disease based disease severity. [10]

Yonekawa Classification: [10]

If further evaluation is needed, stroboscopy is used to examine mucosal waves of the vocal cords. Mucosal waves describe the waves produced by vibration of the vocal cords during speech. Stroboscopes produce flashes of light that are timed to the patient's vocal frequency. Every time the light is flashed, it will create a still frame image of the vocal cords at that particular moment in time. These are combined to produce an image of the wave. In the case of Reinke's edema, structural changes to the vocal cords will result in abnormal wave patterns. [15]

Treatment

The first step in treating Reinke's edema is to eliminate or control those risk factors that are causing the disease. This includes the cessation of smoking, the control of gastric reflux using antacids and/or Proton Pump Inhibitors (PPIs), and the discontinuation of activities that cause vocal distress. [4] Those experiencing a hoarseness of the voice may choose to undergo voice therapy to improve the voice's quality and range. [2] [4] Most cases of Reinke's edema are caused by the long term usage of cigarettes. In this case, it is important to make lifestyle changes to stop smoking. While this will not resolve or improve the edema, the cessation of smoking will halt the disease's progression. [7]

If the elimination of risk factors is not sufficient to improve the patient's symptoms, surgery may be required. The most common type of surgery performed today for Reinke's edema is called surgical microlaryngoscopy. Most procedures follow the microflap technique set in place by Hirano. [7] [10] During surgery, an incision is made into the vocal cord using either microscissors or a CO2 laser. A flap of mucosa is lifted and the affected tissue is removed using suction or a microdebrider. The flap is then re-draped and trimmed to the appropriate size. [7]

Most cases of Reinke's Edema are bilateral - effecting both vocal cords - rather than unilateral. In the case of bilateral edema, the surgeon must choose whether to operate each side of the vocal cord in two separate surgeries or to operate both sides in a single surgery. [7] The complication associated with removing tissue from both sides in a single surgery is that the raw, cut ends of the vocal cords may form an anterior glottis web, in which the two sides grow together in a continuous sheet. [4] [7] Other complications of surgery include tissue scarring due to damage to the vocal ligament during the incision and vocal cord stiffening due to over-suctioning of the superficial lamina propria (Reinke's space). [10]

While surgical microlaryngoscopy has its associated risks, if left untreated, Reinke's edema can lead to a variety of long-term complications. Besides dysphonia (impaired speech), the most serious of these complications is airway obstruction due to severe inflammation of the vocal cords. The risk of complications has decreased drastically with the creation of new tools, such as the CO2 laser for surgical microlaryngoscopy. Before the Hirano microflap method was developed in 1895,[ dubious – discuss ] vocal stripping was the most common procedure used to correct Reinke's Edema. Vocal stripping was often performed without magnification and with a monocular laryngoscope, instead of a binocular scope. This led to major complications such as vocal ligament scarring.

Women are more likely than men to undergo surgery due to a greater change in vocal pitch and quality. Surgery is capable of restoring the voice, with the condition that smoking is not resumed after surgery. Post-operative voice therapy is also advised to restore the voice's strength. Reinke's edema is not a fatal pathology unless the tissue becomes precancerous. [10]

Research

Recent studies have examined the role of specific cell types in Reinke's edema, including the role of vocal cord fibroblasts. In normal tissue, these spindle-shaped CD34+ fibroblasts produce extracellular matrix proteins such as collagen and elastin. Recent findings have shown a morphological change in fibroblasts extracted from the tissue of Reinke's edema to a more dendritic-like shape with several protrusions. Large populations of these altered CD34+ fibroblasts have been found surrounding the areas of edema. They lack normal expression of several cluster of differentiation (CD) proteins and express additional proteins that are not expressed in normal vocal cord fibroblasts. [16] Furthermore, cigarette smoke was discovered to increase COX-2 and PGE2 expression in fibroblasts, which could indicate the role of cigarette smoke in Reinke's edema. [17]

