AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• RELEVANT ANATOMY
• Contraindications
• Workup
• Treatment
• Complications
• Outcome And Prognosis
• Multimedia
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• RELEVANT ANATOMY
• Contraindications
• Workup
• Treatment
• Complications
• Outcome And Prognosis
• Multimedia
• References

The larynx has multiple functions, including the voice production, cough, and airway protection, and it also acts as a conduit for breathing. Pathologic conditions that affect normal laryngeal function can result in poor cough production, aspiration with subsequent pneumonia, change in phonation, and dysphagia. Chondronecrosis of the larynx is a rare complication encountered in otolaryngology.

Incidence may have increased more recently with the increased use of chemotherapy and radiation. When present, chondronecrosis can have severe sequelae. Causes include radiation therapy, relapsing polychondritis, long- and short-term intubation, infection, trauma, tracheotomy, and neoplasms.

Problem

Radiation is the most common cause of chondronecrosis. Many patients with head and neck cancer receive radiation therapy, which attempts to preserve the larynx and its aerodigestive function. Radiation therapy has expected mild adverse effects, but the development of chondronecrosis can be devastating, with significant morbidity and even mortality. Once developed, laryngeal chondronecrosis generally is irreversible. Laryngectomy is often required because of life-threatening laryngeal instability. Any etiology resulting in chondronecrosis of the larynx may cause instability and subsequent airway limitation and possible obstruction. Recognition of perichondritis may prevent progression to chondritis and necrosis. Careful evaluation, early detection, and timely intervention therefore are essential for laryngeal preservation.

Frequency

In a 1982 pathologic study by Keene in which laryngeal specimens prepared by whole organ serial sectioning were reviewed, the incidence of histologic chondronecrosis and osteomyelitis could be correlated with tumor stage. In early stage (pT1-pT2) tumors, the incidence was 2% (1/41), while in advanced staged tumors (pT3-pT4) treated with 4500-6000 rads, the incidence of chondronecrosis was 27% (39/143). The overall incidence in the study was 26%. This was higher than that observed clinically, however. In 1994, Parsons reported that 1-5% of patients receiving radiation therapy to the larynx develop chondronecrosis. Because chondronecrosis may develop at any time, shortly following treatment or even decades later, the true incidence may be underestimated.

Other causes of chondronecrosis occur with less frequency. Relapsing polychondritis has been reported to cause laryngotracheal instability in 13-38% of patients. Chondronecrosis rarely develops secondary to primary infection or trauma.

Etiology

Radiation therapy

Radiation therapy for squamous cell carcinoma of the larynx has become increasingly safe and effective over the last 50 years. The incidence of severe reactions following 5000-6000 rads has decreased from 5-12% in 1970 to approximately 1% in the 1990s. Complications from radiotherapy (RT) typically occur following a latent period of approximately 6 months. The most common complication, persistent laryngeal edema, occurs in 13.7% of patients who receive a dose less than 7000 centigrays (cGy) but rises to 46.2% with doses of 7000 cGy and above.

Radiation therapy has been shown to cause reactive fibrosis and endarteritis. This leads to vascular compromise, depletion of nutrient supply, and tissue hypoxia of dependent cartilages. In 1963, Alexander showed 3 histologic changes that occur: (1) venous subintimal fibrosis and hyalinization, (2) arterial degeneration of elastic fibers in the tunica media, and (3) hyalinization of smooth muscle fibers. This ultimately leads to a decrease in the reparative capacity of normal tissue.

One to 5% of patients undergoing radiotherapy may develop radiation-induced chondronecrosis. Risk factors for the development of chondronecrosis include smoking, tumor invasion, postoperative infection, trauma, and the radiation technique. Age, sex, tumor grade, and previous laryngeal surgery do not appear to increase the risk for chondronecrosis. Laryngeal cartilages with intact perichondrium can tolerate large doses of radiation. However, perichondrial disruption by tumor invasion or trauma allows microorganism access to the cartilage with possible infection. Chronic infection in the necrosed tissue leads to abscess and ultimately fistula formation. In 1982, Keene found the arytenoid and thyroid cartilages to be involved in 51% and 23%, respectively, of examined larynges by histologic examination.

