Polychondritis

Case Reports and Review of Literature

Study objective: To report the first series of patients with severe airway manifestations of relapsing polychondritis (RP) that were managed successfully with self-expandable metallic stents, and to review the literature.

Design: Retrospective review of medical records, and current clinical follow-up.

Setting: Tertiary care referral hospital.

Patients: All patients with airway manifestations of RP that were managed with self-expandable metallic stents at our institution.

Results: All five patients (four women and one man; age, 40 to 69 years old) had severe airway manifestations, and three of them required mechanical ventilation. Spirometry with flow-volume curves showed severe combined obstructive and restrictive ventilatory defects. Bronchoscopy revealed dynamic collapse of the proximal airways. Diagnosis was made 8 months to 13 years after the first symptom of the disease. Pharmacotherapy included prednisone, methotrexate, cyclosporine, and dapsone. A total of 17 self-expandable metallic stents of varying sizes were placed using flexible bronchoscope from 4 to 19 years after the first symptom. The overall outcome was favorable in four patients. Three patients have survived without ventilatory support 16 to 18 months following the first stent placement, and the fourth patient survived for 20 months without ventilatory support before she died. The fifth patient, who was receiving mechanical ventilation, died in 1 week probably due to persistent dynamic collapse of the airways distal to the stents.

Conclusion: Self-expandable metallic tracheobronchial stents should be considered in the management of airway manifestations of RP, especially in patients who require mechanical ventilation.

(CHEST 1999; 116-1669-16 75)

Key words: bronchial obstruction; bronchial stenosis; endoscopic treatment; relapsing polychondritis; metal stents; self-expandable stents; tracheal obstruction; tracheal stenosis; tracheobronchomalacia; Wallstent

Abbreviations: FB = flexible bronchoscope; RP = relapsing polychondritis; SEMS = self-expandable metallic stent

Relapsing polychondritis (RP) is a rare multisystem disorder of unknown etiology that is characterized by recurrent progressive inflammation and degeneration of cartilage and connective tissue.[1] There are no pathognomonic clinical, radiologic, or histopathologic features. Hence, the diagnosis depends on a constellation of clinical features and various diagnostic tests. In 1976, McAdam et al[2] described the clinical diagnostic criteria, and they were modified in 1979 by Damiani and Levine[3] to include histologic features and therapeutic response (Table 1). Airway complications are the most serious manifestations, and they present a diagnostic and therapeutic challenge.[4] There are anecdotal reports on management of the airway manifestations by medical therapy or by stent placement.[1-6] Dunne and Sabanathan[6] described a single patient treated with a stent placed using a flexible bronchoscope (FB) who was weaned off the mechanical ventilator and died shortly thereafter. In this paper, we describe the first series of patients with airway manifestations of RP that were managed successfully with self-expandable metallic stents (SEMSs). We also review the English literature on this topic.

MATERIALS AND METHODS

We reviewed medical records of all patients with airway manifestations of RP who were managed at our institution using a SEMS (Wallstent; Schneider; Minneapolis, MN). The demographic characteristics, clinical features, diagnostic test results, therapeutic interventions, and the latest clinical follow-up were noted. The English-language literature on the management of' airway manifestations of RP was also reviewed. The stents were placed using FB by a technique described previously.[7] The patients who were receiving mechanical ventilation were hospitalized for the procedure.

RESULTS

Between March 1996 and February 1999, five patients with airway manifestations of RP were treated with SEMSs (Table 2). There were four women and one man, with ages ranging from 40 to 69 years (Table 2).

(*) M = male; F = female; RLL = right lower lobe; LUL = left upper lobe.

([dagger]) Age at the time of the first stent insertion.

([double dagger]) Initial symptom/sign.

([sections]) Duration between the first symptom or sign and the diagnosis of RP.

Clinical Features, Diagnostic Tests, and Comorbidities

Each patient had three or more of the six clinical features described by McAdam et al[2] (Table 2). Three patients were receiving mechanical ventilation. The delay in diagnosis was between 8 months and 13 years from the time of the first symptom. The family history was noncontributory. The laboratory testing was unremarkable, except for mild anemia (in all), elevation of erythrocyte sedimentation rate (n = 2), and elevation of anti-nuclear antibody (n = 1). Rheumatoid factor (n = 3) and anti-neutrophilic-cytoplasmic antibody (n = 2) were negative, and thyroid-stimulating hormone (n = 2) was normal in the patients who were investigated using these laboratory tests.