While smoking is a clear risk factor to Reinke's edema, other risk factors are being identified to explain Reinke's edema in nonsmokers. Research has suggested the role of bacterial colonies in non-neoplastic lesions such as Reinke's edema. Using pyrosequencing, strains of S. pseudopneumoniae were found as the dominant bacterial strain across most non-neoplastic lesions. Of all the sequences analyzed, streptococcus represented 72.9% of bacteria found within these lesions. While smoking, gastric reflux, and vocal abuse have been more widely agreed upon in literature as risk factors for Reinke's edema, the altered bacterial cultures could be developed as a diagnostic tool in the future. [18]

The majority of the research within the last ten years focuses on improving surgery for Reinke's edema. Due to the importance of the Reinke's space in speech, it is important that minimally invasive techniques be perfected that minimize the risk of complications. The CO2 laser has been successfully incorporated into the surgical technique, however, there are several other lasers being investigated for use in Reinke's edema. These include photoangiolytic lasers [19] and potassium titanyl phosphate lasers. [20]

See also

Related Research Articles

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Otorhinolaryngology is a surgical subspecialty within medicine that deals with the surgical and medical management of conditions of the head and neck. Doctors who specialize in this area are called otorhinolaryngologists, otolaryngologists, head and neck surgeons, or ENT surgeons or physicians. Patients seek treatment from an otorhinolaryngologist for diseases of the ear, nose, throat, base of the skull, head, and neck. These commonly include functional diseases that affect the senses and activities of eating, drinking, speaking, breathing, swallowing, and hearing. In addition, ENT surgery encompasses the surgical management and reconstruction of cancers and benign tumors of the head and neck as well as plastic surgery of the face and neck.

Vocal cords Folds of throat tissues that help to create sounds through vocalization

In humans, vocal cords, also known as vocal folds or voice reeds, are folds of throat tissues that are key in creating sounds through vocalization. The size of vocal cords affects the pitch of voice. Open when breathing and vibrating for speech or singing, the folds are controlled via the recurrent laryngeal branch of the vagus nerve. They are composed of twin infoldings of mucous membrane stretched horizontally, from back to front, across the larynx. They vibrate, modulating the flow of air being expelled from the lungs during phonation.

Vocal cord nodules are bilaterally symmetrical benign white masses that form at the midpoint of the vocal folds. Although diagnosis involves a physical examination of the head and neck, as well as perceptual voice measures, visualization of the vocal nodules via laryngeal endoscopy remains the primary diagnostic method. Vocal fold nodules interfere with the vibratory characteristics of the vocal folds by increasing the mass of the vocal folds and changing the configuration of the vocal fold closure pattern. Due to these changes, the quality of the voice may be affected. As such, the major perceptual signs of vocal fold nodules include vocal hoarseness and breathiness. Other common symptoms include vocal fatigue, soreness or pain lateral to the larynx, and reduced frequency and intensity range. Airflow levels during speech may also be increased. Vocal fold nodules are thought to be the result of vocal fold tissue trauma caused by excessive mechanical stress, including repeated or chronic vocal overuse, abuse, or misuse. Predisposing factors include profession, gender, dehydration, respiratory infection, and other inflammatory factors.

Vocal fold cysts are benign masses of the membranous vocal folds. These cysts are enclosed, sac-like structures that are typically of a yellow or white colour. They occur unilaterally on the midpoint of the medial edge of the vocal folds. They can also form on the upper/superior, surface of the vocal folds. There are two types of vocal fold cysts:

  1. Sub-epithelial vocal fold cysts- located in the superficial lamina propria of the vocal folds.
  2. Ligament vocal fold cysts- located within the deeper layers of the lamina propria or on the vocal ligament.
Polyp (medicine) Abnormal growth of tissue projecting from a mucous membrane

In anatomy, a polyp is an abnormal growth of tissue projecting from a mucous membrane. If it is attached to the surface by a narrow elongated stalk, it is said to be pedunculated; if it is attached without a stalk, it is said to be sessile. Polyps are commonly found in the colon, stomach, nose, ear, sinus(es), urinary bladder, and uterus. They may also occur elsewhere in the body where there are mucous membranes, including the cervix, vocal folds, and small intestine. Some polyps are tumors (neoplasms) and others are non-neoplastic, for example hyperplastic or dysplastic, which are benign. The neoplastic ones are usually benign, although some can be pre-malignant, or concurrent with a malignancy.