In a 1977 study by Kashima and Holliday, an association existed between chondronecrosis and 3 specific factors: (1) radiation dose/time relations, (2) presence of infection, and (3) general vascular condition of the patient. Chondronecrosis occurs in the patient who receives high-dose radiation combined with disruption of the mucoperichondrium, either by tumor invasion or by trauma. Vascular disease, which can be compromised further by smoking and by the presence of infection, contributes to the likelihood of chondronecrosis. A recent case of chondronecrosis with ulceration of the anterior neck and subsequent tracheal fistula was reported 44 years after irradiation, however. Another case of delayed complications occurred in a patient who, 22 years prior to a laser chordotomy, had radiation therapy to the neck. Following the Nd:YAG chordotomy she developed necrosis of the epiglottis with severe respiratory distress.

Chandler proposed a grading system for laryngeal radionecrosis (see the Table). Grades I and II are common postradiation changes and typically respond favorably to conservative treatment (ie, humidification, voice restraint, discontinuation of smoking, antibiotics). Grade III and IV reactions are more severe, have less favorable outcomes, and are considered complications of radiotherapy.

Chandler Grading System for Laryngeal Radionecrosis

Relapsing polychondritis

Relapsing polychondritis is an autoimmune disorder of the cartilage, central nervous system, eye, blood vessels, and labyrinth. First described by Jaksch-Wartenhorst in 1923 as polychondropathia, the author described a patient with pain, swelling, and deformity of the ears and nose, as well as stenosis of the external auditory canals. It is frequently associated with rheumatoid arthritis, systemic vasculitis, connective tissue diseases, and/or hematologic disorders.

Although the pathogenesis remains unknown, serum antibodies against collagen types II, IX, and XI, as well as cellular immunization against cartilage tissue and binding of both immunoglobulin and complement proteins in affected cartilage have been demonstrated. Further support was obtained in animal models where immunization against type II collagen and noncollagenous cartilage components produced symptoms of polychondritis.

In a study of 435 patients with relapsing polychondritis, laryngotracheal instability was noted in 13-38% of patients. Other symptoms at the time of diagnosis included auricular chondritis (26-91%), arthritis (23-47%), nasal chondritis (16-33%), ocular disorders (14-24%), and hearing loss (6-9%). Approximately 30% of patients developed associated systemic diseases, including polyarthritis, systemic lupus erythematosus, Behçet syndrome, and other vasculitides and connective tissue disorders.

In 1979, Damiani and Levine presented 10 patients with polychondritis, 4 of whom experienced laryngeal chondritis or laryngeal tracheal collapse. Symptoms include hoarseness, dyspnea, stridor, aphonia, choking sensation, and tenderness over the thyroid cartilage. Respiratory distress as an initial symptom is reported in 18% of cases, and eventual respiratory tract complications, including tracheobronchial involvement, is reported in up to 50% of patients.

Perichondritis of the larynx

Perichondritis is an infectious inflammatory process of the perichondrium that precedes chondritis and chondronecrosis. Prior to the advent of antibiotics, infection was the primary etiology. Infectious organisms included tuberculosis (TB), syphilis, typhoid (particularly in the third to fourth weeks), measles, scarlet fever, erysipelas, gonorrhea, diphtheria, anthrax, and mycoses. In a 1985 study by Beg, 37 of 100 patients with pulmonary tuberculosis showed laryngeal involvement, with the posterior aspect of the larynx and the epiglottis as the most common sites involved.

Intubation

Chondronecrosis of the cricoid cartilage has been described after short-term intubation in an 8-month-old patient and a 4-year-old patient. Both patients had been intubated only 2 days. One developed symptoms 10 days following extubation, ultimately requiring a tracheostomy for survival, while the second patient developed symptoms immediately upon extubation. Medical management with intravenous (IV) antibiotics and steroids was successful in the treatment of the second patient.

Contributing factors in these 2 particular cases included pressure by the endotracheal tube on the cricoid cartilage and trauma during emergent intubation. Other authors have described cricoid chondronecrosis in infants and children in the literature.

Using intubation with a gentle technique, using an appropriate size tube, and securing the endotracheal tube can prevent intubation injury. Good hygiene and nursing care may also help prevent trauma to the subglottic airway. Antibiotics can be used prophylactically, and regular check-ups allow earlier identification of potential complications. Selecting the proper size endotracheal tube eliminates excessive pressure and the potential for pressure necrosis and vascular compromise. Estimations can be made using formulas ([age (year) + 16]/4) or simply the width of the fifth fingernail. The use of steroids has been suggested but remains controversial.