In all patients, spirometry prior to specific therapy showed severe combined obstructive and restrictive ventilatory defects, and expiratory obstruction and/or inspiratory obstruction (Table 3). One patient had measurement of total lung capacity and diffusing capacity (69% and 44% predicted, respectively). Findings on chest radiograph and CT were unremarkable, except for narrowing of the trachea and main stem bronchi (n = 2), and atelectasis or infiltrate (n = 3; Table 2; Fig 1). Echocardiograms (n = 3) were normal, except for mild aortic insufficiency in one patient. Audiometry (n = 3) revealed bilateral sensory-neural hearing loss. The histopathology (n = 3) of cartilage from the nasal septum, trachea, or ear pinna was suggestive of RP. All patients were given diagnoses of asthma before RP was diagnosed; only two patients had a bronchodilator response. Other common comorbidities included anemia (in all patients), diabetes mellitus (n = 2), idiopathic thrombocytopenic purpura (n = 1), pseudomonas bronchitis (n = 3), and streptococcal sepsis (n = 2).

[Figure 1 ILLUSTRATION OMITTED]

(*) FVC = forced vital capacity; [FEV.sub.1] % = ratio of [FEV.sub.1] to FVC.

([dagger]) Actual flow measurements not available, but reported as severe combined obstructive and restrictive ventilatory defect with flattening of expiratory and inspiratory curves.

Treatment

Medications included prednisone, methotrexate, cyclosporine, and dapsone in the four patients who received specific medical therapy (Table 4). These medications were administered either alone or in combinations, in varying doses, and for periods of months to years. The response to these medications could not be assessed from the chart review. The decision to place the stents was made after severe shortness of breath (in all patients) or stridor (n = 4) persisted for a period of 2 months to 19 years (Table 4). Multiple weaning attempts failed in the three patients receiving mechanical ventilation, and they were deemed unweanable. Bronchoscopy revealed dynamic expiratory and/or inspiratory collapse with inflammation of the major airways in all patients (Fig 2). When airway collapse was considered significant, SEMSs were placed. In all, 17 stents were placed (Table 4; Fig 3). Seven stents were placed in the trachea (14 to 18 mm x 40 mm), five in the left main stem bronchus (10 to 12 mm x 20 to 40 mm), four in the bronchus intermedius (7 to 10 mm x 20 mm), and one in the right main stem bronchus (10 mm x 20 mm). In three patients, disease progression necessitated additional stent placement in new locations after 3 to 6 months.

[Figures 2-3 ILLUSTRATION OMITTED]

(*) S = stent; LM = left main bronchus; BI = bronchus intermedius; T = trachea; RM = right main bronchus: Pred = prednisone; MTX = methotrexate; Cyclo = cyclosporine; qod = every other day.

([dagger]) Silicone covered stents.

([double dagger]) As of February 1999.

Therapeutic Response to Stent Placement

An immediate improvement in symptoms, wheezing, and ventilation was noted in all patients. The overall long-term results were favorable in four patients (Table 4); three of them are alive without ventilatory support 16 to 18 months after the first stent placement. One patient (patient 4) is fully functional and enjoying a productive lifestyle; the second patient (patient 1) has moderate functional capacity and is able to carry out all routine activities. The third patient (patient 5) is getting rehabilitation therapy to walk without support after surgery for vertebral fracture with spinal cord compression secondary to large doses of steroids. The fourth patient (patient 2) survived for 20 months without ventilatory support after the first stent placement before she died after developing sudden shortness of breath. Two of the three patients receiving mechanical ventilation were weaned off the ventilator each time after the stent placement, the third patients died after 1 week, possibly due to persistent airway collapse distal to the stents.

The complications of stent placement included cough, hemoptysis, mucus plugging, and pneumothorax. The symptom of mild, chronic, or recurrent cough persisted in all patients. Mild recurrent hemoptysis that did not require specific therapy occurred in two patients for the first few days. One patient (patient 3) developed a small right-sided pneumothorax, probably due to mucus plugging and mechanical ventilator-associated trauma. None of our patients experienced migration of the stent or developed granulation tissue that required specific therapy.