Laryngitis Medical condition

Laryngitis is inflammation of the larynx. Symptoms often include a hoarse voice and may include fever, cough, pain in the front of the neck, and trouble swallowing. Typically, these last under two weeks.

Laryngeal papillomatosis Medical condition

Laryngeal papillomatosis, also known as recurrent respiratory papillomatosis (RRP) or glottal papillomatosis, is a rare medical condition in which benign tumors (papilloma) form along the aerodigestive tract. There are two variants based on the age of onset: juvenile and adult laryngeal papillomatosis. The tumors are caused by human papillomavirus (HPV) infection of the throat. The tumors may lead to narrowing of the airway, which may cause vocal changes or airway obstruction. Laryngeal papillomatosis is initially diagnosed through indirect laryngoscopy upon observation of growths on the larynx and can be confirmed through a biopsy. Treatment for laryngeal papillomatosis aims to remove the papillomas and limit their recurrence. Due to the recurrent nature of the virus, repeated treatments usually are needed. Laryngeal papillomatosis is primarily treated surgically, though supplemental nonsurgical and/or medical treatments may be considered in some cases. The evolution of laryngeal papillomatosis is highly variable. Though total recovery may be observed, it is often persistent despite treatment. The number of new cases of laryngeal papillomatosis cases is approximately 4.3 cases per 100,000 children and 1.8 cases per 100,000 adults annually.

Bogart–Bacall syndrome

Bogart–Bacall syndrome (BBS) is a voice disorder that is caused by abuse or overuse of the vocal cords.

Hoarse voice Voice disorder

A hoarse voice, also known as dysphonia or hoarseness, is when the voice involuntarily sounds breathy, raspy, or strained, or is softer in volume or lower in pitch. A hoarse voice, can be associated with a feeling of unease or scratchiness in the throat. Hoarseness is often a symptom of problems in the vocal folds of the larynx. It may be caused by laryngitis, which in turn may be caused by an upper respiratory infection, a cold, or allergies. Cheering at sporting events, speaking loudly in noisy situations, talking for too long without resting one's voice, singing loudly, or speaking with a voice that's too high or too low can also cause temporary hoarseness. A number of other causes for losing one's voice exist, and treatment is generally by resting the voice and treating the underlying cause. If the cause is misuse or overuse of the voice, drinking plenty of water may alleviate the problems.

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Laryngology

Laryngology is a branch of medicine that deals with disorders, diseases and injuries of the larynx, colloquially known as the voice box. Laryngologists treat disorders of the larynx, including diseases that affects the voice, swallowing, or upper airway. Common conditions addressed by laryngologists include vocal fold nodules and cysts, laryngeal cancer, spasmodic dysphonia, laryngopharyngeal reflux, papillomas, and voice misuse/abuse/overuse syndromes. Dysphonia/hoarseness; laryngitis ; *Spasmodic dysphonia; dysphagia; Tracheostomy; Cancer of the larynx; and vocology are included in laryngology.

Contact granuloma Medical condition

Contact granuloma is a condition that develops due to persistent tissue irritation in the posterior larynx. Benign granulomas, not to be confused with other types of granulomas, occur on the vocal process of the vocal folds, where the vocal ligament attaches. Signs and symptoms may include hoarseness of the voice, or a sensation of having a lump in the throat, but contact granulomas may also be without symptoms. There are two common causes associated with contact granulomas; the first common cause is sustained periods of increased pressure on the vocal folds, and is commonly seen in people who use their voice excessively, such as singers. Treatment typically includes voice therapy and changes to lifestyle factors. The second common cause of granulomas is gastroesophageal reflux and is controlled primarily through the use of anti-reflux medication. Other associated causes are discussed below.