Pathophysiology

As mentioned above, radiotherapy induces a hypoxic environment by stimulating reactive fibrosis and endarteritis of blood vessels, as well as obliteration and fibrosis of lymphatics. Edema develops secondary to increased permeability and decreased lymphatic drainage, which leads to further compromise of the nutrient supply. With perichondrial membrane breakdown, ischemic cartilage is exposed to aerodigestive tract bacteria. If not identified and treated early, infection ensues, ultimately leading to frank chondronecrosis.

In relapsing polychondritis, the pathophysiology is incompletely understood. However, serum antibodies against collagen, as well as cellular immunization against cartilage tissue, have been demonstrated. Activation of the immune response therefore can lead to chondritis and chondronecrosis.

Once the perichondrium becomes violated, regardless of the etiology, organisms have access and can initiate a localized infection with progression to chondritis and/or chondronecrosis. Vascular compromise is a result of the infection and promotes the destruction of cartilage. Factors that can interrupt the perichondrium include neoplasms, trauma, and iatrogenic causes. Image 1 depicts how these and other factors contribute to the development of laryngeal chondronecrosis.

Clinical

The cartilaginous framework in a patient with laryngeal chondronecrosis becomes unstable. This alters the airway size, mobility, and structure. Patients may present clinically with any of the following: dysphagia, odynophagia, hoarseness, stridor, dyspnea, respiratory obstruction, and recurrent aspiration. Following radiotherapy, most patients become symptomatic within the first year. However, case reports exist of patients presenting 25 and even 50 years following radiotherapy because fibrosis and endarteritis continue with time.

The typical patient with radiation-induced chondronecrosis initially develops symptoms of hoarseness and breathiness. The cricoarytenoid joint can become affected, and the arytenoids may become partially fixed without complete rotation or medial sliding motion along the cricoid. Because of this limited mobility, the ability to fully abduct or adduct the vocal folds may be impaired. Without full abduction, mild stridor or exercise intolerance may occur and become progressive. If airway distress develops, an emergent tracheotomy may be needed.

Incomplete vocal fold closure causes breathiness and the potential for aspiration. The usual course is to have greater difficulty with liquids than with solids, but progressive dysphagia may occur. The accessory laryngeal muscle activity may become impaired because of fibrosis, and thus, the normal laryngeal elevation needed for swallowing fails, leading to an unprotected airway. If an individual has recurring aspiration secondary to poor swallowing function, pneumonia and respiratory compromise can occur. Recurrent pneumonia is an indication that a definitive treatment such as laryngectomy may be indicated.

Odynophagia and neck pain and stiffness are other late symptoms of chondronecrosis.

RELEVANT ANATOMY

Section 3 of 10  

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• Contraindications
• Workup
• Treatment
• Complications
• Outcome And Prognosis
• Multimedia
• References

See Pathophysiology.

CONTRAINDICATIONS

Section 4 of 10  

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No contraindications exist for the treatment of chondronecrosis of the larynx.

WORKUP

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• References

Lab Studies

• In relapsing polychondritis and chondroradionecrosis, no specific laboratory tests confirm the presence of the disease. However, some common laboratory findings in relapsing polychondritis include normochromic normocytic anemia, mild leukocytosis, and raised erythrocyte sedimentation rate (ESR).

Imaging Studies

• CT scanning allows visualization of cartilage and soft tissue components and can be used to monitor the response to medical management, such as the use of steroid therapy in relapsing polychondritis. However, because MRI has been proven to be more effective at distinguishing between fibrosis, inflammation, and edema than CT scanning, some believe that MRI is a useful adjunct.
• In 1993, Briggs demonstrated that CT scanning and MRI frequently do not differentiate between radionecrosis and recurrent tumor. He sites problems with patient movement artifact secondary to pain, airway compromise, and aspiration during scanning.
• Positron emission tomography (PET) scanning, according to a 1995 study by McGuirt, has proved most reliable, with the ability to differentiate tumor from radiation effect in more than 80% of cases. The resolution of PET scanning, however, is 6 mm. Therefore, microscopic deposits of cancer may not be observed, and larger deposits may be masked by pooled saliva.
• A modified barium swallow may be useful in the evaluation of a patient with laryngeal chondronecrosis, allowing the clinician to evaluate not only the patient's ability to swallow but also the ability to protect the airway. Image 2 and Image 3 are modified barium swallow studies of a patient with thin and thick contrast, respectively, who presented with chondroradionecrosis of the larynx. Significant aspiration can be observed on both studies.
• Image 4 is a videostroboscopy, while Image 5 is a nasopharyngoscopy of the same patient. The patient is noted to have decreased laryngeal elevation, paralysis of the right true vocal cord, and limited mobility of the left true vocal cord. Pooling of saliva is present in the pyriform sinus, and her false and true vocal cords are edematous with punctate hemorrhages.