DISCUSSION

The literature on RP is scanty. In a series of 112 patients with RP, Michet et al[1] described the natural history, clinical features, and predictors of death. Others have described smaller numbers of patients with airway manifestations and their management.[5,6] Another report reviewed serious airway complications in 62 patients.[4]

Demographic and Clinical Features of RP

Cases of RP have been reported in children as well as adults, with ages ranging from 2 to 84 years (median, 50) at the time of diagnosis.[1,2,4] The male-to-female ratio is 1:1; however, among the patients with serious airway manifestations, females predominate (female-to-male ratio, 2.6:1).[1,2,4] Systemic manifestations and comorbid conditions (most commonly autoimmune and rheumatic diseases) have been well described.[1,2] The pathogenesis of the disease is unknown. Although no laboratory tests are diagnostic, they help to rule out other diagnostic possibilities. Histologic features of the cartilage include loss of basophilic staining of the matrix and perichondral inflammation; eventually the cartilage is destroyed and replaced by fibrous tissue.[2]

Airway Manifestations and Pulmonary Function Tests

Airway manifestations are ultimately present in about 50% of patients with RP, although they may not be the presenting features.[1,2] They are the most serious manifestations and predict a poor prognosis. [1,4] The mechanisms of airway obstruction include the following: (1) inflammatory swelling causing airway narrowing in the active stage; (2) progressive destruction of the laryngeal, tracheal, and bronchial cartilage causing dynamic collapse of the airway in the earlier stage; and (3) formation of fibrous tissue causing cicatricial contraction in the later stage.[8] The predominant mechanism of expiratory obstruction is the structural abnormality of the airways, and not the loss of lung elastic forces.[9]

The airway obstruction is commonly diffuse, involving the upper airways. It may be asymptomatic in earlier stages and detected only on pulmonary function testing.[1,4] It is always symptomatic when it involves the glottis, subglottic area, or upper trachea. Tracheal collapse may occur suddenly causing dyspnea, respiratory arrest, asphyxia, and rapid death.[6] Rarely, the obstruction may involve distal airways.[10] Along with airway obstruction, impaired mucociliary clearance and diminished effectiveness of coughing may predispose these patients to develop pneumonia.[8] Severe bronchorrhea may be a one of the presenting features.[11]

The spirometry, flow-volume curves, and airway resistance measurement together are more sensitive than bronchoscopy and radiographic imaging in determining the presence, severity, site, and nature of airway obstruction in RP.[8,9] In the earlier stage, the obstruction is variable, and hence the ratio of maximal expiratory to inspiratory flow at 50% of vital capacity is either reduced (in intrathoracic obstruction) or elevated (in extrathoracic obstruction), and the resistance is normal. In the later stage, the obstruction is fixed due to cicatricial narrowing of the airway, and hence the ratio of maximal expiratory to inspiratory flow at 50% of vital capacity is dose to 1, and the resistance is elevated.[8] Our patients, when compared to those described in the literature, had more severe ventilatory defects as indicated by spirometry (Table 3).[8,9] This is probably because we selected only patients with stents for this study.

Radiographic Imaging

Plain radiography of the respiratory tract in patients with RP should include a lateral view of the neck, together with a penetrated frontal view of the chest.[12] The coronal diameter of the trachea may be smaller in patients with airway manifestations.[12] High-resolution CT scan may demonstrate diffuse, smooth thickening of the tracheobronchial wall, causing narrowing and deformity of the airway lumen; the airway may return to normal with steroid therapy (Fig 1).[4,10,12-14] There may be dense calcium deposits in the tracheal wall, which may be confused with those caused by tracheopathia osteochondroplastica and amyloidosis.[13] The CT scan is also sensitive in detecting lower airway disease causing concentric narrowing in lobar and segmental bronchi, and bronchiectasis in segmental and subsegmental bronchi.[10] In patients with distal airway involvement, tracheostomy or stents to keep proximal airway patent may be of limited value.[10]