Colorectal polyp Medical condition

A colorectal polyp is a polyp occurring on the lining of the colon or rectum. Untreated colorectal polyps can develop into colorectal cancer.

Laryngopharyngeal reflux Medical condition

Laryngopharyngeal reflux (LPR) is the retrograde flow of gastric contents into the larynx, oropharynx and/or the nasopharynx. LPR causes respiratory symptoms such as cough and wheezing and is often associated with head and neck complaints such as dysphonia, globus pharyngis, and dysphagia. LPR may play a role in other diseases, such as sinusitis, otitis media, and rhinitis, and can be a comorbidity of asthma. While LPR is commonly used interchangeably with gastroesophageal reflux disease (GERD), it presents with a different pathophysiology.

Histology is the study of the minute structure, composition, and function of tissues. Mature human vocal cords are composed of layered structures which are quite different at the histological level.

Endoscopic laser cordectomy, also known as Kashima operation, is an endoscopic laser surgical procedure performed for treating the respiratory difficulty caused as a result of bilateral abductor vocal fold paralysis. Bilateral vocal fold paralysis is basically a result of abnormal nerve input to the laryngeal muscles, resulting in weak or total loss of movement of the laryngeal muscles. Most commonly associated nerve is the vagus nerve or in some cases its distal branch, the recurrent laryngeal nerve. Paralysis of the vocal fold may also result from mechanical breakdown of the cricoarytenoid joint. It was first described in by Kashima in 1989.

Arytenoid adduction is a surgical procedure used to treat vocal cord paralysis. A suture is used to emulate the action of the lateral cricoarytenoid muscle and position the paralyzed vocal cord closer to the midline. This allows the two vocal cords to meet and can improve speaking and swallowing ability for affected patients. Arytenoid adduction is often performed in conjunction with medialization thyroplasty.

Muscle tension dysphonia (MTD) was originally coined in 1983 by Morrison and describes a dysphonia caused by increased muscle tension of the muscles surrounding the voice box: the laryngeal and paralaryngeal muscles. MTD is a unifying diagnosis for a previously poorly categorized disease process. It allows for the diagnosis of dysphonia caused by many different etiologies and can be confirmed by history, physical exam, laryngoscopy and videostroboscopy, a technique that allows for the direct visualization of the larynx, vocal cords, and vocal cord motion.

Intubation granuloma Medical condition

Intubation granuloma is a benign growth of granulation tissue in the larynx or trachea, which arises from tissue trauma due to endotracheal intubation. This medical condition is described as a common late complication of tracheal intubation, specifically caused by irritation to the mucosal tissue of the airway during insertion or removal of the patient’s intubation tube.

Vocal cord hemorrhage occurs when a blood vessel in the vocal cords ruptures, which results in leakage of blood into the superficial lamina propria and dysphonia (hoarseness). The rupture usually results from overly forceful or incorrect vocalization, and may be a one-time occurrence or occur repeatedly. According to News Medical.net, "professional singers are at an increased risk of vocal hemorrhage, particularly in cases where gruelling performance schedules are followed". The treatment is vocal rest as failure to rest the voice can result in permanent scarring.