Diagnostic Procedures

• In postradiation therapy, patients with persistent edema may require multiple direct laryngoscopies with biopsies to differentiate between underlying necrosis and tumor recurrence. Because this may damage the mucosa or perichondrium and damage has even reportedly been significant enough to necessitate a laryngectomy, repeated biopsies may be performed only reluctantly. However, given the low risk of inciting a fulminant perichondritis in contrast to the high incidence of residual or recurrent carcinoma in postirradiated patients with persistent edema, biopsy probably is warranted. In a 1997 report, McGuirt referred to biopsy only patients with grade IV characteristics and patients with grade III illness and positive PET scan findings.

Histologic Findings

The elastic fibers of the tunica media show degeneration, and hyalinization of smooth muscle fibers develops in postirradiated larynges. This is more marked in veins than in arteries. Damage to the endothelium of the capillaries and lymphatics results in obliteration, atrophy, and fibrosis. In the presence of concomitant infection, overlying mucosal ulceration and purulent exudate is noted.

The histologic findings in relapsing polychondritis are loss of basophilic staining of the cartilage matrix, perichondrial round cell formation, and destruction of cartilage with replacement by fibrous tissue.

Necrotizing sialometaplasia has also been identified in association with relapsing polychondritis, as well as squamous cell carcinoma.

TREATMENT

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Medical therapy

Treatment of radiation-induced laryngeal chondronecrosis can lead to total laryngectomy, preventing an attempt at organ preservation. Factors such as continued smoking, gastroesophageal reflux, diabetes mellitus, and arteriosclerosis have been implicated as etiologies that may exacerbate the condition. Initial management in Chandler grades I and II cases consists of inhaled steam, corticosteroids, antireflux medications and precautions, and antibiotics.

Ciprofloxacin 750 mg PO bid has been recommended because it produces excellent blood levels and covers organisms found in the upper aerodigestive tract, including Staphylococcus aureus, Pseudomonas species, and enterococcal bacilli. However, in early stage chondritis, initial medical management with culture-directed antibiotics and steroids is suggested. If no improvement is noted after 10 days, surgical exploration with debridement of the necrotic tissue is recommended.

A recent study has shown some encouraging results using adjuvant hyperbaric oxygen therapy for severe radionecrosis. Fibroblast and leukocyte function is impaired when tissue oxygen levels fall below reference range levels. An increase in oxygen tension in already hypoxic tissue is thought to stimulate (1) growth of functional capillaries, (2) fibroblast proliferation and collagen synthesis, and (3) leukocyte bactericidal activity. It also facilitates angiogenesis by acting as a stimulus for the release of growth factors from macrophages. Leukocyte killing has been noted to increase by 40% when the PO₂ is increased from 45 to 150 mm Hg. Furthermore, angiogenesis in irradiated tissue has been shown to raise the oxygen tension to 75-80% of normal. No evidence indicates that hyperbaric oxygen stimulates tumor growth, although this continues to be a concern.

Chondronecrosis in relapsing polychondritis is secondary to inflammation from an autoimmune response. The cornerstone of therapy is corticosteroids. In the acute phase of the disease, a dosage of 0.75-1 mg/kg over 3-8 weeks with a slow taper is recommended. Most patients require long-term prednisone therapy at a dosage of 5-12 mg/d. In a 1998 report, Trentham and Le recommend combination therapy with methotrexate at an average dose of 17.5 mg per week. This allows a prednisone reduction from 19 mg/d to 5 mg/d. In acute bouts of respiratory distress, symptoms typically are a result of edema. Racemic ephedrine is therefore suggested while initiating corticosteroid therapy. Patients with mild disease have been treated with dapsone, aspirin, other NSAIDs, and immunosuppression with agents such as azathioprine, cyclophosphamide, 6-mercaptopurine, penicillamine, and cyclosporin.