Bronchoscopic Findings

Bronchoscopy is essential in identifying the exact site, nature, and severity of airway involvement in RP. It usually reveals inflammation of the tracheobronchial tree, and dynamic collapse or narrowing of the major airways (Fig 2). These findings are more common in patients with expiratory obstruction than in patients with inspiratory obstruction.[9] Bronchoscopy does carry a risk of provoking dyspnea, collapse of the airways, hypoxia, asphyxia, and death.[4]

Treatment

No single medical or surgical treatment is uniformly effective in curing the disease, relieving the symptoms, or preventing progression of airway manifestations. Most patients with airway manifestations are managed with pharmacologic and supportive treatment. The medications tried in single patients or in small series of patients, with variable response, include nonsteroidal anti-inflammatory drugs (aspirin, indomethacin, and phenylbutazone), corticosteroids, and other immunosuppressive medications (cyclosporine, methotrexate, azathioprine, penicillamine, 6-mercatopurine, and dapsone).[1-4,15] Corticosteroids decrease the frequency, duration, and severity of flares, but do not stop disease progression in severe cases.[2] The risk-benefit ratio for use of these medications in RP is not well established, and hence they are not recommended for routine use.

Surgical treatments include the following: tracheostomy, tracheobronchial (intraluminal) stents, external airway splinting, and laryngotracheal reconstruction.[4,5] Tracheostomy, if performed early, may prevent sudden death in patients with localized subglottic involvement. However, tracheostomy itself may be hazardous by making the intubation difficult in the future.[5]

Self-expandable metallic airway stents, as shown in this report, can be used as the sole specific treatment or as an adjunct to other treatment modalities.[7] Advantages of a metallic stent include the following: (1) ease of placement; (2) visibility on ordinary radiograph (Fig 3); (3) dynamic expandability; and (4) maintenance of ventilation even when a bronchial orifice is covered by the stent.[16] Additional advantages offered by a SEMS (eg, Wallstent) include the following: (1) it can be placed by a FB in an outpatient setting under local anesthesia and conscious sedation, avoiding hospitalization and general anesthesia; (2) it can be placed in a patient receiving mechanical ventilation; (3) epithelialization of the stent occurs in few weeks after placement, which preserves mucociliary action and lowers the risk of mucus plugging; (4) it rarely migrates; (5) it conforms to a tortuous airway; and (6) it allows intubation through a tracheal stent, with a tracheostomy tube or with an endotracheal tube, if necessary (Fig 3).[7,16] Complications of stents in general include migration, granulation tissue formation, retention of secretions, bleeding, ulceration, and, rarely, erosion of the tracheobronchial wall into the surrounding structures.[7,16] One of the disadvantages of a SEMS is that once it is placed, it cannot be removed without significant morbidity.[16] Stent placement is best performed early in the course of RP, rather than after prolonged mechanical ventilation that can promote tracheobronchial colonization with pseudomonas or other organisms.[6,17]

External airway splinting using other tissues of the body or Gore-Tex (A. L. Gore; Flagstaff, AZ) is the treatment of choice to prevent collapse in eases of severe tracheobronchial disease.[4] Laryngotracheal reconstruction is considered when tracheal or subglottic stenosis occurs in isolated segments; however, the reported benefits are limited.[5] During general anesthesia, the anesthetist should be aware of the degree of airway and cardiovascular involvement.[6,18] The use of cortieosteroids in the perioperative period may help by reducing inflammation.[6] Tracheal collapse may be prevented by applying continuous positive airway pressure with a mask, by awake intubation with the patient in an upright position, or by intubating over a bronchoscope.[6]

Prognosis

The course of RP may be relatively benign and indolent, or it may be rapidly fatal even after pharmacologic treatment, tracheostomy, and tracheobronchial stent placement.[1,4,6] Death is directly attributable to RP in about half of the fatal eases. Survival rates for 5 and 10 years are 74% and 55% respectively,j Reported death from respiratory tract involvement varies from 10% (4 of 41) to 59% (17 of 29) of total deaths.[1,2] In a series, laryngotracheal stricture was one of the three variables (the other two being age and anemia) that predicted mortality on multivariate analysis.[1]

Summary

Unexplained dyspnea, stridor, hearing deficit, and recurrent ear or nasal inflammation with deformity may be early manifestations of RP. Physicians should have a high index of suspicion in the presence of these manifestations for the early diagnosis and treatment of this rare disease. No single medical or surgical treatment is uniformly effective in curing the disease, in relieving the symptoms, or in preventing the progression of airway manifestations. The management of airway manifestations of RP with self-expandable metallic tracheobronchial stents may provide a long-term palliation. A multidisciplinary team approach by pulmonologists, otolaryngologists, rheumatologists, thoracic surgeons, and interventional radiologists is required for the efficient management of these patients. Further studies are required to determine the ideal type of stent and the optimal timing of its placement to prevent long-term morbidity and mortality from the airway manifestations of RP.

