Commentary on Relapsing Polychondritis—The Otorhinolaryngologist's Perspective

The report by Kut et al. highlights the difficulties faced in both the diagnosis and management of laryngotracheal involvement by relapsing polychondritis (RP), particularly in the pediatric population. This multi-systemic disease of presumptive immune-mediated etiology is extremely rare in children. ¹ It is characterized by recurrent and potentially severe episodes of inflammatory destruction of cartilaginous structures, with the external ears, nose, peripheral joints, and airway being the most frequently affected areas. Such inflammation is not exclusive to cartilaginous tissues, and can affect other structures that contain proteoglycan such as the inner ears, blood vessels, eye, and heart as well. Laryngotracheal involvement occurs in 20–50% of patients, and is a frequent presenting manifestation.^2–4 Such laryngotracheal involvement is considered ominous, portending a poor prognosis, especially in younger patients. ³ The mechanism responsible for airway obstruction depends on the stage of the disease: inflammatory edema is followed by progressive cartilage destruction, which results in intraluminal fibrosis and eventual stenosis. Tracheobronchomalacia secondary to cartilage destruction is a common finding in the adult patient with longstanding RP, but is infrequently seen in children.

The evaluation of a child with progressive stridor should include a thorough history and clinical examination. Salient features include a history of prior endotracheal intubation (whether at birth, electively as for surgery, or urgently as for trauma); airway-specific symptoms such as hoarseness, dyspnea, and dysphagia; and any associated systemic symptoms, including fever, weight loss, neck swelling, and joint pain. Flexible laryngoscopy is necessary to exclude laryngeal pathology and confirm normal vocal fold mobility. The acute onset of the respiratory distress as described in this case report may be secondary to RP involvement of the crico-arytenoid joints with resultant vocal fold paralysis, or may be due to superimposed infectious swelling in a child with RP-related subglottic stenosis.

Lateral neck radiographs can be helpful in identifying laryngotracheal stenosis, and can assist in excluding a foreign body from the differential. Dynamic expiratory computed tomography (CT) is invaluable in the early identification of pulmonary disease. More than 40% of patients with RP have morphologic airway abnormalities on expiratory CT, including the characteristic finding of anterior and lateral tracheobronchial wall thickening with sparing of the posterior membranous wall, as well as calcification and malacia. ⁵ The early identification of airway involvement in RP allows for prompt treatment, which may help to improve outcome. ⁶

Direct operative laryngotracheobronchoscopy utilizing a “tubeless” spontaneous ventilation anesthesia technique is the procedure of choice to exam the airway and assess for laryngotracheal involvement. Staff trained in pediatric airway management should perform this procedure. Pertinent findings include the nature of the stenotic segment (inflamed, soft, or firm), the length of the stenosis, and the distance below the vocal cords at which it commences; associated proximal laryngeal and distal tracheal or bronchial involvement must also be ruled out. Flexible bronchoscopy is of particular benefit in this latter respect. The identification of acute, inflammatory, subglottic stenosis necessitates immediate empiric treatment with high dose oral or intravenous steroids while further workup to determine etiology is performed.

As previously outlined, the clinical presentation of RP can be quite variable, and a high index of suspicion is necessary. The diagnosis of RP is based on the presence of three of six defined clinical features (Table 1). ² Careful exclusion of similarly presenting inflammatory diseases such as Wegner's granulomatosis, sarcoidosis, and lupus needs to be performed. The presence or absence of certain systemic manifestations (particularly audiometric, ophthalmologic and renal), as well specific autoimmune serologic studies, aids in sorting out this differential diagnosis. Notably the only consistently abnormal laboratory test in RP is an elevation of the erythrocyte sediment rate, which often correlates with disease activity.

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Table 1.

McAdams Major Diagnostic Criteria for Relapsing Polychondritis ²

3 of 6 recommended to be present:

1. Recurrent chondritis of both auricles

2. Nonerosive seronegative inflammatory polyarthritis

3. Nasal cartilage chondritis

4. Ocular inflammation, including conjunctivitis, keratitis, scleritis/episcleritis, and uveitis

5. Chondritis of the respiratory tract, involving laryngeal and tracheal cartilages

6. Cochleovestibular involvement, manifested by sensorineural hearing loss, tinnitus, and vertigo

The histopathologic confirmation of RP is not necessary but is helpful to exclude other potential inflammatory etiologies. Biopsy of an acutely inflamed subglottic stenosis is not recommended due to concern of a transient deterioration in respiratory status caused by swelling at the biopsy site. A biopsy may be more easily obtained if there is cartilaginous involvement of other organs such as the ear.

The mainstay of management for RP with airway manifestations is corticosteroid therapy. Dosages up to 1 mg/kg/day of prednisone are recommended, depending on the severity, with higher doses required in acute obstruction. ⁷ Corticosteroids resolve acute chondritic episodes and can decrease the severity, duration, and frequency of attacks including airway symptoms. They may also delay or abate the need for tracheotomy. Most patients require long-term therapy of months or even years. The well-known side effects of glucose intolerance, hypertension, and growth failure need to be very closely monitored in a child. Multidisciplinary management involving rheumatology and endocrinology, in addition to otolaryngology and pulmonology, is paramount.

Many adjunctive therapies such as plasma exchange and a variety of immunosuppressive medications including methotrexate, azathioprine, cyclophosphamide, cyclosporine, penicillamine, and dapsone have been used in an effort to reduce steroid dosages. There are little adult and no pediatric data to compare the therapeutic effects of these various agents; methotrexate and the anti-tumor necrosis factor, infliximab, have shown the most promising results.^8,9

The role of surgical intervention is limited. Balloon dilatation of stenotic airway segments and intralesional steroid injections may provide some short-term relief of obstructive symptoms but have no effect on the eventual course of the disease. ¹⁰ Self-expanding metallic and silicone stents have been used successfully for tracheal and bronchial airway obstruction in RP in adults.^6,11 Stents are used infrequently and reluctantly in the pediatric population because of the associated risks of stent migration, stent occlusion, and erosion of the stent through the tracheal wall; such may occur more frequently in a growing child. Resection of a stenotic tracheal segment is unfortunately of limited value because of subsequent disease activation in the remaining trachea.^12,13

Despite aggressive medical therapy, many patients with RP airway involvement experience symptom progression, and tracheotomy becomes necessary to bypass the severely stenotic proximal airway. Even with a tracheotomy in situ, patients may continue to experience respiratory symptoms due to progressive distal involvement of the tracheobronchial airway.

Serial operative endoscopic examinations of children with subglottic and tracheal RP involvement may be necessary to gauge disease activity. The potential trauma of such airway endoscopy needs to be balanced against the benefit of reducing steroid and immunosuppressive therapy if airway disease appears quiescent. Airway endoscopy is particularly important if an urgent tracheotomy was performed when the underlying diagnosis was unclear. If medical therapy can stabilize the proximal airway (subglottic) inflammation, permanent or temporary decannulation may be possible. This would have a tremendous positive psychosocial impact for both the child and family.

Due to the rarity of RP, management is based on small case report series and on experience with airway disease due to alternative autoimmune conditions. The main goal of treatment is to achieve symptom control and maintain airway patency, with close monitoring of adverse therapeutic effects. No single treatment is curative, and the prognosis of RP with airway involvement remains guarded. Based on information in the adult literature, it appears that early respiratory tract involvement in a young person is predictive of a poor outcome. ⁶