References

  1. ↑ 'Oedema' is the standard form defined in the Concise Oxford English Dictionary (2011), with the precision that the spelling in the United States is 'edema'.
  2. 1 2 3 4 5 6 7 8 9 10 Rubin, John (2014). Diagnosis and Treatment of Voice Disorders. Plural Publishing. p. 104. ISBN   978-1-59756-644-5.
  3. ↑ F. B. Reinke. Untersuchungen über das menschliche Stimmband. Fortschritte der Medizin, München, 1895, 13: 469-478.
  4. 1 2 3 4 5 6 7 8 9 10 Goswami, Saileswar (2003). "A Clinico-pathological Study of Reinke's Oedema". Indian Journal of Otolaryngology and Head & Neck Surgery. 55 (3): 160–5. doi:10.1007/BF02991943. PMC   3451126 . PMID   23119968.
  5. ↑ Hirano, M (1976). "An improvement in surgical treatment for polypoid vocal cord: sucking technique". Otologia (Fukuoka). 22 (5): 583–9.
  6. 1 2 3 Altman MD, PhD, Ken W. (2002). "The Center for Voice @ Northwestern". Benign Vocal Lesions - Nodules, Polyps, Cysts. Archived from the original on 2007-08-17. Retrieved 24 October 2015.
  7. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 Rosen, Clark (2009). Operative Techniques in Laryngology . Springer-Verlag Berlin Heidelberg. p.  113. ISBN   978-3-540-25806-3.
  8. ↑ Hajek, M. (1891). "Anatomische Untersuchungen über das Larynxödem". Langenbecks Arch Chir.
  9. ↑ Tillmann, B. (1995). "Morphological studies on the pathogenesis of Reinke's edema". Eur Arch Otorhinolaryngol. 252 (8): 469–74. doi:10.1007/BF02114753. PMID   8719588. S2CID   10032256.
  10. 1 2 3 4 5 6 7 8 9 Zeitels, Steven (2002). "Management of common voice problems: Committee report". Otolaryngology–Head and Neck Surgery. 126 (4): 333–348. doi:10.1067/mhn.2002.123546. PMID   11997771. S2CID   26308857.
  11. 1 2 3 Verdolini, Katherine (2014). Classification Manual for Voice Disorders-I. Psychology Press. p. 55. ISBN   978-0-8058-5631-6.
  12. 1 2 Martins, Regina Helena Garcia (2009). "Is Reinke's Edema a Precancerous Lesion? Histological and Electron Microscopic Aspects". Journal of Voice. 23 (6): 721–725. doi:10.1016/j.jvoice.2008.03.001. PMID   18619781.
  13. ↑ Jovanovic, Milan (2007). "Contact Telescopy Reveals Blood Vessel Alterations of Vocal Fold Mucosa in Reinke's Edema". Journal of Voice. 21 (3): 355–360. doi:10.1016/j.jvoice.2006.01.004. PMID   16564676.
  14. 1 2 "The Voice Foundation". Diagnosis. Elsevier Health Science. 2015. Retrieved 17 October 2015.
  15. ↑ Krausert, Christopher R (2011). "Mucosal Wave Measurement and Visualization Techniques". J Voice. 25 (4): 395–405. doi:10.1016/j.jvoice.2010.02.001. PMC   2976773 . PMID   20471798.
  16. ↑ Diaz-Flores, Lucio (2014). "CD34-Positive Fibroblasts in Reinke's Edema". Laryngoscope. 124 (3): E73–E80. doi: 10.1002/lary.24407 . PMID   24115077. S2CID   206201456.
  17. ↑ Branski, Ryan C. (2011). "The Effects of Cigarette Smoke Condensate on Vocal Fold Transepithelial Resistance and Inflammatory Signaling in Vocal Fold Fibroblasts". Laryngoscope. 121 (3): 601–605. doi:10.1002/lary.21388. PMC   3132796 . PMID   21298639.
  18. ↑ Hanshew, Alissa S. (2014). "Characterization and comparison of bacterial communities in benign vocal fold lesions". Microbiome. 2: 43. doi:10.1186/2049-2618-2-43. PMC   4323261 . PMID   25671105.
  19. ↑ Koszewski, IJ (2015). "Office-Based Photoangiolytic Laser Treatment of Reinke's Edema: Safety and Voice Outcomes". Otolaryngol Head Neck Surg. 152 (6): 1075–81. doi:10.1177/0194599815577104. PMID   25820581. S2CID   20506230.
  20. ↑ Young, VN (2015). "Analysis of Potassium Titanyl Phosphate Laser Settings and Voice Outcomes in the Treatment of Reinke's Edema". Ann Otol Rhinol Laryngol. 13 (3): 972–7. doi:10.1177/0003489414549155. PMID   5169585. S2CID   10895483.
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