ACKNOWLEDGMENT: The authors thank Jessica Ancker, BA, Medical Editing Services, The Cleveland Clinic Foundation, Cleveland, OH, for her valuable assistance in editing the manuscript.

REFERENCES

[1] Michet CJ, McKenna CH, Luthra HS, et al. Relapsing polychondritis: survival and predictive role of early disease manifestations. Ann Intern Med 1986; 104:74-78

[2] McAdam LP, O'Hanlan MA, Bluestone R, et al. Relapsing polychondritis. Medicine 1976; 55:193-215

[3] Damiani JM, Levine HL. Relapsing polychondritis. Laryngoscope 1979; 89:929-946

[4] Eng J, Sabanathan S. Airway complications in relapsing polychondritis. Ann Thorac Surg 1991; 51:686-692

[5] Spraggs PDR, Tostevin PM J, Howard DJ. Management of laryngotracheobronchial sequelae and complications of relapsing polychondritis. Laryngoscope 1997; 107:936-941

[6] Dunne JA, Sabanathan S. Use of metallic stents in relapsing polychondritis. Chest 1994; 105:864-867

[7] Dasgupta A, Dolmatch BL, Abi-Saleh WJ, et al. Self-expandable metallic airway stent insertion employing flexible bronchoscopy: preliminary results. Chest 1998; 114:106-109

[8] Mohsenifar Z, Tashkin DP, Carson SA, et al. Pulmonary function in patients with relapsing polychondritis. Chest 1982; 81:711-717

[9] Krell WS, Staats BA, Hyatt RE. Pulmonary function in relapsing polychondritis. Am Rev Respir Dis 1986; 133:1120-1123

[10] Davis SD, Berkmen YM, King T. Peripheral bronchial involvement in relapsing polychondritis: demonstration by thin-section CT. Am J Roentgenol 1989; 153:953-954

[11] Chan HS, Pang J. Relapsing polychondritis presenting with bronchorrhoea. Respir Med 1990; 84:341-343

[12] Crockford MP, Kerr IH. Relapsing polychondritis. Clin Radiol 1988; 39:386-390

[13] Im JG, Chung JW, Han SK, et al. CT manifestations of tracheobronchial involvement in relapsing polychondritis. J Comput Assist Tomogr 1988; 12:792-793

[14] Booth A, Dieppe PA, Goddard PL, et al. The radiological manifestations of relapsing polychondritis. Clin Radiol 1989; 40:147-149

[15] Ridgway HB, Hansotia PL, Schorr WF. Relapsing polychondritis: unusual neurological findings and therapeutic efficacy of dapsone. Arch Dermatol 1979; 115:43-45

[16] Nesbitt JC, Carrasco H. Expandable stents. Chest Surg Clin N Am 1996; 6:305-328

[17] Shah R, Sabanathan S, Mearns AJ, et al. Self-expanding tracheobronchial stents in the management of major airway problems. J Cardiovasc Surg 1995; 36:343-348

[18] Hayward AW, Al-shaikh B. Relapsing polychondritis and the anesthetist. Anesthesia 1988; 43:573-577

(*) From the Department of Pulmonary and Critical Care Medicine, Cleveland Clinic Foundation (Drs. Sarodia and Mehta), Cleveland, OH; and the Department of Pulmonary and Critical Care Medicine, Kelsey-Seybold Clinic (Dr. Dasgupta), Houston, TX.

Manuscript received February 25, 1999; revision accepted May 19, 1999.

Correspondence to: Atul C. Mehta, MBBS, FCCP, Department of Pulmonary and Critical Care Medicine, Desk A-90, The Cleveland Clinic Foundation, 9500 Euclid Ave, Cleveland, OH 44195

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