Surgical therapy

Patients with airway instability secondary to chondroradionecrosis may not be candidates for medical therapy. In such cases, tracheotomy is necessary. If the larynx is dysfunctional with life-threatening aspiration or functional with biopsy findings positive for recurrent carcinoma, laryngectomy is recommended. Persistent laryngeal edema for longer than 6 months is a clinical indication of persistent cancer and frequently leads to laryngectomy.

Several surgical approaches for laryngeal preservation following chondroradionecrosis have been described. In 1973, Theissing reported the use of a Y-shaped, tubed, pedicled flap from chest skin in a single patient with subtotal loss of cartilage. In 1980, Draf described a composite deltopectoral skin and cartilage flap on 2 patients. A unipedicled cervicothoracic flap and an osteomyocutaneous flap have also been reported. In 1993, Balm et al described the use of a pectoralis major muscle transposition with split-thickness skin coverage for repair of the defect. Advantages include proximity, single-stage reconstruction, little functional deficit, independent blood supply, and ability to perform a salvage laryngectomy if needed without increasing morbidity.

Relapsing polychondritis is not typically localized to the larynx and usually involves the trachea. Montgomery T-tubes and intraluminal stents have been used to treat laryngotracheal involvement of relapsing polychondritis. Significant complications are possible, however, and include the following: (1) displacement of the stent, leading to asphyxia; (2) erosion through the anterior tracheal wall into the innominate artery; (3) mucosal irritation leading to ulceration and granulation tissue formation; and (4) vertical extension of the stent through the vocal cords, leading to aspiration pneumonia. Results of laryngotracheal reconstruction as a treatment in relapsing polychondritis are not good. Few reports and no large institutional or surgeon series exist.

In 1984, Eliachar used a sternohyoid myocutaneous rotary door flap in his laryngotracheal reconstructions, the advantage being a vascularized myocutaneous flap without the need for transfer of bone or cartilage for support. In 1997, Spraggs described the use of a vascularized medial clavicular graft, where he created a lumen in the clavicular flap and interposed it into the airway, maintaining the placement with a soft silastic stent. Extensive tracheobronchial collapse in relapsing polychondritis is not within the confines of this article. However, external airway splinting is the treatment of choice, and the reader is referred to Spraggs' study for further information.

COMPLICATIONS

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In the early stages (Chandler I-III), the airway cannot be protected, resulting in aspiration, pneumonia, and lung abscess. Furthermore, early stage chondronecrosis can progress to life threatening obstruction secondary to collapse, requiring emergent tracheotomy. Tracheal collapse resulting in sudden death has been reported in relapsing polychondritis. Other complications include dysphagia, odynophagia, and hoarseness.

OUTCOME AND PROGNOSIS

Section 8 of 10  

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• References

With early recognition and medical intervention, the outcome and prognosis is good. In the case of chondroradionecrosis, frequent examination is recommended to detect an early manifestation of recurrent cancer.

A 10% mortality rate is reported in Michet's 1986 study on relapsing polychondritis. Other studies have indicated anywhere from a 28-44% mortality rate. This, however, could be secondary to selective case reporting. No large series have been conducted on the outcome of patients who present with chondronecrosis secondary to other etiologies.

MULTIMEDIA

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• Multimedia
• References

Media file 1:  Chondronecrosis of the larynx. Contributing factors leading to chondronecrosis.
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Media file 2:  Chondronecrosis of the larynx. Modified barium swallow using thin contrast; the study demonstrates significant aspiration.
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Media file 3:  Chondronecrosis of the larynx. Modified barium swallow using thick contrast showing persistent aspiration.
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Media file 4:  Chondronecrosis of the larynx. Videostroboscopy showing decreased vocal cord mobility on the left with paralysis on the right.
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Media file 5:  Chondronecrosis of the larynx. Nasopharyngoscopy showing decreased vocal cord mobility on the left with paralysis on the right as the patient attempts to perform a high-pitched E.
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Media file 6:  Chondronecrosis of the larynx.
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Media file 7:  Chondronecrosis of the larynx.
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Media file 8:  Chondronecrosis of the larynx.
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REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• RELEVANT ANATOMY
• Contraindications
• Workup
• Treatment
• Complications
• Outcome And Prognosis
• Multimedia
• References

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Article Last Updated: Jun 15, 2006